Pyrethroid Resistance Research Articles

Myzus persicae (Sulzer, 1776) (Hemiptera: Aphididae) popülasyonlarında neonikotinoid ve sentetik piretroid insektisitlerin tekli ve karışımlarına karşı direnç durumu

The peach potato aphid, Myzus persicae (Sulzer, 1776) (Hemiptera: Aphididae), a vector of many plant virus diseases, causes damage to its wide range of hosts by direct feeding. Chemical control has been the primary method to control this species, and the intensive use of insecticides has led to the development of resistance. In this study, conducted between the years 2017-2019, firstly resistance ratio of five M. persicae populations from Antalya, Türkiye were determined by leaf-dip bioassay method. The field populations showed significant resistance to thiamethoxam (between 201-332 fold) and lambda-cyhalothrin (between 50-103 fold) when compared to susceptible population. To identify whether resistance mediated by mutations in sodium channel and nicotinic acetylcholine receptor, DNA regions that encompass “mutation hot-spot” were sequenced. This revealed no population contained R81T mutation that has been previously linked with neonicotinoid resistance. As to synthetic pyrethroid resistance, the L1014F kdr mutation was fixed in all field populations. This study is the first description of kdr mutation in M. persicae populations from Türkiye. Bioassay results also indicated that the toxicity of thiamethoxam and lambda-cyhalothrin mixture was higher than that of lambda-cyhalothrin alone. Our findings can make significant contributions to M. persicae resistance management.

Inference of selection pressures that drive insecticide resistance in Anopheles and Culex mosquitoes in Korea

Pyrethroids are primarily used for mosquito control in Korea. However, high frequencies of mutations conferring resistance to not only pyrethroids but also to other insecticides have been found in mosquito populations. This study aimed to examine the hypothesis that insecticides used outside of public health may play a role in selection. Briefly, the resistance mutation frequencies to three insecticide groups (pyrethroids, organophosphates, and cyclodienes) were estimated in two representative groups of mosquito species (Anopheles Hyrcanus Group and Culex pipiens complex). The relationship between these frequencies and the land-use status of the collection sites was investigated through multiple regression analysis. In the Anopheles Hyrcanus Group, the frequencies of both ace1 (organophosphate resistance) and rdl (cyclodiene resistance) mutations were positively correlated with ‘proximity to golf course’, possibly be due to the insecticides used for turf maintenance. They also showed positive correlations with field area and rice paddy area, respectively, suggesting the role of agricultural insecticides in the selection of these resistance traits. For the Cx. pipiens complex, the kdr (pyrethroid resistance), ace1, and rdl mutations were positively correlated with the residential area, field, and rice paddy, respectively. Therefore, pyrethroids used for public health could serve as a direct source of resistance selection pressure against kdr, whereas non-public health insecticides may pose primary selection pressure against the ace1 and rdl traits. The current findings suggest that the insecticides used in agriculture and the golf industry play a significant role in mosquito selection, despite variations in the extent of indirect selection pressure according to the mosquito groups and insecticide classes.

Protocol for a cluster randomised placebo-controlled trial of adjunctive ivermectin mass drug administration for malaria control on the Bijagós Archipelago of Guinea-Bissau: the MATAMAL trial

IntroductionAs malaria declines, innovative tools are required to further reduce transmission and achieve elimination. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) is capable of reducing malaria transmission where...

Phenotypic resistance to pyrethroid associated to metabolic mechanism in Vgsc-L995F-resistant Anopheles gambiae malaria mosquitoes.

Background: The indiscriminate use of insecticides in agriculture and public health lead to a selection of resistance mechanisms in malaria vectors compromising vector control tools and strategies. This study investigated the metabolic response in the Vgsc-L995F Anopheles gambiae Tiassalé resistance strain after long-term exposure of larvae and adults to deltamethrin insecticide. Methods: Vgsc-L995F An. gambiae Tiassalé strain larvae were exposed over 20 generations to deltamethrin (LS) and adults to PermaNet 2.0 (AS) and combining exposure at larvae and adult stages (LAS) and compared to unexposed (NS) group. All four groups were subjected to the standard World Health Organization (WHO) susceptibility tube tests using deltamethrin (0.05%), bendiocarb (0.1%) and malathion (5%). Vgsc-L995F/S knockdown-resistance ( kdr) mutation frequency was screened using multiplex assays based on Taqman real-time polymerase chain reaction (PCR) method. Additionally, expression levels of detoxification enzymes associated to pyrethroid resistance, including CYP4G16, CYP6M2, CYP6P1, CYP6P3, CYP6P4, CYP6Z1 and CYP9K1, and glutathione S-transferase GSTe2 were measured. Results: Our results indicated that deltamethrin resistance was a response to insecticide selection pressure in LS, AS and LAS groups, while susceptibility was observed in NS group. The vectors showed varied mortality rates with bendiocarb and full susceptibility to malathion throughout the selection with LS, AS and LAS groups. Vgsc-L995F mutation stayed at high allelic frequency level in all groups with a frequency between 87% and 100%. Among the overexpressed genes, CYP6P4 gene was the most overexpressed in LS, AS and LAS groups. Conclusion: Long-term exposure of larvae and adults of Vgsc-L995F resistant- An. gambiae Tiassalé strain to deltamethrin and PermaNet 2.0 net induced resistance to deltamethrin under a significant effect of cytochromes P450 detoxification enzymes. These outcomes highlight the necessity of investigating metabolic resistance mechanisms in the target population and not solely kdr resistance mechanisms prior the implementation of vector control strategies for a better impact.

Insecticide resistance and its potential mechanisms in field-collected German cockroaches (Blattodea: Ectobiidae) from Thailand.

We investigated insecticide resistance profiles of field populations of the German cockroach, Blattella germanica (L.), collected from central regions of Thailand. Seven strains (PW, RB, MTH, MTS, TL, AY, and SP) were evaluated with diagnostic doses (DD; 3 × LD95 generated from a susceptible strain) of deltamethrin, fipronil, and imidacloprid using topical assays and compared with a susceptible strain (DMSC). Results showed fipronil (2-27% mortality), deltamethrin (16-58% mortality), and imidacloprid (15-75% mortality) resistance in the field strains. Synergism studies with piperonyl butoxide (PBO) and S,S,S-tributyl phosphorotrithioate (DEF) in combination with the DD of insecticides significantly increased (P < 0.05) mortality of the test insects of the field strains suggesting the involvement of P450 monooxygenase and esterase pathways of detoxification. Gel bait evaluations demonstrated that all field-collected strains were resistant to Maxforce Forte (0.05% fipronil), Maxforce Fusion (2.15% imidacloprid), and Advion Cockroach Gel Bait (0.6% indoxacarb) with mean survival times ranging from 1.87-8.27, 1.77-11.72, and 1.19-3.56 days, respectively. Molecular detection revealed that the Rdl mutation was completely homozygous in all field-collected strains except in the PW strain. Field-collected strains were screened for 3 voltage-gated sodium channel (VGSC) mutations associated with pyrethroid resistance. The L993F mutation was present in 5 strains, but no C764R and E434K mutations were detected.

Toward Overcoming Pyrethroid Resistance in Mosquito Control: The Role of Sodium Channel Blocker Insecticides.

Diseases spread by mosquitoes lead to the death of 700,000 people each year. The main way to reduce transmission is vector control by biting prevention with chemicals. However, the most commonly used insecticides lose efficacy due to the growing resistance. Voltage-gated sodium channels (VGSCs), membrane proteins responsible for the depolarizing phase of an action potential, are targeted by a broad range of neurotoxins, including pyrethroids and sodium channel blocker insecticides (SCBIs). Reduced sensitivity of the target protein due to the point mutations threatened malaria control with pyrethroids. Although SCBIs-indoxacarb (a pre-insecticide bioactivated to DCJW in insects) and metaflumizone-are used in agriculture only, they emerge as promising candidates in mosquito control. Therefore, a thorough understanding of molecular mechanisms of SCBIs action is urgently needed to break the resistance and stop disease transmission. In this study, by performing an extensive combination of equilibrium and enhanced sampling molecular dynamics simulations (3.2 μs in total), we found the DIII-DIV fenestration to be the most probable entry route of DCJW to the central cavity of mosquito VGSC. Our study revealed that F1852 is crucial in limiting SCBI access to their binding site. Our results explain the role of the F1852T mutation found in resistant insects and the increased toxicity of DCJW compared to its bulkier parent compound, indoxacarb. We also delineated residues that contribute to both SCBIs and non-ester pyrethroid etofenprox binding and thus could be involved in the target site cross-resistance.

Frequency and spatial distribution of knock-down resistance (kdr) to pyrethroids in multiple oilseed rape pest species of the genus Ceutorhynchus.

The protection of European oilseed rape (OSR) from damaging insects relies on pyrethroid insecticides, but the development of resistance in key coleopteran pests such as the pollen beetle (Brassicogethes aeneus) and the cabbage stem flea beetle (Psylliodes chrysocephala) has resulted in reduced effectiveness of these insecticides. The sodium channel gene mutation L1014F knock-down resistance (kdr) is a contributing factor in resistance to pyrethroids in B. aeneus and P. chrysocephala, but little is known about the status of resistance in weevils of the genus Ceutorhynchus (Coleoptera: Curculonidae). Therefore, the present study investigated pyrethroid susceptibility and the presence of the kdr mutation in four Ceutorhynchus species. The kdr mutation in either its heterozygous or homozygous form was found in all investigated Ceutorhynchus species (C. picitarsis, C. pallidactylus, C. napi and C. obstrictus). Samples where pyrethroids in bioassays still provided control at 100% field rate or below contained kdr at frequencies of ≤12.5%, whilst bioassays using 100% field rate that did not control Ceutorhynchus populations contained homozygous resistant individuals at frequencies of greater than 55%. Field sampling demonstrated that kdr frequencies in populations of C. picitarsis and C. obstrictus collected from across France and Germany ranged from 0 to 100%. The present study demonstrated the potential of all four Ceutorhynchus species tested to develop pyrethroid resistance via the L1014F (kdr) mutation. Although kdr frequency varies among species and geographic locations, the risk of loss of pyrethroid insecticide effectiveness is high. Integration of other control tools for resistance management is therefore needed. © 2023 Society of Chemical Industry.

Leucine to tryptophane substitution in the pore helix IIP1 confer sodium channel resistance to pyrethroids and DDT

Aedes aegypti is responsible for transmitting a variety of arboviral infectious diseases such as dengue and chikungunya. Insecticides, particularly pyrethroids, are used widely for mosquito control. However, intensive used of pyrethroids has led to the selection of kdr mutations on sodium channels. L982W, locating in the PyR1 (Pyrethroid receptor site 1), was first reported in Ae. aegypti populations collected from Vietnam. Recently, the high frequency of L982W was detected in pyrethroid-resistant populations of Vietnam and Cambodia, and also concomitant mutations L982W + F1534C was detected in both countries. However, the role of L982W in pyrethroid resistance remains unclear. In this study, we examined the effects of L982W on gating properties and pyrethroid sensitivity in Xenopus oocytes. We found that mutations L982W and L982W + F1534C shifted the voltage dependence of activation in the depolarizing direction, however, neither mutations altered the voltage dependence of inactivation. L982W significantly reduced channel sensitivity to Type I pyrethroids, permethrin and bifenthrin, and Type II pyrethroids, deltamethrin and cypermethrin. No enhancement was observed when synergized with F1534C. In addition, L982W and L982W + F1534C mutations reduced the channel sensitivity to DDT. Our results illustrate the molecular basis of resistance mediates by L982W mutation, which will be helpful to understand the interacions of pyrethroids or DDT with sodium channels and develop molecular markers for monitoring pest resistance to pyrethroids and DDT.

High frequency of Voltage-gated sodium channel (VGSC) gene mutations in Aedes albopictus (Diptera: Culicidae) suggest rapid insecticide resistance evolution in Shanghai, China.

Dengue fever is an infectious disease that is imported into Shanghai, China and requires prevention and control measures. Controlling the vector Aedes albopictus through insecticide use is a key approach to dengue control. However, the rapid evolution of insecticide resistance in Ae. albopictus has raised concerns about the failure of dengue control efforts. Knockdown resistance (kdr) caused by point mutations in the voltage-gated sodium channel (VGSC) gene is a primary mechanism of pyrethroid resistance. In this study, we investigated the kdr mutations of Ae. albopictus in Shanghai and evaluated the trend in its evolution. We collected 17 populations of Ae. albopictus from 15 districts in Shanghai in 2020, extracted genomic DNA from individual mosquitoes, and amplified Domain II, III, and IV in VGSC using PCR. Following sequencing, we obtained 658 VGSC sequences. We detected the nonsynonymous mutations V1016G, I1532T, and F1534S/C/I, among which V1016G and F1534C/I were reported in Shanghai for the first time and F1534I was a novel mutant allele in Ae. albopictus. The overall mutation frequency was 84.65%, with individual mutation frequencies ranging from 46.81% to 100%, excluding the Fengxian District population, which had a frequency of 0%. The V1016G and I1532T mutation types accounted for 7.14% and 3.42%, respectively. The mutant allele at codon 1534 accounted for 63.98% of all mutations, including TCC/S (62.77%), TGC/C (1.06%), and ATC/I (0.15%). We identified and classified five intron types in Domain III by length, including A (83 bp, 12.07%), B (68 bp, 87.30%), C (80 bp, 0.16%), D (72 bp, 0.16%), and E (70 bp, 0.31%). Individuals with intron B had a significant mutation tendency at codon 1534 relative to intron A (chi-square test, p < 0.0001). We found no correlation between mutation frequency and the amount of pyrethroid used (Pearson correlation, p = 0.4755). In recent years, kdr mutations in the Ae. albopictus population in Shanghai have rapidly evolved, as evidenced by an increase in mutation types and significantly increased mutation frequency. The F1534I/ATC mutant allele was found to be a novel mutation, F1534C/TGC was reported for the first time in Shanghai, and intron B in Domain III was significantly associated with mutation frequency at codon 1534. Continuous monitoring of resistance changes and strict regulation of insecticide use are required.

Evaluation of resistance of human head lice to pyrethroid insecticides: A meta-analysis study

IntroductionPediculosis is one of the most common annoying infections caused by parasitic lice in humans. Pyrethroids are one of the main insecticides used to treat this infection. But recently, due to the Resistance of lice to this group of insecticides, its insecticidal effects have been affected. The present study was conducted through a meta-analysis to investigate the prevalence of pyrethroid resistance against these insecticides worldwide. MethodsThis study was conducted as a meta-analysis of the prevalence of treatment resistance in human head lice against pyrethroid insecticides worldwide. Based on this, all articles published without a time limit until the end of June 2022 in PubMed/MEDLINE, Web of Science (ISI), Scopus, and Google Scholar databases were extracted and using random-effects meta-analysis model statistical methods in the meta-analysis, Cochrane, Index I2, and funnel plot were analyzed by STATA software. ResultsTwenty studies were included in the meta-analysis process. According to this, the prevalence of pyrethroid resistance insecticides in human head lice was estimated at 59% (CI95%: 50%–68%). Among pyrethroid insecticides, the highest prevalence of pyrethroid resistance against permethrin insecticide was 65%. Regarding the prevalence of Resistance by year, the prevalence before 2004 was estimated at 33%, but after 2015, this rate reached 82%. Also, the majority of pyrethroid resistance was estimated at 68% using genetic diagnosis methods and 43% using clinical diagnosis methods. ConclusionMore than half of human head lice pyrethroid resistance insecticides. Based on this, it is recommended that before using this treatment method to treat human head lice Infestation, it should investigate the prevalence of pyrethroid resistance in that area, and if the majority of Resistance is high, alternative or combined treatment methods should be used.

Status of Acaricide Resistance and Detecting the Knockdown Resistance Mutation T2134A in the Cattle Tick Rhipicephalus microplus (Acari: Ixodidae) from Northeastern Mexico.

Rhipicephalus microplus is the most important tick in veterinary medicine, given its repercussions on animal production. The principal strategy to avoid adverse effects associated with R. microplus is the chemical control of tick populations through organosynthetic acaricides. Therefore, monitoring susceptibility to acaricides is paramount in any control program. This study aimed to analyze the resistance status of 2 populations of R. microplus from northeastern Mexico to the organochlorine (OC) lindane, organophosphates (OP) coumaphos, chlorfenvinphos, diazinon, and chlorpyrifos, and the synthetic pyrethroids (SPs) flumethrin, deltamethrin, and cypermethrin. Discriminating doses (DD) of each acaricide were used in the larval packet bioassay (LPT). Additionally, the presence of the knockdown resistance (kdr) mutation T2134A associated with pyrethroid resistance was evaluated using allele-specific polymerase chain reaction (PCR). The populations of R. microplus showed a high frequency of resistance to SP, with mortality rates of less than 5%; they also showed resistance to the OPs (diazinon and chlorpyrifos) with mortality rates ranging from 1.29% to 34.62%; meanwhile, they were susceptible to coumaphos and chlorfenvinphos. Mortality rates higher than 66% were observed for lindane, indicating susceptibility. The mutant allele of the kdr mutation T2134A was detected in 75% and 100% of the pools analyzed. The populations studied presented a highly resistant profile to pyrethroids, with the presence of the kdr mutant allele A2134. The susceptibility to the organophosphates such as coumaphos and chlorfenvinphos of R. microplus from northeastern Mexico should be noted.

Reconsideration of importance of the point mutation L982W in the voltage-sensitive sodium channel of the pyrethroid resistant Aedes aegypti (L.)(Diptera: Culicidae) in Vietnam.

Pyrethroid resistance in Aedes aegypti is widespread in southern Vietnam because the photostable 2nd generation pyrethroids have been used in large amounts over extensive areas for malaria and dengue vector control. In our previous report in 2009, F1534C, one of the point mutations in the voltage-sensitive sodium channel (VSSC) in Ae. aegypti, was widespread at high frequency in south and central area. However, no significant correlation between the frequency of F1534C and pyrethroid susceptibility was detected primarily because the F1534C mutation frequency in the southern highland area was very low, despite that the bioassay indicated high pyrethroid resistance. The point mutation in the VSSC, L982W, which was not the target mutation in our previous study, was recently determined to be an important mutation causing high-pyrethroid resistance in Vietnamese Ae. aegypti. In the present study, a re-investigation of L982W in the mosquito samples collected in 2006-2008 revealed a greater distribution of this mutation (allelic percentage 59.2%) than F1534C (21.7%) and the greater proportion of homozygous L982W as compared to F1534C provided a plausible answer to the question concerning the unknown resistance factor in the southern highland area. L982W frequencies were uniformly higher in the southern part of Vietnam, including the highland area with a significantly high positive correlation with pyrethroid resistance in Ae. aegypti.

Heterosis and reselection for pyrethroid resistance trait maintenance in the lady beetle Eriopis connexa (Germar)

AbstractExposure of Eriopis connexa (Germar) to pyrethroid residues in agroecosystems has resulted in selection for resistance (R). Pyrethroid resistance allows E. connexa to survive lambda‐cyhalothrin applications. Following a field release of E. connexa, development of resistance in an incipient population may depend on three major factors such as the maintenance of: (i) selection pressure, (ii) frequency of mating with susceptible phenotypes (S) and (iii) differential reproductive performance due to the fitness costs associated with resistance. To investigate the potential effects of these three factors on the development of pyrethroid resistance by progeny of field released E. connexa, our experiments included panmictic mating between R and S phenotypes, followed by descendant rearing with and without insecticide selection pressure, reselection and determination of resistance levels. In addition, we measured the reproductive performance of the parental R and S phenotypes and their descendants to assess the cost of resistance after crossing and reselection. Survival of R × S descendants exposed to lambda‐cyhalothrin was reduced across successive generations in the absence of selection pressure, but still enhanced after four generations indicating the persistent presence of resistant phenotypes in the population. Under selection pressure with exposure to lambda‐cyhalothrin applied at label rates, descendant survival was &gt;50%. Fecundity and survival were higher in the first‐generation of crossed R × S females, but higher fecundity was not sustained after reselection. Adults of the R population exhibited a fitness cost, reduced longevity, when compared to S phenotypes and R × S crossed populations. Therefore, resistance maintenance in E. connexa after release will depend on selection pressures imposed by insecticide exposure. In the absence of selection pressure, the phenotype for resistance was reduced, but not completely lost. Further, resistant phenotypes can be reselected following insecticide exposure and this can explain, in part, the high frequency of field‐evolved resistance to lambda‐cyhalothrin in E. connexa.

Synergism and toxicity of iron nanoparticles derived from Trigonella foenum-graecum against pyrethriod treatment in S. litura and H. armigera (Lepidoptera: Noctuidae)

The tobacco cutworm, Spodoptera litura and cotton bollworm, Helicoverpa armigera (Lepidoptera: Noctuidae) are important pests of various agricultural crops that cause sevier economic loses throughout the world. Indiscriminate and frequent use of insecticide may lead to development of resistance in these pests. Nanotechnology has given an alternative to manage and overcome insecticide resistance for pest management strategies. In the present study the iron nanoparticles derived from Trigonella foenum-graecum leaf extract (FeNPs) was investigated for its ecofriendly management of pyrethroid resistance in two lepidopteron pest species at 24 h, 48 h and 72 h post treatment. The result showed high mortality (92.83% and 91.41%) of S. litura and H. armigera at 72 h treatment upon FeNPs and fenvalerate (Fen + FeNPs) teratment. Probit analysis revealed high LC50 upon Fen + FeNPs treatment (130.31 and 89.32 mg/L) with a synergism ratio of 1.38 and 1.36. Antifeedant activity of six dofferent concentration of FeNPs revelaed increased antifeedant activity with respect to increasing concentration of nanoparticles ranging from 10 to 90% and 20–95% againt both insects (p<0.05). Detoxification activity of carboxylesterase was elevated at 630 μmol/mg protein/min (p<0.05) in fenvalerate treatment, whereas decreased activity was found (392umole/mg protein/min) in FeNPs and Fen + FeNPs treatment (P<0.001). GST and P450 activity was also increased in fenvalerate treatment, whereas decreased activity was observed in FeNPs and Fen + FeNPs. Esterase isoenzyme banding pattern revealed four bands in fenvalerate treatment and two bans (E3 and E4) in Fen + FeNPs combination. Hence the present study concludes that T. foenum-graecum synthesized iron nanoparticles could be an effective alternate for ecofriendly management of S. litura and H. armigera.

Co-occurrence of multiple kdr mutations (F1534C, V1016I, V410L) in Aedes aegypti from coastal areas in Ghana and assessment of the role of mosquito coil in causing pyrethroid resistance

The rapid spread of knockdown-resistance (kdr) mutations in Africa calls for monitoring and investigation into the cause of pyrethroid resistance to inform management strategies. This study investigated the pyrethroid resistance profile of Aedes aegypti from coastal towns in Ghana and the impact of mosquito coil, a popular household pyrethroid-based anti-mosquito tool, on the development of pyrethroid resistance. Susceptibility to deltamethrin and the presence of kdr mutations was determined in adult female mosquitoes reared from larvae. Furthermore, the LT50 of a mosquito coil (0.08% meperfluthrin) against a laboratory colony was determined, and the value was used as a sublethal dose in an experimental study. The laboratory colony of Ae. aegypti was exposed to the sublethal dose of the coil once per generation for six generations (F6). The susceptibility of the exposed colony to deltamethrin (0.05%) was determined. The Ae. aegypti populations from the coastal towns were resistant to deltamethrin with co-occurrence of F1534C, V1016I and V410L kdr mutations. In the experimental study, the LT50 (95% CI) of the selected colony against the coil rose from 8 minutes (95% CI; 6–9) at F0 to 28 minutes (95% CI; 23–34) at F6. Nonetheless, deltamethrin caused similar mortalities in the selected and control colonies. The mutant allele frequencies of 1534C and 410L were similar but 1016I was higher in the selected colony (17%) than in the control (5%). However, the increased tolerance to the coil and high mutant allele frequency of 1016I in the selected colony did not affect the mosquito's resistance level to deltamethrin insecticide. Further study is needed to elucidate the role of pyrethroid-based mosquito coils in the development of insecticide resistance in mosquito vectors.

Differential impact of dual-active ingredient long-lasting insecticidal nets on primary malaria vectors: a secondary analysis of a 3-year, single-blind, cluster-randomised controlled trial in rural Tanzania

Gains in malaria control are threatened by widespread pyrethroid resistance in malaria vectors across sub-Saharan Africa. New long-lasting insecticidal nets (LLINs) containing two active ingredients (dual active-ingredient LLINs) have been developed to interrupt transmission in areas of pyrethroid resistance. We aimed to evaluate the effectiveness of three dual active-ingredient LLINs compared with standard pyrethroid LLINs against pyrethroid-resistant malaria vectors in rural Tanzania. In this study, we did a secondary analysis of entomological data from a four-group, 3 year, single-blind, cluster-randomised controlled trial carried out between Feb 18, 2019, and Dec 6, 2021. We conducted quarterly indoor mosquito collections using the Centers for Disease Control and Prevention light trap, in eight houses in each of the 84 study clusters in the Misungwi district, northwestern Tanzania. Anopheles vectors were then tested for malaria parasites and identified at species level, to distinguish between sibling species of the Anopheles gambiae and Anopheles funestus groups, using molecular laboratory techniques. The primary outcomes were density of different malaria vector species measured as the number of female Anopheles collected per household per night, the entomological inoculation rate (EIR), an indicator of malaria transmission, and sporozoite rate. Entomological outcomes were assessed on the basis of intention to treat, and the effect of the three dual active-ingredient LLINs was compared with the standard pyrethroid LLINs at household level. Dual active-ingredient LLINs had the greatest effect on Anopheles funestus sl, the most efficient vector in the study area, with comparatively weak effect on An arabiensis. An funestus density was 3∙1 per house per night in the pyrethroid LLIN group, 1∙2 in the chlorfenapyr pyrethroid LLIN group (adjusted density ratio [aDR]=0∙26, 95% CI 0∙17-0∙14, p<0∙0001), 1∙4 in the piperonyl-butoxide pyrethroid LLIN group (aDR=0∙49, 0∙32-0∙76, p=0∙0012), and 3∙0 in the pyriproxyfen pyrethroid LLIN group (aDR=0∙72, 0∙47-1∙11, p=0∙15). Malaria transmission intensity was also significantly lower in the chlorfenapyr pyrethroid group, with 0∙01 versus 0∙06 infective bites per household per night in the pyrethroid LLIN group (aDR=0∙21, 0∙14-0∙33, p<0∙0001). Ecological niche models indicated that vector-species distribution was stable following LLIN intervention despite the reductions observed in An funestus sl density. Chlorfenapyr pyrethroid LLINs were the most effective intervention against the main malaria vector An funestus sl over 3 years of community use, whereas the effect of piperonyl-butoxide pyrethroid LLIN was sustained for 2 years. The other vector, An arabiensis, was not controlled by any of the dual active-ingredient LLINs. Additional vector control tools and strategies targeted to locally prevalent vector species evading dual active-ingredient LLINs should be deployed to further reduce malaria transmission and achieve elimination. The Department for International Development, UK Medical Research Council, Wellcome Trust, the Department of Health and Social Care, and The Bill & Melinda Gates Foundation via the Innovative Vector Control Consortium.

Pyrethroid genetic resistance in the dengue vector (Aedes aegypti) in Posadas, Argentina.

Pyrethroids are extensively used to control adult populations of the arboviral vector Aedes aegypti, raising concerns regarding the increasing frequency and distribution of insecticide resistance mutations (kdr: knock-down resistance) in the voltage-gated sodium channel gene (Nav). The widespread use of pyrethroids imposes a threat to the success of mosquito control and the environment. In this study, we investigated the presence of two kdr mutations (V1016I and F1534C) in the Nav gene and their distribution across four neighborhoods in Posadas, Argentina, with different Ae. aegypti abundance and contrasting socioeconomic status (SES). Alleles at each locus were interrogated using TaqMan SNP genotyping assays in DNA extracted from adult females collected in a longitudinal study. We report the presence of both pyrethroid resistance alleles (kdr 1016I = 29.08%; kdr 1534C = 70.70%) among adult females. The frequency of combined kdr genotypes reveals that approximately 70% of local adult females have enhanced resistance to pyrethroids. Both, the proportion of resistant adult females (with at least one kdr allele in each locus) and Ae. aegypti abundance showed an uneven distribution between neighborhoods with different SES (p < 0.001). In high-SES neighborhoods, we found more mosquitoes and a higher frequency of pyrethroid resistance, possibly as a consequence of different public health interventions, social habits, and insecticide use. This is the first report of kdr mutations in Ae. Aegypti in the northeast region of Argentina. Our results focus on the need for within-population (city) distribution analyses of kdr mutations and highlight the relevance of incorporating insecticide resistance monitoring within the Integrated Vector Management initiative.

A major 6 Mb superlocus is involved in pyrethroid resistance in the common bed bug Cimex lectularius.

In the last few years, the bed bug Cimex lectularius has been an increasing problem worldwide, mainly due to the development of insecticide resistance to pyrethroids. The characterization of resistance alleles is a prerequisite to improve surveillance and resistance management. To identify genomic variants associated with pyrethroid resistance in Cimex lectularius, we compared the genetic composition of two recent and resistant populations with that of two ancient-susceptible strains using a genome-wide pool-seq design. We identified a large 6 Mb "superlocus" showing particularly high genetic differentiation and association with the resistance phenotype. This superlocus contained several clustered resistance genes and was also characterized by a high density of structural variants (inversions, duplications). The possibility that this superlocus constitutes a resistance "supergene" that evolved after the clustering of alleles adapted to insecticide and after reduction in recombination is discussed.

The Pampa del Indio project: District-wide quasi-elimination of Triatoma infestans after a 9-year intervention program in the Argentine Chaco.

The elimination of Triatoma infestans, the main domestic vector of Trypanosoma cruzi, is lagging behind expectations in the Gran Chaco region. We implemented an insecticide-based intervention program and assessed its long-term effects on house infestation and bug abundance in a resource-constrained municipality (Pampa del Indio, northeastern Argentina) inhabited by creole and the Qom indigenous people (2007-2016). Key questions were whether district-wide data integration revealed patterns concealed at lower spatial levels; to what extent preintervention infestation and pyrethroid resistance challenged the effectiveness of insecticide-based control efforts, and how much control effort was needed to meet defined targets. Supervised vector control teams i) georeferenced every housing unit at baseline (1,546); ii) evaluated house infestation using timed-manual searches with a dislodging aerosol across four rural areas designated for district-wide scaling up; iii) sprayed with pyrethroid insecticide 92.7% of all houses; iv) periodically monitored infestation and promoted householder-based surveillance, and v) selectively sprayed the infested houses, totaling 1,823 insecticide treatments throughout the program. Baseline house infestation (mean, 26.8%; range, 14.4-41.4%) and bug abundance plummeted over the first year postintervention (YPI). Timed searches at baseline detected 61.4-88.0% of apparent infestations revealed by any of the methods used. Housing dynamics varied widely among areas and between Qom and creole households. Preintervention triatomine abundance and the cumulative frequency of insecticide treatments were spatially aggregated in three large clusters overlapping with pyrethroid resistance, which ranged from susceptible to high. Persistent foci were suppressed with malathion. Aggregation occurred mainly at house compound or village levels. Preintervention domestic infestation and abundance were much greater in Qom than in creole households, whereas the reverse was recorded in peridomestic habitats. House infestation, rare (1.9-3.7%) over 2-6 YPI, averaged 0.66% (95% confidence interval, 0.28-1.29%) at endpoint. Upscale integration revealed multiple coupled heterogeneities (spatial, sociodemographic and biological) that reflect large inequalities, hamper control efforts, and provide opportunities for targeted, sustainable disease control. High-coverage, professional insecticide spraying combined with systematic surveillance-and-response were essential ingredients to achieve the quasi-elimination of T. infestans within 5 YPI and concomitant transmission blockage despite various structural threats and constraints.

Insecticide resistance status of Aedes aegypti and Aedes albopictus mosquitoes in southern Benin, West Africa

BackgroundThe emergence of insecticide resistance in Aedes mosquitoes could undermine efforts to control arboviruses. The present study aims to assess in some communes of Southern Benin, the susceptibility level of Aedes aegypti (Linnaeus, 1762) and Aedes albopictus (Skuse, 1894) to insecticides commonly used in public health, as well as mechanisms involved.MethodsFemales Ae. albopictus and Ae. aegypti collected in Ifangni, Porto-Novo, Avrankou, Adjarra and Kétou from June 2021 to October 2022, were exposed to: deltamethrin 0.05%, permethrin 0.75%, alpha-cypermethrin 0.05%, pirimiphos methyl 0.25% and bendiocarb 0.1%, following the standard WHO susceptibility tube test protocol. In some sites, pre-exposure to the synergist PBO was used to verify if pyrethroid resistance of populations of Aedes was mediated by oxidases.ResultsFull susceptibility to deltamethrin and permethrin was observed in all tested populations of Ae. albopictus. However, with alphacypermethrin, a suspected resistance was observed in Adjarra (94.67%), Ifangni (93%) and Porto-Novo (94%), and a resistance in Avrankou (83%). The PBO-alphacypermethrin tests performed, led to a full susceptibility (100%) in all four sites, which confirms the full involvement of oxidases in resistance of all tested populations of Ae. albopictus to alphacypermethrin. At the opposite, Aedes aegypti was either resistant or suspected of being resistant to all tested pyrethroids in all four sites, except in Ifangni where a full susceptibility to alphacypermethrin was observed. The full susceptibility of Ae. aegypti to bendiocarb and pirimiphos-methyl in all communes suggests that these two insecticides can be good candidates for an effective control of pyrethroid-resistant Aedes vector populations. Use of permethrin and deltamethrin could also be considered for controlling populations of Ae. albopictus.ConclusionResults of the present study will help guide strategy to implement for an effective control of Aedes vector populations in Benin.