Widespread Pyrethroid and DDT Resistance in the Major Malaria Vector Anopheles funestus in East Africa Is Driven by Metabolic Resistance Mechanisms

Abstract

BackgroundEstablishing the extent, geographical distribution and mechanisms of insecticide resistance in malaria vectors is a prerequisite for resistance management. Here, we report a widespread distribution of insecticide resistance in the major malaria vector An. funestus across Uganda and western Kenya under the control of metabolic resistance mechanisms.Methodology/Principal FindingsFemale An. funestus collected throughout Uganda and western Kenya exhibited a Plasmodium infection rate between 4.2 to 10.4%. Widespread resistance against both type I (permethrin) and II (deltamethrin) pyrethroids and DDT was observed across Uganda and western Kenya. All populations remain highly susceptible to carbamate, organophosphate and dieldrin insecticides. Knockdown resistance plays no role in the pyrethroid and DDT resistance as no kdr mutation associated with resistance was detected despite the presence of a F1021C replacement. Additionally, no signature of selection was observed on the sodium channel gene. Synergist assays and qRT-PCR indicated that metabolic resistance plays a major role notably through elevated expression of cytochrome P450s. DDT resistance mechanisms differ from West Africa as the L119F-GSTe2 mutation only explains a small proportion of the genetic variance to DDT resistance.ConclusionThe extensive distribution of pyrethroid and DDT resistance in East African An. funestus populations represents a challenge to the control of this vector. However, the observed carbamate and organophosphate susceptibility offers alternative solutions for resistance management.

Bionomics and insecticides resistance profiling of malaria vectors at a selected site for experimental hut trials in central Cameroon

“…The frequency of the 119F-GSTe2-resistant allele in Mibellon field population (28%) is lower than in the northern part of Cameroon in Gounougou (52%) [5] or in Ghana (44.2%) [42] and Benin (56.25%) [30]. The frequencies in Mibellon are closer to that observed in the eastern part of Africa in Uganda (20.4%) [21, 32]. GSTe2 has been shown to confer cross-resistance between DDT and pyrethroids [42].…”

From silent spring to silent night: Agrochemicals and the anthropocene

“…The harmful consequences of the evolution of insecticide resistance is not only manifest in the harm to crops and the use of even more insecticide (which leads to even more rapid and widespread evolution of resistance), but also seen in adverse impacts on public health, such as the progression of insecticide-resistance in insects that serve as vectors for human disease (e.g. malaria, yellow fever, dengue fever, and Zika virus) (Mulamba et al, 2014, Dang et al, 2015a, Dang et al, 2015b, Dang et al, 2015c, Dykes et al, 2015, Ishak et al, 2015, Owusu et al, 2015, Dalla Bona et al, 2016.…”

“…In addition to changing the genetic landscape via the evolution of resistant pests (Mulamba et al, 2014, Gellatly et al, 2015, Kudom et al, 2015, Wanjala et al, 2015 as a result of widespread heavy use, many pesticides also produce adverse effects on development, growth and reproduction at concentrations well below levels previously considered toxic. In particular, endocrine-disrupting effects have been identified in controlled laboratory studies, are correlated with effects on exposed wildlife, and are associated with adverse effects on human health (references below).…”

“…57, page 4 of 24 the use of even more insecticide (which leads to even more rapid and widespread evolution of resistance), but also seen in adverse impacts on public health, such as the progression of insecticide-resistance in insects that serve as vectors for human disease (e.g. malaria, yellow fever, dengue fever, and Zika virus) (Mulamba et al, 2014, Dang et al, 2015a, Dang et al, 2015b, Dang et al, 2015c, Dykes et al, 2015, Ishak et al, 2015, Owusu et al, 2015, Dalla Bona et al, 2016.Likewise, intense herbicide use in agriculture has led to the evolution of herbicide-resistant weeds. The heavy use of herbicides also began post WWII.…”

Implementation of the global plan for insecticide resistance management in malaria vectors: Progress, challenges, and the way forward

“…These impressive reductions have been achieved largely due to the widespread deployment of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) of insecticides, which target Anopheles malaria vectors. However, the effectiveness of these core malaria interventions is threatened by increases in the distribution and strength (intensity) of insecticide resistance in these mosquitoes [2][3][4]. This is of particular concern for pyrethroids, which are currently the only insecticides used in ITNs and are also widely applied in IRS.…”