Infection of anopheline mosquitoes with Wolbachia: Implications for malaria control

Gomes, Fabio M.; Barillas‐Mury, Carolina

doi:10.1371/journal.ppat.1007333

“…gambiae s.l. are either low intensity and have low efficiency of vertical transmission 12 , or are artefacts produced by contamination 13 . Being intracellular and maternally inherited, many microsporidians have a similar lifestyle to Wolbachia.…”

mentioning

confidence: 99%

A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes

Herren

¹

,

Mbaisi

²

,

Mararo

³

et al. 2020

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A possible malaria control approach involves the dissemination in mosquitoes of inherited symbiotic microbes to block Plasmodium transmission. However, in the Anopheles gambiae complex, the primary African vectors of malaria, there are limited reports of inherited symbionts that impair transmission. We show that a vertically transmitted microsporidian symbiont (Microsporidia MB) in the An. gambiae complex can impair Plasmodium transmission. Microsporidia MB is present at moderate prevalence in geographically dispersed populations of An. arabiensis in Kenya, localized to the mosquito midgut and ovaries, and is not associated with significant reductions in adult host fecundity or survival. Field-collected Microsporidia MB infected An. arabiensis tested negative for P. falciparum gametocytes and, on experimental infection with P. falciparum, sporozoites aren't detected in Microsporidia MB infected mosquitoes. As a microbe that impairs Plasmodium transmission that is non-virulent and vertically transmitted, Microsporidia MB could be investigated as a strategy to limit malaria transmission.

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“…This diploid genome can account for up to 10 different loci or genes with up to 8 different alleles per gene. Four bits are reserved to code for the presence of microbial interventions such as Wolbachia [ 40 ] or other biological insecticides such as Metarhizium [ 41 ] ( S1 Fig ). Microbial interventions are not explored in this article but the modeling of Wolbachia and cytoplasmic incompatibility within EMOD has been covered in previous work [ 38 ].…”

Section: Methodsmentioning

confidence: 99%

Vector genetics, insecticide resistance and gene drives: An agent-based modeling approach to evaluate malaria transmission and elimination

Selvaraj

¹

,

Wenger

²

,

Bridenbecker

³

et al. 2020

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Vector control has been a key component in the fight against malaria for decades, and chemical insecticides are critical to the success of vector control programs worldwide. However, increasing resistance to insecticides threatens to undermine these efforts. Understanding the evolution and propagation of resistance is thus imperative to mitigating loss of intervention effectiveness. Additionally, accelerated research and development of new tools that can be deployed alongside existing vector control strategies is key to eradicating malaria in the near future. Methods such as gene drives that aim to genetically modify large mosquito populations in the wild to either render them refractory to malaria or impair their reproduction may prove invaluable tools. Mathematical models of gene flow in populations, which is the transfer of genetic information from one population to another through migration, can offer invaluable insight into the behavior and potential impact of gene drives as well as the spread of insecticide resistance in the wild. Here, we present the first multi-locus, agent-based model of vector genetics that accounts for mutations and a many-to-many mapping cardinality of genotypes to phenotypes to investigate gene flow, and the propagation of gene drives in Anopheline populations. This model is embedded within a large scale individual-based model of malaria transmission representative of a high burden, high transmission setting characteristic of the Sahel. Results are presented for the selection of insecticide-resistant vectors and the spread of resistance through repeated deployment of insecticide treated nets (ITNs), in addition to scenarios where gene drives act in concert with existing vector control tools such as ITNs. The roles of seasonality, spatial distribution of vector habitat and feed sites, and existing vector control in propagating alleles that confer phenotypic traits via gene drives that result in reduced transmission are explored. The ability to model a spectrum of vector species with different genotypes and phenotypes in the context of malaria transmission allows us to test deployment strategies for existing interventions that reduce the deleterious effects of resistance and allows exploration of the impact of new tools being proposed or developed.

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“…A gene 33 drive system based on preferential inheritance can result in an entire population 34 acquiring an engineered genetic trait and a desired effect within a few generations [16]. 35 Gene drive methods for the purposes of vector control broadly fall under two categories: 36 first, modifying a population to make it refractory to malaria, a practice referred to as 37 population replacement [17], and second, restricting the population of a specific 38 subspecies, which is referred to as population suppression [18]. James et al [19], and 39 Hammond and Galizi [20] provide an overview of different gene drive strategies being 40 currently considered or developed.…”

Section: Introductionmentioning

confidence: 99%

“…This diploid genome can 83 account for up to 10 different loci or genes with up to 8 different alleles per gene. Two 84 bits are reserved to code for the presence of either Wolbachia [36] or other biological 85 insecticides such as Metarhizium [37] (supplementary figure S1). When mating occurs 86 in the model, the male and female produce offspring with a combination of genes and 87 alleles obtained from the gametes of the parents via Mendelian inheritance (Fig 1).…”

mentioning

confidence: 99%

Vector genetics, insecticide resistance and gene drives: an agent-based modeling approach to evaluate malaria transmission and elimination

Selvaraj

¹

,

Wenger

²

,

Bridenbecker

³

et al. 2020

Preprint

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Vector control has been a key component in the fight against malaria for decades, and chemical insecticides are critical to the success of vector control programs worldwide. However, increasing resistance to insecticides threatens to undermine these efforts. Understanding the evolution and propagation of resistance is thus imperative to mitigating loss of intervention effectiveness. Additionally, accelerated research and development of new tools that can be deployed alongside existing vector control strategies is key to eradicating malaria in the near future. Methods such as gene drives that aim to genetically modify large mosquito populations in the wild to either render them refractory to malaria or impair their reproduction may prove invaluable tools. Mathematical models of gene flow in populations, which is the transfer of genetic information from one population to another through migration, can offer invaluable insight into the behavior and potential impact of gene drives as well as the spread of insecticide resistance in the wild. Here, we present the first multi-locus, agent-based model of vector genetics that accounts for mutations and a many-to-many mapping cardinality of genotypes to phenotypes to investigate gene flow, and the propagation of gene drives in Anopheline populations. This model is embedded within a large scale individual-based model of malaria transmission representative of a high burden, high transmission setting characteristic of the Sahel. Results are presented for the selection of insecticide-resistant vectors and the spread of resistance through repeated deployment of insecticide treated nets (ITNs), in addition to scenarios where gene drives act in concert with existing vector control tools such as ITNs. The roles of seasonality, spatial distribution of vector habitat and feed sites, and existing vector control in propagating alleles that confer phenotypic traits via gene drives that result in reduced transmission are explored. The ability to model a spectrum of vector species with different genotypes and phenotypes in the context of malaria transmission allows us to test deployment strategies for existing interventions that reduce the deleterious effects of resistance and allows exploration of the impact of new tools being proposed or developed.Author summaryVector control interventions are essential to the success of global malaria control and elimination efforts but increasing insecticide resistance worldwide threatens to derail these efforts. Releasing genetically modified mosquitoes that use gene drives to pass on desired genes and their associated phenotypic traits to the entire population within a few generations has been proposed to address resistance and other issues such as transmission heterogeneity that can sustain malaria transmission indefinitely. While the ethics and safety of these methods are being debated, mathematical models offer an efficient way of predicting the behavior and estimating the efficacy of these interventions if deployed to specific regions facing challenges to reaching elimination. We have developed a detailed mathematical model of vector genetics where specific genomes code for physical attributes that influence transmission and are affected by the surrounding environment. This is the first model to incorporate an individual-based multi-locus genetic model into a detailed individual-based model of malaria transmission. This model opens the door to investigate a number of subtle but important questions such as the effects of small numbers of mosquitoes in a region sustaining malaria transmission during the low transmission season, and the success of gene drives in regions where extant vector control interventions could kill off gene drive mosquitoes before establishment. Here, we investigate the reduced efficacy of current vector control measures in the presence of insecticide resistance and evaluate the likelihood of achieving local malaria elimination using gene drive mosquitoes released into a high transmission setting alongside other vector control measures.

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Infection of anopheline mosquitoes with Wolbachia: Implications for malaria control

Cited by 22 publications

References 37 publications

A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes

A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes

Vector genetics, insecticide resistance and gene drives: An agent-based modeling approach to evaluate malaria transmission and elimination

Vector genetics, insecticide resistance and gene drives: an agent-based modeling approach to evaluate malaria transmission and elimination

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