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by Apurva Govande
figures by Anna Maurer

Viruses and the globe

In a hidden part of our world exists the vastly diverse microscopic universe. This micro-universe exerts a great amount of influence on our lives via minuscule, unseen molecular packages like viruses. Viruses are tiny structures made of protein that can contain DNA or RNA (the more unstable cousin of DNA) to produce more viruses after infecting a cell or bacterium. Since viruses cannot reproduce without a host cell, there is some debate over whether viruses are considered living organisms or not. But the more pressing issue is usually the end-result of viral infections – disease and, in some cases, death. While some viruses are familiar and seasonal, such as flu-causing influenza, other viruses tend to pop up in outbreaks that need to be quickly quarantined and controlled. Recently, this has been the case for yellow fever virus.

Yellow fever virus: What’s in a name?

Yellow fever virus is closely related to Zika virus and uses RNA as its genetic material. Transmitted mainly through Aedes and Haemagogus mosquitoes, yellow fever virus thrives in wet, tropical regions in South American and sub-Saharan Africa (Yellow Fever Maps – CDC). In most cases, symptoms are mild to flu-like, but 15% of infections progress to a more deadly version of the disease, with symptoms that can include high fever, jaundice, multiple organ failure, hemorrhage, and death (Figure 1). The term “yellow fever” is actually a descriptor of jaundice, the yellowish skin tone of affected individuals, as a compound called bilirubin begins to accumulate from the breakdown of red blood cells. While most cases of yellow fever do not cause serious disease, thanks in part to the development of a vaccine in the 1940s, the virus remains a serious epidemiological concern.

For a long time, it was thought that humans contract the disease through direct contact. Not until 1900 was it established that the virus was transmitted through mosquito bites, and necessary preventative measures could begin. These largely included mosquito control programs and large-scale fumigation. Mosquitoes carry yellow fever virus through at least two defined phases of transmission in the life cycle of the virus. These are primate-to-primate, called the sylvatic or “wilderness cycle,” and human-to-human in the “urban cycle.” In the wilderness, mosquitoes feed on infected primates and spread the virus to more primates when they feed again. The virus can ‘“jump” to the next phase of its life cycle if humans in close proximity to the tropical forests and jungles are bitten by mosquitoes carrying the virus. Now, the virus can spread from human to mosquito to human in urban regions (Figure 2).

Yellow fever prognosis visualization
Figure 1: About 15% of people that are infected with yellow fever virus will progress to a deadlier version of the disease.

Today, preventative measures have expanded to include basic physical and chemical measures, such as mosquito nets, EPA-approved repellents, and the vaccine that was first developed and disseminated in the 1940s. Currently, vaccination is the major preventative treatment in countries where the virus is prevalent, and one commercially available vaccine exists that is extremely effective (one dose of the vaccine essentially provides lifelong immunity against the virus). Due to the possibility of vaccine side-effects (even though they are rare), it is usually not recommended for the very young, very old, or people with faulty immune systems. Since the risk for acquiring the virus requires both the virus and the mosquito that transmits it, countries and regions where the mosquitoes that carry yellow fever virus are not prevalent do not require the vaccine.

In the United States, only special clinics can carry the vaccine, and these health care facilities need to be certified before they can administer the vaccine. Vaccination is currently only recommended for people that are travelling to countries where yellow fever virus is prevalent, and these travel laws differ from country to country.

Yellow fever transmission cycle
Figure 2: The transmission cycle of yellow fever virus depends on mosquitoes that carry the virus. Infected mosquitoes can spread the virus to humans.

Mosquitoes and the infectious pestilence

Yellow fever virus is highly prevalent in South America and Africa, and the range of the virus is inextricably tied to the habitat of the mosquitoes that carry the virus. The first yellow fever epidemics occurred in the 1600s as global trade increased, and ships carrying slaves to the New World often carried mosquitoes as well. This trend has continued today as increased global travel makes it easier for viruses to spread to populations that may not be regularly vaccinated, leading to the risk of an epidemic. While the Aedes mosquito – one of the mosquito species that spreads yellow fever virus – is quite prevalent in both China and India, there are very few reported cases of yellow fever virus for reasons that are not well understood. However, infected travelers returning from countries where the virus is present may inadvertently spread the virus to countries with uninfected, unimmunized populations through the mosquitoes that are already present in those countries. This suggests that countries that are within the range of the carrier mosquitoes should, in fact, invest in providing the vaccine to their populations. But this is easier said than done, especially in impoverished countries with large populations. As an alternative, the countries the mosquitoes inhabit often require yellow fever virus vaccinations for travelers returning from regions where the virus is prevalent.

Something viral this way comes

It seems as if almost every year, there is a new emerging virus outbreak. Most of these epidemics are resurgences of old viruses that infect many people. In recent memory, the Ebola, Zika, and now yellow fever virus outbreaks have done their damage to the global population as increased air and water transport make it much easier for people (and their viruses) to move from place to place. It is incredibly difficult to predict the next viral outbreak, but certain measures for preparedness can be undertaken at any point, including educating the public about how viruses (especially those that are mosquito-borne) can spread, and promoting vaccinations (when a vaccine exists). Viral epidemics will come and go, and while it may be challenging to predict which virus will be involved and where the next epidemic will strike, preparedness is entirely possible.

Apurva Govande is a Ph.D. student in the Virology Program at Harvard Medical School.

For more information:

Yellow Fever – Vector Disease Control International

The Looming Threat of Yellow Fever

How New Orleans cured itself of yellow fever

Cover image credit: ‘Mosquitoes’ by M [CC BY-NC-SA 2.0]

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