Exploring the Mechanisms of Multiple Insecticide Resistance in a Highly Plasmodium-Infected Malaria Vector Anopheles funestus Sensu Stricto from Sahel of Northern Nigeria

Abstract

The Nigerian Government is scaling up the distribution of insecticide-treated bed nets for malaria control, but the lack of surveillance data, especially in the Sudan/Sahel region of the country, may hinder targeting priority populations. Here, the vectorial role and insecticide resistance profile of a population of a major malaria vector Anopheles funestus sensu stricto from Sahel of Nigeria was characterised. An. funestus s.s. was the only vector found, with a high human blood index (100%) and a biting rate of 5.3/person/night. High Plasmodium falciparum infection was discovered (sporozoite rate = 54.55%). The population is resistant to permethrin (mortality = 48.30%, LT50 = 65.76 min), deltamethrin, DDT (dichlorodiphenyltrichloroethane) and bendiocarb, with mortalities of 29.44%, 56.34% and 54.05%, respectively. Cone-bioassays established loss of efficacy of the pyrethroid-only long-lasting insecticidal nets (LLINs); but 100% recovery of susceptibility was obtained for piperonylbutoxide (PBO)-containing PermaNet®3.0. Synergist bioassays with PBO and diethyl maleate recovered susceptibility, implicating CYP450s (permethrin mortality = 78.73%, χ2 = 22.33, P < 0.0001) and GSTs (DDT mortality = 81.44%, χ2 = 19.12, P < 0.0001). A high frequency of 119F GSTe2 mutation (0.84) was observed (OR = 16, χ2 = 3.40, P = 0.05), suggesting the preeminent role of metabolic resistance. These findings highlight challenges associated with deployment of LLINs and indoor residual spraying (IRS) in Nigeria.

A targeted amplicon sequencing panel to simultaneously identify mosquito species and Plasmodium presence across the entire Anopheles genus

“…The quantification of the infection and identification of Plasmodium species are addressed using qPCR, where a multitude of assays have been developed—mostly targeting nuclear 18S rRNA and using various qPCR techniques (Bell & Ranford‐Cartwright, 2004; Murillo et al, 2019; Rockett et al, 2011; Rosanas‐Urgell et al, 2010). For validation of our amplicon sequencing results, we chose a protocol (Bass et al, 2008; Djouaka et al, 2016) that is widely used in vector surveillance (Ibrahim et al, 2020; Menze et al, 2018; Riveron et al, 2019). Despite the original claim of detection limit of 200 fg or about 10 genomes, our dilution series was effective for less than 50 fg, or two genomes—and we achieved similar sensitivity with amplicon sequencing while also generating all the additional data on the mosquito.…”

High pyrethroid/DDT resistance in major malaria vector Anopheles coluzzii from Niger-Delta of Nigeria is probably driven by metabolic resistance mechanisms

“…s . [ 9 – 11 ]. However, Anopheles coluzzii has become the dominant species reported in most parts of Nigeria in recent years, e.g.…”

“…in southwestern Nigeria [ 13 , 22 – 24 ] and in the north, e.g. [ 11 , 15 , 25 ], little information is available from the south-south/Niger-Delta region. Baseline information on the abundance of Anopheles and its distribution [ 26 ], insecticide resistance profiles [ 27 ] are available in this region, without actually going deep into studying the molecular mechanisms involved.…”

Fitness cost of target-site and metabolic resistance to pyrethroids drives restoration of susceptibility in a highly resistant Anopheles gambiae population from Uganda

“…The escalation of pyrethroid and DDT resistance observed in the Mayuge An . gambiae population is higher than resistance reported in other locations such as Kome, southern Chad (permethrin, 26.7% mortality, deltamethrin, 25.4% and DDT, 41.7%) [ 10 ]; and in Auyo, northern Nigeria (deltamethrin, 78.4% mortality and DDT, 44%); and in Djenne [ 35 ]. This increase may be associated with insecticide selective pressure imposed by the massive use of LLINs in Uganda since 2006 combined with agriculture.…”