What animal kills the most people? It depends. Most importantly it depends upon where you live. In the case of contracting and/or dying from an infectious disease, few things are as important as geography—where you live and where you’ve recently traveled. Globally, the mosquito is hands-down the most lethal animal (responsible for an estimated 750,000 to 1 million deaths per year, mostly in Africa).
This week two events related to mosquitoes caught my eye. First, was the publication of Timothy C. Winegard’s scholarly book, The Mosquito: A Human History of Our Deadliest Predator (Dutton). (For an informative review, read Brooke Jarvis’ article Buzz Off in the August 5 issue of The New Yorker.) And the second noteworthy item was The Philippine’s declaration of a national dengue epidemic.
In his book, Winegard makes a compelling case that historically mosquitos have killed more people than any other cause. Of course, the mosquito per se isn’t a killer. Rather it is the pathogens that it carries that are the culprits, most notably the parasite Plasmodium—the cause of malaria. Winegard tells of famous ancient Greeks, Romans, Chinese, and others that succumbed to malaria. And, during the American Civil War, malaria accounted for more than one million episodes of illness and killed 10,000 troops. Fortunately, the National Malaria Eradication Program launched in 1947 was successful in eliminating malaria in the United States by 1951. But, sadly, malaria still exists in more than 100 countries and territories around the world.
In recent years, the capacity of mosquitos to serve as a vector for viruses has captured increased attention. Of the many types of viruses that mosquitos can carry: Zika, chikungunya, yellow fever, West Nile, and dengue, the dengue viruses are the ones causing the most suffering and death. The World Health Organization estimates that 50 to 100 million dengue infections occur annually, including 500,000 cases of the most severe form of disease called dengue hemorrhagic fever. Half a million people are hospitalized due to dengue, and at least 22,000 of its victims die every year.
The four types of dengue virus (DEN1, DEN2, DEN 3, and DEN4) are members of the Flavivirus genus. (Other flaviviruses include Zika virus and yellow fever virus; flavus means yellow in Latin.) While more than 3,000 mosquito species have been identified, only two carry the dengue viruses: Aedes aegypti and Aedes albopictus (also known as the Asian tiger mosquito). The bad news is that about 2.5 billion people, 35% of the world’s population, live in areas of the world where these mosquito species hang out.
To date, there are no drugs to treat dengue. Instead, current treatment focuses on alleviating symptoms. Fortunately, the majority of people who get infected with dengue viruses experience no symptoms at all. But for those who get sick, the symptoms include the sudden onset of fever, headaches, and severe muscle, bone, and joint pain. While most patients recover within two to seven days, as many as 5% develop severe, life-threatening dengue hemorrhagic fever which is treated by administering blood transfusions or otherwise replacing body fluids. For this unfortunate minority, many of whom are children, just as the fever is resolving, there is leakage of plasma from blood vessels, which can accumulate in the abdominal and chest cavities. This depletes the amount of fluid circulating in the body, resulting in shock and decreased blood flow to vital organs. Severe bleeding from the gastrointestinal tract also typically occurs.
Strangely, a prior infection with one type of dengue virus not only doesn’t provide immunity against the other three—it makes you more vulnerable to them. That is, if you’ve already had an infection by one type of dengue virus, and you become infected with another. The earlier infection increases your risk of developing severe illness and dying. This phenomenon has played an important role in the controversy over the use in The Philippines of the dengue vaccine Dengvaxia, a vaccine that targets all four dengue viruses.
While currently licensed in 20 countries, Dengvaxia has some drawbacks. It reduces the risk of adults developing dengue, but it isn’t as effective in children. And it may even increase the risk of severe illness in kids under the age of six when they get infected with a live dengue virus due to the unusual reaction described above. This phenomenon led to curtailment of the use of Dengvaxia in The Philippines, but now that a national epidemic has been declared, this decision is under review.
There are new vaccines under development to prevent dengue. In addition, innovative approaches to controlling mosquitoes are under evaluation. One such strategy is the use of the symbiotic bacterium, Wolbachia, which is sprayed in areas where Aedes mosquitoes live. Wolbachia-infected mosquitoes have a shortened life span, and their ability to transmit the virus is blocked by a mechanism that, to date, isn’t completely understood. Also, it is a master manipulator of the sex life of its hosts; it both feminizes and kills males. On top of that, it doesn’t infect humans. We await the results of a number of trials around the world to see if Wolbachia can serve as an effective pesticide.
But, why do mosquito-borne infections, like dengue, seem to be increasing around the world? The answer, in part, is discussed in an earlier germgems.blog (More Ticked Off!) on the emergence of another vector, the Asian longhorned tick. One of the consequences of warming and increased rain associated with climate change is that certain arachnids (ticks) and insects (mosquitoes) love it. So, long-term control is dependent on development of improved measures for adaptation and mitigation to our warming world.