In December 2015 Angola reported an outbreak of yellow fever in Luanda to the World Health Organisation (WHO). Although yellow fever is endemic in Angola the outbreak was of concern as it was occurring in an urban area and therefore had greater scope than usual to spread and involve more people. Since December there have been 3867 reported cases in Angola and 369 suspected deaths. The virus has spread to the Democratic Republic of Congo who have reported a further 2269 cases; and Kenya and China have had related cases in returned travellers. This is a very large outbreak; to put it in context the last outbreak in Angola, in 1988, affected 37 people and caused 14 deaths. The WHO has so far used 18 million doses of vaccine to try and bring the outbreak under control but it's still ongoing.
Yellow fever is caused by a flavivirus transmitted by day biting mosquitos of the Aedes and Haemagogus groups. It is endemic in many tropical countries in Africa and South and Central America where the natural reservoirs are monkey species. It is estimated that in 2013 there were up to 170,000 cases of yellow fever and 60,000 deaths in endemic countries around the world. Epidemics occur when the virus enters a highly human populated area with a high mosquito density… plenty of people to get the disease and plenty of mosquitos to spread it around!
Whilst travellers to endemic countries are supposed to be vaccinated against yellow fever and have a valid International Certificate of Vaccination or Prophylaxis (ICVP), or be able to prove a medical reason for exemption (see prevention below), the fact that China has managed to import cases of yellow fever proves vaccination in travellers is not always undertaken. It is therefore possible that a traveller could return to the UK and present with yellow fever.
Clinical presentation
It is very difficult to diagnose acute yellow fever as the initial illness is non-specific and resembles almost any other type of infection including malaria, leptospirosis, dengue and viral hepatitis, which all should be part of the differential diagnosis.
The incubation period is 3-6 days followed by fever, headache, muscle pains, nausea, vomiting and fatigue occasionally associated with jaundice (hence the name yellow fever). In most patients the fever then settles after 3-4 days and the patient makes a full recovery. In about 15% of patients a “toxic” phase of infection occurs 24-48 hours after the initial fever settles.
The toxic phase is characterised by liver and renal failure, bleeding from the eyes, nose, mouth and gastrointestinal tract, and severe jaundice. The mortality from this type of yellow fever is up to 50%.
Diagnosis
The most important aspect to diagnosing yellow fever is to take a proper travel history; where has the patient been, what have they been doing and did they receive vaccinations before they went. If someone has been to a yellow fever endemic country (see map below) and not been vaccinated then yellow fever MUST be part of the initial differential diagnosis.
Whilst travellers to endemic countries are supposed to be vaccinated against yellow fever and have a valid International Certificate of Vaccination or Prophylaxis (ICVP), or be able to prove a medical reason for exemption (see prevention below), the fact that China has managed to import cases of yellow fever proves vaccination in travellers is not always undertaken. It is therefore possible that a traveller could return to the UK and present with yellow fever.
Clinical presentation
It is very difficult to diagnose acute yellow fever as the initial illness is non-specific and resembles almost any other type of infection including malaria, leptospirosis, dengue and viral hepatitis, which all should be part of the differential diagnosis.
The incubation period is 3-6 days followed by fever, headache, muscle pains, nausea, vomiting and fatigue occasionally associated with jaundice (hence the name yellow fever). In most patients the fever then settles after 3-4 days and the patient makes a full recovery. In about 15% of patients a “toxic” phase of infection occurs 24-48 hours after the initial fever settles.
The toxic phase is characterised by liver and renal failure, bleeding from the eyes, nose, mouth and gastrointestinal tract, and severe jaundice. The mortality from this type of yellow fever is up to 50%.
Diagnosis
The most important aspect to diagnosing yellow fever is to take a proper travel history; where has the patient been, what have they been doing and did they receive vaccinations before they went. If someone has been to a yellow fever endemic country (see map below) and not been vaccinated then yellow fever MUST be part of the initial differential diagnosis.
Click for larger image
It is possible to detect yellow fever virus in blood of infected patients during the initial acute phase of the infection but the viraemia settles in the toxic phase and so serology (for IgM) is the mainstay of diagnosis in the later phase of infection.
Other clues to the diagnosis are that the white blood cell count drops to below 2.5 x 109/L with an associated neutropaenia and the liver enzymes rise (AST and ALT).
Treatment
There is no specific treatment for yellow fever but good supportive care is essential.
Prevention
Travellers to endemic countries should be vaccinated against yellow fever. The vaccine is incredibly effective. A single dose of vaccine is effective in 99% of people from 30 days after vaccination and provides life-long immunity. Very few other vaccines are this effective at preventing infection!
There are some drawbacks to the vaccine other than the cost (which is approximately £70 per person in the UK). The vaccine contains a live-attenuated virus which can therefore occasional “reactivate” shortly after administration and cause disease. The most serious complications are viscerotropic and neurotropic:
The risk of a vaccine related adverse event is higher in people >60 years old, or those who are severely immunodeficient e.g. HIV/AIDS or have a thymus disorder. The vaccine can still be given to those over 60 years old when the risk of exposure to yellow fever is thought to outweigh the risk of the vaccine (e.g. they are travelling to a country with a known yellow fever outbreak). However the vaccine is contraindicated in immunodeficient patients and those with severe egg or protein allergies.
The vaccine should also not be given in pregnancy or for children under 9 months of age if outside of an outbreak, although in an outbreak the vaccine is given in pregnancy and to children over 6 months of age as the risk of a severe adverse event is outweighed by the risk of dying from yellow fever itself.
Another essential aspect of yellow fever prevention is to avoid being bitten by mosquitos in the first place:
Infection control
There is no human-to-human transmission of yellow fever except in the context of either a needlestick injury or blood transfusion with infected blood. Blood transfusion donation involves questions about travel and disease exposure and therefore it is incredibly unlikely that anyone in the UK would be exposed to yellow fever through a transfusion.
When caring for a yellow fever patient within a hospital in the UK universal precautions for blood and body fluid exposure are enough. It would be prudent that wherever possible patients are cared for by staff who have been vaccinated against yellow fever… just in case.
In endemic countries it is also important to nurse patients under mosquito nets in order to prevent mosquitos feeding on the infected person whilst they are viraemic (from days 3-6 post exposure) and thereby spreading the virus further. This is an essential part of interrupting the cycle of transmission in outbreaks.
So whilst it is very uncommon to see yellow fever in travellers returning to the UK the ongoing outbreak in Sub-Saharan Africa does makes it possible, so it is important that we are all alert and know what to do.
Other clues to the diagnosis are that the white blood cell count drops to below 2.5 x 109/L with an associated neutropaenia and the liver enzymes rise (AST and ALT).
Treatment
There is no specific treatment for yellow fever but good supportive care is essential.
Prevention
Travellers to endemic countries should be vaccinated against yellow fever. The vaccine is incredibly effective. A single dose of vaccine is effective in 99% of people from 30 days after vaccination and provides life-long immunity. Very few other vaccines are this effective at preventing infection!
There are some drawbacks to the vaccine other than the cost (which is approximately £70 per person in the UK). The vaccine contains a live-attenuated virus which can therefore occasional “reactivate” shortly after administration and cause disease. The most serious complications are viscerotropic and neurotropic:
- Viscerotropic (0.4 per 100,000 vaccinations) – severe yellow fever with the vaccine strain and has a 60% mortality
- Neurotropic (0.8 per 100,000 vaccinations) – self-limiting encephalitis
The risk of a vaccine related adverse event is higher in people >60 years old, or those who are severely immunodeficient e.g. HIV/AIDS or have a thymus disorder. The vaccine can still be given to those over 60 years old when the risk of exposure to yellow fever is thought to outweigh the risk of the vaccine (e.g. they are travelling to a country with a known yellow fever outbreak). However the vaccine is contraindicated in immunodeficient patients and those with severe egg or protein allergies.
The vaccine should also not be given in pregnancy or for children under 9 months of age if outside of an outbreak, although in an outbreak the vaccine is given in pregnancy and to children over 6 months of age as the risk of a severe adverse event is outweighed by the risk of dying from yellow fever itself.
Another essential aspect of yellow fever prevention is to avoid being bitten by mosquitos in the first place:
- Do not travel to areas with outbreaks of infectious diseases unless essential
- Use insect repellents
- Sleep under a mosquito net
- Wear long sleeved shirts and long trousers
- Avoid going out in heavily infested areas
- Get vaccinated before travel
Infection control
There is no human-to-human transmission of yellow fever except in the context of either a needlestick injury or blood transfusion with infected blood. Blood transfusion donation involves questions about travel and disease exposure and therefore it is incredibly unlikely that anyone in the UK would be exposed to yellow fever through a transfusion.
When caring for a yellow fever patient within a hospital in the UK universal precautions for blood and body fluid exposure are enough. It would be prudent that wherever possible patients are cared for by staff who have been vaccinated against yellow fever… just in case.
In endemic countries it is also important to nurse patients under mosquito nets in order to prevent mosquitos feeding on the infected person whilst they are viraemic (from days 3-6 post exposure) and thereby spreading the virus further. This is an essential part of interrupting the cycle of transmission in outbreaks.
So whilst it is very uncommon to see yellow fever in travellers returning to the UK the ongoing outbreak in Sub-Saharan Africa does makes it possible, so it is important that we are all alert and know what to do.
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