10. arboviruses

7/27/2019 10. Arboviruses

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ARBOVIRUSESArthropod-borne Viruses


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ARBOVIRUSESThe WHO definition is as follows

Viruses maintained in nature principally or to an

important extent: Through biological transmission between susceptible

vertebrate hosts by haematophagus arthropods

Through transovarian and possibly venereal transmission in

arthropods


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ARBOVIRUSES Arthropod borne viruses (Arboviruses) are transmitted from one host to

another through blood sucking arthropods

(Mosquitoe, ticks, fleas etc.)

They are most prevalent in tropical rain forest with abundance ofanimals and arthropods

There are more than 450 arboviruses, out of these 100 are infective tohumans

Arboviruses may belong to families that includes Togaviridae,Flaviviridae and Bunyaviruses.

Families are enveloped, RNA viruses


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ARBOVIRUSES contd The infection is zoonotic, with humans act as accidental

hosts.

Humans do not play any role in maintenance ortransmission cycle of virus.

Exceptions are urban yellow fever and dengu


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Classification Togaviridae consists of Alphaviruses, Rubivirus and

Arterivirus

Only Alphaviruses and Rubivirus are important incausing human disease

Rubivirus that consists of Rubella virus is NOTtransmitted by arthropod vectors.

Alphaviruses include Sindbis virus, Semliki forest virus, Venezuelan equine

encephalitis virus (VEE)

Eastern equine encephalitis virus (EEE), Western equineencephalitis virus (WEE) and chikungunya virus


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Classification contd.. Flaviviridae consists of Flaviviruses, Pestiviruses and

Hepaciviruses (Hepatitis C Virus)

Flaviviruses are transmitted through arthropods.

Important Flaviviruses include

Dengue virus

Yellow fever virus

Japanese B encephalitis virus

West Nile encephalitis virus,

St. Louis encephalitis virus

Russian spring summer encephalitis virus

Powassan encephalitis virus.


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Classification contd.. Bunyaviruses e.g. Sandfly Fever, Rift Valley Fever, Crimean-

Congo Haemorrhagic Fever


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Naming of Arboviruses Some arboviruses are named after a disease (dengue,

yellow fever)

Geographic area where virus was first isolated (St.Louisencephalitis, West Nile fever)


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Transmission Cycles

Man - arthropod -man

E.g. dengue, urban yellow fever.

Reservoir may be in either man or arthropod vector.

In the arthropod vector transovarial transmission may take place.

Animal - arthropod vector - man

E.g. Japanese encephalitis, EEE, WEE, jungle yellow fever.

The reservoir is in an animal. The virus is maintained in nature in a transmission cycle involving

the arthropod vector and animal. Man becomes infected

incidentally.

Both cycles may be seen with some arboviruses such as yellow fever.


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Man-Arthropod-Man Cycle


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Animal-Arthropod-Man Cycle


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Examples of Arthropod Vectors

Aedes AegytiAssorted Ticks

Phlebotmine SandflyCulex Mosquito


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Animal Reservoirs

In many cases, the actual reservoir is not known. The

following animals are implicated as reservoirs

Birds Japanese encephalitis, St Louis encephalitis,EEE, WEE

Pigs Japanese encephalitis

Monkeys Yellow Fever

Rodents VEE, Russian Spring-Summer encephalitis


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Diseases Caused

Fever and rash - this is usually a non-specific illness

resembling a number of other viral illnesses

Such as influenza, rubella, and enterovirus infections. Thepatients may go on to develop encephalitis or haemorrhagic fever.

Encephalitis - e.g. EEE, WEE, St Louis encephalitis,Japanese encephalitis.

Haemorrhagic fever- e.g. yellow fever, dengue, Crimean-

Congo haemorrhagic fever.

Some arboviruses may be associated with more than one

syndrome, eg, dengue


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Diagnosis

Serology - usually used to make a diagnosis of arbovirus

infections.

Culture - a number of cell lines may be used, includingmosquito cell lines.

However, it is rarely carried out since many of the

pathogens are group 3 or 4 pathogens.

Direct detection tests - e.g detection of antigen and nucleic

acids are available but again there are safety issues.


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Prevention

Surveillance - of disease and vector populations

Control of vector - pesticides, elimination of breeding

grounds

Personal protection - screening of houses, bed nets, insect

repellants

Vaccination - available for a number of arboviralinfections e.g. Yellow fever, Japanese encephalitis,

Russian tick-borne encephalitis


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Alphaviral diseases


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Sindbis Vector is Aedes and other mosquitoes

Natural host are birds

Prevalent in Africa, Australia and India

Disease is manifested from subclinical infection to febrile

illness with or without rash


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Semliki Forest Vector is Aedes and other mosquitoes. Natural host are

birds

Prevalent in East and West Africa

Disease is manifested from subclinical infection to febrileillness with or without rash


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Venezuelan equine encephalitis (VEE) Vectors are Aedes and Culex

Natural host are Rodents and horses

Prevalent in north, south and central America

The disease may range from mild systemic to severe

encephalitis.


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Eastern Equine encephalitis (EEE): Vectors are Aedes and Culex

Natural host are birds and horses

Prevalent in north and south America

The disease may range from mild systemic to severe

encephalitis


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Western equine encephalitis (WEE) Vectors are Culex, Culista

Natural host include birds and horses.

Prevalent in North and south America

Disease may range from mild systemic to encephalitis


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Chikungunya: Vector is Aedes. Natural host include humans and

monkeys

Prevalent in Africa and Asia

Disease manifestation include fever, arthralgia andarthritis


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Flaviviruses


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Yellow Fever It is an acute, febrile, mosquito-borne illness

Severe cases are characterized by jaundice, proteinuria,

and hemorrhage


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Pathogenesis & Pathology Virus is introduced by mosquito through skin and spreads

to local lymph nods, where it multiplies

From lymph nodes, it enters circulating blood and becomes

localized in liver, spleen, kidney, bone marrow and lymphglands

Lesions of yellow fever are due to localization andmultiplication of virus in a particular organ

Death may result from necrotic lesions in liver and kidney Most frequent site of hemorrhage is mucosa at pyloric end

of stomach

Degenerative changes also occur in spleen, lymph nodesand heart.


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Clinical features Classically Yellow Fever at the onset, patient has fever,

chills, headache, backache, nausea, vomiting with highfever and moderate jaundice

In severe cases, increased proteinuria and hemorrhagicmanifestations appear and develop bradycardia (Faget'ssign)

Vomitus may be black with altered blood


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Clinical features contd. 50% of patients with frank YF will develop fatal disease characterized

by severe haemorrhagic manifestations, oliguria and hypotension

Some patients may experience an asymptomatic infection or amild undifferentiated febrile illness


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Laboratory diagnosisIsolation of virus

From patients blood virus can be recovered byintracerebral inoculation of mice

It is identified by neutralization test with specific

antiserum( by serology)


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Epidemiology

Flavivirus, mainly found in West Africa and S America

Yellow fever occurs in 2 major forms:

Urban and jungle (sylvatic) yellow fever.

Jungle YF is the natural reservoir of the disease in a cycle

involving nonhuman primates and forest mosquitoes

Man may become incidentally infected on venturing

into jungle areas.

The urban form is transmitted between humans by the

Aedes aegypti mosquito


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Treatment and prevention There is no specific antiviral treatment

An effective live attenuated vaccine is available

against yellow fever And is used for persons living in or traveling to endemic

areas

17D strain of yellow fever virus is an excellent

attenuated live virus vaccine Control involves mosquito control to prevent urban

yellow fever


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Japanese Encephalitis

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.

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


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Japanese Encephalitis 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 local control

measures will fail

An effective vaccine is available.


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Dengue (Breakbone Fever )

Dengue is the biggest arbovirus problem in the worldtoday with over 2 million cases per year

Dengue is found in SE Asia, Africa and the Caribbeanand S America. Flavivirus, 4 serotypes, transmitted by Aedes

mosquitoes

Which reside in water-filled containers.

Human infections arise from a human-mosquitoe-human cycle


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Characteristics of the AedesMosquito

One distinct physicalfeature black and whitestripes on its body and

legs.

Bites during the day.

Lays its eggs in clean,stagnant water.

Close-up of an Aedes mosquito


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Genome

Positive-sense RNAgenome

Approximately 10.6 kb long

Composed of a one openreading frame

Genes encoding structuraland non-structural proteins

Four major serotypes

DENV-1, DENV-2, DENV-3,and DENV-4

The outer surface of the mature

virus particle consists of a flat

array of E glycoprotein

homodimers


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Distribution of Dengue


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Dengue (Breakbone Fever ) Classically, dengue presents with a high fever,

lymphadenopathy, myalgia, bone and joint pains, headache,

and a maculopapular rash

Dengue should be considered in the differentialdiagnosis of all febrile patients

Severe cases may present with haemorrhagic fever and

shock with a mortality of 5-10%. (Dengue haemorrhagic

fever or Dengue shock syndrome.)


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Dengue (Breakbone Fever )

Dengue haemorrhagic fever and shock

syndrome appear most often in patients

Previously infected by a different serotype of

dengue,

Suggesting an immunopathological mechanism.

Diagnosis is made by serology.


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Dengue (Breakbone Fever ) Encourage bed rest and maintenance of fluids to preventdehydration while the patient is febrile

Control fever

No specific antiviral therapy is available. Prevention of dengue in endemic areas depends on mosquito

eradication.

The population should remove all containers from their

premises which may serve as vessels for egg deposition. A live attenuated vaccine is being tried in Thailand with

encouraging results.


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West Nile Fever It is transmitted by Culex mosquitoes a

Produces viremia and acute, mild febrile disease withlymphadenopathy and rash.

Transitory meningeal involvement occurs during acutestage.

Virus may produce fatal encephalitis in older people

Virus can be recovered from culex mosquitoes, birds andpatient blood in the acute stage

Demonstration of rise in antibody titer between acute andconvalescent stage may be diagnostic


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Bunyaviruses


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Sand Fly Fever (Phlebovirus) It is a mild insect-borne disease transmitted by female

sand fly (Phlebotomus)

In endemic areas, infection is common in childhood

Disease begins after 3-6 days of incubation period

Clinical features include

Head ache, malaise, nausea, fever, photophobia, stiffness of theneck and back, abdominal pain and leucopenia

There is no specific treatment


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Rift Valley Fever Infects sheep and domestic animals

Humans are secondarily infected as zoonisis

Disease in humans is mild febrile illness that is short livedand recovery is complete

Some cases ire may lead to encephalitis or hemorrhagicfever


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Rift Valley Fever contd Permanent loss of vision may occur

Virus may be isolated from blood early in the disease.

Neutralizing and hemagglutination inhibiting antibodiesdevelop and persist for years

Epizootics occur following heavy rains that allow breedingof primary vector and reservoir (Aedes)

Viremia in animals leads to infection of other vectors andtransmission to humans


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ROBOVIRUS

Rodent Borne Viruses

Rodent Borne Hemorrhagic Fevers


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ROBOVIRUS

Zoonotic rodent borne hemorrhagic fevers include

Hantaan virus

Junin

Machupo viruses

Lassa fevers

Marburg

Ebola viruses


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Hantaviruses Forms a separate genus in

the Bunyavirus family

Unlike under bunyaviridae,

its transmission does notinvolve an arthropod vector.

Enveloped ssRNA virus.

Virions 98nm in diameter

with a characteristic squaregrid-like structure

Genome consists of three

RNA segments: L, M, and S.


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History Haemorrhagic Fever with Renal Syndrome (HFRS: later

renamed hantavirus disease)

First came to the attention of the West during the Korean warwhen over 3000 UN troops were afflicted.

It transpired that the disease was not new and had beendescribed by the Chinese 1000 years earlier.


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History In 1974, the causative was isolated from the Korean

Stripped field mice and was called Hantaan virus

In 1995, a new disease entity called hantavirus Pulmonary syndrome was described in the fourcorners region

of the U.S


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Some Subtypes of hantaviruses

associated with human disease Hantaan, Porrogia and related viruses - This group is found in

China, Eastern previous USSR, and some parts of S. Europe

It is responsible for the severe classical type of hantavirusdisease. It is carried by stripped field mice. (Apodemus agrarius)

Seoul type - associated with moderate hantavirus

disease

It is carried by rats and have a worldwide distribution

It has been identified in China, Japan, Western previous USSR,

USA and S.America.


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Puumala type - mainly found in Scandinaviancountries, France, UK and the previous WesternUSSR

It is carried by bank voles (Clethrionomysglareolus)

Causes mild hantavirus disease (nephropathia epidemica).

Sin Nombre - found in many parts of the US,Canada and Mexico

Carried by the Deer Mouse (Peromyscus maniculatus)and

causes hantavirus pulmonary syndrome.

Some Subtypes of hantaviruses

associated with human disease contd..


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Rodent Carriers of Hantaviruses

Stripped field mouse (Apodemus agrarius)

Bank vole (Clethrionomys glareolus)

Deer Mouse (Peromyscus maniculatus) Rat (Rattus)


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Transmission

Virus infections in rodents are life long and withoutdeleterious effects

To human transmission by inhaling aerosols of rodentexcreta

Urine, feces, saliva


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Clinical Features of Hantavirus Disease

Hemorrhagic fever with renal syndrome (HFRS) andHantavirus pulmonary syndrome (HPS)

The multisystem pathology of HVD is characterizedby

Damage to capillaries and small vessel walls, resulting invasodilation and congestion with hemorrhages

Classically, hantavirus disease consists of 5 distinctphases

These phases may be blurred in moderate or mild cases.


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Clinical Features of Hantavirus Diseasecontd..

Febrile phase - abrupt onset of a severe flu-like illness with a

erythematous rash after an incubation period of 2-3 days.

Hypotensive phase - begins at day 5 of illness

Oliguric phase - begins at day 9 of illness.

The patient may develop acute renal failure and shock.

Haemorrhages are usually confined to petechiae

The majority of deaths occur during the hypotensive and

oliguric phases


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Clinical Features of Hantavirus Diseasecontd..

Diuretic phase - this occurs between days 12-14 .

Convalescent phase - this may require up to 4

months.


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Nephropathia Far Eastern Rat-bourne Balkan

Epidermica HVD HVD HVD

Virus type Puumala Hantaan Seoul Porogia

Overall Severity 1-2 2-4 1-3 2-4

ultiphasic Disease occasionally Yes Blurred Yes

Renal Abnormalities 1-2 4 1-2 4

Hepatic abnormalities 0 0-1 1-3 0-1

Haemorrhagic phenomenon 0-1 1-4 1-2 1-4

ortality


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Hantavirus Pulmonary Syndrome (HPS)

More than 250 cases of HPS have been reportedthroughout North and South America with a

mortality rate of 50% In common with classical HVD, HPS has a

similar febrile phase.

However, the damage to the capillaries occurpredominantly in the lungs rather than thekidney.


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Hantavirus Pulmonary Syndrome (HPS)contd.

Shock and cardiac complications may lead to death.

The majority of HPS cases are caused by the Sin Nombrevirus

The other cases are associated with a variety of otherhantaviruses

E.g. New York and Black Creek Canal viruses.


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Diagnosis

Serological diagnosis - a variety of tests including IF, HAI,SRH, ELISAs have been developed for the diagnosis of HVDand HPS.

Direct detection of antigen - this appears to be more sensitivethan serology tests in the early diagnosis of the disease

The virus antigen can be demonstrated in the blood or urine.

RT-PCR - found to of great use in diagnosing hantaviruspulmonary syndrome.


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Diagnosis contd.

Virus isolation - isolation of the virus from urine is successfulearly in hantavirus disease.

Isolation of the virus from the blood is less consistent

Sin Nombre virus has never been isolated from patients with HPS.

Immunohistochemistry - useful in diagnosing HPS.


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Treatment and Prevention

Treatment of HVD and HPS depends mainly on supportive

measures.

Ribavirin - reported to be useful if given early in the course ofhantavirus disease. Its efficacy is uncertain in hantavirus

pulmonary syndrome.

Vaccination - an inactivated vaccine is being tried out in China.

Other candidate vaccines are being prepared.

Rodent Control - control measures should be aimed at reducing

contact between humans and rodents.


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Treatment of HVD and HPS depends mainly on supportive

measures.

Ribavirin - reported to be useful if given early in the course ofhantavirus disease. Its efficacy is uncertain in hantavirus

pulmonary syndrome.

Vaccination - an inactivated vaccine is being tried out in China.

Other candidate vaccines are being prepared.

Rodent Control - control measures should be aimed at reducing

contact between humans and rodents.


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Arenaviruses

Enveloped ssRNA viruses

virions 80-150nm in diameter

genome consists of 2 pieces of

ambisense ssRNA.

7-8 nm spikes protrude from the

envelope.

host cell ribosomes are usually

seen inside the outer membrane

but play no part in replication.

Members of arenaviruses

include Lassa fever, Junin and

Macupo viruses.

Lassa fever virus particles buddingfrom the surface of an infected cell.

(Source: CDC)


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Lassa Fever

Found predominantly in West Africa, in

particular Nigeria, Sierra Leone and

Liberia.

The natural reservoir is multimammate

rat (Mastomys)

Man may get infected through contact

with infected urine and faeces.

Man to man transmission can occur

through infected bodily fluids

Lassa fever had caused well-

documented nosocomial outbreaks.

Mastomys


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Clinical Manifestations

Incubation period of 3-5 days.

Insidious onset of non-specific symptoms such as fever,

malaise, myalgia and a sore throat.

Typical patchy or ulcerative pharyngeal lesions may be

seen.


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Clinical Manifestations

Severe cases may develop the following:

Myocarditis

Pneumonia Encephalopathy

Haemorrhagic manifestations

Shock

The reported mortality rate for hospitalized cases of Lassa feveris 25%

It carries a higher mortality in pregnant women


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Laboratory DiagnosisLassa fever virus is a Group 4 Pathogen. Laboratory diagnosis should only

be carried out in specialized centers.

Detection of Virus Antigen - the presence of viral antigen in sera can be

detected by EIA. The presence of viral antigen precedes that of IgM. Serology - IgM is detected by EIA. Using a combination of antigen and

IgM antibody tests, it was shown that virtually all Lassa virus

infections can be diagnosed early.

Virus Isolation - virus may be cultured from blood, urine and throat

washings. Rarely carried out because of safety concerns.

RT-PCR- being used experimentally.


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Good supportive care is essential.

Ribavirin - had been shown to be effective against Lassa fever with a 2to 3 fold decrease in mortality in high risk Lassa fever patients. Must

be given early in the illness.

Hyperimmune serum - the effects of hyperimmune serum is still

uncertain although dramatic results have been reported in anecdotal

case reports.

Postexposure Prophylaxis - There is no established safe prophylaxis.

Various combinations of hyperimmune immunoglobulin and/or oral

ribavirin may be used.

There is no vaccine available, prevention of the disease depends on

rodent control.


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Junin and Macupo Viruses

Junin and Macupo viruses are the causative agents of Argentine

and Bolivian Haemorrhagic fever respectively.

Calomys musculinis and C callosus are the rodent vectors.

The clinical presentations are similar to that of Lassa fever.

Neurological signs are much more prominent than in Lassa

fever.

Unlike Lassa virus, no secondary human to human spread had

been recorded.

Hyperimmune serum and ribavirin had been shown to be

effective in treatment.

10. arboviruses

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