clothianidin and Malaria

Entomological surveillance provides critical information on vectors for appropriate malaria vector control and strategic decision-making. The widely documented insecticide resistance of malaria vectors in Côte d'Ivoire requires that any vector control intervention deployment be driven by entomological data to optimize its effectiveness and appropriate resource allocations. To achieve this goal, this study documents the results of monthly vector surveillance and insecticide susceptibility tests conducted in 2019 and a review of all previous entomological monitoring data used to guide vector control decision making. Furthermore, susceptibility to pirimiphos-methyl and clothianidin was assessed in addition to chlorfenapyr and pyrethroids (intensity and piperonyl butoxide (PBO) synergism) tests previously reported. Vector bionomic data were conducted monthly in four sites (Sakassou, Béoumi, Dabakala and Nassian) that were selected based on their reported high malaria incidence. Adult mosquitoes were collected using human landing catches (HLCs), pyrethrum spray catches (PSCs), and human-baited CDC light traps to assess vector density, behaviour, species composition and sporozoite infectivity.. Pirimiphos-methyl and clothianidin susceptibility was observed in 8 and 10 sites, respectively, while previous data reported chlorfenapyr (200 µg/bottle) susceptibility in 13 of the sites, high pyrethroid resistance intensity and increased mortality with PBO pre-exposure at all 17 tested sites. Anopheles gambiae sensu lato was the predominant malaria vector collected in all four bionomic sites. Vector density was relatively higher in Sakassou throughout the year with mean biting rates of 278.2 bites per person per night (b/p/n) compared to Béoumi, Dabakala and Nassian (mean of 48.5, 81.4 and 26.6 b/p/n, respectively). The mean entomological inoculation rate (EIR) was 4.44 infective bites per person per night (ib/p/n) in Sakassou, 0.34 ib/p/n in Beoumi, 1.17 ib/p/n in Dabakala and 1.02 ib/p/n in Nassian. The highest EIRs were recorded in October in Béoumi (1.71 ib/p/n) and Nassian (3.22 ib/p/n), in July in Dabakala (4.46 ib/p/n) and in May in Sakassou (15.6 ib/p/n).. Based on all results and data review, the National Malaria Control Programme developed and implemented a stratified insecticide-treated net (ITN) mass distribution in 2021 considering new generation ITNs. These results also supported the selection of clothianidin-based products and an optimal spraying time for the first indoor residual spraying (IRS) campaign in Sakassou and Nassian in 2020.

Topics: Animals; Anopheles; Cote d'Ivoire; Humans; Insecticide Resistance; Insecticides; Malaria; Mosquito Control; Mosquito Vectors

Information on common markers of metabolic resistance in malaria vectors from countries sharing similar eco-climatic characteristics can facilitate coordination of malaria control. Here, we characterized populations of the major malaria vector Anopheles coluzzii from Sahel region, spanning four sub-Saharan African countries: Nigeria, Niger, Chad and Cameroon.. Genome-wide transcriptional analysis identified major genes previously implicated in pyrethroid and/or cross-resistance to other insecticides, overexpressed across the Sahel, including CYP450s, glutathione S-transferases, carboxylesterases and cuticular proteins. Several, well-known markers of insecticide resistance were found in high frequencies-including in the voltage-gated sodium channel (V402L, I940T, L995F, I1527T and N1570Y), the acetylcholinesterase-1 gene (G280S) and the CYP4J5-L43F (which is fixed). High frequencies of the epidemiologically important chromosomal inversion polymorphisms, 2La, 2Rb and 2Rc, were observed (~80% for 2Rb and 2Rc). The 2La alternative arrangement is fixed across the Sahel. Low frequencies of these inversions (<10%) were observed in the fully insecticide susceptible laboratory colony of An. coluzzii (Ngoussou). Several of the most commonly overexpressed metabolic resistance genes sit in these three inversions. Two commonly overexpressed genes, GSTe2 and CYP6Z2, were functionally validated. Transgenic Drosophila melanogaster flies expressing GSTe2 exhibited extremely high DDT and permethrin resistance (mortalities <10% in 24h). Serial deletion of the 5' intergenic region, to identify putative nucleotide(s) associated with GSTe2 overexpression, revealed that simultaneous insertion of adenine nucleotide and a transition (T->C), between Forkhead box L1 and c-EST putative binding sites, were responsible for the high overexpression of GSTe2 in the resistant mosquitoes. Transgenic flies expressing CYP6Z2 exhibited marginal resistance towards 3-phenoxybenzylalcohol (a primary product of pyrethroid hydrolysis by carboxylesterases) and a type II pyrethroid, α-cypermethrin. However, significantly higher mortalities were observed in CYP6Z2 transgenic flies compared with controls, on exposure to the neonicotinoid, clothianidin. This suggests a possible bioactivation of clothianidin into a toxic intermediate, which may make it an ideal insecticide against populations of An. coluzzii overexpressing this P450.. These findings will facilitate regional collaborations within the Sahel region and refine implementation strategies through re-focusing interventions, improving evidence-based, cross-border policies towards local and regional malaria pre-elimination.

Topics: Acetylcholinesterase; Animals; Animals, Genetically Modified; Anopheles; Drosophila melanogaster; Insecticide Resistance; Insecticides; Malaria; Mosquito Vectors; Permethrin

From August 2020 to June 2021, we assessed the efficacy of SumiShield 50WG (clothianidin), Fludora Fusion 56.25WP-SB (mixture of clothianidin and deltamethrin) and Actellic 300CS (pirimiphos-methyl) in experimental huts when partially sprayed against wild, free-flying populations of Anopheles gambiae s.l. in Tiassalé, Côte d'Ivoire. A one-month baseline period of mosquito collections was conducted to determine mosquito density and resting behavior in unsprayed huts, after which two treatments of partial indoor residual spraying (IRS) were tested: spraying only the top half of walls + ceilings or only the bottom half of walls + ceilings. These were compared to fully sprayed applications using the three IRS insecticide formulations, during twenty nights per month of collection for nine consecutive months. Mortality was assessed at the time of collection, and after a 24 h holding period (Actellic) or up to 120 h (SumiShield and Fludora Fusion). Unsprayed huts were used as a negative control. The efficacy of each partially sprayed treatment of each insecticide was compared monthly to the fully sprayed huts over the study period with a non-inferiority margin set at 10%. The residual efficacy of each insecticide sprayed was also monitored. A total of 2197 Anopheles gambiae s.l. were collected during the baseline and 17,835 during the 9-month period after spraying. During baseline, 42.6% were collected on the bottom half versus 24.3% collected on the top half of the walls, and 33.1% on the ceilings. Over the nine-month post treatment period, 73.5% were collected on the bottom half of the wall, 11.6% collected on the top half and 14.8% on the ceilings. For Actellic, the mean mortality over the nine-month period was 88.5% [87.7, 89.3] for fully sprayed huts, 88.3% [85.1, 91.4] for bottom half + ceiling sprayed walls and 80.8% [74.5, 87.1] for the top half + ceiling sprayed huts. For Fludora Fusion an overall mean mortality of 85.6% [81.5, 89.7] was recorded for fully sprayed huts, 83.7% [82.9, 84.5] for bottom half + ceiling sprayed huts and 81.3% [79.6, 83.0] for the top half + ceiling sprayed huts. For SumiShield, the overall mean mortality was 86.7% [85.3, 88.1] for fully sprayed huts, 85.6% [85.4, 85.8] for the bottom half + ceiling sprayed huts and 76.9% [76.6, 77.3] for the top half + ceiling sprayed huts. For Fludora Fusion, both iterations of partial IRS were non-inferior to full spraying. However, for SumiShield and Actellic, this was true only for the hu

Topics: Animals; Anopheles; Cote d'Ivoire; Insecticide Resistance; Insecticides; Malaria; Mosquito Control; Mosquito Vectors; Pyrethrins

Topics: Animals; Anopheles; Drug Resistance; Guanidines; Humans; Insecticides; Malaria; Neonicotinoids; Rwanda; Thiazoles

A new generation of IRS insecticides which can provide improved and prolonged control of pyrethroid-resistant malaria vector populations are being developed. Fludora® Fusion is a new IRS insecticide containing a mixture of deltamethrin and clothianidin, a neonicotinoid.. The efficacy of Fludora® Fusion IRS was evaluated over 11-12 months on concrete and mud substrates in laboratory bioassays and experimental huts against wild free-flying pyrethroid-resistant Anopheles gambiae (sensu lato) in Cové, Benin. A comparison was made with the two active ingredients of the mixture; clothianidin and deltamethrin, applied alone. CDC bottle bioassays were also performed to investigate resistance to clothianidin in the wild vector population.. Fludora® Fusion induced > 80% laboratory cone bioassay mortality with both susceptible and pyrethroid-resistant An. gambiae (s.l.) for 7-9 months on concrete block substrates and 12 months on mud block substrates. The vector population at the experimental hut site was fully susceptible to clothianidin in CDC bottle bioassays. Overall mortality rates of wild free-flying pyrethroid-resistant An. gambiae (s.l.) entering the experimental huts during the 11-month trial were < 15% with deltamethrin and significantly higher with Fludora® Fusion (69-71%) and clothianidin alone (72-78%). Initial high experimental hut mortality rates with Fludora® Fusion (> 80%) only declined by 50% after 8 months. Monthly in situ wall cone bioassay mortality of susceptible mosquitoes was > 80% for 9-12 months with Fludora® Fusion and clothianidin alone. Fludora® Fusion induced significantly higher levels of early exiting of mosquitoes compared to clothianidin alone (55-60% vs 37-38%, P < 0.05).. Indoor residual spraying with Fludora® Fusion induced high and prolonged mortality of wild pyrethroid-resistant malaria vectors for 7-10 months mostly due to the clothianidin component and substantial early exiting of mosquitoes from treated huts due to the pyrethroid component. Fludora® Fusion is an important addition to the current portfolio of IRS insecticides with the potential to significantly reduce transmission of malaria by pyrethroid-resistant mosquito vectors.

Topics: Animals; Anopheles; Benin; Guanidines; Humans; Insecticide Resistance; Insecticides; Laboratories; Malaria; Mosquito Control; Mosquito Vectors; Neonicotinoids; Nitriles; Pyrethrins; Thiazoles

Contact surface bioassays were conducted for 48 weeks on four types of walls (unbaked clay, baked clay, cement, painted cement) in simulated semi-field experimental conditions using two different doses of clothianidin active ingredient (200 mg ai/sq m and 300 mg ai/sq m). Additionally, two types of walls (painted cement and baked clay) were examined in occupied houses using the 300-mg dosage. Laboratory-reared An. arabiensis were exposed to treated surfaces or untreated (controls) for 30 min. Mortality was recorded at 24-h intervals for 120 h.. Under semi-field experimental conditions, there was no significant difference in mortality over time between the two doses of clothianidin. The mortality rates remained above 60% up to 48 weeks on all four wall surface types. The formulation performed better on cement and unbaked clay with a mean final mortality rate above 90%. Under natural conditions, there was no significant difference in response between baked clay and painted cement walls with a mean final mortality rate above 90%. The insecticide also performed significantly better in natural settings compared to semi-field experimental conditions.. Depending on the type of experimental surface, the residual activity of the two doses of clothianidin was between 28 and 48 weeks based on a 60% mortality endpoint. Clothianidin at 300 mg ai/sq m applied on two house walls (baked clay or painted cement) performed equally well (> 80% mortality) on both surfaces up to week 41 (approximately 9.5 months). Extended bioassay holding periods (up to 120 h) may present with excess natural mortality in the untreated controls, thus complicating analysis.

Topics: Aerosols; Animals; Anopheles; Biological Assay; Democratic Republic of the Congo; Female; Guanidines; Insecticides; Malaria; Mosquito Control; Neonicotinoids; Survival Analysis; Thiazoles; Time Factors; Treatment Outcome

Over the past decade, insecticide resistance to malaria vectors has been identified in 71 malaria endemic countries. This has posed a major global health challenge in the fight against malaria, with declining rates of indoor residual spraying coverage attributed to pyrethroid-resistance. As part of its vector control monitoring strategies, the Bioko Island Malaria Control Project (BIMCP) in Equatorial Guinea conducted routine insecticide resistance bioassays using the WHO's standard susceptibility tests from 2013 to 2018. During the same period, the frequency of the target-site knockdown resistance allele (kdr) in the local vector population was also determined via PCR for detection of the L1014 F mutation. Biochemical analysis for metabolic resistance was also conducted in 2015. From 2016-2017, Fludora™ fusion, a formulated combination of clothianidin (a neonicotinoid) and deltamethrin (a pyrethroid) was evaluated for 9 months on Bioko Island, using the WHO's standard test procedure for determining residual effectiveness of insecticides on sprayed surfaces. In 2016, the mortality rate of the vectors on 0.05% deltamethrin was as low as 38%. The frequency of the West African form of knockdown resistance allele, L1014 F, in the vector population was as high as 80%, and metabolic resistance analysis indicated high upregulated cytochrome P450 s. However, the residual effectiveness of Fludora™ fusion recorded mortalities above 80% after 72 h of exposure for 8 months. Although both target-site knockdown resistance and metabolic resistance to pyrethroids were implicated in the local malaria vector population, Fludora™ fusion was effective under field conditions in controlling the resistant vectors for a period of 8 months on wooden surfaces on Bioko Island and represents a valuable addition to IRS programs, especially in regions with high levels of pyrethroid resistance.

Topics: Animals; Anopheles; Equatorial Guinea; Guanidines; Humans; Insecticide Resistance; Insecticides; Islands; Malaria; Mosquito Control; Mosquito Vectors; Neonicotinoids; Nitriles; Pyrethrins; Thiazoles

Malaria vector control is dependent on chemical insecticides applied to walls by indoor residual spraying or on long-lasting insecticidal nets. The emergence and spread of insecticide resistance in major malaria vectors may compromise malaria control and elimination efforts. The aim of this study was to estimate a diagnostic dose for chlorfenapyr (class: pyrrole) and clothianidin (class: neonicotinoid) and assess the baseline susceptibility of three major Anopheles malaria vectors of western Kenya to these two insecticides.. The Centers for Disease Control and Prevention (CDC) bottle assay was used to determine the diagnostic doses of chlorfenapyr and clothianidin insecticides against the susceptible Kisumu strain of Anopheles gambiae. Probit analysis was used to determine the lethal doses at which 50% (LD50) and 99% (LD99) of the susceptible mosquitoes would be killed 24, 48 and 72 h following exposure for 1 h. Insecticidal efficacy of chlorfenapyr, clothianidin and the pyrethroid deltamethrin was then evaluated against field collected female Anopheles mosquitoes sampled from Nyando, Bumula and Ndhiwa sub-Counties in western Kenya. Members of Anopheles funestus and An. gambiae complexes were identified using polymerase chain reaction (PCR).. The determined diagnostic doses of chlorfenapyr and clothianidin insecticides were 50 µg/bottle and 150 µg/bottle, respectively, for An. gambiae, Kisumu strain. When exposed to the diagnostic dose of each insecticide, Anopheles malaria vector populations in western Kenya were susceptible to both insecticides with 100% mortality observed after 72 h. Mortality of mosquitoes exposed to deltamethrin increased over time but did not reach 100%. Mortality of Anopheles arabiensis from Nyando exposed to deltamethrin was 83% at 24 h, 88% at 48 h and 94.5% at 72 h while An. funestus from Ndhiwa was 89% at 24 h, 91.5% at 48 h and 94.5% at 72 h.. Mosquitoes of western Kenya, despite being resistant to pyrethroids, are susceptible to chlorfenapyr and clothianidin. Field evaluations of the formulated product are needed.

Topics: Animals; Anopheles; Dose-Response Relationship, Drug; Guanidines; Insecticides; Kenya; Lethal Dose 50; Malaria; Mosquito Control; Mosquito Vectors; Neonicotinoids; Pyrethrins; Species Specificity; Thiazoles

In 2017, more than 5 million house structures were sprayed through the U.S. President's Malaria Initiative, protecting more than 21 million people in sub-Saharan Africa. New IRS formulations, SumiShield™ 50WG and Fludora Fusion™ WP-SB, became World Health Organization (WHO) prequalified vector control products in 2017 and 2018, respectively. Both formulations contain the neonicotinoid active ingredient, clothianidin. The target site of neonicotinoids represents a novel mode of action for vector control, meaning that cross-resistance through existing mechanisms is less likely. In preparation for rollout of clothianidin formulations as part of national IRS rotation strategies, baseline susceptibility testing was conducted in 16 countries in sub-Saharan Africa.. While work coordinated by the WHO is ongoing to develop a suitable bottle bioassay procedure, there was no published guidance regarding clothianidin susceptibility procedures or diagnostic concentrations. Therefore, a protocol was developed for impregnating filter papers with 2% w/v SumiShield™ 50WG dissolved in distilled water. Susceptibility tests were conducted using insectary-reared reference Anopheles and wild collected malaria vector species. All tests were conducted within 24 h of treating papers, with mortality recorded daily for 7 days, due to the slow-acting nature of clothianidin against mosquitoes. Anopheles gambiae sensu lato (s.l.) adults from wild collected larvae were tested in 14 countries, with wild collected F. One-hundred percent mortality was reached with all susceptible insectary strains and with wild An. gambiae s.l. from all sites in 11 countries. However, tests in at least one location from 5 countries produced mortality below 98%. While this could potentially be a sign of clothianidin resistance, it is more likely that the diagnostic dose or protocol requires further optimization. Repeat testing in 3 sites in Ghana and Zambia, where possible resistance was detected, subsequently produced 100% mortality. Results showed susceptibility to clothianidin in 38 of the 43 sites in sub-Saharan Africa, including malaria vectors with multiple resistance mechanisms to pyrethroids, carbamates and organophosphates.. This study provides an interim diagnostic dose of 2% w/v clothianidin on filter papers which can be utilized by National Malaria Control Programmes and research organizations until the WHO concludes multi-centre studies and provides further guidance.

Topics: Africa South of the Sahara; Animals; Anopheles; Communicable Disease Control; Guanidines; Insecticide Resistance; Insecticides; Malaria; Mosquito Control; Mosquito Vectors; Neonicotinoids; Reference Values; Thiazoles

In recognition of the threat of insecticide resistance in vectors of malaria, the WHO Global Malaria Programme recommends the development of an appropriate and comprehensive response to insecticide resistance. In principle, good resistance management practice requires the application of multiple insecticides of different modes of action, for example, in rotations and mixtures. Insecticides recommended by the World Health Organization for indoor residual spraying and long-lasting insecticide nets are limited. It is, therefore, judicious to prevent the rapid spread of insecticide resistance by evaluating new insecticides formulations with different modes of action and long residual effect.. Fludora. Both the Fludora

Topics: Animals; Anopheles; Benin; Female; Guanidines; Insecticide Resistance; Insecticides; Malaria; Mosquito Control; Mosquito Vectors; Neonicotinoids; Nitriles; Pesticide Residues; Pyrethrins; Thiazoles

There is an urgent need for new insecticides for indoor residual spraying (IRS) which can provide improved and prolonged control of malaria vectors that have developed resistance to existing insecticides. The neonicotinoid, clothianidin represents a class of chemistry new to public health. Clothianidin acts as an agonist on nicotinic acetyl choline receptors. IRS with a mixture of Clothianidin and another WHO approved insecticide such as deltamethrin could provide improved control of insecticide resistant malaria vector populations and serve as a tool for insecticide resistance management.. The efficacy and residual activity of a novel IRS mixture of deltamethrin and clothianidin was evaluated against wild pyrethroid resistant An. gambiae sl in experimental huts in Cove, Benin. Two application rates of the mixture were tested and comparison was made with clothianidin and deltamethrin applied alone. To assess the residual efficacy of the treatments on different local wall substrates, the inner walls of the experimental huts were covered with either cement, mud or plywood.. Clothianidin demonstrated a clear delayed expression in mortality of wild pyrethroid resistant An. gambiae sl in the experimental huts which reached its full effect 120 hours after exposure. Overall mortality over the 12-month hut trial was 15% in the control hut and 24-29% in the deltamethrin-treated huts. The mixture of clothianidin 200mg/m2 and deltamethrin 25mg/m2 induced high overall hut mortality rates (87% on mud walls, 82% on cement walls and 61% on wooden walls) largely due to the clothianidin component and high hut exiting rates (67-76%) mostly due to the deltamethrin component. Mortality rates remained >80% for 8-9 months on mud and cement walls. The residual activity trend was confirmed by results from monthly in situ cone bioassays with laboratory susceptible An. gambiae Kisumu strain.. IRS campaigns with the mixture of clothianidin plus deltamethrin have the potential to provide prolonged control of malaria transmitted by pyrethroid resistant mosquito populations.

Topics: Animals; Anopheles; Benin; Culex; Guanidines; Housing; Humans; Insecticide Resistance; Insecticides; Malaria; Mosquito Control; Neonicotinoids; Pyrethrins; Thiazoles; World Health Organization