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Yellow fever clinical features pathology and management

Yellow fever clinical features pathology and management


Yellow fever is an acute arboviral (arthropod-borne)infection caused by the yellow fever virus, a flavivirus.The illness is characterized by high fever, jaundice andencephalopathy in its severe form. The disease occurs infocal outbreaks in Africa, the Caribbean and Central andSouth America. This condition is prevented by the 17Dattenuated live vaccine strain, which should be given totravellers to endemic areas and to indigenous populationsin outbreaks. There are infrequent occurrences of importationof yellow fever to Europe, which can present asPUO or viral haemorrhagic fever.

Distribution and incidence Sub-Saharan tropical Africa (especially West Africa), theCaribbean islands (most recently Trinidad) and SouthAmerica (Brazil, Peru, Bolivia, Ecuador, Venezuela andColombia) are the areas affected by yellow fever. Relativelysmall numbers of cases occur every year in theseareas, although cases in isolated areas may go unreported.

Transmission and epidemiology In South America,and Central and East Africa, a jungle cycle involvesmonkey-mosquito-monkey and maintains the virus in themosquito reservoir. Haemagogus mosquitoes are thevector. The epidemiology in savannah and forest-savannahareas involves other Aedes species with humans andmonkeys. The insect vector passes infection to the nextgeneration of mosquitoes by transovarial transmission.Non-immune persons of all races, all ages and bothsexes are susceptible to infection. Prior exposure to otherflaviviruses produces some degree of cross-protection.Men are at particular risk of infection because of occupationsthat take them into forests.


Pathology and pathogenesis The liver is the main organ involved and shows mid-zonalnecrosis of hepatocytes. Councilman bodies result from thedegeneration of hepatocytes. The kidneys show acutetubular necrosis which may relate to shock and hypovolaemia.There may be haemorrhage into mucous membranesand the skin, associated with the bleeding tendencythat is common in yellow fever. The underlying pathogenicmechanisms are poorly understood.


Clinical features There is a range of severity of disease, from mild to severelife-threatening illness. The latter constitutes a minority ofall those infected. The incubation period is about 6 daysbefore the onset of headache and fever. More severe illnessis associated with marked limb pains. Proteinuria is usual.High fever, headache, severe limb and back pain, chillsassociated with fetor, haemorrhages in the gums, andnosebleeds are early features in severe cases. There maythen be a short period of remission of symptoms for up to24 hours before the recurrence of fever with vomitingand jaundice. Bleeding into the gut, skin and other sitesis usual in severe cases. Occasional cases are seen with organdamage limited to the heart or kidneys, causing cardiac orrenal failure. Bleeding and renal failure are the main causesof the high mortality (up to 50%) in severe cases. Resolutionin severe cases can take from 3 days to 6 weeks.

Diagnosis The clinical features in severe cases suggest the diagnosis,but in milder cases without evidence of organ dysfunctionthe diagnosis may not be made. Virus can be isolated mostoften from blood taken in the first 4 days of clinical illness.Rising antibody titres in paired sera may also give the diagnosis,but serological tests may not be easy to interpret inpeople exposed to related viruses.

Differential diagnosis In mild cases the range of febrile illnesses to be consideredis extensive and includes malaria, typhoid, the prodromalphase of viral hepatitis, leptospirosis and rickettsialdiseases. The presence of jaundice with fever promptsconsideration of leptospirosis, malaria, East African trypanosomiasis,typhoid, biliary tract sepsis and Marburgvirus diseases. Ebola virus fever and Lassa fever are othercauses of haemorrhagic fever, although marked jaundice isnot usual.Laboratory featuresAnaemia, leukopenia and thrombocytopenia are usualfeatures in more severe cases. Conjugated bilirubin levelsand transaminases are high in jaundiced cases. Coagulationabnormalities comprise prolonged prothrombin time,reduced fibrinogen levels and detectable fibrin degradationproducts. Renal failure with proteinuria, oliguria andraised creatinine and urea may occur.

Prevention and control All travellers to endemic areas - apart from pregnantwomen, infants under 1 year and immunosuppressedpatients - should receive the attenuated 17D yellow fevervaccine. Patients with yellow fever should be nursed undermosquito nets to prevent mosquitoes becoming infected.Vaccination is used to help control epidemics.
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