Mathematical Models of Within-Host and Transmission Dynamics to Determine Effects of Malaria Interventions in a Variety of Transmission Settings

Abstract

A model for Anopheles population dynamics and malaria transmission is combined with a within-host dynamics microsolver to study baseline transmission, the effects of seasonality, and the impact of interventions. The Garki Project is recreated in simulation of the pre-intervention baseline and the different combinations of interventions deployed. Modifications are introduced, and longer project duration, extension of dry-season spraying, and transmission-blocking vaccines together achieve local elimination in some conditions. A variety of interventions are simulated in transmission settings that vary in transmission intensity and underlying seasonality. Adding vaccines to existing vector control efforts extends the ability to achieve elimination to higher baseline transmission and less favorable vector behavior. If one species of the Anopheles gambiae species complex feeds disproportionately outdoors for a given complex average behavior, vector control impacts are less than for a single species. Non-zero dry-season transmission limits seasonal oscillation in parasite dynamics and impact of wet-season interventions.

A second chance to tackle African malaria vector mosquitoes that avoid houses and don't take drugs

“…Crucially, none of the simulations of Eckhoff assume any selection-induced change in such behaviors 1 and are therefore consistent with the long-established view 18,[31][32][33]36 that preexisting behavioral preferences or plasticity define the limits of what is possible with IRS or LLINs before a single house is sprayed or a single net distributed. Although the term behavioral resistance has been applied to the zoophagic, exophagic and exophilic habits of such robust vector populations, this may be misleading because physiological resistance to insecticides is defined in terms of altered frequencies of heritable traits:…”

“…As beautifully outlined with the best empirical data [30][31][32] and models 33 available at the end of the GMEP, the simulations presented here by Eckhoff confirm that heterogeneity of vector population behaviors present a diverse set of targets that no single vector control measure can effectively tackle. 1 Recent studies of residual transmission systems where highly endophagic mosquitoes have been effectively tackled by IRS or LLINs remind us that behavioral avoidance of indoor insecticide exposure, by such a naturally evasive species as An. arabiensis, 6,7,34,35 does not necessarily represent failure, or even waning impact, of these measures but rather their inherent limitations from the outset.…”

“…The timely and lucid modeling analysis presented by Phillip Eckhoff in this issue 1 reminds us all that the challenges and opportunities faced by the malaria control community today remain remarkably similar to those of our predecessors who undertook the Global Malaria Eradication Campaign (GMEP). The anti-malarial drugs we use in 2013 are relatively new to the front lines but they are still overwhelmingly used in the same way for reactive clinical management of symptomatic cases.…”

“…As elegantly outlined by Eckhoff, the modest attenuation of LLIN and IRS impact by zoophagic, exophagic, and exophilic primary vectors simply leaves far too high a level of residual transmission for conventional drug or vaccine-based strategies to completely mop up the reservoir of parasite infection. 1 Perhaps the most important issue highlighted by these simulations is the critical importance of dry season transmission in stabilizing populations of falciparum malaria. Most transmission of Plasmodium falciparum malaria occurs in predictable annual peaks during, or soon after, rainy periods.…”

Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics

“…In the present results, we use the epidemiological modeling (EMOD) model (22,23) to simulate the effect on local mosquito populations and malaria transmission of the release of various types of genetically modified mosquitoes. The EMOD model is an individual-based stochastic model with explicit representation of vector populations, larval dynamics, adult feeding behavior, and closed-loop egg laying for one or more distinct local populations.…”