Effects of Menstrual Health and Hygiene on School Absenteeism and Drop-Out among Adolescent Girls in Rural Gambia.

Poor knowledge and management of menstruation impacts girls' school attendance and academic performance. This paper aims to explore how menstrual hygiene management practices and related factors influence school absenteeism and drop-out among primary and secondary school girls in rural Gambia. Mixed-method studies were conducted among students and key informants from 19 schools from July 2015-December 2017. Focus group discussions, in-depth interviews, cross-sectional surveys, menstrual diaries, and school water, sanitation and hygiene (WASH) facility observations were used. Key findings from the interviews were that menstrual pain, cultural beliefs, fear of peers knowing menstrual status, and poor school WASH facilities led to school absenteeism, however, they had no impact on school drop-out. Of the 561 girls surveyed, 27% reported missing at least one school day per month due to menses. Missing school during the most recent menstrual period was strongly associated with menstrual pain (extreme pain adjusted odds ratio (AOR) = 16.8 (95% CI: 7.29-38.74)), as was having at least one symptom suggestive of urinary tract infection (AOR = 1.71 (95% CI: 1.16-2.52)) or reproductive tract infection (AOR = 1.99 (95% CI: 1.34-2.94)). Clean toilets (AOR = 0.44 (95% CI: 0.26-75)), being happy using school latrines while menstruating (AOR = 0.59 (95% CI: 0.37-0.93)), and soap availability (AOR = 0.46 (95% CI: 0.3-0.73)) were associated with reduced odds of school absenteeism. This study suggests menstrual pain, school WASH facilities, urogenital infections, and cultural beliefs affected school attendance among menstruating girls in rural Gambia

A rite of passage: a mixed methodology study about knowledge, perceptions and practices of menstrual hygiene management in rural Gambia.

BACKGROUND: Appropriate menstrual hygiene management (MHM) is impeded by taboos and secrecy surrounding menstruation. Unhygienic menstrual practices and unpreparedness for managing menstruation has been associated with adverse health and social outcomes among adolescent girls. In The Gambia, there is limited data on menstrual practices among girls and women in rural communities and the sources of information about menstruation for the adolescents. This study aimed to explore knowledge, preparedness and practices of menstruation and its management among adolescents, mothers and teachers in rural Gambia. METHODS: A mixed methods study was conducted in the rural Kiang West district of The Gambia. Twenty focus group discussions and thirteen in-depth interviews were conducted among mothers, adolescents and teachers to explore their views on menstruation, cultural beliefs, sources and level of knowledge on menstruation and MHM practices. In addition, a survey was done among 331 school girls to assess their knowledge, practices and attitudes of menstruation and its management. Inductive content analysis was used to analyse the qualitative data, and descriptive analysis and chi-squared tests were used to analyse quantitative data. RESULTS: All participants had different levels of knowledge about menstruation. Knowledge score was higher among post-menarche girls compare with pre-menarche girls (p = 0.0001). All groups expressed difficulties, embarrassment and shame in relation to discussing menstruation. Two thirds of the surveyed girls reported having learnt about menstruation before menarche, however at menarche most felt unprepared. Teachers were the main source of information, but when asking for advice most girls preferred to ask their mothers. Mothers reported facing difficulties in discussing menstruation with their children and felt that boys did not need to be taught about it, however boys were very curious to know about. Most girls used reusable cloth unless they are given free pads from school. CONCLUSION: Taboos, secrecy and embarrassment associated with discussing menstruation hinder adolescents from seeking advice from parents and teachers on appropriate MHM practices. Strategies to encourage positive social norms towards menstruation would help to promote more open discussions about it at the family, community and national level, which will support improvements in MHM in this and similar communities in low and middle income settings

Prevention of the Recurrence of Anaemia in Gambian Children Following Discharge from Hospital

BACKGROUND: In malaria endemic countries, children who have experienced an episode of severe anaemia are at increased risk of a recurrence of anaemia. There is a need to find ways of protecting these at risk children from malaria and chemoprevention offers a potential way of achieving this objective. METHODS: During the 2003 and 2004 malaria transmission seasons, 1200 Gambian children with moderate or severe anaemia (Hb concentration <7 g/dL) were randomised to receive either monthly sulfadoxine-pyrimethamine (SP) or placebo until the end of the malaria transmission season in which they were enrolled, in a double-blind trial. All study subjects were treated with oral iron for 28 days and morbidity was monitored through surveillance at health centres. The primary endpoint was the proportion of children with moderate or severe anaemia at the end of the transmission season. Secondary endpoints included the incidence of clinical episodes of malaria during the surveillance period, outpatient attendances, the prevalence of parasitaemia and splenomegaly, nutritional status at the end of the malaria transmission season and compliance with the treatment regimen. RESULTS: The proportions of children with a Hb concentration of <7 g/dL at the end of the malaria transmission season were similar in the two study groups, 14/464 (3.0%) in children who received at least one dose of SP and 16/471 (3.4%) in those who received placebo, prevalence ratio 0.89 (0.44,1.8) P = 0.742. The protective efficacy of SP against episodes of clinical malaria was 53% (95% CI 37%, 65%). Treatment with SP was safe and well tolerated; no serious adverse events related to SP administration were observed. Mortality following discharge from hospital was low among children who received SP or placebo (6 in the SP group and 9 in the placebo group respectively). CONCLUSIONS: Intermittent treatment with SP did not reduce the proportion of previously anaemic children with moderate or severe anaemia at the end of the malaria season, although it prevented malaria. The combination of appropriate antimalarial treatment plus one month of iron supplementation and good access to healthcare during follow-up proved effective in restoring haemoglobin to an acceptable level in the Gambian setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT00131716

Further evidence supporting a role for gs signal transduction in severe malaria pathogenesis.

With the functional demonstration of a role in erythrocyte invasion by Plasmodium falciparum parasites, implications in the aetiology of common conditions that prevail in individuals of African origin, and a wealth of pharmacological knowledge, the stimulatory G protein (Gs) signal transduction pathway presents an exciting target for anti-malarial drug intervention. Having previously demonstrated a role for the G-alpha-s gene, GNAS, in severe malaria disease, we sought to identify other important components of the Gs pathway. Using meta-analysis across case-control and family trio (affected child and parental controls) studies of severe malaria from The Gambia and Malawi, we sought evidence of association in six Gs pathway candidate genes: adenosine receptor 2A (ADORA2A) and 2B (ADORA2B), beta-adrenergic receptor kinase 1 (ADRBK1), adenylyl cyclase 9 (ADCY9), G protein beta subunit 3 (GNB3), and regulator of G protein signalling 2 (RGS2). Our study amassed a total of 2278 cases and 2364 controls. Allele-based models of association were investigated in all genes, and genotype and haplotype-based models were investigated where significant allelic associations were identified. Although no significant associations were observed in the other genes, several were identified in ADORA2A. The most significant association was observed at the rs9624472 locus, where the G allele (approximately 20% frequency) appeared to confer enhanced risk to severe malaria [OR = 1.22 (1.09-1.37); P = 0.001]. Further investigation of the ADORA2A gene region is required to validate the associations identified here, and to identify and functionally characterize the responsible causal variant(s). Our results provide further evidence supporting a role of the Gs signal transduction pathway in the regulation of severe malaria, and request further exploration of this pathway in future studies

TLR9 polymorphisms in African populations: no association with severe malaria, but evidence of cis-variants acting on gene expression

Background During malaria infection the Toll-like receptor 9 (TLR9) is activated through induction with plasmodium DNA or another malaria motif not yet identified. Although TLR9 activation by malaria parasites is well reported, the implication to the susceptibility to severe malaria is not clear. The aim of this study was to assess the contribution of genetic variation at TLR9 to severe malaria. Methods This study explores the contribution of TLR9 genetic variants to severe malaria using two approaches. First, an association study of four common single nucleotide polymorphisms was performed on both family- and population-based studies from Malawian and Gambian populations (n>6000 individual). Subsequently, it was assessed whether TLR9 expression is affected by cis-acting variants and if these variants could be mapped. For this work, an allele specific expression (ASE) assay on a panel of HapMap cell lines was carried out. Results No convincing association was found with polymorphisms in TLR9 for malaria severity, in either Gambian or Malawian populations, using both case-control and family based study designs. Using an allele specific expression assay it was observed that TLR9 expression is affected by cis-acting variants, these results were replicated in a second experiment using biological replicates. Conclusion By using the largest cohorts analysed to date, as well as a standardized phenotype definition and study design, no association of TLR9 genetic variants with severe malaria was found. This analysis considered all common variants in the region, but it is remains possible that there are rare variants with association signals. This report also shows that TLR9 expression is potentially modulated through cis-regulatory variants, which may lead to differential inflammatory responses to infection between individuals

TLR9 polymorphisms in African populations: no association with severe malaria, but evidence of cis-variants acting on gene expression

BACKGROUND: During malaria infection the Toll-like receptor 9 (TLR9) is activated through induction with plasmodium DNA or another malaria motif not yet identified. Although TLR9 activation by malaria parasites is well reported, the implication to the susceptibility to severe malaria is not clear. The aim of this study was to assess the contribution of genetic variation at TLR9 to severe malaria. METHODS: This study explores the contribution of TLR9 genetic variants to severe malaria using two approaches. First, an association study of four common single nucleotide polymorphisms was performed on both family- and population-based studies from Malawian and Gambian populations (n>6000 individual). Subsequently, it was assessed whether TLR9 expression is affected by cis-acting variants and if these variants could be mapped. For this work, an allele specific expression (ASE) assay on a panel of HapMap cell lines was carried out. RESULTS: No convincing association was found with polymorphisms in TLR9 for malaria severity, in either Gambian or Malawian populations, using both case-control and family based study designs. Using an allele specific expression assay it was observed that TLR9 expression is affected by cis-acting variants, these results were replicated in a second experiment using biological replicates. CONCLUSION: By using the largest cohorts analysed to date, as well as a standardized phenotype definition and study design, no association of TLR9 genetic variants with severe malaria was found. This analysis considered all common variants in the region, but it is remains possible that there are rare variants with association signals. This report also shows that TLR9 expression is potentially modulated through cis-regulatory variants, which may lead to differential inflammatory responses to infection between individuals

Lack of Association of Interferon Regulatory Factor 1 with Severe Malaria in Affected Child-Parental Trio Studies across Three African Populations

Interferon Regulatory Factor 1 (IRF-1) is a member of the IRF family of transcription factors, which have key and diverse roles in the gene-regulatory networks of the immune system. IRF-1 has been described as a critical mediator of IFN-gamma signalling and as the major player in driving TH1 type responses. It is therefore likely to be crucial in both innate and adaptive responses against intracellular pathogens such as Plasmodium falciparum. Polymorphisms at the human IRF1 locus have been previously found to be associated with the ability to control P. falciparum infection in populations naturally exposed to malaria. In order to test whether genetic variation at the IRF1 locus also affects the risk of developing severe malaria, we performed a family-based test of association for 18 Single Nucleotide Polymorphisms (SNPs) across the gene in three African populations, using genotype data from 961 trios consisting of one affected child and his/her two parents (555 from The Gambia, 204 from Kenya and 202 from Malawi). No significant association with severe malaria or severe malaria subphenotypes (cerebral malaria and severe malaria anaemia) was observed for any of the SNPs/haplotypes tested in any of the study populations. Our results offer no evidence that the molecular pathways regulated by the transcription factor IRF-1 are involved in the immune-based pathogenesis of severe malaria

Clinical features of severe malaria associated with death: a 13-year observational study in the Gambia.

BACKGROUND: Severe malaria (SM) is a major cause of death in sub-Saharan Africa. Identification of both specific and sensitive clinical features to predict death is needed to improve clinical management. METHODS: A 13-year observational study was conducted from 1997 through 2009 of 2,901 children with SM enrolled at the Royal Victoria Teaching Hospital in The Gambia to identify sensitive and specific predictors of poor outcome in Gambian children with severe malaria between the ages 4 months to 14 years. We have measured the sensitivity and specificity of clinical features that predict death or development of neurological sequelae. FINDINGS: Impaired consciousness (odds ratio {OR} 4.4 [95% confidence interval {CI}, 2.7-7.3]), respiratory distress (OR 2.4 [95%CI, 1.7-3.2]), hypoglycemia (OR 1.7 [95%CI, 1.2-2.3]), jaundice (OR 1.9 [95%CI, 1.2-2.9]) and renal failure (OR 11.1 [95%CI, 3.3-36.5]) were independently associated with death in children with SM. The clinical features that showed the highest sensitivity and specificity to predict death were respiratory distress (area under the curve 0.63 [95%CI, 0.60-0.65]) and impaired consciousness (AUC 0.61[95%CI, 0.59-0.63]), which were comparable to the ability of hyperlactatemia (blood lactate>5 mM) to predict death (AUC 0.64 [95%CI, 0.55-0.72]). A Blantyre coma score (BCS) of 2 or less had a sensitivity of 74% and specificity of 67% to predict death (AUC 0.70 [95% C.I. 0.68-0.72]), and sensitivity and specificity of 74% and 69%, respectively to predict development of neurological sequelae (AUC 0.72 [95% CI, 0.67-0.76]).The specificity of this BCS threshold to identify children at risk of dying improved in children less than 3 years of age (AUC 0.74, [95% C.I 0.71-0.76]). CONCLUSION: The BCS is a quantitative predictor of death. A BCS of 2 or less is the most sensitive and specific clinical feature to predict death or development of neurological sequelae in children with SM