Efficacy and safety of hepcidin-based screen-and-treat approaches using two different doses versus a standard universal approach of iron supplementation in young children in rural Gambia: a double-blind randomised controlled trial.

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

Prevalence and risk factors for Staphylococcus aureus nasopharyngeal carriage during a PCV trial.

BACKGROUND: We conducted an ancillary study among individuals who had participated in a cluster-randomized PCV-7 trial in rural Gambia (some clusters were wholly-vaccinated while in others only young children had been vaccinated), to determine the prevalence and risk factors for Staphylococcus aureus nasopharyngeal carriage. METHODS: Two hundred thirty-two children aged 5-10 years were recruited and followed from 4 to 20 months after vaccination started. We collected 1264 nasopharyngeal swabs (NPS). S. aureus was isolated following conventional microbiological methods. Risk factors for carriage were assessed by logistic regression. RESULTS: Prevalence of S. aureus carriage was 25.9%. In the univariable analysis, prevalence of S. aureus carriage was higher among children living in villages wholly-vaccinated with PCV-7 [OR = 1.57 95%CI (1.14 to 2.15)] and children with least 1 year of education [OR = 1.44 95%CI (1.07 to 1.92)]. S. aureus carriage was also higher during the rainy season [OR = 1.59 95%CI (1.20 to 2.11)]. Carriage of S. pneumoniae did not have any effect on S. aureus carriage for any pneumococcal, vaccine-type (VT) or non-vaccine-type (NVT) carriage. Multivariate analysis showed that the higher prevalence of S. aureus observed among children living in villages wholly-vaccinated with PCV-7 occurred only during the rainy season OR 2.72 95%CI (1.61-4.60) and not in the dry season OR 1.28 95%CI (0.78-2.09). CONCLUSIONS: Prevalence of nasopharyngeal carriage of S. aureus among Gambian children increased during the rainy season among those children living in PCV-7 wholly vaccinated communities. However, carriage of S. aureus is not associated with carriage of S. pneumoniae. TRIAL REGISTRATION: ISRCTN51695599 . Registered August 04th 2006

Incidence of macrolide-lincosamide-streptogramin B resistance amongst beta-haemolytic streptococci in The Gambia.

BACKGROUND: In West Africa, penicillin, macrolide and lincosamide resistance among beta-haemolytic streptococci (BHS) isolates has rarely been described. However, such data are critical to detect and track the emergence of antibiotic resistance. METHODS: Beta-haemolytic streptococci were cultured from clinical specimens from patients attending the clinic at the Medical Research Council Unit The Gambia (n = 217) and kept at -70 °C. Of these, 186 were revived and tested for penicillin susceptibility by disc diffusion and E-test methods, and the D-test for determination of constitutive and inducible macrolide-lincosamide (MLSB) resistance phenotypes. RESULTS: The majority of BHS isolates from infections were group A streptococci (GAS) (126/186, 67.7%). Of these, 16% were from invasive disease (30/186). Other BHS isolated included lancefield groups B (19, 10.2%); C (9/186, 4.8%), D (3/186, 1.6%), F (5/186, 2.7%), G (16/186, 8.6%) and non-typeable (8/186, 4.3%). Prevalence of BHS isolated from blood cultures ranges from 0% (2005) to 0.5% (2010). Most (85, 45.7%) of the isolates were from wound infections. Of the 186 BHS isolates, none was resistant to penicillin and 14 (6.1%) were resistant to erythromycin. Of these, 8 (4.3%) demonstrated constitutive MLSB resistance, and 5 (2.7%) were inducible MLSB resistant. All the inducible MLSB isolates were GAS, and majority of the constitutive MLSB isolates (6/8, 75.0%) were non-GAS. CONCLUSIONS: Beta-haemolytic streptococci, predominantly GAS are associated with a wide range of infections in The Gambia. It is reassuring that macrolide and lincosamide resistance is relatively low. However, monitoring of MLSB resistance is necessary with the global spread of resistant BHS strains

Pulmonary non-tuberculous mycobacteria in colonisation and disease in The Gambia

The clinical relevance of pulmonary non-tuberculous mycobacteria (PNTM) in The Gambia is unknown. The aim of this study was to estimate the prevalence of non-tuberculous mycobacteria (NTM) in colonisation, and the burden of clinically relevant pulmonary NTM (PNTM) disease in The Gambia. This was a cross-sectional study of the prevalence of NTM in participants aged ≥ 15 years, in a nationwide tuberculosis (TB) prevalence survey between December 2011 and January 2013. We enrolled 903 participants with suspected NTM and NTM cultures were confirmed by 16S rRNA gene sequencing analyses. We applied the American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) diagnostic criteria to determine clinical relevance of NTM. A total of 575 participants had acid-fast bacilli (AFB) positive Mycobacterial Growth Indicator Tube (MGIT) cultures and 229 (39.8%) were NTM. M. avium complex was by far the most isolated NTM (71.0%), followed by M. fortuitum (9.5%) and M. nonchromogenicum (2.9%). Older participants (> 24 years old) were four times more likely to have NTM in their sputa. Only 20.5% (9/44) NTM cases met the ATS/IDSA criteria for NTM disease. This study provides important data on the prevalence of NTM in pulmonary samples of suspected TB cases with AFB positive cultures from a nationally representative population in The Gambia. Enhanced PNTM surveillance is recommended to better understand the contribution of NTM to pulmonary disease

Pulmonary non-tuberculous mycobacteria in colonisation and disease in The Gambia

The clinical relevance of pulmonary non-tuberculous mycobacteria (PNTM) in The Gambia is unknown. The aim of this study was to estimate the prevalence of non-tuberculous mycobacteria (NTM) in colonisation, and the burden of clinically relevant pulmonary NTM (PNTM) disease in The Gambia. This was a cross-sectional study of the prevalence of NTM in participants aged ≥ 15 years, in a nationwide tuberculosis (TB) prevalence survey between December 2011 and January 2013. We enrolled 903 participants with suspected NTM and NTM cultures were confirmed by 16S rRNA gene sequencing analyses. We applied the American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) diagnostic criteria to determine clinical relevance of NTM. A total of 575 participants had acid-fast bacilli (AFB) positive Mycobacterial Growth Indicator Tube (MGIT) cultures and 229 (39.8%) were NTM. M. avium complex was by far the most isolated NTM (71.0%), followed by M. fortuitum (9.5%) and M. nonchromogenicum (2.9%). Older participants (> 24 years old) were four times more likely to have NTM in their sputa. Only 20.5% (9/44) NTM cases met the ATS/IDSA criteria for NTM disease. This study provides important data on the prevalence of NTM in pulmonary samples of suspected TB cases with AFB positive cultures from a nationally representative population in The Gambia. Enhanced PNTM surveillance is recommended to better understand the contribution of NTM to pulmonary disease

Effects of a multimedia campaign on HIV self-testing and PrEP outcomes among young people in South Africa: a mixed-methods impact evaluation of 'MTV Shuga Down South'.

INTRODUCTION: Innovative HIV technologies can help to reduce HIV incidence, yet uptake of such tools is relatively low among young people. To create awareness and demand among adolescents and young adults, a new campaign of the pan-African MTV Shuga series ('Down South 2'; DS2), featured storylines and messages about HIV self-testing (HIVST) and pre-exposure prophylaxis (PrEP) through television, radio and accompanying multimedia activities in 2019-2020. METHODS: We conducted a mixed-methods evaluation of the new MTV Shuga series among 15-24 years old in Eastern Cape, South Africa, in 2020. Quantitative and qualitative methods were used to investigate complementary evaluations questions, namely, whether and how the DS2 campaign works. A web-based survey, promoted via social media platforms of schools, universities and communities, assessed exposure to MTV Shuga and knowledge of HIV status; secondary outcomes included awareness and uptake of HIVST and PrEP. We used multivariable logistic regression to estimate associations between exposure to DS2 and each outcome, adjusting for sociodemographic factors, media assets and exposure to other media campaigns. An embedded qualitative evaluation explored mechanisms of DS2's impact through deductive and inductive thematic analysis of in-depth individual and group interviews. RESULTS: Among 3431 online survey participants, 43% had engaged with MTV Shuga and 24% with DS2 specifically. Knowledge of HIV status was higher among those exposed to DS2 (71%) vs those who were not (39%; adjusted OR=2.26 (95% CI 1.78 to 2.87)). Exposure was also associated with increased awareness of HIVST (60% vs 28%; aOR=1.99 (1.61 to 2.47)) and use of HIVST (29% vs 10%; aOR=2.49 (1.95 to 3.19)). One-third of respondents were aware of PrEP, with higher proportions among those exposed versus non-exposed to DS2 (52% vs 27%; aOR=1.90 (1.53 to 2.35)). Qualitative insights identified mechanisms by which DS2 increased awareness, confidence and motivation to use HIVST and PrEP, but had less influence on service access. CONCLUSIONS: We found evidence consistent with a positive causal impact of the MTV Shuga DS2 campaign on HIV prevention outcomes among young people in a high-prevalence setting. As diverse testing and PrEP technologies become accessible, an immersive edutainment campaign can help to expand HIV prevention choices and close age and gender gaps in HIV testing and prevention goals

Impact of DREAMS interventions on experiences of violence among adolescent girls and young women: Findings from population-based cohort studies in Kenya and South Africa

DREAMS aims to reduce HIV incidence among adolescent girls and young women (AGYW) by tackling drivers of HIV risk including gender-based violence. We evaluate the impact of DREAMS on recent experiences of violence perpetuated by men against AGYW. AGYW cohorts were randomly selected from demographic platforms in South Africa (rural KwaZulu-Natal) and Kenya (Nairobi informal settlements and rural Gem sub-county). AGYW aged 13-22 years were enrolled in 2017 (Nairobi, KwaZulu-Natal) or 2018 (Gem), with annual follow-up to 2019. We described proportions of AGYW who self-reported experiences of violence perpetrated by males in the 12 months preceding the interview, overall and by form (physical, sexual, emotional). We investigated associations with DREAMS (invitation to participate during 2017-2018) through multivariable propensity score-adjusted logistic regression and estimated the causal effect of DREAMS on experiences of violence, under counter-factual scenarios in which all versus no AGYW were DREAMS beneficiaries. Among 852, 1018 and 1712 AGYW followed-up in 2019 in Nairobi, Gem and KZN, respectively, proportions reporting any violence in 2019 were higher in Nairobi (29%) than Gem (18%) and KwaZulu-Natal (19%). By sub-type, emotional and physical violence were more frequently reported than sexual violence. We found no evidence of an impact attributable to DREAMS on overall levels of violence, in any setting. Nor was there evidence of impact on sub-types of violence, with one exception: an increase in physical violence in Nairobi if all, versus no, AGYW were DREAMS beneficiaries (16% vs 11%; +5% difference [95% CI: +0.2%, +10.0%]). Experiences of gender-based violence were common among AGYW, especially in urban settings, and DREAMS had no measurable impact on reducing violence within three years of implementation. Violence prevention programming that reaches more men and the broader community, sustained for longer periods, may yield greater gains in violence reduction than AGYW-focused programming. Additionally, more investment in implementation research is needed to bridge trial-based study findings from efficacy to population-level effectiveness

Impact of the DREAMS interventions on educational attainment among adolescent girls and young women: Causal analysis of a prospective cohort in urban Kenya.

BACKGROUND: DREAMS promotes a comprehensive HIV prevention approach to reduce HIV incidence among adolescent girls and young women (AGYW). One pathway that DREAMS seeks to impact is to support AGYW to stay in school and achieve secondary education. We assessed the impact of DREAMS on educational outcomes among AGYW in Nairobi, Kenya. METHODS AND FINDINGS: In two informal settlements in Nairobi, 1081 AGYW aged 15-22 years were randomly selected in 2017 and followed-up to 2019. AGYW reporting invitation to participate in DREAMS during 2017-18 were classified as "DREAMS beneficiaries". Our main outcome was being in school and/or completed lower secondary school in 2019. We used multivariable logistic regression to quantify the association between being a DREAMS beneficiary and the outcome; and a causal inference framework to estimate proportions achieving the outcome if all, versus no, AGYW were DREAMS beneficiaries, adjusting for the propensity to be a DREAMS beneficiary. Of AGYW enrolled in 2017, 79% (852/1081) were followed-up to 2019. In unadjusted analysis, DREAMS beneficiaries had higher attainment than non-beneficiaries (85% vs 75% in school or completed lower secondary school, Odds Ratio (OR) = 1.9; 95%CI: 1.3,2.8). The effect weakened with adjustment for age and other confounders, (adjusted OR = 1.4; 95%CI: 0.9,2.4). From the causal analysis, evidence was weak for an impact of DREAMS (estimated 83% vs 79% in school or completed lower secondary school, if all vs no AGYW were beneficiaries, difference = 4%; 95%CI: -2,11%). Among AGYW out of school at baseline, the estimated differences were 21% (95%CI: -3,43%) among 15-17 year olds; and 4% (95%CI: -8,17%) among 18-22 year olds. CONCLUSIONS: DREAMS had a modest impact on educational attainment among AGYW in informal settlements in Kenya, by supporting both retention and re-enrolment in school. Larger impact might be achieved if more AGYW were reached with educational subsidies, alongside other DREAMS interventions

Reaching early adolescents with a complex intervention for HIV prevention: findings from a cohort study to evaluate DREAMS in two informal settlements in Nairobi, Kenya.

BACKGROUND: The DREAMS Partnership promotes combination HIV prevention among adolescent girls and young women. We examined the extent to which DREAMS interventions reached early adolescent girls (EAG; aged 10-14 years) in two informal settlements in Nairobi, and the characteristics of those reached, after 3 years of implementation. METHODS: We utilized three data rounds from a randomly-sampled cohort of EAG established in 2017 in Korogocho and Viwandani informal settlements where DREAMS interventions were implemented. Interventions were classified as individual or contextual-level, with individual interventions further categorised as primary (prioritised for this age group), or secondary. We summarised self-reported invitation to participate in DREAMS, and uptake of eight interventions that were supported by DREAMS, during 2017-2019. Multivariable logistic regression analysis was used to identify individual and household characteristics associated with invitation to DREAMS and uptake of primary interventions. RESULTS: Data were available for 606, 516 (retention rate of 85%) and 494 (82%) EAG in 2017, 2018 and 2019, respectively. Proportions invited to DREAMS increased from 49% in 2017, to 77% by 2018, and to 88% by 2019. School-based HIV and violence prevention, and HIV testing and counselling were the most accessed interventions (both at 82%). Cumulative uptake of interventions was higher among those invited to participate in DREAMS compared to those never invited, particularly for new interventions such as social asset building and financial capability training. Contextual-level interventions were accessed infrequently. Most of those invited both in 2017 and 2018 accessed ≥3 interventions (96%), and 55% received all three primary interventions by 2019. CONCLUSIONS: Uptake of DREAMS interventions among a representative sample of EAG was high and quickly increased over the implementation period. The majority accessed multiple interventions, indicating that it is feasible to integrate and deliver a package of interventions to EAG in a challenging informal context

Flowering margins support natural enemies between cropping seasons

Here we investigated how agricultural landscapes support natural pest regulating insects between cropping seasons; an important challenge in Pest Management by Small-Holder Farmers so aligns with this special issue. Smallholders in East Africa clear margins to provide fodder for cattle or livestock or simply to reduce the ingression of weeds into crop fields. We show that there was a significant seasonal variation in plant species richness and diversity around crops and the abundance of margin plants was strongly linked to abundance of natural enemies in the off season. The time since harvesting was also a significant factor influencing the overall abundance of natural enemies. Our paper reinforces our understanding of the importance flowering plants in agricultural systems as a refuge for natural enemies and other beneficial insects but uniquely emphasising the time between cropping seasons. Improving agricultural landscapes between crops to better support invertebrates will lead to more effective natural pest regulation early in the following crop with positive outcomes for the farmers and their families