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Microbiology 3.12 LECTURER: Dr.

Rosario
Emerging and Re-Emerging Infectious Diseases DATE: Oct. 1, 2013

OUTLINE Table 1. Dengue Virus Reported Cases 2012-2013


I. Definition
II. Background
III. Dengue
IV. Chinkungunya Virus
V. MERS-CoV
VI. Influenza
a. Avian Influenza (H5N1)
b. Avian Influenza (H7N9)
VII. Polio Virus
VIII. Enterovirus
IX. Vibrio Cholerae The WHO has reportedcumulative cases of 38,000, which is 2-3 times the
X. Rabies reported cases in the nearby countries.

OBJECTIVES  First recognized in the 1950s during the dengue epidemics in the
1. To know the various infectious disease threats Philippines and Thailand
a. To learn the epidemiology, clinical manifestations,  Transmission: Bites of infected Aedes mosquito
modes of transmission, prevention, and treatment  Recovery from infection by one provides lifelong immunity against
that serotype but confers only partial and transient protection against
DEFINITION subsequent infection by the other three(ex. If you have dengue this
 Emerging Infections year with the endemic virus serotype type 2 and you have another
o Outbreaks of previously unknown deiseases dengue infection next year or 2 years after and what is endemic then is
o Incidence has increased significantly in the past 2 decades the virus serotype type 3, you will still have dengue.)
 Re-emerging infections
o Known diseases that have re-appeared after significant decline
in incidence
o In the viral area, measles
o Bacterial clostridium infections diarrhea, leptospirosis
BACKGROUND
 14th century Plague: 50% of deaths in England
 1918 (Spanish) Influenza Pandemic: affected half a billionindividuals,
causing >20M deaths
 2009-2010 H1N1 Influenza Pandemic: > 200K deaths;83,300 CV deaths
o 80% in < 65 y/o; 51% in Southeast Asia, Africa
 HIV in the 1980s, now still a distressing human affliction
o >30M globally living with HIV/AIDS
 Nearly 2M adults and children die annually

How do infections emerge?


Figure 1. Clinical Course of Dengue Virus
1. Changes in human behavior, mobility
2. Changes in pathogens
The clinical course of the Dengue virus composes of three phases: Febrile,
3. Changes in environment, natural disasters
Critical, and Recovery phases. In febrile (fever) phase, it is heralded by high
4. Antimicrobial use
grade fever for 2-7days. Cytokines will be produced because of the fever
(In addition, there is an increase in number of people in the world who will
which will have effects like anorexia and dehydration. Lab tests will show
most likely be travelling, and an increasing number of population who
viraemia during this phase. In critical phase, the virus is suppressed and
practice needle sharing[thus spread the disease]. Clearing of jungle and
fever is already gone. By this time, platelet count will drop, hematocrit may
forests for housing purposes, hunting, and transport of animals, brings
also drop depending on how hydrated the patient is. This is where the
people closer to animals that may be infected. Lastly, the absence of
complicated course of the disease is seen (i.e. patient can vomit even
adequate sewage and safe water.)
without fever, severe headache, or may go into septic shock or bleeding). In
DENGUE
recovery phase, patient will recover after 2-3days without fever and there
 Most common mosquito-borne viral disease that hasbecome a major
is also reabsorption of fluid (physicians should not hydrate the patient too
international public health concern
much as this can lead to accumulation of fluid in the cavities). Platelet count
 Globally, 2.5 billion people live in areas where dengueviruses can be
is expected to rise (WBC count will rise first) and antibodies are positive
transmitted
during serologic testing.
 Hyperendemic in many urban centers of the tropics
o Driven by the unprecedented urban growth and modern Diagnosis: Clinical
transportation, and the lack of effective mosquito control in
 Viral isolation
the tropical regions in the world
 PCR
 Ag-Ab test

Treatment:
 Supportive (fluids, symptomatic relief of fever)

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MICROBIOLOGY 3.12

Dengue Virus Vaccines Diagnosis: Clinical


 5 tetravalent vaccines are currently being evaluated  Antigen test
 aimed at providing long-term protection against all four serotypes at  PCR
once reducing immuneenhancement (IE) risk
 3 live attenuated vaccines – 1 already on phase 3trial Treatment:
o Initial studies showed safety and relative efficacy  Supportive (fluids, pain relievers)
*Droplet in platelet count is not as bad as compared to the dengue virus
CHINGKUGUNYA VIRUS infection
 Positive strand alpha virus
 Transmitted to humans by the same mosquito that carries dengue MERS-CoV
(Aedes)  Middle East Respiratory Syndrome Corona Virus
 Exist in equatorial Africa, India, Southeast Asia, and the island nations
of the Indian Ocean (Madagascar and Reunion Islands) Epidemiology
 First reported in 1950s in Tanzania  1st reported in April, 2012 in Saudi Arabia
 Re-emerged in 2005-2006 in the Reunion islandsaffecting > 200,000  Has affected 9 countries todate
with almost 1000 deaths reported o total of 114 cases and 54deaths as of Sept. 12,2013
 2007: > 1 M got infected in India, Malaysia, Sri Lankaand Indonesia o Cases in Western Europehave been imported fromthe Middle East
 Imported cases reported in Europe, Australia and USA
 In the Philippines: Clinical Manifestations
o Endemic, having caused sporadic outbreaks in 1954,1956, 1968,  Symptoms: chills, cough, fever, dyspnea, myalgia (less often, nausea
and 1985 to 1986 and diarrhea)
o 1986, an outbreak of Chikungunya was reportedamong U.S.  The majority in patients with co-morbidities
Peace Corps volunteers stationed in thePhilippines (Mindanao,  Few cases with mild or asymptomatic infection have been reported
Cebu and Masbate) o Close contacts of patients have been infected, but there
o 1996, 156 patients in Indang, Cavite developed thedisease is not sustained chain of human to human infection
o 2009, several Filipino tourists acquired Chikungunya inThailand outside the hospital that has occurred when you
o 2013 compare it to SARS Corona Virus
 Less than the 600 cases in 2012 and 1,200 in 2011 o 21 of 23 cases in a recent report– transmission within
 175 cases as of September in Western Visayas health facilities
 More than 100 patients in Mountain Province  The incubation period was 5.2 days (95%CI: 1.9-14.7days)
andQuezon(therefore, it is not a REGIONAL type of disease)  No animal source has been identified
 Cynomolgus monkeys (Macacafascicularis) areimplicated as o They have discovered and isolated the virus in a cave
reservoirs near the home an individual case
 Peak respiratory symptoms as well as viral shedding is reached
approximately 3-4 days after inoculation
 The virus replicates well in ciliated epithelial cells, causing degeneration
of these cells  outpouring of chemokines and interleukins  common
cold symptom comparative to a Rhinovirus infection

Diagnosis and Treatment


 No vaccine or antiviral therapy is available
 Medical intervention: supportive
 Diagnostic tests through the CDC (special request)

INFLUENZA
History
 Spreads across countries and across ages
Figure 2. Clinical Course of CHIKV  Discovered back in 412 BC, as reported by Hippocrates who noted
an epidemic
Following the transmission of the mosquito bite, the individual will
 In early 1800s, reported epidemics in Russia which came from Asia
experience an acute onset of the disease 2-4days after the infection.
 1918 – Spanish Influenza affected more than 20-40 million people
Symptoms include high grade fever, rash (petechial or maculopapular),
 1933 – The first human influenza virus was discovered
rigor, headache, and severe joint pain in most individuals (this is what
 1957 - Asian Influenza
distinguishes it from dengue virus). Patient may complain more of the joint
pains rather than the fever. Rash appears during the febrile phase (as  1988 – Hong Kong flu
opposed to dengue wherein rash appears mostly by the time the fever is  2009 – Swine flu
gone). Disease onset will coincide with the rising viral titer and this rise in
the viral titer will trigger an activation of chemokines even with the Characteristics
production of interferons. Patient will successfully clear the virus however,  Contagious respiratory illness caused by influenza viruses that
around after a week, individual will develop antibodies and T-cells. infect the nose, throat, and lungs
Sequelae (joint pains, joint swelling) (orange arrows) can last from months  Spectrum - Can cause mild to severe illness, at times can lead to
to years. death
 Epidemic nature of the disease

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MICROBIOLOGY 3.12

Transmission AVIAN INFLUENZA (H7N9)


 Droplet and Fomites  Update as of August 11, 2013 – last reported case of 51 y/o female
 Spread mainly by droplets made when people with flu, cough, from Guangdong, China
sneeze or talk, or by touch or contact  135 total number of lab-confirmed cases
 Period of infectiousness: 1 day before symptoms develop and up to  44 deaths (36%)
5 to 7 days after becoming sick  Coexisting medical conditions are a significant risk factor for those
who will develop acute respiratory distress syndrome.
Diagnosis  Patients will present with:
 mainly clinical
o Fatigue
o no conjunctivitis
Treatment
o cough
 Supportive
o sputum production
 Antiviral drugs
o may have hemoptysis
 Oseltamivir*, Zanamivir o shortness of breath
 Amantadine*, rimantadine
o diarrhea
Note * available in Philippines o vomiting
Complications
 Bacterial superinfections  Recommendations for this virus are based on the following
o Bacterial pneumonia
considerations:
o Respiratory disorders
 Decompensation of chronic diseases o lack of vaccine
o Pulmonary disease o substantial mortality
o Heart disease o limited human to human transmission but the potential for
o Renal insufficiency increase transmission in the future
o Metabolic disease
Prevention:
Prevention o mostly infection control (air borne and droplet) – use a surgical
 infection control mask or a respirator
o Avoid exposure
 cough and cold etiquette
o There is currently a lack of vaccine for this virus!
 Vaccination (Southern Hemisphere Recommendation
 Once a year, preferably between February and June wherein an
H7N9 Avian Flu Treatment
expected increase in influenza activity from June to November
Uncomplicated
o Oseltamivir
o Inhaled zanamivir
Hospitalized
o Oseltamivir
o IV zanamivir

Note: Rapid diagnostic test is done simultaneously with treatment, for both
conditions.
POLIO VIRUS
 Disease caused by a virus that is mainly spread by eating or drinking
items contaminated with the feces of an infected person
 Pathologic lesion will involve neurons in the gray matter especially in
the anterior horns of the spinal cord
 Updates as of August 16, 2013
o 100 cases reported from Somalia in 2013
Fig.3 Southern Hemisphere Recommendation  First wild poliovirus cases reported in Somalia since 2007
o 10 cases have been reported from Kenya
AVIAN INFLUENZA (H5N1)  First wild poliovirus cases confirmed in Kenya since July
 First reported to infect a human in 1997 in Hong Kong 2011
o 6 additional confirmed, 2 possible cases during thesubsequent 7
months Clinical Manifestations
o total of 18 cases with 6 deaths Incubation period
 continuing sporadic cases, small clusters  9 to 12 days (range, 5 to 35 days) from presumed contact until
o high case-fatality proportion (59%) in humans the onset of the prodromal symptom
 During 2012: 32 human infections from Bangladesh, Cambodia, China,  11 to 17 days (range, 8 to 36 days) until the onset of paralysis
Egypt, Indonesia, Vietnam
 Most associated with exposure to poultry, and 20 (62.5%) of cases were
fatal
 Potential for mutations that would yield greater transmissibility among
mammals
 Potential to cause substantial global mortality

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MICROBIOLOGY 3.12

o sometimes, dyspnea
Management
 Specific acting viral drugs for the treatment of polio are not
available
 Management is mainly supportive directed to relieve symptoms

Prevention
 Vaccine – inactivated polio vaccine, oral polio vaccine
 Eat clean and safe food and water
 Don’t eat raw food, sold in the streets, served in room
temperature
 Practice hygiene and cleanliness

ENTEROVIRUS
Similar to polio virus in causing severe neurologic disease but compared to
the polio virus, present more with muscle weakness

 Caused large outbreaks in Southeast Asia


 Associated with severe CNS disease and deaths
 Primary clinical manifestations
Fig.4 Polio Virus Clinical Manifestations o Non-specific febrile illness
o HFMD (hand foot and mouth disease)
Asymptomatic or unapparent infection o ~2 in 10,000 children experience severe morbidity: brainstem
- occurs to 90 to 95 % will have encephalitis, pulmonary edema, and hemorrhage
- recognized only by the isolation of the virus from the feces or  Most patient will complain with sore throat or sore mouth (affected
oropharynx, or by performing an antibody titer for polio young children will be unable to eat because of the mouth sores)
Abortive poliomyelitis  Temperature ranges for 38 to 39°C lasting for 1 to 2 days
- will occur to 4% to 8%  Always accompanied by vesicles in the oral cavity, chiefly in the
- Characterized by:
buccal mucosa and the tongue
o 2 to 3 days of fever
o Listlessness  Several lesions may coalesce and for bullae and may even ulcerate
o anorexia  The lesions can occur in the extensor surface of the hands and feet,
o chills and sometimes in the buttocks or the genital
o headache  A Re-emerging virus
o vomiting  The outbreak in Cambodia: July 2012
o abdominal pain
o an outbreak of unknown etiology
- Because neurologic exam is normal, one cannot be distinguished
o 61 children high fever, neurologic and/or respiratory signs and
from other viral infections
symptoms
 can be clinically suspected only during an epidemic when
o 46 died w/in 24 hours of admission; majority of the others died
there are too many patients having the same symptoms.
w/in 3 days.
Non paralytic type of polio
 The outbreak in Vietnam:
- Differs from the abortive type because of the presence of
meningeal irritation. o July 2011: significant surge of cases reported from the south of
- Identical to meningitis symptoms produced by other the country
enteroviruses. o December 2012: there were over 148, 366 cases with 45 deaths
- Systemic manifestations are more severe.
- Paralysis is flaccid. VIBRIO CHOLERAE
 DTR are initially hyperactive but eventually become  Curved G- bacilli
absent if you keep doing the neurologic physical exam.  Thiosulfate citrate bile salts sucrose agar and tellurite taurocholate
 Most characteristic feature of the paralysis is the gelatin agar
asymmetric distribution which affects muscle groups  Dark field microscopy of stool sample of patients positive of cholera
while sparing others.
 Production of enterotoxin promotes secretion of fluids and
 Proximal muscles are more affected than the distal
muscles electrolytes by the small intestine
 Legs are more commonly involved, then the arms  The infectious dose varies
 Large muscle groups of the forearms or the hand are o Water: more bacteria (103 to 106) are needed to cause disease
more affected than the small ones 2 4
o Food: 10 to 10
Bulbar Poliomyelitis  Incubation period varies with infectious dose and gastric acidity; lasts
- paralysis involves the group of cranial nerves occurring in the soft
12 to 72 hours
palate and pharynx
- patient will present with:  Dark field microscopy of stool sample of patients positive of cholera
o dysphagia  Toxin has 5 A sub units and 2 B sub-units, all affecting the mucosa of
o nasal speech the intestine

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MICROBIOLOGY 3.12

 A subunit acted by adenylate cyclase activation of cAMPblock SOURCES:


Na and Clsecretion of electrolytes and water voluminous watery  Minette Claire O. Rosario, MD., FPCP, DPSMIDpowerpoint lecture
diarrheadiarrhea: electrolyte concentration equals of plasma

Fig.5 Hierarchal model of Cholera transmission

 Several factors: Seasonal effects, climate variability, socio-economics,


Demographics, Sanitation which will contribute for the proliferation of
bacteria in the copepods you see in the waters and algae. Injecting
infectious dose of cholera presenting the disease
 The bacteria will not invade the intestinal wall the fecalysis will show
very neutrophils, almost none, zero. WBC= 0 to 1
 Produces enterotoxins that promote secretion of electrolytes & fluids
by the small intestine

RABIES
 Worldwide zoonotic disease
 Human mortality (WHO estimate): 55,000 deaths annually worldwide
o 31,000 deaths in Asia alone (1 death every 20 minutes)
o Around 2.5 billion people at risk
o Locally (2008), 250 human rabies deaths
 Endemic in the Philippines
o Locally, about 400k seek consult
for rabies exposure annually
o 14k-20k new consultations for dog/cat bites every year
 Incidence
o 6-8/million population
o 300-500 cases/year
 SEA under-reporting of this disease
 Patient after animal bite: Fever, depression, agitation, spasms,
salivation, death within a week if no vaccine was introduced
 Tx: hospitalization, Ig injection, anti-rabies vaccine
 Cats, dogs, hamsters, skunks, fox,monkeys are the usual carriers

 CDC website: Pop-Culture of Zombies since 1950’s we can relate to it


easily.
Relate zombie phenomena to rabies virus. Knowing the transmission of
disease, we can protect ourselves. See appendix

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MICROBIOLOGY 3.12

Appendix

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Microbiology 3.12 LECTURER: Dr. Rosario
Emerging and Re-Emerging Infectious Diseases DATE: Oct. 1, 2013

Primary Transmission Comments


Emerging Diseases
Avian influenza A H5N1 Zoonotic (close contact with poultry) 325 reported cases, 224 deaths in Indonesia, Vietnam, Thailand, Cambodia, Laos, and
Myanmar5
Pandemic influenza A H1N1 Respiratory 5290 reported cases, eight deaths in all ten countries6
(2009)

SARS Respiratory 331 reported probable cases, 44 deaths in Singapore, Vietnam, Thailand, Malaysia, and
Indonesia7
Nipah virus Zoonotic (close contact with pigs) First known human cases in Malaysia; 276 cases, 106 deaths in Malaysia and Singapore8
Re-emerging Diseases
Chikungunya fever Vector-borne Endemic in many southeast Asian countries; re-emerged in Singapore (2008),
Malaysia (2007),9 Thailand (2009), and Indonesia (2010)
Dengue fever Vector-borne Originated in southeast Asia; 398 340 cases and 1596 deaths in 2008 with high burden
in Indonesia, Vietnam, Thailand, Malaysia, the Philippines, Myanmar, and Cambodia;
estimated 253 000 DALYs lost in 20041
Japanese encephalitis Vector-borne and zoonotic Only 68 reported cases in Thailand in 2009;10 estimated 243 000 DALYs lost in 20041
Rabies Zoonotic (bite or scratch from rabid animal) 587 cases and deaths in 2009 in Indonesia, the Philippines, Vietnam, Myanmar, and
Thailand10
HIV/AIDS Sexual, injecting drug use, vertical High adult HIV prevalence (more than 0·5%) in Thailand, Cambodia, and Myanmar, with
more than 200 000 HIV-positive people in Thailand, Vietnam, Indonesia, and Myanmar;11
estimated 2 952 000 DALYs lost in 20041
Streptococcus suis Zoonotic (close contact with pigs) Case reports from Thailand and Vietnam12
Leptospirosis Zoonotic (skin contact with urine of rodents) 5697 cases and 83 deaths in 2009 with high burden in Thailand and reported cases in
Indonesia and Myanmar10
Drug-resistant Diseases
MDR tuberculosis Respiratory 2332 cases in 2008;13 high-burden countries are the Philippines, Myanmar, Indonesia,
and Thailand
XDR tuberculosis Respiratory Detected in Myanmar, the Philippines, Singapore, Thailand, and Vietnam13
MDR Plasmodium falciparum Vector-borne Documented on Cambodia’s border with Thailand14
malaria
SARS=severe acute respiratory syndrome. DALYs=disability-adjusted life-years. MDR=multidrug resistant. XDR=extensively drug resistant.
Highlighted are the ones discussed.

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