Previous mosquito bites increase risk of later West Nile infection

Blogging on Peer-Reviewed ResearchYou become infected with West Nile Virus (WNV) when a mosquito vector bites you. As the mosquito sucks your blood (the protein meal makes it possible for her to ovulate), she replaces some of it with her saliva. The virus is in the saliva and if it finds a suitable cell to infect, we're off to the races.

If you are bitten by an uninfected mosquito you obviously can't get infected. But a new set of experiments in mice shows that having been previously bitten by the same species of mosquito markedly increases the chance and severity of infection with WNV in subsequent bites:.

In their experiments, researchers exposed sedated mice to feeding by between 15 and 20 Aedes aegypti mosquitoes for an hour once a week. Scientists then allowed a single West Nile virus-infected mosquito to feed once on each of these mice and also on each of a control group of mice that were previously unbitten by mosquitoes.

The results were striking: 68 percent of mice exposed to two weekly mosquito feedings died of West Nile virus, and those exposed to four weekly mosquito feedings suffered a 91 percent mortality rate. By contrast, the virus killed only 27 percent of the mice previously unexposed to saliva from mosquitoes that were free of West Nile infection. Analyses of responses of the mouse immune systems also showed a strong contrast between the previously exposed and unexposed mice. (ScienceDaily)

The research team, from the University of Texas Medical Branch in Galveston, had good reasons from previous work to think the immune system was involved, and this turned out to be the case here. The saliva modifies the immune response at the site of the bite and the virus seems to be taking advantage of it. Exactly how the sensitization to mosquito saliva increases the risks of infection isn't completely understood, but the researchers saw an increase in early viral replication, an upturn in expression of the immune signaling protein interleukin-10, and a recruitment to the bite location of WNV susceptible cell types. This is a beautiful example of how the virus uses the reaction to the mosquito to increase its ability to make copies of itself, essentially the only viral activity that counts in the long run. That it was the mouse immune reaction that was directly involved was shown by reproducing the effects by injecting unbitten mice with sensitized serum from mice that had been previously bitten. So humoral immunity is definitely involved. Whether cell mediated immunity might also play some role isn't known. Still, quite nice.

This is the first time this phenomenon has been seen. It doesn't happen with parasite and bacterial vectorborne diseases, where previous uninfected bites protect against rather than exacerbate later infected bites. There are some intriguing new avenues of research here. How does the immune state of the host affect reactions to vector borne diseases? What role does the immune reaction play in the risk of infection? Is there cross reactivity between species of mosquitoes? Is the mouse model relevant to human infection?

So many questions. So little time.

You can find the article here at PLoS ONE. Open Access means you can read it without cost


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This result is entirely consistent with our approach to treating WNV, since we aim to suppress the "cytokine storm."

My biotech company has had encouraging results treating West Nile virus encephalitis since 2003: 81% treatment success rate in people (21 of 26), 75% in horses (6 of 8), and 50% in birds (6 of 12).

Our first 8 WNV patients were published in a peer-reviewed medical journal in 2004 (1). Many of our patients were elderly.

The drugs we use already exist, and are FDA-approved for blood pressure. They appear to be anti-inflammatory. People with a normal immune system who get sick from the West Nile virus appear to overdo their immune response to the virus. Our approach is meant to safely calm down their exaggerated immune response (the so-called "cytokine storm.")

Anybody who wants to download the WNV trial protocol can do so for free at any time by clicking on the "West Nile trial" link on our homepage at

The same approach should work for most viruses, including pandemic flu. The beauty of our approach is that the drugs are already stockpiled, in one form or other, in every drugstore on earth.


1: Moskowitz DW, Johnson FE. The central role of angiotensin I-converting enzyme in vertebrate pathophysiology. Curr Top Med Chem. 2004;4(13):1433-54. PMID: 15379656 (For PDF file, click on paper #6 at: -- see Table 2 for WNV patients

Dave Moskowitz MD FACP
CEO, GenoMed, Inc.
Our business is public health
Ticker symbol: GMED.PK

This is true. You do become infected with the West Nile Virus when a mosquito vector bites you. The transmission occurs when the pathogen, being the infected vector, through a blood meal, like you had said, by the vector. (Ruef, 2002)

The West Nile Virus is very difficult. This is one of many ways to detect. Transmission is difficult to predict, not to mention prevent. (Gubler, 2007)

Also, to go along with the difficulty, there are many ways it can be transmitted. One crucial way is in the realm of blood transfusions. (Rios, Daniel, Chancey, Hewlett, & Stramer, 2007)

Many people are awaiting blood transfusions. People who are able to donate blood for such transfusions are actually screened for West Nile Virus. This will prevent further transmission of the virus.

As far as your statement on uninfected mosquitos and chances later on, I found nothing on that I would like to know where you got that. If anything you would think maybe wed have more immunization towards subsequent bites.

Gubler, D. J. (2007). The Continuing Spread of West Nile Virus in the Western Hemisphere. Clinical Infectious Diseases, 45(8), 1039-1046.

Rios, M., Daniel, S., Chancey, C., Hewlett, I. K., & Stramer, S. L. (2007). West Nile Virus Adheres to Human Red Blood Cells in Whole Blood. Clinical Infectious Diseases, 45(2), 181-186.

Ruef, C. (2002). Vectorborne Infectious Diseases. Infection, 30(1), 1.

By Trevor Klock (not verified) on 19 Nov 2007 #permalink

Trevor: Link to the article is in the post (at the end).

From 1937 until 1999, West Nile virus (WNV) garnered scant medical attention as the cause of febrile illness and sporadic encephalitis in parts of Africa, Asia, and Europe. After the surprising detection of WNV in New York City in 1999, the virus has spread dramatically westward across the United States, southward into Central America and the Caribbean, and northward into Canada, resulting in the largest epidemics of neuroinvasive WNV disease ever reported. From 1999 to 2004, >7,000 neuroinvasive WNV disease cases were reported in the United States. In 2002, WNV transmission through blood transfusion and organ transplantation was described for the first time, intrauterine transmission was first documented, and possible transmission through breastfeeding was reported.
WNV is transmitted primarily by the bite of infected mosquitoes that acquire the virus by feeding on infected birds. The intensity of transmission to humans is dependent on abundance and feeding patterns of infected mosquitoes and on local ecology and behavior that influence human exposure to mosquitoes. Although up to 55% of affected populations became infected during epidemics in Africa, more recent outbreaks in Europe and North America have yielded much lower attack rates. In the area of most intense WNV transmission in Queens, New York, in 1999, [approximately equal to] 2.6% of residents were infected (most of these were asymptomatic infections), and similarly low prevalence of infection has been seen in other areas of the United States. WNV outbreaks in Europe and the Middle East since 1995 appear to have caused infection in <5% of affected populations. These levels of infection are too low to decrease the frequency of epidemics or modulate their intensity through protective immunity.( Edward B. Hayes)

Hayes, Edward B., Nicholas Komar, Roger S. Nasci, Susan P. Montgomery, Daniel R. O'Leary, and Grant L. Campbell. "Epidemiology and transmission dynamics of West Nile virus disease." Emerging Infectious Diseases 11.8 (August 2005): 1167(7). Health Reference Center Academic. Gale. Potsdam Libraries - SUNY. 19 Nov. 2007

By rena deshane (not verified) on 19 Nov 2007 #permalink

for some reason I could not finish my article above so here is the rest of it:

<5% of affected populations. These levels of infection are too low to decrease the frequency of epidemics or modulate their intensity through protective immunity. Data on the incidence of WNV in most of the world are not readily available. WNV transmission has been reported in Europe, the Middle East, Africa, India, parts of Asia, Australia (in the form of Kunjin virus, a subtype of WNV), North America, and parts of Central America and the Caribbean. Since the virus was detected in New York from 1999 through 2004, 16,706 cases have been reported to the Centers for Disease Control and Prevention (CDC); 7,096 of these were classified as neuroinvasive disease, 9,268 as West Nile fever (WNF), and 342 had other or unspecified clinical presentation (reported through June 8, 2005; the proportion of total cases reported that are neuroinvasive disease is artificially higher than what is believed to occur naturally since neuroinvasive disease is more likely to be reported than WNF or asymptomatic infection. The incidence of WNV disease is seasonal in the temperate zones of North America, Europe, and the Mediterranean Basin, with peak activity from July through October. In the United States, the transmission season has lengthened as the virus has moved south; in 2003, onset of human illness began as late as December, and in 2004 as early as April (CDC, unpub. data). Transmission of WNV in southern Africa and of Kunjin virus in Australia increases in the early months of the year after heavy spring and summer rainfall. In the United States, persons of all ages appear to be equally susceptible to WNV infection, but the incidence of neuroinvasive WNV disease and death increases with age, especially among those 60 to 89 years of age, and is slightly higher among male patients. (Edward B. Hayes)

Hayes, Edward B., Nicholas Komar, Roger S. Nasci, Susan P. Montgomery, Daniel R. O'Leary, and Grant L. Campbell. "Epidemiology and transmission dynamics of West Nile virus disease." Emerging Infectious Diseases 11.8 (August 2005): 1167(7). Health Reference Center Academic. Gale. Potsdam Libraries - SUNY. 19 Nov. 2007

By rena deshane (not verified) on 19 Nov 2007 #permalink

The west nile virus has increasingly become more and more prevalent in the past few years. WNV was first identified in the United States in 1999. West nile weakens the immune system, leaving the person more suceptable to other sicknesses. It is interesting to read that saliva can compromise the immune system as well, leaving a person more easily susceptible to WNV. There are many antibiotics now that can be used for the virus, but with this information it seems like we will be needed better prevention strategies for all mosquito bites!

Teitelbaum, Bruce A., Tricia L. Newman, and David J. Tresley. "Occlusive retinal vasculitis in a patient with West Nile virus.(Author abstract)(Report)." Clinical and Experimental Optometry 90.6 (Nov 2007): 463(5). Health Reference Center Academic. Gale. Potsdam Libraries - SUNY. 20 Nov. 2007

By Danielle LaPointe (not verified) on 20 Nov 2007 #permalink