The Coming War on Mosquitoes

Dov Michaeli

Posted 1/14/12 on The Doctor Weighs In

Aedes Aegypti. Caught in the act.

I consider myself an animal lover; I am even fascinated by insects. But Mosquitoes? they are a class by themselves. To paraphrase Rick Perry, if every single one of them gets “executed” I wouldn’t lose much sleep over it. My granddaughter once asked me plaintively “why do we have mosquitoes?” I mumbled somthing inane about the ecology. But why indeed?

The mosquito and H. sapiens

A fascinating theory was proposed by Dr. Varki, a glycobiologist in U.C. San Diego, which we wrote about in TDWI.

Humans are not susceptible to the malaria organism Plasmodium reichenowi, that afflicts other species. This parasite attaches itself to the cell surface by binding to a sugar molecule called Neu5Gc. We are not susceptible to this organism because of a lucky mutation: the last step in the biosynthesis of this surface sugar became inactivated so we ended up we the molecule of the penultimate step, Neu5Ac. End result: we don’t get the malaria that afflicts chimps and gorillas, for instance.

But evolution works in strange ways; another malaria-causing species of Plasmodium, P. falciparum, was capable of gaining entry into human cells through the newly mutated surface sugar. And this malaria parasite was transmitted through mosquito species likeAnopheles and Aedes aegypti. Interestingly, genetic analysis of Anopheles showed that the species evolved in Africa , alongside the evolving humans, and it accompanied the bands of early humans as they migrated out of Africa.

Anopheles. Note the blood-filled abdomen.

The plagues inflicted on us by mosquitoes don’t end with malaria; Aedes aegyptitransmits a virus that causes dengue fever, and another that causes yellow fever. This mosquito also originated in Africa and was introduced into South America in the 16th century with the slave trade.

We are not very familiar with Dengue fever in the U.S. It is the most prevalent mosquito-borne viral disease in humans and it exists almost exclusively in the tropical and sub-tropical regions of South America and Africa. Around 40% of the world’s population is at risk of infection with dengue virus. Every year, the virus infects 50 -100 million people, causing the classical dengue flu-like syndrome, as well as the more severe symptoms like dengue hemorrhagic fever and dengue shock syndrome. But we can’t ignore the disease just because it is still not in our backyard: regardless whether you are a believer or not- global warming is causing this disease, like other diseases of the tropics, to move northward.

The enemy within

The problem with controlling the disease is that all attempts at developing a vaccine have so far ended up in failure. And unlike Anopheles mosquitoes, A. aegypti is active during the day, so that attempts to protect people with window screens and bed nets are ineffective.

Two papers in Nature (Walker et al. and Hoffmann et al.) report on a remarkable new approach to wiping out A. aegypti.

First, some fascinating biology. The bacterium Wolbachia lives inside the cells of many insects, including A. aegypti. It is transmitted by the females through the eggs to its female progeny, and using various manipulations of the reproductive process the bacterium maximizes the number of infected females in the next generation, which allows it to spread rapidly through populations. So why is this important? Because once a mosquito is infected with the bacterium it is sort of immunized; it cannot be infected with many other parasites, including the dengeue virus.

To test the possibility of “immunizing” caged mosquitoes in the lab with Wolbachiaagainst carrying the dengue virus the investigators infected some of the mosquitoes and followed its spread through the population; and it worked -100% of the subsequent generation became infected.

Losing little time, they initiated a study in Queensland, Australia, where there  had been sporadic outbreaks of dengue fever. In the 2 sites where they released Wolbachia-infected mosquitoes over two and half months, one site had 100% and the other 80% infected females.

Just think about it: a whole population was replaced with dengue- resistant mosquitoes. Not only that, this resistance is self-perpetuating, courtesy of Wolbachia’s talent of maximizing its spread through the females of subsequent generations.

The genetic attack

To tell the truth, I was a bit disappointed by the Wolbachia approach. Yes, it promises to wipe out dengue fever, and may be even malaria; but it doesn’t solve the problem of the irritating nay, infuriating, nocturnal buzz at before the those blood-sucking bugs get you. Can’t we just get rid of the buggers?

Yes we can! in a paper published in the Proceedings of the National academy of Sciences scientists at the University of California, Irvine, have added genes to Aedes aegypti that block the development of flight muscles in females. When a genetically-modified male mates with a wild female (genetically, not behaviorally-speaking) he passes his engineered genes to the offspring. The females, those buzzing and blood-sucking bugs, can’t fly -they just sit motionless on the water and eventually die. The males, in contrast, continue to mate with wild females (lucky, they) and spread their female-killing genes. Result? in time, the population crashed, at least in the lab. After weekly introductions of males carrying the flightless gene the population crashed within 10-20 weeks. Will it work in the wild? The scientists are now introducing the genetically-engineered males at several sites in the state of Chiapas in southern Mexico. Results are not yet in.

There is another approach to sterilizing males: radiation treatment. Once the irradiated males mate, the deluded female thinks that she was fertilized, and lays those useless eggs. A major problem with this approach, in addition to the risk and expense of radiation, is that the irradiated males are less successful than wild-type males in competing for females – a fatal flaw in the dog-eat-dog Darwinian world. On the other hand, the genetically-modified males were almost as vigorous as their wild-type cousins, which increases the chance that this approach will prove successful.

Of course, every change raises the heckles of critics, this one is no exception. Is it ethical to eliminate a whole species? The specter of mosquito genocide has been raised. More to the point, what is it going to do to the food chain? What about birds who feast on insects, among  them mosquitoes? Hard to answer definitively, but remember: mosquitoes co-evolved and adapted to humans. So the impact, if any, on other animals should be minimal, and I’m sure many warm-blooded mammals would actually be quite grateful.

The KISS approach

It never ceases to delight me when complex problems are solved with simple solutions. It evokes in me the half-question, half self-reproach ”why didn’t I think of it?”.

Drs. Yosef Schlein, a parasitologist at the Hebrew University and his research partner Günther Müller took advantage of the fact that mosquitoes feed on flower and fruit nectar. The female also feeds on warm-blooded animals like us because without a blood meal to provide iron and protein her eggs will not develop. So they concocted a solution of rotting nectarine juice (as an attractant), brown sugar solution (as bait) and added Sinosad, a bacterial insecticide that is safe for humans and most beneficial insects. They put the solution in empty soda bottles, placed them in socks, and added a wick to keep the socks wet with the delicious elixir. They tried it at an oasis near the Red Sea and reduced the mosquito population by 90%. They also checked the sex of the trapped mosquitoes, and they got a nice bonus-most of the insects were mature females, the ones that are ripe for laying eggs. They repeated the experiment around the water cisterns at a Greek monastery in the Judean hills. Again, over 90% reduction of the mosquito population, the female population totally collapsed, and the area remained mosquito-free at least one month. The Bill and Melinda Charitable Foundation took notice and awarded them the princely sum of $1 million to try it in Mali, Africa. There they used juice of local fruits, Guava and melons with identical results –within one week the mosquito population dropped more than 90%, and the female count was essentially zero. In another area they sprayed the solution on tree branches, and had the same results. They are now expanding their studies to other areas of the world and trying other natural insecticides. And all this on a grant of one million dollars!

Which approach is going to win out? time will tell. My guess is that a combination of approaches will be needed, depending on local conditions.

But one thing is almost certain: your days are numbered, you blood-sucking buggers!

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