Efficacy Of Vector Control Interventions Research Articles

Multiple Anopheles species complicate downstream analysis and decision-making in a malaria pre-elimination area in southern Mozambique

BackgroundDifferent anopheline species (even within a species group/complex) can differ in their feeding and resting behaviours, which impact both malaria transmission patterns as well as the efficacy of vector control interventions. While morphological identification of sampled specimens is an important first step towards understanding species diversity and abundance, misidentification can result in the implementation of less effective vector control measures, and consequently smaller reductions in the number of local malaria cases. Focusing on southern Mozambique, a malaria pre-elimination area where malaria remains persistent, the aims of this preliminary study were to use molecular identification (CO1 and ITS2 barcoding) to (1) validate the results from the morphological identification (with a particular focus on Anopheles pharoensis and Anopheles squamosus), and (2) have a closer look at the Anopheles coustani group (which includes Anopheles tenebrosus and Anopheles ziemanni).MethodsFemale anopheline mosquitoes (n = 81) were identified morphologically and subsequently sequenced at the ribosomal DNA internal transcribed spacer region 2 (ITS2) and/or cytochrome oxidase subunit 1 (CO1) loci towards species determination.ResultsOut of the 62 specimens that were identified morphologically to species, 4 (6.5%) were misidentified. Regarding the An. coustani group, morphological identification showed that several members are present in southern Mozambique, including An. coustani sensu lato (s.l.), An. ziemanni and An. tenebrosus. However, based on both ITS2 and CO1 sequences, the exact species remains unknown for the latter two members until voucher sequences are available for comparison.ConclusionThe reason(s) for morphological misidentification of anopheline mosquitoes need to be mitigated. This is usually related to both the capacity (i.e. training) of the microscopist to identify anopheline species, and the information provided in the dichotomous identification key. As the An. coustani complex contributes to (residual) malaria transmission in sub-Saharan Africa, it may play a role in the observed persistent malaria in southern Mozambique. A better baseline characterizing of the local anophelines species diversity and behaviours will allow us to improve entomological surveillance strategies, better understand the impact of vector control on each local vector species, and identify new approaches to target those vector species.

Genomic surveillance of Anopheles mosquitoes on the Bijagós Archipelago using custom targeted amplicon sequencing identifies mutations associated with insecticide resistance

BackgroundInsecticide resistance is reducing the efficacy of vector control interventions, consequently threatening efforts to control vector-borne diseases, including malaria. Investigating the prevalence of molecular markers of resistance is a useful tool for monitoring the spread of insecticide resistance in disease vectors. The Bijagós Archipelago (Bijagós) in Guinea-Bissau is a region of stable malaria transmission where insecticide-treated nets are the mainstay for malaria control. However, the prevalence of molecular markers of insecticide resistance in malaria vectors is not well understood.MethodsA total of 214 Anopheles mosquitoes were analysed from 13 islands across the Bijagós. These mosquitoes were collected using CDC light traps in November 2019, during the peak malaria transmission season. High-throughput multiplex amplicon sequencing was used to investigate the prevalence of 17 different molecular markers associated with insecticide resistance in four genes: vgsc, rdl, ace1 and gste2.ResultsOf the 17 screened mutations, four were identified in mosquitoes from the Bijagós: vgsc L995F (12.2%), N1570Y (6.2%) and A1746S (0.7%) and rdl A269G (1.1%). This study is the first to report the L995F knock-down resistance (kdr)-west allele in Anopheles melas on the Archipelago. An additional eight non-synonymous single-nucleotide polymorphisms were identified across the four genes which have not been described previously. The prevalences of the vgsc L995F and N1570Y mutations were higher on Bubaque Island than on the other islands in this study; Bubaque is the most populous island in the archipelago, with the greatest population mobility and connection to continental Guinea-Bissau.ConclusionsThis study provides the first surveillance data for genetic markers present in malaria vectors from islands across the Bijagós Archipelago. Overall prevalence of insecticide resistance mutations was found to be low. However, the identification of the vgsc L995F and N1570Y mutations associated with pyrethroid resistance warrants further monitoring. This is particularly important as the mainstay of malaria control on the islands is the use of pyrethroid insecticide-treated nets.Graphical

An archetypes approach to malaria intervention impact mapping: a new framework and example application

BackgroundAs both mechanistic and geospatial malaria modeling methods become more integrated into malaria policy decisions, there is increasing demand for strategies that combine these two methods. This paper introduces a novel archetypes-based methodology for generating high-resolution intervention impact maps based on mechanistic model simulations. An example configuration of the framework is described and explored.MethodsFirst, dimensionality reduction and clustering techniques were applied to rasterized geospatial environmental and mosquito covariates to find archetypal malaria transmission patterns. Next, mechanistic models were run on a representative site from each archetype to assess intervention impact. Finally, these mechanistic results were reprojected onto each pixel to generate full maps of intervention impact. The example configuration used ERA5 and Malaria Atlas Project covariates, singular value decomposition, k-means clustering, and the Institute for Disease Modeling’s EMOD model to explore a range of three-year malaria interventions primarily focused on vector control and case management.ResultsRainfall, temperature, and mosquito abundance layers were clustered into ten transmission archetypes with distinct properties. Example intervention impact curves and maps highlighted archetype-specific variation in efficacy of vector control interventions. A sensitivity analysis showed that the procedure for selecting representative sites to simulate worked well in all but one archetype.ConclusionThis paper introduces a novel methodology which combines the richness of spatiotemporal mapping with the rigor of mechanistic modeling to create a multi-purpose infrastructure for answering a broad range of important questions in the malaria policy space. It is flexible and adaptable to a range of input covariates, mechanistic models, and mapping strategies and can be adapted to the modelers’ setting of choice.

A systematic review to understand the value of entomological endpoints for assessing the efficacy of vector control interventions

To guide implementation of vector control interventions in Europe, a stronger evidence base of their efficacy and effectiveness is needed. Currently, epidemiological endpoints are used to demonstrate the public health value of a vector control intervention. This systematic literature review aimed to help assess whether entomological endpoints (such as mosquito abundance, infection rates, inoculation rates, parity rate as proxy for longevity, or others) can be used on their own as evidence of efficacy of vector control interventions against vector-borne diseases. We searched electronic bibliographic databases (The Cochrane Library, CAB Abstracts, MEDLINE and Web of Science) for intervention trials where vector control interventions were evaluated and extracted epidemiological and entomological effect size estimates. The selection process resulted in 31 studies (extracted from 35 publications) for which both types of endpoints were available. The final database included studies on malaria (n=16), dengue (n=9), leishmaniasis (n=5) and tick-borne diseases (n=1). Epidemiological and entomological effect sizes often pointed in the same direction (i.e. both favouring intervention or favouring control). However, based on the statistical inference (whether the effect size estimate is significantly different from no-effect) of the results, we observed some disagreement between endpoints, though we rarely saw complete disagreement in effect estimates. This review illustrates the complex relation between entomological and epidemiological endpoints. Based on this review, it is concluded that evaluating interventions on entomological endpoints only is insufficient to understand their potential epidemiological impact. To better asses the value of entomological endpoints for the assessment of efficacy of vector control intervention, there is a need for studies to be powered for both epidemiological and entomological endpoints.

First report on the application of near-infrared spectroscopy to predict the age of Aedes albopictus Skuse

To date, no methodology has been described for predicting the age of Aedes albopictus Skuse mosquitoes, commonly known as Asian tiger mosquitoes. In this study, we report the potential of near-infrared spectroscopy (NIRS) technique for characterizing the age of female laboratory reared Ae. albopictus. Using leave-one-out cross-validation analysis on a training set, laboratory reared mosquitoes preserved in RNAlater for up to a month were assessed at 1, 3, 7, 9, 13, 16, 20 and 25 days post emergence. Mosquitoes (N = 322) were differentiated into two age classes (< or ≥ 7 days) with 93% accuracy, into three age classes (<7, 7–13 and >13 days old) with 76% accuracy, and on a continuous age scale to within ±3 days of their actual average age. Similarly, models predicted mosquitoes (N = 146) excluded from the training model with 94% and 71% accuracy to the two and the three age groups, respectively. We show for the first time that NIRS, with an improved spectrometer and fibre configuration, can be used to predict the age of laboratory reared female Ae. albopictus. Characterization of the age of Ae. albopictus populations is crucial for determining the efficacy of vector control interventions that target their survival.

Human IgG Antibody Response to Aedes Nterm-34kDa Salivary Peptide, an Epidemiological Tool to Assess Vector Control in Chikungunya and Dengue Transmission Area.

BackgroundArboviral diseases are an important public health concerns. Vector control remains the sole strategy to fight against these diseases. Because of the important limits of methods currently used to assess human exposure to Aedes mosquito bites, much effort is being devoted to develop new indicators. Recent studies have reported that human antibody (Ab) responses to Aedes aegypti Nterm-34kDa salivary peptide represent a promising biomarker tool to evaluate the human-Aedes contact. The present study aims investigate whether such biomarker could be used for assessing the efficacy of vector control against Aedes.Methodology/Principal findingsSpecific human IgG response to the Nterm-34kDa peptide was assessed from 102 individuals living in urban area of Saint-Denis at La Reunion Island, Indian Ocean, before and after the implementation of vector control against Aedes mosquitoes. IgG response decreased after 2 weeks (P < 0.0001), and remained low for 4 weeks post-intervention (P = 0.0002). The specific IgG decrease was associated with the decline of Aedes mosquito density, as estimated by entomological parameters and closely correlated to vector control implementation and was not associated with the use of individual protection, daily commuting outside of the house, sex and age. Our findings indicate a probable short-term decrease of human exposure to Aedes bites just after vector control implementation.Conclusion/SignificanceResults provided in the present study indicate that IgG Ab response to Aedes aegypti Nterm-34kDa salivary peptide could be a relevant short-time indicator for evaluating the efficacy of vector control interventions against Aedes species.

Dynamics of pyrethroid resistance in malaria vectors in southern Benin following a large scale implementation of vector control interventions.

BackgroundLarge-scale implementation of Indoor Residual Spraying and Insecticide Treated Nets has been implemented in Plateau Department, Benin between 2011 and 2014. The purpose of this study was to monitor the frequency and mechanisms of pyrethroid resistance in malaria vectors following the implementation of vector control tools for malaria prevention.MethodsAnopheles larvae were collected in 13 villages twice a year from 2012 to 2014. WHO tube tests were used to assess the phenotypic resistance of each population to 0.05 % deltamethrin. Sibling species within Anopheles gambiae complex were identified by PCR techniques. Taqman and biochemical assays were performed to identify the presence of kdr mutations in individual mosquitoes and to detect any increase in the activity of enzymes putatively involved in insecticide metabolism (oxidases, esterase and glutathione-S-transferases). Quantitative real time PCR was used to measure the expression of three metabolic genes involved in pyrethroid resistance (CYP6P3, CYP6M2 and GSTD3).ResultsAnopheles populations showed < 90 % mortality to deltamethrin in all villages and at all time points. The 1014 F kdr allele frequency was close to fixation (> 0.9) over the sampling periods in both An. gambiae and An. coluzzii. Biochemical assays showed higher activities of alpha esterase and GST in field malaria vector populations compared to susceptible mosquitoes. qPCR assays showed a significant increase of CYP6P3, CYP6M2 GSTD3 expression in An. gambiae after a three-year implementation of LLINs.ConclusionThe study confirmed that deltamethrin resistance is widespread in malaria vectors in Southern Benin. We suspect that the increase in deltamethrin resistance between 2012 and 2014 resulted from an increased expression of metabolic detoxification genes (CYP6M2 and CYP6P3) rather than from kdr mutations. It is urgent to evaluate further the impact of metabolic resistance on the efficacy of vector control interventions using pyrethroid insecticides.

Status of insecticide resistance in high-risk malaria provinces in Afghanistan.

BackgroundInsecticide resistance seriously threatens the efficacy of vector control interventions in malaria endemic countries. In Afghanistan, the status of insecticide resistance is largely unknown while distribution of long-lasting insecticidal nets has intensified in recent years. The main objective of this study was thus to measure the level of resistance to four classes of insecticides in provinces with medium to high risk of malaria transmission.MethodsAdult female mosquitoes were reared from larvae successively collected in the provinces of Nangarhar, Kunar, Badakhshan, Ghazni and Laghman from August to October 2014. WHO insecticide susceptibility tests were performed with DDT (4 %), malathion (5 %), bendiocarb (0.1 %), permethrin (0.75 %) and deltamethrin (0.05 %). In addition, the presence of kdr mutations was investigated in deltamethrin resistant and susceptible Anopheles stephensi mosquitoes collected in the eastern provinces of Nangarhar and Kunar.ResultsAnalyses of mortality rates revealed emerging resistance against all four classes of insecticides in the provinces located east and south of the Hindu Kush mountain range. Resistance is observed in both An. stephensi and Anopheles culicifacies, the two dominant malaria vectors in these provinces. Anopheles superpictus in the northern province of Badakhshan shows a different pattern of susceptibility with suspected resistance observed only for deltamethrin and bendiocarb. Genotype analysis of knock down resistance (kdr) mutations at the voltage-gated channel gene from An. stephensi mosquitoes shows the presence of the known resistant alleles L1014S and L1014F. However, a significant fraction of deltamethrin-resistant mosquitoes were homozygous for the 1014L wild type allele indicating that other mechanisms must be considered to account for the observed pyrethroid resistance.ConclusionsThis study confirms the importance of monitoring insecticide resistance for the development of an integrated vector management in Afghanistan. The validation of the kdr genotyping PCR assay applied to An. stephensi collected in Afghanistan paves the way for further studies into the mechanisms of insecticide resistance of malaria vectors in this region.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1149-1) contains supplementary material, which is available to authorized users.

The Anopheles gambiae cE5 salivary protein: a sensitive biomarker to evaluate the efficacy of insecticide-treated nets in malaria vector control

Evaluation of vector control is crucial for improving malaria containment and, according to World Health Organization, new complementary indicators would be very valuable. In this study the IgG response to the Anopheles-specific cE5 salivary protein was tested as a tool to evaluate the efficacy of insecticide-treated nets in reducing human exposure to malaria vectors. Sera collected during a longitudinal study carried out in Angola, and including entomological and parasitological data, were used to assess the IgG response to the Anopheles gambiae cE5 in both children and adults, before and after the application of insecticide-treated nets. Seasonal fluctuation of specific IgG antibody levels according to exposure was only found in children (up to ≈14 years old) whose anti-cE5 IgG response dropped after bed nets installation. These results were fully consistent with previous findings obtained with the same set of sera and indicating a substantial reduction of human-vector contact shortly after nets implementation. Overall, children IgG response to the cE5 protein appeared a very sensitive biomarker, which allowed for the detection of even weak exposure to Anopheles bites, indicating it may represent a reliable additional tool to evaluate the efficacy of vector control interventions.

Biochemical and molecular analyses to determine pyrethroid resistance in Aedes aegypti

Dengue fever is an important mosquito-borne viral disease in Taiwan. Insecticide resistance has been shown to significantly reduce the efficacy of vector control interventions. The detection of insecticide resistance is an important component in mosquito abatement programs. In this study, we used the insecticide-impregnated papers bioassay method to reveal high levels of resistance to permethrin in the LYPR and field strains of Aedes aegypti. We used the standard glass cylinder method to observe the knockdown effect of paralysis within 2 to 4 minutes after exposing mosquitoes to pyrethroid vapors. Biochemical assays showed elevated detoxification enzyme activities. Glutathione S-transferases, monooxygenases and β-esterases were the enzymes predominantly responsible for the permethrin resistance of Ae. aegypti in Taiwan. Molecular screening for common insecticide target-site mutations revealed the presence of V1023G and D1794Y mutations. Pearson’s correlation analysis was used to investigate the correlations between the allelic frequency of kdr mutation associated increase with the LC50 values of permethrin and the KT50 values of pyrethroid vaporizers. These findings will be used to assess resistance levels, estimate resistance potential, and formulate monitoring and resistance management strategies.

Determining Airborne Concentrations of Spatial Repellent Chemicals in Mosquito Behavior Assay Systems

BackgroundMosquito behavior assays have been used to evaluate the efficacy of vector control interventions to include spatial repellents (SR). Current analytical methods are not optimized to determine short duration concentrations of SR active ingredients (AI) in air spaces during entomological evaluations. The aim of this study was to expand on our previous research to further validate a novel air sampling method to detect and quantitate airborne concentrations of a SR under laboratory and field conditions.Methodology/Principal FindingsA thermal desorption (TD) gas chromatography-mass spectrometry (GC-MS) method was used to determine the amount of dichlorodiphenyltrichloroethane (DDT) in samples of air. During laboratory experiments, 1 L volumes of air were collected over 10 min intervals from a three-chamber mosquito behavior assay system. Significantly higher levels of airborne DDT were measured in the chamber containing textiles treated with DDT compared to chambers free of AI. In the field, 57 samples of air were collected from experimental huts with and without DDT for onsite analysis. Airborne DDT was detected in samples collected from treated huts. The mean DDT air concentrations in these two huts over a period of four days with variable ambient temperature were 0.74 µg/m3 (n = 17; SD = 0.45) and 1.42 µg/m3 (n = 30; SD = 0.96).Conclusions/SignificanceThe results from laboratory experiments confirmed that significantly different DDT exposure conditions existed in the three-chamber system establishing a chemical gradient to evaluate mosquito deterrency. The TD GC-MS method addresses a need to measure short-term (<1 h) SR concentrations in small volume (<100 L) samples of air and should be considered for standard evaluation of airborne AI levels in mosquito behavior assay systems. Future studies include the use of TD GC-MS to measure other semi-volatile vector control compounds.

First Attempt To Validate Human IgG Antibody Response to Nterm-34kDa Salivary Peptide as Biomarker for Evaluating Exposure to Aedes aegypti Bites

BackgroundMuch effort is being devoted for developing new indicators to evaluate the human exposure to Aedes mosquito bites and the risk of arbovirus transmission. Human antibody (Ab) responses to mosquito salivary components could represent a promising tool for evaluating the human-vector contact.Methodology/Principal findingsTo develop a specific biomarker of human exposure to Aedes aegypti bites, we measured IgG Ab response to Ae. aegypti Nterm-34 kDa salivary peptide in exposed children in 7 villages of Southern Benin (West Africa). Results showed that specific IgG response presented high inter-individual heterogeneity between villages. IgG response was associated with rainfall and IgG level increased from dry (low exposure) to rainy (high exposure) seasons. These findings indicate that IgG Ab to Nterm-34 kDa salivary peptide may represent a reliable biomarker to detect variation in human exposure to Ae. aegypti bites.Conclusion/SignificanceThis preliminary study highlights the potential use of Ab response to this salivary peptide for evaluating human exposure to Ae. aegypti. This biomarker could represent a new promising tool for assessing the risk of arbovirus transmission and for evaluating the efficacy of vector control interventions.

Insecticide resistance in the dengue vector Aedes aegypti from Martinique: distribution, mechanisms and relations with environmental factors.

Dengue is an important mosquito borne viral disease in Martinique Island (French West Indies). The viruses responsible for dengue are transmitted by Aedes aegypti, an indoor day-biting mosquito. The most effective proven method for disease prevention has been by vector control by various chemical or biological means. Unfortunately insecticide resistance has already been observed on the Island and recently showed to significantly reduce the efficacy of vector control interventions. In this study, we investigated the distribution of resistance and the underlying mechanisms in nine Ae. aegypti populations. Statistical multifactorial approach was used to investigate the correlations between insecticide resistance levels, associated mechanisms and environmental factors characterizing the mosquito populations. Bioassays revealed high levels of resistance to temephos and deltamethrin and susceptibility to Bti in the 9 populations tested. Biochemical assays showed elevated detoxification enzyme activities of monooxygenases, carboxylesterases and glutathione S-tranferases in most of the populations. Molecular screening for common insecticide target-site mutations, revealed the presence of the “knock-down resistance” V1016I Kdr mutation at high frequency (>87%). Real time quantitative RT-PCR showed the potential involvement of several candidate detoxification genes in insecticide resistance. Principal Component Analysis (PCA) performed with variables characterizing Ae. aegypti from Martinique permitted to underline potential links existing between resistance distribution and other variables such as agriculture practices, vector control interventions and urbanization. Insecticide resistance is widespread but not homogeneously distributed across Martinique. The influence of environmental and operational factors on the evolution of the resistance and mechanisms are discussed.