FEDERAL STATE-FINANCED EDUCATIONAL INSTITUTION

OF HIGHER EDUCATION
"KURSK STATE MEDICAL UNIVERSITY"
MINISTRY OF HEALTH OF THE RUSSIAN FEDERATION
The department of the infectious diseases and epidemiology

Belokonova L.V., Titareva L.V., Kiseleva V.V., Rogova Y.A., Shamara L.F.

Course of lectures of infectious diseases

The guidance manual
FOR FOREIGN STUDENTS
Part II

Kursk – 2017

1
 УДК Печатается по решению
ББК: редакционно-издательского совета
ФГБОУ ВО КГМУ Минздрава
России

Belokonova L.V., Titareva L.V., Kiseleva V.V., Rogova Y.A., Shamara L.F.
Course of lectures of infectious diseases: the guidance manual for foreign students.
Part II– Kursk: KSMU, 2017 – 115 p.

The guidance manual may help foreign students to study same actual
questions of infectious diseases and helps to put the very latest knowledge
about etiology, pathogenesis, clinical manifestations, diagnosis, treatment and
prevention of infectious diseases.

Reviewers: d.m.s., professor of the department

d.m.s., professor of the department of

ISBN:

ББК

© Belokonova L.V., Kiseleva V.V., Rogova Y.A., Titareva L.V.

© ФГБОУ ВО КГМУ МЗ РФ, 2017

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 CONTENTS

Influenza____________________________________________ 4
Parainfluenza_________________________________________ 9
Adenovirus Infections__________________________________ 10
Rhinovirus infection____________________________________ 13
Respiratory syncytial virus infection________________________ 14
Coronaviruses__________________________________________ 15
Erysipelas______________________________________________ 16
Lyme disease____________________________________________ 20
Anthrax________________________________________________ 30
Staphylococcal infection___________________________________ 38
Meningococcal infections__________________________________ 42
Hemorrhagic fever with renal syndrome (HFRS)________________ 48
Ebola hemorrhagic fever___________________________________ 52
Marburg hemorrhagic fever_________________________________ 55
Plague__________________________________________________ 58
Tularemia_______________________________________________ 65
Rabies___________________________________________________ 71
Brucellosis_______________________________________________ 76
Chickenpox______________________________________________ 83
Herpes zoster_____________________________________________ 88
Ornithosis_______________________________________________ 90
Diphtheria_______________________________________________ 95
Malaria_________________________________________________104

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 Influenza
Etiology. Influenza viruses are single-stranded negative sense RNA viruses
of the family Orthomyxoviridae. Three types (A, B, and C) of influenza viruses
infect humans. Type A and B viruses are known to cause significant human
disease. The genome contains eight gene segments that code for 11 proteins,
including the two main surface glycoproteins, hemagglutinin (HA) and
neuraminidase (NA). Type A viruses are further classified into subtypes based on
their HA and NA proteins. Currently circulating human influenza, a subtypes
include A (H1N1) and A (H3N2) viruses. Human influenza viruses bind to and
replicate primarily in epithelial cells of the upper respiratory tract.
Influenza viruses are evolving continuously through a process called
“antigenic drift” in which random point mutations in the HA gene result in changes
to the HA surface protein. Minor changes in the genetic composition of influenza
viruses can create new virus strains that are not prevented by existing vaccines.
Humoral immunity is based largely on strain-specific HA antibodies and is reduced
in young children and in immunosuppressed, immunocompromised, and elderly
persons. Antigenic drift is the reason that influenza virus strain surveillance must
be conducted worldwide year round; vaccine strains must be updated each year,
and thus, annual influenza vaccination is needed.
“Antigenic shift,” as opposed to “drift,” is the emergence of a novel
influenza A subtype virus in humans. If the novel influenza A virus acquires the
ability for sustained human to human transmission, a pandemic can result. This can
occur through direct mutation from an avian influenza A virus (such as the H1N1
pandemic virus that caused the 1918–19 “Spanish flu” resulting in an estimated
20–100 million deaths) or genetic assortment between human and avian influenza
A virus. The natural reservoir for all influenza A virus subtypes is in wild aquatic
ducks and geese. The 1957–58“Asian influenza” H2N2 and 1968–69 “Hong Kong
influenza”H3N2 pandemic viruses originated through genetic assortment between
human influenza A and low pathogenic avian influenza A virus. See Chapter 71,
Avian Influenza A(H5N1).
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 Influenza viruses are intracellular parasites. The virus is unstable in the
environment, is rapidly destroyed on heating, drying, and by various disinfectants;
it withstands frosting.
Influenza viruses are cultivated and isolated on chick embryo. Among
laboratory animals, hamsters, mice and pole cats are most susceptible to the
influenza virus.
Epidemiology. Diseased humans, especially during the first days of the
disease, are the main source of infection. The virus is released from the patient
during sneezing, coughing and talking till the 4-7thday of the disease. If influenza is
complicated by pneumonia, the virus is liberated for 10-12 days. Patients with
abortive and asymptomatic diseases are dangerous for the surrounding, because the
quantity of such patients is much greater than of patients with clinical symptoms,
and they continue actively infecting people.
Infection is transmitted by air-borne route in enclosures where an influenza
patient is present. Infection spread is facilitated by inadequate living conditions,
overcrowding that promotes close contacts with the patient, inadequate labor
conditions, intensive migration of population.
Since the influenza virus is unstable in the external environment, fomites
(dishes, toys, towels, etc.) are not substantially important. Influenza occurs as
sporadic infections and epidemic outbreaks, pandemics. Influenza A epidemic is
characterized by a rapid spread, which is due to generation of new antigenic
variants of the virus.
During an epidemic outbreak, the number of influenza cases and acute
respiratory diseases increases 10-20 times. Within a short lapse of time (1-11/2
months) residents of many cities and countries become involved (the sick rate from
30 to 40 per cent). People of almost all age groups are equally involved. The
duration of circulation of all new virus A serotypes is 10-11 years. During this
period, each serotype gives 3-4 antigenic variants, which, in turn, become the
cause of new epidemic outbreaks of influenza every 2 or3 years.

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 During the past seventy years, virus A changed its antigenic structure five
times. One virus type superseded the other: A0-A1-A2-A3. Late in 1977, when
cases with influenza A3 were still reported, a new influenza appeared due to
serotype A(H1N1). Since the last pandemic caused by this serotype was in 1956,
people aged under 25 years were mostly afflicted.
Stable immunity to serotype A(H1N1) in persons who sustained this
infection in the past was thus discovered. Epidemics due to virus B develop slowly
and involve to 10-25 percent of population; they occur every 2 or 3 years. Virus C
causes sporadic infections mostly among children.
The spread of influenza is thus promoted by the instability of the antigenic
structure of virus A under the influence of immunity in those who sustained the
disease in the past. The spread is also promoted by high natural susceptibility of
population, by a considerable proportion of asymptomatic (abortive) forms of the
disease, by the short-lasting incubation period, and by the easiness of infection
transmission through the droplet mechanism. The influenza incidence increases
during the autumn and winter, and also in the spring.
Pathogenesis. The portal of infection is mucosa of the upper airways.
Columnar epithelium of the trachea is afflicted selectively. As the virus multiplies
in the epithelium it causes its degeneration and necrosis. The underlying tissues are
affected by edema, the vessels become permeable to cause epistaxis, blood in the
sputum, etc. Toxemia evokes the lesion of the nervous and cardiovascular system.
Suppressed immunity facilitates development of secondary complications due to
exogenic and endogenic microorganisms; chronic diseases are exacerbated.
Multiplication of the virus is inhibited by interferon that is formed from the very
first hours of the disease in the infected cells. By the end of the first week, the titer
of the specific antibodies increases. The type-specific immunity after the sustained
disease persists for 20 years.
Clinical picture. The incubation period lasts 1-2 days with variations from a
few hours to 3 days. Influenza can be mild, moderate and severe. The disease can
have a typical or atypical clinical manifestations.
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 A typical influenza begins acutely with elevation of body temperature and
chilliness. In 4-5 hours the body temperature can be as high as 38.7-40 °C. If the
disease is mild, the body temperature can be sub febrile. The condition of the
patient worsens. He complains of headache, mostly frontal and retro-ocular, which
is accentuated by the movement of the eyes, pain in the muscles and bones,
insomnia, cough, nasal obstruction, dry throat, sneezing, sweating, and weakness.
Examination reveals hyperemic face and neck, and injected scleral vessels.
There are also tachypnea and arterial hypotension; the heart sounds are dull; the
pulse is slow (disagrees with body temperature). Nosebleed is possible. Among the
respiratory symptoms are catarrh of the upper airways: stuffy nose, sneezing,
hoarse voice, dry cough. The fauces are hyperemic, the tongue is coated.
Cough can persist in the young for 10-12 days, and in the elderly for longer
time. The influenza virus and its toxins affect the peripheral nervous system and
bone marrow, which is manifested by neuralgia, neuritis and symptoms of
encephalitis.
If influenza is not aggravated by complications, fever persists for2-4 days,
less frequently 5 days, or it may be as short as 1 day.
A severe (toxic) form of influenza is characterized by marked symptoms of
toxemia: severe headache, hyperpyrexia (to 40 °C), dyspnea, cyanosis,
hypotension, weak and fast pulse, insomnia or somnolence, sometimes delirium,
nausea, vomiting, loss of consciousness, muscular cramping, symptoms of
meningitis; hemorrhages in the skin can develop. Severe forms of influenza usually
occur during the first two weeks of an epidemic.
Influenza is characterized by specific leucopenia with relative lymphocytosis
and a neutrophilic shift to the left, and an eosinophilia.
Complications. The chief complications are pneumonias due to the virus or
secondary bacterial infection (pneumococci, staphylococci, hemolytic streptococci,
etc.). Acute cardiovascular failure, laryngitis, tracheobronchitis, bronchitis,
bronchiolitis, frontal sinusitis, maxillary sinusitis, otitis and various hemorrhages,

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from epistaxis to hemorrhagic edema of the lungs, are also complications of
influenza.
Diagnosis. Influenza can be confirmed by a variety of testing methods. It is
important to obtain the appropriate upper respiratory specimens during the time of
viral shedding. The best clinical specimens are nasopharyngeal or nasal swabs or
aspirates collected from acutely ill patients as close to illness onset as possible, and
ideally within 4 days after fever onset.
Throat and sputum specimens are more likely to yield false negative results.
Tests that are most useful for the ED setting include rapid influenza diagnostic
tests and immunofluorescence (direct and indirect fluorescent antibody staining)
tests. Reverse transcriptase polymerase chain reaction (RT-PCR) and viral culture
may be available at some hospitals, but results will likely not be available for
timely clinical management.
Rapid influenza diagnostic tests are screening tests that can yield results in
less than 30 minutes and include tests that only detect influenza A, tests that detect
(but do not distinguish between) influenza A and B, and tests that detect and
distinguish between influenza A and B. The most important factor influencing the
accuracy of rapid tests is how prevalent influenza activity is among the patient
population being tested. The sensitivities of rapid influenza tests are moderate
compared to viral culture. Positive test results are most likely accurate and negative
results are frequently inaccurate during peak community influenza activity. The
peripheral white blood cell count (WBC) may reveal leukopenia and lymphopenia
but may also be normal or slightly elevated. Transaminases may be mildly
elevated.
Treatment. Only these medicines have proved clinical effect for influenza
treatment:
Oseltamivir 75 mg - 2 times daily in capsules for 5 days.
Zanamivir 10 mg - 2 times daily inhalation for 5 days.
Two other antiviral medicines Rematadine and Amantadine were used in
past and are not effective now because of viral resistance. Rest until disease is fully
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resolve, fluids in the case of intoxication, acetaminophen against temperature
(aspirin is strictly contraindicated in children before 18, because of Reye
syndrome).
Severe forms of influenza should be treated by repeated administrations of
anti-influenza immunoglobulin, detoxicating fluids (isotonic sodium chloride
solution, haemodez, polyglucin, rheopolyglucin), 800-1000 ml a day, with an
obligatory administration of Lasix, Brinaldix (saluretics), or urea and mannitol.
Development of complications is an indication for antibiotic therapy.
Prevention and control. Annual trivalent influenza vaccination is
recommended for persons at high risk for complications from influenza, for their
household contacts, and for all health care providers. Each year, the three influenza
virus vaccine strains (influenza A [H1N1], A [H3N2], and influenza B) may be
updated based on global strain surveillance data. Live attenuated influenza virus
vaccine for intranasal administration is available in the United States for healthy
individuals aged 2–49 years. When significant antigenic drift in circulating strains
distinct from vaccine strains occurs, influenza vaccine effectiveness is reduced.
Acute care physicians should not discount the possibility of influenza in persons
who have received influenza vaccine.
Parainfluenza
Etiology. The disease is caused by the virus belonging to the family of
Paramyxoviridae. The parainfluenza virus contains RNA. Four serotypes are
known that afflict humans. In laboratory conditions they are cultivated in cells of
human embryo kidney. The viruses are unstable in the environment.
Epidemiology. The source of infection is a diseased human. Infection is
transmitted by air-borne route. Infants are mostly affected, although adults can also
develop the disease. A sufficiently stable immunity to a specific virus is produced
in those who sustained the disease. Parainfluenza occurs during the whole year as
sporadic infection, but seasonal rise in the morbidity (during the spring and the
cold season) is also observed.
Pathogenesis. This is the same as in influenza.
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 Clinical picture. The incubation period lasts from 3 to 4 days with
variations from 2 to 7 days. As a rule, the disease develops gradually and runs a
sluggish course of 3-5 days. Catarrhal phenomena are not pronounced: cough, mild
rhinorrhea, less frequently sub febrile temperature. The patient complains of
chilliness, headache, and slight fatigue. Hoarseness and chest pain are due to
laryngitis (the most common symptom of parainfluenza) and laryngotracheitis.
Nasal breathing is impeded. Serous nasal discharge gradually thickens and
becomes mucous or mucopurulent due to secondary infection.
Children, and especially infants, develop severe laryngitis, which is often
attended by the clinical symptoms of laryngeal stenosis and croup. The entire
respiratory tract can be involved in parainfluenza. Bronchitis runs a severer course
and is attended by lesion of small bronchi (bronchiolitis) and lung parenchyma
(pneumonia).
Complications. Croup, pneumonia, acute tonsillitis, sinusitis, otitis and
some other diseases develop; these usually occur in infants with rickets, anemia
and other disease due to secondary infection.
Diagnosis. As distinct from influenza, toxemia is not manifest in
parainfluenza infection. Cardiovascular and nervous lesions are absent;
involvement of the larynx and the lower airways is more pronounced. The
diagnosis is verified in the laboratory by virological tests (isolation of the
parainfluenza virus from nasopharyngeal washings), serologic (blood serum tests)
and immunofluorescence.
Treatment. Treatment is symptomatic. Anti-influenza immunoglobulin can
be administered intramuscularly for therapeutic and prophylactic purposes.
Antibiotics, sulpha drugs and inhalations should be given for complications.
Prophylaxis is the same as in influenza.
Adenovirus Infections
Etiology. The causative agent belongs to the family of Adenoviridae.
Among the 32 types of adenovirus isolated from man, types 3, 4, 7, 14, and 21
cause severe diseases. Type 8 causes keratoconjunctivitis in susceptible persons.
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Adenoviruses contain DNA. They are more stable in the environment than the
influenza virus.
Epidemiology. The source of infection is a diseased person, who liberates
adenoviruses with nasal, nasopharyngeal mucus, sputum, and conjunctival
discharge during the first 5-6 days of the disease.
Virus carriers are another source of infection. At later terms of the disease
adenoviruses are shed with faeces. The infection is mainly transmitted by the air-
borne route. Since the virus is stable in the environment, infection can spread by
contact, food or water (bathing in swimming pools, ponds, lakes, etc.).
Infants aged from 6 months to 3 years are usually afflicted. Type-specific
immunity is produced in convalescents. Adenovirus infections occur as sporadic
cases and epidemic outbreaks in children's institutions. The morbidity rises in the
autumn and winter. Since the incubation period lasts from 3 to 12days, outbreaks
of adenoviral infection last longer than those of influenza.
Pathogenesis. Adenoviruses mostly affect respiratory mucosa, and less
frequently conjunctiva. They can multiply in the intestinal mucosa as well. The
lymphoid tissue of the regional lymph nodes is damaged, the vegetative nervous
and endocrine systems are also upset with subsequent vascular disorders (pallor,
tachycardia).
Clinical picture. The incubation period lasts from 3 to 12 days, most
frequently from 5 to 6 days. Acute adenoviral infection is characterized by the
following clinical symptoms: rhino pharyngitis, rhinopharyngotonsillitis,
rhinopharyngobronchitis, pharyngoconjunctival fever, membranous or follicular
conjunctivitis, and pneumonia. Rhinopharyngotonsillitis and
rhinopharyngoconjunctivitis are more common.
The incubation period lasts 5-6 days. The disease onset is usually gradual (2-
3 days). The general symptoms are marked: malaise, chilliness, fever, headache.
Local symptoms develop early: stuffy nose, hyperemia of the fauces and the
posterior wall of the pharynx, difficult swallowing, cough (dry or with
expectoration of sputum) and chest pain. Some patients complain of abdominal
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pain, intestinal disorders, sometimes hepatic enlargement. Fever lasts from2 to 7
days. Malaise and other general symptoms abate with normalization of body
temperature, but catarrh can persist for1-2 days more.
Acute rhinopharyngoconjunctivitis is characterized by a moderate
impairment of the general condition, inflammation of the respiratory mucosa, the
fauces, and the eyes (rhinitis, tonsillitis, pharyngitis, nasopharyngitis, laryngitis,
tracheitis, bronchitis, conjunctivitis). The internal organs can be involved
separately or in various combinations. Respiratory mucosa and the mucosa of the
eyes can be involved simultaneously, but sometimes only pharyngitis or only
conjunctivitis can develop.
Conjunctivitis lasts from several days to 2 weeks and longer. The eyelid
mucosa and the eyeballs are injected, the conjunctiva can be affected with edema
and gentle granularity (catarrhal or follicular conjunctivitis). Membranous
conjunctivitis is also possible. The eye secretion is meagre and serous in character.
The cornea and the iris remain usually uninvolved. Among rare symptoms are
nosebleed, nausea, vomiting and diarrhea.
In addition to the mentioned symptoms, small round foci of corneal opacity
develop in several days (to 2 weeks) after the onset of keratoconjunctivitis. The
foci sometimes fuse together. The disease lasts 2-4 weeks and usually ends in
complete recovery.
Pneumonia is the most severe form of adenoviral infection. It usually afflicts
infants under 1 year of age. Pneumonia can occur with other forms of adenoviral
infection. Pneumonia is usually focal(bronchopneumonia). The body temperature
can remain high for 1-2weeks and longer. Dyspnea, cyanosis, and symptoms of
toxemia develop.
Complications. The condition can be complicated by otitis, sinusitis,
pneumonia, pleuritis, arthritis, which are due to secondary infections. Adenoviral
infection can be the cause of exacerbation of chronic diseases.
Diagnosis. Adenoviral infection is characterized by pronounced exudation;
toxemia is absent; conjunctivitis, especially membranous, is typical of the
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infection. An accurate diagnosis can be established only in the laboratory:
virologically (isolation of the adenovirus in tissue culture), serologically, and by
the immunofluorescent method.
Treatment. Symptomatic treatment is used: analgesics, cardiacs,
antitussives. Severe cases should be treated with immunoglobulin, interferon,
desoxyribonuclease. To prevent complications, the patient must remain in bed.
Food must be adequate and rich in vitamins.
Prevention. Cases with severe course of the disease should only be
hospitalized. The other patients should be isolated in home conditions till complete
recovery. Chlorination of water in swimming pools is used to prevent outbreaks of
the infection. For other preventive measures see "Influenza".
Rhinovirus infection
Etiology. The rhinoviruses (RVs) are among the most common of the
pathogens that infect humans. These viruses have been implicated in 30% to 50%
of all cases of acute respiratory disease and are the most important cause of the
common cold. RVs are small RNA viruses of the Picornaviridae family. More than
100 different serotypes have been identified until now.
Pathogenesis. Rhinovirus infections occur throughout the year, but usually
there are distinct peaks of illness in the fall and spring. Delivery of virus to the
nasal mucosa can potentially occur either by aerosols or by direct contact.
Rhinovirus preferentially infects the upper respiratory tract.
Clinical features. The incubation period is 12-72 hours. Nasal dryness or
irritation may be the first symptom of RV infection. A sore throat or throat
irritation is also a common initial symptom and is frequently the most intense of
the early symptoms. This is followed by nasal discharge, nasal congestion, and
sneezing, which intensify over the next 2-3 days. Nasal secretions typically
become thicker and colored after the first few days of illness. Other associated
complaints include headache, facial and ear pressure. Systemic signs and
symptoms, such as fever and malaise, are unusual.

13
 Diagnosis. If findings from a thorough history and physical examination are
consistent with a viral etiology and no complications are noted, an additional
laboratory workup is rarely necessary.
Treatment. Rhinovirus infections are predominantly mild and self-limited;
thus, treatment is generally focused on symptomatic relief and prevention of
person-to-person spread and complications. Symptomatic treatment with
analgesics, decongestants, antihistamines usually needed.
Prevention. Because infection is spread by hand-to-hand contact,
autoinoculation, and, possibly, aerosol particles, it is important to emphasize
appropriate handwashing, avoidance of finger-to-eyes or finger-to-nose contact.
Respiratory syncytial virus infection
Etiology. Respiratory syncytial virus (RSV) is one of the major causes of
lower respiratory tract illness. RSV belongs to the family Paramyxoviridae. RSV is
a medium-sized RNA virus. Most frequent RSV clinical manifestations are
bronchiolitis, pneumonia, tracheobronchitis.
Pathogenesis. Infection with RSV is primarily acquired through close
contact with an infected individual or direct inoculation into the eyes and nose of
infectious secretions. RSV replicates in respiratory epithelium. Spread of the virus
down the respiratory tract occurs through cell-to-cell transfer of the virus along
intracytoplasmic bridges (syncytia) from the upper to the lower respiratory tract.
Clinical features. The illness may begin with upper respiratory symptoms
and progress rapidly over 1-2 days to the development of diffuse small airway
disease characterized by cough, coryza, wheezing and rales, low-grade fever.
Among healthy adults RSV infection is symptomatic in 84% and 22% have lower
respiratory tract manifestations (pneumonia or bronchiolitis). In comparison to
influenza infection occurring in these same individuals, fever is less frequent, but
earache and sinus pain and a persistent productive cough are significantly more
common with RSV infection.
Diagnosis. Secretions can be analyzed for RSV in the laboratory by means
of culture, antigen-revealing techniques, or polymerase chain reaction (PCR).
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 Treatment. For most of the patient’s symptomatic care has to be given,
fever control, and adequate fluid intake. In case of immunocompromised patients
(i.e. transplant recipients, chemotherapy patients) RSV-immunoglobulin may be
prescribed. One of the new treatment possibilities for immunocompromised
patients with RSV is palivizumab, a humanized monoclonal antibody directed
against the F (fusion) protein of RSV.
Prevention. Special preventive measures against RSV are not indicated for
healthy adults.
Coronaviruses
Etiology. Coronaviruses are moderate-sized (100 to 150 nm), enveloped,
single-stranded RNA viruses named for their distinctive club-shaped surface
projections, which resemble a crown. Two antigenic types of human coronavirus
(229E and OC43) have been recognized.
Epidemiology. Coronaviruses are the second most frequently documented
cause of common colds. Coronaviruses account for 4% to 15% of cases of acute
respiratory disease annually and as many as 35% during peak periods. Most
coronavirus infections occur in winter and early spring, but infections have been
detected throughout the year. Immunity to infection is short-lived, and reinfection
is common.
Clinical features. The incubation period of coronavirus colds ranges from 2
to 5 days, longer than that of rhinovirus colds. Infections produce a typical coryzal
illness that is indistinguishable from colds caused by other viruses. Lower
respiratory manifestations are pneumonia in children, military recruits, and
possibly immunocompromised hosts and exacerbation of asthma in children and of
chronic airway disease in adults. Reported associations with Gl disease, including
necrotizing enterocolitis in infants, are controversial.
Diagnosis. Virus isolation is impractical, and infection can be confirmed
with serology or by detection of coronavirus RNA. Culture of virus in human
embryonic trachea cells is the most sensitive cell culture system for recovering
coronavirus, but other methods (serology, IF, and RNA detection with RT-PCR)
15
are more practical.
Treatment. Effective antivirals or vaccines are unavailable. Intranasal
interferon Alfa is protective against experimental coronavirus colds. Treatment is
symptomatic.
Erysipelas
Background: Erysipelas is a superficial bacterial skin infection that
characteristically extends into the cutaneous lymphatics. This disease has been
traced back to the Middle Ages where it was referred to as “St. Anthony’s Fire”,
named after an Egyptian healer who was known for successfully treating the
infection. Historically, this infection occurred on the face and was caused by
Streptococcus pyogenes. However, a shift in distribution and etiology of the
disease has occurred, with most erysipelas infections now occurring on the legs
and with non-group A streptococcus sometimes being identified as the etiologic
agents.
Pathophysiology: Bacterial inoculation into an area of skin trauma is the
initial event in developing erysipelas. Thus, local factors, such as venous
insufficiency, stasis ulcerations, inflammatory dermatoses, dermatophyte
infections, insect bites, and surgical incisions, have been implicated as portals of
entry. The source of the bacteria in facial erysipelas is often the host’s
nasopharynx, and a history of recent streptococcal pharyngitis has been reported in
up to one third of cases. Other predisposing factors include diabetes, alcohol abuse,
HIV infection, nephritic syndrome, other immunocompromising conditions, and
vagrant lifestyle.
The infection rapidly invades and spreads through the lymphatic vessels.
This can produce overlying skin “streaking” and regional lymph node swelling and
tenderness. Immunity does not develop to the inciting organism.
Frequency:
• The incidence of erysipelas declined throughout the mid-20th century,
possibly due to antibiotic development, improved sanitation, and decreased
virulence. The change in distribution from the face to the lower extremities is most
16
likely related to an aging population with risk factors such as lymphedema.
Approximately 85% of cases occur on the legs rather than the face.
• Internationally: Erysipelas is somewhat more common in European
countries.
Mortality/Morbidity: The most common complaints during the acute
infection include tenderness of the involved area, fever, chills, and swelling. Death
as a direct result of erysipelas is exceedingly rare. Predisposed patients often
develop local recurrence, and this can lead to disfiguring and disabling healing
reactions, such as elephantiasis. This chronic warty, edematous condition is caused
by lymphatic destruction from repeated infection.
Race: Erysipelas infections affect all races.
Sex: Erysipelas has been reported to be more common in females, but
occurring at an earlier age in males because of their more aggressive activities.
Other studies indicate that predisposing factors, rather than gender, account for any
male/female differences in incidence.
Age: Cases of erysipelas have been reported in all age groups, but it does
appear that infants, young children and elderly patients are the most commonly
affected groups. The peak incidence has been reported to be in patience’s aged 60-
80years, especially in patients who are considered high-risk and
immunocompromised or those with lymphatic drainage problems (e.g., after
mastectomy, pelvic surgery, bypass grafting).
History: Patients often cannot recall an inciting event, but there may be a
history of recent trauma or pharyngitis. Prodromal symptoms, such as malaise,
chills, and high fever, often begin before the onset of the skin lesions and usually
are presented within 48 hours of cutaneous involvement. Pruritus, burning and
tenderness are typical complaints.
Clinical features. Erysipelas begins as a small erythematous patch that
progresses to a fiery red, indurated, tense, and shiny plaque. The lesion classically
exhibits raised sharply demarcated advancing margins. The skin often has a peaud
orange texture, which is thought to reflect involvement of superficial lymphatics;
17
superficial blebs or bullae may form, usually 2 or 3 days after onset. The lesion
typically develops over a few hours and is associated with fever and chills. Local
signs of inflammation, such as warmth, edema, and tenderness, are universal.
Lymphatic involvement often is manifested by overlying skin streaking and
regional lymphadenopathy. More severe infections may exhibit numerous vesicles
and bullae along with petechial and even frank necrosis. With treatment, the lesion
often desquamates and can resolve with pigmentary changes that may or may not
resolve over time.
Erysipelas tends to occur in certain characteristic locations: the malar area of
the face (often with extension over the bridge of the nose to the contralateral malar
region) and the lower extremities.
Classification:
1. According to clinical forms: erythematous, erythematous-bullas, bullas-
hemorrhagic.
2. According to the time of appearance: primary, relapsing, secondary.
Relapsing form is characterized by the following:
1. Interval between the appearing the symptoms of this disease and first
attack is less than 2 years.
2. Pathological process is localized at the same place.
Secondary form is characterized by the following:
1. Interval between appearing the symptoms and first attack is more than 2
years.
2. Pathological process is localized at the other place.
Erysipelas can be differentiated from cellulites by its characteristically raised
advancing edges and sharply demarcated borders, reflecting its more superficial
nature. Cellulites have no lymphatics components and exhibit.
Diagnosis. In classic erysipelas, no laboratory workup is required for
diagnosis or treatment.
Routine blood and tissue are not cost-effective because they have a low yield
and results have a minimal impact on management. Cultures are perhaps best
18
reserved for very immunosuppressed hosts in whom an atypical etiologic agent
might more likely.
Bacterial cultures from the portal of entry may be most helpful in persons
with atypical clinical presentations.
Treatment. Elevation and rest of the affected limb are recommended to
reduce local swelling, inflammation, and pain.
Saline wet dressings should be applied to ulcerated and necrotic lesion and
changed every 2-12 hours, depending on the severity of the infection.
Streptococci cause most cases of erysipelas; thus, penicillin has remained
first-line therapy. Penicillin administered orally or intramuscularly is sufficient for
most of classic erysipelas and should be given for 10-12 days.
A cephalosporin or macrolide such as erythromycin or azithromycin, may be
used if the patient has an allergy to penicillin. Cephalosporin’s may cross-react
with penicillin first-generation cephalosporin’s and should not be used in patients.
Hospitalization for close monitoring and intravenous antibiotics is
recommended in severe cases and in infants, elderly patients, and patients who are
immunocompromised.
Patients with recurrent erysipelas should be educated regarding local
antisepsis and general wound care. Predisposing lower extremity skin lesions
should be treated aggressively to prevent superinfection.
Long-term prophylactic antibiotic therapy generally is accepted, but no true
guidelines are available. Treatment regimens should be tailored to the patient. One
reported regimen is benzathine penicillin at 2,4 MU intramuscularly every 3 weeks
for up to 2 years.
Complications. The most common complications of erysipelas include
abscess, gangrene, and thrombophlebitis. Less common complications (<1%) are
acute glomerulonephritis, endocarditis, septicemia, and streptococcal shock
syndrome. Rare osteoarticular complications involve joints contiguous with the
erysipelas plagues and include bursitis, osteitis, arthritis.

19
 Prognosis. The prognosis for patients with erysipelas is excellent.
Complications of the infection usually are not life threatening, and most cases
resolve after antibiotic therapy without sequelae. However, local recurrence has
been reported in up to 20% of patient with predisposing conditions.
Lyme disease
Definition. Lyme borreliosis or Lyme disease (LD) is caused by a
spirochete, Borrelia burgdorferi sensu lato, that is transmitted by ticks of the
Ixodes ricinus complex. It’s a multisystem illness that affected primarily the skin,
nervous system, heart and joints.
Etiology. B. burgdorferi sensu lato is a fastidious gram-negative bacterium.
There are a lot of genomospecies of B. burgorferi s.l. but the LD is caused
primarily by three pathogenic Geno species: B. burgdorferi sensu stricto, Borrelia
garinii and Borrelia afzelii. All three Geno species are found in Europe.
Epidemiology. The principal vectors of LD in Europe, – Ixodes ricinus, in
Asia – I. persulcatus, in USA – I.scapularis and I.pacificus. These ticks may
transmit other diseases as well (tick-borne encephalitis, anaplasmosis, erlichiosis,
babesiosis et al.). Ticks of the I. ricinus complex have larval, nymphal and adult
stages. They require a blood meal at each stage. The risk of infection in a given
area depends largely on the density of these ticks as well as their feeding habits and
animal hosts. Because of the small size of ticks most patients do not remember the
preceding tick bite.
LD is now the most common vector-borne infection in the United States and
Europe. During recent years the number of cases in the Europe.
Clinical manifestations. Clinical features of Lyme disease are typically
divided into three general stages termed early localized, early disseminated, and
late persistent infection. These stages may overlap, and most patients do not
exhibit all stages. Direct invasion of the organism with a resultant vigorous
inflammatory reaction has been demonstrated to be responsible for many of the
clinical manifestations associated with Lyme disease, and the manifestations
respond to antibiotic therapy. Some features, such as late neurologic deficits and
20
chronic arthritis, may respond poorly to treatment. It is not clear that live
organisms are responsible for these later symptoms. Seroconversion can occur in
asymptomatic individuals but is rare with strict surveillance.
Early Localized Disease
Erythema migrans (EM), the hallmark of Lyme disease, begins at the site of
a deer tick bite after 3 to 32 days. It is reported by 60% to 80% of patients,
appearing as a centrifugally expanding erythematous macule or papule, often with
central clearing. The thigh, groin, and axilla are common sites. The lesion may be
warm, pruritic, and painful but is often asymptomatic and easily missed if out of
sight. Occasionally, these lesions may develop blistering or scabbing in the center,
remain an even, intense red without clearing, or develop a bluish discoloration.
Spirochetes are present in the EM lesion and can be readily cultured from the
expanding edge. Mild musculoskeletal flulike symptoms such as a low-grade fever,
chills, malaise, headache, fatigue, arthralgia’s, and myalgia may accompany EM
lesions. Theoretically such symptoms can occur without dissemination of the
organism via local generation of cytokines. Untreated EM resolves within several
weeks and treated lesions within several days.
Early Disseminated Disease
In some patients the spirochete disseminates hematogenously to multiple
sites causing characteristic clinical features. Secondary annular lesions, sites of
metastatic foci of Borrelia in the skin, develop within days of onset of EM in about
half of patients. They are similar in appearance to EM but are generally smaller,
migrate less, and lack indurated centers. In addition to musculoskeletal flulike
symptoms, mild hepatitis, splenomegaly, sore throat, nonproductive cough,
testicular swelling, conjunctivitis, and regional and generalized lymphadenopathy
may sometimes occur during early stages.
Diagnosis of early localized and early disseminated Lyme disease is based
on clinical presentation, because serologic confirmation is often lacking and
culture not readily available. A history of a tick bite and residence or travel in an

21
endemic area should be sought in patients presenting with rashes compatible with
EM or a flulike illness in summer.
Specific immunoglobulin M (IgM) antibody responses against B.
burgdorferi develop 2 to 6 weeks after the onset of EM. Immunoglobulin G (IgG)
antibody levels appear approximately 6 weeks after disease onset but may not peak
until months or even years into the illness. The highest titers occur during arthritis.
Antibodies are typically detected using indirect immunofluorescence, enzyme
linked immunosorbent assay (ELISA), and immunoblotting (Western blot).
Antibody responses may persist for months to years after successful eradication of
infection.
Late Disease
Late manifestations of Lyme disease typically occur months to years after
the initial infection. Arthritis is the dominant feature of late Lyme disease, reported
in approximately 60% of untreated individuals. Less often, individuals develop late
chronic neurologic disease. Another late finding (years) associated with this
infection is a chronic skin lesion, acrodermatitis, chronica atrophicans, well known
in Europe but rare in the United States. These late manifestations are discussed
below.
Therapy
EARLY LYME DISEASE
The symptoms of early Lyme disease resolve spontaneously in most cases;
therefore, the goals of therapy for early localized and mild early disseminated
Lyme disease are to shorten the duration of symptoms and reduce the risk of
developing serious late manifestations of infection. Treatment of these stages with
oral antibiotics is adequate in the majority of patients. In patients with acute
disseminated Lyme disease but without meningitis, oral doxycycline appears to be
equally as effective as parenteral ceftriaxone in preventing the late manifestations
of disease. Initial studies of treatment for early Lyme disease reported therapy with
phenoxymethyl penicillin, erythromycin, and tetracycline, in doses of 250 mg 4
times a day for 10 to 20 days, shortened the duration of symptoms of early Lyme
22
disease. Phenoxymethyl penicillin and tetracycline were superior to erythromycin
in preventing late manifestations of disease. Subsequent clinical trials have proven
amoxicillin and doxycycline to be equally efficacious. Amoxicillin has largely
replaced penicillin because of greater in vitro activity against B. burgdorferi. It is
the preferred antibiotic choice in children younger than 8 years. Concomitant use
of probenecid has not been definitively shown to improve clinical outcome and is
associated with a higher incidence of side effects. Doxycycline is usually selected
over tetracycline because of its twice-daily dose schedule, increased
gastrointestinal absorption and tolerability, and greater central nervous system
(CNS) penetration. Doxycycline is effective in treating Anaplasma
phagocytophilum (formerly known as Ehrlichia phagocytophila), an organism also
transmitted by Ixodes scapularis ticks; amoxicillin is not. Cefuroxime axetil, an
oral second-generation cephalosporin, has been shown to be about as effective as
amoxicillin and doxycycline in treating early Lyme disease; azithromycin, an
azilide analogue of erythromycin, somewhat less so. Macrolide antibiotics are not
recommended as first-line therapy for early Lyme disease. Long-term follow-up of
patients treated during early stages of Lyme disease support the current dosing
regimens. Patients who received a 14- to 21-day course of a recommended
antibiotic rarely developed late manifestations of illness. Recent studies have
indicated that a 10-day course of doxycycline is adequate therapy for EM. Jarisch-
Herxheimer-like reactions, an increased discomfort in skin lesions and temperature
elevation occurring within hours after the start of antibiotic treatment, have been
encountered in 14% of patients treated for early Lyme disease.
They typically occur within 2 to 4hours of starting therapy, are more
common in severe disease, and are presumably due to rapid killing of a large
number of spirochetes.
Minor symptoms, including arthralgia, fatigue, headaches, and transient
facial palsy, are common following treatment and generally resolve over a 6-month
period. Patients with disseminated disease are most likely to experience persistent
symptoms. These symptoms may be due to retained antigen rather than ongoing
23
infection with B. burgdorferi, because longer courses of antibiotics have not be
shown to shorten their duration. Prolonged courses of antibiotics should be
reserved for those patients with evidence of persistent infection with B.
burgdorferi.
Lyme Carditis
Cardiac involvement occurs in up to 10% of untreated patients. Transient
and varying degrees of atrioventricular block several weeks to months after a tick
bite are the most common manifestations. Other features are pericarditis,
myocarditis, ventricular tachycardia, and, on rare occasions, a dilated
cardiomyopathy; valvular disease is not seen. Carditis is typically mild and self-
limited, although patients may present quite dramatically in complete heart block,
and some require the insertion of a temporary pacemaker. In most cases, carditis
resolves completely, even without treatment with antibiotics. Studies examining
endomyocardial biopsy specimens from patients with Lyme carditis have indicated
that direct invasion of B. burgdorferi into myocardium and an associated
inflammatory reaction are responsible for the clinical events. Although optimal
treatment of carditis is unknown, oral therapy for mild forms of cardiac
involvement is usually sufficient. Intravenous antibiotics and cardiac monitoring
are recommended for patients with varying high-degree heart block and more
serious cardiac involvement. The benefit of concomitant use of aspirin or
prednisone and antibiotics in treating patients with Lyme carditis is uncertain.
Despite the generally benign course of Lyme carditis, several cases of permanent
heart block have been reported, presumably caused by a vigorous inflammatory
response. Short courses of prednisone may be considered in patients with
prolonged dense heart block despite adequate antibiotic therapy.
Dilated cardiomyopathy is a rare complication of Lyme disease reported in
Europe but not yet in the United States. The majority of the patients were from
endemic areas for Lyme disease, had other clinical features of disease, and were
seropositive for anti-B. burgdorferi antibodies. Their myopathy was cured by
antibiotic treatment.
24
 Early Neurologic Disease
Early neurologic involvement occurs in 15% to 20% of untreated patients
and appears within 2 to 8 weeks after the onset of disease. Manifestations include
cranial nerve palsies, meningitis or meningoencephalitis, and peripheral neuritis or
radiculoneuritis, often appearing in combination. Unilateral or bilateral seventh
nerve palsies are the most common neurologic abnormalities. Presenting symptoms
depend on the area of the nervous system involved: Patients with meningitis
present with fever, headache, and a stiff neck; those with Bannwarth's syndrome
(primarily in Europe) develop severe and migrating radicular pain lasting weeks to
several months; and those with encephalitis have concentration deficits, emotional
lability, and fatigue. In patients with early CNS involvement, analysis of
cerebrospinal fluid (CSF) typically reveals a lymphocytic pleocytosis. Specific
antibodies against B. burgdorferi may also be present and concentrated in the CSF
relative to the serum concentration; they are useful to confirm diagnoses.
Intravenous antibiotics are recommended for all cases of neuroborreliosis
except isolated seventh nerve palsy. Patients presenting with a Bell-like palsy who
have features that suggest possible CNS involvement, such as high fever,
headache, or stiff neck, should undergo a lumber puncture looking for evidence of
more extensive disease. The most experience in the treatment of CNS Lyme
disease has been with aqueous penicillin and third-generation cephalosporins.
Although optimal duration of therapy is unknown, it is recommended that patients
be treated for 2 to 4 weeks. Ceftriaxone, in doses of 1 to 2 g per day, is the agent of
choice because of better CNS penetration and ease of administration. Patients with
persistent symptoms after recommended antibiotic therapy pose a particular
management problem. It is often unclear whether these symptoms are due to
resolving inflammation or ongoing infection. Meningitis and sensory symptoms
usually resolve within days to weeks; other features may take months to improve.
In most cases it is not necessary to continue antibiotic therapy until complete
recovery.
Late Manifestations
25
 ARTHRITIS
Arthritis is the dominant feature of late Lyme disease, occurring in up to
60% of untreated patient’s days to years after initial infection (mean of 6 months).
The initial pattern of involvement may be migratory arthralgia (early) followed in
60% of patients by intermittent attacks of arthritis lasting from days to months.
Large joints, particularly the knee, are most commonly involved. Swelling is often
prominent, with large effusions and Baker cysts. Serologic testing in patients
presenting with arthritis is positive in almost all cases. Lyme arthritis has been
treated successfully with oral and intravenous antibiotics. In early studies
examining response to benzathine penicillin, 2.4 million units intramuscularly
weekly for 3 weeks, 7 of 20 patients responded compared with 0 of 20 in the
control group. Intravenous ceftriaxone, 2 to 4 g daily for 2 to 4 weeks, has been
thought to be superior to benzathine penicillin. Oral regimens using doxycycline,
100 mg twice a day for 4 weeks, and amoxicillin plus probenecid, 500 mg of each
orally 4 times a day for 4 weeks, have re-ported success in 18 of 20 patients and 16
of 18 patients, respectively. However, in 6 patients in each group, resolution of
arthritis did not occur until 1 to 2 months after the 1-month treatment regimen (i.e.,
resolution after sufficient treatment may be slow). Thus, a recommendation of an
additional 4 weeks of oral antibiotics for those with persistent arthritis after the
first month, is arguable. Some effusions take months to resolve completely.
A small subgroup of Lyme arthritis patients develops a chronic, potentially
erosive arthritis unresponsive to antibiotics. These patients often have major
histocompatibility class II gene products, human leukocyte antigen death receptor
4 (HLA DR4) accompanied by strong serum IgG responses to Borrelia outer
surface proteins A or В (OspA or OspB). Repeated courses of antibiotics have not
been shown to improve clinical outcome. Treatment with anti-inflammatory
medications and intra-articular steroid injections can be helpful in reducing joint
swelling. Surgical synovectomy has cured a number of such patients. Resolution of
the arthritis eventually occurs; in some patients it may take 3 to 5 years.
Late Neurologic Lyme Disease
26
 Chronic neurologic syndromes, which are relatively uncommon, may occur
months to years after initial infection. Cognitive dysfunction, affective changes,
seizures, ataxia, peripheral neuropathies, and chronic fatigue have all been
reported. The most common late-stage neurologic syndrome reported in the United
States, called Lyme encephalopathy, is characterized by subtle cognitive
impairment. Because these complaints are often nonspecific, and may be
associated with post-Lyme syndromes, it is important to look for and document
evidence of ongoing B. burgdorferi infection. Lymphocytic pleocytosis is
uncommon in late neurologic disease, but increased intrathecal B. burgdorferi-
specific antibodies may well be present.
Careful evaluation with neuropsychological testing can help to distinguish
cognitive abnormalities in Lyme disease from those associated with chronic fatigue
states and depression. Chronic neurologic dysfunction usually improves with
antibiotics but may not completely reverse. Late neurologic manifestations of
Lyme disease are treated with intravenous antibiotics. Agents with demonstrated
efficacy are aqueous penicillin and third-generation cephalosporins. Doxycycline,
both oral and intravenous forms, have been reported to be successful in treating
late CNS Lyme disease in Europe.
Ocular Disease
Ocular lesions in Lyme disease are rare but have involved every portion of
the eye and vary depending on the stage of the disease. The most common
ophthalmic presentations in early disease include conjunctivitis, photophobia, and
neuroophthalmological manifestations due to cranial nerve palsies. The incidence
of seventh nerve palsies are similar in Europe and the United States. The most
severe ocular manifestations occur in late stages they include episcleritis,
symblepharon, keratitis, iritis, choroiditis, panuveitis, and retina, vasculitis.
Serologic testing in these patients is typically positive.
Experience treating late ocular lesions in Lyme disease is scanty. The most
success has been with the use of intravenous ceftriaxone in doses of 2 to 4 g daily
for 10 to 14 days.
27
 Tick Bites
The risk of infection from a deer tick bite in a Lyme disease endemic area is
low. In mice, infected ticks have been attached for over a 36-hour period before
significant risk of developing Lyme disease occurred. In a controlled double-blind
study in patients with tick bites, no patient asymptomatically seroconverted, no
treated patient developed EM, and the 2 of 182 untreated patients who did develop
EM were successfully treated with oral antibiotics. These results support marking
and watching a tick bite, and should EM develop, treating it early, when antibiotics
are most effective. A single dose of doxycycline has been shown to be effective in
reducing the development of Lyme disease. The Infectious Diseases Society of
America (IDSA) guidelines recommend offering the single-dose doxycycline if the
attached tick can be reliably identified as an adult or nymphal I. scapularis tick, it
is estimated to have been attached for >36 hours, prophylaxis can be started within
72 hours after tick attachment, and the local rate of infection of these ticks with B.
burgdorferi is greater than 20%. Doxycycline prophylaxis for children under 8
years is not recommended.
Seropositive Patients with Nonspecific Symptoms
Patients with nonspecific symptoms such as myalgia, arthralgia,
concentration difficulties, and fatigue are frequently tested for Lyme disease. Some
patients, especially those from endemic areas, test positively and are treated for
presumed Lyme disease, often without improvement in their symptoms. In several
studies, over 50% of patients reporting to Lyme disease clinics did not have
evidence of Lyme disease, and the reason for a lack of response to antibiotics was
an incorrect diagnosis. Objective clinical evidence in support of the diagnosis of
Lyme disease should be sought before initiating antibiotics, treatment should be
given for the recommended duration and then discontinued, and the patient should
be observed for resolution of symptoms.
Post-Lyme Disease Syndrome
Some patients continue to have subjective symptoms after completion of
recommended courses of antibiotics for Lyme disease. Symptoms typically include
28
arthralgia, myalgia, fatigue, and neurocognitive difficulties. A recent study of
patients treated for EM reported that approximately 5% to 15% of patients
experienced subjective symptoms when evaluated 6 to 12 months after treatment.
Such symptoms may persist for 5 or more years after treatment. This syndrome
does not appear to be related to persistent infection with B. burgdorferi. In a study
of patients with post-Lyme disease syndrome there were no significant outcome
differences between the groups who received intravenous ceftriaxone for 30 days
followed by oral doxycycline for 60 days and those that received placebo. The
IDSA guidelines do not recommend antibiotic therapy for patients with chronic
(>6 months) subjective symptoms after recommended treatment regimens for
Lyme disease.
Prevention of Lyme Disease
Recommended personal protective measures against tick bites include
wearing light-colored clothing, long-sleeve shirts, and long pants; tucking pant legs
into socks; using a tick repellent on clothing and exposed skin; and performing
regular body checks for ticks- strategies that require significant self-motivation.
Environmental strategies include the application of acaricides onto vegetation
where the ticks live, acaricides delivered directly to tick hosts to kill ticks on the
animals, and exclusion of deer from targeted areas. The last is not practical in most
environments.
Public interest in human and veterinary vaccines prompted researchers to
develop a safe and effective human vaccine for the prevention of Lyme disease.
The results of two large safety and efficacy trials using recombinant OspA
preparations reported the vaccines to be safe and effective in preventing Lyme
disease in most people. LYMErix was approved by the Food and Drug
Administration (FDA) in 1999 for use in individuals aged 15 and older. The
vaccine manufacturer discontinued production in 2002, citing insufficient
consumer demand. Protection provided by this vaccine diminishes over time.
Individuals who received the Lyme disease vaccine prior to 2002 are probably no
longer protected against Lyme disease.
29
 Anthrax
Bacillus anthracis (anthrax) is a Gram-positive rod-shaped organism that
forms hardy spores and inhabits the soil. The spore form may survive for decades
in the soil under the right environmental conditions.
In nature, anthrax is primarily a disease of herbivores, grazing animals such
as cattle that ingest the organism.
Humans may be infected by three main potential routes of exposure: by
dermal contact, by ingestion and by inhalation. Three types of disease are produced
by these routes, respectively: cutaneous anthrax, oropharyngeal or gastrointestinal
anthrax and inhalational anthrax.
Cutaneous disease is by far the most common human form and is fairly
easily treated with antibiotics. Gastrointestinal and inhalational anthrax cases are
often very severe and have a high case-fatality rate, but may be cured if treated
early and aggressively with antibiotics and intensive supportive care.
Anthrax is widely considered to be a key potential agent of biological
warfare and bioterrorism by the aerosol route.
Epidemiology. Anthrax, derived from the Greek for coal or carbuncle, and
the middle English anthrax for a 'malignant boil', occurs worldwide in animals,
especially in Africa, Asia and in south-eastern Australia. Domestic herbivores
(cattle, sheep, goats, and horses) or wild animals become infected when they ingest
infective B. anthracis spores while grazing in contaminated areas or by eating
contaminated feed or meat. Ingested spores are transformed in vivo into the
vegetative bacilli that cause disease. When the animal dies, the contaminated
carcass and infectious fluids re-contaminate the environment. Some geographic
areas become endemic, where numerous animal cases have occurred, such as in the
American Midwest and Southwest, where cattle were raised and driven to market
over and over. Soil in these areas may be heavily spore-contaminated. The
organism may be spread in the environment as fomites by insects or on the legs of
vultures that have fed on contaminated carcasses.

30
 Human cases occur when humans are exposed to infected animals or animal
products, including hair and wool, meat, hides, carcasses and bone. The majority of
human cases are cutaneous and associated with dermal exposure; more rarely
gastrointestinal cases are caused by ingestion of contaminated meat and
inhalational cases by inhalation of spores. In developed countries, cases tend to be
sporadic and relatively rare, but in the developing world, large outbreaks can
occasionally occur such as the one seen in Zimbabwe from 1978 to 1980, with an
estimated 6000-10000 cases. Inhalational anthrax has been referred to historically
as 'wool-sorters' disease' because it had a propensity to occur in industrial settings
where spore-contaminated animal hides were handled. In 1957, five cases of
inhalational anthrax occurred in a plant in Manchester, New Hampshire,
culminating in four deaths. However, inhalational disease is relatively rare - only
18 cases were reported in the USA in the twentieth century. In the 1800s, a number
of cases occurred in the Bradford district of Britain, where a number of animal hair
factories were located.
Anthrax is also often mentioned prominently as a potential agent of bio
warfare and bioterrorism. In the 1950s and 1960s, both the USA and the former
Soviet Union developed anthrax as a biological weapon, as have other countries
such as Iraq, more recently. An accidental release of air-borne anthrax spores from
a bioweapons production facility in the town of Sverdlovsk (now Ekaterinburg) in
the former USSR (now Russia) in April of 1979, caused at least 66 deaths in
persons downwind of the factory. In the autumn of 2001, a perpetrator mailed
anthrax-laced letters to several high-profile sites along the East Coast of the USA,
causing 22 cases of disease (11 inhalational and 11 cutaneous), five deaths among
the inhalational cases, and contamination of newsrooms, congressional office
buildings and postal facilities.
Pathogenesis and Pathophysiology. Anthrax is caused by a large, aerobic,
non-motile, Gram-positive rod that forms spores under certain environmental
conditions. The spores are relatively resistant to heat, desiccation and ultraviolet
light exposure, especially in soil. The vegetative bacilli form grey-white colonies
31
on growth media; colonies which have a ground-glass appearance. Most isolates
are non-hemolytic. Many different strains of anthrax exist and there is genetic
diversity even within strains.
The pathology produced by Bacillus anthracis is related to a number of
virulence mechanisms. These include the antiphagocytic capsule of the vegetative
organism, encoded on a plasmid called pX02, and several toxins encoded on
another plasmid called pXO1. Included among these are protective antigen (PA),
lethal factor (LF) and edema factor (EF).
After exposure to anthrax spores, macrophages engulf the spores and carry
them into the lymphatics, where they germinate into vegetative Gram-positive rod-
shaped bacilli. The toxin-producing bacilli multiply and, after cytolysis, enter the
bloodstream and are carried throughout the body. The bacilli release protective
antigen (B subunit) and edema and lethal factors (A subunits). PA combines with
edema factor to form edema toxin; likewise, lethal factor and PA combine to form
lethal toxin. EF is a calcium- and calmodulin-dependent adenylate cyclase,
whereas LF is a zinc-dependent metalloprotease. PA forms a heptameric structure
after attaching to anthrax toxin receptors on cell surfaces - this structure functions
to facilitate endocytosis of bound lethal factor and edema factor into cells,
followed by translocation of the toxins into endosomes. The toxins are released
inside the cell and mediate increases of cyclic AMP with alterations of cell water
homeostasis (EF), impairment of neutrophil function (EF), and inhibition of other
pathways involving immune function and signal transduction, as well as cytolysis
and release of proinflammatory mediators and lysosomal enzymes (LF). Full
virulence of the anthrax organism requires the presence of the antiphagocytic
capsule and all three toxin components. The anthrax toxins themselves may also
cause significant alterations in peripheral vascular function and direct deleterious
effects on myocardial and renal function thus contributing directly to the
pathogenesis of severe anthrax disease. It has recently been demonstrated that there
is human genetic variation in cellular sensitivity to anthrax toxins because of
differences in genetic expression of several host cell surface proteins that function
32
as receptors for the PA-LF and PA-EF toxins. In 254 people studied, the cells of
three persons were virtually insensitive to the toxins, whereas the cells of some
were hundreds of times more sensitive than those of others.
In inhalational anthrax, spores are carried to the perihilar and mediastinal
lymph nodes, where they germinate and the organisms multiply rapidly, producing
a hemorrhagic thoracic lymphadenitis, mediastinitis and pleural effusions.
Septicemia and toxemia then occur and microbiological concentrations of bacilli in
blood and body fluids can become very high. Over-whelming infection leads to
sepsis, spreads to other organ systems, impairs ventilatory function, acidemia and
ultimately death. Inhalational anthrax has been said to have an 80-100% case-
fatality rate, however with modern intensive supportive care and aggressive
antibiotic treatment, 45% of inhalational anthrax patients in the 2001 mail attacks
survived.
Clinical features. Clinical features of anthrax depend on the route of
exposure to the organism. The most common clinical form of the disease is
cutaneous anthrax, due to dermal exposure, accounting for 95% of all cases.
Cutaneous anthrax tends to occur in areas where the skin is abraded or cut,
allowing penetration and localized infection. After 1-5 days, a small erythematous
papule develops at the site of inoculation and develops into a vesicle containing
fluid, serosanguineous in nature, in 1-2 more days. The vesicle then ruptures and a
necrotic ulcer forms centrally; the central ulcer may also be surrounded by smaller
peripheral vesicles. The ulcer then evolves into a central black eschar of 1-3 cm
diameter over a week or so. The eschar finally separates after 1-2 more weeks,
leaving a scar. The lesion is often surrounded by edema that in some cases may be
extensive, and patients often have fever, malaise and headache. The skin lesion is
characteristically non-pruritic and non-purulent. The timing and progression of the
skin lesion may not be changed significantly by antibiotic therapy. Mortality of
cutaneous anthrax is less than 5% with adequate antibiotic treatment, and sepsis is
rare.

33
 Gastrointestinal anthrax results from the consumption of contaminated meat
and is extremely rare. Ingestion of spores results in a full-blown hemorrhagic
gastroenteritis. Signs and symptoms may include fever, abdominal pain that may
be severe, hematemesis, bloody diarrhea, hypovolemia and prostration. Intestinal
obstruction or perforation and ascites may occur. Sepsis is common and the case
fatality rate is high, at 25-75%. There is also a rare oropharyngeal form of disease
associated with spore ingestion. This form presents with severe sore throat, neck
swelling, adenopathy, and dysphagia. Tonsillar or pharyngeal pseudo membrane
formation and respiratory compromise may occur.
Inhalational anthrax results from inhalation of infectious spores that are
usually from 1 to 5 microns (µm) in size. The estimated LD50 calculated from
animal studies is 8000-10000 spores, although, because of host factors, a much
smaller spore dose may cause infection and death in some individuals. The small
spore size allows penetration of the agent deep into the lungs and into the terminal
bronchioles and pulmonary alveoli. Pulmonary macrophages take up the spores
and they migrate to the perihilar and mediastinal lymph nodes where the spores
germinate and form vegetative bacilli. Localized mediastinal and nodal infection
occurs and bacilli are released into the bloodstream, causing toxemia and
septicemia. Animal studies have revealed that bacilli and toxins appear in the
bloodstream late on day 2 or on day 3, after aerosol challenge. Spread to other
organ systems such as the CNS occurs. After an incubation period of 1-6 days,
patients with the inhalational form of the disease develop fever, malaise and
fatigue, often with chest discomfort and a non-productive cough; headache,
drenching sweats, nausea and vomiting, myalgia and confusion may also occur.
These manifestations may last 2-3 days, sometimes followed by a brief period of
symptomatic improvement. These early phases are then followed by sudden
deterioration, with severe respiratory distress, dyspnea and stridor, diaphoresis and
cyanosis. Chest radiographs at this stage may reveal significant mediastinal
widening and often, pleural effusions that may be hemorrhagic. Pneumonic
infiltrates or consolidation may be seen on chest X-ray or CT scan but actual
34
bronchoalveolar pneumonia is rarely found on autopsy. Sepsis, shock and death
typically occur within 24-36 hours of clinical deterioration. Hemorrhagic
meningitis is present in about 50% of cases of inhalational anthrax. Mortality in
inhalational anthrax is very high: 80-90% if untreated. Even with aggressive
intravenous antibiotic treatment and intensive supportive care, mortality is still
almost 50% (5 out of 11 patients died in the 2001 anthrax mail attacks). Survivors
may have significant sequelae for months or even years.
Differential diagnosis of cutaneous anthrax may include cutaneous
diphtheria ulcer glandular tularemia, localized rickettsia infection after a tick-bite,
bubonic plague, bacterial infection such as Staphylococcus aureus or Streptococcus
pyogenes, and necrotizing arachnidism (spider envenomation). Oropharyngeal
anthrax may be confused with diphtheria clinically. Inhalational anthrax would
usually only be suspected clinically with potential occupational exposure or in a
known bioterrorism attack. A high index of suspicion by an astute clinician is
critical to the diagnosis. The inhalational form might be confused with other forms
of severe respiratory disease, pneumonia, septicemia and meningitis.
Diagnosis. Inhalational anthrax is initially a clinical diagnosis requiring a
high index of suspicion. Recent history of occupational exposure or a bioterrorism
attack is helpful. In such a historical setting, a severe infectious illness with
respiratory compromise and widening of the mediastinum with or without pleural
effusions on chest radiograph should be considered pathognomonic. Pleural fluid
or CSF is often bloody. Fever, tachycardia, hypotension and hypoxemia with
elevated alveolar-arterial oxygen gradient may be present.
Clinical laboratory features may include an elevated leukocyte count,
neutrophilia, elevated transaminases, metabolic acidosis and elevated creatinine.
Definitive laboratory diagnosis can involve a number of tests. Gram-staining
of infected fluids or blood may reveal numerous Gram-positive rods in high
concentration. The gold standard and most sensitive test is still classical
microbiological culture of the organism from skin lesion aspirate, blood, pleural
fluid or cerebrospinal fluid. Standard blood culture should show growth within 24
35
hours. Colonies are non-hemolytic on 5% sheep blood agar and are tyrosine
deaminase negative.
Several other tests are useful in the reference laboratory. These include IFA
with microscopy, ELISA, gamma-phage sensitivity, electro-chemiluminescence
and nucleic acid amplification (PCR).
Pathology may also be helpful. Examination of punch biopsy specimens
from a skin lesion may reveal the characteristic rod-shaped organisms. Postmortem
pathological findings may include thoracic hemorrhagic lymphadenitis,
hemorrhagic necrotizing mediastinitis and hemorrhagic meningitis.
Treatment. Management and treatment of the different clinical forms of
anthrax is complex and depends on: the potential route(s) of exposure; infectious
dose to which exposed; host immunocompetence; age; possibility of pregnancy;
severity of illness and other factors. All the nuances of management and antibiotic
treatment are beyond the scope of this chapter and the reader should refer to more
comprehensive, definitive references for consensus treatment recommendations,
including antibiotic options and dosages.
Cutaneous anthrax in a setting where there is no risk of inhalational infection
and no immune compromise may involve treatment with only 7-10 days of
antibiotics. Oral penicillin, ciprofloxacin and doxycycline are the antibiotic
options. Consensus recommendations call for ciprofloxacin or doxycycline until
penicillin sensitivity is proven. A total of 60 days of treatment is recommended if
there has been risk of aerosol exposure and the possibility of retained spores in the
lung.
Antibiotic options for inhalational anthrax also include penicillin,
ciprofloxacin and doxycycline. Antibiotics should be started immediately if the
disease is suspected. Patients treated early, before severe disease develops, are
more likely to survive. Penicillin was the classic treatment historically, as most
natural strains are sensitive, however concerns about penicillin resistance or
bioengineered resistant strains have prompted a recommendation for initial
treatment with IV ciprofloxacin, especially in the setting of a suspected
36
bioterrorism attack, until antibiotic sensitivities are determined. In patients with
inhalational anthrax following the 2001 attacks, there was clinical information to
suggest that patients treated with two or more antibiotics active against B. anthracis
were more likely to survive. Thus, consensus recommendations in the wake of
those attacks suggested that two or more antibiotics with in vitro activity should be
used initially. In addition to ciprofloxacin (and other fluoroquinolones) and
doxycycline, antibiotics with in vitro activity against B. anthracis include
clindamycin, rifampin, imipenem, aminoglycosides, chloramphenicol,
vancomycin, cefazolin, tetracycline, linezolid and the macrolides. Even in patients
with full-blown inhalational anthrax who recover, antibiotic treatment for 60 days
(switch to oral treatment after clinical recovery) due to the possibility of retained
un-germinated spores in the lung, is recommended. Consideration of CNS
penetration of antibiotics through the blood-brain barrier may be important in cases
where anthrax meningitis is present.
Intensive supportive care in the ICU is critically important for inhalational
anthrax patients. Antibiotics may sterilize the blood after a few doses, yet in
patients where antibiotic therapy is begun after clinical deterioration, the outcome
is usually poor. Ventilatory support, maintenance of adequate perfusion and
oxygenation, and fluid management are all very important. Newer therapies that
may be available, including anthrax immune globulin (AIG) and monoclonal
antibody treatments against anthrax toxins, may be important for enhanced
survival.
Prevention. Prevention of anthrax poisoning involves either prevention of
exposure in occupational settings or immunization. In high-risk settings,
immunization is preferred. In the USA, there is one FDA-licensed anthrax vaccine
- Anthrax Vaccine Adsorbed (AVA, trade name BioThrax) - produced by a
company called Emergent Biosolutions (formerly known as Bioport Corporation).
This vaccine is a protective antigen-based product and works by stimulating
antibodies to PA, thus inhibiting the ability of EF and LF toxins to enter human
cells. It is given intramuscularly (IM) in the deltoid muscle in a five-dose series at
37
0 and 4 weeks, with three more injections at 6, 12 and 18 months. If risk of
exposure continues, yearly boosters are recommended. Although there has been
some resistance to use of AVA in some groups at risk (postal workers after 9/11
and a very small percentage of military recipients), it has been shown to be a
generally safe and effective vaccine with relatively mild side-effects such as
erythema and swelling at the injection site. Next-generation recombinant-PA
vaccine candidates are under development but thus far none are licensed in the
USA.
In the setting of a suspected bioterrorism event, those suspected of aerosol
exposure to anthrax should receive post exposure prophylaxis (PEP). PEP consists
of 60 days of oral antibiotics, usually ciprofloxacin or doxycycline, with or without
vaccination with AVA. Although animal studies have shown that 30 days of
antibiotics in combination with anthrax immunization during the same period
protects against inhalational anthrax after antibiotic cessation, the official
recommendation has been 60 days of antibiotics, regardless of whether the patient
receives AVA immunization, due to concern about retained viable spores in the
lungs that might still germinate after the end of PEP antibiotic therapy. Patient
compliance with 60 days of antibiotics may be poor, especially in well-feeling
individuals, and close monitoring of those with potential aerosol exposure for onset
of fever or other characteristic symptoms is important.
Staphylococcal infection
Staphylococcal infection - is a group of infections caused by Staphylococcus
aureus, occurring from relatively minor skin infections (skin inflammation) to
more serious infections (pneumonia, sepsis (inflammation in all organs of a person
or "blood-poisoning")).
Etiology. Cause of the disease - staphylococci which are Gram-positive
cocci, belong to the Micrococcaceae family. These bacteria have a regular
spherical shape and are fixed. In a smear staphylococcus aureus form clusters or
bunches of grapes. There are three types of staphylococci causing pathology: S.

38
aureus – the most dangerous, S. epidermidis – less dangerous, but also pathogenic,
S. saprophyticus – almost indifferent, but able to cause disease.
Characteristics of bacteria: Staphylococci are facultative anaerobes that can
live and multiply in the presence of oxygen, and without it. They get their energy
by oxidative and fermentative ways.
Bacteria are resistant to frost, heat, sunlight and to certain chemicals
intervention. Staphylococcal enterotoxin is destroyed by a long time boiling or by
hydrogen peroxide intervention.
Antibiotics resistance is a problem of modern medicine. In health-care
centers new multiresistant strains are constantly formed. Methicillin-resistant
staphylococci are important in epidemiological terms.
Pathogenicity factors: enzymes are hyaluronidase, fibrinolysin, lecithinase;
Toxins are hemolysin, leukocidin, enterotoxins, exfoliatin. Fibrinolysin
helps microbes to penetrate into the blood and to develop sepsis or blood
poisoning.
Hemolysin suppresses the activity of immune cells and helps staphylococci
to exist in areas of inflammation for a long time. Due to these factors children and
the elderly people have a multisystem type of infection. Exfoliatin damages skin
cells.
Leukocidin destroys white blood cells. Enterotoxin is a strong poison
produced by staphylococci and causes food toxic infection.
Epidemiology. Sources of infection are patients and bacilli carriers. Germs
enter the human body through scrapes and scratches on the skin and through
mucous membranes of the respiratory system, urinary and digestive system.
The main ways of pathogen transmission: airborne, airborne dust, home,
alimentary.
Factors contributing to the development of infection: weakened immune
system, long-term use of antibiotics, hormones or immunosuppressant, endocrine
disorders, viral infections, acute exacerbation of chronic diseases, long term
chemotherapy or radiotherapy, environmental hazards exposure.
39
 Pathogenesis. Germs enter the body through the skin, orally, through
respiratory system, digestive system, eyes. Staphylococci implementation develop
purulonecrotic inflammation. The further process can have two scenarios:
1.Strong specific immunity does not develop the disease and contributes to
the rapid focus elimination.
2. The weakened immune system cannot fight off the infection. The
pathogen and toxins being in blood develop bacteremia and intoxication. With the
generalization process staphylococcus affects the internals with the development of
septicemia and septicopyemia.
Pathomorphological changes. Staphylococci areas form the focus which
consists of microbial cells, serous or hemorrhagic discharge, leukocyte infiltration
around the necrotic changes in tissues. Boils, cellulitis and carbuncles appear when
the skin is infected. Bacterial oropharynx damage leads to the development of sore
throat or stomatitis. In the lungs there are signs of abscess pneumonia with the
presence of large subpleural focuses. In the intestine staphylococcus causes the
ulcer, catarrh or inflammation with necrotic lesions of the epithelium and the
deeper tissues, infiltration of the mucosa, blood circulation disorder and the
formation of ulcers.
Sepsis is characterized by hematogenous germs spread, their penetration into
the internals, bones, central nervous system with the development of metastatic
focuses of inflammation.
Clinical signs of disease are determined by the area of bacteria
implementation, by the degree of its pathogenicity and the activity of the person’s
immune system.
Skin affected by staph develops pyoderma. The pathology presents as an
infection of a hair follicle, which causes a pus-filled bump to develop. Necrotic
staphylococcal skin diseases include boils and carbuncles, which are acute
inflammation of the hair follicle, sebaceous gland, skin around and subcutaneous
fat. Particular danger to a person’s health is the location of inflammatory lesions on
the face and head. In case of unfavorable course of disease, the formation of
40
abscesses in the brain or the development of purulent meningitis are possible.
Purulent fusion of deep-seated tissue is called abscess or cellulitis. Abscess
inflammation is limited to the capsule, which prevents the spread of the process of
the surrounding tissue. Cellulitis is diffuse purulent inflammation of the
subcutaneous fat. Purulent fusion of deep-seated tissue is called abscess or
cellulitis.
Staphylococcal etiology pneumonia is a heavy but quite rare pathology. The
manifestations of pneumonia are intoxication and pain syndromes, respiratory
failure with pronounced dyspnea. Complications of the disease are lung abscess
and empyema.
Purulent inflammation of the meninges of staphylococcal origin developed
by the penetration of bacteria through the bloodstream from focuses of infection of
the face, in the nasal cavity or paranasal sinuses. Patients have advanced
neurological symptoms, signs of meningism, epilepsy, alteration of consciousness.
Osteomyelitis is a purulent infectious-inflammatory disease that affects the
bone, the periosteum and bone marrow. Purulent lesions located in the bone, often
break out. Signs of the disease are pain, tissue swelling, pus formation of fistulas.
Staphylococci often affect large joints with the development of
arthrempyesis, which causes pain, stiffness and limited excursion, joint deformity
and the intoxication development.
Staphylococcal endocarditis is an infectious inflammation of the connective
tissue of the heart lining its inner cavity and valves. Symptoms of the disease are
fever, pain in muscles and joints, chills, sweating, pale skin, appearance of rashes
and small dark red nodules on the palms and feet. Auscultation detects heart
murmur. Endocarditis is a severe pathology, leading to the development of heart
failure and is characterized by a high mortality.
Infectious-toxic shock syndrome is a medical emergency determined by
bacteria and their toxins influence on the human body. It is manifested by severe
intoxication, dyspepsia, confusion, symptoms of cardiovascular and kidney failure,
collapse.
41
 Food toxicosis develops as a result of consumption of toxins containing food
staphylococcus, and often proceeds by type of acute gastritis. After a short
incubation period - 1-2 hours - there are severe intoxication and indigestion.
Vomiting is often the result of dehydration.
Diagnosis of staphylococcal infection is based on the data from
epidemiological anamnesis, patient complaints, common clinical picture and
results of laboratory tests.
The main diagnostic method is a microbiological examination of nasal
discharge. For this purpose, patients are usually taken a throat swab for
staphylococcus. The material for the study can be blood, pus, ears, nose, wound
and eyes discharge, pleural exudate, feces, gastric washings, vomit, Fluor cervical
(for women), urine. The aim of the study is to identify completely the pathogen for
the genus and type.
The examined material is used to prepare a series of decimal dilutions and
seeded with the required amount of one of the elective substrate - milky bile-salt or
egg yolk-salt agar. The number of colonies is counted and studied.
To determine staphylococcal enterotoxin in the test samples the method of
enzyme immunoassay or gel precipitation test are used.
Serodiagnosis identifies the blood serum of antibodies to antigens of
staphylococcus. For this purpose, hemolysis inhibition test, passive
hemagglutination test and EIA are used.
Meningococcal infections
Meningococcal infection is still a worldwide problem. The causative agent
of meningococcal infection is Neisseria meningitides (meningococcus) is a gram-
negative bacterium that is often called Diplococcus. Neisseria meningitides can
cause a variety of infections; bacteremia and meningitis are most common. The
clinical manifestations are varied and range from transient bacteremia to fulminant
disease culminating in death within hours of the onset of symptoms.
Etiology. Neisseria meningitides is classified into different serotypes on the
basis of its capsular polysaccharides. Most cases of meningococcal infection are
42
associated with serotypes A, B and C. But in general we саn recognize now at least
13 serogroupes. Serogroupes В and C responsible for the majority of cases in
Europe and America, serogroupes A and C in Asia and Africa.
Epidemiology. Humans are the only natural reservoir of Neisseria
meningitides (anthroponotic disease). It can be:
1. Asymptomatic carries (from 5 to 10% of population are asymptomatic
carries).
2. Patients with localized or generalized forms of meningococcal infection.
Transmission route:
1. The main transmission route for meningococci is the air-borne-droplet
mechanism, generally over short distances.
2. Direct contact transmission of infection is possible through contact with
respiratory secretions.
Neisseria meningitides frequently lives in the upper respiratory tract with no
evidence of illness. Some event is thought to trigger the onset of aggressive
behavior of the organism and sporadic cases of meningococcemia and meningitis
appear.
Family members and those closely exposed to an infected individual are at
increased risk. The infection occurs more frequently in winter and early spring.
Pathogenesis. The portal of entry is the mucosa of the fauces and the
nasopharynx where inflammation develops (catarrh of the upper respiratory tract,
rhinitis, nasopharyngitis). Only in a small portion of the patients, meningococci
overcome the local barrier (lymphatic throat ring) and enter the blood that carries
them to various organs and tissues to cause bacteremia. If the disease is mild,
bacteremia is manifested by polymorphous rash which subsides in few hours.
In person’s sensitive to meningococci, the disease runs the course of
meningococcaemia that can be attended by arthritis, endocarditis, lesions of the
renal vessels, etc. In some patients, the microbes reach the pia mater to provoke
suppurative inflammation. If the grey substance is involved, meningoencephalitis
develops.
43
 Toxic and allergic components play an important role in the pathogenesis of
meningococcal infection. Toxemia is more pronounced in severe septic forms of
the disease. In view of massive decay of meningococci, endotoxin is produced
which affects small blood vessels and impairs circulation of blood, causes
hemorrhage into the skin, mucosa, serous membranes, and into the parenchyma of
the internal organs. Purulent meningitis is due to transportation of the microbes by
the blood into the pia mater encephali and spinalis.
Profuse purulent exudate on the surface of the frontal and temporal lobes of
the brain looks like a pus cap.
Clinical picture. The incubation period lasts 4-6 days with extremes of 2
and 10 days.
Principle clinical forms:
1. Localized forms (carrier form, acute nasopharyngitis).
2. Generalized forms (meningococcemia, meningitis, meningoencephalitis,
mixed forms).
3. Rare forms (endocarditis, polyarthritis, pneumonia, iridociclitis).
Acute nasopharyngitis is diagnosed mostly during epidemic outbreaks, it
can be an independent manifestation of the disease or a prodromal stage of
meningitis or meningococcaemia.
The main symptoms are headache, vertigo, lassitude, pallor, dry cough, sore
throat, edema and hyperemia of the posterior pharyngeal wall, hyperplasia of the
lymphoid follicles, herpes, and stuffy nose. The body temperature is elevated
during 1-3 days, mucosal inflammation persists for 5-7 days, and follicular
hyperplasia to 2 weeks.
Pneumonia of meningococcal etiology usually runs a severe course with
liberation of great amounts of sputum; pleurisy is common.
Meningococcaemia begins suddenly with a chill, headache, and elevation of
temperature to 40 °C and higher (intermittent or continuous fever). Hemorrhagic
rash is a specific symptom. Rash is usually petechial with irregular firm eruptions
of various size, which are slightly raised over the skin of the buttocks, dorsal
44
surface of the thighs and shins. Hemorrhage into the sclera and faucial mucosa,
micro- and macrohaematuria, lesions of the joints, pneumonia and endocarditis are
possible. The symptoms of toxemia are pronounced: tachycardia, low arterial
pressure, cyanosis, dyspnea, dry skin, and thirst. The symptoms of meningitis are
absent. Leukocytosis is marked (with the shift to the left).
Fulminating meningococcal sepsis with shock and adrenal hemorrhage (the
Waterhouse-Friderichsen syndrome), meningococcaemia with acute adrenal failure
develops suddenly, in full health. Within few hours the body temperature rises, the
patient experiences chill, vertigo, weakness, confusion, myalgia, vomiting, and
convulsions. Cyanosis and dyspnea then develop, the body temperature drops to
normal and the arterial pressure becomes low.
The pulse is thread, fast, and soon becomes indeterminable. Petechial lesions
and intensive haemorrhages develop in the skin. Nosebleed, gastric and uterine
hemorrhage are also possible. The symptoms of meningitis are marked (mixed
form).
Neutrophilic leukocytosis is seen. The cerebrospinal fluid is usually
serosanguinous.
Meningitis usually begins suddenly with a shaking chill. The body
temperature rapidly rises to 39-40 °C; severe headache, vertigo and vomiting
develop. Nurslings can develop convulsions, comatose state and the fontanelle
triad (protrusion of the frontal fontanelle, its tension, and the absence of normal
pulsation).
Skin hyperesthesia, hypersensitivity to light and sound stimuli, stable
dermographism, herpes on the lips and the face can also develop. By the end of the
first day, or early on the second day, signs of meningeal involvement become
apparent: stiff neck (the patient cannot bend his head to touch the chest with the
chin), the Kernig symptom (the patient is unable to extend the leg when the thigh is
flexed on the abdomen), and the Brudzinski sign (an attempted flexion of the neck
usually results in flexion of the thigh and leg). The abdomen is sunken. The patient

45
assumes the specific posture with his head tilted back and the thighs raised to the
abdomen.
The cranial nerves can be involved to cause strabismus, anisocoric, paresis
of the facial nerve, and lesion of the acoustic and abducent nerves. The psychic
activity can also be upset: the patient can be drowsy, his consciousness can be
confused or lost, delirium can develop.
Tachycardia is followed by bradycardia due to swelling and edema of the
brain. Leukocytosis is marked (20-40 x 109/1) with a neutrophilic shift; ESR is
high and an eosinophilia is seen.
During puncture, the cerebrospinal fluid issues under pressure. On the first
day of the disease it is clear, but later it turns cloudy and purulent. The examination
of the cerebrospinal fluid reveals neutrophilic cytosis (12-30 x 109/1) and high
protein content (to 1-3 g/1). The cerebrospinal fluid can ooze by slow drops due to
its high viscosity, high cytosis and protein content, and also due to partial blockage
of liquor ducts. If treatment begins timely, the disease usually ends by complete
recovery in 12-14 days.
The clinical forms of meningitis are varied. The meningeal symptoms are
mild in meningoencephalitis, while the symptoms of encephalitis are more
pronounced. These are deranged consciousness, muscular cramping, early paralysis
and paresis. The hypertoxic fulminating form of meningitis, the main meningeal
symptoms are quite pronounced. Symptoms of severe toxemia are manifested:
incoercible vomiting, muscular cramping, confusion, cardiovascular failure;
swelling of the brain and wedging of the cerebellar tonsils into the great foramen,
which is manifested by severe headache, drowsiness, stupor, motor anxiety,
hyperemic face and neck, and confusion. Arterial pressure increases.
Cardiac and/or respiratory failure develops and the patient can die during the
first day of the disease.
Prognosis. Early treatment results in a good outcome. When the shock
develops, the outcome is more guarded. Profound shock, DIC (a severe bleeding

46
disorder), and adrenal collapse all predispose the patient to a poor prognosis with
possibility of a death.
Complications. Profound shock, dissemination intravascular coagulopathy
(DIC), Waterhous-Frideric syndrome.
Diagnosis. Meningitis is diagnosed on the basis of clinical and
epidemiologic findings.
Other tests include the following:
1 Elevated white blood cell (WBC) count
2 Spinal tap for spinal fluid (CSF) showing increased white blood cells
(more then 1000/ml, neutrophilic pleocytotosis - 80 %, color is gray, opening
pressure increase.
3 CSF culture growing meningococci
4 Meningococci usually саn be isolated from blood and CSF and
occasionally are found in the petechial aspirate, pleural ore pericardial fluid.
Treatment. Acute nasopharyngitis of moderate severity should be treated
with sulpha drugs in a dose of 4-6 g a day for adults and 0.3 g/kg for children in
the course of 3-5 days. Prolonged action sulpha drugs (sulphapyridazine or
sulphadimethoxin) can be given to adults in a dose of 2 g during the first day and 1
g during subsequent 4 days.
Meningitis and meningococcaemia patients are treated with antibiotics.
Penicillin should be given in daily doses of 300 000 U/kg for 5-8 days for adults
and 300000-400000 U/kg for infants under 3 months of age. The daily dose is
given intramuscularly at a 4-hourinterval maximum, and to infants under 2 months,
at 3-hour intervals. Treatment should be continued for 5-8 days (until the
cerebrospinal fluid normalizes). Chloramphenicol sodium succinate given in a dose
of 0.05-0.1 g/kg for 6-8 days is highly effective.
Ampicillin (0.15-0.2 g/kg a day) and other antibiotics can also be prescribed.
Aetiotropic therapy is given simultaneously with pathogenetic treatment which
depends on severity of the disease and the presence of complications. Toxemia can
be controlled by administering a sufficient amount of fluid containing the
47
necessary amounts of salts to maintain the electrolyte balance. The liquid can be
given per os or intravenously (polyion solutions, glucose, haemodez, plasma).
Dehydration is attained by diuretics. Septic shock should be managed by infusion
of polyion solutions (Locke- Ringer solution, etc.), a 5 per cent glucose and colloid
solutions (polyglucin, plasma, albumin, protein) that should be injected until pulse
reappears, and then the solution should be given by drip.
Glucocorticosteroids (hydrocortisone, prednisolone) should also be given. In
order to improve the cardiovascular function, strophanthin, corglucon,
cocarboxylase, and ascorbic acid should be administered.
Acidosis is corrected by a 4 per cent sodium hydrocarbonate or lactate
solution. Symptomatic treatment and adequate nutrition are also necessary.
Adequate patient care is important too.

Hemorrhagic fever with renal syndrome (HFRS)

This disease is known as HFRS, epidemic hemorrhagic fever, Korean

hemorrhagic fever, epidemic nephritis nephropathica, epidemic Balkan
hemorrhagic fever.
HFRS occurs mainly in Europe, Asia and characterized by fever and renal
failure and hemorrhagic manifestations.
First this disease was recognized between 1913 and 1930 by soviet scientists
during sporadic outbreaks of fever with renal syndrome in the eastern Soviet
Union. Later disease occurs in North America, Korea, Europe.
Etiology. The disease is caused by the arbovirus, genus hantavirus, it is
RNA virus, lipid envelope, deactivating one’s ordinary disinfectants. The severity
of illness depends on the type of infecting virus and on the geographic distribution.
Korean hemorrhagic fever is a severe type of HFRS observed in Asia and
caused by hantavirus.
Balkan hemorrhagic fever is a severe type of HFRS and caused by Dobsava
virus, observed in Balkan continent.

48
 Nephropathia epidemica is a mild borne of HFRS, which occurs in Europe,
China and caused by the Puumala virus.
Epidemiology. HFRS is caused by an airborne contact with secretions from
rodent hosts, infected with the group of viruses. The severity of this disease
depends on the type of virus and on the geographic distribution.
-Korean HF is transmitted by the infected apodemus agrarius (field mouse)
and is a severe form of HFRS. This disease is observed in Asia.
- Balkan HF is a severe type of HFRS caused by the Dobrava virus, and
transmitted by the infected apodemus flavicollis (yellow-necked field mouse), it
occurs in Balkan continent .
- HFRS due to Seoul virus is transmitted by the infected Rattus rattus (black
rat) or the Rattus norvegiculis (urban rat) and it is mild or moderate form of the
disease.
- nephropathia epidemica is a mild form of HFRS observed in Europe
caused by the Puumala virus and transmitted by the infected clethrionomys
glareolus (European bank vole).
Inoculation of the microorganism into human in the natural body is by
acrogenic route, by contact and alimentary route. Sporadic cases of HFRS are
registered during all year, predominantly in human. Group disease occurs
predominantly in summer and autumn.
Pathogenesis. The immune mechanisms play an important role in HFRS
pathogenesis. The cytokine production, complement pathway activation or an
increase in circulating complexes occur and play an important role during febrile
and hypotensive stages. Damage of the vascular endothelium, leakage, capillary
dilation is significant features of the disease.
Nitric oxide productions increase in the active phase of disease. In the
kidneys venous stage with serous – hemorrhagic edema development causes
degenerative changes in the epithelium cells and appearing of fibrin into kidneys
caniculla.

49
 So serous-hemorrhagic nephritis in both kidneys and acute destructive and
obstructive hydronephrosis may develop.
Clinical manifestation. The incubation period in HFRS may range from 1
to 2 weeks in average, but may last until to 8 weeks. The disease may range from
mild to severe subclinical infection are especially common among children. The
onset of disease is sudden. Initially infancy headache, back, abdominal pain, fever
chills, nausea.
Hushing of the face, inflammation or redness of cyst or rash, later – low
blood pressure, vascular leakage, acute kidney values.
The severity of the disease is associated with type of HFRS agent.
Hantavirus and Dobravas virus infection are usually severe, Seoul, Searemaa,
Rumula virus infections are usually moderate course of disease can include five
stages.
1. Febrile stage lasts about 4-6 days. The asset of disease is abrupt with
high fever up to 40C. The patient complaints are headache, chills, abdominal, back
pain and malaise. During examination of patients can be revealed blushing of the
face, neck, chest, petechiae on the soft palate, axilla. Subconjunctival hemorrhage
bradycardia may be noted.
2. The hypotensive stage lasts from a few hours to 2 days. It is
characterized by decreasing of the blood pressure, tachycardia, acute abdominal
pain, convulsion or purposeless movements. Blood examination in this stage may
reveal the changes of coagulation profile such as elevation of the prothrombin
time, activation of partial thromboplastin time, prolongation of bleeding time.
3. The oliguria stage lasts about 3 to 6 days. The main signs in this stage
are oliguria, elevation of the blood pressure, tendency to bleeding, edema
(including pulmonary edema) thrombocytopenia. Anuria may be preserved then.
4. The diuretic stage lasts 2-3 weeks and is characterized by increasing
of the diuresis (until 3 to 6 litters daily) rapid signs of dehydration and severe
shock in some cases. The main signs of previous stage disappear in many cases.

50
 5. The convalescent stage lasts for as long as 3 to 6 months. The main
signs of hemorrhagic fever with renal syndrome begin to disappear from the
second week of disease, glomerular filtration rate normalizes during 3 to 6 months.
The renal tubular concentrating capacity recovers many mouths.
Diagnostics. Diagnosis of HFRS is based on the geographic distribution of
the disease, epidemiological and clinical data, laboratory evaluations.
Blood picture abnormalities revealed are the following: leucocytosis,
thrombocytopenia, elevation of hematocrit; prolonged bleeding time, elevation of
prothrombin time, activation of thromboplastin time in hypo stage; elevation of
live enzymes, blood urea nitrogen; hematuria, proteinuria can be evident;
hypernatremia, hyperphasphatemia, hyperpotassemia.
Serological tests can help in diagnosis. Enzymes linked immunosorbent
assay is useful for section of antibodies. For field rise in titer IgM for 1 week
against Hantaviruses are evident.
Hantavirus antigen can be detected in different tissues, in microvasculature
by immunohistochemical methods.
Treatment. The treatment depends on the stage of the disease, status of
hydration and overall hemodynamic patient’s condition. A low sodium diet with
restriction of fluid during oliguria stage is recommended.
Maintaining fluid and electrolyte balance is mandatory in the acute disease.
Early and effective fluid therapy is the cornerstone in the renal failure. The use of
vasoactive agents and albumin is recommended in shock period: excessive
administration of fluid can lead to extravasation due by vascular leak, especially
during the febrile and hypotensive stages. In oliguric stages diuretic is
recommended.
Dialysis is indicated if the patient is oliguric for a prolonged time with no
response to diuretics and renal failure is rapid with electrolyte abnormality and
worsening fluid. Corticosteroids, prednisolone, hydrocortisone inhibitors of
proteolysis (contrical), vitamins (C, P) other symptomatic drugs can be used.
Ribaverin intravenous that is indicated within 4 days of illness can reduce
51
morbidity and used only in some countries. Antihypertensive agent, vasoactive
drugs, colloids or diuretics may be needed to control hypertension, treat shock, to
induce diuresis.
After discharging from the hospital patients must be examined in outpatient
department during 3 to 6 months.

Ebola hemorrhagic fever

Ebola hemorrhagic fever is an acute virus quarantine dangerous disease

which is characterized by severe course, pronounced hemorrhagic syndrome and
high mortality rate.
Etiology. Ebola hemorrhagic fever is caused by four or five viruses
classified in the genus Ebola virus family Filoviridae . They are Zaire Ebola virus (
Ebo-z), Sudan Ebola virus (Ebola-s) , Ebola Ivory Coast ( EBOCI), Bundibugon
Ebola virus ( BDBV). The filth Reston virus is thought to be a pathogenic for
humans, it is pathogenic for monkeys. Ebola virus has different forms, the virions
are tubular and variable in shape and may appear as “U”, “6” coiled, circular or
branched shape. The virions are generally 80mm in diameter, can be up do 1400
mm long. This virus is RWA- containing microorganism complexed with the
proteins NP, LVP 30 and VP35. In the so- called matrix space of microorganism
the viral proteins VP 40 and VP 24 are colaced.
This virus is highly infectious, can change very quickly, is not resistant to
damaged factors of the external environment (ph. humidity, insulation) all Ebola
virus subtypes are originated from Africa, except subtype Reston, which is from
Philippines.
Epidemiology. The reservoirs of infection in EHF are chimpanzees, spiders,
sold ticks, fluid bats, monkeys, gorillas, plants, fruit bats. The sick patients are
dangerous for other people. The mechanisms of transmission are the following:
• Through the close contact with infected animal blood and cell cultures

52
 • Through the contact with blood and discharges of infected human
(semen feces, vomitus, mucus, urine)
• Through inhalation of infected small particle aerosols
Humans can be infected with different routes: by air –droplets, contact
injections or sometimes sexually.
The susceptibility to this disease is high, immunity is stable, secondary
disease is rare (about 5 %).
In 7 to 10% of the population in endemic areas have antibody to Ebola virus.
First cases of EHF was first discovered in 1976 near the Ebola, rivers in what is
now the Democratic Republic of the Congo, now Zaire.
Pathogenesis. The portal entries for Ebola viruses are mucous membranes
and skin. After infection the virus lead to the lymph nodes and spleen with
following virus replication there and intensive virusemia development. About 1
week after infection the begins attaching blood and lives cells. If the pathological
process will progress the virus can destroy vital organs such as the liver, kidneys,
leading to massive internal bleeding. As a result of primary toxic effect of the virus
and autoimmune reaction the decreasing of thrombocytes production damaging of
vessels epithelium in internal organs with necrotic foci and hemorrhage are noted.
The main changes are located in the liver, spleen, lymph nodes, kidneys, brain,
ovaries. In fatal cases non-effective immune response could be due to
immunosuppressive amino acid sequence in filovirus glucoprotein.
Clinical manifestation. The incubation period is 3to 10 days, ranges from 2
to 21 days. The onset of EHF is abrupt with high fever (39-40C), frontal and
temporal headache, myalgia, arthralgias, abdominal pain, nausea, vomiting.
The chest pain, cough, pharyngitis can be noted too. These early symptoms
are easily mistaken for typhoid fever, malaria, influenza or various bacterial
infection.
Later disease may process to cause more serious symptoms. On 2-3 days of
the disease blood vomiting, diarrhea, dark or bloody feces, lethargy, change in
menation are noted. An enanthema of the palate and tonsils, cervical
53
lymphadenopathy has revealed during the first week of illness. The maculopapular
rash begins on the 5-7 day on the face, neck and spreads centrifugally to the
extremities. A line desquamation of the affected skin, especially on the palms and
soles appears 4-5 days later.
Hemorrhagic syndrome, which occurs on 3-5 day of disease is the most
common. Epistaxis, hematemesis, petechia, purpura, ecchymosis, bleeding
erosions in mucosa of mouth, bleeding from needle- puncture sites are
characteristics. In severe cases gastrointestinal, renal, vaginal and / or conjunctival
bleeding develop in sick patients.
Somnolence, delirium, coma, hypotension, tachycardia, paresthesia, crams
can be pronounced. During the first weak the temperature remains, around 40 0 C,
decreasing by lysis, for the second week, only to increase again on 12-14 days. On
the 2-nd week splenomegaly, hepatomegaly, edema scrotum or labia.
Complications. Myocarditis, pancreatitis, orchitis (which lead to testicular
atrophy).
Mortality rate is high (range from 50-90%). The cause of death is usually
due to hypovolemia shock or organ failure often accompany by DVS and liver
failure (on the 8-16 day of illness). Recovery is often protracted over 3 to 4 weeks’
period. During their period loss of hai , intermittent abdominal pain , poor appetite,
prolonged psychotic disturbances have been later – transverse myelitis and uveitis
have been reported.
Diagnostics. Laboratory findings in EHV include leucopenia ( low as
1000/ul) from the first day of disease with neutrophilia by the fourth day ;
thrombocytopenia ( often with fewer than 10000 cells/ul) on 6-12 days; elevation
of transaminase levels ( sat > alt ) . Fatal cases may include evidence of
disseminated intravascular coagulation.
Specific diagnostics requires isolation of the Ebola virus or detection of
serological evidence of infection in paired serum samples. Viremia coincides with
the febrile stage of disease; virus has been isolated from tissue, urine, semen, treat,

54
rectal swabs. These investigations may be done only in specialized high – security
laboratories ELISA, PSR.
Treatment. The therapy of EHF is supportive. The administration of
convalescent –phase serum from recovered patient has been proposed. Interferon,
in DI S – heparin, replacement of coagulation factors and platelets can be used.
Prevention. The patients must be isolated in special department with strong
regime. The prevention of EHV includes:
• Proper sterilization of injection equipment
• Protect from body fluids during dealing with cadavers
• Routine barrier nursing precautions, strict isolation, respiratory
protection
• Extensive quarantine precautions
• Producing of effective vaccine for humans

Marburg hemorrhagic fever

Marburg hemorrhagic fever (MHF) is acute zoonotic disease with high

mortality rate, pronounced intoxication and universal capillary toxicosis.
Marburg virus is known after outbreaks of hemorrhagic fever in Germany in
1967 year.
Etiology. The agent of this disease is Marburg virus family Filaviridae. The
viral parts are polymorphic ( as threats, spirals, or oval forms) 790 mm long and 80
mm diameter. This microorganism contains negative one threading RWA and
lipoprotein. There are 7 proteins in the virions. The protein contents of Marburg
virus mimic Ebola virus but strain specific antigens in Marburg virus is
concentrates in areas of 6 p protein and group specific antigens- in areas of Np
protein. Hemagglutinin and hemolysin didn't revealed in Marburg virus. This
microorganism is resistant to external environment factors.
Epidemiology. The source of MHF virus is monkeys predominantly African
marmosets. The mechanisms of transmission are by contact, aerosols, ardiphicial.

55
The routers of transmission are by air – droplets, by contact, by injections. The
MHF virus can be in blood, nasopharyngeal mucus, urine, sperm during 3 months.
The human infection is possible in primary contact with blood and organs of
monkeys through damaged skin (in injections, cuts), through the conjunctiva
sexual mechanism of transmission was described too.
The susceptibility to Marburg virus is high. Secondary cases of MHF are
absent. The immunity after disease is stable. Jason depending characteristics of
their disease didn't described.
MHF occurs in the central and West Africa and south of this Continent.
Pathogenesis. The portals entry of MHF are damaged, skin, mucous
membranes of mouth and eyes. The primary replication of MHF happens in
mononuclear cells and macrophages dater viremia which is accompanied by
suppression of the immune system function develops. Together with generalized
microcirculation disturbances. These changes lead to revealing of DIS and
polyorganic disturbances. In the lungs, myocardial, liver, kidneys, spleen,
suprarenal glands and other organs can have revealed foci of necrosis and
hemorrhages.
Clinical manifestation. The incubation period in MHF is 3-16 days. The
onset of disease is acute with pronounced intoxication. The fever is high during 2
weeks, which is accompanied by headache, myalgia, predominantly in lumbar –
sacral area.
During examination in initial period conjunctivitis, enanthems, vesicular –
erosive changes in month bradycardia can revealed. To us of muscles has been
increased and muscles is painful.
On 3-4 days vomiting and watery diarrhea appear which can lead to
dehydration.
On 5-6 days’ maculopapular eruptions with following desquamation is
possible.

56
 On 6-7 days’ hemorrhagic manifestations (such as skin hemorrhages, nasal,
gastrointestinal and other hemorrhages), signs of hepatitis, myocarditis, damaging
of kidneys are noted.
The damaging of central nervous system can be done. Adynamia,
meningismus are characteristics for CNS damaging at the end of first week signs of
toxic shock and dehydration can be pronounced.
The patient’s condition become worse on the 8-10 days and 15-17 days after
onset of the disease. The fatal outcomes can be in these days. Generally, mortality
rate in MHF ranges from 25-50. The reasons of death are edema of lungs and
brain, hypovolemic shock, acute renal insufficiency, DTS syndrome development.
In the favorable outcomes in convalescent period appearing of long diarrhea,
asthenic syndrome sign, psychic abnormalities, balding can be noted.
Complication. Complication of MHF are hepatitis, myocarditis, orchids,
shock, uveitis, sometimes pneumonia and psychosis.
Diagnostics. Clinical diagnostics is difficult because pathognomonic
symptoms of MHF is absent. Epidemiological data (stay in places with natural foci
of MHF), contact with green marmosets, contact with patients and results of
serological virological, electron – microscopic investigations.
Specific investigations mimic Ebola hemorrhagic fever diagnostics
(revealing of the virus culture, PCR, IFA, NA, CFT and others).
In fatal outcomes electron microscopic investigation or NYF assay for
revealing of virus are used.
Blood picture investigation revealed the following changes: anemia,
anisocytosis, poikilocytosis, leucocytosis, sniff to the left, thrombocytopenia.
Elevation of the transaminase level; the signs of hypocoagulation and metabolic
acidosis.
Treatment. The patients with MHF must be hospitalized with strong regime
in department of hospital. Diet is 4 without exception of the protein and sodium
chloride. Pathogenetic therapy is the main management. The aims of this therapy

57
are dehydration, treatment of toxic shock and hemorrhagic syndrome.
Reconvalescent serum, interferon, plasmapheresis can be used.
Prognosis serious with 25% in average fatality rate or prolonged
convalescent period.

Plague

Etiology. The disease is due to Yersinia pestis, the bacillus of the genus
Yersinia, the family Enterobacteriaceae. It is a barrel-shaped gram-negative non-
motile bacillus. Its pathogenicity toward humans and animals is very high. The
bacillus remains viable outside the macroorganism for a long time. In dead rodents,
Yersinia pestis can live 5 months (at 0°C); in dead (frozen) humans the bacillus can
survive from 7 to 12 months. In the sputum the bacillus remains viable from
several days to 5 months, in pus, to 40 days, and in water, to 3 months. Its stability
toward disinfectants is low. At 100 °C the plague agent is killed in few seconds.
Epidemiology. Plague is a typical disease of rodents which are the primary
source of the disease among humans. Rodents such as marmots, sousliks, hamsters,
field mice and voles, brown and grey rats, house mice, etc. are highly susceptible
to plague. The primary reservoir of plague infection are sousliks, voles, marmots
and rats.
Rodents usually develop an acute form of plague and die. But some of them
(hibernating sousliks, marmots) develop the latent disease which remains in them
till next year. Other animals are also involved in the epizootics. Spontaneous
infection with plague has been observed in 300 species of rodents and 29 species
of other animals (camels, monkeys, jackals, hedgehogs, etc.). Ectoparasites, such
as fleas are involved in the spread of plague and its maintenance in nature. Fleas
are the main vector of infection. They leave dead animals and attack another host.
Fleas can survive in burrows of the dead for a year until the hole is occupied by a
new animal.
Humans are a great danger to the surrounding as a source of infection. These
are patients with primary and secondary pneumonic types of the disease and the

58
septicemic form. Patients with uncomplicated bubonic forms are practically not
dangerous. The main route of infection transmission from an infected rodent to a
human being is through a bite of an infected flea. The flea is infected through
ingestion of blood of a bacteremia animal. As the bacillus multiplies in the
intestinal tract of the flea, a Jell is formed at the entrance to the stomach that
prevents the passage of subsequent meals. As a result, the bacilli are regurgitated
when the infected flea attempts to ingest another blood meal. The flea remains
hungry and its activity increases. In the absence of rats, the flea attacks humans to
infect them.
If a human being hunts in the focus of plague he may get contaminated by
direct contacts with marmots, hares or other infected animals, either dead or
captured. If an individual damages the skin when removing the pelt, or touches the
mucosa with the contaminated hands, he gets infected. People also get infected
during funeral ceremonies because the fluid issuing from the mouth or nose of the
dead contains the plague agent.
Ingestion of contaminated food also leads to penetration of the plague
bacillus into the gastrointestinal mucosa. Susceptibility of humans to plague is
extremely high. When infected from an animal, the patient usually develops the
bubonic form. Bubonic plague is characterized by slowly increasing incidence. In
primary or secondary pneumonic plague, the infection is transmitted from person
to person by air-borne route which is a great epidemiologic danger because the
disease can spread widely within a short period of time. Pulmonic plague usually
follows the bubonic form and very soon it becomes the main clinical form. The
immunity developed in the plague patient is rather stable and repeated infections
are rare.
Pathogenesis. The pathogenesis depends on the route by which the plague
agent penetrates the body. If the infection gains entrance through the skin, the
bacillus is carried to the regional lymph nodes where the microbes propagate to
cause various inflammations with hemorrhagic infiltration. The whole group of the
lymph nodes and the adjacent subcutaneous fat are involved in the inflammation. A
59
primary bubo is thus formed. From the bubo, the microbes enter the blood stream
to cause bacteremia. The microbes enter the internal organs and lymph nodes that
are remote from the portal of entry; secondary buboes are thus formed. Secondary
plague pneumonia is especially dangerous. Less frequently, a papule or vesicle
(that transforms later into a pustule, filled with sanguine purulent exudate) is
formed at the portal of entry of the infection. The pustule turns into an ulcer with
raised margins. The regional lymph nodes are also involved in the process.
If a person is infected by the air-borne route, hemorrhagic pneumonia and
sepsis occur (primary pulmonic and secondary septicemic forms). In alimentary
infection, the disease is manifested by hemorrhagic enteritis and sepsis (intestinal
and secondary septicaemic forms). In primary septicemia, the lymphatic barrier is
weak (usually due to incomplete phagocytosis of the plague agent, and due to the
massive dose of infection and low body reactivity).
Carried by the blood stream, the plague agent therefore generalizes the
process.
The plague microbe forms exo- and endotoxins which cause toxemia. The
cardiovascular and the nervous systems are first of all involved: the pulse changes,
arterial pressure falls, the patient is excited and delirious. Vascular changes are
manifested by necrosis, infiltration and serous impregnation of the vascular walls.
Clinical picture. The incubation period lasts from 2 to 6 days. It is shorter
in the pulmonic form while in the vaccinated it can be as long as 8-10 days. Plague
begins suddenly with a severe chill and rapid elevation of temperature to 39 °C and
higher. Toxemia rapidly develops in all clinical forms. It is manifested by severe
headache and vertigo, insomnia, myalgia, weakness, nausea and vomiting. The
patient is first excited. His face and conjunctiva are hyperemic, the tongue is white
and swollen, speech becomes inarticulate. All these symptoms (unsteady gait
included) resemble those of alcoholic intoxication. Circulatory disorder is marked;
tachycardia develops (120-160 beats per minute); arterial pressure falls; arrhythmia
occurs in severe cases. Severe cases are also characterized by cyanosis,
pointedness of the features (expression of fright on the face of some patients),
60
delirium and hallucinations. Neutrophilic leukocytosis with a shift to the left and
accelerated ESR are seen in the blood. The diuresis decreases; the urine contains
protein, granular and hyaline casts and red blood cells. In addition to the symptoms
that are common for all forms of plague, each particular form is also characterized
by its specific symptoms.
Depending on the route of infection transmission, the patient may develop
either a localized form of plague, such as cutaneous, bubonic, cutaneous-bubonic,
or tonsillar (pharyngeal), or a generalized form, such as primary septicaemic,
secondary septicaemic, primary pulmonic, secondary pulmonic or intestinal
plague.
In the cutaneous-bubonic form, a spot is first seen at the portal of entry,
which is then converted into a papule, a vesicle, a pustule, and an ulcer. The ulcer
is surrounded by a zone of red, later it becomes covered with a dark crust and does
not heal for a long time. As distinct from anthrax, a plague carbuncle is painful.
The regional lymph nodes are almost always involved.
Lymphadenitis (plague bubo) develops on the first or second day of the
bubonic form. The bubo is tender not only during movement but also at rest. The
patient is therefore motionless. Pain makes him assume a forced position. If the
bubo is m the inguinal area, the patient flexes his leg. In the presence of an axillary
bubo, the patient lies on his back with the arm set apart from the trunk. The bubo
fuses with the subcutaneous cellular tissue; the overlying skin is tense and
cyanotic. The bubo either resolves spontaneously or purulates and scleroses.
Cutaneous-bubonic forms can be complicated by secondary buboes,
secondary pulmonic and secondary septicaemic plague.
The tonsillar (pharyngeal) plague lasts 2-3 days. The toxemia is weak, the
body temperature rises to 38 °C, the submandibular and neck lymph nodes are
enlarged.
The primary septicaemic form is characterized by delirious hyperactivity or
complete adynamia, dyspnea, rapid and weak pulse, Hemorrhagic rash and

61
hemorrhages into the skin and mucosa develop, hematemesis and bleeding can be
seen. Untreated patient dies during first days of the disease.
The intestinal form is characterized by high body temperature, extreme
weakness, loss of appetite, nausea, recurrent vomiting, ample liquid stools with
streaks of blood and mucus, severe abdominal pain during the defecation.
Primary pulmonic plague is characterized by a fulminating course with
dyspnea (40-60 breaths a minute), severe chest pain, cough with liberation of
liquid blood-stained foaming sputum. Cardiovascular failure develops on the very
first days of the disease.
In the pre-antibiotic era, pulmonic plague transformed into its secondary
septicaemic form in 1-2 days and the patient died. The prognosis is more favorable
today.
Diagnosis. The diagnosis is based on clinical, epidemiologic and laboratory
findings. Special precautions must be observed when taking infected material, its
transportation and further handling in the laboratory. The following specimens are
taken: bubo contents, spontaneously draining exudate from ruptured buboes,
vesicles, pustules, carbuncles and ulcers; sputum is taken from patients with the
pulmonic form; if sputum is absent, faucial mucus is taken.
Faeces should be taken from patients with intestinal lesions. Blood
specimens of patients with all forms of the disease are studied. The dead should be
autopsied and pieces of the buboes, cutaneous lesions, lymph nodes and the
parenchymatous organs (spleen, liver, lung), as well as blood from the heart or
large vessels should be examined in the laboratory.
Exudates from buboes, vesicles, or pustules should be taken by a sterile
syringe. Since the amount of the material is small, about 0.5 ml of a sterile broth is
taken in the same syringe and the contents are wide-mouth bottles with ground-in
stoppers. Blood (10 ml) is taken from the cubital vein. Several smears (4-5) are
prepared at the patient's bedside. A 5-ml portion of blood is inoculated in a vial
containing 50 ml of broth, while the remaining blood is placed in a sterile test tube.
If the laboratory is remote, the blood is placed in two 5-ml test tubes and examined
62
in the laboratory not later than 5-6 hours (in the absence of a refrigerator). In the
laboratory, the smears are stained with Gram's stain and methylene blue (Loeffler).
The serologic luminescence analysis should be conducted if a luminescent
microscope is available. Hottinger's or Martin's culture media containing sodium
sulphite and gentian violet are inoculated. The remaining material is used for
infection of guinea pigs and albino mice. The serologic method is used for
retrospective diagnosis in those who sustained a suspected plague, in patients to
whom antibiotics were given, and in studies on the material taken from decaying
corpses. Indirect hemagglutination and indirect agglutination inhibition tests are
commonly used. The latter test with an antigen diagnosticum is used to control
specificity of the positive indirect haemagglutination test. Serologic reactions
should be conducted on the 5th day of the disease and then at 5-day intervals till
the patient is discharged from hospital. The reaction of fluorescent antibodies can
be used to detect the plague agent within 2 hours.
Fleas and rodents, and also dead animals, especially camels, should be
examined bacteriologically in the focus of infection.
Treatment. Treatment of the patient must be complex. Specific treatment
includes the tetracyclines (tetracycline, doxycycline, oxycycline, methacycline) 0.2
g 6 times a day.
In order to prevent complications due to the antibiotics, dimedrol, 0.03 g 2-3
times a day, and vitamins (B1; B6, B12, C, K) should be given. A 40 per cent
glucose solution should be infused to patients with marked toxemia. It should be
given in the amount of 20-40 ml.
A 5 per cent glucose should be given in the amount of 500-1000 ml. Isotonic
sodium chloride solution or sodium hydrocarbonate should be given in marked
acidosis. Haemodez, rheopolyglucin and plasma can also be given.
Lasix, furosemide and other diuretics should be given if liquid is retained in
the patient. Cordiamine, camphor, caffeine, ephedrine, adrenaline and strophanthin
should be used to correct cardiovascular disorders.

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 Prevention and control. Quarantine is necessary. The presence of natural
nidi in various countries and reports of plague cases in them indicate possible
export of the disease to other countries.
The anti-plague measures should be taken in airports, sea ports, and railway
border posts in accordance with the international requirements. Persons with
plague should be detected and isolated. Those suspected for plague should also be
isolated and observed. All persons who had contacts with plague patients should be
observed.
Objects suspected for contamination should be examined bacteriologically.
Vaccination is necessary. Current and final disinfection, disinsection,
deratization and quarantine measures are necessary.
Special anti-plague institutions should be involved in prevention and anti-
epidemic measures in natural nidi of plague.
Measures in the focus. Plague patients and people suspected for plague are
placed in special hospitals. Any room is suitable for preliminary isolation. All
people must be removed from the room where the patient was present. The plague
case should immediately be reported to higher medical authorities. Each
hospitalized patient must be placed in a separate room or at least screened from the
other patients in the room. The hospital must be guarded. The personnel must wear
special anti-plague overalls.
Persons who had contacts with plague patients should be isolated for 6 days.
Persons who had contacts with pulmonic plague patients should be isolated in
individual rooms. All persons who had contacts with patients or the dead (with
pediculosis) must have their body temperature measured at least twice a day and
must be given preventive treatment for 5 days with doxycycline (0.2 g once a
day\=intramuscularly) or tetracycline (0.5 g three times a day).
The dead must be buried in coffins (or without coffins) to a depth of 1.5-2
meters. Dry chlorinated lime should be placed on the bottom of the grave. The
dead can be burned.

64
 If hospitalization of all contacts is impossible in view of their multitude,
observation is especially important. People should be observed at home with
obligatory thermometry. Patients with fever should be examined by the physician
(who must establish the preliminary diagnosis) and sent to the corresponding
hospital.
Whenever necessary, observation should be combined with vaccination and
health education of population.
Current disinfection in the focus should be conducted when taking care of
patients, during evacuation of patients and persons who had contacts with them.
Final disinfection should be conducted in residential houses after evacuation of the
patients and contacts, and also after burying the dead. Disinsection and deratization
should also be conducted.

Tularaemia

Etiology. Tularaemia is caused by Francisella tularenis of the genus

Francisella, the family Brucellaceae.The disease is highly contagious for humans
and some animals. The stability of the agent in the environment depends on
ambient temperature and other factors. In water at 4 °C, the microbe survives for
more than 4 months, in frozen foodstuffs for 3-4 months, in dried pelts to 2 months
and in grains and straw (at 20-30 °C) for 20 days. When exposed to direct sunrays
tularaemia agents are killed in 20-30 minutes. They are sensitive to disinfectants in
normal concentrations and to high temperatures. When boiled, they are killed
instantaneously; at a temperature of 60 °C, they are destroyed in 10 minutes.
Epidemiology. The main reservoir and source of infection are rodents. The
causative agent can survive in the outside for a long time. The reservoirs of
infection in natural foci are water rats, small rodents (such as voles or house mice),
hares, muskrats, and hamsters.
The agent multiplies in the rodent. This process rapidly becomes
generalized, and the bacillus is dissipated in the environment with the urine and
faeces. More than 60 species of animals can be the source of the infection.

65
Squirrels, foxes, cats, dogs, goats, cattle and sheep are of secondary importance,
because the process proceeds in these animals with insignificant insemination of
the internal organs, without bacteremia, and hence without excretion of the bacillus
into the environment. Human patients are not contagious.
The infection is spread among animals by blood sucking ectoparasites, and
also through infected water and foods.
The infection is transmitted from animal to human by air-borne route, by
direct contact (during skinning of infected rodents), by ingestion of contaminated
foodstuffs or drinking infected water (bathing included), and by the bites of
infected arthropods: ticks, lice, mosquitoes, etc.
Depending on location of the focus, the number of rodent populations,
human activities and the quantity of immune population, the disease can occur as
sporadic cases or epidemic outbreaks.
Increased risk of epidemic tularaemia exists among agricultural workers,
shepherds, farmers, hunters, laboratory workers and other occupations dealing with
susceptible animals. Epidemic outbreaks of transmissible tularaemia occur in 72-
85 per cent of tularaemia cases.
Water- and food-borne infections come second. Susceptibility of humans to
tularaemia is high. Stable immunity develops in those who sustained the disease. In
some persons this immunity persists for life.
Tularaemia occurs in many countries of America, Europe and Asia. The
disease owes its name to the district of Tulare in California, where it was first
discovered.
Pathogenesis. The tularaemia agent can gain entrance to the human body
through the skin, mucosa of the mouth, nasopharynx, gastrointestinal tract,
respiratory ducts and the eyes. Less frequently the agent causes inflammation of
the skin at the portal of entry. More frequently it rapidly reaches the regional
lymph nodes and later the blood stream.
Primary buboes are formed at sites of accumulation of the organisms (in the
regional lymph nodes). Specific granulomas contain leucocytes, fibrin, plasma and
66
eosinophil cells. Tularaemia granulomas are necrotized, degraded, and look like
tubercles. As the microbes propagate, they can cause secondary buboes.
Circulation of the tularaemia agent with the blood stream causes toxemia with
involvement of various organs and formation of specific granulomas in them.
Clinical picture. The clinical picture of the disease depends on the route by
which the agent gains entrance to the individual. The incubation period lasts from
2 to 8 days. All clinical forms of tularaemia are characterized by some common
symptoms. The disease begins suddenly: a short-lasting chill is followed by
elevation of temperature to 38.5-40 °C. The patient complains of headache,
muscular and lumbar pain, weakness, hyperhidrosis, and poor appetite.
Examination reveals hyperemic face and conjunctivitis.
The spleen and the liver are enlarged by the end of the first week.
Leucopenia, moderate shift to the left, relative lympho- and monocytosis are
seen; ESR is high. Fever can last from 5 to 30 days. Remittent and intermittent
fevers are common. The temperature falls by lysis. The mentioned general
symptoms are supplemented by specific signs of the disease that depend on the
portal of entry of infection.
The following clinical forms of tularaemia are differentiated: bubonic,
ulceroglandular, oculoglandular, angioglandular, gastrointestinal, pulmonic and
primary septic (generalized) forms.
In bubonic form, infection penetrates through the skin and mucosa to the
regional lymph nodes, where it causes lymphadenitis (bubo). The location of a
bubo depends on the route of infection. Ulnar and axillary buboes usually occur in
persons who were infected occupationally by direct contact with infected animals.
Submandibular and neck lymph nodes are involved in water- and food-borne
infections. The size of a bubo varies from the size of a nut to that of an egg, and
greater. A group of lymph nodes is often involved. The nodes do not fuse between
themselves or with the surrounding cellular tissue.

67
 The nodes are only slightly tender. As the body temperature falls, the buboes
slowly resolve. If treatment is untimely, an abscess can be formed that ruptures and
drains spontaneously with liberation of thick cream-like pus.
In ulceroglandular tularaemia, a spot at the site of the agent to a vesicle,
pustule, and finally to an ulcer with simultaneously developing processes in the
nearest lymph node (bubo). Primary lesion of the skin is common for the
transmissive form of tularaemia.
In oculoglandular tularaemia, the agent enters through the eye tunics with
development of follicular proliferations over the conjunctiva and simultaneous
enlargement of the lymph nodes (parotid, anterior neck, submandibular nodes,
etc.). The eyelids become swollen, papules and ulcers can appear on the eye tunic.
The angioglandular form is characterized by hyperplasia of the tonsils with
subsequent formation of a greyish white necrotic coat, and formation of deep
slowly healing ulcers. Unilateral involvement is more common. Since the
tularaemia agent invades the regional lymph nodes, submandibular, neck and other
buboes develop. The angioglandular form is common in water-borne outbreaks.
The gastrointestinal form of tularaemia develops on ingestion of the
tularaemia agent with food. This form is characterized (in addition to the general
symptoms) by severe abdominal pain (which is due to involvement of the
mesenteric lymph nodes), nausea, vomiting and diarrhea. The diagnosis of the
gastrointestinal form is difficult.
Primary inflammation in pulmonic tularaemia occurs in the lungs. The
disease is attended by development of focal pneumonia with a flaccid and long-
standing course. X-ray studies and skin-allergic tests are decisive diagnostically.
The septic form of tularaemia is characterized by development of general
symptoms without primary local and regional reaction at the portal of entry of the
infection. Clinically this form has a more pronounced picture of toxemia.
Polymorphous erythematous rash is more common in this from of the disease.
During the recovery stage, specific complications can develop: secondary

68
pneumonia, nervous and cardiovascular diseases (vegetative neuroses,
degenerative changes in the myocardium, etc.).
Working capacity and appetite are restored very slowly in convalescents.
Tularaemia relapses and conversion of the disease into the protracted form (lasting
2-3 months) are possible.
Diagnosis. Tularaemia is diagnosed on the basis of clinical, epidemiologic
and (in the pulmonic form) X-ray findings. Laboratory studies (allergic, biologic
and serologic tests) are important diagnostically. Skin-allergic tests can be
conducted on the 3rd-5th day of the disease: 0.1 ml of tularin (diagnosticum) is
injected intracutaneously in the upper third of the volar surface of the forearm. If a
hyperaemic infiltration of at least 0.5 cm in diameter appears at the site of
injection, the test is considered positive. The result can be assessed in 24, 36 and
48 hours.
Abrasion cutireaction can be used instead of the intracutaneous test.
The biologic tests are performed on albino mice and guinea pigs. The
following inoculating material is necessary for subcutaneous or intra-abdominal
infection of the laboratory animals: bubonic exudates taken before the 14th day of
the disease; pustular contents; exudate from the ulcer bottom taken before the 8-
12th day of the disease (this should be mixed with isotonic sodium chloride
solution before inoculating the animals); conjunctival secretion taken before the
15-17th day of the disease; blood (5-6 ml) taken before the 6th day of the disease.
The animals are observed for 15-20 days. Infected animals die in 3-4 days. The
microbe is identified by the tularaemia agglutinating serum after death of the
animal.
A 2-3 ml blood specimen taken on the 7-10th day of the disease is sent to the
laboratory for the agglutination reaction. This reaction is repeated 2-3 times at 4-5
day intervals in order to follow the progress in the titer values. The agglutination
reaction is considered positive with serum dilutions of 1:100 and higher. Indirect
haemagglutination test is more sensitive and the result is ready earlier (red cells
sensitized with tularaemia antigen are used as the diagnosticum).
69
 Treatment. The tetracyclines produce the specific effect. They are given in
a dose of 0.2 g 4 times a day. Chloramphenicol can also be given in a dose of 0.5 g
4 times a day for 7-10 days. Isotonic sodium acid is given intravenously. Cardiacs
are given whenever necessary.
Vaccinotherapy should be used in long-standing cases. From 8 to 12
injections should be given at 5-6 day intervals. The dose for one injection is 50 000
(0.1 ml) to 250 000 (0.5 ml) microbes. The vaccine is given subcutaneously,
intramuscularly and intravenously.
Prevention. Vaccination with a dry vaccine is the most effective means of
prophylaxis. Population of enzootic areas, and also persons exposed to the risk of
infection should be vaccinated and re-vaccinated. Vaccination can be given for
epidemic indications as well. An area is considered enzootic if cases were reported
or tularaemia agent was isolated in the past.
Vaccination is done by scarification or by intracutaneous injections. Various
dilutions of the vaccine are used. The results are assessed in 5 and 7 days. If the
local reaction is absent, another vaccination is done in 12-15 days.
Revaccination should be done in 5 years. All population in enzootic areas
should be vaccinated except infants under 7 and persons to whom vaccination is
contraindicated.
People can be vaccinated simultaneously against tularaemia and brucellosis,
tularaemia and plague, or against all these infections simultaneously.
Complex preventive measures aimed at improvement of health in the
enzootic area are important. These include flooding sites of rat habitation, drying
of swamps over large areas, ploughing land and observation of all agricultural
requirements such as timely harvesting, ploughing, weed control, timely
withdrawal of straw and hay from fields, eradication of rodents and flying blood
sucking insects, protection of foods and water from contamination with tularaemia
agent, observation of safety rules when handling sources of infection and materials
suspected for contamination, and also measures aimed to prevent export of
contaminated materials from the infected areas.
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 Health education among population of enzootic areas is necessary.

Rabies

Etiology. The rabies virus is the type species of the Lyssavirus genus, in the
family Rillhabdoviridae, order Mononegavirales. Lyssaviruses have helical
symmetry, with a length of about 180 nm and a cross-section of about 75 nm.
These viruses are enveloped and have a single-stranded RNA genome with
negative sense. The genetic information is packed as a ribonucleoprotein complex
in which RNA is tightly bound by the viral nucleoprotein. The RNA genome of the
virus encodes five genes whose order is highly conserved: nucleoprotein (N),
phosphoprotein (P), matrix protein (M), glycoprotein (G), and the viral RNA
polymerase.
Epidemiology. The source of infection are animals. The main reservoir are
foxes, wolves, jackals and polar foxes which infect domestic animals such as dogs
or cats. Cattle, goats and sheep, horses, swine, cats, mice, rats and some other
animals develop rabies. The contagious period begins 7-10 days before the clinical
signs of the disease develop, and persists till the death of the animal. The
incubation period in dogs is 14-30 days.
Humans are usually infected by dogs, cats and foxes. The infection is
transmitted with the saliva through the bite of an infected animal or when the
saliva gets on an injured skin. Humans are highly susceptible to the virus.
The duration of the incubation period depends on the character of bite, the
location of the wound, its area and depth, amount of saliva that contaminates the
skin, etc. Entrance of the virus through the skin of the head, neck or fingers, is
especially dangerous.
Pathogenesis. Rabies is a viral zoonotic disease that transmitted to human
through biting of rabid animal. Once of symptoms of rabies have developed, the
disease is nearly always fatal. The virus damages the central nervous system,
which includes the brain and spinal cord. The rabies virus travels to the brain by
following the peripheral nerves, from the point of the entry, the virus travels

71
quickly along the neural pathways into the CNS and then future into other organs.
The salivary glands receive high concentrations of virus thus allowing future
transmission. Symptoms in humans may take from several days to more than a
year to appear, although most cases will develop within 4 to 6 weeks.
Clinical picture. The period between infection and the first flu-like
symptoms is typically 2 to 12 weeks in humans. The incubation period of disease
depends on how far from virus must travel to reach the CNS. And it depends on
several factors such as: 1. dose of inoculum; 2. the severity of the wound; 3. the
length of the neural path from the wound to the brain. Wound on face have the
shorter incubation period then wound in the legs. Once the infection reaches the
CNS and symptoms begin to show, the infection is practically untreatable and
usual fatal within days.
Three periods of the disease are distinguished: prodrome, excitation, and
paralysis. The prodrome is characterized by pain at the site of inoculation and
along he courses of the local nervous trunk. The general signs of the disease
develop next: apprehension, fears, depression, deranged sleep, oppression in the
chest, tachycardia and subfebrile temperature. The period lasts 2-3 days.
The excitation period is characterized by progressive respiratory distress and
cardiovascular dysfunction. The inspiration is deep and noisy; all respiratory
muscles are involved in the excursions. The expiration act consists of 2-3
spasmodic contractions of the diaphragm.
The most pathognomonic sign soon develops: hydrophobia. As a cup of
water is brought close to the patient's mouth, the glottal spasm occurs; although
thirsty, the patient is unable to swallow water and throws away the cup. The patient
is excited; his behavior is maniacal. Aerophobia soon develops: even gentle
breezes provoke convulsions. The pupils are irregular, pulse is fast, body
temperature rises to 40 °C and higher. Hallucinations, delirium, aggressiveness and
hyperexcitation can develop. The traditional picture of the "foaming at the mouth"
can be seen. The patient cannot swallow the foam because of deranged deglutition.

72
 In 2-3 days’ convulsions abate and paralysis develops. The lower extremities
are first involved but paralysis rapidly extends over the whole body. In 12-20 hours
the patient dies of apnea and heart failure.
The disease may begin directly with the excitation period or paralysis.
Hydrophobia and excitation can be absent in children.
Complications involving cardiovascular system, CNS, and the respiratory
system eventually develop and contribute to death. Raised intracranial pressure
contributes to the decreased level of consciousness and to focal convulsion. Other
CNS complications include disturbance of thermoregulation, autonomic
dysfunction, and convulse.
Diagnosis. Hematologic picture; high leucocyte count (to 30 x 109/1)
combined with neutrophilia, monocytosis, and an eosinophilia.
The reference method for diagnosing rabies is the fluorescent antibody test
(FAT), an immunohistochemistry procedure, which is recommended by the World
Health Organization (WHO). Virus cultivation- the most definitive.
Postmortem Diagnosis in Humans
All the methods mentioned above may confirm the diagnosis postmortem,
especially if the clinical illness was very short. Virus isolation from secretions is
usually unsuccessful after 2 weeks of illness, but culture of brain tissue should be
possible post mortem, even if the IFA staining is negative. Samples can be
obtained without a full postmortem examination. Brain necropsies are taken with a
Vim-Silverman or other long biopsy needle via the medial canthus of the eye,
through the superior orbital fissure or an occipital approach through the foramen
magnum. Cerebral malaria and other encephalitides may also be diagnosed from
these specimens.
Retrospective rabies diagnosis from formalin-fixed brain specimens is
possible by trypsin digestion and labelled antibody staining with
immunofluorescent, enzymatic or in situ hybridization methods.

73
 The differential diagnosis in a case of suspected human rabies may initially
include any cause of encephalitis, in particular infection with viruses such as
herpesviruses, enteroviruses, and arboviruses such as West Nile virus.
The most important viruses to rule out are herpes simplex virus type one,
varicella zoster virus,
Treatment. Effective treatment is unknown. As a rule, treatment is aimed at
decreasing the psychomotor excitement and at lessening the patient's sufferings.
Salt solutions, glucose and vitamins should be infused parenterally to supply the
patient with the necessary nutrients and to replenish the liquid loss. Chloral hydrate
(2 g in 100 g of starch solution), morphine, aminazine, dimedrol and cardiac are
indicated. Curare-like preparations and intensive respiratory support can prolong
the life of the patient for 2-3 days. The patient should be placed in an isolated
shaded room.
Prevention.
CONTROL OF ANIMAL RABIES
The optimal method of protecting man from rabies infection or associated
financial loss varies greatly in different endemic areas. The species of vector, its
prevalence and interaction with man dictate whether vaccination of animals and
perhaps elimination of the virus is possible, appropriate and economically feasible.
RABIES PROPHYLAXIS IN HUMANS
Although prophylaxis is usually given post-exposure as an emergency
procedure after possible inoculation of the virus, there are immunological, practical
and financial advantages in immunizing people at risk of infection in advance by
pre-exposure vaccination.
Post-exposure Prophylaxis
This treatment is needed after suspected contact with rabies virus through an
open wound or mucous membrane. Intact skin is a barrier against infection. Post-
exposure treatment is aimed at killing or neutralizing rabies virus in a wound
before it enters a nerve ending. Once within the nervous system, virions are
apparently inaccessible to immune attack and disease is inevitable. Post-exposure
74
treatment has three components: wound treatment, active immunization and
passive immunization with rabies immune globulin.
Assessing the Risk of Rabies Infection
Knowledge of the local epidemiology of rabies vectors, the circumstances of
the animal bite or contact and the health and behavior of the animal, all contribute
to assessment of the risk of exposure to rabies. An unprovoked attack by an
unvaccinated sick animal indicates a high risk, but so does contact with a paralyzed
or unusually tame wild mammal. Unusual contact with a bat is a potential risk even
if a wound is not visible. Vaccinated animals have also transmitted rabies. In
endemic areas, strenuous efforts should be made to have the biting animal put
down and its brain examined for rabies. If the animal has escaped or there is any
doubt, post-exposure prophylaxis should be given, irrespective of the length of
time since the bite.
Wound Treatment. Immediate cleaning of the wound or site of contact with a
rabid animal is imperative by scrubbing all wounds with concentrated soap
solution or detergent and copious running water for 5 minutes or more. If possible,
swab with a virucidal agent: iodine solutions or 40-70% alcohol. Concentrated
quaternary ammonium compounds (at least 1% benzalkonium chloride) are
effective against rabies but they are neutralized by soap and are not generally
recommended. Energetic wound cleaning may require local or even general
anesthesia. Suturing should be delayed or avoided to prevent inoculation of virus
deeper into the tissues.
Tetanus prophylaxis may be required, and other bacterial infections
associated with mammal bites may be treated with antibiotics, e.g. Pasteurella
multocida is usually sensitive to ampicillin, tetracycline and co-trimoxazole.
Active Immunization: Vaccine Treatment. All current human rabies vaccines
contain inactivated whole virus which has been grown on a variety of substrates,
usually in tissue culture. Two vaccines are now widely exported: a purified chick
embryo cell vaccine (PCECV) Rabipur® or RabA-vert® manufactured in
Germany or India, and a French purified vero cell vaccine (PVRV) Verorab®.
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 Post-exposure Vaccine Regimens for Tissue Culture Vaccines.
The standard intramuscular (IM) 5-dose (Essen) regimen is as follows: days
0, 3, 7, 14 and 28: one vial IM into the deltoid (or anterolateral thigh in children,
but never the gluteal region).
Passive Immunization. Rabies immune globulin (RIG) provides passive
protection by neutralizing virus in a wound in the interval before vaccine-induced
antibody appears, 7-10 days after starting a primary post-exposure course.
A dose of 40 IU/kg of equine RIG or 20 IU/kg of human RIG should ideally
accompany every primary post-exposure vaccine course, but it is essential
following severe bites: that is, on the head, neck or hands, and multiple or deep
bites.
A large study showed an incidence of reactions to equine and human RIG of
1.8% and 0.09%, respectively, and serum sickness occurred in 0.72% and 0.007%
of recipients. An intradermal skin test does not predict anaphylaxis or most other
reactions and it is no longer recommended. Adrenaline (epinephrine) should be at
hand in case of anaphylaxis.

Brucellosis

Etiology. This infection is caused by microorganisms of six species Human

brucellosis is due to the following three species: B. melitensis (goats), B. suis
(hogs) and B. abortus (cattle). The microorganisms were discovered by the English
physician David Bruce in 1886 in preparations of human cadaveric spleen. (Hence
the names of the pathogenic microorganism, Brucella, and the disease due to these
causative agents, brucellosis.)
The causative agent of brucellosis in goats, B. melitensis, is the most
pathogenic to humans.
Brucella is sufficiently stable in the environment. In soil it survives for 3
months, in milk for 10 days, in sheep cheese to 45 days, and in wool to 3 months.
It is sensitive to high temperature and boiling kills it instantaneously; heating to 60

76
°C for 30 minutes is also detrimental. The microorganisms are sensitive to
disinfectants (3 per cent Lysol solution, 5 per cent solution of lime chloride).
Epidemiology. Brucellosis is a typical zoonosis because the reservoir of
infection is domestic animals. It has already been said that goats and sheep are the
commonest source of infection in man. Cattle and swine are less important. If
healthy and diseased animals of various species are raised together, brucella
migrates from goats to cattle and other animals. Outbreaks of the disease in man
thus become possible.
Cats, dogs, camels, deer, horses are a secondary reservoir of the infection.
A diseased man presents no danger to the surrounding people.
Diseased animals shed the pathogenic microorganisms with amniotic fluid,
abortus, urine, dung, and milk. Besides, the organisms are contained in the blood
and flesh of the animals. The infection is usually transmitted by direct contact with
the animal excrements and objects infected by these excrements. Humans get
infected when taking care of the animals, during milking, shearing, etc. Another
route of infection transmission is through infected foods, such as raw milk, curds,
sheep cheese prepared from raw milk, and also through meat of the diseased
animal. There is still another, although rare, route of infection transmission: by air-
borne droplets. Humans get infected during processing wool of the diseased
animals. Since brucella survives for a long time in water, water-borne infection
should not be excluded either.
Brucellosis is an occupational disease of animal breeders and farm workers.
Immunity, that is produced in those who sustained the disease, is unstable.
The highest incidence of the disease is during the spring and summer. The
first wave of morbidity is seen in the early spring. It is associated with bearing the
young and miscarriages. The infection is spread by direct contact due to intensive
liberation of the organisms with miscarriages, placenta, amniotic fluid, and the
like. Another wave of seasonal morbidity occurs during maximum lactation in
domestic animals; the main mechanism is alimentary. The incidence of brucellosis

77
among the workers of slaughterhouses and meat processing plants coincides with
the time of mass-scale slaughter of cattle.
Pathogenesis. When the pathogenic organism gets inside a human through a
damaged skin or mucosa, it passes with the lymph to regional lymph nodes where
it multiplies during the entire incubation period. By the moment when the disease
becomes clinically manifest, brucella enters the blood and is carried to various
organs and systems: the liver, spleen, bone marrow, and the lymph nodes.
Secondary foci of infection thus develop. In a considerable number of persons, the
acquired immunity does not ensure elimination of the causative agent. Retention
and multiplication of brucella in the infection focus, repeated release of the
organisms into the blood, and endotoxaemia account for the sensitization of the
person to various allergens. If untreated, the disease converts into its chronic form
with periodic exacerbation and remissions.
Allergic changes are manifested by systemic lesion of the vessels,
inflammation in the organs, arthritis, fibrositis, etc.
Clinical picture. The incubation period lasts for 2-3 weeks, with variation
from one week to two months. The clinical manifestations of brucellosis are
varied. The disease is sometimes asymptomatic and can only be diagnosed in the
laboratory. Acute brucellosis (lasting to 3 months from the onset of the disease),
subacute (from 3 to 6 months), chronic brucellosis (longer than 6 months) and
residual phenomena following clinical recovery are distinguished.
According to severity, the disease is classed as mild, moderate and severe.
An acute form of brucellosis often begins with a prodromal period. The patient
complains of malaise, lassitude, depression, deranged sleep, lumbar pain, myalgia
and arthralgia, chills. The prodromal period lasts from several days to a few weeks.
The period of precursors is followed by a manifest clinical picture of brucellosis.
The body temperature suddenly rises to hyperpyrexia. The elevation of temperature
is attended by chills. The fever then lessens and sweating is profuse. Despite fever,
the patient's general condition remains normal and his working capacity is
preserved. The patient then complains of rapid fatigue, headache, irritability,
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transient pain in some large joints. Fever can be undulant, remittent, intermittent,
or, less frequently, continuous.
Lymph nodes, usually submandibular and cervical, less frequently axillary
and inguinal lymph nodes are enlarged in some patients. The spleen and liver are
enlarged from the first days of fever; the condition persists for a long time. These
organs become firm.
Among permanent symptoms of brucellosis in man is pain. By the end of the
second week of the disease the patient develops pain in some large joints. Pain
comes in attacks (undulant). It is due to arthritis and periarthritis, periostitis,
bursitis, myositis, fibrositis, cellusitis, etc.
Headache and pallor are due to the lesion of the central nervous system.
Excitability and whining are characteristic. Leucopenia (3 x 109/1) with relative
lymphocytosis, an eosinophilia, neutropenia, thrombocytopenia and high ESR are
seen.
Late treatment of patients with weak reactivity facilitates the transition of the
disease to its subacute and chronic forms.
Subacute brucellosis, in addition to the mentioned symptoms, is also
characterized by focal allergic lesions in the form of arthritis, neuritis, plexitis, etc.
Subacute brucellosis can gradually transform into chronic brucellosis which
is characterized by a further reconstruction of allergic response with involvement
of other organs and systems. The body temperature is usually subfebrile or normal
during weeks and months (remissions). The chronic form of the disease is usually
characterized by stable changes in the locomotorium (arthritis, bursitis,
tendovaginitis, periostitis, perichondritis) and in the nervous system (radiculitis,
ischioradiculitis, plexitis, neuralgia). The genital system is also involved: orchitis
(inflammation of the testes), orchiepididymitis (inflammation of the testes and the
epididymis) in males and oophoritis (inflammation of the ovaries and the tubes),
endometritis, and abnormal menstrual cycle in women.
Chronic brucellosis proceeds with relapses and remissions and can last 2-3
years.
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 After the patient recovers, residual phenomena are possible: pain in the
joints and muscles, headache, irritability, organic changes in the locomotorium
with deformation of the joints, etc.
The clinical picture of the disease has lately somewhat changed. Severe
forms of brucellosis are rare.
Complications. The commonest complications are orchitis and epididymitis,
salpingitis and oophoritis, bursitis, pneumonia, acute and subacute endocarditis,
plexitis and neuritis of the peripheral nerves, etc.
Diagnosis. The high variability of the symptoms complicates the diagnosis
of brucellosis. A properly collected epidemiologic anamnesis and laboratory
studies help establish a correct diagnosis. Isolation of brucella from the blood,
bone marrow, urine, and the lymph nodes is diagnostically decisive although these
studies take much time. Blood cultures are inoculated with 5-10 ml blood
specimens taken from the ulnar vein of patients before the antibiotic therapy is
started. It is recommended to cultivate specimens of blood, bone marrow and
lymph nodes of patients with chronic brucellosis during exacerbation before
treatment begins (test for the presence of the L forms of Brucella). The result is
ready only in 5-10 days, and sometimes in 29-30 days. Serologic tests, the
immunofluorescent method, Coombs' test, direct haemagglutination test, and
intracutaneous allergic test are used for serologic diagnosis of brucellosis. Wright
and Huddleson tests are positive beginning with the 8-9th day of the disease, while
the Burnet test in 7-8 days and later. A specimen of blood taken from the finger or
the vein (1-2 ml) is tested (Wright's reaction) and result is considered positive with
serum dilution of 1:200 and more. The Huddleson test can be carried out at
patient's bedside (1 ml of blood). But this reaction is qualitative and the
agglutination titres remain unknown. The test is suitable for screening of
population before prophylactic vaccination.
The reaction of direct haemagglutination is more specific. It is positive with
the dilution of 1:100.

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 The Burnet intracutaneous test is performed after the 10th day of the disease.
Brucellin is injected into the skin on the palmar surface of the middle third of the
forearm. A painful edema develops in 24-48 hours (positive test). The size of the
edema is measured: if the edema is from 1 to 3 cm in diameter, the reaction is
weakly positive, if 4-6 cm-positive, and greater than 6 cm-highly positive.
Coombs' test is used in chronic forms of infection. The reaction is based on
the detection of incomplete antibodies using antiglobulin serum.
The luminescent serologic test consists in applying a fixed smear of labelled
serum in the working dilution. The smear is examined in a luminescent
microscope.
Treatment. Patients with acute brucellosis and exacerbated chronic
brucellosis should be taken to hospital.
Antibiotics are given to patients with acute, subacute and exacerbated
chronic brucellosis with signs of marked toxemia and high fever. The tetracyclines
and terramycin are most efficacious. They are given in a dose of 0.3 g 4 times a
day. Chloramphenicol (0.5 g 4 times a day) and other antibiotics are also useful.
The mentioned preparations are given per os for 5-7 days. The course is repeated at
a 5-day interval. Vaccine therapy is indicated after 2-3 courses. The vaccine should
preferably be given intravenously. In the presence of contraindications, it can be
given intracutaneously.
The dose of the vaccine depends on the patient's condition, the route of
administration, allergization of the patient (the result of the Burnet test), and on the
response to the previous vaccination. In order to lessen the response, the vaccine is
administered intravenously in two steps. The daily dose of the vaccine is
administered not by a single injection but in two portions at a 90-120-minute
interval. From 7 to 10 administrations are necessary at 3-5 day intervals between
the injections. The sensitivity is determined by administering 1-2 million microbes
at 2-3 day intervals, and then subsequently 5, 10,25, 75, 100 and 125 million
microbes. In 2-3 hours following the administration, the patient develops chill,
arthralgia intensifies, and the body temperature rises to 38-40 °C in 6-8 hours. The
81
temperature normalizes in 1-2 days, the patient sweats profusely, the liver and the
spleen are enlarged. Subsequent administration of the vaccine is attended by
desensitization of the body, lessening of pain, fall of body temperature, and
improvement of the patient's condition.
Especially severe cases of brucellosis with involvement of the joints, the
central and peripheral nervous system, orchitis, etc., are treated with prednisolone
and prednisone (in addition to antibiotics), given in a dose of 20-30 mg for 4-6
days. The corticosteroid therapy is combined with butadione and other anti-
inflammatory preparations. Symptomatic treatment should also be given:
invigorating measures, preparations improving appetite, vitamins B and ascorbic
acid, cardiacs and analgesics. To release arthralgia, 3, 5 or 10 ml of a 0.25 per cent
Novocain solution are injected intravenously.
Physiotherapy is widely used in brucellosis. Residual phenomena should be
corrected by medical exercises and massage. Health-resort therapy is indicated in 6
months after recovery.
Prevention. Measures to prevent brucellosis in humans should be directed at
eradication of the infection among agricultural animals and decontamination of
environmental objects, foods and raw materials of animal origin, and protection of
people against contamination. The intracutaneous Burnet test and serologic
reactions should be performed in areas where brucellosis cases are reported in
order to reveal timely the diseased animals. People should be protected by taking
general sanitary measures and also by using means of individual protection. These
include observation of disinfection requirements at animal farms and in industry
where animal materials are processed; observation of sanitary requirements during
slaughtering the diseased animals with subsequent disinfection of enclosures,
equipment, etc.; observation of rules for handling animals, and provision of means
for individual protection of the personnel (overalls, rubber gloves, special
footwear, aprons, etc.). The workers must be provided with detergents,
disinfectants, hot water, and the like.

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 Materials obtained from diseased animals should be decontaminated: milk
should be boiled or pasteurized, dairy products should be prepared only from
pasteurized or boiled milk. Meat should be treated thermally. Sheep cheese should
be cured for 60 days.
Prophylactic vaccination is necessary in endemic areas. Quarantines are also
necessary to prevent the infection spread. In order to prevent brucellosis in
humans, planned vaccinations (revaccinations) should be performed in people who
are exposed occupationally to the risk of infection with goat brucellosis.
Single epicutaneous vaccination, and revaccination in 8-12 months (also
epicutaneously) should be carried out. Vaccinated and revaccinated are people with
negative serologic and allergic tests forbrucellosis at the age over 18 years, and
also people to whom vaccination is not contraindicated.
Dry live vaccine (B. abortus) is used. Vaccination and revaccination are
performed 1-2 months before hiring for jobs associated with possible danger of
infection, before intensive seasonal work begins (sheep shearing, mass-scale
slaughtering, etc.). Persons exposed to the danger of brucellosis infection (animal
breeders, slaughterhouse workers, etc.) should be observed regularly in outpatient
conditions. The observation includes inspection by the general therapist and
laboratory testing.
Health education of population is necessary in areas where brucellosis cases
are reported.
Herpetic infection
Chickenpox
Herpetic infection is a chronic recurrent infection caused by herpes simplex
virus and predominantly characterized by covering tissue and nerve cells disease.
A person is a reservoir and source of herpes infection: an infection carrier or
a patient. Isolation of the pathogen can last for a long time.
Etiology. Virus is transmitted by contact mechanism; the virus is released to
the surface of the mucous membranes and skin. In addition to the basic
transmission ways Type I virus can also be realized as airborne virus, as airborne
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dust virus, and Type II can be transmitted vertically from mother to child
(transplacental and intrapartum).
Types of herpes simplex virus:
1. HSV type 1 (herpes simplex virus type 1) causes genital herpes, herpes of
the lips, eyes, pneumonia, brain damage.
2. HSV type 2: the same genital herpes, intrauterine infection of the fetus.
Shingles: causes such infection as chicken pox and herpes zoster.
3. HSV type 6 (HHV-6: can represent etiological agent (cause) for multiple
sclerosis and newborn fever with convulsive disorders, infectious mononucleosis
negative for the virus Epstein-Barr virus (EBV) and cytomegalovirus (CMV) and
associated with HHV-6 encephalitis.
4. HSV type 7: is responsible for what the mass media calls - "chronic
fatigue syndrome".
5. HSV type 8: Kaposi’s sarcoma is a malignant tumor which HIV-infected
people and people with weakened immune systems have.
Herpesviruses include cytomegalovirus, affecting many organs and systems
in utero of the fetus, as well as the Epstein - Barr virus: infectious mononucleosis,
nasopharyngeal carcinoma.
The most common diseases caused by the herpes simplex virus: Varicella
(chickenpox); Herpes Zoster.
Epidemiology. Varicella (chickenpox) is an acute, anthroponotic viral
infection spread by airborne droplets and by contact, accompanied by a vesicular
rash and related intoxication.
A source of a chicken pox and shingles is an ill person. Patients are
contagious one day before the catarrhal symptoms, and within 5 days after the rash
appears.
Ways of transmission are airborne (talking, coughing, crying loudly,
screaming), home (infected saliva or vesicles parts) and contact (with the direct
touch), and transplacental (spread of the virus through the placenta).

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 Clinical picture. The incubation period for varicella (from the introduction
to the first signs of chickenpox) is 11-23 days. During this period, there is
penetration of the pathogen through the mucosa of the upper respiratory tract, then
multiplication and accumulation of the virus in the epithelial cells of the mucous
membranes.
After maximum accumulation of the pathogen of chickenpox it spreads
through the lymph and blood vessels, causing the occurrence of the following
periods - prodromal period or rashes.
Prodromal period of chickenpox - (this period may not be) is specific to
some people and lasts for 1 day. It is characterized by scarlatini form rash,
retaining for a few hours and then disappearing, the temperature rises to 37-38⁰C
and intoxication. Often this period is a reaction to viremia.
Rash Period - varicella begins badly (or immediately after the prodromal
period) and lasts for 3-4 days or more. As well as the prodromal period, it is a
response to viremia characterized by the following symptoms:
• lymphadenopathy (may not be)
•. fever up to 37-39 ° C is maintained throughout the rash period and each
new onset of the rash is accompanied by a temperature rise.
•New spots can keep appearing in waves for five days after the chickenpox
rash begins. Thus, there is an impression of a false polymorphism (different
clusters of spots may be at different stages of blistering or drying out). The spots
normally appear in clusters and tend to be anywhere (rash may even be over the
scalp - an important differential diagnostic sign; inside the mouth, inside the nappy
area (for girls), conjunctiva / cornea, larynx, followed by ulceration and healing
within 5 days). Although the rash starts as small red spots, these in one day
develop a blister on top and after a day or two, the fluid in the blisters gets cloudy
and they begin to dry out and crust over. After 1 to 3 weeks, the crusting skin will
fall off naturally.
Diagnosis. An infected person is not contagious once new spots stop
appearing and begin to dry out. The rash can become intensely itchy. Recovery
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period lasts for 3 weeks and is characterized by crusting skin falling off and the
formation of life-long immunity. After crusting skin falls off there are dark spots
kept for a few weeks. No scars are left if there was no secondary infection.
1. Virological method - abjection of chickenpox vesicles and exfoliated skin
lesions. But it takes time and is only used in cases of dispute.
2. Rapid test method - IFA (immunofluorescence reaction), helps to detect
viral antibodies.
3. The serum - ELISA (enzyme-linked immunosorbent assay) - is aimed at
the detection of specific IgM antibodies to the virus and G varicella; M appears
during the incubation period (4-7 days after infection) and lasts for 2 months, their
presence shows the acute period; G –appear on the 2nd-3d week and usually stays
in the body, testifying to the immunization, i.e. to protection.
4. The genetic method - the use of PCR (polymerase chain reaction) is aimed
for the DNA virus detection.
5. General clinical tests: FBC (↓ A ^, ↑ Lf, normal ESR). Immunological
examination: ↓ T-lymphocytes, in violation of the cell unit, ↑ activity of NF and
macrophages, ↑ CIC (circulating immune complexes).
Treatment. Etiotropic treatment of chicken pox
Antiviral medications are aimed specifically against the herpes virus:
• Acyclovir = Zovirax = viroleks (from the age of 2);
• valtsiklovir (from the age of 12)
• famciclovir (from the age of 17), Isoprinosine;
Also Acyclovir Ointment can be used on rash and conjunctivitis (eye
disease).
Immunomodulators: interferon, viferon
Immunostimulants: cyclopheron, anaferon
Antibiotics such as 3D cephalosporins are used for secondary bacterial
complications.
In severe cases of chickenpox intravenous immunoglobulins are used.
Pathogenetic treatment of chicken pox
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 -Bedrest for 3-5 days.
Careful skin and mucous membranes care:
• hygienic bath / shower, no rub and slightly dab dry,
• use green disinfectant to prevent secondary infection,
• Protect the mouth - rinse with furacillin or sulfacyl sodium or sodium
hydrocarbonate;
• conjunctivitis can be treated by acyclovir ointment; to prevent bacterial
complications - sulfacetamide 20%, laevomycetin or tetracycline ointment are
used.
- Excessive alkaline drinking
- When severe bouts use stronger immunomodulators (timolin, timogen,
IRS-19) and cytokine medication (ronkeylikin)
- Multivitamins, probiotics (bifidum-lactobacillus, Linex), enterosorbent
(smecta), medicine for metabolic therapy (Riboxinum, cocarboxylase), mucolytic /
expectorants (ambroxol, bromhexine, a decoction of thyme, breast tea №1) and
anti-spray for dry cough (Erespal), antiplatelet agents (aktovegil, cavinton etc.),
antihistamines (when intense itching use topical fenistil gel or gistan gel, or other
antihistamine ointments; and ingest use antihistamines like suprastin, tavegil, etc.);
antipyretics (ibuprofen, nurofen, or physical cooling methods as wrap).
Symptomatic treatment
It belongs to the groups of pathogenic agents and is appointed for more
serious complications - cardiac glycosides.
Treatment is continued for about 2 weeks (including pharmacotherapy).
Rehabilitation after chickenpox
• one month after the doctor examines the recovery, immunological
examination and specialist’s consultations are appointed,
• protective regime within 2 weeks after recovery (no physical activity)
• no preventive vaccination for 2 months,
• within a month: multivitamins and / or vitamin-mineral complexes,
metabolic therapy and herbal adaptogens.
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 Prevention.
• In the absence of contraindications at the age of 2 it is allowed to vaccinate
against chickenpox - vaccine Varilriks, Okavaks, Prevenar or Pneumo-2.
• Passive immunization is used by intake of VZIG, that is necessary for:
Persons with EDS;
All newborns whose mothers had not had chickenpox or been infected for a
few days before giving birth;
All preterm up to 1kg, regardless of the mother's history of infection.
• Non-specific prevention of chickenpox - Quarantine (isolation of the
patient) within 5-7 days of onset of rash, with frequent aeration and wet cleaning.
No contacts with unimmunized up to 21 days.

Herpes zoster

Herpes zoster is called a viral disease that is characterized by a painful rash

on one side of the body, typically preceded by pain.
Causes of disease. The virus which causes symptoms of herpes zoster is
called "Varicella zoster", or "varicella virus". It is called "herpes zoster" or "herpes
virus type 3". It belongs to the family of herpes viruses, and has much in common
with herpes simplex type 1 virus, which causes the well-known cold sore.
The main feature of the varicella-zoster virus is its tremendous virulence: the
infection in almost 100% of cases starts in the organism without specific immunity
to the virus.
There are the following types of the disease:
-Blister. Characterized by big fluid blisters.
-Abortive. No rash or pain.
-Hemorrhagic. Characterized by the presence of blood in blisters.
-Eye type. Skin areas around the eyes are damaged and may develop
keratitis, iritis and glaucoma this type often causes facial nerve disturbance,
paralysis and loss of vision.

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 -Ear type. Results with severe pain in the auditory passage, and frequently
with hearing loss.
- Meningoencephalitis type. Nerve tissue, the brain tunic and the brain itself
can be disturbed. This type is characterized by hallucinations, ataxia, hemiplegia,
and by a high mortality rate - more than 60%.
- Gangrenous. Leads to tissue necrosis in the rash area and results with lots
of scars.
Clinical picture. Shingles is always localized along the nerve trunks, very
often in the intercostal nerve, and in the branches of the trigeminal nerve; common
symptoms - one-sided destruction and pain. In most cases, rash appear on the body,
but can appear on the face and even over the sculp. Skin rash is almost always
preceded by malaise, itching, low-grade body temperature, neuralgic pain and
tingling in the future rash area.
The next stage is characterized by the appearance of swollen pink spots that
within 3-4 days are grouped into erythematous rash that quickly turns into blisters.
After 6-8 days’ blisters begin to dry out and crust over, the crusting skin will fall
off naturally, remaining slight pigmentation. After the rash disappearance some
patients may have postherpetic neuralgia, which is very difficult to treat.
The term of uncomplicated condition of herpes zoster is approximately 3-4
weeks. Pain can continue within a few months. In very rare uncomplicated cases
herpes zoster runs easy and almost painless.
Diagnosis. The following methods are used:
-microscopy - varicella zoster virus is large enough and is visible even in
normal light microscope.
-serologic methods, based on the determination of the titer of antibodies
specific to the virus Varicella zoster.
-immunofluorescence method.
-culture method of growing the virus in culture medium.
Treatment. The main objectives of the disease treatment:
-the acceleration of the healing process;
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 -maximum pain reduction;
-prevention of possible complications;
- reduction of chance of postherpetic neuralgia.
For herpes zoster treatment various antiviral medications are used:
Isoprinosine, valacyclovir, acyclovir, penciclovir, famvir.
These medications penetrate into the viral DNA, allowing to disrupt viral
replication, i.e. to suppress the process of its reproduction.
At the initial stage of the disease the use of antiviral drugs can reduce pain,
reduce the duration of the disease and reduce the chance of post-herpetic neuralgia.
Treatment of herpes zoster often involves taking pain relievers:
dexketoprofen, naproxen, ibuprofen, ketorolac and ketoprofen.
Prevention. The specifics of protective preventive measures against herpes
zoster is not to allow the virus to present again:
-Vitamin support of the body
-Healthy lifestyle
-Serious attitude to any somatic diseases
-Special vaccines use for weak immune system

Ornithosis

Etiology. The causative agent of ornithosis belongs to the genus

Chlamydiales, the family of Chlamydiaceae. The bacteria are quite large, with an
average diameter of 400-1200 nm. The bacteria synthesize both DNA and RNA;
they are sensitive to antibiotics, especially to the tetracyclines. They are stable in
the environment and against the chemical and physical factors such as low
temperatures. At a temperature of — 20 °C, they persist for 10 months and at — 7
°C can survive for over two years; they withstand drying, and are killed by a 2 per
cent chloramine solution only in 24-72 hours. The bacteria are sensitive to high
temperature: they are killed at 70 °C.
Epidemiology. The natural harbor of the ornithosis agent are birds (wild and
domesticated). Chlamydial psittaci has been isolated from more than 140 species

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of birds. Humans are usually infected by poultry (ducks, turkeys, less frequently
hens). Pigeons are the most dangerous psittacine birds. Besides natural and
secondary foci of ornithosis, epizootics occur at poultry-raising farms the origin of
which is difficult to relate to any natural nidus or to transmission of the disease by
wild birds or pigeons. The source of infection can in such cases be birds in which
the infection is latent. The infection generalizes due to decreasing resistance during
laying eggs, overcrowding, cold, or other adverse factors. It is believed that a
ornithosis s patient is not contagious; nevertheless, hospital-acquired infections
have been reported. The main routes of infection transmission are dust- and air-
borne; hence the lungs are usually involved. Infection is transmitted through
infected down and feather, during inhalation of dust containing the bacteria, by
contamination of the mouth or eye mucosa with soiled hands. This happens in
poultry raisers, during slaughtering and processing of poultry, or eating unboil
eggs. Outbreaks of occupational disease among poultry raisers and slaughterhouse
workers usually occur during the spring or autumn which is connected with care of
the young birds and mass-scale slaughter of poultry. The susceptibility to
ornithosis is high. Women are usually affected occupationally. The immunity
produced in those who sustained the disease is unstable.
Pathogenesis. The main portal of entry is the mucosa of the upper airways.
Multiplication and accumulation of the agent occurs in the lungs where it is
brought with the blood. From the lungs, the pathogenic microbe is brought back to
the blood that carries it to the liver, spleen, adrenal glands, nervous system, or
myocardium where it multiplies to cause fine foci of degenerative and proliferative
changes and hemorrhages. The agent circulates for 7-10 days. Chlamydia produce
a toxic effect that accounts for the main clinical symptoms.
Depending on the organs and tissues involved, the following clinical forms
of the disease are distinguished: influenza-like, pneumonic, typhoid, and
meningeal. The pathogenic agent is retained in the cells of macrophage systems
which causes relapses of the disease and its conversion into chronic forms.

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 Clinical picture. The incubation period usually lasts from 7 to 10 days with
extremes of 6 and 25 days. The onset is usually acute: the patient develops chills,
headache, myalgia and pyrexia (remittent fever). Hyperhidrosis, nausea, vomiting
and poor appetite are also among the symptoms.
The influenza-like form is manifested by dry cough and the symptoms of
laryngitis and tracheobronchitis that develop in 2-3 days.
In pneumonia-like form, cough intensifies on the 5-7th day and the patient
expectorates mucoid or mucopurulent sputum; moist rales can be heard in the
lower portions of the lungs; respiration is weak.
X-ray examinations reveal fine focal, confluent, segmental and interstitial
changes in the lungs that persist for a long time after body temperature normalizes.
Depending on involvement of the conventionally pathogenic bacteria in the
inflammatory process, the disease can run the course of a macrofocal or lobar
pneumonia.
The blood changes are characterized by leucopenia with the shift to the left,
an eosinophilia, and high ESR.
The fever period lasts from 2 to 4 weeks. The body temperature decreases
lytically and the recovery phase begins slowly. Exacerbations and relapses of the
disease are possible. In severe ornithosis, coma develops in 4-5 days and the
patient dies of cardiac and/or respiratory failure. The patient can die in 2-3 weeks
due to lung edema.
The typhoid form is characterized by signs of toxemia. The patient
complains of poor appetite, constipation, aching pain in the entire body. Hepatic
and splenic enlargement becomes obvious in 5-7 days. Examination fails to reveal
any symptoms of lung involvement.
The meningeal form is rare. The disease begins acutely; the symptoms of
meningitis supervene in 2-4 days. Fever persists for 3-4 weeks.
The disease can run mild, moderate and severe course.
In severe cases, the nervous and the cardiovascular systems are involved; the
patient complains of severe headache, insomnia, irritability and delirium. The skin
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is pallid; the arterial pressure is low; bradycardia can be superseded by tachycardia.
Renal involvement is manifested by decreased diuresis, albuminuria, and by the
presence of single red cells and hyaline casts in the urine. In about 20 per cent of
patients, early relapses develop (in 2-4 weeks); later relapses (in 3-6 months) are
also possible in them. The chronic form of ornithosis can persist from 2 to 10
years.
Complications. Thrombophlebitis, hepatitis, pneumosclerosis, pleurisy,
paralysis of the vocal cords, polyneuritis, and meningitis are possible.
Diagnosis. The diagnosis is based on epidemiologic anamnesis (contact with
birds), clinical picture of the disease, and the results of x-ray and laboratory
examinations.
Laboratory examinations include direct and indirect complement fixation
tests and haemagglutination. A 5-ml specimen of blood is taken from the cubital
vein into a dry sterile test tube in 4-7 days after the onset of the disease. At least
two portions of the blood are tested at 7-10-day interval. Antibiotic therapy slows
down accumulation of antibodies; therefore, the third portion of blood should be
tested in 20-30 days from the onset of the disease. Titres lower than 1:8 to 1:16 can
be considered positive. The diagnosis of psittacosis is confirmed if at least two-fold
increase in the antibody titre is noted.
Haemagglutination reaction, inhibition of haemagglutination and indirect
haemagglutination reactions are also used.
In order to detect the pathogenic agent, material taken during the first days
of the disease (before the antibiotic therapy is started) should be sent to the
laboratory. It is recommended that blood and sputum be taken simultaneously. The
blood specimen (5 ml) is taken from the cubital vein into a sterile test tube, and the
sputum is taken in the morning, before meal. Specimens of the lung tissue, spleen
and pleural effusion are taken from the dead patients.
The materials are placed in sterile containers provided with ground-in
stoppers, or into wide-mouth bacteriologic test tubes, which are then sealed tightly
(either by soldering or by tight rubber plugs) and placed into metal containers. The
93
sealed container should be placed into solid carbon dioxide or in a vacuum flask
containing ice.
The material is administered to albino mice (intramuscularly, through the
nose, or into the brain). After the mice dies, smears are prepared from their lungs
and other organs, and stained after Romanovsky, Giemsa, or Castaneda to reveal
the agent. Ornithosis agents can also be cultivated on chick embryos. The most
rapid method is the intracutaneous test with the psittacosis antigen that can be
performed on the second or third day of the disease (till the second or third month).
The result is ready in 24-48 hours. The test is positive if the size of the hyperaemic
area is 0.5 x 0.5 cm (+), 1 x 1 cm (+ +), or 2 x 2 cm (+ + +).
Treatment. The tetracyclines (tetracycline, oxytetracycline, terramycin,
etc.) are most effective. They are given in doses from 1.2 g to 2 g a day, depending
on severity of the disease and the body weight of the patient. Duration of the
therapy is from 3-5 to 9-10 days after normalization of body temperature.
Oxygen therapy, vitamins and cardiacs are given for special indications.
Plasma or blood (autohaemotherapy included) should be given during the recovery
phase. In the presence of contraindications, vaccinotherapy should be given for
chronic psittacosis.
Prevention. It is necessary to control psittacosis in domestic birds. If the
disease is detected at poultry farms, 6-month quarantine should be established. All
birds with the disease should be treated (for 14-21 days, tetracycline is added to the
fodder in the amount of 200 g per ton), or the diseased poultry can be killed and
processed at the same poultry farm. Their meat should be processed thermally
before using as food. Feather and down should be burned or disinfected with live
steam at a temperature of 105 °C for 30 minutes. Eggs collected at poultry farms
with quarantine should also be treated thermally before using as food.
Infected farms should be disinfected with a 5 per cent clarified lime chloride
or 10 per cent Lysol solution.
The personnel should wear overalls, goggles and masks. If diseased poultry
is processed at plants, rooms should be washed with a 2 per cent chloramine
94
solution at 3-hour intervals. Excrements and feather should be treated with a 10 per
cent Lysol solution. The most effective method to prevent psittacosis is aerosol
immunization.
Measures in the focus. Psittacosis patients should be treated in infectious
hospitals. Persons exposed to the danger of infection should be observed for 16
days.
Diphtheria
Etiology. This disease is produced by Corynebacterium diphtheriae, non-
motile, gram-positive rod with a characteristic swelling at one end. Neisser-stained
bacilli viewed microscopically by the fluorescent method demonstrate the presence
of volutin grains (Babes-Erns granules) in their ends.
The genus Corynebacterium diphtheriae includes toxicogenic (causative
agent of diphtheria) and non-toxicogenic corynebacteriae which do not cause
diseases with clinical symptoms of diphtheria. By their cultural biochemical and
other properties Corynebacteria diphtheriae are classed into mitis, gravis, and
intermedins groups.
As the bacteria multiply they produce exotoxin which evokes the main
clinical manifestations of the disease. Corynebacteria diphtheriae are stable in the
environment. In the dry state they can survive on various objects, such as toys,
dishes, linen, for many days; in milk and other foods they remain viable for 10-15
days. The bacteria are stable to low temperatures but are sensitive to high
temperature. All disinfectants in common concentrations (3-5 per cent) kill the
bacteria in 20-30 minutes.
Epidemiology. The source of infection is a diphtheria patient with clinically
manifest symptoms or with an asymptomatic course of the disease, convalescents,
and carriers of toxicogenic strains of the bacteria.
The infected person can be the source of infection during the last days of the
incubation period and remain contagious for the entire duration of the disease.
From the epidemiologic standpoint, the greatest danger are patients with mild and

95
obliterated forms of the disease that now prevail and can be mistaken for lacunar or
catarrhal tonsillitis, rhinitis, and the like.
Eradication of the agent from convalescents usually ends in 15-20 days, less
frequently in 1-2 months. Healthy carriers of toxicogenic strains of the bacteria are
dangerous because their number is much greater than of diphtheria patients and
convalescents.
The number of toxicogenic carriers depends on the morbidity; their number
is much greater in the foci of diphtheria. Overcrowding and duration of contacts
are important for the rate of carrier state. In closed collective bodies the number of
carriers is 2-3 times greater than in other communities.
The main transmission mechanism is air-borne, because patients and carriers
dissipate the bacteria with droplets of mucus during coughing, sneezing, crying, or
talking. The infection can be transmitted through the fomites (dishes, toys), food
(milk, cold dishes) that may be infected from a patient or a carrier.
Not all infected develop the disease; some become healthy carriers. The
percentage of carriers in the focus of infection can be as high as. The presence of
antitoxic immunity in vaccinated children does not exclude toxigenic carrier state,
while disease does not develop.
Diphtheria occurs as sporadic infections with rises during the cold season.
Stable immunity is induced in those who sustained the disease.
Pathogenesis. The portal of entry is the mucosa of the upper airways. Less
frequently the bacteria enter through the mucosa of the eyes, external genitalia or
injured skin. The bacteria multiply at the site of their entry and produce toxin.
Local changes and general manifestations of the disease are associated with
toxemia of the patient. Local changes in diphtheria are manifested by necrosis of
the mucosa and formation of a fibrinous membrane that tightly adheres to the
underlying tissue. Grey or yellow membrane consisting of fibrin, leucocytes,
desquamated epithelium of the mucosa and bacteria can be seen on the surface of
inflamed mucosa. As the disease progresses, not only the multilayered epithelium
of the faucial or pharyngeal mucosa is necrotized, but also the basement
96
membrane. The thick fibrous membrane is detached from the underlying tissue
with difficulty (diphtheritis inflammation). After the membrane is removed with a
cotton tampon or a spatula, the tonsillar surface bleeds.
When the tracheal and bronchial mucosa (which is lined with a single layer
of columnar epithelium) is involved, only the epithelial layer is usually necrotized
and the formed membrane is therefore loosely adherent to the underlying tissue
and is easily detachable (croupous inflammation). Regional lymph nodes are also
involved.
The toxic form of diphtheria is attended by edema of the facial and
pharyngeal mucosa and by edema of the neck connective tissue. The diphtheria
toxin affects first of all the nervous and cardiovascular system, the adrenal glands
and the kidneys.
Clinical picture. The incubation period is from 2 to 10 days (usually 3-5
days). According to location of the primary lesion, the following clinical forms are
distinguished: faucial diphtheria, laryngeal diphtheria, nasal diphtheria, and
diphtheria of rare location (in the eye, ear, genitalia, skin, wound). Each of these
forms is divided according to severity into mild and toxic forms. The toxic form is,
in turn, subdivided into subtoxic, toxic (degrees I, II, III), hypertoxic and
hemorrhagic.
Faucial diphtheria. The region of the tonsils is only involved (local form). If
the membrane extends from the tonsils onto the mucosa of the palatine arches,
uvula, fauces, the disease is diffuse. In the toxic form of the disease, in addition to
the vast process in the fauces (Plate IV), involved also are the regional lymph
nodes with toxic edema of the neck cellular tissue; the condition is characterized
by toxemia.
The localized form of diphtheria is most common. The catarrhal (without
membrane) and insular (separate islands of membrane can be seen on the tonsils)
subtypes are distinguished. The onset of the disease is gradual, with moderate
elevation of temperature to 38 °C, malaise, poor appetite, headache and slight pain
during swallowing. The fauces become hyperaemic by the end of the first or
97
second day. Greyish-white membrane of moderate thickness appears on one or,
most frequently, both tonsils. When removed by a cotton tampon or a spatula,
bleeding surface is exposed. Submandibular and anterior neck lymph nodes are
slightly enlarged. Signs of toxemia are absent. Timely treatment eliminates the
membrane in 2-5 days; the temperature normalizes.
The diffuse form of the disease usually begins acutely, the body temperature
rises to 38.5-39 °C, the patient complains of chill, weakness, headache, and
deranged sleep. The tonsils are edematous and enlarged, with a thick grey
membrane on both sides of the tonsils. It extends to the palatine arches, the soft
palate and the nasopharynx. The regional lymph nodes are tender and enlarged to a
slightly greater extent than in the localized form. The diffuse form of diphtheria is
often the result of untreated local form. Timely specific treatment leads to recovery
of the patient in 7-10 days.
Toxic form of faucial diphtheria. The onset of the toxic faucial diphtheria is
usually fulminant: the body temperature rises to 39-40 °C, weakness is severe, the
face is pallid and slightly edematous. The heart sounds are dull; tachycardia is seen
(140-160 beats per minute). The membrane is thick, greyish-white or brownish-
grey; it covers the tonsils and extends to the soft and even hard palate. The
nasopharynx and the nasal cavity can also be involved. Nasal discharge is
serosanguineous. The breath is foul and sweetish. Edema of the faucial mucosa and
the membrane can mechanically impede respiration which becomes noisy and
hoarse.
Changes in the upper neck lymph nodes and edema of the neck are a specific
symptom of toxic diphtheria. The extent of edema of the subcutaneous fat
corresponds to the degree of toxemia; the following three degrees of toxic
diphtheria are distinguished in this connection: degree I-edema extends to the
middle of the neck, degree II - edema extends to the clavicle, and degree III -
below the clavicle.
After specific treatment with antidiphtheria serum, the edema and membrane
disappear only in 5-10 days. Local symptoms of the disease subside.
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 Hypertoxic form is characterized by severe fulminant local process in the
fauces, toxemia attended by quickly developing cardiovascular failure. The
patients often die in the first 4-5 days.
Laryngeal diphtheria (diphtheritic or true croup). The disease can be
independent, or it can be superimposed upon faucial or nasal diphtheria (secondary
croup). Three stages are distinguished in the course of laryngeal diphtheria. The
dysphonic stage of the disease begins with elevation of body temperature, malaise,
and hoarseness. The patient complains of barking cough, which becomes' voiceless
with progression of dysphonia to aphonia.
In 1-3days, the disease transforms into the stenotic phase. Its early symptom
is noisy respiration that resembles the sound of a saw cutting a wet wood. Another
symptom of stenosis of the upper airways is retraction of the yielding parts of the
chest during inspiration (due to rarefaction in the chest). Accessory muscles are
involved in the respiration act. Duration of the stenotic stage varies from several
hours to 2-3 days. If the patient is not given operative treatment (intubation,
tracheostomy), asphyxia develops.
Asphyxia is characterized by marked anxiety of the child which is then
followed by drowsiness, and cyanosis of the lips, the nose and the nails.
Respiration is fast and shallow, pulse is weak and arrhythmic, arterial pressure
decreases, the forehead is covered with cold sweat; convulsions develop and the
patient dies of suffocation.
Nasal diphtheria. This disease is usually seen in infants. The body
temperature is subfebrile or normal, nasal breathing is impeded, the nasal discharge
is serosanguineous. Excoriation and fissures appear at the nostrils. Membranes and
ulcers covered with crusts develop on the nasal mucosa. Toxemia is mild.
Diphtheria of rare location occurs mostly in infants due to secondary faucial
and nasal diphtheria.
The clinical picture of diphtheria has substantially changed in connection
with vaccination of children. Faucial diphtheria often runs the same course as
catarrhal or lacunar tonsillitis.
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 Complications. Myocarditis. Overall, approximately 10% of patients with
diphtheria develop myocarditis, although two-thirds of patients with severe infec-
tion will have some evidence of cardiac involvement. Myocarditis can be predicted
on admission by the extent of the pseudomembrane, and is almost invariable if
there is a bull neck. The first evidence of cardiac toxicity usually occurs in the
second week of illness. Clinical signs include soft heart sounds, a gallop rhythm,
and less commonly signs of congestive heart failure. Incompetent murmurs may
develop as the ventricles dilate. The mortality rate associated with diphtheritic
myocarditis is approximately 50%. Echocardiography shows dilated, poorly
contracting ventricles. Electrocardiographic (ECG) abnormalities are more
common than clinical signs of myocarditis and include frequent supraventricular
and ventricular ectopic, bursts of tachyarrhythmia, broadening of the QRS
complex, ST and T wave changes, varying degrees of heart block, and
bradyarrhythmias. The loss of anterior R waves or the development of complete
heart block is an ominous sign. Patients with bundle branch block and complete
heart block have a very high mortality rate (more than 80%). Levels of cardiac
enzymes (creatine phosphokinase MB, myoglobin and troponin) rise in proportion
to the degree of cardiac damage. Although early reports suggested that diphtheria
might cause conduction disturbances to arise after recovery, this has not been
confirmed in recent series.
Neuropathy. Neurotoxicity is evident in 10-20% of cases. As with
myocardial damage, the extent and severity of nervous system involvement is
determined by the extent and severity of the primary (usually) oropharyngeal
infection. The exotoxin causes segmental degeneration of the myelin sheath and in
severe cases, degeneration of the axon cylinder. Polyneuritis is uncommon in mild
diphtheria but occurs in approximately 7-10% of moderate and severe cases.
Neurological complications develop late, usually between 3 and 8 weeks after the
onset of local symptoms, and often when other severe manifestations are resolving.
Paralysis of the soft palate is a characteristic and early manifestation of
neuropathy. It does not occur with cutaneous diphtheria and therefore probably
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results from local toxin spread in the oropharyngeal tissues. This results in a nasal
voice and regurgitation of ingested fluids through the nose. Later, blurred vision
may occur because of paralysis of the muscles of accommodation together with
paralysis of the pharynx, larynx and respiratory muscles. The IX and X cranial
nerves are most commonly affected, followed by the VII nerve, and the nerves to
the external ocular muscles (III, IV and VI). Quadriparesis is common, and death
from respiratory failure may result either from paralysis of the respiratory muscles
or paralytic closure of the larynx. Limb weakness| occurs in about half of those
with neuropathy. Sensory deficit affects proprioception in particular. Autonomic
dysfunction is common, and sudden hypotension may occur between the fourth
and seventh weeks of disease. The evolution of the neurological deficit is often
asynchronous such that cranial nerve deficits may be improving while peripheral
nerve deficits worsen. In comparing diphtheria with Guillain-Barre syndrome
(GBS), diphtheric polyneuropathy is much more likely than GBS to have a bulbar
onset, to lead to respiratory failure, to evolve more slowly, to take a biphasic
course, and to cause death or long-term disability. In a recent series of adults with
diphtheria from Latvia, 41% of those with limb weakness still could not work at
their 1-year follow-up. Antitoxin seems ineffective in preventing neuropathy if
administered after the second day of diphtheritic symptoms.
Diagnosis. In many parts of the world, especially in developing countries,
diphtheria is still a common disease. It should be considered in any patient with the
following symptoms: tonsillitis and/or pharyngitis with pseudomembrane,
hoarseness and stridor, cervical adenopathy or cervical swelling (bull neck),
unilateral bloody nasal discharge or paralysis of the palate. Direct smears of
infected areas of the throat are often made, but these are unreliable. The diagnosis
is confirmed by isolation and identification of C. diphtheriae from infected sites,
but cultures are often negative, particularly if the patient has received antibiotics
before admission to hospital. The differential diagnosis includes streptococcal or
viral pharyngitis and tonsillitis, and Vincent's angina. Common and sometimes
tragic errors are to diagnose tonsillar diphtheria as infectious mononucleosis, or a
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case of ‘bull neck’ (malignant diphtheria) as mumps. If possible, cardiac enzymes
or troponin should be monitored along with the electrocardiogram to anticipate
myocardial dysfunction and conduction disturbances.
Treatment. Emergency tracheostomy should be performed to anticipate or
relieve respiratory obstruction in laryngeal diphtheria. The procedure must not be
delayed until the patient develops cyanosis. Agitation and the use of the accessory
respiratory muscles are indications for immediate tracheostomy. As the mortality
rate of diphtheria increases with delay in antitoxin administration, treatment with
diphtheria antitoxin should be started on clinical suspicion, without waiting for
definitive laboratory confirmation. The dose of antitoxin depends on the site of
primary infection, the extent of pseudomembrane, and the delay between the onset
and the antitoxin administration: 20 000-40 000 units for faucial diphtheria of less
than 48 hours' duration, or cutaneous infection; 40 000-80 000 units for faucial
diphtheria of more than 48 hours' duration, or laryngeal infection; 80000-100000
units for malignant diphtheria (bull neck, toxic state). Adrenaline (epinephrine)
should be available to cope with rare anaphylactic reactions to the antitoxin.
Antibiotics will stop toxin production and prevent further spread of
organisms in the host. C. diphtheriae is susceptible to a variety of antibiotics
including penicillin, cephalosporins, erythromycin and tetracycline. In a
randomized comparison in Vietnam, the use of penicillin was associated with
shorter fever clearance (median 27 hours) compared with 46 hours for
erythromycin recipients and, whereas there was no penicillin resistance, 27% of the
C. diphtheriae isolated were resistant to erythromycin. The recommended
antibiotic treatment regimen is therefore penicillin G, 50000 units/kg daily in 4
divided doses, with erythromycin, parenterally or orally, 5 mg/ kg four times daily
as an alternative for penicillin-allergic patients. Antibiotic susceptibility should be
checked when cultures are positive. Erythromycin is considered to be more effec-
tive in eliminating the carrier state, although there are limited data to support this.
Bed rest is recommended during the acute phase, but there is no proof of its
benefit. Close electrocardiographic monitoring is indicated, particularly after the
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first week, to detect early signs of cardiac involvement. Angiotensin-converting
enzyme inhibitors (captopril) have been used in patients, but there have been no
randomized trials. If there is high-grade or complete heart block, then temporary
pacing should be performed, although again there have been no large trials to
determine whether these measures influence outcome. One study has suggested
that carnitine may be beneficial by decreasing the incidence of myocarditis, but
additional evidence of its efficacy is required. The administration of corticosteroids
may benefit laryngeal diphtheria by reducing swelling, but otherwise is of no
benefit.
Insertion of a temporary pacemaker is indicated in complete heart block with
bradycardia, although the mortality remains high.
Prevention. Diphtheria is readily preventable by vaccine administration.
This is included in the triple vaccine: diphtheria, tetanus and pertussis vaccine
(DTP) or the quintuple diphtheria, tetanus, pertussis, polio and Hib vaccine. The
recommended primary course of immunization of children aged up to 7 years
consists of three doses: the first at 6-8 weeks of age, the second at 3 months and
the third at 4 months. A booster dose of diphtheria, tetanus, pertussis, and polio
(dTaP/IPV or DTaP/IPV) vaccine is given between 40 months and 5 years of age.
A final immunization with diphtheria, tetanus, polio (Td/IPV) vaccine is given
between 13 and 18 years of age. If primary immunization is delayed until 7 years
of age, or is interrupted, a series of three doses of tetanus and diphtheria toxoid
adsorbed (DT ads), which contains less diphtheria toxoid than DTP, should be
completed, giving the second dose 4—8 weeks after the first, and the third 6-12
months later. Immunity wanes over time; decennial booster doses are required to
maintain protective antibody levels. Large populations of older adults may be
susceptible to diphtheria in developed countries as well as in developing countries.
Research continues into combination vaccines and the intranasal delivery route.
Patients with diphtheria should receive active immunization after recovery. Close
contacts should be screened for C. diphtheriae with throat swab culture.

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 If the immunization status is unclear, they should be treated with an
appropriate antibiotic if culture positive, and receive primary immunization
according to their age. Immunity following immunization can be assessed by
means of the Schick test. A standardized sterile diluted filtrate from a culture of C.
diphtheriae (the Schick test toxin) is injected intradermally (0.2 mL) into the
flexor surface of the left forearm. An equal volume (0.2 mL) of heat-inactivated
filtrate (Schick test control) is injected intradermally into the right forearm. The
injection sites are inspected after 24-48 hours and again at 5-7 days. A lack of
inflammation indicates adequate antitoxic immunity, sometimes nonspecific
reactions (pseudoreactions) occur, but these are usually equal in both arms (i.e.
toxin and control elicit an equal inflammatory reaction). Schick-negative patients
are either resistant to disease or, with gravis and intermedius strains, they may
sometimes develop mild disease.

Malaria
Malaria is a vector-born infection disease. It is widespread in tropical and
subtropical region; it causes disease in approximately 515 ml people and kills
between 1 to 3 ml people The disease is caused by protozoa of the genus
Plasmodium (class Sporozoa).
More than 100 types of malarial plasmodia are known. Four of them are
parasitic in man: P. vivax, the causative organism of tertian malaria; P. malariae,
the causative agent of quartan malaria; P. falciparum, the agent of falciparum
malaria; and P. ovale, the causative agent of ovale malaria, a mild variant of tertian
malaria.
The most serious type is falciparum malaria. It саn bе life-threatening. The
other 3 types of malaria (vivax, ovale and malaria) are generally less serious and
are not life-threatening.
The life cycle of malarial plasmodia includes two hosts: the final host -
stromal mosquito of the genus Anopheles, in which the sexual phase of growth

104
occurs (known as sporogony); and the intermediate host, which is a human or a
vertebrate (in which the asexual multiplication occurs, known as schizogony).
The formed zygote converts into an ookinete that is embedded into the
submucous layer of the mosquito stomach where it divides with subsequent
formation of oocysts and sporocysts. After rupture of the sporocyst into the
haemolymph, the salivary glands of the mosquito release 10 000-15 000 and more
sporozoites which are inoculated into a human subject at the next feeding.
Sporogony continues from 7 to 14 days. The process discontinues at temperatures
below 16 °C. The sporozoites remain viable in the salivary glands of a female
anopheles from 40 to 60 days.
Schizogony. Inside a human body, plasmodia pass through two stages of
asexual multiplication: the exoerythrocytic and erythrocytic stage of schizogony.
Sporozoites are carried by the blood stream to the hepatocytes where they develop
into schizoites and merozoites, which develop and multiply only in red blood cells.
The exoerythrocytic stage lasts 8-10 days in P. vivax and P. ovale, 6-8 days in P.
falciparum, and 15-20 days in P. malariae.
Sporogony. While feeding upon an infected multiplication occurs, In the
causative agent of malaria falciparum, exoerythrocytic schizogony occurs only
during the incubation period that precedes infection of the red cells (the pre-
erythrocytic cycle). In other malarial agents (P. vivax, P. ovale), merozoites invade
not only the erythrocytes, where erythrocytic schizogony begins, but also other
hepatocytes where a new exoerythrocytic cycle begins. P. vivax can undergo the
exoerythrocytic stage of its growth for years. Besides, P. vivax and P. ovale are not
genetically homogeneous. As a result, following a bite of an infected mosquito,
sporozoites of various phenotypes gain entrance to the body. They can undergo
schizogony immediately after invasion of the hepatocytes (tachysporozoites) or
following a period of quiescence (bradysporozoites) that can last 2-14 months and
more. The erythrocytic stage accounts for the malarial attacks.
Merozoite parasitizes in the erythrocyte and develops into trophozoites and
schizonts which divide to give a morula with subsequent formation from 4 to 48
105
merozoites. The newly formed merozoites invade new erythrocytes (after decay of
the former erythrocytes), and the cycle is repeated. Schizogony in the erythrocytes
lasts 48 hours in P. vivax, P. falciparum and P. ovale, and 72 hours in P. malariae.
Part of merozoites invading the red cells, after passing several asexual cycles
of growth, give rise to the sexual forms.
Epidemiology. The source of infection is infected human, whose blood
contains gametocytes, patients with primary or relapsing form of malaria, and
carriers. Humans can infect mosquitoes during the very first days of malaria
induced by P. vivax, P. ovale, and P. malariae, and remain so until the parasites are
contained in the blood.
Malaria falciparum patients become contagious only in 10-12 days after
development of the first malarial attacks, because gametocytes are formed in the
capillaries of the internal organs during 9-11 days.
The life of plasmodia in a human body varies depending on the type of the
parasite: P. falciparum survives for 18 months, some African species can live to 3
years; P. vivax can live to 3 years, P. ovale to 41/2 years while P. malariae can
survive for decades without inducing apparent clinical symptoms and the disease is
only revealed occasionally after transfusion of blood from such infected donors.
Only erythrocytic schizogony occurs in such persons.
Malarial plasmodia can be transmitted from an infected mother to the fetus
through the placenta, during labor or blood transfusion, through syringes and
needles, etc.
Susceptibility to malaria is high, especially in children, who make the
prevalent incidence in endemic areas. Strictly specific immunity to a given species
and strain is induced in persons who sustained malaria. The immunity persists only
on the condition of repeated infections. Immunity can be lost if a person leaves the
endemic area.
Pathogenesis. Paroxysms of malaria are associated with the response of the
thermoregulation centers to the release into blood of a great number of merozoites
and other proteins that are formed during division of schizonts and decay of red
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blood cells. Foreign proteins cause a toxic allergic response in the patient. This
response is characterized by edema of tissues and proliferation of
immunocompetent cells (lymphocytes, monocytes, stellar reticuloendotheliocytes,
etc.). Destruction of erythrocytes by the parasites and autoantibodies, inhibition of
physiologic regeneration of red blood cells in the bone marrow due to splenic
hyperfunction cause progressive anemia, leucopenia, and thrombocytopenia.
Anemia evokes dystrophic changes in the myocardium, central nervous system,
liver and other parenchymatous organs.
Malarial plasmodia and their metabolites, the malarial pigment, and the
products of protein degradation evoke anaphylaxis: hyperadrenalinaemia,
hyperglycemia, hypercholesterolemia, hyperkalemia, and relative hyponatremia.
Hyperadrenalinaemia provokes hypertension, tachycardia, spasm of the peripheral
vessels and upsets microcirculation in the internal organs.
Increased immunoglobulins (IgM, IgG), activated phagocytosis of invaded
erythrocytes and decay of the parasites in macrophages stop the first series of
paroxysms after the second or third attack. The disease passes into its next phase,
secondary occult period, or early (short) interparoxysmal period. Due to imperfect
initial immune reactions, the blood fails to be completely freed from the parasites.
Decreased immune reactions promote an increase in the number of malarial
plasmodia and development of a new wave of attacks-early relapses. They follow
in 2 weeks to 3 months after termination of the first series of paroxysms.
During early relapses, the developed immunity becomes sufficiently strong
to suppress schizogony and to promote clinical recovery.
Clinical picture. The clinical symptoms depend on the specific causative
agent of the disease that invades the patient. Four forms of malaria are thus
distinguished: tertian or vivax malaria, quartan malaria, falciparum malaria, and
ovale malaria. Each form can be mild, moderate or severe. The following periods
are distinguished in the course of the disease: incubation period, primary (acute)
manifestations, occult period, relapses, and the recovery period.

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 The incubation period of tertian (vivax) malaria is from 10-21 days to 6-14
months; of quartan malaria, 3-6 weeks; of falciparum malaria, 8-16 days; and of
ovale malaria, 7-20 days. In the early stages, malaria symptoms similar to those of
many other caused by bacteria, viruses, or parasites. Symptoms may include: fever,
chills, headache, sweats, fatigue, nausea and vomiting.
Paroxysms are characteristic of the disease. A typical paroxysm includes the
"cold stage", the "hot stage" and the "wet stage". The malarial paroxysm begins
with the cold stage: the patient is attacked by shaking chill that cannot be managed
by warm cover.
The lips, nose tip and the fingers become cyanotic. The body temperature
rapidly rises to 40-41 °C within 90-120 minutes. The chill lasts 1-3 hours and is
followed by the hot stage (fever). The face reddens, the skin becomes dry. The
patient removes all covers and his underwear, he becomes restless, complains of
thirst, headache, and lumbar pain. Respiration rate increases, tachycardia and
convulsions develop, consciousness is confused. Nausea, vomiting, and pain in the
spleen occur. In 5-8 hours, the body temperature falls critically to subnormal with
profuse sweating. The patient is exhausted and drowsy. A paroxysm lasts 8-12
hours. It usually begins in the morning. The subjective condition of patients
improves in the interparoxysmal periods.
Paroxysms recur at regular intervals: every other day in tertian malaria, and
every third day in quartan malaria. During the first week of the disease, this
regularity can be absent in non-immune persons; fever can be irregular. Despite a
prolonged schizogony in falciparum malaria (48 hours), paroxysms can occur daily
or even twice a day. This is due to the onset of erythrocytic schizogony at various
terms.
After 1-2 paroxysms, the skin and the visible mucosa of many patients turns
pale yellow. Herpes labials and nasalis occur. The spleen and the liver are
enlarged. Palpation reveals their tenderness and firm consistency. The changes in
the blood are the following: the hemoglobin and erythrocyte count decrease;

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leucopenia, often with relative lymphocytosis, thrombocytopenia, and aniso- and
poikilocytosis are seen; ESR accelerates. Plasmodia can be found in blood smears.
In the interparoxysmal periods (apyrexia), the patient preserves his working
capacity. As the number of paroxysms increases, the patient develops weakness
during the afebrile periods; he complains of headache, myalgia, and arthralgia. The
skin acquires a greyish hue; jaundice and hepatosplenomegaly intensify. The
number of paroxysms in primary malaria varies from 10 to 12. The body
temperature is maximum on the second week of the disease, but during later
paroxysms it gradually decreases, the number of parasites in the blood decreases
too, and paroxysms cease. In untreated or inadequately treated cases, a short
afebrile period is followed by a reinvasion of the blood stream with the parasites to
cause early relapses, during which the temperature reaction acquires the
intermitting character, specific for each particular type of malaria.
Early relapses in vivax and ovale malaria are followed by an occult period
lasting 8-10 months (and longer), which ends in late exoerythrocytic relapses due
to multiplication of new generations of exoerythrocytic merozoites and reinvasion
of the blood stream (true relapses).
Late relapses in quartan malaria are due to multiplication of persistent
erythrocytic forms of Plasmodia. The clinical course of late relapses is milder than
attacks of the early period. The latent period or relapses are absent in falciparum
malaria.
The severest course is characteristic of falciparum malaria. Its fever is
irregular and the paroxysms are long (lasting 24-36 hours and longer). The afebrile
periods are less pronounced. Chills and sweating are not characteristic because the
temperature variations are not very marked. Parasitaemia increases rapidly to attain
a high level in few hours.
If diagnosed untimely and not treated, falciparum malaria runs a malignant
course with cerebral complications (malarial coma, psychosis), algid malaria with
severe vascular failure (septic shock), and acute renal failure.

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 Tertian malaria (vivax and ovale) runs a benign course. Attacks of vivax
malaria usually develops in the morning; while in ovale malaria macroorganism
and the parasites is attained; it can Tertian malaria (vivax and ovale) runs a benign
course. Attacks of vivax malaria usually develop in the morning; while in ovale
malaria they are more common in the evening.
Quartan malaria is usually benign. It is characterized by a prolonged course
and a great number of relapses over many years. The patient can remain the source
of infection that can be transmitted parenterally (schizont malaria).
Malaria in pregnant women is the cause of frequent abortion, eclampsia,
premature labor, and stillbirth. Due to marked vegetative endocrine shifts and
decreased immune defense in the pregnant, malaria runs a severe course with
marked anemia, jaundice and edema. Early diagnosis and timely treatment are
therefore very important. Antimalarial preparations such as delagil or amodiaquine
do not produce adverse effect on pregnancy or fetal growth.
Diagnosis. Diagnosis is established on the basis of history of being in
endemic area, clinical symptoms, epidemiologic and laboratory findings.
The laboratory methods include microscopy of thin (species identification)
and thick (detect organism) blood smears in which plasmodia are detected. The
number of malarial plasmodia are not great during the first attacks. Blood should
therefore be studied up to 3 times a day during 2-3 days. Blood specimens should
be taken at the height of fever as well as during apyrexia. In the blood analyses
develop anemia. Reasons of anemia: both hemolysis and decreased red cells
production, splenomegaly, bone marrow depressed, fixed immune complex in
membrane of erythrocytes.
Specific diagnosis of malaria is possible with serologic studies: indirect
immunofluorescent test, indirect haemagglutination and enzyme-labelled antibody
tests. These methods are used to examine blood donors (to reveal carriers of P.
malariae), to reveal malaria in persons who took antimalarial preparations before
attendance for medical aid, and to establish the absence of disease transmission in
endemic areas.
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 Treatment. Treatment of malaria patients is aimed at termination of acute
paroxysms, prevention of relapses and elimination of gamonts.
All antimalarial preparations are divided into four groups:
1. Gametoschizotropic drugs, preventing development of erythrocytic
schizoites: quinine, mepacrine, proguanil, derivatives of 4- aminoquinoline:
chloroquine (chloroquine diphosphate), nivaquine (chloroquine sulphate),
plaquenil, amodiaquine, pyrimethamine.
2. Histoschizotropic preparations preventing development of trophozoites:
proguanil, 8-aminoquinoline derivatives (primaquine)
3. Gametocides destroying gamonts: pyrimethamine, 8-aminoquinoline
derivatives.
4. Sporontocides preventing maturation and growth of gamonts in the
mosquito stomach: proguanil, pyrimethamine, and 8-aminoquinoline derivatives.
In order to abate acute symptoms of all types of malaria, 4-aminoquinoline
derivatives are given to adults (after meals) in the following doses: chloroquine or
nivaquine, 2-2.5 g per course. The dose for the first intake is 1 g (4 tablets of 0.25
g), 0.5 g in 6-8 hours; on the second and third day, 0.5 g given for one intake.
Falciparum malaria is treated during five days (in the absence of immunity
in the patient), a dose of 0.5 g is given for one intake on the 4th and 5th day.
Plaquenil's effect is similar to that of chloroquine. It is given per os, 2 g for
adults for a course. The first intake is 0.8 g (4 tablets of 0.2 g); in 6-8 hours, the
dose is 0.4 g; and 0.4 g is given for one intake on the second and third day.
Falciparum malaria is treated for 5 days: a dose of 0.4 g is given for one
intake on the 4th and 5th day.
Population of endemic regions has immunity against malaria and only one
third of the mentioned doses should be given. The duration of the therapy is also
shorter.
Therapy with chloroquine and plaquenil terminates malarial paroxysms in
24-48 hours, and the plasmodia disappear from the blood in 48-72 hours after the
beginning of the therapy, if malaria is due to the strain sensitive to 4-
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aminoquinolines. Radical treatment of patients (eradication of sexual and asexual
parasites) is attained with gametocides and histoschizotropic drugs. Falciparum
malaria patients are given pyrimethamine, simultaneously with or after the above
mentioned drugs. The doses for adults are 0.03 g (6 tablets of 0.01 g can be given
on the first day), or primaquine, 0.045 g during three days. The drugs are given per
os. In order to prevent late relapses in tertian malaria, primaquine or quinocide
should be given after mentioned therapy in a dose of 0.27%"a day (3 tablets of
0.09 g) for 14 days, and 0.03 g (3 tablets of 0.01 g) for 10 days, respectively.
The sexual forms of P. vivax, P. ovale, and P. malariae are destroyed after
termination of the erythrocytic schizogony. Gametotropic preparations are
therefore not used to treat malaria.
Malaria due to the chloroquine-resistant strains P. falciparum and P. vivax
should be treated with quinine hydrochloride. The dose of 0.65 g (3V4 tablets of
0.2 g) should be given 3 times a day for 10-14 days; or a combination of
pyrimethamine (0.25 g) and sulphadoxine (0.5 g), 2-3 times a day for 2-3 days, or a
combination of sulphalene (0.2 g) and sulphadoxine (0.5 g), or a combination of
pyrimethamine (0.025 g) and sulphalene (0.5 g) should be prescribed.
Radical cure is attained with a combination of quinine and tetracycline (0.5 g
4 times a day for 7 days).
In pyrimethamine-resistant cases, in order to attain a sporontocide effect,
primaquine is given in a single dose of 0.045 g (5 tablets of 0.009 g).
Malignant forms of falciparum malaria should be treated with quinine or
chloroquine base preparations given in a dose of 5-10 mg/kg 2 times a day (900 mg
of chloroquine base maximum).
Pathogenetic therapy is aimed at decreasing vascular permeability,
eliminating brain edema and hyperazotaemia, and at maintaining diuresis. To that
end, along with the aetiotropic therapy, it is necessary to give glucocorticosteroids,
antihistaminic (dimedrol, suprastin), rheopolyglucin, haemodez, salt solutions and
a 5 per cent glucose, diuretics (Lasix, mannitol) and cardiovascular preparations.

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 Prophylaxis. The complex of antimalarial measures acts on all three factors
of the epidemic process: the source of infection, routes of infection transmission
and susceptibility of population. The choice of the leading measure depends on the
malaria infection rate. Control of the source of infection is decisive.
This can be attained during the first visit to malaria patients and by active
screening of population. Parasitoscopy of population is an important factor in this
respect. All screened patients and parasite carriers should be given obligatory
treatment.
Malaria patients with acute clinical symptoms should be placed in hospitals
or treated at home. Patients with severe clinical forms of malaria, children and
pregnant women should be hospitalized.
Convalescents may be discharged from hospital not sooner than in 1-2 days
after disappearance of the plasmodia from the blood.
Convalescents and parasite carriers should be observed in outpatient
conditions for 21/2 years in tertian malaria and l1/2 year in falciparum malaria.
Measures aimed at reduction of the number of infection transmitters include
elimination of sites of mosquito multiplication, elimination of their larvae and
imagoes. Water bodies that have no economic importance should be dried on the
area with the radius of 3 km around populated places; swamps should be irrigated;
all open water basins or watering systems should be given proper sanitary control.
In foci of malaria and in places where such foci reappeared, or where
anophelogenic danger increased, it is necessary to control the malaria vector
(mosquito populations). Foci of infection should be regularly revealed. If mosquito
populations increase, they should be controlled by destroying the larvae and the
imagoes.
Open water bodies should be treated with chemicals. Irrigation of fields
should be intermittent so that the larvae of mosquitoes could be destroyed before
they turn into imagoes. Waterfowl and fishes feeding on the larvae should be
raised in open water bodies.

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 Chemical preparations should be used to control mosquitoes in populated
places. Buildings should be treated before the larvae turn into the winged insects.
Depending on residual effect of the chemical poison, treatment can be given on
one or two occasions.
If malaria incidence in a populated place is high, all residential and other
buildings, and also cattle sheds should be treated. In large towns, all residential and
other buildings, as well as cattle sheds should be treated in the vicinity of the
anophelogenic water body.
Treatment of the focus can be sufficient if the infection rate is low.
Only those houses where malaria patients or parasite carriers reside, and also
the neighboring houses, should be treated. Mechanical protection of housing
(especially of bedrooms) is attained with screens, mosquito netting on the windows
and doors. Means of individual protection and repellents should be used. In order
to kill mosquitoes within enclosures, it is recommended to use aerosols of
pyrethrum or pyrethrin.
Chemotherapy is important in control of malaria and its prevention among
population. Chemoprophylaxis of population in endemic areas begins 1-2 weeks
before appearance of the first generation of mosquitoes and is conducted during the
entire epidemic period, and also 6 weeks after its termination. Travelers to the
endemic areas should receive chemoprophylaxis too. The following preparations
can be used for chemoprophylaxis: chloroquine or novaquine in a dose of 0.5 g or
pyrimethamine 0.025-0.05 g once a week.
The preparation is given twice a week. An obligatory condition for effective
prophylaxis is regular administration of chemical preparations. The selection of a
particular prophylactic preparation depends on the dominating parasite, its
sensitivity to a given preparation, individual tolerance of the given preparation and
the presence of contraindications. The preparations are given after meals with at
least half-glass of water.

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