Susceptibility testing of Anopheles malaria vectors with the neonicotinoid insecticide clothianidin; results from 16 African countries, in preparation for indoor residual spraying with new insecticide formulations

Abstract

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.

Resistance to clothianidin reduces the efficacy of SumiShield® 50WG, a neonicotinoid formulation for indoor residual spraying, againstAnopheles gambiae

“…Despite these difficulties, the susceptibility of wild Anopheles populations from several African countries has been successfully evaluated using the recommended diagnostic doses of clothianidin [18,22,35,37 arabiensis [18,22,35,37]. Resistance to clothianidin was not detected among populations from 16 countries where 100% mortality was reached on average 72 h following exposure in all populations tested either with WHO tube tests [18,37] or with CDC bottle assays [22,35]. Our study confirms that susceptible populations of [18].…”

“…We used a diagnostic dose of 2% w/v clothianidin (13.2 mg active ingredient per paper) based on guidance from Sumitomo Corporation and the US President's Malaria Initiative. This dose has been successfully used to test the toxicity of clothianidin towards wild anopheline populations from Sub-Saharan Africa [18,37]. We prepared a stock solution by diluting 264 mg SumiShield 50WG in 20 ml distilled water.…”

“…Assessing clothianidin susceptibility in Anopheles mosquitoes using conventional bioassays has been met with some technical challenges so far [18,22,35,37,44]. Clothianidin is difficult to solubilize in solvents commonly used in bioassays, which has made the design of standard protocols more laborious than usual [18,35,37]. In addition, because this active ingredient acts slowly, resistance profiles are revealed via laboratory bioassays only if exposed populations are rigorously monitored during a long holding period, which can last seven days or more.…”

“…In addition, because this active ingredient acts slowly, resistance profiles are revealed via laboratory bioassays only if exposed populations are rigorously monitored during a long holding period, which can last seven days or more. Despite these difficulties, the susceptibility of wild Anopheles populations from several African countries has been successfully evaluated using the recommended diagnostic doses of clothianidin [18,22,35,37 arabiensis [18,22,35,37]. Resistance to clothianidin was not detected among populations from 16 countries where 100% mortality was reached on average 72 h following exposure in all populations tested either with WHO tube tests [18,37] or with CDC bottle assays [22,35].…”

An. gambiae s.l. exhibit high intensity pyrethroid resistance throughout Southern and Central Mali (2016-2018); PBO or next generation LLINs may provide greater control

“…gambiae and An. arabiensis [14]. The diagnostic dose was set at 2% weight/volume (w/v) SumiShield™ 50WG (i.e.…”