Population replacement gene drive characteristics for malaria elimination in a range of seasonal transmission settings: a modelling study

Abstract

Background Gene drives are a genetic engineering method where a suite of genes is inherited at higher than Mendelian rates and has been proposed as a promising new vector control strategy to reinvigorate the fight against malaria in sub-Saharan Africa. Methods Using an agent-based model of malaria transmission with vector genetics, the impacts of releasing population-replacement gene drive mosquitoes on malaria transmission are examined and the population replacement gene drive system parameters required to achieve local elimination within a spatially-resolved, seasonal Sahelian setting are quantified. The performance of two different gene drive systems—“classic” and “integral”—are evaluated. Various transmission regimes (low, moderate, and high—corresponding to annual entomological inoculation rates of 10, 30, and 80 infectious bites per person) and other simultaneous interventions, including deployment of insecticide-treated nets (ITNs) and passive healthcare-seeking, are also simulated. Results Local elimination probabilities decreased with pre-existing population target site resistance frequency, increased with transmission-blocking effectiveness of the introduced antiparasitic gene and drive efficiency, and were context dependent with respect to fitness costs associated with the introduced gene. Of the four parameters, transmission-blocking effectiveness may be the most important to focus on for improvements to future gene drive strains because a single release of classic gene drive mosquitoes is likely to locally eliminate malaria in low to moderate transmission settings only when transmission-blocking effectiveness is very high (above ~ 80–90%). However, simultaneously deploying ITNs and releasing integral rather than classic gene drive mosquitoes significantly boosts elimination probabilities, such that elimination remains highly likely in low to moderate transmission regimes down to transmission-blocking effectiveness values as low as ~ 50% and in high transmission regimes with transmission-blocking effectiveness values above ~ 80–90%. Conclusion A single release of currently achievable population replacement gene drive mosquitoes, in combination with traditional forms of vector control, can likely locally eliminate malaria in low to moderate transmission regimes within the Sahel. In a high transmission regime, higher levels of transmission-blocking effectiveness than are currently available may be required.

Considerations for first field trials of low-threshold gene drive for malaria vector control

“…While the time to impact of releases of gene drive systems for malaria vector has been investigated in a number of modelling studies, most of these have focused on post-trial implementation that have typically involved annual releases of low numbers of mosquitoes at relatively dispersed locations yielding time to entomological or epidemiological impacts on the order of one to two years after releases have commenced [ 23 , 99 , 165 ]. However, a recent modelling study of initial field releases of a population modification gene drive system on an island setting suggested that, under at least some circumstances, a significant reduction in malaria incidence could be anticipated within three to six months [ 148 ].…”

Assessing the Impact of Relapse, Reinfection and Recrudescence on Malaria Eradication Policy: A Bifurcation and Optimal Control Analysis

“…As mentioned by several authors [ 4 , 63 ], vector bias has an essential role in determining the success of malaria eradication programs. Another important factor that needs to be discussed is the seasonal impact on malaria transmission, as mentioned by many authors [ 64 , 65 ]. Including these factors in our model will be the future quest in order to obtain a better understanding of malaria transmission.…”

Perspectives of vector management in the control and elimination of vector-borne zoonoses

“…Gene drive is another genetic engineering concept that has enjoyed a great push in vector control research following the establishment of CRISPR/Cas9 technology. The CRISPR/Cas9- integrated gene drive method allows the targeted genes to be propagated and inherited much more rapidly than the Mendelian rates, resulting in fast replacement or displacement of the targeted traits in a population ( Leung et al, 2022 ). Recently, this technology has been applied on An.…”