Search

Background: Menstrual health (MH) is a recognised global public health challenge. Poor MH may lead to absence from school and work, and adverse health outcomes. However, reviews suggest a lack of rigorous evidence for the effectiveness of MH interventions on health and education outcomes. The objective of this paper is to describe the methods used in a cluster-randomised controlled trial to estimate the effect of a multi-component intervention to improve MH and school attendance in The Gambia. Methods: The design ensured half the schools (25) were randomised to receive the intervention which comprised of the following components: (i) Peer education camps and menstrual hygiene laboratories in schools, (ii) Mother's outreach sessions, (iii) Community meetings, and (iv) minor improvements of school Water Sanitation and Hygiene (WASH) facilities and maintenance. The intervention was run over a three-month period, and the evaluation was conducted at least three months after the last intervention activity was completed in the school or community. The other 25 schools acted as controls. Of these 25 control schools one Arabic school dropped out due to COVID-19. The primary outcome was the prevalence of girls missing at least one day of school during their last period. Secondary outcomes included: Urinary Tract Infection (UTI) symptoms, biochemical markers of UTI in urine, Reproductive Tract Infection symptoms, self-reported menstruation related wellbeing, social support and knowledge, perceptions and practices towards menstruation and MH in target school girls. In addition, a process evaluation using observations, routine monitoring data, survey data and interviews was undertaken to assess dose and reach (quantitative data) and assess acceptability, fidelity, context and possible mechanisms of impact (qualitative data). Cost and cost-effectiveness of the intervention package will also be assessed. Conclusion: Results will add to scarce resources available on effectiveness of MH interventions on school attendance. A positive result may encourage policy makers to increase their commitment to improve operation and maintenance of school WASH facilities and include more information on menstruation into the curriculum and help in the reporting and management of infections related to adolescent menstruation. Trial Registration PACTR, PACTR201809769868245, Registered 14th August 2018, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3539 [ABSTRACT FROM AUTHOR]

Musca sorbens (Diptera: Muscidae) flies are thought to be vectors of the blinding eye disease trachoma, carrying the bacterium Chlamydia trachomatis (Ct) between the eyes of individuals. While their role as vectors has been convincingly demonstrated via randomised controlled trials in The Gambia, studies of fly-borne trachoma transmission remain scant and as such our understanding of their ability to transmit Ct remains poor. We examined fly-eye contact and caught eye-seeking flies from 494 individuals (79% aged ≤9 years) in Oromia, Ethiopia. Ct-carrying flies (harbouring Ct DNA) were found to cluster spatially in and nearby to households in which at least one resident had Ct infection. Fly-eye contact was positively associated with the presence of trachoma (disease), lower human body weight and increased human body temperature. Studies of laboratory-reared M. sorbens indicated that Ct is found both externally and internally following feeds to Ct culture, with scanning electron microscopy revealing how Ct bodies can cling to fly hairs (setae). Testing for Ct on field-caught M. sorbens found fly 'bodies' (thorax, wings and abdomen) to consistently test positive for Ct while legs and heads were infrequently Ct-positive. These studies strongly support the role of M. sorbens as vectors of trachoma and highlight the need for improved understanding of fly-borne trachoma transmission dynamics and vector competence. Author summary: Trachoma is a blinding eye disease caused by an infection of the eye by the bacterium Chlamydia trachomatis (Ct). Trachoma is responsible for vision impairment or blindness in 1.8 million people and is the leading infectious cause of blindness worldwide. The presence of flies around the eyes of young children is a common feature of life in trachoma endemic communities worldwide. This fly is most often Musca sorbens, an understudied species thought to transmit Ct. In order to understand more about Musca sorbens flies and their relationship with Ct, the researchers studied 247 households in the Oromia region of Ethiopia, where there is known to be a lot of trachoma. The authors found evidence of Ct on flies and that flies in households containing children with Ct infection were much more likely themselves to be carrying Ct, adding to evidence that M. sorbens flies contribute to transmission of the bacterium. They also found that children who weigh less and currently have trachoma were more likely to have flies land on their face. Should further studies clearly elucidate a role for M. sorbens as vectors of trachoma, controlling fly populations or preventing fly-eye contact may become an important aspect of trachoma disease control. [ABSTRACT FROM AUTHOR]

Background We investigated whether adding community scheduled malaria screening and treatment (CSST) with artemether-lumefantrine by community health workers (CHWs) to standard intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) would improve maternal and infant health. Methods In this 2-arm cluster-randomized, controlled trial, villages in Burkina Faso, The Gambia, and Benin were randomized to receive CSST plus IPTp-SP or IPTp-SP alone. CHWs in the intervention arm performed monthly CSST during pregnancy. At each contact, filter paper and blood slides were collected, and at delivery, a placental biopsy was collected. Primary and secondary endpoints were the prevalence of placental malaria, maternal anemia, maternal peripheral infection, low birth weight, antenatal clinic (ANC) attendance, and IPTp-SP coverage. Results Malaria infection was detected at least once for 3.8% women in The Gambia, 16.9% in Benin, and 31.6% in Burkina Faso. There was no difference between study arms in terms of placenta malaria after adjusting for birth season, parity, and IPTp-SP doses (adjusted odds ratio, 1.06 [95% confidence interval,.78–1.44]; P =.72). No difference between the study arms was found for peripheral maternal infection, anemia, and adverse pregnancy outcomes. ANC attendance was significantly higher in the intervention arm in Burkina Faso but not in The Gambia and Benin. Increasing number of IPTp-SP doses was associated with a significantly lower risk of placenta malaria, anemia at delivery, and low birth weight. Conclusions Adding CSST to existing IPTp-SP strategies did not reduce malaria in pregnancy. Increasing the number of IPTp-SP doses given during pregnancy is a priority. Clinical Trials Registration NCT01941264; ISRCTN37259296. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the effectiveness of PPFP counselling on contraceptives knowledge, attitudes and intention among women attending a general hospital in The Gambia. Materials and Methods: A quasi-experimental design with an intervention and comparison group was used. The intervention was PPFP counselling using the GATHER approach. A sample size of 674 participants was determined by a formula for comparison between the two groups. The questionnaire was developed based on a literature review and was pre-tested on 10% of the total study sample size (68). A reliability of 0.731 was obtained. A systematic random sampling method was employed to select study participants who met the inclusion criteria. Data were collected during face-to-face interviews in local languages with a 100% response rate at baseline and 96% at post-test. Data were analysed using the SPSS version 21.00 and the statistical analysis included both descriptive and inferential methods. An ethical approval was obtained from the Research and Ethics Committee, School of Basic Medical Sciences, College of Medicine, University of Benin (CMS/REC/2017/017) and the Gambia Government/Medical Research Council Laboratories Joint Ethics Committee (R017016Av1.1). Results: Baseline respondents' socio-demographic characteristics revealed that the two groups had similar characteristics. A statistically significant difference existed on knowledge, attitude, and intention to use contraceptive methods between the intervention and comparison groups at post-intervention (p< 0.05) while no significant difference was observed at baseline. Significant gains were achieved in the intervention group in terms of knowledge, attitude, and intention post-intervention. Conclusion: PPFP counselling during the postpartum period and before the discharge of women from the hospital may improve knowledge, attitude and intention to use contraceptives and, therefore, increase the likelihood of contraceptive uptake and thus prevent unwanted and closely spaced pregnancies. [ABSTRACT FROM AUTHOR]

Background: New strategies to increase measles and rubella vaccine coverage, particularly in low- and middle-income countries, are needed if elimination goals are to be achieved. With this regard, measles and rubella vaccine microneedle patches (MRV-MNP), in which the vaccine is embedded in dissolving microneedles, offer several potential advantages over subcutaneous delivery. These include ease of administration, increased thermostability, an absence of sharps waste, reduced overall costs and pain-free administration. This trial will provide the first clinical trial data on MRV-MNP use and the first clinical vaccine trial of MNP technology in children and infants.Methods: This is a phase 1/2, randomized, active-controlled, double-blind, double-dummy, age de-escalation trial. Based on the defined eligibility criteria for the trial, including screening laboratory investigations, 45 adults [18-40 years] followed by 120 toddlers [15-18 months] and 120 infants [9-10 months] will be enrolled in series. To allow double-blinding, participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) subcutaneous (SC) injection or a placebo MNP and the MRV by SC injection (MRV-SC). Local and systemic adverse event data will be collected for 14 days following study product administration. Safety laboratories will be repeated on day 7 and, in the adult cohort alone, on day 14. Unsolicited adverse events including serious adverse events will be collected until the final study visit for each participant on day 180. Measles and rubella serum neutralizing antibodies will be measured at baseline, on day 42 and on day 180. Cohort progression will be dependent on review of the unblinded safety data by an independent data monitoring committee.Discussion: This trial will provide the first clinical data on the use of a MNP to deliver the MRV and the first data on the use of MNPs in a paediatric population. It will guide future product development decisions for what may be a key technology for future measles and rubella elimination.Trial Registration: Pan-African Clinical Trials Registry 202008836432905 .Clinicaltrials: gov NCT04394689. [ABSTRACT FROM AUTHOR]

Background: Ensuring individual free and informed decision-making for research participation is challenging. It is thought that preliminarily informing communities through 'community sensitization' procedures may improve individual decision-making. This study set out to assess the relevance of community sensitization for individual decision-making in research participation in rural Gambia.Methods: This anthropological mixed-methods study triangulated qualitative methods and quantitative survey methods in the context of an observational study and a clinical trial on malaria carried out by the Medical Research Council Unit Gambia.Results/discussion: Although 38.7% of the respondents were present during sensitization sessions, 91.1% of the respondents were inclined to participate in the trial when surveyed after the sensitization and prior to the informed consent process. This difference can be explained by the informal transmission of information within the community after the community sensitization, expectations such as the benefits of participation based on previous research experiences, and the positive reputation of the research institute. Commonly mentioned barriers to participation were blood sampling and the potential disapproval of the household head.Conclusion: Community sensitization is effective in providing first-hand, reliable information to communities as the information is cascaded to those who could not attend the sessions. However, further research is needed to assess how the informal spread of information further shapes people's expectations, how the process engages with existing social relations and hierarchies (e.g. local political power structures; permissions of heads of households) and how this influences or changes individual consent. [ABSTRACT FROM AUTHOR]

Background: The benefit of zinc as an adjunct therapy for severe pneumonia is not established. We assessed the benefit of adjunct zinc therapy for severe pneumonia in children and determined whether the study children were zinc deficient.Methods: This was a randomized, parallel group, double-blind, placebo-controlled trial with an allocation ratio of 1:1 conducted in children with severe pneumonia to evaluate the efficacy of daily zinc as an adjunct treatment in preventing 'treatment failure' (presence of any sign of severe pneumonia) on day-5 and day-10 and in reducing the time to resolution of signs of severe pneumonia. Six hundred and four children 2-59 months of age presenting with severe pneumonia at six urban and rural health care facilities in The Gambia were individually randomised to receive placebo (n = 301) or zinc (n = 303) for seven days. To determine if the study children were zinc deficient, supplementation was continued in a randomly selected subgroup of 121 children from each arm for six months post-enrolment, and height-gain, nutritional status, plasma zinc concentrations, and immune competence were compared.Results: Percentage of treatment failure were similar in placebo and zinc arms both on day 5 (14.0% vs 14.1%) and day 10 (5.2% vs 5.9%). The time to recovery from lower chest wall indrawing and sternal retraction was longer in the placebo compared to zinc arm (24.4 vs 23.0 hours; P = 0.011 and 18.7 vs 11.0 hours; P = 0.006 respectively). The time to resolution for all respiratory symptoms of severity was not significantly different between placebo and zinc arms (42.3 vs 30.9 hours respectively; P = 0.242). In the six months follow-up sub-group, there was no significant difference in height gain, height-for-age and weight-for-height Z-scores, mid upper arm circumference, plasma zinc concentrations, and anergy at six months post-enrolment.Conclusions: In this population, zinc given as an adjunct treatment for severe pneumonia showed no benefit in treatment failure rates, or clinically important benefit in time to recovery from respiratory symptoms and showed marginal benefit in rapidity of resolution of some signs of severity. This finding does not support routine use of zinc as an adjunct treatment in severe pneumonia in generally zinc replete children.Trial Registration: ISRCTN33548493. [ABSTRACT FROM AUTHOR]

Background: Multiple micronutrients (MMN) are commonly prescribed in pediatric primary healthcare in sub-Saharan Africa to improve nutritional status and appetite without evidence for their effectiveness or international clinical guidelines. Community-wide MMN supplementation has shown limited and heterogeneous impact on growth and morbidity. Short-term ready-to-use therapeutic foods in acutely sick children in a hospital setting also had limited efficacy regarding subsequent growth. The effectiveness of MMN in improving morbidity or growth in sick children presenting for primary care has not been assessed. Methods and findings: We undertook a double-blind randomised controlled trial of small-quantity lipid-based nutrient supplements (SQ-LNS) fortified with 23 micronutrients in children aged 6 months (mo) to 5 years (y) presenting with an illness at a rural primary healthcare centre in The Gambia. Primary outcomes were repeat clinic presentations and growth over 24 wk. Participants were randomly assigned to receive 1 of 3 interventions: (1) supplementation with micronutrient-fortified SQ-LNS for 12 wk (MMN-12), (2) supplementation with micronutrient-fortified SQ-LNS for 6 wk followed by unfortified SQ-LNS for 6 wk (MMN-6), or (3) supplementation with unfortified SQ-LNS for 12 wk (MMN-0) to be consumed in daily portions. Treatment masking used 16 letters per 6-wk block in the randomisation process. Blinded intention-to-treat analysis based on a prespecified statistical analysis plan included all participants eligible and correctly enrolled. Between December 2009 and June 2011, 1,101 children (age 6–60 mo, mean 25.5 mo) were enrolled, and 1,085 were assessed (MMN-0 = 361, MMN-6 = 362, MMN-12 = 362). MMN supplementation was associated with a small increase in height-for-age z-scores 24 wk after recruitment (effect size for MMN groups combined: 0.084 SD/24 wk, 95% CI: 0.005, 0.168; p = 0.037; equivalent to 2–5 mm depending on age). No significant difference in frequency of morbidity measured by the number of visits to the clinic within 24 wk follow-up was detected with 0.09 presentations per wk for all groups (MMN-0 versus MMN-6: adjusted incidence rate ratio [IRR] 1.03, 95% CI: 0.92, 1.16; MMN-0 versus MMN-12: 1.05, 95% CI: 0.93, 1.18). In post hoc analysis, clinic visits significantly increased by 43% over the first 3 wk of fortified versus unfortified SQ-LNS (adjusted IRR 1.43; 95% CI: 1.07, 1.92; p = 0.016), with respiratory presentations increasing by 52% with fortified SQ-LNS (adjusted IRR 1.52; 95% CI: 1.01, 2.30; p = 0.046). The number of severe adverse events during supplementation were similar between groups (MMN-0 = 20 [1 death]; MMN-6 = 21 [1 death]; MMN-12 = 20 [0 death]). No participant withdrew due to adverse effects. Study limitations included the lack of supervision of daily supplementation. Conclusion: Prescribing micronutrient-fortified SQ-LNS to ill children presenting for primary care in rural Gambia had a very small effect on linear growth and did not reduce morbidity compared to unfortified SQ-LNS. An early increase in repeat visits indicates a need for the establishment of evidence-based guidelines and caution with systematic prescribing of MMN. Future research should be directed at understanding the mechanisms behind the lack of effect of MMN supplementation on morbidity measures and limited effect on growth. Trial registration: ISRCTN 73571031. In a randomised double-blind placebo-controlled trial, Stefan Unger and colleagues examine the impact of fortified versus unfortified lipid-based supplements on morbidity and nutritional status in ill Gambian children. Author summary: Why was this study done?: Multiple micronutrients (MMN) are prescribed widely in low- and middle-income settings. There are currently no established evidence-based international clinical guidelines for the use of MMN in ill children. Community-wide trials of MMN within a lipid-base supplement have shown improvement in linear growth in some settings, although the effect on morbidity is underresearched. Our study was designed to investigate the effect of lipid-based MMN in ill children in relation to the frequency of subsequent primary health clinic visits and growth. What did the research do and find?: We performed a prospective, double-blind randomised controlled trial of small-quantity lipid-based MMN in ill children presenting to a rural primary healthcare clinic in West Africa. We enrolled 1,100 children aged 6 months (mo) to 5 years (y). Children were supplemented either with the lipid-base alone or a micronutrient-enriched lipid-based supplement for 6 wk or 12 wk. The trial showed no effect of small-quantity lipid-based MMN supplementation compared to unfortified supplement on subsequent all-cause morbidity as assessed by clinic visits over 6 mo, but post hoc analysis revealed a significant 43% increase in clinic presentations over the first 3 wk of supplementation. Despite a significant increase in children's reported appetite, there was only a small benefit on linear growth. What do these findings mean?: Randomised trials have so far failed to demonstrate consistent beneficial effects of MMN supplementation (lipid-based or not) on growth and morbidity, and there is some evidence of potentially harmful effects, likely related to iron in the supplements. Blanket prescribing of MMN in primary health clinics in similar settings is not supported by current evidence. [ABSTRACT FROM AUTHOR]

Prenatal supplementation with protein-energy (PE) and/or multiple-micronutrients (MMNs) may improve fetal growth, but trials of lipid-based nutritional supplements (LNSs) have reported inconsistent results. We conducted a post-hoc analysis of non-primary outcomes in a trial in Gambia, with the aim to test the associations of LNS with fetal growth and explore how efficacy varies depending on nutritional status. The sample comprised 620 pregnant women in an individually randomized, partially blinded trial with four arms: (a) iron and folic acid (FeFol) tablet (usual care, referent group), (b) MMN tablet, (c) PE LNS, and (d) PE + MMN LNS. Analysis of variance examined unadjusted differences in fetal biometry z-scores at 20 and 30 weeks and neonatal anthropometry z-scores, while regression tested for modification of intervention-outcome associations by season and maternal height, body mass index, and weight gain. Despite evidence of between-arm differences in some fetal biometry, z-scores at birth were not greater in the intervention arms than the FeFol arm (e.g., birth weight z-scores: FeFol −0.71, MMN −0.63, PE −0.64, PE + MMN −0.62; group-wise p = .796). In regression analyses, intervention associations with birth weight and head circumference were modified by maternal weight gain between booking and 30 weeks gestation (e.g., PE + MMN associations with birth weight were +0.462 z-scores (95% CI [0.097, 0.826]) in the highest quartile of weight gain but -0.099 z-scores (−0.459, 0.260) in the lowest). In conclusion, we found no strong evidence that a prenatal LNS intervention was associated with better fetal growth in the whole sample. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency prevalence rates frequently exceed 50 % in young children in low-income countries. The World Health Organization (WHO) recommended universal supplementation of young children where anaemia rates are >40 %. However, large randomized trials have revealed that provision of iron to young children caused serious adverse effects because iron powerfully promotes microbial growth. Hepcidin - the master regulator of iron metabolism that integrates signals of infection and iron deficiency - offers the possibility of new solutions to diagnose and combat global iron deficiency. We aim to evaluate a hepcidin-screening-based iron supplementation intervention using hepcidin cut-offs designed to indicate that an individual requires iron, is safe to receive it and will absorb it.Methods: The study is a proof-of-concept, three-arm, double blind, randomised controlled, prospective, parallel-group non-inferiority trial. Children will be randomised to receive, for a duration of 12 weeks, one of three multiple micronutrient powders (MNP) containing: A) 12 mg iron daily; B) 12 mg or 0 mg iron daily based on a weekly hepcidin screening indicating if iron can be given for the next seven days or not; C) 6 mg or 0 mg iron daily based on a weekly hepcidin screening indicating if iron can be given for the next seven days or not. The inclusion criteria are age 6-23 months, haemoglobin (Hb) concentration between 7 and 11 g/dL, z-scores for Height-for-Age, Weight-for-Age and Weight-for-Height > -3 SD and free of malaria. Hb concentration at 12 weeks will be used to test whether the screen-and-treat approaches are non-inferior to universal supplementation. Safety will be assessed using caregiver reports of infections, in vitro bacterial and P. falciparum growth assays and by determining the changes in the gut microbiota during the study period.Discussion: A screen-and-treat approach using hepcidin has the potential to make iron administration safer in areas with widespread infections. If this proof-of-concept study shows promising results the development of a point-of-care diagnostic test will be the next step.Trial Registration: ISRCTN07210906 , 07/16/2014. [ABSTRACT FROM AUTHOR]

Background: In malaria-endemic areas, residents of modern houses have less malaria than those living in traditional houses. This study will determine if modern housing provides incremental protection against clinical malaria over the current best practice of long-lasting insecticidal nets (LLINs) and prompt treatment in The Gambia, determine the incremental cost-effectiveness of the interventions, and analyze the housing market in The Gambia.Methods/design: A two-armed, household, cluster-randomized, controlled study will be conducted to assess whether improved housing and LLINs combine to provide better protection against clinical malaria in children than LLINs alone in The Gambia. The unit of randomization will be the household, defined as a house and its occupants. A total of 800 households will be enrolled and will receive LLINs, and 400 will receive improved housing before clinical follow-up. One child aged 6 months to 13 years will be enrolled from each household and followed for clinical malaria using active case detection to estimate malaria incidence for two malaria transmission seasons. Episodes of clinical malaria will be the primary endpoint. Study children will be surveyed at the end of each transmission season to estimate the prevalence of Plasmodium falciparum infection, parasite density, and the prevalence of anemia. Exposure to malaria parasites will be assessed using light traps, followed by detection of Anopheles gambiae species and sporozoite infection. Ancillary economic and social science studies will undertake a cost-effectiveness analysis and use qualitative and participatory methods to explore the acceptability of the housing modifications and to design strategies for scaling-up housing interventions.Discussion: The study is the first of its kind to measure the efficacy of housing on reducing clinical malaria, assess the incremental cost-effectiveness of improved housing, and identify mechanisms for scaling up housing interventions. Trial findings will help inform policy makers on improved housing for malaria control in sub-Saharan Africa.Trial Registration: ISRCTN Registry, ISRCTN02622179 . Registered on 23 September 2014. [ABSTRACT FROM AUTHOR]

Background: A village-randomized trial of a seven-valent pneumococcal-conjugate-vaccine (PCV-7) conducted in rural Gambia showed a decrease of vaccine-type (VT) and a non-significant increase in non-vaccine-type (NVT) nasopharyngeal carriage of pneumococci two years after vaccination. Here, we report findings four years after vaccination. Methods: PCV-7 was given to all children below 30 months of age enrolled in the trial and to those born during its course in all study villages. Villages were randomized (older children and adults) to receive PCV-7 (wholly vaccinated villages) or serogroup-C-meningococcal-conjugate-vaccine (partly vaccinated villages). Cross-sectional surveys (CSS) to collect nasopharyngeal swabs were conducted before and at various intervals after vaccination. Sixteen of these randomized villages (8 wholly vaccinated and 8 partly vaccinated) participated in a CSS conducted four years after vaccination started. Results: Four years after vaccination, the prevalence of VT pneumococcal carriage was slightly higher in partly than in wholly vaccinated villages [6.4% versus 3.9% (p = 0.120)] compared to 24.4% in the pre-vaccination CSS (p<0.001). Prevalence of NVT four years after vaccination was similar between study groups [32.7% versus 29.8% (p = 0.392), respectively] compared to 51.1% in the pre-vaccination CSS (p<0.001). Four years after vaccination started, lower prevalence of serotype 6A was detected in wholly vaccinated than in partly vaccinated villages (1.6% versus 3.5%, p = 0.093) whilst the prevalence of serotype 19A was similar between groups (2.9% versus 2.5%, p = 0.779). The most prevalent serotype 19A clone was ST 847. The most prevalent serotype 6A clone before vaccination was ST3324 whilst after vaccination ST913 and ST1737 predominated. Fourteen out of 26 STs detected among the serotype 6A isolates were new while no new 19A serotype ST was found. Conclusions: The decline in prevalence of VT pneumococci seen shortly after PCV-7 vaccination was sustained four years later with only a small difference between study arms. No significant serotype replacement was detected. Trial Registration: ClinicalTrials.gov ISRCTN51695599 [ABSTRACT FROM AUTHOR]

Background: Chlorproguanil-dapsone (Lapdap), developed as a low-cost antimalarial, was withdrawn in 2008 after concerns about safety in G6PD deficient patients. This trial was conducted in 2004 to evaluate the safety and effectiveness of CD and comparison with artemether-lumefantrine (AL) under conditions of routine use in G6PD normal and G6PD deficient patients with uncomplicated malaria in The Gambia. We also examined the effects of a common genetic variant that affects chlorproguanil metabolism on risk of treatment failure. Methods: 1238 children aged 6 months to 10 years with uncomplicated malaria were randomized to receive CD or artemether-lumefantrine (AL) and followed for 28 days. The first dose was supervised, subsequent doses given unsupervised at home. G6PD genotype was determined to assess the interaction between treatment and G6PD status in their effects on anaemia. The main endpoints were clinical treatment failure by day 28, incidence of severe anaemia (Hb<5 g/dL), and haemoglobin concentration on day 3. Findings: One third of patients treated with AL, and 6% of patients treated with CD, did not complete their course of medication. 18% (109/595) of children treated with CD and 6.1% (36/587) with AL required rescue medication within 4 weeks, risk difference 12% (95%CI 8.9%-16%). 23 children developed severe anaemia (17 (2.9%) treated with CD and 6 (1.0%) with AL, risk difference 1.8%, 95%CI 0.3%-3.4%, P = 0.02). Haemoglobin concentration on day 3 was lower among children treated with CD than AL (difference 0.43 g/dL, 95% CI 0.24 to 0.62), and within the CD group was lower among those children who had higher parasite density at enrolment. Only 17 out of 1069 children who were typed were G6PD Adeficient, of these 2/9 treated with CD and 1/8 treated with AL developed severe anaemia. 5/9 treated with CD had a fall of 2 g/dL or more in haemoglobin concentration by day 3. Interpretation: AL was well tolerated and highly effective and when given under operational conditions despite poor adherence to the six-dose regimen. There were more cases of severe malaria and anaemia after CD treatment although G6PD deficiency was uncommon. Trial Registration: Clinicaltrials.gov NCT00118794 [ABSTRACT FROM AUTHOR]

Background: The Expanded Programme on Immunisation (EPI) provides an effective way of delivering intermittent preventive treatment for malaria (IPT) to infants. However, it is uncertain how IPT can be delivered most effectively to older children. Therefore, we have compared two approaches to the delivery of IPT to Gambian children: distribution by village health workers (VHWs) or through reproductive and child health (RCH) trekking teams. In rural areas, RCH trekking teams provide most of the health care to children under the age of 5 years in the Infant Welfare Clinic, and provide antenatal care for pregnant women. Methods and Findings: During the 2006 malaria transmission season, the catchment populations of 26 RCH trekking clinics in The Gambia, each with 400-500 children 6 years of age and under, were randomly allocated to receive IPT from an RCH trekking team or from a VHW. Treatment with a single dose of sulfadoxine pyrimethamine (SP) plus three doses of amodiaquine (AQ) were given at monthly intervals during the malaria transmission season. Morbidity from malaria was monitored passively throughout the malaria transmission season in all children, and a random sample of study children from each cluster was examined at the end of the malaria transmission season. The primary study endpoint was the incidence of malaria. Secondary endpoints included coverage of IPTc, mean haemoglobin (Hb) concentration, and the prevalence of asexual malaria parasitaemia at the end of malaria transmission period. Financial and economic costs associated with the two delivery strategies were collected and incremental cost and effects were compared. A nested casecontrol study was used to estimate efficacy of IPT treatment courses. Treatment with SP plus AQ was safe and well tolerated. There were 49 cases of malaria with parasitaemia above 5,000/μl in the areas where IPT was delivered through RCH clinics and 21 cases in the areas where IPT was delivered by VHWs, (incidence rates 2.8 and 1.2 per 1,000 child months, respectively, rate difference 1.6 [95% confidence interval (CI) 20.24 to 3.5]). Delivery through VHWs achieved a substantially higher coverage level of three courses of IPT than delivery by RCH trekking teams (74% versus 48%, a difference of 27% [95% CI 16%-38%]). For both methods of delivery, coverage was unrelated to indices of wealth, with similar coverage being achieved in the poorest and wealthiest groups. The prevalence of anaemia was low in both arms of the trial at the end of the transmission season. Efficacy of IPTc against malaria during the month after each treatment course was 87% (95% CI 54%-96%). Delivery of IPTc by VHWs was less costly in both economic and financial terms than delivery through RCH trekking teams, resulting in incremental savings of US$872 and US$1,244 respectively. The annual economic cost of delivering at least the first dose of each course of IPTc was US$3.47 and US$1.63 per child using trekking team and VHWs respectively. Conclusions: In this setting in The Gambia, delivery of IPTc to children 6 years of age and under by VHWs is more effective and less costly than delivery through RCH trekking clinics. [ABSTRACT FROM AUTHOR]

Objectives: Trachoma is the principal cause of infectious blindness. As part of its strategy to eliminate trachoma, the World Health Organization recommends annual mass antibiotic treatment for at least 3 years with an 80% population coverage target. However, to date, ideal population coverage and mass treatment duration have not been determined and further evaluation of treatment recommendations in areas of varying endemicity is warranted. The studies presented here evaluate the impact of coverage level and frequency of mass treatment with single dose azithromycin on trachoma and ocular C. trachomatis infection. Methods: The Partnership for the Rapid Elimination of Trachoma supervises 2 randomized, community-based clinical trials in Tanzania and The Gambia. Although each trial is a stand-alone effort, protocols, data collection, and analytic approaches have been harmonized to permit generalizations. Communities in each site were randomized using a 2X2 factorial design to standard (80%--90.0%) versus high (over 90.0%) treatment coverage; communities were further randomized to annual treatment for 3 years versus a ''graduation'' rule where evidence indicates an absence of follicular trachoma or infection and annual treatment is halted. Results: Average prevalence of follicular trachoma in children age less than 5 years was 32.2% in Tanzania and 5.96% in The Gambia. Randomization appeared to be effective, as prevalence was not statistically different between the arms within each country. Conclusions: There are challenges in harmonizing 2, large trials in Africa. Study outcomes will provide critical data to national trachoma control programs on treatment methodology and resource allocation toward elimination of the disease. [ABSTRACT FROM AUTHOR]

Background: Blinding trachoma, caused by ocular infection with Chlamydia trachomatis, is targeted for global elimination by 2020. Knowledge of risk factors can help target control interventions. Methodology/Principal Findings: As part of a cluster randomised controlled trial, we assessed the baseline prevalence of, and risk factors for, active trachoma and ocular C. trachomatis infection in randomly selected children aged 0-5 years from 48 Gambian and 36 Tanzanian communities. Both children's eyes were examined according to the World Health Organization (WHO) simplified grading system, and an ocular swab was taken from each child's right eye and processed by Amplicor polymerase chain reaction to test for the presence of C. trachomatis DNA. Prevalence of active trachoma was 6.7% (335/5033) in The Gambia and 32.3% (1008/3122) in Tanzania. The countries' corresponding Amplicor positive prevalences were 0.8% and 21.9%. After adjustment, risk factors for follicular trachoma (TF) in both countries were ocular or nasal discharge, a low level of household head education, and being aged $1 year. Additional risk factors in Tanzania were flies on the child's face, being Amplicor positive, and crowding (the number of children per household). The risk factors for being Amplicor positive in Tanzania were similar to those for TF, with the exclusion of flies and crowding. In The Gambia, only ocular discharge was associated with being Amplicor positive. Conclusions/Significance: These results indicate that although the prevalence of active trachoma and Amplicor positives were very different between the two countries, the risk factors for active trachoma were similar but those for being Amplicor positive were different. The lack of an association between being Amplicor positive and TF in The Gambia highlights the poor correlation between the presence of trachoma clinical signs and evidence of C. trachomatis infection in this setting. Only ocular discharge was associated with evidence of C. trachomatis DNA in The Gambia, suggesting that at this low endemicity, this may be the most important risk factor. [ABSTRACT FROM AUTHOR]

Background: Results from trials of intermittent preventive treatment (IPT) in infants and children have shown that IPT provides significant protection against clinical malaria. Sulfadoxine-pyrimethamine (SP) given alone or in combination with other drugs has been used for most IPT programmes. However, SP resistance is increasing in many parts of Africa. Thus, we have investigated whether SP plus AQ, SP plus piperaquine (PQ) and dihydroartemisinin (DHA) plus PQ might be equally safe and effective when used for IPT in children in an area of seasonal transmission. Methods: During the 2007 malaria transmission season, 1008 Gambian children were individually randomized to receive SP plus amodiaquine (AQ), SP plus piperaquine (PQ) or dihydroartemisinin (DHA) plus PQ at monthly intervals on three occasions during the peak malaria transmission season. To determine the risk of side effects following drug administration, participants in each treatment group were visited at home three days after the start of each round of drug administration and a side effects questionnaire completed. To help establish whether adverse events were drug related, the same questionnaire was administered to 286 age matched control children recruited from adjacent villages. Morbidity was monitored throughout the malaria transmission season and study children were seen at the end of the malaria transmission season. Results: All three treatment regimens showed good safety profiles. No severe adverse event related to IPT was reported. The most frequent adverse events reported were coughing, diarrhoea, vomiting, abdominal pain and loss of appetite. Cough was present in 15.2%, 15.4% and 18.7% of study subjects who received SP plus AQ, DHA plus PQ or SP plus PQ respectively, compared to 19.2% in a control group. The incidence of malaria in the DHA plus PQ, SP plus AQ and SP plus PQ groups were 0.10 cases per child year (95% CI: 0.05, 0.22), 0.06 (95% CI: 0.022, 0.16) and 0.06 (95% CI: 0.02, 0.15) respectively. The incidence of malaria in the control group was 0.79 cases per child year (0.58, 1.08). Conclusion: All the three regimens of IPT in children were safe and highly efficacious. [ABSTRACT FROM AUTHOR]

Background: In the pre-intervention year of a randomized controlled trial investigating the protective effects of house screening against malaria-transmitting vectors, a multi-factorial risk factor analysis study was used to identify factors that influence mosquito house entry. Methods: Mosquitoes were sampled using CDC light traps in 976 houses, each on one night, in Farafenni town and surrounding villages during the malaria-transmission season in The Gambia. Catches from individual houses were both (a) left unadjusted and (b) adjusted relative to the number of mosquitoes caught in four sentinel houses that were operated nightly throughout the period, to allow for night-tonight variation. Houses were characterized by location, architecture, human occupancy and their mosquito control activities, and the number and type of domestic animals within the compound. Results: 106,536 mosquitoes were caught, of which 55% were Anopheles gambiae sensu lato, the major malaria vectors in the region. There were seven fold higher numbers of An. gambiae s.l. in the villages (geometric mean per trap night = 43.7, 95% confidence intervals, CIs = 39.5-48.4) than in Farafenni town (6.3, 5.7-7.2) and significant variation between residential blocks (p < 0.001). A negative binomial multivariate model performed equally well using unadjusted or adjusted trap data. Using the unadjusted data the presence of nuisance mosquitoes was reduced if the house was located in the town (odds ratio, OR = 0.11, 95% CIs = 0.09-0.13), the eaves were closed (OR = 0.71, 0.60-0.85), a horse was tethered near the house (OR = 0.77, 0.73-0.82), and churai, a local incense, was burned in the room at night (OR = 0.56, 0.47-0.66). Mosquito numbers increased per additional person in the house (OR = 1.04, 1.02-1.06) or trapping room (OR = 1.19, 1.13-1.25) and when the walls were made of mud blocks compared with concrete (OR = 1.44, 1.10-1.87). Conclusion: This study demonstrates that the risk of malaria transmission is greatest in rural areas, where large numbers of people sleep in houses made of mud blocks, where the eaves are open, horses are not tethered nearby and where churai is not burnt at night. These factors need to be considered in the design and analysis of intervention studies designed to reduce malaria transmission in The Gambia and other parts of sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: Delays in accessing skilled delivery services are a major contributor to high maternal mortality in resource-limited settings. In 2015, the government of The Gambia initiated a results-based financing intervention that sought to increase uptake of skilled delivery. We performed a midline evaluation to determine the impact of the intervention and explore causes of delays.Methods: A mixed methods design was used to measure changes in uptake of skilled delivery and explore underlying reasons, with communities randomly assigned to four arms: (1) community-based intervention, (2) facility-based intervention, (3) community- and facility-based intervention, and (4) control. We obtained quantitative data from household surveys conducted at baseline (n = 1423) and midline (n = 1573). Qualitative data came from semi-structured interviews (baseline n = 20; midline n = 20) and focus group discussions (baseline n = 27; midline n = 39) with a range of stakeholders. Multivariable linear regression models were estimated using pooled data from baseline and midline. Qualitative data were recorded, transcribed, translated and thematically analyzed.Results: No increase was found in uptake of skilled delivery services between baseline and midline. However, relative to the control group, significant increases in referral to health facilities for delivery were found in areas receiving the community-based intervention (beta = 0.078, p < 0.10) and areas receiving both the community-based and facility-based interventions (beta = 0.198, p < 0.05). There was also an increase in accompaniment to health facilities for delivery in areas receiving only community-based interventions (beta = 0.095, p < 0.05). Transportation to health facilities for delivery increased in areas with both interventions (beta = 0.102, p < 0.05). Qualitative data indicate that delays in the decision to seek institutional delivery usually occurred when women had limited knowledge of delivery indications. Delays in reaching a health facility typically occurred due to transportation-related challenges. Although health workers noted shortages in supplies and equipment, women reported being supported by staff and experiencing minimal delays in receiving skilled delivery care once at the facility.Conclusions: Focusing efforts on informing the decision to seek care and overcoming transportation barriers can reduce delays in care-seeking among pregnant women and facilitate efforts to increase uptake of skilled delivery services through results-based financing mechanisms. [ABSTRACT FROM AUTHOR]