Virus Isolation

Although the Yellow Fever vector was discovered in the early 1900’s, the virus itself was not isolated until almost 1930 as a result of the formation of the second West African Yellow Fever Commission. The commission was formed in 1925. The expedition, lead by Major Henry Beeuwkes, was charged with furthering research into Leptospira (a bacterium considered a potential causative agent), studying the epidemiology of the disease, and determining whether African Yellow Fever was similar to South American Yellow Fever.

In the summer of 1927, blood was taken from a mildly ill African and injected into a monkey, imported from India, which then became the first laboratory host to become infected. Unfortunately, the scientist who made the discovery, a professor from London by the name of Adrian Stokes, died from Yellow Fever not long after. He was, in the grand tradition of science history, quickly replaced by selfish incompetence in the form of a scientist by the name of Hideyo Noguchi. Noguchi had previously attempted to prove a species Leptospira to the be the causative agent and he rekindled his efforts in Africa, though Stokes had already attempted and failed to verify the Leptospira theory.

Not only did Noguchi have a hard time letting go of his theories, he was also a careless and secretive and nobody liked him. He also died of Yellow Fever in 1928, followed by another scientist, William Young, who autopsied Noguchi. As was the case for Reed’s team during the mosquito experiments, this Yellow Fever investigation once again proved itself to be a dangerous puzzle.

Vaccine Development

The development of the Yellow Fever vaccine is long and complex, with many adjustments being made along the way. While this post will not cover every aspect of the process, it is likely to be a bit longer and drier than previous posts. Do your best, dear readers (all 5 of you) to bear with me for the moment. I’ll be starting my second topic this weekend, but I still wanted to finish up with Yellow Fever.

Several years prior to the formation of the West African Yellow Fever Commission, the Rockefeller Foundation’s International Health Commission sent a team to Ecuador to attempt mosquito control. Included in that team was Hideyo Noguchi who, though not completely unimpressive as a person, was evidently not prepared for his theories to be incorrect. Despite the fact that bacteria-based vaccines had been abandoned (since no one had previously been able to filter out a bacterial pathogen) Noguchi claimed he’d been able to find a similar, but not identical, bacteria to the cause of Weil’s disease in the livers of Yellow Fever patients.

While it’s possible he did find bacteria in these patients, it could easily have been a co-infection or even something different from Yellow Fever entirely. After all, many illnesses do share symptoms. In any case, he created a new bacteria-based vaccine for Yellow Fever and began to distribute it widely throughout several countries plagued by the disease. Unfortunately, though likely unsurprisingly to the reader, despite Noguchi’s claims of more than 7,000 successful vaccine administrations, no other scientists were able to replicate his results. In 1926 the vaccine was discontinued.

Following the initial isolation of the virus in a laboratory animal, some attempts were made at creating a vaccine. However, these relied on virus preserved in liver tissue and it became clear pretty quickly that a live virus would be required as well as a more economically feasible laboratory host. Max Theiler, who earlier demonstrated the flaws in Noguchi’s research, knew that mice had been used to grow other viruses and was able to successfully repeat the process using the Yellow Fever virus. He joined the International Health Division of the Rockefeller Institute’s Yellow Fever lab and began work on a vaccine that was needed, initially, to protect researchers.

In 1931 the first viral vaccine was put to trial. Dr. Bruce Wilson, the first to be given the new vaccine, was hospitalized and monitored closely. There were only very minor side effects. While this vaccine created by the Rockefeller Institute was considered the safest of currently available vaccines (others had simultaneously developed a different version) the fact that it required human serum made it expensive and not ideal for large-scale use. Luckily, Hugh Smith, who worked with Theiler, had noticed earlier that a mutated version of the virus appeared to be safer than other versions and could be administered more broadly. It was called 17D and it was put to the test in 1937. By 1939 over a million people had been vaccinated.

Unfortunately, and after a reasonably short time, severe complications began to appear. Over 100 cases of encephalitis (brain swelling, not good) occurred in Brazil and while that was addressed fairly quickly, cases of jaundice were also appearing. During World War II over 7 million vaccines were given and over 25,000 cases of jaundice resulted. The cause was later found to be from people who had donated human serum to be used in the vaccine. While most of the donors were healthy, a few had a history of jaundice that was not discovered until after the vaccine-related cases began appearing in large enough numbers to warrant a strict investigation.

In the 1960’s another complication arose that involved contamination with avian leukosis virus, which is related to the development of cancer cells in mammals. However, filtration and inoculation of the vaccines with antibodies against avian leukosis virus took care of those issues and by the 1980’s there were no more contaminants in the vaccine.

The majority of the information in this post comes from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892770/

Present Day

Yellow Fever is far from being a thing of the past. In fact, cases have been increasing over the past 20 years or so, with over 90% of those cases occurring in Africa. This increase is likely a result of increased urbanization and movement of populations in endemic areas, as well as deforestation. The endemic regions include the tropics in both Africa and South America, which includes a population of over 900 million in over 45 different countries. While a vaccine is available to travelers, the disease should not be completely dismissed by people in the United States. The more the number of cases increases, the more likely we are to the see the virus spread to other regions. After all, it’s not as if we’re lacking the vector and it only takes one mosquito to bite one unvaccinated person before we’ve got a problem.