Plasmodium species co-infections in Anopheles mosquitoes: a pilot study of parasite-vector interactions that define transmission in Africa

• Applicant: Professor Dr. Steffen Borrmann
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 380545594

The elimination of malaria will require species-transcending interventions. Currently, the vast majority of efforts are focused on P. falciparum and to a lesser degree on P. vivax.Starting in January 2019 we have embarked on studying the transmission dynamics of P. malariae at household level, re-tooling established experimental transmission protocols to study P. malariae parasite-vector interaction and thereby, train a new generation of African medical entomologists. So far, we have demonstrated robust infection rates of P. malariae co- and single infections in An. gambiae colonies. We have also achieved an experimental breakthrough by showing that cryo-preserved P. malariae isolates from P. malariae gametocyte-positive donors preserve their infectious capacity and can thus be used to (i) build a unique P. malariae isolate bank, (ii) dramatically upscale throughput of our experimental transmission phenotype/genotype screen and (iii) enable experimental reproducibility. In addition, we were able to confirm substantial prevalence rates of P. malariae in field-collected An. mosquitoes. Of note, P. malariae sporozoite carrier rates detected by qPCR in mosquito heads and thoraces tended to be lower than oocyst carrier rates in midguts when compared to the respective rates of P. falciparum in the same set of field-captured mosquitoes, suggesting a developmental deficit of P. malariae in An. funestus.Here, we propose to expand the scope of the current investigations on the determinants of the transmission of P. malariae by focusing on a detailed genetic dissection of the susceptibility of two contrasting lines of Anopheles mosquitoes. We will apply both vector and parasite genetics in parallel and broaden our investigations on the whole journey of P. malariae through its insect vector. Importantly, these proposed new analyses will directly benefit from our new and unique ability to use cryo-preserved P. malariae isolates for experimental transmission experiments. We will also compensate for COVID-19 related disruptions and complete the large cross-sectional household-based survey of both parasite and vector populations in four African countries. For the ongoing training of young scientists in medical entomology we will synergise with other Central African networks and benefit from new digital media for promoting an engaging scientific exchange and training environment despite the current pandemic.Our long-term aim remains to capitalise on our new experimental platform for non-P. falciparum malaria parasites for (i) replenishing a discovery pipeline of novel transmission-blocking interventions such as a species-transcending vaccine necessary for malaria elimination, (ii) enabling future controlled human malaria infection studies and (iii) expanding a collaborative training platform integrating medical entomology, epidemiology, parasitology and genetics.

• DFG Programme: Research Grants
• International Connection: Benin, Cameroon, Gabon, Republic of the Congo, United Kingdom
• Co-Investigator: Dr. Nicolas Casadei
• Cooperation Partners: Professor Taane Clark, Ph.D.; Professor Mario Recker, Ph.D.
• International Co-Applicants: Professor Dr. Ayola Akim Adegnika, Ph.D.; Professor Dr. Salako Luc Djogbénou, Ph.D.; Professorin Dr. Francine Ntoumi; Professor Dr. Charles Wondji