Yellow fever (YF) is an acute viral haemorrhagic disease, caused by an arbovirus of the genus Flavivirus and family Flaviviridae. It is transmitted by the bite of female mosquitoes (several species of the Haemogogus and Aedes including Aedes aegypti). Primates and several species of mosquitoes are the only hosts. YF is endemic in the sylvatic setting in sub-Saharan Africa and the tropical regions of South America, but not in Asia. In the jungle form, YF is spread from mosquitoes to monkeys and also to humans (zoonosis). Urban YF may cause large outbreaks in cities and suburbs, in which infected mosquitoes transmit the virus to human. Outbreaks occur periodically in Africa and sporadically in South America. The presence of Aedes mosquito vector in Asia may contribute to its potential occurrence. Malaysia is vulnerable to YF transmission.
The incubation period is 2-5 days. Some cases are asymptomatic but most lead to an acute illness characterised by two phases. The infection is characterised by flu-like symptoms, including fever, headache, muscle pain, backache, anorexia, nausea, and vomiting, often with bradycardia. About 15% will develop a second phase with severe symptoms within 48 hours, including vomiting, abdominal pain, jaundice, haemorrhage, shock, and multiple organ failure. Haemorrhagic manifestations include epistaxis, gingival bleeding, haematemesis, melaena, and liver and renal failure. The acute form of the disease is viral haemorrhagic fever which can lead to death within 10-14 days in 50% of cases in non-indigenous individuals (namely travelers) and during epidemic. Among the indigenous populations in endemic areas, fatality is around 5%. There is no specific treatment for yellow fever. Patients are advised plenty of rest, fluids and regular painkillers (e.g. paracetamol or ibuprofen) for symptomatic relief of fever or aches.
WHO recommends that all endemic countries should introduce YF vaccine into their routine immunisation programmes. Preventive mass vaccination campaigns are recommended for inhabitants of areas at risk of YF where there is low vaccination coverage. Vaccination is recommended to be given to everyone aged ≥ 9 months, in any area with reported cases. Reported cases of human disease is the principal indicator of disease risk, but may be absent due to a high level of immunity in population, or not detected due to lack of surveillance. Travelers to endemic countries with risk of YF transmission of Africa, Central and South America are at risk. Some countries require proof of YF vaccination for entry. When traveling to low risk YF areas, travelers should take adequate measures to prevent mosquito bites during the daytime.
There are 3 reasons for YF vaccination:
- To provide individual protection and reduces the risks of infection for those living in epidemic and endemic YF areas.
- To protect individual travelers who may be exposed to YF infection.
- To prevent the spread of YF by viraemic travelers on an international scale.
This is to protect countries from the risk of importing or further spreading YF virus by establishing entry requirements on YF vaccination for travelers. The countries that require proof of vaccination are those where the disease may or may not occur, and where the mosquito vector and potential non-human primate hosts of YF are present.
Following an update by the World Health Assembly in 2014, WHO announced that as of 11 July 2016, existing and new YF vaccination certificates are valid for life starting 10 days after vaccination. Countries can no longer require travelers to show proof of re-vaccination or a booster dose as a condition of entry.
YF vaccine has been available for more than 80 years. It is a live attenuated freeze dried preparation of the 17D strain of yellow fever virus. A single dose correctly given, provides lifelong protection in nearly 100% of recipients. It is a safe and effective vaccine, which is recommended for people aged 9 months or older and who are traveling to or living in areas at risk for YF virus in Africa and South America. YF vaccine may be required for entry into certain countries.
Vaccines Available in Malaysia
1. Stamaril (live attenuated, 17D-204 strain vaccine)
Sanofi Aventis (M) Sdn Bhd/Sanofi Pasteur, France
Certification of vaccination can be obtained from the Virology Division, Infectious Diseases Research Centre, The Institute for Medical Research Kuala Lumpur and various other designated centres in the country. Details on Yellow Fever Vaccination Centres in Malaysia can be obtained from the Ministry of Health website:
Mode of Administration
The vaccine should be given by subcutaneous injection as a single 0.5mL dose.
Children aged 9 months and older: a single dose of 0.5 ml of the reconstituted vaccine.
Children from 6 to 9 months of age: vaccination against yellow fever is not recommended in children aged from 6 months up to 9 months except in specific circumstances and in accordance with available official recommendations, in which case the dose is the same as in children aged 9 months and older.
Children under 6 months of age: Stamaril is contraindicated in children less than 6 months of age.
YF vaccine may be administered simultaneously with other vaccines.
Contraindications and Adverse Effects
The vaccine is contraindicated in:
Immunocompromised or on immunosuppressive or immunomodulatory therapies
Individuals allergic to eggs.
Children before 6 months of age.
HIV patients with CD4 <200 /mm3 or symptomatic HIV infection.
Persons with thymus disorders, malignant neoplasms
Pregnant and lactating mothers: noting that YF is a live vaccine, a risk-benefit assessment should be undertaken for all pregnant and lactating women. In areas where YF is endemic, or during outbreaks, the benefits of YF vaccination are likely to far outweigh the risk of potential transmission of vaccine virus to the fetus or infant.
If vaccination is contraindicated for medical reasons, an exemption letter or waiver should be issued to the traveler. However, acceptance or acknowledgment of such a letter is at the discretion of the destination country, and entry might be denied.
The adverse effects include local site reactions and systemic reactions such as headache, myalgia and pyrexia.
To date, the reported adverse events for YF vaccines received by the National Pharmaceutical Regulatory Agency (NPRA) include fever, headache and abdominal pain.
Target Groups in Malaysia
Yellow fever vaccination is recommended for all travelers ≥9 months old in areas where there is evidence of persistent or periodic yellow fever virus transmission.
Some categories of travelers should consider vaccination depending on risk assessment of YF infection at their destination and a country’s entry requirement:
Children between the ages of 6 to 8 months
Persons over 60 years
HIV patients with CD4 ≥200 /mm3
Pregnant or breastfeeding women.
Laboratory personnel who may be exposed to the virulent virus.
YF vaccination is recommended for persons travelling or living in areas in which YF infections occur.
Vaccination is mandatory for all persons travelling from or to countries endemic to YF (refer to the WHO website for the current list of countries www.who.int/ith).
A single dose of YF vaccine is sufficient to confer sustained life-long protective immunity against YF disease. A booster dose is not necessary, but may still be required by some countries. Adjustments of the provisions for the duration of validity of certificates under the IHR are ongoing.
A YF vaccination certificate is required from all visitors (Malaysians and foreigners) coming from or going to/through countries with risk of YF transmission (As stated in International Health Regulations 2005 and Prevention and Control of Infectious Disease Act 1988).
YF vaccination is also required for travelers having transited more than 12 hours through the airport of a country with risk of YF transmission.
Travelers or delegates without a valid YF vaccination or prophylaxis certificate shall be quarantined upon arrival in Malaysia for a period not exceeding 6 days.
Travelers are advised to take the vaccination at least 10 days before the date of departure to countries with risk of YF transmission for protection against infection. International certificate of vaccination or prophylaxis becomes valid 10 days after the date of vaccination.
The International Certificate of Vaccination or Prophylaxis, International Health Regulations (2005) is available at WHO website, https://www.who.int/ihr/IVC200_06_26.pdf
To carry the international certificate of vaccination during travel for health check.
To get the vaccination at the Approved Yellow Fever vaccinating centres in Malaysia.
To report to Entry Point Health Office on arrival in Malaysia for health check.
YF vaccination is generally not recommended in areas where there is low potential for YF virus exposure (no human YF cases ever reported and evidence to suggest only low levels of YF virus transmission in the past). However, vaccination might be considered for travelers to these areas, who are at increased risk of exposure to mosquitoes or unable to avoid mosquito bites.
When considering vaccination, a risk-benefit assessment should be undertaken; the risk of being infected with YF virus, country entry requirements, as well as individual risk factors for serious vaccine-associated adverse events such as age and immune status.
Healthcare workers are not at an increased risk. There is currently no specific recommendation regarding HCWs.
Evidence for Effectiveness
Close to 100% seroconversion rates have been shown with YF vaccines. Factors that have been associated with failure to respond immunologically to YF vaccine include HIV infection, pregnancy, and malnutrition.
A single dose of YF vaccine is sufficient to confer sustained life-long protective immunity against YF disease; a booster dose is not necessary except in select cases.
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