Malaria is caused by a parasite called Plasmodium that mosquitoes transmit to humans. Only few types of mosquitoes can transmit the parasites. Among them, some species have a high degree of probability of transmitting the parasite and are considered particularly dangerous. Scientist Elena Levashina discovered the TEP1 gene in mosquitoes in a lab setting eighteen years ago. Depending on the version, it makes the mosquitoes more or less resistant to the parasite and can thus reduce the mosquito capacity to transmit the deadly parasite. Up to now it has remained unclear whether this laboratory finding can also be applied to nature.
To prove that there are also TEP1-resistant mosquitoes in nature, Elena Levashina's team conducted a field study in Africa. The international team worked with researchers in Mali, Burkina Faso, Kenya and Cameroon and collected and analyzed thousands of mosquitoes for four years. "A project like this can only succeed if there is a mutual exchange," explains Markus Gildenhard, one of the project's scientists. "The experts in field research are the people who live and work on site."
The scientists found the same versions of TEP1 gene in mosquito species in the wild as in the laboratory. Surprisingly, the resistant form of the gene was only detected in Anopheles coluzzii but not in Anopheles gambiae, two otherwise closely related mosquito species. After this success, the team focused on a collection site in the Sahel zone of Mali, where the two species breed together.
In a new approach, the researchers collected thousands of mosquito samples throughout two rainy seasons. They observed that the size and species composition of the mosquito population changed throughout the season and decided to use a method developed for predicting stock prices to see how differences in mosquito the populations impacted Plasmodium abundance. Markus Gildenhard, scientist in Elena Levashina's team, used this test and created a model to predict the number of mosquitoes infected with parasites. Then the researchers checked whether such variables as temperature, total number of mosquitoes, or ratio of mosquito species improve the prediction of parasite abundance.
Species composition determines parasite abundance
The result was truly surprising: only the ratio between the two sympatric species was predictive of the parasite abundance. Until now, A. coluzzi and A. gambiae have both been considered to be dangerous carriers of malaria parasites. However, the model predicted that an increase in the percentage of A. coluzzi, the species carrying the resistant version of TEP1, should decrease the number of infected mosquitoes. Conversely, an increase in the susceptible A. gambiae raised the numbers of infected mosquitoes. The increase in the number of infected mosquitoes will directly impact human exposure to Plasmodium parasites.
Models like this are urgently needed to predict how rapidly changing climate conditions will affect regional malaria incidence in Africa and worldwide. As genetic composition of mosquito populations shapes transmission of the malaria parasite, further research should focus on factors that structure mosquito populations. In order to develop tools for genetically-based control measures, researchers have to identify and target the local mosquito species that drive Plasmodium transmission. Gene drive technology in mosquitoes promise to provide a new attractive strategy to fight malaria. Researchers have developed methods to drive genes of interest into targeted mosquito species. However, as Elena Levashina's research shows, the efficiency of the intervention depends on the targeted mosquito species. If the wrong malaria mosquito is removed from an ecosystem (for example, Anopheles coluzzii in the studied site in Mali), the more dangerous Anopheles gambiae will swiftly replace it with grave consequences for human health.