Arthropod-Borne Viruses Part One

7/28/2019 Arthropod-Borne Viruses Part One

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Dr.T.V.Rao MD

Dr.T.V.Rao MD 1

Arboviruses

Arthropod-Borne VirusesPart 1


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What Is An Arbovirus?

Arbovirus = arthropod-borne viruses

Arboviruses are maintained in nature

through biological transmissionbetween susceptible vertebrate

hosts by blood-feeding arthropods

Vertebrate infection occurs when the

infected arthropod takes a blood

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Arboviral Infections.

100s of Arbovirus,

Around 100 are Human pathogens,

Prevalent in Temperate and Tropical

areas.

Most common in tropics,

Out of Many 10 are very important.

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Arthropod-borne Viruses

Arthropod-borne

viruses (arbovirus)

are viruses that canbe transmitted to

man by arthropod

vectors.

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The WHO definition is as follows

Viruses maintained in natureprincipally, or to an important

extent, through biological transmissionbetween susceptiblevertebrate hosts byhaematophagus arthropods or

through trans ovarian and possiblyvenereal transmission inarthropods.

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Arbovirus belong to

Arbovirus belong to three families

1. Toga viruses e.g. EEE, WEE, and VEE

2. Bunya viruses e.g. Sandfly Fever, RiftValley Fever, Crimean-Congo

Haemorrhagic Fever

3. Flavivirus e.g. Yellow Fever, dengue,

Japanese Encephalitis

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Disease Mechanisms of Toga viruses and FlavivirusViruses are cytolytic, except for rubella.

Viruses establish systemic infection and viremia.

Viruses are good inducers of interferon, which can account for the flulikesymptoms of infection.

Viruses, except rubella and hepatitis C, are arboviruses.

Flavivirus can infect cells of the monocyte-macrophage lineage. Non-

neutralizing antibody can enhance Flavivirus infection via Fc receptors on

the macrophage.

Flulike Syndrome Encephalitis Hepatitis Hemorrhage Shock

Dengue + + + +

Yellow fever + + + +

St. Louis encephalitis + +West Nile encephalitis + +

Venezuelan encephalitis + +

Western equine encephalitis + +

Eastern equine encephalitis + +

Japanese encephalitis + +Dr.T.V.Rao MD 7


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Man-Arthropod-Man Cycle

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Animal-Arthropod-Man

Cycle

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INDIAN SCENARIO

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Arboviral are Basically Zoonotic

All arboviral encephalitis's are zoonotic,being maintained in complex life cycles

involving a nonhuman primary

vertebrate host and a primary arthropod

vector. These cycles usually remain

undetected until humans encroach on a

natural focus, or the virus escapes this

focus via a secondary vector or

vertebrate host as the result of some

ecolo ic chan eDr.T.V.Rao MD 11


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Arthropod Vectors

MosquitoesJapanese encephalitis, dengue, yellow fever, St.

Louis encephalitis, EEE, WEE, VEE etc.TicksCrimean-Congo hemorrhagic fever, various tick-

borne encephalitis's etc.SandfliesSicilian sandfly fever, Rift valley fever.

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Examples of Arthropod Vectors

Aedes AegytiAssorted Ticks

Phlebotmine SandflyCulex Mosquito Dr.T.V.Rao MD 13


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Major Arboviral Diseases

1.Yellow fever

2.Dengue,

3.Japanese B Encephalitis,4.St Louis Encephalitis,

5.Russian spring summer encephalitis.

6.Eastren Equine Encephalitis,7.West Nile Fever,

8.Sand fly Fever

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Major Arboviruses That Cause

Encephalitis

Flaviviridae

Japanese encephalitis

St. Louis encephalitis

West Nile

Togaviridae

Eastern equine encephalitis

Western equine encephalitis Bunyaviridae

La Crosse encephalitis

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17/80http://www.cdc.gov/ncidod/dvbid/arbor/schemat.pdf

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St. Louis Encephalitis

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St. Louis Encephalitis

Flavivirus

Most common

mosquito-transmitted

human pathogen

in the US Leading cause of

epidemic flaviviral

encephalitis Dr.T.V.Rao MD 20


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Eastern Equine Encephalitis

Toga virus

Caused by a virus transmitted tohumans and horses by the bite ofan infected mosquito.

200 confirmed cases in the US

1964-present Average of 4 cases per year

States with largest number ofcases Florida, Georgia,Massachusetts, and New Jersey.

Human cases occur relativelyinfrequently, largely because theprimary transmission cycle takesplace in swamp areas wherepopulations tend to be limited.

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Western Equine Encephalitis

Toga virus

Mosquito-borne

639 confirmed cases in

the US since 1964 Important cause of

encephalitis in horsesand humans in North

America, mainly in theWestern parts of the USand Canada

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La Crosse Encephalitis Bunyaviruses

On average 75 cases per yearreported to the CDC

Most cases occur in children under16 years old

Zoonotic pathogen that cycles

between the daytime biting tree holemosquito, and vertebrate amplifierhosts (chipmunk, tree squirrel) indeciduous forest habitats

Most cases occur in the upperMidwestern state, but recently caseshave been reported in the Mid-

Atlantic region and the Southeast 1963 isolated in La Crosse, WI from

the brain of a child who died fromencephalitis

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Togaviridae

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Togaviridae

The name

Togaviridae

derived fromToga meaning

roman mantle or

clack refers tothe viral surface

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TOGAVIRIDAE

Chikungunya virus Infection

1952 Epidemic in Tanzania.

Manifest as Bend Up with Severe

Joint pains.

Spread from wild primates

Mosquito-Man

Appears , reappears,

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Indian outbreaks

The virus first appeared in India in

1958 the virus caused large

epidemics in Thailand In 1963 India Chikungunya

outbreaks occurred at irregular

intervals along the east coast of India

and in Maharashtra

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Viral Morphology

Spherical 50 - 70

nm

Bears theNucleocapsid, 42

capsomeres

Positive sense ssstranded RNA

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Prevalence of Chikungunya

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Transmission of Infection

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Man to Man infection with Mosquito

bites

Chikungunya virusrequires an agent fortransmission and hencedirect human to human

transmission is notpossible. Usuallytransmission occurswhen a mosquito bites

an infected person andthen later bites a noninfected person.

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Clinical Manifestations

Crippling Joint pains

Conjunctivitis Lymphadenopathy

Hemorrhagictendencies.

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Diagnosis

Isolation of

viruses,

Serology Ig M

Nt and HI

tests,

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Control and Prevention.

Mosquito control

No vaccines,

Other diseases like

Chikungunya

1 Onyong Nyong Viruses

2 Simliki Forest VirusesDr.T.V.Rao MD 34


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Japanese B Encephalitis

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Flaviviridae

Flavivirus

The name is derived from

the Latin flavus

Flavus means yellow

Refers to yellow fever virus

Enveloped

Single stranded RNA virus

Morphology not well

defined

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Japanese Encephalitis belongs to

Genus Flavivirus

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Flaviviridae

Genus Flavivirus, Important Diseases,

1. St Louis encephalitis,

2.Ilheus virus

3.West Nile Virus,

4.Murray valley encephalitis,

5.Japanese B encephalitis,Dr.T.V.Rao MD 37


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First discovered and originally restricted

to Japan. Now large scale epidemics occur

in China, India and other parts of Asia. Flavivirus, transmitted by culex

mosquitoes.

The virus is maintained in nature in a

transmission cycle involving mosquitoes,

birds and pigs.


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Most human infections are subclinical: the inapparent to clinical cases is 300:1

In clinical cases, a life-threatening encephalitis

occurs. The disease is usually diagnosed by serology.

No specific therapy is available.

Since Culex has a flight range of 20km, all localcontrol measures will fail. An effective vaccineis available.

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1870s: Japan Summer encephalitis epidemics

1924: Great epidemic in Japan

6,125 human cases; 3,797 deaths

1935: First isolated

From a fatal human encephalitis case

1938: Isolated from Culex

tritaeniorhynchusDr.T.V.Rao MD

History

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Genus - Flavivirus Japanese B encephalitis

virus is

Spherical, 40 60 nm in

diameter

Contain a positive sense

Single stranded RNA, 11 kb

in size

RNA genome is infectious

Several viruses in this group

are related.

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Infection is caused by a flavivirus, a singlestranded RNA virus. It is transmitted bythe bite of the Culex tritaeniorhynchus

mosquito. The virus multiplies at the siteof the bite and in regional lymph nodesbefore viraemia develops. Viraemia canlead to inflammatory changes in the

heart, lungs, liver, andreticuloendothelial system.

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Japanese B virus Infection


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The outer envelope isformed by envelope (E)protein and is the protectiveantigen. It aids in entry ofthe virus to the inside of thecell. The genome alsoencodes several non-structural proteins also(NS1,NS2a,NS2b,NS3,N4a,N

S4b,NS5). NS1 is producedas secretary form also. NS3is a putative helicase, andNS5 is the viral polymerase.

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Structure of Virus


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Japanese encephalitis( previously

known as Japanese B encephalitis is a

disease caused by the mosquito-borne

Japanese encephalitis virus. The

Japanese encephalitis virus is a virus

from the family Flaviviridae. Domestic

pigs and wild birds are reservoirs of the

virus; transmission to humans may occur

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A Flavivirus


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INDIAN SCENARIO

Japanese encephalitis ( previously known

as Japanese B encephalitis is a disease

caused by the mosquito-borne Japanese

encephalitis virus. The Japanese

encephalitis virus is a virus from the

family Flaviviridae. Domestic pigs and

wild birds are reservoirs of the virus;

transmission to humans may occur

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1940-1978

Disease spread with epidemics in China,

Korea, and India

1983: Immunization in South Korea

Started as early as age 3

Endemic areas started earlier

1983-1987: Vaccine available in U.S. on

investigational basisDr.T.V.Rao MD

History

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Japanese

encephalitis is the

leading cause of viral

encephalitis in Asia,with 30,00050,000

cases reported

annually. Case-fatality rates range

from 0.3% to 60%

and depends on theDr.T.V.Rao MD 47

A leading cause of viral Encephalitis


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Animal-Arthropod-Man Cycle

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C l f I f ti i J B


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Cycle of Infection in Japanese B

Viral Infection


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Vector-borne disease

Enzootic cycle

Mosquitoes: Culexspecies

Culex tritaeniorhynchus

Reservoir/Amplifying hosts

Pigs, bats

Ardeid (wading) birds

Possibly reptiles and amphibians Incidental hosts

Horses, humans, others

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Transmission

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http://whyfiles.org/shorties/085fast_evolution/images/mosquito.jpg


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Most important global

cause of arboviral

encephalitis with > 50,000

cases and 15,000 deaths

reported each year. Only about 1 in 250 JE

infections result in

symptomatic illness.

Primarily affects children 1to 15 years of age.

Incubation period is 5 to 14

days.

Japanese Encephalitis (JE)

If unrecognized, mortality is up to 30% with half ofsurvivors sustain severe neurological sequelae.

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Leading cause of viral encephalitis in Asia

with 30-50,000 cases reported annually

Fewer than 1 case/year in U.S. civilians

and military personnel travelling to and

living in Asia

Rare outbreaks in U.S. territories in

Western Pacific

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INCIDENCE


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Many poor people are Infected

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Cycle of Spread of Japanese


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Cycle of Spread of Japanese

Encephalitis

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C cle of E ents in Japanese B


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Cycle of Events in Japanese B

Encephalitis


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Pass through two prominent Hosts

Herons act as

reservoir hosts and

pigs as amplifier

hosts.

Human infection is a

tangential dead end

and infections arespread when the

infected mosquitoes

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The incubation period is 6 to 16 days.

There is a prodrome of fever, headache, nausea,diarrhoea, vomiting, and myalgia, which may last forseveral days.

This may be followed by a spectrum of neurologicaldisease ranging from mild confusion, to agitation, toovert coma.

Two thirds of patients have seizures. It is morecommon in children, while headache and meningismare more common in adults.

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Clinical Manifestations

Common symptoms of encephalitis


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LethargySudden fever

Vomiting anddiarrhea

Tremors or

convulsions

Headache Change in

consciousness

Irritability or

restlessness

Common symptoms of encephalitis

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Tremor or other involuntary movementsare common.

Mutism has been described as a

presenting symptom. So has a syndromeof acute flaccid paralysis.

Fever resolves by the second week, and

choreoathetosisor extra pyramidalsymptoms develop as the otherneurological symptoms disappear.

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Can lead to Neurological damage


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The isolation of virus from Blood, CSF,

or tissues.

Detection of Arbovirus specific RNA inblood,CSF, or Tissue

However very few reference laboratories

can perform the isolation in view of the

biosafety considerations

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Diagnosis of Japanese B Encephalitis


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IgM capture enzyme-linked immunoassay (ELISA) ofserum or CSF is the standard diagnostic test.Sensitivity is nearly 100% when both serum and CSFare tested. False-negatives may result if the samples

are tested too early, as in the first week of illness. New IgM dot enzyme immunoassays for CSF and

serum are portable and simple tests that can be usedin the field. Compared with ELISA as the gold

standard, the sensitivity and specificity are around98 and 99% respectively.

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Serology by ELISA


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Japanese Encephalitis B Vaccine has beenproduced since 1992. The vaccine is effectivebut not without risks and the substantial risks

of the disease and the risks of the vaccinehave to be balanced, especially for stays ofbrief duration. These are discussed more fullyin the article on that subject.

As with malaria, prophylaxis must besupplemented by techniques to avoid beingbitten by mosquitoes.

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Japanese Encephalitis B Vaccine


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Preventive measures include mosquito control

and locating piggeries away from human

dwellings

A formalin inactivated mouse brain vaccineusing the Nakayama strain has been employed

in human immunization in Japan Two doses

at two weeks interval followed by a booster 6 12 months later constitute a full course.

However the immunity was short lived

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Preventive measures


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Two vaccines are manufactured and distributedexclusively in Peoples Republic of China

Inactivated vaccine grown in primary hamster kidney cells

Live attenuated vaccine (SA14-14-2) grown in hamster

kidney cells

The third is manufactured in Japan and distributedabroad by arrangement with Sanofi-Pasteur

Licensed as JE-VAXR and is the only FDA approved vaccine

for use in the U.S. Has been in wide use worldwide since the 1960s

Three subcutaneous injections over a month with abooster at 3 years

91% efficacy in a large field trial in Thailand

Emerging Vaccines for JE virus

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Live attenuated vaccine

Used in equine and swine

Successful for reducing incidence

Inactivated vaccine (JE-VAX)

Used for humans

Japan, Korea, Taiwan, India, Thailand

Used for endemic or epidemic areas

Recommended for travelers

Visiting endemic areas for > 30 days

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Vaccination

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A live attenuated vaccine has been developed

in China from JE strain SA 14-14-2, passed

through weanling mice

The vaccine is produced in primary bayhamster kidney cells.

Administered in two doses, one year apart,

the vaccine has been reportedly effective inpreventing clinical disease

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Later vaccines

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Vector control Eliminate mosquito breeding areas

Adult and larvae control

Vaccination Equine and swine

Humans

Personal protective measures Avoid prime mosquito hours

Use of repellants containing DEET

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Prevention

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Yellow Fever


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Yellow Fever,

Flaviviridae - Family

Mosquito Borne disease

Present in Africa, Centraland South America.

Absent in India.

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Fl i i


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Flavivirus Spherical 40-60 nm in diameter

glycosylated. Diameter,

Ss-RNA positive sense Three or Four structural polypeptides,

Two are glycosylated.

Replicates in Cytoplasm.

Produces Councilman bodies

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Pathogenesis and Pathology

Mosquito ( Ades aegypti )Through skin-

Lymphatic's, Lymph nodes, circulation liver,

Spleen, Kidney, Bone marrow, Lymph glands.

Necrotic lesions in liver , kidney,

Mid zone liver

Fatty degeneration kidney,

Hemorrhages/Circulatory collapse.

Injury to Myocardium

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Clinical Features

Incubation period 3-6 days,

Fever, chills,

Intoxication, Fever, Jaundice

Clotting disorders,

Mortality > 20%

May recover totally

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Laboratory Diagnosis

Intracerebralinoculation,

Mosquito cell

lines, P C R

Serology

ELISA Ig M Raiseof titers,

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Immunity and Epidemiology

Nt Antibodies protects,

Epidemiology

Urban yellow fever,

Jungle yellow fever.

Monkey,Not Invaded Asia Not present in

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Programme Created by Dr.T.V.Rao MD

for medical Students in the Developing

World

Email; [email protected]

Arthropod-Borne Viruses Part One

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