AsianScientist (Nov. 16, 2015) – Despite having worked on dengue throughout my time in graduate school and as a post-doc, I was completely unprepared for the experience of actually getting the mosquito-borne disease. I came down with it last year, and the fever, rash, and lingering fatigue combined to make me the sickest I’ve ever felt. I did get off easily—I didn’t need to be hospitalized, unlike some friends I later traded dengue war stories with.
I apologize for the unsolicited medical history, but I do have a point to make. Clinically, dengue can run the gamut from mild to severe—some people experience no apparent symptoms, while others may come down with potentially life-threatening dengue hemorrhagic fever.
Fortunately, the former situation turns out to be a lot more common—three-quarters of the estimated 400 million dengue infections that occur every year are thought to be asymptomatic (no reported or detected symptoms) or mildly symptomatic.
Scientists have long wondered about how large a role this group plays in disease transmission. Because dengue virus levels in the blood are correlated with disease severity (the higher the viremia, the more severe the illness), it’s been assumed that asymptomatic people do not harbor enough virus to infect mosquitoes that bite them.
Researchers at the Institut Pasteur in Cambodia recently decided to put this assumption to the test. Their findings, published this month in the Proceedings of the National Academy of Sciences, indicate that asymptomatic people are in fact not dead-end hosts for dengue virus—they can be infectious to mosquitoes, and for a given level of viremia, are even more so than patients with symptomatic infections.
Finding silent cases
How does one find asymptomatic people? Working in Kampong Cham, a province located about 120 kilometers northeast of Phnom Penh, the researchers would first identify index cases—patients with symptomatic dengue who sought treatment at the hospital. Within 24 hours, they would then visit the homes of these index cases to test people in their households and those of their immediate neighbors for virus. This sampling design allowed the researchers to find asymptomatic but dengue-positive individuals, as well as symptomatic individuals who did not seek medical attention.
Dengue-positive people who consented to the study were then asked to allow laboratory-reared Aedes aegypti mosquitoes to feed on their legs. The mosquitoes, confirmed to be free of viral pathogens and contained in mesh-covered cups, were fed on patients 25 at a time, for five minutes. Indirect feeding, where patient blood was drawn and fed to mosquitoes using artificial membrane feeders, was also carried out. In total, more than 3,000 mosquitoes were fed on blood from 181 individuals.
After incubating the mosquitoes for about two weeks to allow the virus to replicate and spread, the researchers tested their legs and wings for dengue. The virus must actually spread to mosquito saliva to be transmitted back to humans, but collecting saliva from a mosquito is as tedious and finicky as it sounds, so legs and wings were used as a proxy.
They found that although asymptomatic individuals had lower viremia levels on average, they were indeed capable of infecting mosquitoes. So were presymptomatic individuals—people who were asymptomatic at the time of feeding, but who later developed symptoms.
In fact, at a given level of viremia, asymptomatic and presymptomatic individuals were actually more likely to infect mosquitoes than people with symptoms. Further, the mosquitoes they infected ended up with higher viral loads, suggesting that they in turn might also be more infectious to humans.
We don’t quite know why this is the case. One possibility is that the more potent immune response mounted during a symptomatic infection may somehow make humans less infectious to mosquitoes. This is supported by data from an earlier direct feeding study, which found that reduced infectiousness to mosquitoes was associated with increasing anti-dengue antibody levels.
The implications
Whatever the mechanism may be, the study showed that asymptomatic people—who account for the majority of dengue infections—can contribute to the population of infected mosquitoes, and hence to disease transmission. Since people who don’t feel sick go about their daily lives as per normal, they are also more likely to encounter mosquitoes, and to transport the virus well beyond a mosquito’s flight range.
All this underscores the importance of detecting outbreaks very early on, so that public health measures—increased disease surveillance and vector control measures for example—will stand a better chance of success. Also, trials of interventions aimed at blocking transmission, such as vaccines and the release of dengue-resistant mosquitoes, will need to focus on measuring more than just symptomatic disease.
Many questions remain, of course—further studies are needed to more precisely quantify the contribution of asymptomatic individuals to transmission. But it appears that in disease control, as in politics, ignoring the silent majority is not an option.
This article is from a monthly column called The Bug Report. Click here to see the other articles in this series.
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Copyright: Asian Scientist Magazine; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
