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Background Thioester-containing protein 1 (TEP1) is a highly polymorphic gene playing an important role in mosquito immunity to parasite development and associated with Anopheles gambiae vectorial competence. Allelic variations in TEP1 could render mosquito either susceptible or resistant to parasite infection. Despite reports of TEP1 genetic variations in An. gambiae, the correlation between TEP1 allelic variants and transmission patterns in malaria endemic settings remains unclear. Methods TEP1 allelic variants were characterized by PCR from archived genomic DNA of > 1000 An. gambiae mosquitoes collected at 3 time points between 2009 and 2019 from eastern Gambia, where malaria transmission remains moderately high, and western regions with low transmission. Results Eight common TEP1 allelic variants were identified at varying frequencies in An. gambiae from both transmission settings. These comprised the wild type TEP1, homozygous susceptible genotype, TEP1s; homozygous resistance genotypes: TEP1rA and TEP1rB, and the heterozygous resistance genotypes: TEP1srA, TEP1srB, TEP1rArB and TEP1srArB. There was no significant disproportionate distribution of the TEP1 alleles by transmission setting and the temporal distribution of alleles was also consistent across the transmission settings. TEP1s was the most common in all vector species in both settings (allele frequencies: East = 21.4–68.4%. West = 23.5–67.2%). In Anopheles arabiensis, the frequency of wild type TEP1 and susceptible TEP1s was significantly higher in low transmission setting than in high transmission setting (TEP1: Z = − 4.831, P TEP1s: Z = − 2.073, P = 0.038). Conclusions The distribution of TEP1 allele variants does not distinctly correlate with malaria endemicity pattern in The Gambia. Further studies are needed to understand the link between genetic variations in vector population and transmission pattern in the study settings. Future studies on the implication for targeting TEP1 gene for vector control strategy such as gene drive systems in this settings is also recommended.

Background Carriers of persistent asymptomatic Plasmodium falciparum infections constitute an infectious reservoir that maintains malaria transmission. Understanding the extent of carriage and characteristics of carriers specific to endemic areas could guide use of interventions to reduce infectious reservoir. Methods In eastern Gambia, an all-age cohort from four villages was followed up from 2012 to 2016. Each year, cross-sectional surveys were conducted at the start and end of the malaria transmission season to determine asymptomatic P. falciparum carriage by microscopy while passive case detection was conducted during the transmission to determine incidence of clinical malaria. Association between carriage at the end of a season and at the start of the next and risk factors for this were assessed. Effect of carriage at the start of the season on risk of clinical malaria during the season was also examined. Results A total of 1403 individuals − 1154 from a semi-urban village and 249 from three rural villages were enrolled; median age was 12 years (IQR 6, 30) and 12 years (IQR 7, 27) respectively. In adjusted analysis, asymptomatic P. falciparum carriage at the end of a transmission season and at the start of the next were strongly associated (OR = 19.99; 95% CI 12.57–31.77, P P. falciparum carriage at the end of a transmission season strongly predicts carriage at the start the next season. Odds of carriage across seasons was higher in villages with relatively higher transmission and in older children. Interventions that reduce persistent asymptomatic infections can be applied in a targeted manner and may supress the initiation of yearly seasonal malaria transmission.

Background Recent reports of a change in the resting behaviour of malaria vectors, from predominantly indoor resting to outdoor resting following blood feeding, have been attributed to selection pressure from use of vector control tools such as indoor residual spraying and long-lasting insecticide-treated nets. Recent studies have observed vectors resting predominantly outdoors in settings where anti-vector tools are extensively deployed. This present study examined if the outdoor resting behaviour in the vector population, is random or indicative of a consistent preference of one resting site over the other. Methods Mark-release-recapture (MRR) experiments were conducted with outdoor-resting Anopheles gambiae and An. funestus mosquitoes collected from pit shelters, animal houses and granaries in two villages in Northern Ghana during rainy and dry seasons. Mosquitoes were marked with fluorescent dyes and released indoors. The experiments were controlled with indoor-resting mosquitoes, which were marked and released outdoors. Species of all recaptured mosquitoes were identified and assessed for consistency in their resting behaviour. Results A total of 4,460 outdoor-resting mosquitoes comprising An. gambiae sensu lato (s.l.) (2,630, 59%) and An. funestus complex (1,830, 41%) were marked and released. Overall, 31 (0.7%) mosquitoes were recaptured mostly from outdoor location comprising 25 (81%) An. gambiae s.l. and 6 (19%) An. funestus complex. Only 3 (10%) of the recaptured mosquitoes were found resting indoors where they were released. The majority of the outdoor-recaptured mosquitoes were An. arabiensis (11, 39%), followed by An. coluzzii (7, 25%); whereas all indoor-recaptured mosquitoes were An. coluzzii. For the control experiment, 324 indoor-resting mosquitoes constituting 313 (97%) An. gambiae s.l. and 11 (3%) An. funestus complex were marked and released. However, none of these was recaptured neither indoors nor outdoors. More mosquitoes were significantly captured and recaptured during rainy season ( Z = 6.579, P

Background The scale-up of indoor residual spraying and long-lasting insecticidal nets, together with other interventions have considerably reduced the malaria burden in The Gambia. This study examined the biting and resting preferences of the local insecticide-resistant vector populations few years following scale-up of anti-vector interventions. Method Indoor and outdoor-resting Anopheles gambiae mosquitoes were collected between July and October 2019 from ten villages in five regions in The Gambia using pyrethrum spray collection (indoor) and prokopack aspirator from pit traps (outdoor). Polymerase chain reaction assays were performed to identify molecular species, insecticide resistance mutations, Plasmodium infection rate and host blood meal. Results A total of 844 mosquitoes were collected both indoors (421, 49.9%) and outdoors (423, 50.1%). Four main vector species were identified, including An. arabiensis (indoor: 15%, outdoor: 26%); An. coluzzii (indoor: 19%, outdoor: 6%), An. gambiae s.s. (indoor: 11%, outdoor: 16%), An. melas (indoor: 2%, outdoor: 0.1%) and hybrids of An. coluzzii-An. gambiae s.s (indoors: 3%, outdoors: 2%). A significant preference for outdoor resting was observed in An. arabiensis (Pearson X2 = 22.7, df = 4, PAn. coluzzii (Pearson X2 = 55.0, df = 4, PVgsc)-1014S was significantly higher in the indoor-resting (allele freq. = 0.96, 95%CI: 0.78–1, P = 0.03) than outdoor-resting (allele freq. = 0.82, 95%CI: 0.76–0.87) An. arabiensis population. For An. coluzzii, the prevalence of most mutation markers was higher in the outdoor (allele freq. = 0.92, 95%CI: 0.81–0.98) than indoor-resting (allele freq. = 0.78, 95%CI: 0.56–0.86) mosquitoes. However, in An. gambiae s.s., the prevalence of Vgsc-1014F, Vgsc-1575Y and GSTe2-114T was high (allele freq. = 0.96–1), but did not vary by resting location. The overall sporozoite positivity rate was 1.3% (95% CI: 0.5–2%) in mosquito populations. Indoor-resting An. coluzzii had mainly fed on human blood while indoor-resting An. arabiensis fed on animal blood. Conclusion In this study, high levels of resistance mutations were observed that could be influencing the mosquito populations to rest indoors or outdoors. The prevalent animal-biting behaviour demonstrated in the mosquito populations suggest that larval source management could be an intervention to complement vector control in this setting.

BackgroundThe scale-up of indoor residual spraying and long-lasting insecticidal nets, together with other interventions have considerably reduced the malaria burden in The Gambia. This study examined the biting and resting preferences of the local insecticide-resistant vector populations few years following scale-up of anti-vector interventions.MethodIndoor and outdoor-resting Anopheles gambiae mosquitoes were collected between July and October 2019 from ten villages in five regions in The Gambia using pyrethrum spray collection (indoor) and prokopack aspirator from pit traps (outdoor). Polymerase chain reaction assays were performed to identify molecular species, insecticide resistance mutations, Plasmodium infection rate and host blood meal. ResultsA total of 844 mosquitoes were collected both indoors (421, 49.9%) and outdoors (423, 50.1%). Four main vector species were identified, including An. arabiensis (indoor: 15%, outdoor: 26%); An. coluzzii (indoor: 19%, outdoor: 6%), An. gambiae s.s. (indoor: 11%, outdoor: 16%), An. melas (indoor: 2%, outdoor: 0.1%) and hybrids of An. coluzzii-An. gambiae (indoors: 3%, outdoors: 2%). A significant preference for outdoor resting was observed in An. arabiensis (Pearson X2=22.7, df=4, PAn. coluzzii (Pearson X2=55.0, df=4, PVgsc)-1014S was higher in the indoor-resting (allele freq. = 0.96, 95%CI: 0.78–1) than outdoor-resting (allele freq. = 0.82, 95%CI: 0.76–0.87) An. arabiensis population. For An. coluzzii, the prevalence of most mutation markers were higher in the outdoor (allele freq. = 0.92, 95%CI: 0.81–0.98) than indoor-resting (allele freq. = 0.78, 95%CI: 0.56–0.86) mosquitoes. Sporozoite positivity rate was 1.3% (95% CI: 0.5–2%). Indoor-resting An. coluzzii had mainly fed on human blood while indoor-resting An. arabiensis, animal blood.ConclusionThe indoor-resting behavior of An. arabiensis that preferred animal blood and had low sporozoite rates, may be determined by the Vgsc-1014S mutation. Control interventions may include complementary vector control approaches such as zooprophylaxis.

Background: Selection pressure from continued exposure to insecticides drives the development of insecticide resistance and changes in resting behavior of malaria vectors, which may support residual transmission in several endemic settings. There is a need to understand how resistance drives changes in resting behavior within vector species. Here, we examined the association between insecticide resistance and resting behavior of Anopheles gambiae s.l. in Northern Ghana. Methods: Adult mosquitoes were collected both indoors and outdoors from two communities using mouth aspirators and pit shelters. F1 progenies from a subset of mosquitoes were exposed to dichloro diphenyl trichloroethane (DDT), deltamethrin, malathion and bendiocarb using WHO insecticide susceptibility tests. Insecticide resistance markers including voltage-gated sodium channel (Vgsc)- 1014F, Vgsc-1014S, Vgsc-1575Y, glutathione-S-transferase epsilon 2 (GSTe2)-114T and acetylcholinesterase (Ace1)-119S, as well as blood meal sources were investigated using PCR methods. Activities of metabolic enzymes, acetylcholine esterase (AChE), non-specific β-esterases, glutathione-S-transferase (GST) and monooxygenases (oxidases) were measured from unexposed F1 progenies using microplate assays. Results: Susceptibility of An. coluzzii to deltamethrin 24hr post-exposure was significantly higher in indoor (mortality=5%) than the outdoor (mortality=2.5%) populations (P=0.02). The mosquitoes were fully susceptible to malathion (mortality: indoor=98%, outdoor=100%). Susceptibility to DDT was significantly higher in outdoor (mortality=9%) than indoor (mortality=0%) mosquitoes (P=0.006). Mosquitoes were also found with suspected resistance to bendiocarb but mortality was not statistically different (mortality: indoor=90%, outdoor=95%. P=0.30). The frequencies of all resistance alleles were higher in F1 outdoor (0.11-0.85) than indoor (0.04-0.65) mosquito populations, while Vgsc-1014F in F0 An. gambiae s.s significantly associated with outdoor-resting behavior (P=0.01). Activities of non-specific β-esterase enzymes were significantly higher in outdoor than indoor mosquitoes (Mean enzyme activity: Outdoor=: 1.70/mg protein; Indoor=1.35/mg protein. PConclusions: These findings revealed higher phenotypic resistance in indoor than outdoor-resting mosquitoes, but genotypic and metabolic resistance levels were higher in outdoor than the indoor mosquito populations. However, the overall results did not establish that there was a significant preference of resistant malaria vectors to solely rest indoors or outdoors, but varied depending on the resistant alleles present. Indication that human and animal blood meal indices were more prevalent in indoor-resting mosquitoes was also shown. Continued monitoring of changes in resting behavior within An. gambiae s.l. populations is recommended.

Background Selection pressure from continued exposure to insecticides drives development of insecticide resistance and changes in resting behaviour of malaria vectors. There is need to understand how resistance drives changes in resting behaviour within vector species. The association between insecticide resistance and resting behaviour of Anopheles gambiae sensu lato (s.l.) in Northern Ghana was examined. Methods F1 progenies from adult mosquitoes collected indoors and outdoors were exposed to DDT, deltamethrin, malathion and bendiocarb using WHO insecticide susceptibility tests. Insecticide resistance markers including voltage-gated sodium channel (Vgsc)-1014F, Vgsc-1014S, Vgsc-1575Y, glutathione-S-transferase epsilon 2 (GSTe2)-114T and acetylcholinesterase (Ace1)-119S, as well as blood meal sources were investigated using PCR methods. Activities of metabolic enzymes, acetylcholine esterase (AChE), non-specific β-esterases, glutathione-S-transferase (GST) and monooxygenases were measured from unexposed F1 progenies using microplate assays. Results Susceptibility of Anopheles coluzzii to deltamethrin 24 h post-exposure was significantly higher in indoor (mortality = 5%) than outdoor (mortality = 2.5%) populations (P = 0.02). Mosquitoes were fully susceptible to malathion (mortality: indoor = 98%, outdoor = 100%). Susceptibility to DDT was significantly higher in outdoor (mortality = 9%) than indoor (mortality = 0%) mosquitoes (P = 0.006). Mosquitoes were also found with suspected resistance to bendiocarb but mortality was not statistically different (mortality: indoor = 90%, outdoor = 95%. P = 0.30). Frequencies of all resistance alleles were higher in F1 outdoor (0.11–0.85) than indoor (0.04–0.65) mosquito populations, while Vgsc-1014F in F0An. gambiae sensu stricto (s.s) was significantly associated with outdoor-resting behaviour (P = 0.01). Activities of non-specific β-esterase enzymes were significantly higher in outdoor than indoor mosquitoes (Mean enzyme activity: Outdoor = : 1.70/mg protein; Indoor = 1.35/mg protein. P Conclusions The overall results did not establish that there was a significant preference of resistant malaria vectors to solely rest indoors or outdoors, but varied depending on the resistant alleles present. Phenotypic resistance was higher in indoor than outdoor-resting mosquitoes, but genotypic and metabolic resistance levels were higher in outdoor than the indoor populations. Continued monitoring of changes in resting behaviour within An. gambiae s.l. populations is recommended.

Background Insecticide resistance threatens malaria control in sub-Saharan Africa. Knockdown resistance to pyrethroids and organochlorines in Anopheles gambiae sensu lato (s.l.) is commonly caused by mutations in the gene encoding a voltage-gated sodium channel which is the target site for the insecticide. The study aimed to examine risk factors for knockdown resistance in An. gambiae s.l. and its relationship with malaria infection in children in rural Gambia. Point mutations at the Vgsc-1014 locus, were measured in An. gambiae s.l. during a 2-year trial. Cross-sectional surveys were conducted at the end of the transmission season to measure malaria infection in children aged 6 months–14 years. Results Whilst few Anopheles arabiensis and Anopheles coluzzii had Vgsc-1014 mutations, the proportion of An. gambiae sensu stricto (s.s.) mosquitoes homozygous for the Vgsc-1014F mutation increased from 64.8 to 90.9% during the study. The Vgsc-1014S or 1014F mutation was 80% higher in 2011 compared to 2010, and 27% higher in the villages with indoor residual spraying compared to those without. An increase in the proportion of An. gambiae s.l. mosquitoes with homozygous Vgsc-1014F mutations and an increase in the proportion of An. gambiae s.s. in a cluster were each associated with increased childhood malaria infection. Homozygous Vgsc-1014F mutations were, however, most common in An. gambiae s.s. and almost reached saturation during the study meaning that the two variables were colinear. Conclusions As a result of colinearity between homozygous Vgsc-1014F mutations and An. gambiae s.s., it was not possible to determine whether insecticide resistance or species composition increased the risk of childhood malaria infection. Electronic supplementary material The online version of this article (10.1186/s12936-018-2348-8) contains supplementary material, which is available to authorized users.

Contains fulltext : 182386.pdf (Publisher’s version ) (Open Access) Over the last decades, malaria has declined substantially in The Gambia but its transmission has not been interrupted. In order to better target control interventions, it is essential to understand the dynamics of residual transmission. This prospective cohort study was conducted between June 2013 and April 2014 in six pairs of villages across The Gambia. Blood samples were collected monthly during the transmission season (June-December) from all residents aged >/=6 months (4,194 individuals) and then in April (dry season). Entomological data were collected monthly throughout the malaria transmission season. Ownership of Long-Lasting Insecticidal Nets was 71.5% (2766/3869). Incidence of malaria infection and clinical disease varied significantly across the country, with the highest values in eastern (1.7/PYAR) than in central (0.2 /PYAR) and western (0.1/PYAR) Gambia. Malaria infection at the beginning of the transmission season was significantly higher in individuals who slept outdoors (HR = 1.51, 95% CI: 1.02-2.23, p = 0.04) and in those who had travelled outside the village (HR = 2.47, 95% CI: 1.83-3.34, p

Aims: Antimalarial biguanides are metabolized by CYP2C19, thus genetic variation at the CYP2C locus might affect pharmacokinetics and so treatment outcome for malaria. Materials & methods: Polymorphisms in CYP2C19 and CYP2C9 in 43 adult Gambians treated with chlorproguanil/dapsone for uncomplicated malaria were assessed. Chlorcycloguanil pharmacokinetics were measured and associations with CYP2C19 and CYP2C9 alleles and CYP2C19 metabolizer groups investigated. Results: All CYP2C19/CYP2C9 alleles obeyed Hardy–Weinberg equilibrium. There were 15 CYP2C19/2C9 haplotypes with a common haplotype frequency of 0.23. Participants with the CYP2C19*17 allele had higher chlorcycloguanil area under the concentration versus curve at 24 h (AUC0–24) than those without (geometric means: 317 vs 216 ng.h/ml; ratio of geometric means: 1.46; 95% CI: 1.03 to 2.09; p = 0.0363) and higher Cmax (geometric mean ratio: 1.52; 95% CI: 1.13 to 2.05; p = 0.0071). Conclusion: CYP2C19*17 determines antimalarial biguanide metabolic profile at the CYP2C19/CYP2C9 locus.