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

Abstract

In the fight against malaria, transmission blocking interventions (TBIs) such as transmission blocking vaccines or drugs, are promising approaches to complement conventional tools. They aim to prevent the infection of 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 in absence of intervention. In mosquitoes exposed to a high intensity of infection, 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 investigated the consequences of changes in oocyst intensity on subsequent parasite development and mosquito survival. To address this, we experimentally produced different intensities of infection for Anopheles gambiae females from Burkina Faso by diluting gametocytes from three natural Plasmodium falciparum local 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 the extrinsic incubation period (EIP) of P. falciparum and mosquito survival did not vary with parasite density but differed significantly between parasite isolates with estimated EIP ₅₀ of 16 (95% CI: 15–18), 14 (95% CI: 12–16) and 12 (95% CI: 12–13) days and median longevity of 25 (95% CI: 22–29), 15 (95% CI: 13–15) and 18 (95% CI: 17–19) days for the three isolates respectively. Our results here do not identify 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 use of 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 such as transmission blocking vaccines or drugs, aim to block the development of the parasites within mosquito vectors. This approach should prevent infection in most mosquitoes feeding on infectious hosts and thus block 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 mosquitoes or increase the longevity of the mosquitoes, undesirable consequences may occur with an increased efficiency of these vectors to transmit infection to humans. We tested these hypotheses and experimentally produced different infection loads in Anopheles gambiae by using dilutions of Plasmodium falciparum isolates from naturally infected human donors. We observed that the longevity of 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 identified and thus strengthens the potential of transmission blocking interventions in the toolbox to combat malaria.