BackgroundThe impact of indoor residual spraying (IRS) and long-lasting insecticide nets (LLINs), key components of the national malaria control strategy of Mali, is threatened by vector insecticide resistance. The objective of this study was to assess the level of insecticide resistance in Anopheles gambiae sensu lato populations from Mali against four classes of insecticide recommended for IRS: organochlorines (OCs), pyrethroids (PYs), carbamates (CAs) and organophosphates (OPs). Characterization of resistance was done in 13 sites across southern Mali and assessed presence and distribution of physiological mechanisms that included target-site modifications: knockdown resistance (kdr) and altered acetycholinesterase (AChE), and/or metabolic mechanisms: elevated esterases, glutathione S-transferases (GSTs), and monooxygenases.MethodsThe World Health Organization (WHO) tube test was used to determine phenotypic resistance of An.gambiae s.l. to: dichlorodiphenyltrichloroethane (DDT) (OC), deltamethrin (PY), lambda-cyhalothrin (PY), bendiocarb (CA), and fenitrothion (OP). Identification of sibling species and presence of the ace-1R and Leu-Phe kdr, resistance-associated mutations, were determined using polymerase chain reaction (PCR) technology. Biochemical assays were conducted to detect increased activity of GSTs, oxidases and esterases.ResultsPopulations tested showed high levels of resistance to DDT in all 13 sites, as well as increased resistance to deltamethrin and lambda-cyhalothrin in 12 out of 13 sites. Resistance to fenitrothion and bendiocarb was detected in 1 and 4 out of 13 sites, respectively. Anopheles coluzzii, An. gambiae sensu stricto and Anopheles arabiensis were identified with high allelic frequencies of kdr in all sites where each of the species were found (13, 12 and 10 sites, respectively). Relatively low allelic frequencies of ace-1R were detected in four sites where this assessment was conducted. Evidence of elevated insecticide metabolism, based on oxidase, GSTs and esterase detoxification, was also documented.ConclusionMultiple insecticide-resistance mechanisms have evolved in An. coluzzii, An. gambiae s.s. and An.arabiensis in Mali. These include at least two target site modifications: kdr, and ace-1R, as well as elevated metabolic detoxification systems (monooxygenases and esterases). The selection pressure for resistance could have risen from the use of these insecticides in agriculture, as well as in public health. Resistance management strategies, based on routine resistance monitoring to inform insecticide-based malaria vector control in Mali, are recommended.

BackgroundIndoor residual spraying (IRS) is the application of insecticide to the interior walls of household structures that often serve as resting sites for mosquito vectors of malaria. Human exposure to malaria vectors is reduced when IRS involves proper application of pre-determined concentrations of the active ingredient specific to the insecticide formulation of choice. The impact of IRS can be affected by the dosage of insecticide, spray coverage, vector behavior, vector susceptibility to insecticides, and the residual efficacy of the insecticide applied. This report compiles data on the residual efficacy of insecticides used in IRS campaigns implemented by the United States President’s Malaria Initiative (PMI)/United States Agency for International Development (USAID) in 17 African countries and compares observed length of efficacy to ranges proposed in World Health Organization (WHO) guidelines. Additionally, this study provides initial analysis on variation of mosquito mortality depending on the surface material of sprayed structures, country spray program, year of implementation, source of tested mosquitoes, and type of insecticide.MethodsResidual efficacy of the insecticides used for PMI/USAID-supported IRS campaigns was measured in Benin, Burkina Faso, Ethiopia, Ghana, Kenya, Liberia, Madagascar, Malawi, Mali, Mozambique, Nigeria, Rwanda, Senegal, Tanzania, Uganda, Zambia and Zimbabwe. The WHO cone bioassay tests were used to assess the mortality rate of mosquitoes exposed to insecticide-treated mud, wood, cement, and other commonly used housing materials. Baseline tests were performed within weeks of IRS application and follow-up tests were continued until the mortality of exposed mosquitoes dropped below 80% or the program monitoring period ended. Residual efficacy in months was then evaluated with respect to WHO guidelines that provide suggested ranges of residual efficacy for insecticide formulations recommended for use in IRS. Where the data allowed, direct comparisons of mosquito mortality rates were then made to determine any significant differences when comparing insecticide formulation, country, year, surface type, and the source of the mosquitoes used in testing.ResultsThe residual efficacy of alpha-cypermethrin ranged from 4 to 10 months (average = 6.4 months), with no reported incidents of underperformance when compared to the efficacy range provided in WHO guidelines. Deltamethrin residual efficacy results reported a range of 1 to 10 months (average = 4.9 months), with two instances of underperformance. The residual efficacy of bendiocarb ranged from 2 weeks to 7 months (average = 2.8 months) and failed to achieve proposed minimum efficacy on 14 occasions. Lastly, long-lasting pirimiphos-methyl efficacy ranged from 2 months to 9 months (average = 5.3 months), but reported 13 incidents of underperformance.ConclusionsMuch of the data used to determine application rate and expected efficacy of insecticides approved for use in IRS programs are collected in controlled laboratory or pilot fiel...

Background 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. Methods 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 0 Anopheles funestus s.l. tested in Mozambique and Zambia. Results 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. Conclusions 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. Electronic supplementary material The online version of this article (10.1186/s12936-019-2888-6) contains supplementary material, which is available to authorized users.

BackgroundWith the emergence and spread of vector resistance to pyrethroids and DDT in Africa, several countries have recently switched or are considering switching to carbamates and/or organophosphates for indoor residual spraying (IRS). However, data collected on the residual life of bendiocarb used for IRS in some areas indicate shorter than expected bio-efficacy. This study evaluated the effect of pH and wall type on the residual life of the carbamates bendiocarb and propoxur as measured by the standard World Health Organization (WHO) cone bioassay test.MethodsIn phase I of this study, bendiocarb and propoxur were mixed with buffered low pH (pH 4.3) local water and non-buffered high pH (pH 8.0) local water and sprayed on two types of wall surface, mud and dung, in experimental huts. In the six month phase II study, the two insecticides were mixed with high pH local water and sprayed on four different surfaces: painted, dung, mud and mud pre-wetted with water. The residual bio-efficacy of the insecticides was assessed monthly using standard WHO cone bioassay tests.ResultsIn phase I, bendiocarb mixed with high pH water killed more than 80 % of susceptible Anopheles arabiensis mosquitoes for two months on both dung and mud surfaces. On dung surfaces, the 80 % mortality threshold was achieved for three months when the bendiocarb was mixed with low pH water and four months when it was mixed with high pH water. Propoxur lasted longer than bendiocarb on dung surfaces, staying above the 80 % mortality threshold for four and five months when mixed with high and low pH water, respectively. Phase II results also showed that the type of surface sprayed has a significant impact on the bio-efficacy of bendiocarb. Keeping the spray water constant at the same high pH of 8.0, bendiocarb killed 100 % of exposed mosquitoes on impervious painted surfaces for the six months of the study period compared with less than one month on mud surfaces.ConclusionsMixing the insecticides in alkaline water did not reduce the residual bio-efficacy of bendiocarb. However, bendiocarb performed much better on impervious (painted) surfaces than on porous dung or mud ones. Propoxur was less affected by wall type than was bendiocarb. Studies on the interaction between wall materials, soil, humidity, temperature and pH and the residual bio-efficacy of new and existing insecticides are recommended prior to their wide use in IRS.