Field performance of the malaria highly sensitive rapid diagnostic test in a setting of varying malaria transmission.

BACKGROUND: The Gambia has successfully reduced malaria transmission. The human reservoir of infection could further decrease if malaria-infected individuals could be identified by highly sensitive, field-based, diagnostic tools and then treated. METHODS: A cross-sectional survey was done at the peak of the 2017 malaria season in 47 Gambian villages. From each village, 100 residents were randomly selected for finger-prick blood samples to detect Plasmodium falciparum infections using highly sensitive rapid diagnostic tests (HS-RDT) and PCR. The sensitivity and specificity of the HS-RDT were estimated (assuming PCR as the gold standard) across varying transmission intensities and in different age groups. A deterministic, age-structured, dynamic model of malaria transmission was used to estimate the impact of mass testing and treatment (MTAT) with HS-RDT in four different scenarios of malaria prevalence by PCR: 5, 15, 30, and 60%, and with seasonal transmission. The impact was compared both to MTAT with conventional RDT and mass drug administration (MDA). RESULTS: Malaria prevalence by HS-RDT was 15% (570/3798; 95% CI 13.9-16.1). The HS-RDT sensitivity and specificity were 38.4% (191/497, 95% CI 34.2-42.71) and 88.5% (2922/3301; 95% CI 87.4-89.6), respectively. Sensitivity was the highest (50.9%, 95% CI 43.3-58.5%) in high prevalence villages (20-50% by PCR). The model predicted that in very low transmission areas (≤ 5%), three monthly rounds of MTAT with HS-RDT, starting towards the end of the dry season and testing 65 or 85% of the population for 2 consecutive years, would avert 62 or 78% of malaria cases (over 2 years), respectively. The effect of the intervention would be lower in a moderate transmission setting. In all settings, MDA would be superior to MTAT with HS-RDT which would be superior to MTAT with conventional RDT. CONCLUSION: The HS-RDT's field sensitivity was modest and varied by transmission intensity. In low to very low transmission areas, three monthly rounds per year of MTAT with HS-RDT at 85% coverage for 2 consecutive years would reduce malaria prevalence to such low levels that additional strategies may achieve elimination. The model prediction would need to be confirmed by cluster-randomized trials.

Correction to: Emergence of knock-down resistance in the Anopheles gambiae complex in the Upper River Region, The Gambia, and its relationship with malaria infection in children.

Unfortunately, the original article [1] contained an error mistakenly carried forward by the Production department handling this article whereby some figures and their captions were interchanged. The correct figures (Figs. 1, 2, 3, 4, 5) and captions are presented in this erratum. The original article has also been updated to reflect this correction.

Emergence of knock-down resistance in the Anopheles gambiae complex in the Upper River Region, The Gambia, and its relationship with malaria infection in children.

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.

Is chronic malnutrition associated with an increase in malaria incidence? A cohort study in children aged under 5 years in rural Gambia.

BACKGROUND: Malnutrition is common in children in sub-Saharan Africa and is thought to increase the risk of infectious diseases, including malaria. The relationship between malnutrition and malaria was examined in a cohort of 6-59 month-old children in rural Gambia, in an area of seasonal malaria transmission. The study used data from a clinical trial in which a cohort of children was established and followed for clinical malaria during the 2011 transmission season. A cross-sectional survey to determine the prevalence of malaria and anaemia, and measure the height and weight of these children was carried out at the beginning and end of the transmission season. Standard anthropometric indices (stunting, wasting and underweight) were calculated using z-scores. RESULTS: At the beginning of the transmission season, 31.7% of children were stunted, 10.8% wasted and 24.8% underweight. Stunting was more common in Fula children than other ethnicities and in children from traditionally constructed houses compared to more modern houses. Stunted children and underweight children were significantly more likely to have mild or moderate anaemia. During the transmission season, 13.7% of children had at least one episode of clinical malaria. There was no association between stunting and malaria incidence (odds ratio = 0.79, 95% CI: 0.60-1.05). Malaria was not associated with differences in weight or height gain. CONCLUSIONS: Chronic malnutrition remains a problem in rural Gambia, particularly among the poor and Fula ethnic group, but it was not associated with an increased risk of malaria. TRIAL REGISTRATION: Trial registration: ISRCTN, ISRCTN01738840 , registered: 27/08/2010 (Retrospectively registered).

To assess whether indoor residual spraying can provide additional protection against clinical malaria over current best practice of long-lasting insecticidal mosquito nets in The Gambia: study protocol for a two-armed cluster-randomised trial.

BACKGROUND: Recently, there has been mounting interest in scaling-up vector control against malaria in Africa. It needs to be determined if indoor residual spraying (IRS with DDT) will provide significant marginal protection against malaria over current best practice of long-lasting insecticidal nets (LLINs) and prompt treatment in a controlled trial, given that DDT is currently the most persistent insecticide for IRS. METHODS: A 2 armed cluster-randomised controlled trial will be conducted to assess whether DDT IRS and LLINs combined provide better protection against clinical malaria in children than LLINs alone in rural Gambia. Each cluster will be a village, or a group of small adjacent villages; all clusters will receive LLINs and half will receive IRS in addition. Study children, aged 6 months to 13 years, will be enrolled from all clusters and followed for clinical malaria using passive case detection to estimate malaria incidence for 2 malaria transmission seasons in 2010 and 2011. This will be the primary endpoint. Exposure to malaria parasites will be assessed using light and exit traps followed by detection of Anopheles gambiae species and sporozoite infection. Study children will be surveyed at the end of each transmission season to estimate the prevalence of Plasmodium falciparum infection and the prevalence of anaemia. DISCUSSION: Practical issues concerning intervention implementation, as well as the potential benefits and risks of the study, are discussed. TRIAL REGISTRATION: ISRCTN01738840 - Spraying And Nets Towards malaria Elimination (SANTE).