Resistance of Anopheles gambiae to the new insecticide clothianidin associated with unrestricted use of agricultural neonicotinoids in Yaoundé, Cameroon

AbstractBackgroundNew active ingredients, mostly repurposed from the agricultural sector, are gradually being introduced into malaria vector control programs. Prior to scaling up novel insecticides, it is vital to assess if their use in agriculture has already selected mosquito populations with reduced susceptibility in some areas. The aim of the present study was to determine if the use of neonicotinoids in agricultural pest management could drive resistance to clothianidin—a neonicotinoid recently prequalified by WHO for indoor residual spraying.MethodsWe carried out intensive sampling of Anopheles gambiae, An. coluzzii and Culex sp. larvae from a large suburban farm and from 4 surrounding locations belonging to the rural and urban ecosystems of Yaoundé, Cameroon. Using WHO tube tests and CDC bottle bioassays, we tested the recommended diagnostic doses of clothianidin against field-collected populations using two laboratory strains as susceptible controls. We exposed adult mosquitoes to the insecticide for 1 h and monitored mortality rates for seven consecutive days.ResultsAn. coluzzii and Culex sp. mosquitoes were fully susceptible to clothianidin reaching 100% mortality by day 3. By contrast, An. gambiae populations revealed heterogeneous profiles ranging from susceptibility to strong resistance. Populations from the suburban farm, where neonicotinoids are routinely used, displayed the lowest mortality rate (46.5 % ± 5.65) and were capable of surviving 5X and 10X the diagnostic dose of clothianidin. When clothianidin was tested in combination with the synergist piperonyl butoxide, mortality of resistant populations increased from 46.5 % to 92.7 % implying that Cytochrome P450 enzymes play an integral role in the genetic mechanism underlying clothianidin resistance in An. gambiae.ConclusionsThese findings show that small clusters of resistance to clothianidin may exist around farmlands where agricultural neonicotinoids are being used. Patches of intensive agriculture should be particularly monitored in indoor residual spraying target areas.

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Potential Metabolic Resistance Mechanisms to Ivermectin in Anopheles Gambiae: A Synergist Bioassay Study

10.21203/rs.3.rs-121991/v1 ◽

2020 ◽

Author(s):

Patricia Nicolas ◽

Caroline Kiuru ◽

Martin Wagah ◽

Martha Muturi ◽

Urs Duthaler ◽

...

Keyword(s):

Cytochrome P450 ◽

Anopheles Gambiae ◽

Control Strategies ◽

Resistance Mechanisms ◽

World Health ◽

Malaria Vectors ◽

Malaria Vector Control ◽

Cytochrome P450 Enzymes ◽

Metabolic Resistance ◽

Active Efflux

Abstract Background Despite remarkable success obtained with current malaria vector control strategies in the last 15 years, additional innovative measures will be needed to achieve the ambitious goals set for 2030 by the World Health Organization (WHO). New tools will need to address insecticide resistance and residual transmission as key challenges. Endectocides such as ivermectin are drugs that kill mosquitoes which feed on treated subjects. Mass administration of ivermectin can effectively target outdoor and early biting vectors, complementing the still effective conventional tools. Although this approach has garnered attention, development of ivermectin resistance is a potential pitfall. Herein, we evaluate the potential role of xenobiotic pumps and cytochrome P450 enzymes in protecting mosquitoes against ivermectin by active efflux and metabolic detoxification, respectively. Methods We determined the lethal-concentration 50 for ivermectin in colonized Anopheles gambiae, then we used chemical inhibitors and inducers of xenobiotic pumps and cytochrome P450 enzymes in combination with ivermectin to probe the mechanism of ivermectin detoxification. Results Dual inhibition of xenobiotic pumps and cytochromes have a synergistic effect with ivermectin, greatly increasing mosquito mortality. Inhibition of xenobiotic pumps alone had no effect on ivermectin-induced mortality. Induction of xenobiotic pumps and cytochromes may confer partial protection from ivermectin.Conclusion there is a clear pathway for development of ivermectin resistance in malaria vectors. Detoxification mechanisms mediated by cytochrome P450 enzymes are more important than xenobiotic pumps in protecting mosquitoes against ivermectin.

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Population Dynamics of Anopheles gambiae s.l. and Culex quinquefasciatus in Rural and Urban Settings Before an Indoor Residual Spraying Campaign in Northern Benin

Vector-Borne and Zoonotic Diseases ◽

10.1089/vbz.2018.2409 ◽

2019 ◽

Vol 19 (9) ◽

pp. 674-684

Author(s):

Albert Sourou Salako ◽

Razaki Ossè ◽

Gil G. Padonou ◽

Fortuné Dagnon ◽

Rock Aïkpon ◽

...

Keyword(s):

Population Dynamics ◽

Anopheles Gambiae ◽

Culex Quinquefasciatus ◽

Indoor Residual Spraying ◽

Urban Settings ◽

Rural And Urban ◽

Anopheles Gambiae S.L

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Impact of Long-Lasting Insecticidal Nets and Indoor Residual Sprayings on Susceptibility of Anopheles gambiae (Diptera: Culicidae) in Western Côte d'Ivoire

ISRN Infectious Diseases ◽

10.5402/2013/914714 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7

Author(s):

Mahama Touré ◽

Pierre Carnevale ◽

Fabrice Chandre

Keyword(s):

Anopheles Gambiae ◽

Cote D'ivoire ◽

Côte D’Ivoire ◽

Indoor Residual Spraying ◽

Malaria Vector Control ◽

Cote D’Ivoire ◽

Pyrethroid Insecticides ◽

Côte D'ivoire ◽

Significant Difference ◽

And Control

Pyrethroid insecticides resistance in several Anopheles species represents a threat for the success of malaria vector control based on using treated nets and indoor sprayings. Impact of the long-lasting insecticidal net (LLIN) of Permanet type and indoor residual spraying (IRS) with deltamethrin on the levels of susceptibility to pyrethroids and DDT were investigated in field populations of Anopheles gambiae in 12 villages located in the Danané area in Western Côte d'Ivoire. From May 2001 to July 2002, adult An. gambiae reared from larvae collected from these villages were tested with 0.05% deltamethrin, 1% permethrin, and 4% DDT impregnated papers using WHO standard test kits. Knockdown times for 50% of adult mosquitoes (kdT50) of field specimens from LLINs, untreated nets, IRS, and control villages significantly differed from those of the Kisumu susceptible strain. However, the resistance ratios of the kdT50 were very low. KdT50 did not significantly differ with all treatments, chemicals (LLINs and IRS), physical (untreated nets), and control. The mortalities were above 80% indicating susceptible populations of An. gambiae in the Danané area. There was no significant difference between mortality rates from the different treatments.

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Modeling consensus and distance to delivering indoor residual spray (IRS) implementation strategies to control malaria transmission

10.1101/2020.05.07.082982 ◽

2020 ◽

Author(s):

Sadie Ryan ◽

Anne C. Martin ◽

Bhavneet Walia ◽

Anna Winters ◽

David A Larsen

Keyword(s):

Indoor Residual Spraying ◽

Implementation Strategies ◽

Network Models ◽

Malaria Vector Control ◽

Human Community ◽

Control Programs ◽

Malaria Burden ◽

Risk Prioritization ◽

Mosquito Nets ◽

Vector Control Intervention

AbstractBackgroundIndoor residual spraying (IRS) is an effective method to control malaria-transmitting Anopheles mosquitoes and often complements insecticide-treated mosquito nets, the predominant malaria vector control intervention. With insufficient funds to cover every household, malaria control programs must balance the malaria risk to a particular human community against the financial cost of spraying that community. This study creates a framework for modeling the distance to households for targeting IRS implementation, and applies it to potential risk prioritization strategies in four provinces (Luapula, Muchinga, Eastern, and Northern) in Zambia.MethodsWe used optimal network models to assess the travel distance of routes between operations bases and human communities identified through remote sensing. We compared network travel distances to Euclidean distances, to demonstrate the importance of accounting for road route costs. We then compared the distance to reaching communities for different risk prioritization strategies assuming sufficient funds to spray 50% of households, using four underlying malarial risk maps: a) predicted Plasmodium falciparum parasite rate in 2-10 year olds (PfPR), or b) predicted probability of the presence of each of three main malaria transmitting anopheline vectors (An. arabiensis, An. funestus, An. gambiae)ResultsThe estimated one-way network route distance to reach communities to deliver IRS ranged from 0.05 – 115.69 Km. Euclidean distance over and under-estimated these routes by −101.21 – 41.79 Km per trip, as compared to the network route method. There was little overlap between risk map prioritization strategies, both at a district-by-district scale, and across all four provinces. At both scales, agreement for inclusion or exclusion from IRS across all four prioritization strategies occurred in less than 10% of houses. The distances to reaching prioritized communities were either lower, or not statistically different from non-prioritized communities, at both scales of strategy.ConclusionVariation in distance to targeted communities differed depending on risk prioritization strategy used, and higher risk prioritization did not necessarily translate into greater distances in reaching a human community. These findings from Zambia suggest that areas with higher malaria burden may not necessarily be more remote than areas with lower malaria burden.

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Potential metabolic resistance mechanisms to ivermectin in Anopheles gambiae: a synergist bioassay study

Parasites & Vectors ◽

10.1186/s13071-021-04675-9 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Patricia Nicolas ◽

Caroline Kiuru ◽

Martin G. Wagah ◽

Martha Muturi ◽

Urs Duthaler ◽

...

Keyword(s):

Cytochrome P450 ◽

Anopheles Gambiae ◽

Control Strategies ◽

Resistance Mechanisms ◽

World Health ◽

Malaria Vectors ◽

Malaria Vector Control ◽

Cytochrome P450 Enzymes ◽

Metabolic Resistance ◽

Active Efflux

Abstract Background Despite remarkable success obtained with current malaria vector control strategies in the last 15 years, additional innovative measures will be needed to achieve the ambitious goals for malaria control set for 2030 by the World Health Organization (WHO). New tools will need to address insecticide resistance and residual transmission as key challenges. Endectocides such as ivermectin are drugs that kill mosquitoes which feed on treated subjects. Mass administration of ivermectin can effectively target outdoor and early biting vectors, complementing the still effective conventional tools. Although this approach has garnered attention, development of ivermectin resistance is a potential pitfall. Herein, we evaluate the potential role of xenobiotic pumps and cytochrome P450 enzymes in protecting mosquitoes against ivermectin by active efflux and metabolic detoxification, respectively. Methods We determined the lethal concentration 50 for ivermectin in colonized Anopheles gambiae; then we used chemical inhibitors and inducers of xenobiotic pumps and cytochrome P450 enzymes in combination with ivermectin to probe the mechanism of ivermectin detoxification. Results Dual inhibition of xenobiotic pumps and cytochromes was found to have a synergistic effect with ivermectin, greatly increasing mosquito mortality. Inhibition of xenobiotic pumps alone had no effect on ivermectin-induced mortality. Induction of xenobiotic pumps and cytochromes may confer partial protection from ivermectin. Conclusion There is a clear pathway for development of ivermectin resistance in malaria vectors. Detoxification mechanisms mediated by cytochrome P450 enzymes are more important than xenobiotic pumps in protecting mosquitoes against ivermectin.

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Insecticide resistance status of malaria vectors Anopheles gambiae (s.l.) of southwest Burkina Faso and residual efficacy of indoor residual spraying with microencapsulated pirimiphos-methyl insecticide

Parasites & Vectors ◽

10.1186/s13071-020-04563-8 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Dieudonné Diloma Soma ◽

Barnabas Zogo ◽

Domonbabele François de Sales Hien ◽

Aristide Sawdetuo Hien ◽

Didier Alexandre Kaboré ◽

...

Keyword(s):

Insecticide Resistance ◽

Burkina Faso ◽

Anopheles Gambiae ◽

Local Population ◽

Residual Activity ◽

Indoor Residual Spraying ◽

Susceptible Strain ◽

Malaria Vectors ◽

Pirimiphos Methyl ◽

Residual Efficacy

Abstract Background The rapid spread of insecticide resistance in malaria vectors and the rebound in malaria cases observed recently in some endemic areas underscore the urgent need to evaluate and deploy new effective control interventions. A randomized control trial (RCT) was conducted with the aim to investigate the benefit of deploying complementary strategies, including indoor residual spraying (IRS) with pirimiphos-methyl in addition to long-lasting insecticidal nets (LLINs) in Diébougou, southwest Burkina Faso. Methods We measured the susceptibility of the Anopheles gambiae (s.l.) population from Diébougou to conventional insecticides. We further monitored the efficacy and residual activity of pirimiphos-methyl on both cement and mud walls using a laboratory susceptible strain (Kisumu) and the local An. gambiae (s.l.) population. Results An. gambiae (s.l.) from Diébougou was resistant to DDT, pyrethroids (deltamethrin, permethrin and alphacypermethrin) and bendiocarb but showed susceptibility to organophosphates (pirimiphos-methyl and chlorpyrimiphos-methyl). A mixed-effect generalized linear model predicted that pirimiphos-methyl applied on cement or mud walls was effective for 210 days against the laboratory susceptible strain and 247 days against the local population. The residual efficacy of pirimiphos-methyl against the local population on walls made of mud was similar to that of cement (OR = 0.792, [0.55–1.12], Tukey’s test p-value = 0.19). Conclusions If data on malaria transmission and malaria cases (as measured trough the RCT) are consistent with data on residual activity of pirimiphos-methyl regardless of the type of wall, one round of IRS with pirimiphos-methyl would have the potential to control malaria in a context of multi-resistant An. gambiae (s.l.) for at least 7 months.

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Impact of seasonality and malaria control interventions on Anopheles density and species composition from three areas of Uganda with differing malaria endemicity

Malaria Journal ◽

10.1186/s12936-021-03675-5 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Henry Ddumba Mawejje ◽

Maxwell Kilama ◽

Simon P. Kigozi ◽

Alex K. Musiime ◽

Moses Kamya ◽

...

Keyword(s):

Species Composition ◽

Vector Control ◽

Malaria Control ◽

Mosquito Species ◽

Density Ratio ◽

Indoor Residual Spraying ◽

Sub Saharan Africa ◽

Malaria Vector Control ◽

Vector Density ◽

Llin Distribution

Abstract Background Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the malaria control interventions primarily responsible for reductions in transmission intensity across sub-Saharan Africa. These interventions, however, may have differential impact on Anopheles species composition and density. This study examined the changing pattern of Anopheles species in three areas of Uganda with markedly different transmission intensities and different levels of vector control. Methods From October 2011 to June 2016 mosquitoes were collected monthly using CDC light traps from 100 randomly selected households in three areas: Walukuba (low transmission), Kihihi (moderate transmission) and Nagongera (high transmission). LLINs were distributed in November 2013 in Walukuba and Nagongera and in June 2014 in Kihihi. IRS was implemented only in Nagongera, with three rounds of bendiocarb delivered between December 2014 and June 2015. Mosquito species were identified morphologically and by PCR (Polymerase Chain Reaction). Results In Walukuba, LLIN distribution was associated with a decline in Anopheles funestus vector density (0.07 vs 0.02 mosquitoes per house per night, density ratio [DR] 0.34, 95% CI: 0.18–0.65, p = 0.001), but not Anopheles gambiae sensu stricto (s.s.) nor Anopheles arabiensis. In Kihihi, over 98% of mosquitoes were An. gambiae s.s. and LLIN distribution was associated with a decline in An. gambiae s.s. vector density (4.00 vs 2.46, DR 0.68, 95% CI: 0.49–0.94, p = 0.02). In Nagongera, the combination of LLINs and multiple rounds of IRS was associated with almost complete elimination of An. gambiae s.s. (28.0 vs 0.17, DR 0.004, 95% CI: 0.002–0.009, p < 0.001), and An. funestus sensu lato (s.l.) (3.90 vs 0.006, DR 0.001, 95% CI: 0.0005–0.004, p < 0.001), with a less pronounced decline in An. arabiensis (9.18 vs 2.00, DR 0.15 95% CI: 0.07–0.33, p < 0.001). Conclusions LLIN distribution was associated with reductions in An. funestus s.l. in the lowest transmission site and An. gambiae s.s. in the moderate transmission site. In the highest transmission site, a combination of LLINs and multiple rounds of IRS was associated with the near collapse of An. gambiae s.s. and An. funestus s.l. Following IRS, An. arabiensis, a behaviourally resilient vector, became the predominant species, which may have implications for malaria vector control activities. Development of interventions targeted at outdoor biting remains a priority.

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Addressing key gaps in implementation of mosquito larviciding to accelerate malaria vector control in southern Tanzania: results of a stakeholder engagement process in local district councils

Malaria Journal ◽

10.1186/s12936-021-03661-x ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Salum A. Mapua ◽

Marceline F. Finda ◽

Ismail H. Nambunga ◽

Betwel J. Msugupakulya ◽

Kusirye Ukio ◽

...

Keyword(s):

Malaria Control ◽

Public Engagement ◽

Indoor Residual Spraying ◽

Malaria Vectors ◽

Malaria Vector Control ◽

Production Plant ◽

Community Members ◽

Key Informants ◽

Larval Source Management ◽

Source Management

Abstract Background Larval source management was historically one of the most effective malaria control methods but is now widely deprioritized in Africa, where insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are preferred. However, in Tanzania, following initial successes in urban Dar-es-Salaam starting early-2000s, the government now encourages larviciding in both rural and urban councils nationwide to complement other efforts; and a biolarvicide production-plant has been established outside the commercial capital. This study investigated key obstacles and opportunities relevant to effective rollout of larviciding for malaria control, with a focus on the meso-endemic region of Morogoro, southern Tanzania. Methods Key-informants were interviewed to assess awareness and perceptions regarding larviciding among designated health officials (malaria focal persons, vector surveillance officers and ward health officers) in nine administrative councils (n = 27). Interviewer-administered questionnaires were used to assess awareness and perceptions of community members in selected areas regarding larviciding (n = 490). Thematic content analysis was done and descriptive statistics used to summarize the findings. Results A majority of malaria control officials had participated in larviciding at least once over the previous three years. A majority of community members had neutral perceptions towards positive aspects of larviciding, but overall support for larviciding was high, although several challenges were expressed, notably: (i) insufficient knowledge for identifying relevant aquatic habitats of malaria vectors and applying larvicides, (ii) inadequate monitoring of programme effectiveness, (iii) limited financing, and (iv) lack of personal protective equipment. Although the key-informants reported sensitizing local communities, most community members were still unaware of larviciding and its potential. Conclusions The larviciding programme was widely supported by both communities and malaria control officials, but there were gaps in technical knowledge, implementation and public engagement. To improve overall impact, it is important to: (i) intensify training efforts, particularly for identifying habitats of important vectors, (ii) adopt standard technical principles for applying larvicides or larval source management, (iii) improve financing for local implementation and (iv) improve public engagement to boost community awareness and participation. These lessons could also be valuable for other malaria endemic areas wishing to deploy larviciding for malaria control or elimination.

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Efficacy of broflanilide (VECTRON T500), a new meta-diamide insecticide, for indoor residual spraying against pyrethroid-resistant malaria vectors

Scientific Reports ◽

10.1038/s41598-021-86935-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Corine Ngufor ◽

Renaud Govoetchan ◽

Augustin Fongnikin ◽

Estelle Vigninou ◽

Thomas Syme ◽

...

Keyword(s):

Indoor Residual Spraying ◽

Malaria Vectors ◽

Cross Resistance ◽

Malaria Vector Control ◽

Mosquito Vectors ◽

Experimental Huts ◽

Application Rates ◽

Wettable Powder ◽

Cone Bioassay ◽

Pirimiphos Methyl

AbstractThe rotational use of insecticides with different modes of action for indoor residual spraying (IRS) is recommended for improving malaria vector control and managing insecticide resistance. Insecticides with new chemistries are urgently needed. Broflanilide is a newly discovered insecticide under consideration. We investigated the efficacy of a wettable powder (WP) formulation of broflanilide (VECTRON T500) for IRS on mud and cement wall substrates in laboratory and experimental hut studies against pyrethroid-resistant malaria vectors in Benin, in comparison with pirimiphos-methyl CS (Actellic 300CS). There was no evidence of cross-resistance to pyrethroids and broflanilide in CDC bottle bioassays. In laboratory cone bioassays, broflanilide WP-treated substrates killed > 80% of susceptible and pyrethroid-resistant An. gambiae sl for 6–14 months. At application rates of 100 mg/m2 and 150 mg/m2, mortality of wild pyrethroid-resistant An. gambiae sl entering experimental huts in Covè, Benin treated with VECTRON T500 was similar to pirimiphos-methyl CS (57–66% vs. 56%, P > 0.05). Throughout the 6-month hut trial, monthly wall cone bioassay mortality on VECTRON T500 treated hut walls remained > 80%. IRS with broflanilide shows potential to significantly improve the control of malaria transmitted by pyrethroid-resistant mosquito vectors and could thus be a crucial addition to the current portfolio of IRS insecticides.

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