SummaryBackgroundScale-up of insecticide-based interventions has averted more than 500 million malaria cases since 2000. Increasing insecticide resistance could herald a rebound in disease and mortality. We aimed to investigate whether insecticide resistance was associated with loss of effectiveness of long-lasting insecticidal nets and increased malaria disease burden.MethodsThis WHO-coordinated, prospective, observational cohort study was done at 279 clusters (villages or groups of villages in which phenotypic resistance was measurable) in Benin, Cameroon, India, Kenya, and Sudan. Pyrethroid long-lasting insecticidal nets were the principal form of malaria vector control in all study areas; in Sudan this approach was supplemented by indoor residual spraying. Cohorts of children from randomly selected households in each cluster were recruited and followed up by community health workers to measure incidence of clinical malaria and prevalence of infection. Mosquitoes were assessed for susceptibility to pyrethroids using the standard WHO bioassay test. Country-specific results were combined using meta-analysis.FindingsBetween June 2, 2012, and Nov 4, 2016, 40 000 children were enrolled and assessed for clinical incidence during 1·4 million follow-up visits. 80 000 mosquitoes were assessed for insecticide resistance. Long-lasting insecticidal net users had lower infection prevalence (adjusted odds ratio [OR] 0·63, 95% CI 0·51–0·78) and disease incidence (adjusted rate ratio [RR] 0·62, 0·41–0·94) than did non-users across a range of resistance levels. We found no evidence of an association between insecticide resistance and infection prevalence (adjusted OR 0·86, 0·70–1·06) or incidence (adjusted RR 0·89, 0·72–1·10). Users of nets, although significantly better protected than non-users, were nevertheless subject to high malaria infection risk (ranging from an average incidence in net users of 0·023, [95% CI 0·016–0·033] per person-year in India, to 0·80 [0·65–0·97] per person year in Kenya; and an average infection prevalence in net users of 0·8% [0·5–1·3] in India to an average infection prevalence of 50·8% [43·4–58·2] in Benin).InterpretationIrrespective of resistance, populations in malaria endemic areas should continue to use long-lasting insecticidal nets to reduce their risk of infection. As nets provide only partial protection, the development of additional vector control tools should be prioritised to reduce the unacceptably high malaria burden.FundingBill & Melinda Gates Foundation, UK Medical Research Council, and UK Department for International Development.

We report the first finding of the knockdown Leu-Phe and Leu-Ser mutations associated with resistance to pyrethroids and DDT insecticides in the malaria mosquito Anopheles gambiae from Cameroon. The Leu-Phe mutation was found in both the M and S molecular forms of An. gambiae. Importantly, two specimens of the S molecular form were found to carry both mutations in a heterozygous state.

A large-scale survey of Anopheles gambiae Giles, 1902 susceptibility to DDT, dieldrin, permethrin, and deltamethrin was conducted in the Republic of Cameroon. 15 field populations from various geographical areas were tested using World Health Organization test kits for adult mosquitoes. The laboratory Kisumu susceptible reference strain was tested as a control. Results showed that dieldrin and DDT resistance was still present in some populations, and indicated permethrin or deltamethrin resistance. Within the Anopheles gambiae complex, resistant individuals belonged to An. gambiae s.s. and An. arabiensis species. Both M and S molecular forms of An. gambiae s.s. were found resistant. In most of resistant populations, the knockdown times were 2-5-folds increased. However, none of the surviving mosquitoes was positive to the kdr "Leu-Phe" mutation using polymerase chain reaction (PCR) diagnostic test. These results likely suggested involvement of other resistance mechanism(s), such as enzyme detoxification or kdr "Leu-Ser" mutation. Researches on An. gambiae s.l. resistance should be promoted in Cameroon, to improve malaria vector control programs and to implement resistance management strategies.

SummaryWe have produced maps of Plasmodium falciparum malaria transmission in West and Central Africa using the Mapping Malaria Risk in Africa (MARA) database comprising all malaria prevalence surveys in these regions that could be geolocated. The 1846 malaria surveys analysed were carried out during different seasons, and were reported using different age groupings of the human population. To allow comparison between these, we used the Garki malaria transmission model to convert the malaria prevalence data at each of the 976 locations sampled to a single estimate of transmission intensity E, making use of a seasonality model based on Normalized Difference Vegetation Index (NDVI), temperature and rainfall data. We fitted a Bayesian geostatistical model to E using further environmental covariates and applied Bayesian kriging to obtain smooth maps of E and hence of age-specific prevalence. The product is the first detailed empirical map of variations in malaria transmission intensity that includes Central Africa. It has been validated by expert opinion and in general confirms known patterns of malaria transmission, providing a baseline against which interventions such as insecticidetreated nets programmes and trends in drug resistance can be evaluated. There is considerable geographical variation in the precision of the model estimates and, in some parts of West Africa, the predictions differ substantially from those of other risk maps. The consequent uncertainties indicate zones where further survey data are needed most urgently. Malaria risk maps based on compilations of heterogeneous survey data are highly sensitive to the analytical methodology.keywords entomological inoculation rate, kriging, malaria, markov chain monte carlo, parasite prevalence, vectorial capacity

The spread of insecticide resistance genes in Anopheles gambiae Giles sensu stricto threatens to compromise vector-based malaria control programs. Two mutations at the same locus in the voltage-gated sodium channel gene are known to confer knockdown resistance (kdr) to pyrethroids and DDT. Kdr-e involves a leucine-serine substitution, and it was until recently thought to be restricted to East Africa, whereas kdr-w, which involves a leucine-phenylalanine substitution, is associated with resistance in West Africa. In this study, we analyze the frequency and relationship between the kdr genotypes and resistance to type I and type II pyrethroids and DDT by using WHO test kits in both the Forest-M and S molecular forms of An. gambiae in Cameroon. Both kdr-w and kdr-e polymorphisms were found in sympatric An. gambiae, and in many cases in the same mosquito. Kdr-e and kdr-w were detected in both forms, but they were predominant in the S form. Both kdr-e and kdr-w were closely associated with resistance to DDT and weakly associated with resistance to type II pyrethroids. Kdr-w conferred greater resistance to permethrin than kdr-e. We also describe a modified diagnostic designed to detect both resistant alleles simultaneously.