Viro Finals

HEPATITIS VIRUSES
o
o
o
o
o
5 types: A-E
main target organ: liver
differ: structure, mode of replication, course of disease, mode of
transmission
classic signs: jaundice plus elevated liver enzymes
NB. Histopathologic lesions in the liver are identical regardless of the
virus type
Hepatitis A
o
caused by a picornavirus, under the new genus Hepatovirus
o
spherical particle containing ssRNA
o
spread by fecal-oral route
o
incubation period: about 1 month
o
does not cause chronic liver disease
o
often results from: eating contaminated shellfish or other food &
water
o
rarely causes fatal disease
Serology
1. HAV : the agent
2. Anti-HAV : detectable at onset of symptoms; persists throughout
life
3. IgM anti-HAV : indicates recent infection; (+) 4-6 months after
infection
Tx, Prevn, Control

o
hygienic measures
o
water chlorination
o
immune globulin (Ig):
o
80% effective if given before or early in the incubation period
Hepatitis B
o
due to a hepadnavirus
o
spread parenterally (blood,
needle, sex, perinatal)
o
median incubation period: 3 mo
o
5-10% develops chronic hepatitis
o
causally associated with primary hepatocellular carcinoma
o
3 morphologic forms:
1. small spherical particles most numerous, HBsAg
2. tubular or filamentous HBsAg
3. large spherical virions ( Dane particle) HBsAg envelop, HBcAg
core
o
circular dsDNA
o
four phenotypes of HBsAg : adw, ayw, adr, ayr
o
stable at -20C for over 20 yr, 37C for 60 min, dried & stored at 25C
for 1 wk, pH 2.4 for 6 hr
o
not destroyed by UV
The picornavirus structure of the HAV. The icosahedral capsid is made up of four viral
polypeptides (VP1 to VP4). Inside the capsid is a single-stranded, positive-sense RNA
(ssRNA) that has a genomic viral protein (VPg) on the 5 end.
o
o
o
one serotype; seven genotypes

stable at pH 1.0 for 2 hr, 60C for 1 hr, dried & stored at 25C for 1
mo, -20C for years
destroyed by autoclave for 20 min,
boiling for 5 min, dry
heat for 1 hr, UV for 1 min, formalin for 3 days at 37C, chlorine for
30 min
Epidemiology
o
responsible for about 40% of all hepatitis cases high concentration of
virus in feces esp. 2 weeks before jaundice
o
90% of children & 50% of adults have inapparent but productive
infections
o
outbreaks usually originate from a common source (eg. water supply)
o
incidence directly related to poor hygiene & over-crowding
o
seropositivity in adults:
13%- Sweden
88%- Taiwan
Clinical Syndromes
o
due to immune-mediated damage to the liver
o
disease in children: milder & usually
asymptomatic
o
symptoms usually wanes during icteric phase
o
complete recovery: about 99%
o
fulminant hepatitis: 1-3 per 1000 with 80% mortality
Laboratory Diagnosis
Epidemiology
o
US: 300,000 infected annually
o
high rates of sero-positives: Italy, Greece, Africa, Southeast Asia
o
chronic carrier: HBsAg positive on 2 occasions at least 6 months apart
o
major risk factors: sexual promiscuity & drug abuse
3 Clinical Syndromes
o
acute infection
o
chronic infection
o
primary hepatocellular ca
Hep
o
o
o
o
o
o
o
B: Acute infection
only 25% of those infected are clinically apparent
characterized by long incubation period & an insidious onset
S/S: fever, malaise, anorexia
then: nausea, vomiting, abdominal discomfort, chills
next: jaundice, dark urine, pale stools
1st sign of recovery: renewed appetite
fulminant cases: 1% of icteric cases
Hep B: Chronic infection

o
occurs in 5-10% of HBV infections (95% of neonates)
o
usually occurs after mild or inapparent illness
o
o
usually detected by elevated liver enzymes on routine chemistry

10% of chronic cases develops cirrhosis & liver failure
Primary Hepatocellular Carcinoma

o
WHO: 80% of all PHC cases are secondary to chronic Hepatitis B
infection usually fatal
o
latent period between HBV infection & PHC: 9-35 years
Pathophysiology: PHC
The virus induces carcinoma by promoting continued liver repair and cell
growth in response to tissue damage OR by integrating into host
chromosomes & stimulates growth.
PATHOLOGY
o
spotty parenchymal cell degeneration
o
diffuse lobular inflammatory reaction
o
disruption of liver cell cords
o
screening: agglutination test
o
confirmatory:
ELISA (Ag & Ab detection)
PCR (for viral DNA)

Hepatitis B
o
HBV: the agent
o
HBsAg: surface antigen
o
HBeAg: indicates viral replication
o
HBcAg: core antigen
o
Anti-HBs: indicates past infection
o
Anti-HBe: suggest presence of HBV
o
Anti-HBc: indicates past infection
Major determinants of acute and chronic HBV injection. HBV infects the liver but
does not cause direct cytopathology. Cell-mediated immune lysis of infected cells,
potentially triggered by interferon action, produces the symptoms and resolves the
infection. Insufficient immunity can lead to chronic disease. Chronic HBV disease
predisposes a person to more serious outcomes. Purple arrows indicate symptoms;
green arrows indicate a possible outcome.
Serologic Markers: Hepatitis B

Exposure
0 time
HBsAg
2 weeks
HBeAg
1 month
Anti-HBc
6 weeks
Anti-HBe
5months
Anti-HBs
6 months
(SGPT: 2-5mon; symptoms: 2 1/2-4mon)
Tx,
o
o
o
o
o
Prevn, Control
no specific treatment
trials: interferon, adenine arabinoside, steroids, azathioprine
blood screening
vaccination
Hepatitis B Immune-globulin
(SGPT: 2-5mon; symptoms: 21/2-4mon)
Hep B immune-globulin
For post-exposure prophylaxis for newborns of HBsAg(+) mothers & per
mucosal exposure to secretions of individuals who are HBsAg positive
Serologic events associated with the typical course of acute hepatitis B disease.
Tx, Prevn, Control
No specific treatment
Trials: interferon, adenine arabinoside, steroids, azathioprine
Blood screening
Vaccination
Hepatitis B Immune-globulin
Hep B immune-globulin
For post-exposure prophylaxis for newborns of HBsAg(+) mothers &

per mucosal exposure to secretions of individuals who are
HBsAg positive
Hepatitis C
o
family Flaviviridae, genus Hepacivirus
o
positive-stranded RNA virus
o
6 genotypes; >70 subtypes
o
accounts for about 90% of NANBH infection
o
major cause of post-transfusion hepatitis
o
70-90% of HCV patients develop chronic hepatitis
Epidemiology
o
spread: parenteral & sexual
o
risk factors: IV drug users, blood recipients
o
suspicion: HBV-negative, posttransfusion hepatitis
o
occurs in 5-10% of transfusion recipients
Clinical Syndromes
1. Acute Form: similar to acute Hepatitis A & B but inflammatory response
is less and symptoms are milder
2. Chronic Form: more prevalent than HBV, often leads to cirrhosis
o
Anti-HCV is not protective
o
ELISA (antibody detection)
o
RT-PCR (HCV-RNA)
o
markers:
1. HCV: the agent
2. Anti-HCV: the antibody
Tx, Prevn, Control
o
Interferon alfa and ribavirin:
o
the only effective treatment
o
(50% response rate)
o
liver transplant
o
supportive
o
blood screening
accounts for 90% of the cases of NANBH virus infection and is the
major cause of posttransfusion hepatitis.
a flavivirus with a positive sense RNA genome and is enveloped.
HCV has an inclination to establish noncytolytic persistent infections
and therefore chronic disease
Epidemiology of HBV, HCV, and HDV
DISEASE/VIRAL FACTORS
o
o
o
TRANSMISSION
o
o
In blood, semen, and vaginal secretions (HBV); saliva and

mothers milk).
Via transfusion, needlestick injury, shared drug
paraphernalia, sex, and breast-feeding.
WHO IS AT RISK?
o
o
o
o
Enveloped virus is labile to drying. HBV is less sensitive to

detergents than other enveloped viruses.
Virus is shed during asymptomatic periods.
Virus causes chronic disease with potential shedding.
Children: mild asymptomatic disease with establishment of

chronic infection.
Adults: insidious onset of hepatitis.
HBV-infected people co-infected or superinfected with HDV:
abrupt, more severe symptoms with possible fulminant
disease.
Adults with chronic HBV: at high risk for primary
hepatocellular carcinoma.
In acute infection, it is similar to HAV and HBV but symptoms are

usually milder
Chronic persistent hepatitis caused by HCV is even more prevalent
than that caused by HBV, often progressing to chronic active
hepatitis, cirrhosis, and finally liver failure
Cell-mediated immunopathology is responsible mainly for producing
the tissue damage.
Continual liver repair and induction of cell growth occurring during
chronic HCV infection are predisposing factors in the dev of PHC.
ELISA detection of Antibody
Seroconversion occurs w/in 7-31 weeks of infection
The presence of the virion RNA in serum I s a better indicator of the

disease
RT-PCR can detect HCV RNA in seronegative people

Treatment, Prevention and Control
Recombinant interferon-alpha is the only known effective treatment

for HCV.
Supportive therapy
Hepatitis D
o
Delta agent: HDAg surrounded by HBsAg envelope
o
HDV: ssRNA, smallest of known human pathogens
o
responsible for about 40% of fulminant hepatitis
o
NB. dependent on HBV for replication: (can replicate only in HBVinfected cells)
Epidemiology
o
agent infects children & adults with underlying HBV infection
o
distribution: worldwide
o
high risk: drug users & hemophiliacs
Clinical Syndromes
o
agent increases severity of Hepatitis B infection
o
Delta agent carriers: more likely to develop fulminant hepatitis
o
ELISA & RIA (Ag /Ab detection)
o
HDV-RNA by PCR
o
Markers:
o
HDV: the agent
o
HD Ag: delta antigen; detectable in early acute infection
o
Anti-HDV: indicates past or present infection
Tx, Prevn, Control
o
no known specific treatment
o
Hep B vaccine protective for Delta infection
Approx. 15 M people are infected with HDV (delta agent)

Responsible for causing 40% of fulminant hepatitis infections
Uses HBV and target cell proteins to replicate and produce its one
protein
A viral parasite
The HBsAg is essential for packaging the virus
ELISA and RIA to detect the delta

antigen or antibodies
Delta agent can be detected in blood in
acute phase
MODES OF CONTROL
o
o
Avoidance of high-risk behavior

HBV: vaccine and screening of blood supply.
Clinical Syndrome
HCV can cause acute infection but is more likely to establish chronic
infections.
A viremia can be detected w/in 1-3 weeks of a transfusion of HCVcontaminated blood
The viremia lasts 4-6 months in people with an acute infection
Pathogenesis
the delta agent is spread in blood, semen, and vaginal secretions.

It can only replicate and cause disease only in people with active HBV
infections
It is transmitted through the same routes as HBV. A person then
becomes co-infected with HBV and the delta agent.
A person w/ chronic HBV can also be superinfected with the delta
agent
A more rapid, severe progression occurs in HBV carriers superinfected

w/ HDV than in co-infected w/ HBV and the HDV.
Replication of delta agent results in cytotoxicity and liver damage
Protection stems from the immune response to HBsAg because it is
the external antigen and viral attachment protein for HDV
Damage to the liver occurs as a result of the direct CPE of the delta
agent combined with immunopathology of the HBV disease
Hepatits G Virus
ss RNA virus of Flaviviridae family
27% homology with HCV, 95% with GBV
A transfusion-transmitted hepatitis
o
(also sexually and from mother to infants)
The recently isolated GB-C virus is likely the same as the

hepatitis G virus ,
is similar to the hepatitis C virus but

o
clearly a distinct species
GB was a 34 year-old surgeon who contracted hepatitis

GB Agent in his serum abs been passed in monkeys over the
years
GB Agent contains 2 flavivirus sequences related to but distinct
from HCV
ssRNA virus of family Flaviviridae
A transfusion-transmitted infection
HGV co-infection is observed in 6& of chronic HBV infections and
10% in chronic HCV infections
Unclear if HGV is actually pathogenic
Diagnostic tests: Anti-HGV, HGV RNA by PCR.
REO, ROTA, CALICI VIRUS

Clinical Syndromes
fulminant hepatitis is more likely to develop in people infected with

the delta agent than in those infected with the other hepatitis virus
can result in hepatic encephalopathy (w/ altered mental capacity)

and massive hepatic necrosis
no specific treatment for HDV hepatitis
prevention of infection w/ HBV will prevent HDV infection
Hepatitis E
o
Enterically transmitted: fecal-oral or water-borne transmission
o
causes large epidemics in Asia & North Africa
o
distribution: worldwide, but more problematic in developing
countries
o
NB: virus is unclassified
o
symptoms & course: very similar to HAV, causes only acute disease
o
mortality: 1-2% (about 10X that of HAV)
o
most serious in pregnant women (mortality about 20%)
o
o
o
o
o
o
o
HEV (E-NANBH) (the E stands for enteric or epidemic) is

predominantly spread by the fecal-oral route, esp in contaminated
water
Resembles calicivirus and Norwalk agent in size and structure
Problematic in developing countries
Symptoms and course of HEV are similar to those of HAV disease
Causes only acute disease
Poor serum IgG response
Has a ss-polyA RNA genome
Hepatitis Viruses
o
A infectious
o
B serum
o
C post transfusion non A non B
o
D delta
o
E enteric non A non B
Hepatitis
F Virus
27-37 nm Virus-Like Particles (VLP)
genome: dsDNA
thought to be a mutant strain of HBV
virus was seen in the cytoplasm of hepatocytes in ONE
experimental monkey
infection is sporadic and enterically transmitted
viral antigens (feces) and elevation of transaminases appear in
20 days
assume a fatality course in 20% of cases
HFV antigen has been detected by ELISA in 66% of cases
1. Reovirus
not known to cause human disease
3 distinct but related types
can cause many inapparent infections
(most people have Ab by early adulthood)
Human volunteers: failure to demonstrate a clear cause-andeffect relationship to human illness
Unique Features of Reoviridae
Double-layered capsid virion (60 to 80 nm) has icosahedral symmetry

containing 10 to 12 double-stranded genomic segments (depending
on the virus)
Virion is resistant to environmental and gastrointestinal conditions
(e.g. detergents, acidic pH, drying0
Rotavirus and orthoreovirus virions are activated by mild proteolysis
to intermediate/infectious subviral particles (ISVP), increasing their
infectivity
Inner capsid contains a complete transcription system, including
enzymes for 5 capping and polyadenylate addition.
Viral replication occurs in the cytoplasm. Double-stranded RNA
remains in the inner core
Rotavirus inner capsid aggregates in the cytoplasm and then buds into
the endoplasmic reticulum, acquiring its outer capsid and a
membrane, which then lost
Virus is released by cell lysis
Serologic diagnosis of infection requires the documentation of a

fourfold or greater increase in virus specific antibody between an
acute and convalescent specimen, since antibodies to orthoreoviruses
typically are present in healthy children and adults.
The techniques used to detect orthoreovirus antibody include

hemagglutination inhibition, neutralization, complement fixation and
indirect immunofluorescence but are not routinely performed
Treatment
No specific antiviral therapy available.
2. Rotavirus
the most important cause of infantile gastroenteritis in the world
5 groups: A B C D E
Group A: most frequent pathogen
incubation period: 1-3 days
S/S: fever, abdominal pain, vomiting, watery diarrhea, dehydration
viral excretion in stools: up to 50 days after onset of diarrhea
NB. About half have diarrhea
Pathogenesis ROTA
affects villi of small intestine, impairs transport mechanism (gastric &

colonic mucosa spared)
diarrhea is due to impaired sodium and glucose absorption
3-8 wk for restoration of

normal function
Treatment and Control
symptomatic & supportive
careful disposal of stools
effective hand washing
careful processing of food
purification of drinking water & swimming pool water
no vaccine is available
Epidemiology
transmission: fecal-oral route
most cases are sporadic
worse in developing countries
Laboratory diagnosis
RT-PCR - most widely used for viral detection in feces and vomitus, food &
water
ELISA - most efficient in detecting soluble & particulate antigens; antibody
responses
IEM
RETROVIRUSES (RNA TUMOR VIRUSES)

UNIQUE CHARACTERISTICS OF RETROVIRUSES
Duration of Illness
about one week (3-8 days)
recover completely
usual complications:
o
dehydration & metabolic acidosis
Immuno-deficient children have severe and prolonged disease

Host Response
Initially: IgM
Later: IgG & secretory IgA
Lab Diagnosis
demonstration of virus in stool

[IEM, LPA, ELISA]
rise in antibody titer by ELISA
genotyping of virus nucleic acid

from stool by PCR
[the most sensitive method]
Treatment and Prevention
supportive
immunization
waste water treatment
sanitation
virus has enveloped spherical virion that is

80 to 120 nm in diameter and that encloses a capsid containing two
copies of the positive-strand RNA genome
RNA-dependent DNA polymerase (reverse
transcriptase) and integrase enzymes are carried in the virion.
Virus receptor is the initial determinant of
tissue tropism.
Replication proceeds through a DNA
intermediate, termed provirus
The provirus integrates randomly into the
host chromosome and becomes a cellular gene.
Transcription of the genome is regulated by
the interaction of host transcription factors with promoter and
enhancer elements in the long-terminal repeat (ltr) portion of the
genome
Simple Retroviruses encode gag, pol, and
env genes. Complex viruses also encode accessory genes (e.g., tat,
rev, nef, vif, vpu for HIV)
Virus assembles and buds from the plasma
membrane.
Final morphogenesis of HIV requires protease
cleavage of gag and gag-pol polypeptides after envelopment.
3. Calicivirus
important agents of viral gastroenteritis
5 Ag types; star of David appearance
most important member: Norwalk virus
incubation period: 24-48 hr
characterized by: rapid onset, brief clinical course (12-60 hr)
S/S: nausea, vomiting, abdominal pain, low-grade fever,

headache, malaise, diarrhea
Norwalk Virus
NB. the most important cause of epidemic viral gastroenteritis in adults
Characterized by:
1. absence of bacterial pathogen
2. rapid onset and recovery & relatively mild systemic signs
3. a pattern that spreads rapidly with no particular age nor geographic
predilection
Small, non-enveloped 27nm particle with ss-RNA genome
Self-limited gastroenteritis
1969: GE outbreak in Norwalk, Ohio
Most important cause of epidemic

viral gastroenteritis in
adults
Epidemiology
Usually occurs in schools, recreational camps, nursing homes
Infection is mainly through food & water and person-to-person
Agent occurs worldwide &

outbreaks all-year round
Clinical Infection
incubation period: 24-48 hr
S/S: nausea, vomiting, abdominal pain, fever, headache,

malaise, diarrhea
symptoms lasts for 12-60 hours
stools: non-bloody & non-mucoid
Cross section of HIV. The enveloped

virion contains two identical RNA strands,
RNA polymerase, integrase, and two
tRNAs base-paired to the genome w/in
the protein core. This is surrounded by
proteins and a lipid bilayer. The envelope
spikes are the glycoprotein (gp) 120
attachment protein and gp4` fusion
protein.
RETROVIRUS GENES AND THEIR FUNCTION

GENE
gag
pol
env
tax
tat
rex
VIRU
S
All
All
All
HTLV
HIV-1
HTLV
rev
HIV-1
nef
HIV-1
vif
vpu
vpr
(vpx*)
LTR
HIV-1
HIV-1
HIV-1
All
FUNCTION
Group-specific antigen: core and capsid proteins
Polymerase; reverse transcriptase, protease, integrase
Envelope: glycoproteins
Transactivation of viral and cellular genes
Transactivation of viral and cellular genes
Regulation of RNA splicing and promotion of export to
cytoplasm
Regulation of RNA splicing and promotion of export to
cytoplasm
Alteration of cell activation signals; progression to AIDS
(essential)
Virus infectivity, promotion of assembly
Facilitation of release of virus, decrease of cell surface CD4
Transport of complementary DNA to nucleus, arresting of cell
growth
Promoter, enhancer elements
HUMAN IMMUNODEFICIENCY VIRUS
Morphological distinction of retrovirions. The morphology and position of the

nucleocapsid core are used to classify the viruses. A-type particles are immature
intracytoplasmic forms that bud through the plasma membrane into mature B-type,
C-type and D-type particles.
CLASSIFICATION OF RETROVIRUSES
SUBFAMILY
Oncovirinae
CHARACTERISTICS
Are associated with cancer and
neurological disorders
EXAMPLES
-
Have eccentric nucleocapsid core

in mature virion
Mouse mammary tumor

virus
Have centrally located

nucleocapsid core in mature
virion
Human Tlymphotrophic virus

(HTLOV-1, HTLV-2,
HTLV-5), Rous sarcoma
virus (chickens)
Have nucleocapsid core with

cylindrical form
Have slow onset of disease; casue
neurological disorders and
immunosuppression; are viruses
with D-type, cylindrical
nucleoapsid core
Cause no clinical disease but
characteristic vacuolated foamy
cytopathology
Lentivirinae
Spumavirinae
Mason-Phizer monkey
virus
Human foamy virus
Human foamy virus
The life cycle of

HIV. HIV binds to
CD4 and
chemokine coreceptors and
enters by fusion.
The genome is
reverse
transcribed into
DNA in the
cytoplasm and
integrated into
the nuclear
DNA.
Transcription
and translation
of the genome
occurs in a
fashion similar
to that of HTLV1. the virus
assembles at the
plasma
membrane and
matures after
budding from
the cell.
Pathogenesis of HIV. HIV causes lytic and latent infection of CD4 T cells and persistent
infection of cells of the monocyte/macrophage family and disrupts neurons. The
outcomes of these actions are immunodeficiency and AIDS dementia.
Time course and stages of HIV disease. A long clinical latency period follows the
initial mononucleosis-like symptoms. The progressive decrease in the number of CD4
T cells, even during the latency period, allows opportunistic infections to occur. The
stages in HIV disease are defined by the CD4 T-cell levels and occurrence of
opportunistic diseases.
CD4 T cells play a critical role in the regulation of the human immune response by
mediating the release of soluble factors and the DTH response toward intracellular
pathogens. HIV-induced loss of the CD4 T cells results in loss of the functions shown,
especially the DTH responses and the lymphokine control of immune responses.
ENDOGENOUS RETROVIRUSES
complete and partial provirus sequences with gene sequences similar

to those of HTLV, mouse mammary tumor virus and other retroviruses
can be detected in humans
these endogenous viruses generally lack the ability to replicate

because of deletions or the insertion of termination codons or
because they are poorly transcribed.
PICORNAVIRIDAE
HUMAN T-LYMPHOTROPIC VIRUS AND OTHER ONCOGENIC RETROVIRUSES
the oncovirinae were originally called RNA tumor viruses and have
been associated with the development of leukemias, sarcomas, and
lymphomas in many animals
these viruses are not cytolytic
the members of this family are distinguished by the mechanism of
cell transformation and thus the length of the latency period between
infection and the development of the disease.
The sarcoma and acute leukemia viruses have incorporated cellular
genes (protooncogenes) encoding growth-controlling factors into their
genome.
These viruses can cause transformation and are highly oncogenic.
Transformation results from the overproduction or altered activity of
growth-stimulating oncogene product
Increased cell growth then promotes transcription, which also
promotes viral replication
The incorporation of the oncogene into many of these viruses causes
the coding sequences for the gag, pol, or env genes to be replaced,
such that these viruses are defective and require helper viruses for
replication.
The leukemia viruses, including HTLV-1, are competent in terms of
replication but cannot transform cells in vitro. They cause cancer
after a long latency period of at least 30 years
HTLV-1 is cell associated and is spread in cells after blood
transfusion, sexual intercourse, or breast-feeding.
The virus enters the bloodstream and infects the CD4 helper and DTH
T cells
infections are usually asymptomatic

do not usually cause enteric disease but are transmitted by the
fecal-oral route
Poliovirus is the prototype
The upper respiratory tract, oropharynx and intestinal tract are
portals of entry
Virions are impervious to stomach acid, proteases and bile
Replication is initiated in the mucosa and lymphoid tissue of the
tonsils and pharynx, it later infects the peyers patches and
underlying intestinal mucosa
Primary viremia spreats virus to receptor-bearing target tissues
(where 2nd phase of replication begins)
In polioviruses the virus must cross the blood-brain barrier or may
gain access to the brain by infecting skeletal muscle and traveling
up the innervating nerves to the brain
Polio virus has one of the narrowest tissue tropisms, recognizing a
receptor expressed on anterior horn cells of the spinal cord, dorsal
root ganglia, motor neurons, skeletal muscle cells, lymphoid cells
Coxsackieviruses and echoviruses recognize receptors expressed on
more cell types and tissues
Receptors are rpesent on cells of the CNS, heart, lung, pancrease,
mucosa
Most enteroviruses are cytolytic, replicating rapidly and causing
direct damage to target cells
Antibody is the major protective immune response to the
enteroviruses; it can prevent initial infection in the oropharynx and
GIT; prevents spread to target tissue
Cell-mediated immunity is not usually involved in protection but
may play a role in pathogenesis

1.
2.
3.
4.
poliovirus may cause one of four outcomes in unvaccinated people,

depending on the progression of the infection
Asymptomatic illness. Infection limited to the oropharynx and gut. At
least 90% are asymptomatic
Abortive poliomyelitis (minor illness). Non-febrile illness, 5%. Fever,
headache, malaise, sore throat, vomiting
Nonparalytic poliomyelitis (aseptic meningitis). 1-2%. Virus
progresses into the CNS and the meningitis, causing back pain and
muscle spasms + symptoms of minor illness
Paralytic polio (major illness). 0.1-2%. Appears 3-4 days after the
minor illness has subsided, producing a biphasic illness. Virus spreads
from blood to anterior horn cells of SC and motor cortex of the brain.
Paralytic poliomyelitis. Characterized by asymmetrical flaccid
paralysis with no sensory loss.
Bulbar poliomyelitis. Involve the muscles of the pharynx, vocal
cords and respiration. Results in death of 75% of patients
Postpolio syndrome. Sequelae of poliomyelitis that may occur
much later in life (30-40 yrs)
pathogenesis of enterovirus infection. The target tissue infected by the

enterovirus determines the predominant disease caused by the virus.
EPIDEMIOLOGY
Infection is often asymptomatic
Virion is resistant to environmental conditions (detergents,

acid, drying, mild sewage treatment and heat)
TRANSMISSION
Fecal-oral route; poor hygiene, dirty diapers
Ingestion via contaminated food and water
Contact w/ infected hands and fomites
Inhalation of infectious aerosols
WHO IS AT RISK?
Young children: at risk for polio (asymptomatic or mild disease)
Older children/adults: polio (asymptomatic or paralytic

disease)
Newborns and neonates: highest risk for coxsackievirus and

enterovirus disease
CLINICAL SYNDROMES ASSOCIATED WITH MAJOR ENETROVIRUS GROUPS

SYNDROME
OCCURRENC
PO
COX
COX
ECH
E
L
A
B
O
Paralytic disease
Sporadic
+
+
+
+
Encephalitis, meningitis
Outbreaks
+
+
+
+
carditis
Sporadic
+
+
+
Neonatal disease
Outbreaks
+
+
Pleurodynia
Outbreaks
+
Herpangina
Common
+
Hand-foot-and-mouth
Common
+
disease
Rash disease
Common
+
+
+
Acute hemorrhagic
Epidemics
+
conjunctivitis
Respiratory tract
Common
+
+
+
+
infections
Undifferentiated fever
Common
+
+
+
+
Diarrhea,
Uncommon
+
gastrointestinal disease
Diabetes, pancreatitis
Uncommon
+
Orchitis
Uncommon
+
Disease in
+
+
+
immunodeficient
patients
Congenital anomalies
Uncommon
+
+
CLINICAL SYNDROMES
incubation period for enterovirus disease varies from 1-35 days,

depending on the virus, target tissue and the persons age
viruses that affect oral and respiratory sites have the shortest
incubation periods
Polio infections
Progression of poliovirus infection. Infection may be asymptomatic or

progress to minor or major disease.
Coxsackievirus and Echovirius Infections
coxsackie A viruses are assoc with diseases with vesicular lesions

(herpangina) whereas coxsackie B (b for body) are associated with
myocarditis and pleurodynia.
Herpangina is casued by several types of coxsackie A virus. Fever,

sore throat, pain
Classic finding is vesicular ulcerated lesions around the soft

palate and uvula
Virus can be recovered from lesions or feces
Requires only symptomatic management
Hand-foot-and-Mouth disease is a vesicular exanthema caused by

an enterovirus usually cox A16.
Lesions on hands, feet, mouth and tongue
Pleurodynia (Bornholm disease) aka devils grip, is a acute illness

in w/c patients have sudden onset of fever and unilateral low
thoracic, pleuritic chest pain
Myocardial and Pericardial infections caused by coxB. Neonates

have febrile illnesses and sudden onset of unexplained heart failure
Cyanosis, tachycardia, cardiomegaly and hepatomegaly occur
Acute benign pericarditis affects young adults; symptoms

resemble those of MI but fever is more severe.
Viral (aseptic) meningitis, acute febrile illness accompanied by

headache and signs of meningeal irritation including nuchal rigidity.
Petechiae or skin rash may occur in patients
Fever and rash may occur in Px infected with Echo and Cox.
Eruptions are usually maculopapular but may occasionally be
petechial or vesicular
Transmission of enteroviruses.
The capsid structure is resistant
to mild sewage treatment,
saltwater, detergents, and
temp changes, allowing these
viruses to be transmitted by
fecal-oral route and on hands.
LABORATORY DIAGNOSIS
Clinical chemistry
CSF from poliovirus or enterovirus aseptic meningitis reveals a

predominantly lymphocytic pleocytosis
In viral meningitis, the CSF glucose level is usually normal or

slightly low
Culture
Poliovirus may be isolated from patients pharynx
It grows well on monkey kidney tissue culture
The specific type of enterovirus can be determined by using

specific antibody and assays (IF, ELISA)
Serology
Detection of IgM or finding a 4-fold increase in Ab titer bet time

of acute illness and period of convalescence
1. Morbilivirus
2. Paramyxovirus
3. Pneumovirus
THE PARAMYXOVIRUS FAMILY
UNIQUE FEATURES OF THE PARAMYXOVIRIDAE
Large virion consisting of a negative RNA genome in a helical

nucleocapsid surrounded by an envelope containing a viral
attachment protein (HN: paramyxovirus; H: morbilivirus; G:
pneumovirus) and a fusion glycoprotein (F)
The three genera can be distinguished by the activities of the viral

attachment protein: HN of paramyxovirus has hemagglutin and
neuraminidase activity; H of morbilivirus has hemagglutin activity; G
of pneumovirus lacks these activities
Virus replicates in the cytoplasm
Virions penetrate the cell by fusion with the plasma membrane
Viruses induce cell-cell fusion, causing multinucleated giant cells
Paramyxoviridae are transmitted in respiratory droplets and initiate

infection in the respiratory tract
Cell-mediated immunity causes many of the symptoms but is essential

for control of the infection
TREATMENT, PREVENTION AND CONTROL
no specific antiviral therapy
supportive therapy
2 types of polio vaccine exist
inactivated polio vaccine (IPV)
live attenuated oral polio vaccine (OPV).

both are effective but OPV is used due to its ease of delivery
and capacity to elicit a lifelong immunity
1. MORBILLIVIRUS (measles virus)

Epidemiology of Measles
o
Large relatively unstable envelope virion, easily inactivated
o
Contagion period precedes symptoms
o
Host range is limited to humans
o
Only one serotype
o
Immunity is lifelong
TRANSMISSION
WHO IS AT RISK
o
o
The family Paramyxoviridae consist of three genera:
Unvaccinated individuals
Immunocompromised individuals; more serious outcome
GEOGRAPHY/SEASON
o
o
serum and secretory antibody response to intramuscular inoculation of IPV

and to live attenuated OPV. Note the presence of secretory IgA induced by
the live polio vaccine.
INFLUENZA
PARAMYXOVIRIDAE
Inhalation via large droplet aerosols
Worldwide
Endemic in fall to spring, possibly because of crowding indoors
Disease Mechanism of Measles Virus
Infects epithelial cells of respiratory tract
Spread systemically in lymphocytes and by viremia
Replicates in cells of the conjunctiva, respiratory tract,

gastrointestinal tract, urinary tract, lymphatic system, blood vessels
and central nervous system
Rash is caused by T-cell response to virus-infected epithelial cell

lining the capillaries
Cell-mediated immunity is essential to control of infection, antibody

is not sufficient due to measles ability to spread cell to cell
Sequelae in the central nervous system may result from
immunopathogenesis (postinfectious measles encephalitis) or
development of defective mutants (subacute sclerosing
panencephalitis, SSPE)
Clinical Consequences of Measles Virus Infection
A Defective measles virus persists in

the
brain and acts as a slow virus

Time course of Measles Virus Infection
Clinically, measles is usually so characteristic that it is rarely

necessary to perform laboratory tests to make a diagnosis. Measles
virus is difficult to isolate and grow. The virus can be grown in
primary human or monkey cell cultures.
Respiratory tract secretions, urine, blood, and brain tissue are

recommended specimens. Respiratory and blood specimens are best
collected during the prodromal stage up to 1 to 2 days after the
appearance of the rash.
Measles antigen can be detected by immunofluorescence in

pharyngeal cells or urinary sediment, but this test is not generally
available. Characteristic cytopathologic effects including
multinucleated giant cells with cytoplasmic and nuclear inclusion
bodies can be seen in Giemsa-stained cells taken from the upper
respiratory tract and urinary sediment.
Antibody, especially IgM, can be detected when the rash is present.

Seroconversion or a fourfold increase in measles-specific antibodies
between acute and convalescent sera represent the best method of
confirming measles. Immune status testing to determine past
infection or immunization is being used to document childhood
immunization.
Treatment, Prevention and Control]
A live attenuated measles vaccine in use since 1963. Live attenuated

vaccine is given to all children after 6 months of age, in combination
with mumps and rubella vaccine (MMR vaccine) at 15 months
Inactivated killed vaccines are no longer available, even for the
immunocompromised, because of the subsequent effect on naturally
acquired measles virus infection (atypical measles). No specific
antiviral treatment is available for measles.
Exposed susceptible individuals who are immunocompromised should
be given immune serum globulin to modify their measles infection.
This product is most effective if given within 6 days of exposure.
2. PARAMYXOVIRUS
Endemic in late winter and early spring
Disease Mechanism of Mumps Virus
Infects epithelial cells of respiratory tract
Spreads systemically by viremia
Systemic infection, especially of parotid gland, testes, and central

nervous system
Principal symptom is swelling of parotid glands because of

inflammation
Cell-mediated immunity is essential for control of infection and

responsible for a portion of the symptoms. Antibody is not sufficient
due to mumps ability to spread cell to cell
PARAINFLUENZA VIRUS
Epidemiology of Parainfluenza Virus Infection
o
Large relatively unstable enveloped virion, easily inactivated
o
Contagion period precedes symptoms and may occur in the
absence of symptoms
o
o
Reinfection later in life can occur
TRANSMISSION
WHO ARE AT RISK?
o
o
Inhalation of large droplet aerosols
Children: mild diseaae, croup

Adults: reinfection with milder symptoms
GEOGRAPHY/SEASON
Ubiquitous and worldwide
Disease Mechanism of Parainfluenza Viruses
Four serotypes of viruses
Infection is limited to respiratory tract, upper respiratory tract

disease is most common, but significant disease can occur upon lower
respiratory tract infection
Parainfluenza viruses are not systemic and do not cause viremia
Diseases include coldlike symptoms, bronchitis (inflammation of

bronchial tubes), bronchiolitis (inflammation of bronchioles), croup
(laryngotracheobronchitis)
Infection induces protective immunity of short duration

Parainfluenza virus isolated from nasal washings and respiratory

secretions grow well in primary monkey kidney cells. However, like
the other paramyxovirus, the virions are labile during transit to the
lab. Virus-infected cells in aspirates or in cell culture can be
identified by immunofluorescence.
No specific antiviral agents are available.
Vaccination with killed vaccines is ineffective possibly because they

fail to induce local secretory antibody and appropriate cellular
immunity. No live attenuated vaccine is presently available.
a.
MUMPS VIRUS
Epidemiology of Mumps Virus
o
o
Contagion period precedes symptoms
o
May cause asymptomatic shedding
o
o
Only one serotype
o
Immunity is lifelong
TRANSMISSION
o
o
Large droplet aerosols
WHO IS AT RISK?
Unvaccinated individuals
Immunocompromised individuals, more serious outcome
GEOGRAPHY/SEASON
Worldwide
Virus can be recovered from saliva, urine, pharyx, secretions from

Stensens duct, and cerebrospinal fluid. Virus is present in saliva for
approximately 5 days after the onset of symptoms and in urine for as
long as 2 weeks. Mumps virus grows well in monkey kidney cells and
can be recognized by the development of a cytopathogenic effect
characterized by multinucleated giant cells.
A clinical diagnosis can be confirmed by serologic testing. A fourfold

increase in virus-specific antibody level or the detection of mumpsspecific IgM antibody indicates active infection. Hemagglutination
inhibition (HI), ELISA and immunoflourescence tests can be used to
detect mumps virus, antigen or antibody.
Given the difficulties of controlling the spread of mumps, vaccine

provide the only effective means for reducing infection. Since the
introduction of the live attenuated vaccine (Jeryl Lynn vaccine) in the
United States in 1967 and its administration as part of the MMR
vaccine, the yearly incidence of cases has declined from 76 to 2 per
100,000. Unfortunately, use of this vaccine in the world is limited.
Antiviral agents are not available.

o
o
o
3. PNEUMOVIRUS (Respiratory Syncytial Virus)

Epidemiology of Respiratory Syncytial Virus
Inhalation of large droplet aerosols
WHO ARE AT RISK?
o
o
o
Rubella: respiratory route
Rubella: children: mild exanthematous disease

neonates (<20 weeks): congenital defects
Adults: more severe disease with arthritis or arthralgia
GEOGRAPHY/SEASON
Rubella: worldwide
WHO ARE AT RISK?
o
o
o

Contagion period precedes symptoms and may occur in the
absence of symptoms
TRANSMISSION
TRANSMISSION
o
o
soap and detergents

Rubella infects man and can be asymptomatic
Virus causes asymptomatic disease
There is one serotype
Infants: lower tract infection; bronchiolitis and pneumonia

Children: spectrum of disease; mild to pneumonia
Adults: reinfection with milder symptoms
GEOGRAPHY/SEASON
o
o
Ubiquitous and worldwide

Seasonal
Disease Mechanisms of Respiratory Syncytial Virus
Localized infection of respiratory tract

Does not cause viremia or systemic spread
Pneumonia results from cytopathic effect of virus (including syncytia)
Narrow airways of young infants readily obstructed by virus-induced
pathology
Maternal antibody does not protect infant from infection
Natural infection does not prevent reinfection
Vaccination increases severity of disease
Clinical Syndromes
Upper respiratory infection in

older children and adults who
are being reinfected against a
background of partial immunity
Respiratory syncytial virus is difficult to isolate in cell culture. Direct

detection of viral antigen in infected cells and in nasal washings has
been developed using immunofluorescence and enzyme immunoassay
In otherwise healthy infants, treatment is supportive, with oxygen,

intravenous fluids, and nebulized cold stream. Ribavarin, a guanosine
analogue, is administered by inhalation (nebulization) and is
approved for treatment of patients predisposed to a more severe
course (e.g. premature or immunocompromised infants.
Currently no vaccine is available for RSV prophylaxis. A previous

vaccine containing inactivated RSV actually caused recipients to have
more severe RSV infection when subsequently exposed to live virus.
This is thought to have resulted from a heightened immunological
response at the time of wild virus exposure.
RUBELLA VIRUS (Rubivirus of the Togaviridae and Flaviviridae Family)
Epidemiology of Togaviruses (Rubella Virus)
o
Enveloped virus must stay wet and can be inactivated by drying,
Rubella infection is usually not cytolytic, and the disease is normally

benign in children. The symptoms in children are a 3-day rash and
swollen glands. Infection of adults can be more severe, leading to
outcomes such as arthralgia, arthritis and (rarely) thrombocytopenia,
and a postinfectious encephalitis similar to postinfectious measles
encephalitis.
different strains
Epidemiology of Influenza A and B
o
o
o
Isolation of rubella virus is difficult and rarely done. The diagnosis is

usually confirmed by the presence of anti-rubella-specific IgM. A
fourfold increase in specific IgG antibody titer between acute and
convalescent sera is also used to indicate a recent infection
No treatment has been found for rubella
The best means of preventing rubella is vaccination with the live

cold-adapted RA27/3 vaccine strain of virus. The live rubella vaccine
is usually administered in conjunction with the measles and mumps
vaccines (MMR vaccine). The triple vaccine is included routinely in
well-baby care. Vaccination induces both humoral and cellular
immunity
ORTHOMYXOVIRUSES
(Orthomyxoviridae)
Influenza Virus
belong to family Orthomyxoviridae
Ortho true or regular (to

differentiate them from
paramyxoviruses)
Myxo mucus (refers to their

ability to attach to mucoproteins on the cell surface
100-200 nm in diameter
spherical
500 projecting spikes
80% hemagglutinin antigen
20% neuraminidase
Hemagglutinins
rod-shaped glycoprotein with a triangular

cross-section
first identified by its ability to agglutinate

erythrocytes
plays a role in the attachment and entry

of the virus to the hosts cells
determines virulence
Neuraminidase
mushroom-like spikes
an enzyme that destroy neuraminic (sialic) acid, a component of the

specific cell receptor for these viruses
main function is the release of the new

virus from cells
o
o
o
o
Enveloped virion with a genome of 8

negative-sense RNA nuclocapsid
segments
The hemagglutinin, (HA) glycoprotein is
the VAP, fusion protein, and elicits
neutralizing, protective antibody
responses
Influenza transcribes and replicates its
genome in the target cell nucleus but
assembles and buds from the plasma
membrane
The antiviral drugs amantadine and
rimatadine inhibit an uncoating step and most likely target the M 2
protein
The segmented genome promotes genetic diversity caused by
mutation and reassortment of segments upon infection with two
Seronegative individuals
Adults Classic flu syndrome
Children: Asymptomatic to severe respiratory infections
High-risk groups: elderly, immunosuppressed individuals with
underlying cardiac or respiratory problems including asthma and
smokers
GEOGRAPHY/SEASON
o
o
Worldwide occurrence; epidemics local; pandemics worldwide

Disease more common in winter
Three Species of Influenza Virus (based on matrix (M) and

nucleoprotein (NP) antigens):
1. Influenza A
2. Influenza B
3. Influenza C (does not cause significant human disease)
Genetic
1.
-
Variation in Influenza Virus A:

Antigenic Drift:
involves Influenza A and B viruses
due to point mutation (two or three amino acid substitution on
the viral polypeptides)
slowly progressive and cumulative
cases more frequent but localized outbreaks (epidemics)
2. Antigenic Shift:
only in Influenza A
involves gene swapping or reassortment between two viruses
herd immunity of previously infected population will not be
effective against the reassortant strains
results in pandemics
Human Influenza Pandemics in the 20th Century
SPANISH FLU
o
o
o
o
o
Unique Features of the Influenza A & B Virus
Inhalation of small aerosol droplets released by talking,

breathing, coughing
Virus likes cool, less humid atmosphere (e.g. winter heating
season)
Spread extensively by school children
WHO ARE AT RISK?
o
o
o
o
Influenza infects many vertebrate species including other

mammals and birds
Co-infection with animal and human strains of virus can generate
very different virus strains by genetic reassortment
Transmission of virus often precedes symptoms
TRANSMISSION
Influenza is enveloped and is inactivated by detergents

Segmented genome facilitates major genetic strain changes,
especially the targets of the humoral immune response, HA and
NA
ASIAN FLU
o
Year 1957
Subtype H2N2
o
Origin China
o
Viral genes reassortment with avian virus
o
Mortality - >1 million worldwide; ~70T in US
HONGKONG FLU
o
Year 1968
o
Subtype H3N2
Year 1918-1919
Subtype H1N1
Origin China? Europe? North America?
Viral genes contain mammalian and avian genes
Mortality 25-50 million worldwide;500T in US
Origin China
o
Viral genes reassortment of avian virus
o
Mortality - >1 million worldwide; ~34T in US
RUSSIAN FLU
o
o
o
o
Year 1977
Subtype H1N1
Origin China, Russia
Viral genes reappearance of 1950s H1N1 virus (from frozen
source?)
o
Mortality low mortality worldwide and in the US
Clinical Syndromes
Depending on the degree of immunity to the infecting strain of virus

and other factors, the infection may range from asymptomatic to
severe. Patients with underlying cardiorespiratory disease or immune
deficiency, even that associated with pregnancy, are more
predisposed to severe diseases.
After an incubation period of 1 to 4 days, the flu syndrome begins

with a brief prodrome of malaise and headache lasting a few hours.
This is followed by the abrupt onset of fever, severe myalgia, and
usually a nonproductive cough. The illness persists for approximately
3 days, then, unless a complication occurs, recovery is complete.
Acute Influenza Infection in Children
Acute disease similar to adults but having higher fever,

gastrointestinal symptoms (abdominal pain, vomiting) otitis media,
myositis, and croup more frequently
Complications of Influenza Virus Infection
Primary viral pneumonia
Secondary bacterial pneumonia
Myositis and cardiac involvement
Neurological syndromes
o
Guillain-Barre syndrome
o
Encephalopathy
o
Encephalitis
o
Reyes syndrome
The characteristic symptoms of influenza combined with the presence

of community outbreak are often sufficient for a diagnosis.
Influenza viruses from respiratory secretions can generally be isolated
in primary monkey kidney cell cultures or Madin Darby Canine Kidney
(MDCK) cell line. Occasional strains may require chick embryo
inoculation for primary isolation.
Specific identification of the influenza virus requires immunological
tests such as immunofluorescence or inhibition of hemadsorption or
hemagglutination with specific antibody.
Enzyme immunoassay or immunofluorescence can be used to detect
viral antigen in exfoliated cells, respiratory secretion, or cell culture.
Serology is too slow to aid the diagnosis and is generally used for
epidemiological purposes.
Amantadine and its analogue, rimantadine, are effective for

prophylactic use and for treatment during the first 24 48 hours after
the onset of Influenza A illness.
Immunization
Natural from prior exposure
Formalin inactivated vaccine (strain of the year)

AVIAN INFLUENZA (AI) Bird Flu
an infectious disease of birds caused by Type A strains of the

influenza virus
first identified in Italy in 1878 affecting chickens
occurs worldwide
Epidemiology
highly contagious, affecting all avian species

incubation period is 3-5 days
highly pathogenic avian influenza isolates have been obtained
primarily from chickens and turkeys
Sources of Virus
Feces
Respiratory secretions
Characteristics of Influenza Virus
can survive in feces for several months
can survive in water for up to 4 days at 22oC, more than 30 days at

0oC and indefinitely in frozen material
killed by alcohol, bleach, formalin, or iodine compounds
5% bleach solution is appropriate for dealing with biohazardous

spillage
killed by heat
Time
Temperature
3 hrs
56o C
30 mins
60o C
1 min
70o C
Transmission:
direct contact with secretions from infected birds, especially feces
contaminated feed, water, equipment and clothing
clinically normal waterfowl and sea birds may introduce the virus into
the flocks
broken contaminated eggs may infect chicks in the incubator
Clinical Types
1. Low Pathogenic Avian Influenza (LPAI)
causes mild disease (decreased egg production, mild respiratory
symptoms)
as it circulate, may mutate w/in 6-9 months into a highly
pathogenic strain
2. Highly Pathogenic Avian Influenza (HPAI) (Fowl Plague)
coughing, sneezing, excessive lacrimation
cyanosis of unfeathered skin
edema of the head
ruffled feathers
diarrhea
nervous system disorders
sudden death without clinical signs
due to subtypes H5 0r H7
100% mortality
Previous Outbreaks of Highly Pathogenic Avian Influenza
ITALY
o
o
o
HONGKONG (CHINA)
o
o
o
Year 2002
Domestic bird affected chicken
Strain H5N1
CHILE
o
o
o
Year 1999-2000
Domestic bird affected turkey
Strain H7N1
Year 2002
Strain H7N3
NETHERLANDS
o
o
o
Year 2003
Strain H7N7
Control Measures in Outbreaks
slaughtering of all birds (culling)
disposal of carcasses and all animal products
clearing and disinfection of poultry
allow at least 21 days before restocking

Problems associated with outbreaks
1. Extremely difficult to control even under favorable conditions
1983 Pennsylvania (USA) outbreak took 2 years to control
1995 Mexico outbreak H5N2 strain has never been entirely
eliminated up to the present
2.
3.
Severe Economic Loss

1983 Pennsylvania (USA) outbreak:
o
17 million birds were destroyed
o
direct cost in US is $62 million
o
indirect cost in US is $250 million
1999-2001 Italy
o
13 million birds were destroyed
2003 Netherlands (reached Belgium and Germany)
o
birds destroyed:
30M in Netherlands
2.7M in Belgium
400T in Germany
Bird to human transmission
close human contact with live animals provides an ideal
environment for the zoonotic transfer and evolution of infectious
disease agent (live animal market or wet markets)
since 1977, 7 confirmed outbreaks of human infections with
avian influenza
Clinical Features
HONGKONG 1997
o
o
o
o
o
o
influenza-like illness with pneumonia

liver dysfunction
abnormal clotting profiles
gastrointestinal manifestations
renal failure
pancytopenia (hemophagocytic syndrome)
VIETNAM 2004
of the 10 patients, 9 had direct contact with poultry (chicken or

ducks)
o
incubation period of 2-4 days (mean 3 days)
o
fever
o
cough
o
diarrhea
o
shortness of breath
o
lymphopenia
o
diffuse, multifocal, patch infiltrates or segmented/lobular
consolidations
Optimal specimen for Influenza virus detection is nasopharyngeal

aspirate obtained within 3 days of the onset of symptoms, however,
nasopharyngeal swabs and other specimen can be used
rapid antigen detection assay - commercially available, provides

results in 15-30 minutes but not sensitive or specific
Virus culture
o
Enables further antigenic and genetic characterization, drug
susceptibility and vaccine preparation
o
Takes 2-10 days
o
Must be performed under Biosafety level 3+ laboratory
conditions
Reverse Transcriptase PCR

o
Detects diverse Influenza A viruses including Avian H 5N1 strains
o
Can be performed in standard Biosafety level 2 laboratory
o
Indication for laboratory testing

1. Hospitalized Patients
o
Radiographically confirmed pneumonia, acute respiratory
distress syndrome, or other severe respiratory illness for which
an alternate diagnosis has not been established and
o
History of travel to a country with documented H5N1 avian
influenza within 10 days of symptom onset
2. Case to case basis
Temperature > 38C and
One or more of the following: cough, sore throat, shortness of
breath and
o
History of contact with domestic poultry (eg. Visited a poultry
farm, household raising poultry, or bird market) or a known or
suspected human case of influenza H5N1 -affected country
within 10 days of symptom onset.
Antiviral Treatment:
o
Current H5N1 strains are resistant to Amantadine and
Rimantandine but sensitive to neuraminidase inhibitors
(Oseltamivir and Zanamivir)
Preventive Measures:
o
avoid contact with poultry
o
thorough and frequent hand hygiene using soap and water or
alcohol - based hand rubs
o
poultry, including eggs should be cooked thoroughly
o
Persons involved in outbreak eradication should use appropriate
personal protective equipment (gloves, disposable clothing, shoe
covers, safety goggles, and particulate respirators.
Isolation Precautions for patients hospitalized with suspected or
confirmed Avian Influenza H5N1
o
Standard Precaution strict hand hygiene before and after all
patients contact
o
Contact Precautions use gloves and gown for all patients
contact
o
Eye Protection wear when within 3 feet (1 m) of the patient
o
Airborne Precaution
Place patient in an airborne isolation room (negative air

pressure with 6-12 air exchange per hour)
Use of fit tested respirator when entering a room (N-95

o
o
filtering facepiece respirator

Vaccination
o
Human Influenza Vaccine
current inactivated trivalent human influenza vaccine

provides no protection against H5 and H7 avian influenza
strains.
given to people at risk of avian and human influenza viruses

simultaneously and to decrease the possibility of
reassortment.
o
H5N1 Vaccine
a prototype vaccine have been developed using plasmidbased reverse genetic technology.
clinical trials and safety testing must be completed before

it can be commercially available.
RHINOVIRUS (Picornaviridae)
Characteristics
Belong to family Picornaviridae
More than 100 serotypes
Most important cause of the common cold and upper respiratory tract
infections
Epidemiology
VIRAL FACTORS
o
Resistant to drying and detergent
o
Labile at acidic pH
o
Optimum growth is at 33C
TRANSMISSION
o
o
Direct contact via infected hand and fomites

Inhalation of infected droplets
WHO ARE AT RISK?
All ages
Most common cause of epidemic diarrhea in infants

Can also cause diarrhea in animals
Genome: 11 segments of ds:RNA
Groups A-F have been described
Group A: most common cause of GE in children
Epidemiology
Transmission: fecal-oral route
Most cases are sporadic
Cases are worse in developing countries

Clinical Manifestations
Abrupt onset of diarrhea
Usually non-bloody & non-mucoid
Other S/S: fever & vomiting
Most severely affected: infants 6-24 months old
Incubation period: 2-5 days

Duration of Illness
About one week
Usual complications: dehydration & metabolic acidosis
Diarrhea is due to decreased absorption

Host Response
Initially: IgM
Followed by: IgG & secretory IgA

Diagnosis
Cell culture
EM, IEM, ELISA
LPA, Gel Electrophoresis

Treatment & Prevention
Supportive
Immunization
Clinical Syndromes
Most common cause of common cold sneezing followed by

rhinorrhea then nasal obstruction
Mild sore throat
Headache
Malaise
Fever
Chills
Unnecessary unless the physician needs to establish which of the

many respiratory viruses cause the illness
Culture
Serology
Supportive
No effective antiviral drug
Handwashing and disinfection of contaminated objects are the best

means of preventing the spread of the virus
Viruses in GIT Infections
Rotaviruses
Norwalk-like agent
Coronaviruses
Fastidious(Enteric) Adenoviruses
Astroviruses
Caliciviruses
others: Picorna-Parvo-like viruses

Generalities
Disease is manifested mainly as diarrhea
Affect all age group
Sporadic or epidemic form
Most cases are self-limited
Infection is usually asymptomatic

1. ROTAVIRUSES (from the family Reoviridae)
2. NORWALK-LIKE GROUP (miscellaneous virus)
Small, non-enveloped 27nm particle with ss-RNA genome
Self-limited gastroenteritis
1969: GE outbreak in Norwalk, Ohio
Epidemiology
Usually occurs in schools, recreational camps, nursing homes
Infection is mainly through food & water and person-to-person
Agent occurs worldwide & outbreaks all-year round

Clinical Infection
Most have: nausea, vomiting, abdominal pain
About half: diarrhea
Some: chills & fever
Symptoms lasts for 24 hours
Stools: non-bloody & non-mucoid
Diagnosis
Best: IEM & RIA
RIA & ELISA: most efficient in detecting soluble & particulate antigens
3. CORONAVIRUSES
Pleomorphic, enveloped ss-RNA
Can cause respiratory & intestinal disease in animals
Human strains: 1st associated with URTD & LRTD
Illness: mild to moderate, lasts 6-9 days, occurs any month of the
year
Diagnosis
virus in stool (EM, ELISA, etc.)

5. ASTROVIRUSES (miscellaneous virus)
Described in 1975
28-30 nm particle
Shed in stools in very large numbers
Present in the stools of infants with or without acute gastroenteritis
5-to 6-pointed star-shaped particles
Associated with disease in many countries: pediatric wards, schools,

nursing homes
See Box 64-3

S/S
Malaise
low-grade fever
watery diarrhea for 3 days

Diagnosis
EM, IEM, IF of cell cultures

Incubation period
1-3 days
6. CALICIVIRUSES (miscellaneous virus)
Epidemiology
Tend to occur in small outbreaks & sporadic cases
Re-infection is frequent
Diarrhea in older children & young adults
Prolonged viral excretion (about 18 months)
Usually: poor-hygiene environment
35-39 nm particles
star of David appearance
5 antigenic types
Almost all children are (+) for antibodies by 5 years
Diarrhea & asymptomatic infections have been documented
See Box 64.3
Illness
similar to Rotavirus diarrhea

Transmission
Fecal-oral spread occurs, as well as food-borne
Diagnosis
EM, IEM, ELISA
7. OTHER VIRUSES
A.
PICORNA-PARVOVIRUS-LIKE
o
have also been isolated in stools of patients with diarrhea &
asymptomatic patients
B.
MINIREOVIRUS & MINIROTAVIRUS

o
have been visualized in stools of children with diarrhea & in
infants who have acquired diarrhea within hospital setting
Treatment
supportive
4. FASTIDIOUS (ENTERIC) ADENOVIRUSES
1st described in 1975
Do not grow easily in cell culture
Causally associated with enteric illness
Significant pathogen of diarrheal illness

in children (2nd to
Rotavirus in frequency)
All belong to serogroup F & only serotypes 40 & 41 Responsible for

diarrhea in infants < 1 year old
RHABDOVIRUSES
Incubation period
3-10 days
Other S/S
cough
rhinorrhea
wheezing
pneumonia
conjunctivitis
Duration
PHYSIOLOGY, STRUCTURE AND REPLICATION
within the envelope, the helical nucleocapsid is coiled symmetrically

into a cylindrical structure, giving the appearance of striations.
The nucleocapsid is composed of:
1 ss (-) RNA
nucleoprotein (N) major structural protein of the virus
maintains RNA in a configuration acceptable for transcription
protects RNA from ribonuclease digestion

o
large (L) proteins
o
nonstructural proteins (NS)
Matrix (M) protein lies between the envelope and the nucleocapsid
L and NS constitute the RNA polymerase
Assembly of the virion occurs in 2 places:
o
Nucleocapsid cytoplasm
o
Envelopment and release at cell plasma layer
o
o
DISEASE MECHANISMS OF RABIES VIRUS

Rabies is usually transmitted in saliva and is acquired from the bite
of a rabid animal
Rabies virus is not very cytolytic and seems to remain cell
associated
Virus replicates in the muscle at the site of the bite, with minimal
or no symptoms (incubation phase)
The length of the incubation phase is determined by the infectious
dose and the proximity of the infection site to the CNS and
brain.
After weeks to months, the virus infects the peripheral nerves and
travels up the CNS to the brain (prodrome phase).
Infection of the brain causes classic symptoms, coma, and death
(neurological phase).
During the neurological phase, the virus spreads to the glands, skin,
and other body parts, including the salivary glands, from where
it is transmitted.
Rabies infection does not elicit an antibody response until the late
stages of the disease, when the virus has spread from the CNS to
other sites.
Antibody can block the progression of the virus.
The long incubation period allows active immunization as a
postexposure treatment.
PATHOGENESIS AND IMMUNITY
1. virus may directly infect nerve endings by binding to nicotinic
acetylcholine receptors or muscle at the site of inoculation
2. virus remains at the site for days to months before progressing
to the CNS
3. virus travels by retrograde axoplasmic transport to the dorsal
root ganglia and to the spinal cord
4. affected areas include the hippocampus, BS, ganglionic cells of
the pontine nuclei and purkinje cells
5. virus disseminates via afferent neurons to highly innervated sites
6. after the virus invades the brain and SC, an encephalitis
develops and neurons degenerate
neutralizing antibodies are not apparent until after the clinical
disease is well established
antibody can block the spread of virus to the CNS and to the brain if
administered or generated during the incubation period
period is often long enough to allow generation of a therapeutic
protective antibody response
1) virus inoculated 2) viral replication in muscle 3) virion enters PNS 4) passive ascent
via sensory fibers 5) replication in dorsal ganglion 6) rapid ascent in spinal cord 7)
infection of SC, BS, cerebellum and other brain structures 8) descending infection via
nervous system to eye, salivary glands, skin and other organs.
EPIDEMIOLOGY
Disease has long, asymptomatic incubation period
Enveloped virus must stay wet but can be inactivated
by soap and detergents

TRANSMISSION
Zoonosis:
Reservoir: wild animals
Vector: wild animals and unvaccinated dogs and
cats
Source of virus:
Major: saliva in bite
Minor: aerosols in bat caves containing rabid bats
WHO IS AT RISK?
Vets and animal handlers
Countries w/ no vaccine programs
HISTORICAL DEVELOPMENT
1884
1911
1957
1964
Pasteur vaccine. Historical interest

Sample vaccine. Phenol-inactivated virion. Vaccine prepared from
brains of rabbit, sheep or goats. Widely used in dev. Countries.
Cheap. Liable to cause neuroparalytic rxn
Duck embryo vaccine. B-propiolactone inactivated. Cause allergic
rxn. Ineffective antigen
Human diploid cell strain virus (HDCS). Virus inactivated w/ Bpropiolactone
TREATMENT
Nature of contact
Status of animal
treatment
Indirect contact
only
Appears healthy or
has signs suggesting
rabies
Appear healthy or has
signs
a. under
observation <
10 days
b. escaped
c. killed
HRIG (passive
immunization)
No needed
Licks to skin
Bites
FILOVIRUSES
Start immediately
Start immediately
at site
IM
includes the Marburg and Ebola viruses

are filamentous, enveloped, negative-strande RNA viruses
agents cause severe or fatal hemorrhagic fevers and are endemic in
Africa
STRUCTURE AND REPLICATION
ssRNA genome that encodes 7 proteins
replicates in the cytoplasm similar to the rhabdoviruses

PATHOGENESIS
filoviruses replicate efficiently, producing large amounts of virus and

causing tissue necrosis in parenchymal cells of liver, spleen, lymph
nodes and lungs
widespread hemorrhage causes edema and hypovolemic shock
STRUCTURE AND PHYSIOLOGY
the slow virus agents were suspected to be viruses because they can
pass through filters that block the passage of particles greater than
100nm
the prototype of these agents is scrapie; scrapie-infected hamsters

have scrapie-associated fibrils in their brain; these are infectious and
contain prions
prions lack detectable nucleic acids and consists of aggregates of

protease-resistant, hydrophobic glycoprotein
PATHOGENESIS
EPIDEMIOLOGY
Marburg virus was first detected in laboratory workers in Marburg,

Germany who had been exposed to tissues from African green
monkeys
Also in Zimbabwe and Kenya
Outbreaks of Ebola have occurred in Zaire and Sudan

CLINICAL SYNDROME
most severe causes of viral hemorrhagic fevers
begins w/ influenza-like symptoms
death occurs in as many as 90% of patients w/ clinically evident

disease
handling requires level 4 isolation procedures
Marburg can be grown on tissue culture
Ebola needs animal host
Infected cells have large eosinophilic cytoplasmic inclusion bodies
Antigens can be detected by immunofluorescence
spongiform encephalopathy characteristic degeneration of neurons

and axons of the gray matter that occurs in affected patients
vacuolation of the neurons, formation of amyloid-containing plaques
and fibrirls, proliferation and hypertrophy of astrocytes, fusion of
neurons and adjacent glial cells
no inflammation or immune response to the agent is generated
incubation for CJD and kuru may be as long as 30 yrs but the patient
dies w/in a year when symptoms become evident
TREATMENT
antibody-containing serum and interferon therapies

SUBACUTE SPONGIFORM ENCEPHALOPATHIES AND UNCONVENTIONAL
AGENTS
cause spongiform encephalopathies (slow neurodegenerative

diseases)
include the human diseases kuru, Creutzfeldt-jakob disease (CJD),

Gerstmann-Straussler-Scheniker (GSS) disease, and fatal familial
insomnia (FFI)
include the animal diseases scrapie, bovine spongiform

encephalopathy (mad cow disease), chronic wasting disease and
transmissible mink encephalopathy
it has no virion structure or genome, no immune response is elicited

and agents are resistant to inactivation by heat, disinfectants and
radiation
The slow virus agent appears to be a modified host protein known as

a prion (a small proteinaceous infectious particle)
Long incubation period which can last 30 years in humans
EPIDEMIOLOGY
Agents are impervious to standard viral disinfection
procedures
Diseases have very long incuation periods (30 yrs)
TRANSMISSION
Transmission is via infected tissue, or syndrome may
be inherited
Infection occurs through cuts in skin, transplantation
of contaminated medical devices and potentially
through ingestion of infected tissue
WHO IS AT RISK?
Women and children of the Fore tribe in New Guinea
were at risk for kuru

Surgeons, transplant and brain surgery patients
CLINICAL SYNDROME
cause a progressive, degenerative neurological disease w/ long
incubation period but with rapid progress to death after onset of

symptoms
loss of muscle control, leading to shivering, myoclonic jerks,
tremors, loss of coordination and progressive dementia
no methods for directly detecting virus using EM, antigen detection
or nucleic acid probes
no serological tests can detect antibody
diagnosis is made on clinical grounds w/ confirmation by the
characteristic histological changes in brain tissue
TREATMENT, PREVENTION, CONTROL
no treatment for kuru or CJD
autoclaving at 15 psi for 1 hr, treatment w/ 5% hypochlorite solution
or 1.0M sodium hydroxide
ENTEROVIRUS
pathogenesis of enterovirus infection. The target tissue infected by the enterovirus

determines the predominant disease caused by the virus.
EPIDEMIOLOGY
Infection is often asymptomatic
Virion is resistant to environmental conditions (detergents,
acid, drying, mild sewage treatment and heat)

TRANSMISSION
Fecal-oral route; poor hygiene, dirty diapers
Ingestion via contaminated food and water
Contact w/ infected hands and fomites
Inhalation of infectious aerosols

WHO IS AT RISK?
Young children: at risk for polio (asymptomatic or mild disease)
Older children/adults: polio (asymptomatic or paralytic
infections are usually asymptomatic

do not usually cause enteric disease but are transmitted by the
fecal-oral route
Poliovirus is the prototype
The upper respiratory tract, oropharynx and intestinal tract are
portals of entry
Virions are impervious to stomach acid, proteases and bile
Replication is initiated in the mucosa and lymphoid tissue of the
tonsils and pharynx, it later infects the peyers patches and
underlying intestinal mucosa
Primary viremia spreats virus to receptor-bearing target tissues
(where 2nd phase of replication begins)
In polioviruses the virus must cross the blood-brain barrier or may
gain access to the brain by infecting skeletal muscle and
traveling up the innervating nerves to the brain
Polio virus has one of the narrowest tissue tropisms, recognizing a
receptor expressed on anterior horn cells of the spinal cord,
dorsal root ganglia, motor neurons, skeletal muscle cells,
lymphoid cells
Coxsackieviruses and echoviruses recognize receptors expressed on
more cell types and tissues
Receptors are rpesent on cells of the CNS, heart, lung, pancrease,
mucosa
Most enteroviruses are cytolytic, replicating rapidly and causing
direct damage to target cells
Antibody is the major protective immune response to the
enteroviruses; it can prevent initial infection in the oropharynx
and GIT; prevents spread to target tissue
Cell-mediated immunity is not usually involved in protection but
may play a role in pathogenesis
disease)
Newborns and neonates: highest risk for coxsackievirus and
enterovirus disease
CLINICAL SYNDROMES ASSOCIATED WITH MAJOR ENETROVIRUS GROUPS

SYNDROME
Paralytic disease
Encephalitis, meningitis
carditis
Neonatal disease
Pleurodynia
Herpangina
Hand-foot-and-mouth disease
Rash disease
Acute hemorrhagic
conjunctivitis
Respiratory tract infections
Undifferentiated fever
Diarrhea, gastrointestinal
disease
Diabetes, pancreatitis
Orchitis
Disease in immunodeficient
patients
Congenital anomalies
OCCURRENC
E
Sporadic
Outbreaks
Sporadic
Outbreaks
Outbreaks
Common
Common
Common
Epidemics
PO
L
+
+
Common
Common
Uncommon
+
+
COX
A
+
+
+
+
+
+
+
+
+
Uncommon
Uncommon
ECH
O
+
+
+
+
+
+
+
+
+
+
+
+
Uncommon
COX
B
+
+
+
+
+
+
+
+
+
CLINICAL SYNDROMES
incubation period for enterovirus disease varies from 1-35 days,
depending on the virus, target tissue and the persons age
viruses that affect oral and respiratory sites have the shortest
incubation periods
poliovirus may cause one of four outcomes in unvaccinated people,
depending on the progression of the infection
1. Asymptomatic illness. Infection limited to the oropharynx and gut.
At least 90% are asymptomatic
2. Abortive poliomyelitis (minor illness). Non-febrile illness, 5%.
Fever, headache, malaise, sore throat, vomiting
3. Nonparalytic poliomyelitis (aseptic meningitis). 1-2%. Virus
4.
progresses into the CNS and the meningitis, causing back pain and
muscle spasms + symptoms of minor illness
Paralytic polio (major illness). 0.1-2%. Appears 3-4 days after the
minor illness has subsided, producing a biphasic illness. Virus
spreads from blood to anterior horn cells of SC and motor cortex of
the brain.
Paralytic poliomyelitis. Characterized by asymmetrical flaccid
paralysis with no sensory loss.
Bulbar poliomyelitis. Involve the muscles of the pharynx, vocal
cords and respiration. Results in death of 75% of patients
Postpolio syndrome. Sequelae of poliomyelitis that may occur
much later in life (30-40 yrs)
Clinical chemistry
CSF from
poliovirus
or
enterovirus
aseptic
meningitis
reveals a
Progression of poliovirus
infection. Infection may be
asymptomatic or progress to
minor or major disease.
Culture
Serology
Coxsackievirus and Echovirius Infections

coxsackie A viruses are assoc with diseases with vesicular lesions
(herpangina) whereas coxsackie B (b for body) are associated
with myocarditis and pleurodynia.
Herpangina is casued by several types of coxsackie A virus. Fever,
sore throat, pain
Classic finding is vesicular ulcerated lesions around the soft

palate and uvula
Virus can be recovered from lesions or feces
Requires only symptomatic management

Hand-foot-and-Mouth disease is a vesicular exanthema caused by
an enterovirus usually cox A16.
Lesions on hands, feet, mouth and tongue

Pleurodynia (Bornholm disease) aka devils grip, is a acute illness
in w/c patients have sudden onset of fever and unilateral low
thoracic, pleuritic chest pain
Myocardial and Pericardial infections caused by coxB. Neonates
have febrile illnesses and sudden onset of unexplained heart
failure
Cyanosis, tachycardia, cardiomegaly and hepatomegaly occur
Acute benign pericarditis affects young adults; symptoms

resemble those of MI but fever is more severe.
Viral (aseptic) meningitis, acute febrile illness accompanied by
headache and signs of meningeal irritation including nuchal
rigidity.
Petechiae or skin rash may occur in patients

Fever and rash may occur in Px infected with Echo and Cox.
Eruptions are usually maculopapular but may occasionally be
petechial or vesicular
Transmission of enteroviruses. The capsid structure is resistant to mild sewage

treatment, saltwater, detergents, and temp changes, allowing these viruses to be
transmitted by fecal-oral route and on hands.
predominantly lymphocytic pleocytosis

In viral meningitis, the CSF glucose level is usually
normal or slightly low
Poliovirus may be isolated from patients pharynx

It grows well on monkey kidney tissue culture
The specific type of enterovirus can be determined by
using specific antibody and assays (IF, ELISA)
Detection of IgM or finding a 4-fold increase in Ab titer

bet
time of
acute
illness
and
period
of
convalescence
TREATMENT, PREVENTION AND CONTROL
no specific antiviral therapy
supportive therapy
2 types of polio vaccine exist
inactivated polio vaccine (IPV)
live attenuated oral polio vaccine (OPV).

both are effective but OPV is used due to its ease of delivery
and capacity to elicit a lifelong immunity
serum and secretory antibody response to intramuscular inoculation of IPV and to live
attenuated OPV. Note the presence of secretory IgA induced by the live polio vaccine.
ALPHAVIRUSES AND FLAVIVIRUSES
Historically classified as arboviruses, because they are usually spread

by arthropod vectors: arthropod-borne
Host: vertebrates & invertebrates
Hepatitis C: recently classified as a Flavivirus
o
MODES OF CONTROL
o
o
ARBOVIRUSES
The members of the Togaviridae and Flaviviridae families are

enveloped, positive, ssRNA viruses
Most are transmitted by arthropods and are therefore arboviruses

(arthropod borne)
The Togaviruses can be classified into three major genera

1. Alphavirus
2. Rubivirus (Rubella virus)
3. Arterivirus
The Flaviviridae include:

1. flaviviruses
2. Pestivirus
3. hepatitis C and G
Alphaviruses and Flaviviruses are discussed together because of

similarities in the disease they cause and their epidemiology
in urband areas and in pools of water.

Culex mosquito, which causes St. Louis encephalitis, is found in
forest and urban areas.
Disease is more common in summer
Mosquito breeding sites and mosquitoes should be eliminated
Live attenuated vaccines are available for yellow fever virus and
Japanese encephalitis virus.
Patterns of alphavirus and flavivirus transmission. The cycle of arbovirus transmission

maintains and amplifies the virus in the environment. Host-vector relationships that
can provide this cycle are indicated by the double arrow. Dead-end infections with
not transmission of the virus back to the vector are indicated by the single arrow. For
St. Louis encephalitis, yellow fever, and dengue viruses, humans are not dead-end
hosts and support an urban cycle. The Russian spring-summer encephalitis virus can
be transmitted to humans by a tick bite and in milk form from infected goats.
ALPHAVIRUSES
1.
2.
3.
4.
5.
6.
Epidemiology (of Togavirus and Flavivirus Infection)
Both alpha- and flaviviruses are prototypical arboviruses
Most common vector: mosquito
Others: ticks & sandflies
Usual reservoir: birds & small

mammals
o
Enveloped virus must stay wet and can be inactivated by drying,
o
o
soap, and detergents.

Virus can infect mammals, birds, reptiles, and insects
Asymptomatic or nonspecific (flulike fecer or chills),
encephalitis, hemorrhagic fever, or arthritis.
TRANSMISSION
o
Togaviruses and flaviviruses: specific arthropods characteristic of
each virus (zoonosis: arbovirus).
WHO IS AT RISK?
o
People who enter ecological niche of arthropod: arboviruses
GEOGRAPHY/SEASON
o
Endemic regions for each arbovirus are determined by habitat of
o
mosquito or other vector

Aedes mosquito, which causes dengue and yellow fever, is found
Venezuelan Equine Encephalitis

Eastern Equine Encephalitis
Western Equine Encephalitis
Chikungunya
Semliki
Sindbis
FLAVIVIRUSES
1. Dengue
2. Yellow Fever
3. Japanese Encephalitis
4. West Nile
5. St. Louis Encephalitis
6. Russian spring-summer encephalitis
7. Powassan
Arboviruses (main characteristics)
1. Should infect both vertebrates & invertebrates
2. Initiate a sufficient viremia in the vertebrate host to allow
acquisition by the invertebrate vector
3. Initiate a persistent infection of the salivary gland of the vector
to
provide virus for infecting other vertebrate hosts
Clinical Syndromes
Infection with Alphaviruses

o
EEE,WEE,VEE: can progress to encephalitis in humans
o
S/S: chills, fever, rash, aches
o
Sindbis & Chikungunya: cause only systemic disease more of a
problem to livestock than to humans
Infection with Flaviviruses

o
relatively benign (although encephalitis or hemorrhagic disease
can still occur)
o
encephalitis viruses: St. Louis, Japanese, Murray Valley, Russian
spring-summer
o
hemorrhagic viruses: Dengue & Yellow Fever
DENGUE
Usually mild & self-limited but when re-challenged with a related

strain can cause severe hemorrhagic/shock symptoms
DHF/DSS: due to rupture of vasculature, internal bleeding, loss of

plasma
Pathogenesis
Lesions are in small blood vessels, with endothelial swelling,

perivascular edema and mononuclear infiltrates
DHF/DSS
are altered manifestations of dengue, often in epidemic form
Pathogenesis: not well understood, but seems to involve pre-existing

dengue antibodies
DHF: abrupt course & is assoc with hypoprotenemia,

thrombocytopenia,
prolonged BT, elevated PT
DSS: characterized by shock & hemoconcentration

YELLOW FEVER
Severe systemic disease with degeneration of liver, kidney, heart &

hemorrhage of blood vessels
Lesions are due to the localization & propagation of the virus in a

particular organ
Mortality: as high as 50%

Cell culture (both vertebrate & invertebrate cell line)
Cytopathology, IF, hemadsorption of avian erythrocytes
ELISA, HI, LPA

Tx,
Prevn, Control
Mainly supportive
No specific treatment
Vector elimination
Avoidance of endemic places
Vaccination: Yellow Fever, Jap enceph, EEE, WEE, Russian springsummer
Vaccine for VEE: only for domestic animals
because of the loss of luids from the vasculature.
Disease Mechanisms of Togavirus and Flavivirus
Viruses are cytolytic, except for rubella.
Viruses establish systemic infection and viremia.
Viruses are good inducers of interferon, which can account for the
influenza-like symptoms of infection.
Viruses, except rubella and hepatitis C, are arboviruses
Flaviviruses infect cells of the monocyte-macrophage lineage.
Non-neutralizing antibody can enhance flavivirus infection via Fc

receptors on the macrophage.
Influenzalike
syndrome
Dengue
Yellow F.
St. Louis E
Venezuelan
E
Western
equine E
Eastern
equine E
Japanese E
Encephalitis
+
+
+
+
+
+
Hepatitis
Hemorrhage
Shock
+
+
+
+
+
+
ARENAVIRUSES
Generalities
Include lymphocytic choriomenigitis(LCM) & hemorrhagic fever viruses

(Lassa fever, Junin, Machupo)
Zoonoses (persistent infection of specific rodents)
Virus becomes endemic in the habitat of the rodent
Pathogenesis
Infect macrophages, cause vascular damage and tissue destruction

Epidemiology
Mainly found: tropical Africa & South America
Infect specific rodents & are

endemic to their habitat
Infection of humans: aerosol,

contamination of food or fomites
Human-to-human: Lassa fever

Lymphocytic Choriomenigitis
o
fever with myalgia occurs more often than meningitis
o
menigeal illness: subacute & persists for several months
o
brain & meninges: perivascular mononuclear infiltrates
Lassa Fever, etc.

o
endemic: West Africa, Argentina (Junin), Bolivia (Machupo)
o
S/S: fever, coagulopathy, petechiae, occasional visceral
hemorrhages, liver & spleen necrosis
o
others: pharingitis, diarrhea, vomiting
o
Dx: recent travel to endemic areas
Serology (due to the danger of routine isolation)
Disease syndromes of alphaviruses and flaviviruses. Primary viremia may be

associated with mild systemic disease. Most infections are limited to this. If sufficient
virus is produced during the secondary viremia to escape immune protection and to
reach critical target tissue, severe systemic disease or encephalitis may result. For
dengue hemorrhagic fever (DHF), which can cause dengue shock syndrome (DSS)
Tx, Prevn, Control
For Lassa fever: Ribavirin (although with limited activity)
Supportive
Limit contact with vectors

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HEPATITIS VIRUSES

Tx, Prevn, Control

one serotype; seven genotypes

Hep B: Chronic infection

usually detected by elevated liver enzymes on routine chemistry

Primary Hepatocellular Carcinoma

ELISA (Ag & Ab detection)

PCR (for viral DNA)

Serologic Markers: Hepatitis B

(SGPT: 2-5mon; symptoms: 21/2-4mon)

Tx, Prevn, Control

For post-exposure prophylaxis for newborns of HBsAg(+) mothers &

Epidemiology of HBV, HCV, and HDV

In blood, semen, and vaginal secretions (HBV); saliva and

Enveloped virus is labile to drying. HBV is less sensitive to

Children: mild asymptomatic disease with establishment of

In acute infection, it is similar to HAV and HBV but symptoms are

ELISA detection of Antibody

Seroconversion occurs w/in 7-31 weeks of infection

The presence of the virion RNA in serum I s a better indicator of the

RT-PCR can detect HCV RNA in seronegative people

Recombinant interferon-alpha is the only known effective treatment

Approx. 15 M people are infected with HDV (delta agent)

ELISA and RIA to detect the delta

Avoidance of high-risk behavior

A viremia can be detected w/in 1-3 weeks of a transfusion of HCVcontaminated blood

The viremia lasts 4-6 months in people with an acute infection

the delta agent is spread in blood, semen, and vaginal secretions.

A more rapid, severe progression occurs in HBV carriers superinfected

ss RNA virus of Flaviviridae family

27% homology with HCV, 95% with GBV

The recently isolated GB-C virus is likely the same as the

is similar to the hepatitis C virus but

GB was a 34 year-old surgeon who contracted hepatitis

REO, ROTA, CALICI VIRUS

fulminant hepatitis is more likely to develop in people infected with

can result in hepatic encephalopathy (w/ altered mental capacity)

no specific treatment for HDV hepatitis

prevention of infection w/ HBV will prevent HDV infection

HEV (E-NANBH) (the E stands for enteric or epidemic) is

not known to cause human disease

3 distinct but related types

can cause many inapparent infections

(most people have Ab by early adulthood)

Human volunteers: failure to demonstrate a clear cause-andeffect relationship to human illness

Unique Features of Reoviridae

Double-layered capsid virion (60 to 80 nm) has icosahedral symmetry

Serologic diagnosis of infection requires the documentation of a

The techniques used to detect orthoreovirus antibody include

No specific antiviral therapy available.

the most important cause of infantile gastroenteritis in the world

Group A: most frequent pathogen

incubation period: 1-3 days

S/S: fever, abdominal pain, vomiting, watery diarrhea, dehydration

viral excretion in stools: up to 50 days after onset of diarrhea

NB. About half have diarrhea

affects villi of small intestine, impairs transport mechanism (gastric &

diarrhea is due to impaired sodium and glucose absorption

3-8 wk for restoration of

Treatment and Control

symptomatic & supportive

careful disposal of stools