World Malaria Day 2016: The War on the Anophelines

It is shortly after the Second World War and armies of men with canisters full of DDT invade villages and cities of Europe and the USA. Their mission? To kill the anopheline mosquitoes and once and for all eliminate malaria from these places. The heavily armed offence did its job in eliminating malaria - it is now difficult to imagine malaria pestering European citizens a mere decades ago. The anopheline mosquito however persisted, in some areas even in large numbers.

The Anopheles mosquito is a ruthless serial killer

The Anopheles mosquito is a ruthless serial killer. Responsible for approximately 590,000 annual deaths it by far bypasses other animals more popularly seen as dangerous such as the shark (10 deaths), crocodile (1,000 deaths) and snake (50,000 deaths). However, just as most serial killers are harmless without a weapon, the Anopheles mosquito is harmless without the malaria parasite. Without malaria, it is merely left as a nuisance that keeps you up at night.

Malaria is many millions years old, indeed, it has recently been shown to have even killed dinosaurs. But it took us humans millions of years to figure out that a mosquito was the transmitting agent, in fact, it was only discovered a little over 100 years ago. With this discovery, our attack on the mosquitoes began.

Responsible for approximately 590,000 annual deaths it by far bypasses other animals more popularly seen as dangerous

The war on the anophelines is a multi-frontal attack. Our first front is to harness any weaknesses in their biology, e.g. by cutting off their water supply through reducing breeding site availability, using the odor cues that they use to locate us to trap them, and exploiting their natural predators and pathogens, such as fish and Bacillus thuringiensis (Bti), to kill their larvae.

The next front is a chemical warfare: insecticides are sprayed inside people’s homes, impregnated on their bednets and added to potential breeding sites. Additionally, endectocides such as ivermectin can be given to potential hosts – human and/or domestic animals – to kill any bloodfeeding mosquito. Our newest potential front is a genetic war: using modern tools we can genetically modify mosquitoes that cannot transmit malaria or produce sterile male mosquitoes that will be released in the field to reduce numbers of malaria-transmitting anophelines.

The war on the anophelines is a multi-frontal attack

Anophelines, however, have so far always found ways to outsmart us. Several species in sub-Saharan Africa can lay their eggs in water pools as small as a rain-filled hoof print; breeding sites that are impossible to target on a continent as big as Africa and absent of predatory fish. As a strike back against the chemical warfare, anophelines have evolved resistance against many insecticides and moreover changed their behavior to start biting people outside – where there is no insecticide – plus moving their preferred biting time a little earlier so people are not yet protected by their bednet. The genetic warfare has not yet been implemented on grand scale, but when it will, we should not be surprised to observe the anophelines outsmarting us yet again by changing their biology and behaviors.

Thus, what can we do to outsmart these little serial killers? As a first step, a bigger artillery is needed. Just as what we have learned to outsmart HIV and antibiotic resistant ´superbugs´, we need to combine more insecticides as it is more difficult to become resistant against multiple insecticides than it is against one. And when we do, we need to think about how we employ our artillery; do we use them all at once or rotate them to make it more difficult to adapt? What kind of evidence do we need to base these decisions on?

We also need to understand our foe better: who are they, where are they and when do they attack? We seem to have chased many mosquitoes out of the houses, but where are they now? If IRS and LLINs are not affecting them, we need to come up with a novel strategy of attack. And finally, which species are actually transmitting malaria? There are hundreds of anopheline mosquito species, out of which 30 to 40 transmit malaria, yet we are focusing on a handful of the usual suspects. While we are chasing the gang leaders, are the gang members killing us behind our backs?

At ISGlobal and “la Caixa” against Malaria, we have initiated our battle against the anophelines within the Mozambican Alliance Towards Malaria Elimination (MALTEM)

At ISGlobal and the “la Caixa” against Malaria programme, we have initiated our battle against the anophelines in southern Mozambique within the Mozambican Alliance Towards Malaria Elimination (MALTEM).  Supported by the “la Caixa” Foundation and the Bill and Melinda Gates Foundation and in partnership with the Government of Mozambique and other actors, such as the Manhiça Health Research Centre, the alliance has an ambitious goal: to eliminate malaria from the most southern part of the country by 2020 using a combination of mass drug administration and vector control.

Here we face the opposition of the anophelines first-hand as long lasting insecticidal nets (LLINs) are scarcely more effective than an untreated bednet due to resistance and the role of outdoor transmission appears to be growing. It is clear that we need a better understanding of the evolution of mosquito biology and behavior or we will never be able to suppress vector populations to such levels that malaria elimination is achievable.

A war is never won by keeping on doing what has proven not to work. The mosquito war has been a success in the USA and Europe but real opposition has come from the corners of sub-Saharan Africa, Asia and South America. Novel strategies are needed to jump a surprise attack on the anophelines and we should expect them to strike back and be ready to respond. However, remember, the anopheline is innocent without the malaria parasite: this really isn´t a war against the anophelines, it is a war against the malaria parasite. The war against the anophelines is just one pillar that will help collapse the malaria parasite empire.

More information

Infographic: Usual suspects: 6 tiny vectors that represent a huge treat to our health. 001 Anopheles Mosquito".