Asymptomatic dengue-infected humans can transmit the virus to mosquitoes

Aedes_aegypti_resting_position_E-A-Goeldi_1905
A drawing of a female Aedes aegypti mosquito (Credit: E.A. Goeldi)

An estimated 3.9 billion people in 128 countries are at risk of dengue virus infection. Of the estimated 390 million dengue infections that occur each year, 96 million will manifest clinically with flu-like symptoms including fever, headache, nausea and muscle and joint pain. Unlike the flu virus, dengue virus cannot be transmitted directly from person to person. It instead relies on an insect vector, the mosquito Aedes aegypti. Female mosquitoes contract the virus when they bite and feed on an infected human. After a period of four to ten days, the virus disseminates to various tissues in the mosquito, where it remains for the rest of the mosquito’s life. At this point, the mosquito is infectious and can transmit the virus through its saliva and bite.

Earlier studies showed that the time during which dengue virus-infected humans can transmit the virus to mosquitoes coincides with the onset of clinical symptoms and an increase in viral load in their blood. These observations led to the assumption that infected, asymptomatic humans are so-called “dead-end hosts” for the virus because their viral levels are so low as to make them noninfectious to mosquitoes, essentially breaking the transmission chain.

In a new paper published last week in the Proceedings of the National Academy of Sciences, an international group of researchers challenged a long-held assumption that asymptomatic patients infected with the dengue virus are not infectious. The team sought to experimentally test the assumption that asymptomatic people are noninfectious and to determine how human-to-mosquito transmission varied with timing of symptom onset.

To identify potentially asymptomatic, infected people, the researchers devised a strategy wherein hospitalized patients confirmed as having a dengue virus infection were treated as index cases. The researchers then sent out teams to recruit “cluster participants”: family members from the index patient’s household or neighbours living in houses within a 200 m radius or in the 20 closest houses. The researchers used blood tests to determine their infection status and conducted follow up visits to monitor symptom development. They also took blood samples to measure the amount of viral RNA in their blood.

So how does one measure the transmission of dengue virus from humans to mosquitoes? By letting the mosquitoes feed on human blood and then measuring the amount of the virus’ genetic material in the mosquito. In the direct feeding technique, two groups of 25 hungry female mosquitoes were trapped underneath a plastic cup on a participant’s leg for five minutes and allowed to feast. In the indirect method, blood samples were taken from the participant and placed in feeders with hungry female mosquitoes.

dengue-virus-particles-that-were-revealed-in-this-tissue-specimen-555x544
Dengue virus particles (dark circles) in a tissue specimen. (Credit: Frederick Murphy and Cynthia Goldsmith)

The study recruited a total of 181 participants: 126 participants had symptoms of dengue fever when the mosquito feedings took place; 42 were classified as presymptomatic because they did not develop symptoms until after the mosquito feedings; and 13 asymptomatic participants remained symptom-free from recruitment through to the 10 day follow-up period.

 

For symptomatic and presymptomatic participants, dengue virus levels in the blood peaked between day zero, when clinical symptoms were first observed, and two days thereafter, although viral RNA would still be detected in some patients as far eight days after symptom onset. Using both the direct and indirect feeding methods, the researchers showed that the human-to-mosquito transmission occurred primarily from two days before symptoms appear to six days after the onset of illness. Not surprisingly, asymptomatic participants had, on average, lower levels of dengue virus in their blood than presymptomatic or symptomatic individuals. The average viral load in asymptomatic individuals was similar to that in symptomatic patients two to three days before or five to eight days after symptom onset.

The researchers unexpectedly found that asymptomatic dengue virus-infected participants were significantly more infectious to mosquitoes than symptomatic participants at all times during the course of the illness, except between days zero and two. Both asymptomatic and presymptomatic participants were more likely to transmit the virus to feeding mosquitoes than symptomatic patients, regardless of the viral load in the individual’s blood. The 50% mosquito infectious dose, which is the amount of virus needed in the blood to infect 50% of mosquitoes, was roughly 100 times lower for asymptomatic and presymptomatic infections than for symptomatic cases. What’s more, mosquitoes infected by asymptomatic or presymptomatic participants had higher viral loads than those infected by symptomatic participants.

So even though the asymptomatic participants had lower viral loads in their blood, they had a higher transmission potential with a greater proportion of mosquitoes being infected and those mosquitoes themselves having a higher viral load.

As paradigm-shifting as these results are, there were a number of limitations to this study. First, the numbers of presymptomatic and asymptomatic participants were actually quite small. It will be interesting to see if these effects hold up in a larger population. Second, in this study, the data on how infectiousness changed over the course of the illness were generated from a composite of the data from all the participants, who were all tested at different points in their illness. This is because each participant only participated in mosquito feeding once. Ideally, you would want to determine the infectiousness of the same individual every day before, during and after symptoms appear. That would mean either subjecting someone to mosquito bites every day to allow direct feeding or taking daily blood samples for the indirect feeding technique, neither of which sound particularly enjoyable. Presumably, if you compile single data points from enough participants to make a time course composite, the individual differences will average out and you should be left with a fairly reliable infectiousness profile. But again, more participants equal more power.

These findings challenge the hypothesis that asymptomatically infected people are dead-end hosts for dengue virus and add a new dimension to the transmission dynamics and epidemiology of this disease. Within a public health context, these results highlight the need to be able to detect all infections quickly, both symptomatic and asymptomatic, and to broaden surveillance efforts to include those who are likely to be exposed to the virus but do not have any clinical signs of disease. A more complete understanding of transmission dynamics will inform better prevention strategies and more effective control measures, both of which are desperately needed in the fight against dengue.

ReferenceDuong V, Lambrechts L, Paul RE, Ly S, Lay RS, Long KC, Huy R, Tarantola A, Scott TW, Sakuntabhai A, & Buchy P (2015). Asymptomatic humans transmit dengue virus to mosquitoes. Proceedings of the National Academy of Sciences of the United States of America PMID: 26553981

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3 thoughts on “Asymptomatic dengue-infected humans can transmit the virus to mosquitoes

  1. Talk about ironies in life, you’ve helped me to discover yet another one.You said that an “estimated 3.9 billion people in 128 countries are at risk of dengue virus infection. Of the estimated 390 million dengue infections that occur each year, 96 million will manifest clinically with flu-like symptoms including fever, headache, nausea and muscle and joint pain.”

    Interestingly, there are an estimated 3.5 billion people in this world that find themselves without running water, sewage, food or shelter. Kinda reminds me of that old Tennessee Ernie Ford song, “Sixteen Tons.” Part of the wording is as follows, “…if the right one don’t get ya, then the left one will.” If the dengue virus infection don’t get ya, then dehydration, malnutrition and exposure to the elements of weather will.

    Isn’t this tantamount to putting the wagon before the horse? The money being spent to defeat a “dengue infection” should follow AFTER we see to such basic problems as dehydration, starvation and lack of a place to put one’s head each night. But, what do I know.

    It just seems to make sense to me to solve the very basic needs of all human beings, BECAUSE they are human beings–food, shelter, water, sanitary facilities. These very basics would make them strong enough to better combat similar problems you posit. Does this make sense?

    Bill

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    1. Hi Bill,

      Thanks for taking the time to read my post and leave a comment. I absolutely agree with you that sanitation, food, clean drinking water and shelter are all important basic human rights that should be top priorities for the global development community. However, these development goals are not mutually exclusive of infectious disease prevention and control strategies. Rather than treating this as an “either or” situation where we must choose to support one over the other, we can instead focus on efforts to tackle both problems that can be complementary and produce improvements on both fronts.

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      1. Hey, Betty! First, how can they be “basic human rights,” food, water, housing, sewage, when literally half the world’s population are clearly without such things? There is a much bigger problem on this planet than disease and pestilence. It’s called corporate/political (the two are not mutually exclusive) greed and corruption,

        Because of governments world-wide and their zeal for wars, since 1900 there have been approximately 20 million souls killed on this planet! Too, one out of every four people survived the black plague, and that at a time when medical science was almost unheard of. Those survivors did so without the aid of any sciences. Their immune systems, a product of God, successfully combated the plague. Seems to me we should be devoting our time to eliminating the greatest disease ever, all governments.

        As well, what is the point of combating this disease and that when half the world’s population are at the brink of death? So science solves the problem(s) of “asymptomatic dengue infection,” thus saving a few, yet half the world is still dying because of the denial of these “basic human rights?”

        Additionally, there are more people in this country killed by hospitals, doctors and pharmaceutics than all people killed by Cancer and heart disease. Also, one out of every two people in the United States are in poverty, mostly living from paycheck to paycheck. But, what can I possibly know? I’m not a scientist.

        This is not for the purpose of argument, rather for the point of another approach to these problems.

        God bless…

        Bill

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