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Analyzing Uncertainties Around Gene Drives: A Case Study of Mosquitos in Sub-Saharan Africa

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Malaria is a disease that has plagued human populations throughout history. Malaria is cause by the parasite Plasmodium, which uses mosquitoes as a vector for transfer. Current methods for controlling malaria include issuing bed nets to citizens, spraying home with

Malaria is a disease that has plagued human populations throughout history. Malaria is cause by the parasite Plasmodium, which uses mosquitoes as a vector for transfer. Current methods for controlling malaria include issuing bed nets to citizens, spraying home with insecticides, and reactive medical care. However, using Clustered Regularly Interspaced Short Palindromic repeats (CRISPR) in conjunction with the Cas9 protein found in bacteria, the genomes of mosquitoes can be edited to remove the ability of mosquitoes to host Plasmodium or to create sex bias in which the birth rate of males is increased so as to make reproduction near impossible. Using CRISPR, this genome edit can be ‘driven’ through a population by increasing the likelihood of that gene being passed onto subsequent generations until the entire population possesses that gene; a gene drive can theoretically be used to eliminate malaria around the world. This paper identifies uncertainties concerning scientific, environmental, governance, economic ,and social aspects of researching and implementing gene drives and makes recommendations concerning these areas for the emerging technology of gene drives concerning the eradication of malaria using Sub-Saharan Africa as a case study

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2017-05

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Plasmodium Cost of Resistance and Life Stage Development within the Mosquito Vector

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Hundreds of thousands of people die annually from malaria; a protozoan of the genus Plasmodium is responsible for this mortality. The Plasmodium parasite undergoes several life stages within the mosquito vector, the transition between which require passage across the lumen

Hundreds of thousands of people die annually from malaria; a protozoan of the genus Plasmodium is responsible for this mortality. The Plasmodium parasite undergoes several life stages within the mosquito vector, the transition between which require passage across the lumen of the mosquito midgut. It has been observed that in about 15% of parasites that develop ookinetes in the mosquito abdomen, sporozoites never develop in the salivary glands, indicating that passage across the midgut lumen is a significant barrier in parasite development (Gamage-Mendis et al., 1993). We aim to investigate a possible correlation between passage through the midgut lumen and drug-resistance trends in Plasmodium falciparum parasites. This study contains a total of 1024 Anopheles mosquitoes: 187 Anopheles gambiae and 837 Anopheles funestus samples collected in high malaria transmission areas of Mozambique between March and June of 2016. Sanger sequencing will be used to determine the prevalence of known resistance alleles for anti-malarial drugs: chloroquine resistance transporter (pfcrt), multidrug resistance (pfmdr1) gene, dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr). We compare prevalence of resistance between abdomen and head/thorax in order to determine whether drug resistant parasites are disproportionately hindered during their passage through the midgut lumen. A statistically significant difference between resistance alleles in the two studied body sections supports the efficacy of new anti-malarial gene surveillance strategies in areas of high malaria transmission.

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2021-05