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Yellow Fever

Overview

Yellow fever is a viral haemorrhagic disease which is transmitted through the bite of the primary vector, infected Aedes or Haemagogus mosquitos. The ‘yellow’ in the name refers to the appearance of jaundice which presents in some infected individuals. The causative organism is an RNA virus which belongs to the genus Flavivirus and is related to the West Nile and Japanese encephalitis viruses. Yellow fever originated in Africa but became introduced to America by mosquito-infested slave-trading ships. The virus is now endemic to Africa and South America. Without treatment, up to 50% of severely affected cases will end in fatality. The World Health Organisation estimates that 200,000 cases occur annually, of which 30,000 result in death. 90% of reported deaths occur in Africa. Over the past two decades, the number of reported cases has increased as a result of deforestation, urbanisation, population movements, climate change and a reduced population immunity to the infection.

 

Signs and symptoms

The incubation period lasts for 3-6 days. After this time the virus will present with the acute phase:

  • Fever

  • Myalgia

  • Prominent backache

  • Headache

  • Shivers

  • Loss of appetite

  • Nausea

  • Vomiting

  • Weakness

 

Most individuals improve from the acute phase and their symptoms will disappear after 3-4 days.

 

Alternatively, 15% of patients enter the second, more toxic phase within 24 hours of the initial

remission to present with:

  • High fever

  • Jaundice

  • Abdominal pain

  • Vomiting

  • Bleeding from the mouth, nose, eyes or stomach – gastric erosions

  • Blood in the vomit and faeces

  • Kidney function deteriorates – renal impairment

  • Hepatocellular damage with lobular necrosis

  • Shock

  • Multiple organ failure

 

Neurological impairment can occur as a result of oedema and haemorrhage rather than the virus acting on the brain directly. Rarer features include coagulation deficiency, myocarditis and systemic inflammatory response syndrome.

50% of individuals who enter the toxic phase will die within 10-14 days. The other 50% will improve without significant organ damage and will now have lasting immunity against subsequent infections.

 

Causes

Mosquitos become infected with the virus by feeding on infected primates

(human or non-human). The virus is then transmitted to other primates when

subsequent feeding occurs. Individuals infected with the virus can go on to

infect other mosquitos shortly before the presentation of symptoms and for

up to 5 days after the onset.

 

Yellow fever has 3 alternative transmission cycles:

  1. Jungle (Sylvatic) cycle: the virus is transmitted between monkeys and                                                                                   mosquito species inhabiting the forest canopy. Infected mosquitoes then                                                                                   transmit the virus from monkeys to humans when individuals enter the                                                                               jungle area.

  2. Intermediate (Savannah) cycle: the virus is transmitted from mosquitoes                                                                                   to humans in jungle border areas. The virus can be transmitted from monkey to human or from human to human via infected mosquitoes. This cycle is the most common throughout Africa.

  3. Urban cycle: the virus is trans­mitted between humans and urban mosquitoes (usually Aedes aegypti). The virus is commonly brought to the urban setting by a viremic human who was previously infected in the jungle or savannah. Large epidemics occur in this cycle as the virus is introduced into densely populated areas with a high population of non-immune individuals.

 

Once an individual has been bitten by an infected mosquito, the virus replicates in local lymph nodes before it spreads to other lymphoid areas and tissues via the bloodstream.

 

Risk factors / at risk groups

  • Travel to an endemic area

  • Being outside whilst mosquitos are at their most active

  • Visiting endemic areas after the rainy season when mosquito population                                                                                   is at the highest

 

Diagnosis / microbiology testing

Yellow fever resembles other viral diseases which commonly occur in Africa                                                                                 and South America. As a result, microbiology testing is required for definite                                                                                     diagnosis.

  • Viral detection of viral antigens/virus culture

  • IgM detection using ELISA

  • Neutralisation assays most specific

 

Treatment

There is no recommended antiviral treatment for yellow fever. Instead, treatment is symptomatic and supportive. Fluids, analgesics and antipyretics are used to treat dehydration, pain and fever respectively. Aspirin and NSAIDs should be avoided due to the increased risk of bleeding which could exacerbate symptoms. Blood transfusions may be required in cases with severe bleeding. In cases with renal failure, dialysis may be needed. Any associated bacterial complications can be treated with antibiotics. Patients should be protected from further exposure to mosquitos in order to prevent reinfection through the transmission cycle.

 

Vaccine / preventative measures

A vaccine is available as a live-attenuated strain of the yellow fever virus. The number of reported cases of yellow fever has substantially reduced following the introduction of this vaccine. The 17D vaccine is recommended for any individual aged ≥9 months who will be travelling to/ living in areas at risk in South America and Africa. The yellow fever vaccine is required for entry into certain countries. Once administered, the vaccine provides effective immunity against yellow fever within 10 days for 80–100% of individuals. Within 30 days, the vaccine provides 99% immunity. A single dose of the vaccine is sufficient to provide sustained immunity and life-long protection.

 

However, in February 2015, the Centers for Disease Control and Prevention advisory committee on immunization practices published new recommendations for certain individuals to receive additional vaccine doses. Individuals include:

  • Women who were pregnant when first vaccinated

  • Individuals who have received a haematopoietic stem cell transplant following the last dose of yellow fever vaccine

  • HIV positive individuals

  • Travellers who received the vaccine at least 10 years ago and will be in a higher-risk setting during their next travel episode

  • Laboratory workers who routinely handle wild-type yellow fever virus

 

Preventative measures include:

  • Applying insecticides to mosquito breeding sites

  • Avoid outdoor activities at times mosquitos are most active

  • Wear long-sleeved tops and long trousers where possible

  • Stay in air-conditioned or screened accommodation

  • Sleep under a mosquito net if outdoors

  • Apply insect repellent (DEET) to exposed areas of skin

  • Apply permethrin-containing repellent to clothing and bed netting

     

     

     

     

     

     

     

     

     

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