Intervention reducing malaria parasite load in vector mosquitoes: no impact on Plasmodium falciparum extrinsic incubation period and the survival of Anopheles gambiae

In the fight against malaria, transmission blocking interventions (TBIs) are promising approaches to complement conventional tools. They aim to prevent the infection of the vectors and thereby reduce the subsequent exposure of a human population to infectious mosquitoes. The effectiveness of these approaches has been shown to depend on the initial intensity of infection in mosquitoes, often measured as the mean number of oocysts resulting from an infectious blood meal prior to intervention. In mosquitoes exposed to a high infection load, current TBI candidates are expected to be ineffective at completely blocking infection but will decrease parasite load and therefore, potentially also affect key parameters of vector transmission. The present study aims to investigate the consequences of changes in oocyst intensity on downstream parasite development and mosquito survival. To address this, we experimentally produced different infection intensities in Anopheles gambiae females by diluting gametocytes from natural Plasmodium falciparum isolates and used a newly developed non-destructive method based on the exploitation of mosquito sugar feeding to track parasite and mosquito life history traits throughout sporogonic development. Our results indicate that P. falciparum extrinsic incubation period (EIP) and mosquito survival did not vary with parasite density but differed significantly between parasite isolates. Our results do not identify here unintended consequences of the decrease of parasite loads in mosquitoes on the parasite incubation period or on mosquito survival, two key parameters of vectorial capacity, and hence support the transmission blocking strategies to control malaria. Author summary In the fight against malaria, it is recognized that the use of several complementary strategies is necessary to significantly reduce transmission and improve human health. Among these, transmission blocking strategies aim at blocking the development of the parasites within the mosquito vectors. This approach should prevent infection in most of mosquitoes feeding on infectious hosts and thus block the transmission. However, in some cases it may only reduce parasite load without fully clearing the infection. Here we identified potential risks: if reducing parasite load would reduce the incubation period of the parasite in the mosquitoes or increase the longevity of the mosquitoes, undesirable consequences may occur with an increased efficiency of these mosquitoes to transmit parasites to human. We therefore tested these hypotheses and experimentally produced different infection loads in vector mosquitoes Anopheles gambiae by using dilutions of Plasmodium falciparum isolates from naturally infected human donors. We observed that the longevity of the mosquitoes and the incubation period of the parasites were not affected by the parasite load. This is not consistent with the unintended risks that we investigated and thus strengthens the potential of transmission blocking interventions in the toolbox to combat malaria. ### Competing Interest Statement The authors have declared no competing interest.