By Philip R. Fischer, MD, DTM&H

Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN

Dr. Fischer reports no financial relationships relevant to this field of study.

SYNOPSIS: A non-pathogenic microsporidian organism can infect Anopheles mosquitoes and block the transmission of malaria parasites, without negatively altering the life of the mosquito. This organism potentially could be used for widespread malaria control.

SOURCE: Herren JK, Mbaisi L, Mararo E, et al. A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes. Nat Commun 2020;11:2187.

Widespread use of insecticide-treated bed nets earlier this century was associated with a marked reduction in malaria mortality. Over the past few years, though, the decline in the number of malaria cases has stalled. Current malaria control efforts are insufficient.

Some symbiotic microorganisms, living within mosquitoes, can alter the transmission of viral pathogens to humans. So far, no such organism had been identified that could alter malaria transmission significantly and sustainably. So, Herren and colleagues pursued a series of studies of a non-pathogenic microsporidian to see if it could reduce transmission of Plasmodium falciparum.

First, Microsporidia MB was found in up to 9% of Anopheles arabiensis mosquitoes in areas of Kenya. These organisms are of a different clade than (and, therefore, are distinct from) the previous microsporidians found in mosquitoes. Microsporidia MB followed seasonal patterns and was most prevalent after times of heavy rain. The organisms are transmitted vertically from mother to offspring through the ovaries.

Second, Herren and colleagues found that Microsporidia MB-infected mosquitoes could ingest Plasmodium parasites with blood meals, but that the parasites then would not progress through necessary stages of development and migration to reach the salivary glands of the mosquitoes.

Third, the researchers noted that Microsporidia MB did not alter the survival or reproductive potential of the infected mosquitoes. Thus, infection by the symbiotic microsporidian would not be a “dead end,” but is associated with the production of subsequent generations of infected mosquitoes that also would be able to block the development and transmission of malaria parasites.

Fourth, the genetic effects of Microsporidia MB infection were evaluated. The symbiont promoted increased transcription of genes related to digestion, immunity, and salivary gland activity. Thus, the mechanism by which Microsporidia MB acts on the mosquito not only blocks malaria transmission but also might enhance the health of the mosquito.

Herren and colleagues concluded that Microsporidia MB could be a realistic candidate to infect mosquito populations and facilitate development of a stable vector that could replace current mosquito populations. The blockage of malaria transmission coupled with the passage of microsporidia from one generation to the next with no adverse health effects on the mosquito could make Microsporidia MB an attractive option for the control of malaria.

COMMENTARY

Through all the tragedy and politicization of the current COVID-19 pandemic, most everyone agrees that society was not adequately prepared to deal with widespread transmission of such a devastating virus. With heavy expenditures of human and material resources, there is rapid progress against SARS-CoV-2 infection.

Unlike COVID-19, malaria is neither new nor novel; it has been around for millennia. At the time of this writing, nearly 4 million people have been infected by COVID-19. Malaria infects 200 million per year. COVID-19 already is responsible for nearly 300,000 deaths; malaria kills one and a half times that many people every year. Despite the extensive resources put into malaria control efforts, malaria is not yet under control.

Widespread use of insecticides, such as dichlorodiphenyltrichloroethane (DDT), held promise of eradicating malaria, but resistance of mosquitoes to DDT and environmental toxicity limited the usefulness of those efforts. Preventive medication was sensible, but delivery systems and access to care limited those interventions. Improved medications became available as resistance developed, but medications alone were not able to stop malaria’s devastation. Insecticide-treated bed nets led to huge gains, and mortality from malaria plummeted, but then plateaued.

Biologic warfare, using commensal organisms living within mosquitoes, has long been postulated as a possible weapon in the fight against malaria, but the limited reduction in Plasmodium transmission and/or the resulting weakness of the infected mosquitoes limited the value of those efforts.

Now, Microsporidia might be a game-changer. This organism appears to be extremely effective in prompting an essentially complete blockage of the transmission of malaria parasites through the mosquito, and the germs are effectively transmitted trans-ovarially to the next generation of mosquitoes, prolonging the effect.

Further studies will be needed to confirm these findings and to evaluate the feasibility of introducing these infected vectors into the population in ways that would allow them to increase to well beyond the current 9% prevalence of infection in Kenyan mosquitoes. At the same time, other species of Anopheles also could be evaluated as potential malaria-blocking vectors.