Dataset Information

Mutations Linked to Insecticide Resistance Not Detected in the Ace-1 or VGSC Genes in Nyssorhynchus darlingi from Multiple Localities in Amazonian Brazil and Peru.

ABSTRACT: Indoor residual spray (IRS), mainly employing pyrethroid insecticides, is the most common intervention for preventing malaria transmission in many regions of Latin America; the use of long-lasting insecticidal nets (LLINs) has been more limited. Knockdown resistance (kdr) is a well-characterized target-site resistance mechanism associated with pyrethroid and DDT resistance. Most mutations detected in acetylcholinesterase-1 (Ace-1) and voltage-gated sodium channel (VGSC) genes are non-synonymous, resulting in a change in amino acid, leading to the non-binding of the insecticide. In the present study, we analyzed target-site resistance in Nyssorhynchus darlingi, the primary malaria vector in the Amazon, in multiple malaria endemic localities. We screened 988 wild-caught specimens of Ny. darlingi from three localities in Amazonian Peru and four in Amazonian Brazil. Collections were conducted between 2014 and 2021. The criteria were Amazonian localities with a recent history as malaria hotspots, primary transmission by Ny. darlingi, and the use of both IRS and LLINs as interventions. Fragments of Ace-1 (456 bp) and VGSC (228 bp) were amplified, sequenced, and aligned with Ny. darlingi sequences available in GenBank. We detected only synonymous mutations in the frequently reported Ace-1 codon 280 known to confer resistance to organophosphates and carbamates, but detected three non-synonymous mutations in other regions of the gene. Similarly, no mutations linked to insecticide resistance were detected in the frequently reported codon (995) at the S6 segment of domain II of VGSC. The lack of genotypic detection of insecticide resistance mutations by sequencing the Ace-1 and VGSC genes from multiple Ny. darlingi populations in Brazil and Peru could be associated with low-intensity resistance, or possibly the main resistance mechanism is metabolic.

SUBMITTER: Bickersmith SA

PROVIDER: S-EPMC10606710 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Mutations Linked to Insecticide Resistance Not Detected in the Ace-1 or VGSC Genes in Nyssorhynchus darlingi from Multiple Localities in Amazonian Brazil and Peru.

Bickersmith Sara A SA Jurczynski John D JD Sallum Maria Anice Mureb MAM Chaves Leonardo S M LSM Bergo Eduardo S ES Rodriguez Gloria A D GAD Morante Clara A CA Rios Carlos T CT Saavedra Marlon P MP Alava Freddy F Gamboa Dionicia D Vinetz Joseph M JM Conn Jan E JE

Genes 20230929 10

Indoor residual spray (IRS), mainly employing pyrethroid insecticides, is the most common intervention for preventing malaria transmission in many regions of Latin America; the use of long-lasting insecticidal nets (LLINs) has been more limited. Knockdown resistance (kdr) is a well-characterized target-site resistance mechanism associated with pyrethroid and DDT resistance. Most mutations detected in acetylcholinesterase-1 (Ace-1) and voltage-gated sodium channel (VGSC) gene ...[more]

PMID: 37895241

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Project description:BackgroundBrazilian malaria control programmes successfully reduced the incidence and mortality rates from 2005 to 2016. Since 2017, increased malaria has been reported across the Amazon. Few field studies focus on the primary malaria vector in high to moderate endemic areas, Nyssorhynchus darlingi, as the key entomological component of malaria risk, and on the metrics of Plasmodium vivax propagation in Amazonian rural communities.MethodsHuman landing catch collections were carried out in 36 houses of 26 communities in five municipalities in the Brazilian states of Acre, Amazonas and Rondônia states, with API (> 30). In addition, data on the number of locally acquired symptomatic infections were employed in mathematical modelling analyses carried out to determine Ny. darlingi vector competence and vectorial capacity to P. vivax; and to calculate the basic reproduction number for P. vivax.ResultsEntomological indices and malaria metrics ranged among localities: prevalence of P. vivax infection in Ny. darlingi, from 0.243% in Mâncio Lima, Acre to 3.96% in Machadinho D'Oeste, Rondônia; daily human-biting rate per person from 23 ± 1.18 in Cruzeiro do Sul, Acre, to 66 ± 2.41 in Lábrea, Amazonas; vector competence from 0.00456 in São Gabriel da Cachoeira, Amazonas to 0.04764 in Mâncio Lima, Acre; vectorial capacity from 0.0836 in Mâncio Lima, to 1.5 in Machadinho D'Oeste. The estimated R0 for P. vivax (PvR0) was 3.3 in Mâncio Lima, 7.0 in Lábrea, 16.8 in Cruzeiro do Sul, 55.5 in São Gabriel da Cachoeira, and 58.7 in Machadinho D'Oeste. Correlation between P. vivax prevalence in Ny. darlingi and vector competence was non-linear whereas association between prevalence of P. vivax in mosquitoes, vectorial capacity and R0 was linear and positive.ConclusionsIn spite of low vector competence of Ny. darlingi to P. vivax, parasite propagation in the human population is enhanced by the high human-biting rate, and relatively high vectorial capacity. The high PvR0 values suggest hyperendemicity in Machadinho D'Oeste and São Gabriel da Cachoeira at levels similar to those found for P. falciparum in sub-Saharan Africa regions. Mass screening for parasite reservoirs, effective anti-malarial drugs and vector control interventions will be necessary to shrinking transmission in Amazonian rural communities, Brazil.

Project description:BackgroundIn Loreto Department, Peru, a successful 2005-2010 malaria control programme (known as PAMAFRO) included massive distribution of long-lasting insecticidal nets (LLINs). Additional local distribution of LLINs occurred in individual villages, but not between 2012 and 2015. A 2011-2012 study of the primary regional malaria vector Anopheles darlingi detected a trend of increased exophagy compared with pre-PAMAFRO behaviour. For the present study, An. darlingi were collected in three villages in Loreto in 2013-2015 to test two hypotheses: (1) that between LLIN distributions, An. darlingi reverted to pre-intervention biting behaviour; and, (2) that there are separate sub-populations of An. darlingi in Loreto with distinct biting behaviour.ResultsIn 2013-2015 An. darlingi were collected by human landing catch during the rainy and dry seasons in the villages of Lupuna and Cahuide. The abundance of An. darlingi varied substantially across years, villages and time periods, and there was a twofold decrease in the ratio of exophagic:endophagic An. darlingi over the study period. Unexpectedly, there was evidence of a rainy season population decline in An. darlingi. Plasmodium-infected An. darlingi were detected indoors and outdoors throughout the night, and the monthly An. darlingi human biting rate was correlated with the number of malaria cases. Using nextRAD genotyping-by-sequencing, 162 exophagic and endophagic An. darlingi collected at different times during the night were genotyped at 1021 loci. Based on model-based and non-model-based analyses, all genotyped An. darlingi belonged to a homogeneous population, with no evidence for genetic differentiation by biting location or time.ConclusionsThis study identified a decreasing proportion of exophagic An. darlingi in two villages in the years between LLIN distributions. As there was no evidence for genetic differentiation between endophagic and exophagic An. darlingi, this shift in biting behaviour may be the result of behavioural plasticity in An. darlingi, which shifted towards increased exophagy due to repellence by insecticides used to impregnate LLINs and subsequently reverted to increased endophagy as the nets aged. This study highlights the need to target vector control interventions to the biting behaviour of local vectors, which, like malaria risk, shows high temporal and spatial heterogeneity.

Dataset Information

Mutations Linked to Insecticide Resistance Not Detected in the Ace-1 or VGSC Genes in Nyssorhynchus darlingi from Multiple Localities in Amazonian Brazil and Peru.

Publications

Mutations Linked to Insecticide Resistance Not Detected in the <i>Ace-1</i> or <i>VGSC</i> Genes in <i>Nyssorhynchus darlingi</i> from Multiple Localities in Amazonian Brazil and Peru.

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