Search

Background: Pyrethroid resistance poses a major threat to the efficacy of insecticide-treated nets (ITNs) in Burkina Faso and throughout sub-Saharan Africa, particularly where resistance is present at high intensity. For such areas, there are alternative ITNs available, including the synergist piperonyl butoxide (PBO)-based ITNs and dual active ingredient ITNs such as Interceptor G2 (treated with chlorfenapyr and alpha-cypermethrin). Before deploying alternative ITNs on a large scale it is crucial to characterize the resistance profiles of primary malaria vector species for evidence-based decision making. Methods: Larvae from the predominant vector, Anopheles gambiae sensu lato (s.l.) were collected from 15 sites located throughout Burkina Faso and reared to adults for bioassays to assess insecticide resistance status. Resistance intensity assays were conducted using WHO tube tests to determine the level of resistance to pyrethroids commonly used on ITNs at 1×, 5 × and 10 × times the diagnostic dose. WHO tube tests were also used for PBO synergist bioassays with deltamethrin and permethrin. Bottle bioassays were conducted to determine susceptibility to chlorfenapyr at a dose of 100 µg/bottle. Results: WHO tube tests revealed high intensity resistance in An. gambiae s.l. to deltamethrin and alpha-cypermethrin in all sites tested. Resistance intensity to permethrin was either moderate or high in 13 sites. PBO pre-exposure followed by deltamethrin restored full susceptibility in one site and partially restored susceptibility in all but one of the remaining sites (often reaching mortality greater than 80%). PBO pre-exposure followed by permethrin partially restored susceptibility in 12 sites. There was no significant increase in permethrin mortality after PBO pre-exposure in Kampti, Karangasso-Vigué or Mangodara; while in Seguenega, Orodara and Bobo-Dioulasso there was a significant increase in mortality, but rates remained below 50%. Susceptibility to chlorfenapyr was confirmed in 14 sites. Conclusion: High pyrethroid resistance intensity in An. gambiae s.l. is widespread across Burkina Faso and may be a predictor of reduced pyrethroid ITN effectiveness. PBO + deltamethrin ITNs would likely provide greater control than pyrethroid nets. However, since susceptibility in bioassays was not restored in most sites following pre-exposure to PBO, Interceptor G2 may be a better long-term solution as susceptibility was recorded to chlorfenapyr in nearly all sites. This study provides evidence supporting the introduction of both Interceptor G2 nets and PBO nets, which were distributed in Burkina Faso in 2019 as part of a mass campaign. [ABSTRACT FROM AUTHOR]

The scale up of indoor residual spraying (IRS) and insecticide treated nets have contributed significantly to global reductions in malaria prevalence over the last two decades. However, widespread pyrethroid resistance has necessitated the use of new and more expensive insecticides for IRS. Partial IRS with pirimiphos-methyl in experimental huts and houses in a village-wide trial was evaluated against Anopheles gambiae s.l. in northern Ghana. Four different scenarios in which either only the top or bottom half of the walls of experimental huts were sprayed, with or without also spraying the ceiling were compared. Mortality of An. gambiae s.l. on partially sprayed walls was compared with the standard procedures in which all walls and ceiling surfaces are sprayed. A small-scale trial was then conducted to assess the effectiveness, feasibility, and cost of spraying only the upper walls and ceiling as compared to full IRS and no spraying in northern Ghana. Human landing catches were conducted to estimate entomological indices and determine the effectiveness of partial IRS. An established transmission dynamics model was parameterized by an analysis of the experimental hut data and used to predict the epidemiological impact and cost effectiveness of partial IRS for malaria control in northern Ghana. In the experimental huts, partial IRS of the top (IRR 0.89, p = 0.13) or bottom (IRR 0.90, p = 0.15) half of walls and the ceiling was not significantly less effective than full IRS in terms of mosquito mortality. In the village trial, the annual entomological inoculation rate was higher for the unsprayed control (217 infective bites/person/year (ib/p/yr)) compared with the fully and partially sprayed sites, with 28 and 38 ib/p/yr, respectively. The transmission model predicts that the efficacy of partial IRS against all-age prevalence of malaria after six months would be broadly equivalent to a full IRS campaign in which 40% reduction is expected relative to no spray campaign. At scale, partial IRS in northern Ghana would have resulted in a 33% cost savings ($496,426) that would enable spraying of 36,000 additional rooms. These findings suggest that partial IRS is an effective, feasible, and cost saving approach to IRS that could be adopted to sustain and expand implementation of this key malaria control intervention. [ABSTRACT FROM AUTHOR]

Background: Millions of pyrethroid LLINs have been distributed in Mali during the past 20 years which, along with agricultural use, has increased the selection pressure on malaria vector populations. This study investigated pyrethroid resistance intensity and susceptible status of malaria vectors to alternative insecticides to guide choice of insecticides for LLINs and IRS for effective control of malaria vectors. Methods: For 3 years between 2016 and 2018, susceptibility testing was conducted annually in 14–16 sites covering southern and central Mali. Anopheles gambiae (s.l.) were collected from larval sites and adult mosquitoes exposed in WHO tube tests to diagnostic doses of bendiocarb (0.1%) and pirimiphos-methyl (0.25%). Resistance intensity tests were conducted using CDC bottle bioassays (2016–2017) and WHO tube tests (2018) at 1×, 2×, 5×, and 10× the diagnostic concentration of permethrin, deltamethrin and alpha-cypermethrin. WHO tube tests were conducted with pre-exposure to the synergist PBO followed by permethrin or deltamethrin. Chlorfenapyr was tested in CDC bottle bioassays at 100 µg active ingredient per bottle and clothianidin at 2% in WHO tube tests. PCR was performed to identify species within the An. gambiae complex. Results: In all sites An. gambiae (s.l.) showed high intensity resistance to permethrin and deltamethrin in CDC bottle bioassay tests in 2016 and 2017. In 2018, the WHO intensity tests resulted in survivors at all sites for permethrin, deltamethrin and alpha-cypermethrin when tested at 10× the diagnostic dose. Across all sites mean mortality was 33.7% with permethrin (0.75%) compared with 71.8% when pre-exposed to PBO (4%), representing a 2.13-fold increase in mortality. A similar trend was recorded for deltamethrin. There was susceptibility to pirimiphos-methyl, chlorfenapyr and clothianidin in all surveyed sites, including current IRS sites in Mopti Region. An. coluzzii was the primary species in 4 of 6 regions. Conclusions: Widespread high intensity pyrethroid resistance was recorded during 2016–2018 and is likely to compromise the effectiveness of pyrethroid LLINs in Mali. PBO or chlorfenapyr LLINs should provide improved control of An. gambiae (s.l.). Clothianidin and pirimiphos-methyl insecticides are currently being used for IRS as part of a rotation strategy based on susceptibility being confirmed in this study. [ABSTRACT FROM AUTHOR]

Background: Indoor 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. Methods: Residual 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. Results: The 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. Conclusions: Much 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 field studies. However, the generalizability of the results obtained under controlled conditions are limited and unlikely to account for variation in locally sourced housing materials, climate, and the myriad other factors that may influence the bio-efficacy of insecticides. Here, data are presented that confirm the variation in residual efficacy observed when monitoring household surfaces sprayed during PMI/USAID-supported IRS campaigns. All insecticides except alpha-cypermethrin showed evidence of failing to meet the minimum range of residual efficacy proposed in WHO criteria at least once. However, this initial effort in characterizing program-wide insecticide bio-efficacy indicates that some insecticides, such as bendiocarb and pirimiphos-methyl, may be vulnerable to variations in the local environment. Additionally, the comparative analysis performed in this study provides evidence that mosquito mortality rates differ with respect to factors including: the types of insecticide sprayed, surface material, geographical location, year of spraying, and tested mosquitoes. It is, therefore, important to locally assess the residual efficacy of insecticides on various surfaces to inform IRS programming. [ABSTRACT FROM AUTHOR]

Background: With 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. Methods: In 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. Results: In 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. Conclusions: Mixing 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. [ABSTRACT FROM AUTHOR]

Background: The 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-trans-ferases (GSTs), and monooxygenases. Methods: The 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. Results: Populations 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. Conclusion: Multiple 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. [ABSTRACT FROM AUTHOR]