Abstract
I
Progress on the understanding of arthropod-borne diseases has been driven by yellow fever due to its impact in terms of human deaths and commerce. YFV was the first virus to be demonstrated as mosquito-borne and the first for which a safe, efficacious, live attenuated vaccine was produced. It was the first virus to establish a jungle transmission cycle in a region to which it was introduced (South and Central America) that involved new vector species and new species of vertebrates.
YFV vaccine is probably the safest of any human vaccines. Approximately 500 million doses of this vaccine have been administered with less than 50 documented vaccine-associated fatalities. Recent advances in molecular virology have resulted in YFV vaccine being used as the delivery vehicle for the world's first commercially available dengue vaccine and a single-dose vaccine against Japanese encephalitis. Vaccines based on this YFV backbone were also developed against West Nile virus and commercialized for horses, and the technology is being applied to Zika.
Even though YFV vaccine is relatively inexpensive to produce, widely available, and mandated for travelers to some countries, cases of yellow fever continue to occur annually in Africa and in some South American countries. In 1997, Vector-Borne and Zoonotic Diseases (VBZ) editorial board member, Pedro Vasconcelos, reported (Vasconcelos et al. 1997) on the largest sylvatic epidemic in Brazil for more than 20 years—a 1993–1994 epidemic with more than 70 seropositive human cases, with lack of vaccination being the principal reason for the epidemic. In 2001, together with others, he documented the first cases of vaccine-associated viscerotropic disease caused by yellow fever 17D virus vaccines (Vasconcelos et al. 2001). The seriousness of yellow fever infection cannot be underestimated. In 1995, an epidemic in Peru involved more than 800 cases with a 38% case fatality rate. Research on YFV requires a biosafety level three (BSL-3) containment with a mandatory vaccination of personnel. Were it not for the availability of the vaccine, YFV would likely require use of BSL-4 containment. As a hemorrhagic disease, symptoms and fatality rates of YFV are remarkably, almost frighteningly, similar to those of Ebola virus.
On many platforms, over the past 20 years, VBZ editorial board member Tom Monath has frequently expressed his concern that there is a significant risk of an urban epidemic of yellow fever in the Americas. Risk factors are the ease and frequency of international travel from endemic areas and erosion of effective vector control programs. A very serious concern is that supplies of approved vaccine could rapidly become exhausted.
The recent spread of chikungunya virus into the Americas and the ongoing epidemic of Zika in the Americas are testimony to the widespread distribution and abundance of Ae. aegypti in many urban areas. The continuing spread of the Asian tiger mosquito, Ae. albopictus, around the globe, is an additional concern since it is a competent vector for multiple viruses. There has been much discussion on how, if vaccines had been available for Ebola, chikungunya, and Zika viruses, hundreds of thousands of cases, and in the case of Ebola, thousands of deaths could have been prevented.
There is still much to learn about the natural transmission cycles of YFV. Little work on this is funded in today's world and focused on cell biology and viral pathogenesis. It is unclear why yellow fever outbreaks appear at cyclic intervals, and what factors influence transmission. The ecology and role of multiple sylvatic vectors of YFV are poorly understood and new species have been found carrying the virus during outbreaks.
The short communication published in this issue by Vasconcelos and Monath (2016) is poignant, timely, and should be seen as realistic rather than alarmist. The Olympics in Brazil may bring countless numbers of visitors to areas where mosquito vectors are yet to be controlled and where healthcare and infrastructure are inadequately financed. The Brazilian Ministry of Health will require travelers from Angola and the Democratic Republic of Congo to have an International Certificate of Vaccination or Prophylaxis, indicating that authorities are taking the threat seriously, at least in the context of this event. This does, however, coincide with Rio State declaring public calamity of finances. As chikungunya and Zika have shown us, these viruses can strike unseen, travel far, and rapidly escalate to a level where control is ineffective if not impossible. Warning bells are being rung, and one can only hope that they are being heard.