In Angola, the worst outbreak of yellow fever in three decades may result in a vaccine shortage. If this happens, fractional dosing — giving one-fifth the standard amount of vaccine — could be used to control an outbreak of the viral hemorrhagic disease, according to a group of experts convened by the World Health Organization.
In Angola, just under 3,300 people have been infected with yellow fever since December, and at least 347 people have died. The outbreak began in the capital city, Luanda, but has spread to at least 16 of the country’s 18 provinces. The majority of cases are among males between the ages of 9 and 19 years old. Health officials are concerned it could spread to areas where people are not vaccinated, including the neighboring countries of Namibia and Zambia.
“The massive vaccination activities have reached more than 10 million people. However, new cases continue to be reported, indicating that some pockets of unvaccinated people still exist,” the WHO said in its latest report on the outbreak (PDF), released Monday.
After reviewing all existing data, the WHO’s advisory group, which was tasked with considering potential vaccine shortages, said that one-fifth the dose would still provide protection for 12 months, possibly longer. A standard dose of the vaccine offers lifelong protection against this disease, which is transmitted by infected mosquitoes.
Symptoms include fever, headache, jaundice, muscle pain, nausea, vomiting and fatigue. A small proportion of patients develop severe symptoms, and nearly half of these die within 10 days.
Imported cases of yellow fever through non-immunized travelers have occurred in three countries: the Democratic Republic of Congo (59 cases), Kenya (two cases) and China (11 cases).
The outbreak of yellow fever in Congo was declared April 23. The total number of suspected cases there appears to have recently spiked. As of June 8, WHO reports reflected only three probable cases and 57 laboratory-confirmed cases in Congo; as of June 20, the WHO had received reports of 1,106 cases (68 confirmed) with 75 deaths.
Six additional countries — Brazil, Chad, Colombia, Ghana, Peru and Uganda — are reporting either yellow fever outbreaks or sporadic cases not linked to the Angolan outbreak, according to the WHO.
Emergency vaccination campaigns to control the outbreak in Angola and its spread to Congo have placed unprecedented demands on the vaccine supply. More than 15 million doses of vaccine have been delivered to Angola and Congo, the WHO reported on Wednesday.
“Right now, we have enough vaccines in the global stockpile to cope with the ongoing outbreaks if there are no further extensions,” said Dr. Jon Abramson, chairman of the WHO Strategic Advisory Group of Experts on Immunization.
Given continuing infections in Angola and the potential for an outbreak in Kinshasa, Congo’s capital city of 11.6 million people, experts have begun to consider a new dose-sparing strategy. They have to plan now because the vaccine, which is made by four companies, takes about 12 months to produce.
The stockpile usually has 6 million doses of the yellow fever vaccine, but that supply has been depleted twice this year. Usually, only 4 million doses are needed to quell an outbreak in one country. This situation, the WHO said, is a first.
The vaccine, which provides immunity within 30 days for 99% of people vaccinated, is safe and affordable. Abramson and his colleagues say more research is needed to see whether fractional doses would be effective in young children, who may have a weaker immune response to the vaccine.
The vaccine was developed in the 1930s by Max Theiler, who earned a Nobel Prize for his work. It’s been in use since 1937, and more than 650 million doses have been distributed in the past 75 years.
The virus is endemic in tropical areas of 47 countries in Africa and Central and South America. Since 2006, more than 105 million people have been vaccinated in mass campaigns.
According to the WHO, there are an estimated 84,000 and 170,000 severe cases of yellow fever worldwide each year, and as many as 60,000 of those cases are fatal.
Formal recommendations on the use of lower doses of vaccine by the expert committee are expected in October. In the interim, it has found sufficient evidence that fractional dosing could be effective to control urban outbreaks in situations of a temporary vaccine shortage. Practical issues need further investigation, though, including obtaining suitable syringes to administer the vaccine, which is injected into a muscle or just under the skin.
