Yellow FeverYellow Fever

IntroductionIntroduction EpidemiologyEpidemiology Lifecycle of vectorLifecycle of vector Transmission of diseaseTransmission of disease Clinical features and diagnosisClinical features and diagnosis Control Control

Introduction Introduction

Yellow fever is an acute mosquito-transmitted Yellow fever is an acute mosquito-transmitted viral infection which is endemic and viral infection which is endemic and occasionally epidemic in many countries of occasionally epidemic in many countries of tropical Africa and South America. tropical Africa and South America.

It is also refered to as It is also refered to as yellow jack, black vomit, yellow jack, black vomit, American plaque, and Asian FetishAmerican plaque, and Asian Fetish

Main vectors are Aedes and Haemagogus Main vectors are Aedes and Haemagogus mosquitoesmosquitoes

Epidemiology Epidemiology Yellow Fever is now found only in Sub-Saharan Africa, the Yellow Fever is now found only in Sub-Saharan Africa, the

Amazonian region of South America, and occasionally in Amazonian region of South America, and occasionally in Trinidad.Trinidad.

Africa accounts for around 90% of the cases. Africa accounts for around 90% of the cases. Yellow fever is grossly underreported due to unrecognized Yellow fever is grossly underreported due to unrecognized

cases, unavailability of laboratory facilities to make the cases, unavailability of laboratory facilities to make the diagnosis, and poor surveillance. diagnosis, and poor surveillance.

The WHO estimates that there are 200,000 cases a year with The WHO estimates that there are 200,000 cases a year with 30,000 deaths. 30,000 deaths.

Yellow fever appears to be on the rise due to deforestation, Yellow fever appears to be on the rise due to deforestation, urbanization, and the increases of global travel.urbanization, and the increases of global travel.

EpidemiologyEpidemiology

Yellow fever epidemicsYellow fever epidemics Philadelphia 1793Philadelphia 1793 Haiti 1805Haiti 1805 Norfolk, Virginia 1855Norfolk, Virginia 1855

EpidemiologyEpidemiology

Yellow fever belt in Africa lies between Yellow fever belt in Africa lies between latitude 15latitude 15° to 10° south of the equator° to 10° south of the equator

Nigeria 1986/7 10,000 cases with about 5,000 Nigeria 1986/7 10,000 cases with about 5,000 deaths were reported.deaths were reported.

In Ghana in 1996 aIn Ghana in 1996 a total of 27 cases of yellow total of 27 cases of yellow fever with 5 deaths has been reported over a fever with 5 deaths has been reported over a period of a few weeks in the Upper East period of a few weeks in the Upper East Region of the countryRegion of the country

Lifecycle of vector Lifecycle of vector The female Aedes mosquito lays eggs above water as The female Aedes mosquito lays eggs above water as

compared to other mosquitoescompared to other mosquitoes Eggs are laid singly or in a group (raft). These eggs Eggs are laid singly or in a group (raft). These eggs

have the ability to survive in dry conditions hence have the ability to survive in dry conditions hence increasing the spread of the disease.increasing the spread of the disease.

Eggs hatch into larvae which extend in the water and Eggs hatch into larvae which extend in the water and have short siphons and may dive to bottom if have short siphons and may dive to bottom if disturbed disturbed

After 4 molts the larvae develop to become pupae After 4 molts the larvae develop to become pupae which have 2 trumpets and after 4 days they become which have 2 trumpets and after 4 days they become the adult mosquito which flies to find a mate the adult mosquito which flies to find a mate

Yellow Fever VirusYellow Fever Virus

It is a flavivirus 45-60nmIt is a flavivirus 45-60nm An RNA enveloped virusAn RNA enveloped virus Also classified ecologically as an arbovirus as Also classified ecologically as an arbovirus as

it’s cycle involve the arthropods as vector and it’s cycle involve the arthropods as vector and it has been observed that viral infection does it has been observed that viral infection does not harming the vectornot harming the vector

Transmission Transmission The vector is the The vector is the Aedes aegyptiAedes aegypti or Haemagogus mosquito. or Haemagogus mosquito.

There are two modes of transmission of the virus-vertical and There are two modes of transmission of the virus-vertical and horizontalhorizontal

Vertical transmission occurs when the virus is passed on to the Vertical transmission occurs when the virus is passed on to the mosquito's ovum. mosquito's ovum.

This is advantageous for continuation of the life cycle during This is advantageous for continuation of the life cycle during the dry season when the eggs may lay dormant. the dry season when the eggs may lay dormant.

When the rainy season returns, the eggs hatch, allowing the When the rainy season returns, the eggs hatch, allowing the virus to carry on.virus to carry on.

Horizontal transmission occurs when either an animal Horizontal transmission occurs when either an animal (typically monkeys) or humans are infected by the mosquito.(typically monkeys) or humans are infected by the mosquito.

TransmissionTransmission

There are several different transmission cycles in There are several different transmission cycles in yellow fever: yellow fever: sylvaticsylvatic, , intermediateintermediate, and , and urbanurban. .

All three occur in Africa, but only sylvatic and urban All three occur in Africa, but only sylvatic and urban occur in South America. occur in South America.

Sylvatic (or jungle )Sylvatic (or jungle ) yellow fever occurs in tropical yellow fever occurs in tropical rainforests where monkeys are infected. Here humans rainforests where monkeys are infected. Here humans are infected as a result of entering the forest. Risk are infected as a result of entering the forest. Risk groups include hunters, farmers, chain saw operators, groups include hunters, farmers, chain saw operators, construction workers.construction workers.

TransmissionTransmission

IntermediateIntermediate yellow fever occurs in the yellow fever occurs in the humid or semi-humid savannahs of Africa humid or semi-humid savannahs of Africa where small epidemics occur in villages. Here where small epidemics occur in villages. Here mosquitoes infect both monkeys and humans mosquitoes infect both monkeys and humans at this zone of emergence. at this zone of emergence.

UrbanUrban yellow fever can occur in large yellow fever can occur in large epidemics where the virus is passed from epidemics where the virus is passed from human to human via domestic Aedes human to human via domestic Aedes mosquito. mosquito.

Sylvatic or Jungle yellow FeverSylvatic or Jungle yellow Fever Sylvatic yellow fever is spread to humans by the bites of Sylvatic yellow fever is spread to humans by the bites of

Haemagogus sppHaemagogus spp (south America) and (south America) and A. africanusA. africanus (Africa) (Africa) mosquitoes. mosquitoes.

These mosquitoes are infected when they feed on viraemic These mosquitoes are infected when they feed on viraemic monkeys or because they inherited the infection by monkeys or because they inherited the infection by transovarial transmission from their mother. transovarial transmission from their mother.

Sylvatic yellow fever is usually sporadic, but it is also the Sylvatic yellow fever is usually sporadic, but it is also the ultimate source of urban yellow fever. ultimate source of urban yellow fever.

Sylvatic yellow fever is maintained in a natural enzootic cycle Sylvatic yellow fever is maintained in a natural enzootic cycle between a number between a number AedesAedes species which breed in tree holes and species which breed in tree holes and the monkeys they feed upon. the monkeys they feed upon.

A. simpsoni,A. simpsoni, A A furcifer furcifer and and A. luteocephalus A. luteocephalus found at the edge found at the edge of forests are also important vectors.of forests are also important vectors.

Urban Yellow Fever Urban Yellow Fever Urban yellow fever occurs in more populated areas Urban yellow fever occurs in more populated areas

and is usually transmitted by and is usually transmitted by Aedes aegypti whichAedes aegypti which deposit their eggs in any container which can hold deposit their eggs in any container which can hold water, in or around houses perpetuating a mosquito-water, in or around houses perpetuating a mosquito-to-human-to-mosquito transmission cycle.to-human-to-mosquito transmission cycle.

Their ability to rear offspring in household water Their ability to rear offspring in household water makes makes Aedes aegyptiAedes aegypti a threat for yellow fever a threat for yellow fever transmission in areas of very low rainfall, or during transmission in areas of very low rainfall, or during the dry season (when water is stored inside houses or the dry season (when water is stored inside houses or very close by). very close by).

Thus, these mosquitoes complete their life cycle from Thus, these mosquitoes complete their life cycle from eggs to adults in very close proximity to humans. eggs to adults in very close proximity to humans.

Urban Yellow Fever_2Urban Yellow Fever_2 When a female When a female Aedes aegyptiAedes aegypti feeds on blood infected with yellow fever feeds on blood infected with yellow fever

virus, her salivary glands and her ovaries become infected, and she passes virus, her salivary glands and her ovaries become infected, and she passes this infection into her eggs through her ovaries this infection into her eggs through her ovaries (transovarial (transovarial transmissiontransmission). ).

The infected eggs develop into infected adults, and the adult females are The infected eggs develop into infected adults, and the adult females are able to transmit yellow fever virus to humans as soon as they begin feeding able to transmit yellow fever virus to humans as soon as they begin feeding on humans. on humans.

This ability of This ability of Aedes Aedes mosquitoes to transmit virus transovarially — and mosquitoes to transmit virus transovarially — and thus to rapidly multiply the numbers of infected adult mosquitoes — is the thus to rapidly multiply the numbers of infected adult mosquitoes — is the reason why it is important to use insecticide treated-bednets with yellow reason why it is important to use insecticide treated-bednets with yellow fever patients.fever patients.

After several mosquito generations, transovarial transmission ends if After several mosquito generations, transovarial transmission ends if

yellow fever virus is not consumed naturally in a blood meal.yellow fever virus is not consumed naturally in a blood meal.

Pathophysiology Pathophysiology Bite from an infected mosquito leads to viral spread to lymph Bite from an infected mosquito leads to viral spread to lymph

nodes where they multiply and from there enter the circulationnodes where they multiply and from there enter the circulation Localises in the liver, spleen, bone marrow, and lymph glands Localises in the liver, spleen, bone marrow, and lymph glands

persisting for days in these areas.persisting for days in these areas. Localisation and propagation of the virus in a particular organ Localisation and propagation of the virus in a particular organ

constitutes the lesions of yellow feverconstitutes the lesions of yellow fever Haemorrhage in the mucosa of the pylorus of the stomach, Haemorrhage in the mucosa of the pylorus of the stomach,

kidney and liver necrosis (mid zonal, with councilman bodies), kidney and liver necrosis (mid zonal, with councilman bodies), perivascular infiltraion of the brain with mononuclear cellsperivascular infiltraion of the brain with mononuclear cells

Degenerative changes in heart, spleen lymph nodes also occurDegenerative changes in heart, spleen lymph nodes also occur Bleeding is the result of a hemorrhagic diathesisBleeding is the result of a hemorrhagic diathesis

Incubation periodIncubation period

Extrinsic incubation period- 12-14 days period Extrinsic incubation period- 12-14 days period when an infected vector is not infectiouswhen an infected vector is not infectious

Incubation period-3to 6 days period when an Incubation period-3to 6 days period when an infected individual is asymptomaticinfected individual is asymptomatic

Clinical findings 1Clinical findings 1 Fever, chills, headache and backache followed by nausea and Fever, chills, headache and backache followed by nausea and

vomiting, suffused conjunctivae, retro bulbar pain.vomiting, suffused conjunctivae, retro bulbar pain. On about the fourth day the period of intoxication starts with a On about the fourth day the period of intoxication starts with a

slow pulse relative to a high fever (Faget’s sign), and slow pulse relative to a high fever (Faget’s sign), and moderate jaundicemoderate jaundice

In severe cases marked proteinuria and haemorrhagic In severe cases marked proteinuria and haemorrhagic manifestations, black vomitus, epigastric painmanifestations, black vomitus, epigastric pain

The degree of jaundice and black vomitus correlated with The degree of jaundice and black vomitus correlated with severity of disease and hence fatality severity of disease and hence fatality

After 3 to 5 days of the disease, either the patient recovers or After 3 to 5 days of the disease, either the patient recovers or goes onto the next stage of fulminate disease. goes onto the next stage of fulminate disease.

Clinical Findings 2Clinical Findings 2 In fulminant disease there is significant hepatic injury with In fulminant disease there is significant hepatic injury with

jaundice occurring, hence the name "yellow fever." jaundice occurring, hence the name "yellow fever." Renal failure is not uncommon. Renal failure is not uncommon. A hemorrhagic diathesis may occur causing of epistaxis, A hemorrhagic diathesis may occur causing of epistaxis,

oozing at the gums, petechiae, ecchymosis, haematemesis: oozing at the gums, petechiae, ecchymosis, haematemesis: ("black vomit"), melena, haematuria, thrombocytopenia, and ("black vomit"), melena, haematuria, thrombocytopenia, and disseminated intravascular coagulation. disseminated intravascular coagulation.

Myocarditis, encephalopathy, and shock may also ensue. Myocarditis, encephalopathy, and shock may also ensue. From 20% to 50% of patients with classic symptoms die, with From 20% to 50% of patients with classic symptoms die, with

deepening scleral icterus, hemorrhages, shock, deepening scleral icterus, hemorrhages, shock, encephalopathy, and renal failure. encephalopathy, and renal failure.

If one survives, a full recovery can be expected.If one survives, a full recovery can be expected.

ImmunityImmunity

Disease presentation can be subclinical, Disease presentation can be subclinical, however, once an individual acquires the however, once an individual acquires the infection one acquires a life long immunity.infection one acquires a life long immunity.

Diagnosis Diagnosis

ClinicalClinical SerologySerology CultureCulture BiopsyBiopsy

Differential DiagnosisDifferential Diagnosis

The differential diagnosis of yellow fever includes:The differential diagnosis of yellow fever includes: Leptospirosis, Leptospirosis, Relapsing fever,Relapsing fever, Malaria, Malaria, Typhoid, Typhoid, Viral hepatitis (especially hepatitis E) Viral hepatitis (especially hepatitis E)

Treatment Treatment

Treatment for yellow fever is supportive in Treatment for yellow fever is supportive in nature.nature.

Bed rest under insecticide treated netsBed rest under insecticide treated nets AnalgesicsAnalgesics Fluid and electrolyte balanceFluid and electrolyte balance

ControlControl

VaccinationVaccination

Vector controlVector control

SurveillanceSurveillance

Control Control

The 17D yellow fever vaccination is the only strain The 17D yellow fever vaccination is the only strain available. available.

It is a live, attenuated vaccine and has several It is a live, attenuated vaccine and has several contraindications including: contraindications including:

children under 9 months of age, children under 9 months of age, pregnancy, pregnancy, immunosuppression. immunosuppression. International regulations require a booster every 10 International regulations require a booster every 10

years to enter or depart from endemic yellow fever years to enter or depart from endemic yellow fever regions.regions.

ControlControl

Vector controlVector control

Elimination of breeding sitesElimination of breeding sites

InsecticidesInsecticides

Repellant creamsRepellant creams

ITNITN SurveillanceSurveillance

Prompt detection and management of casesPrompt detection and management of cases

ReferencesReferences

Monath TP. Yellow Fever: A medically neglected Monath TP. Yellow Fever: A medically neglected disease. Report on a seminar. disease. Report on a seminar. Reviews Infect DisReviews Infect Dis 1987;9(1):1651987;9(1):165

Cahill KM, O'Brien W. Cahill KM, O'Brien W. Tropical Medicine A Clinical Tropical Medicine A Clinical TextText.. Mount Salus Press, Dublin ,1989, p104-105Mount Salus Press, Dublin ,1989, p104-105

World Health Organization, Yellow Fever Fact Sheet, World Health Organization, Yellow Fever Fact Sheet, WHO Fact SheetsWHO Fact Sheets 1999 August, #100 1999 August, #100

Guerrant RL, Walker DH, Weller PF. Guerrant RL, Walker DH, Weller PF. Tropical Tropical Infectious Diseases. Infectious Diseases. Churchill Livingstone. Churchill Livingstone. Philadelphia 1999, p 1262Philadelphia 1999, p 1262