Even as Zika dominates headlines, another mosquito-transmitted disease has been marching steadily across Africa: yellow fever. With over 900 confirmed cases and thousands more suspected in Angola and the Democratic Republic of Congo, health officials are scrambling to vaccinate populations in these areas in time to halt the virus’ spread. The problem: there isn’t enough of the vaccine to go around.
The yellow fever vaccine stockpile, which usually stands at 6 million doses, has already been depleted twice this year. Producing more takes nearly six months—time Africa doesn’t have. Last week, the dire situation led the World Health Organization to approve the use of a mini-dose—just 20 percent of the full vaccination—to help struggling populations make it through this latest epidemic.
According to WHO, the fractional dosing measure likely protects against the disease for at least 12 months, compared to the lifetime protection that regular vaccination usually affords. “We don't have any data on long-term durability,” says Anna Durbin, a researcher specializing in vaccines at John Hopkins Bloomberg School of Public Health. In fact, the vaccination decision illustrates a broken system when it comes to vaccine supply and demand.
Around 1 billion people in 46 countries are at risk for yellow fever, a mosquito-transmitted disease primarily found in South America and Africa that belongs to the same genus as Zika, Dengue and West Nile. About 15 percent of those who are infected fully develop the disease, whose symptoms include fever, chills, body aches, nausea, weakness and jaundice—the yellowing of the skin and eyes that inspired the virus’ name. Up to 50 percent die.
Once you have it, yellow fever is incurable; doctors can only treat the symptoms. But it can easily be prevented. A single dose of the highly-effective yellow fever vaccine can impart lifetime immunity. The yellow fever vaccine is a live attenuated vaccine, which means it contains a form of the live virus that has been altered to prevent it from causing disease. Injecting this hobbled virus stimulates the body to produce antibodies that guard against yellow fever infection.
This latest outbreak has proved to be unexpectedly virulent. “It is the largest outbreak [of yellow fever] that we've seen in a very, very long time,” says Durbin. The WHO and its partners have so far delivered an estimated 18 million vaccine doses to Angola, Democratic Republic of the Congo and Uganda. But it hasn’t been enough to quell the spread—hence the mini-doses.
In the past, fractional dosing has successfully been used for rabies and is currently being used for Polio, according to Sarah Cumberland, a spokesperson for WHO. Clinical trials have shown it elicits a similar antibody response as the full injection. In fact, some trials suggest that the dose can be reduced to as little as ten percent.
But no research has yet tested fractional dosing on children, notes Cumberland. It is still unclear how children respond to the vaccine, but some suggest they have a weaker response than adults, so the lower doses may not impart full immunity.
The latest recommendation for yellow fever is not a permanent mandate. Once vaccines become available again, WHO notes that doctors should return to full potency vaccines—and routine, preventative vaccinations—for all. “Vaccine shipments are being reprogrammed to prioritize the emergency response, but at the same time we are rescheduling vaccine supplies for routine vaccination,” says Cumberland.
Yet at the root of this outbreak and the repeated vaccine shortages lurks a cyclical problem. As vaccine shortages grow, fewer people are routinely vaccinated and the population as a whole becomes more susceptible to the virus. This, in turn, could provoke more outbreaks that place even greater strain on the limited stores. “With the regular shortage of the vaccine, what we are seeing is less vaccine being given…as part of the routine immunization programs,” says Durbin. This lack of routine vaccination adds to the "vicious cycle" of perpetual shortage.
Increasing production of the vaccine is no small task. Current methods rely on growing the weakened virus in an in a chicken egg, a nearly 80-year-old method that takes up to six months and requires pathogen-free chicken eggs, which are hard to come by. Advancements in modern cell-culture technology may ultimately speed up yellow fever vaccine production. But making such a large change in production will take time and research to ensure the new products are safe.
The problem is, vaccines aren’t particularly profitable. They cost millions or billions of dollars to develop, and the resulting product is sold at low prices to impoverished regions. Plus, people only need one or two shots in a lifetime.
“In the past, a lot of companies dropped out of making vaccines,” says Art Reingold, an epidemiologist at Berkeley School of Public Health who serves on the Advisory Committee on Immunization Practices. Ultimately, these companies realized that “they could make more profit by producing a drug that old people in the United States have to take every day of their life—to lower their cholesterol or their blood pressure or to give them an erection—than they could by making a vaccine to give to poor children that, when you give them one or two doses, they are protected for life,” he says.
As a result, today there are only six manufacturers worldwide producing yellow fever vaccines, and stores fall short nearly every year.
Fear and anti-vaccine sentiment further perpetuate these troubles, Reingold adds. Along with the cost of vaccination, fear also likely drives the black-market trade of fake yellow fever vaccination certificates, placing even more people at risk of contracting the disease.
But if we want vaccines, which have prevented millions of deaths and illnesses throughout history, then “somebody has to do the research, somebody needs to do the development, and somebody needs to invest the money in it,” says Reingold. If not, then these kinds of perpetual vaccine shortages will swiftly become the new normal.