Community-based strategies to increase coverage of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine in sub-Saharan Africa: a systematic review, meta-analysis, meta-ethnography, and economic assessment.

BACKGROUND: Community-based approaches might increase uptake of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). We assessed the effects of community-based approaches on IPTp-SP and antenatal care coverage, and barriers and facilitators to implementation in sub-Saharan Africa. METHODS: We did a systematic review, meta-analysis, meta-ethnography, and economic assessment. We searched the WHO International Clinical Trials Registry Platform, PubMed, the Malaria in Pregnancy Library database, Medline, Global Health and Global Health Archives, and the Cochrane Library for trials, mixed-methods, qualitative, and cost-effectiveness studies of community health worker promotion of antenatal care, IPTp-SP delivery, or both, with no language restrictions, published before March 21, 2024. Information on interventions, number of IPTp-SP doses, antenatal care visits, and barriers and facilitators were extracted. We did a meta-analysis (random effects) comparing effects on two or more or three or more IPTp-SP doses and one or more or four or more antenatal care visits. We followed Noblit and Hare's method of meta-ethnography to synthesise qualitative findings, using reciprocal translation and line-of-argument synthesis. We developed a theory for increased community IPTp-SP uptake. We also summarised cost and cost-effectiveness studies. This study is registered with PROSPERO, CRD42022364114. FINDINGS: Of 4753 records screened, we included 23 (0·5%) reporting on 15 studies. Community health worker involvement was associated with an increase in two or more IPTp-SP doses (pooled risk ratio 1·48, [95% CI 1·24-1·75]; 12 sub-studies; I2 94·7%) and three or more IPTp-SP doses (1·73 [1·19-2·50]; ten sub-studies, I2 97·5%), with no decrease in four or more antenatal care visits (1·17 [1·00-1·36]; 13 sub-studies; I2 90·3%). Cluster-randomised controlled trials showed a lower increase in coverage of three or more IPTp-SP doses (1·08 [1·00-1·16]; I2 0·0%; six studies) compared with before-and-after studies (2·86 [1·29-6·33]; I2 98·9%; four studies; subgroup analysis p=0·019). Barriers to community health worker delivery of IPTp-SP included women's fear of side-effects, lack of knowledge, lack of trust in community health workers, and sociocultural factors. Community sensitisation, engagement of husbands, pre-established community health worker networks, and trained and supported community health workers facilitated IPTp-SP delivery by community health workers. Incremental cost-effectiveness ratios ranged from $1·1 to $543 per disability-adjusted life-year averted. INTERPRETATION: Community-based approaches increased IPTp-SP coverage and might have a positive effect on the number of antenatal care visits in addition to being cost-effective, although we found high heterogeneity among studies. Community sensitisation and engagement in addition to established, trained, and supported community health workers can facilitate acceptability, delivery, and uptake of IPTp-SP delivered by community health workers. FUNDING: EDCTP-2 supported by the European Union. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Increased reproductive tract infections among secondary school girls during the COVID-19 pandemic: associations with pandemic-related stress, mental health, and domestic safety.

Background: Kenya, like many countries, shuttered schools during COVID-19, with subsequent increases in poor mental health, sexual activity, and pregnancy. Aim: We sought to understand how the COVID-19 pandemic may mediate the risk of reproductive tract infections. Methods: We analyzed data from a cohort of 436 secondary schoolgirls in western Kenya. Baseline and 6-, 12-, and 18-month study visits occurred from April 2018 to December 2019 (pre-COVID-19), and 30-, 36-, and 48-month study visits occurred from September 2020 to July 2022 (COVID-19 period). Participants self-completed a survey for sociodemographics and sexual activity and provided self-collected vaginal swabs for bacterial vaginosis (BV) testing, with sexually transmitted infection (STI) testing at annual visits. We hypothesized that greater COVID-19-related stress would mediate risk via mental health, feeling safe inside the home, and sexual exposure, given the pandemic mitigation-related impacts of school closures on these factors. COVID-19-related stress was measured with a standardized scale and dichotomized at the highest quartile. Mixed effects modeling quantified how BV and STI changed over time. Longitudinal mediation analysis quantified how the relationship between COVID-19 stress and increased BV was mediated. Outcomes: Analysis outcomes were BV and STI. Results: BV and STI prevalence increased from 12.1% and 10.7% pre-COVID-19 to 24.5% and 18.1% during COVID-19, respectively. This equated to 26% (95% CI, 1.00-1.59) and 36% (95% CI, 0.98-1.88) higher relative prevalence of BV and STIs in the COVID-19 vs pre-COVID-19 periods, adjusted for numerous sociodemographic and behavioral factors. Higher COVID-19-related stress was associated with elevated depressive symptoms and feeling less safe inside the home, which were each associated with a greater likelihood of having a boyfriend. In mediation analyses, the direct effect of COVID-19-related stress on BV was small and nonsignificant, indicating that the increased BV was due to the constellation of factors that were affected during the COVID-19 pandemic. Clinical Translation: These results highlight factors to help maintain reproductive health for adolescent girls in future crises, such as anticipating and mitigating mental health impacts, domestic safety concerns, and maintaining sexual health services. Strengths and Limitations: Impacts of the COVID-19 pandemic on drivers of reproductive tract health among those who did not attend school or who live in different settings may differ. Conclusions: In this cohort of adolescent girls, BV and STIs increased following COVID-19-related school closures, and risk was mediated by depressive symptoms and feeling less safe in the home, which led to a higher likelihood of sexual exposures.

"He'll come with some sugar." A qualitative study exploring the drivers and consequences of schoolgirls transactional sex behaviours.

Intoduction: Transactional sex (TS) is common in areas of sub-Saharan Africa, motivated by reasons beyond financial support. Through this qualitative study we sought to understand the motivation driving TS among adolescent schoolgirls in rural western Kenya where rates are reportedly high. Identifying and understanding drivers within the local context is necessary for implementation of successful public health policy and programming to reduce the associated harms impacting health and wellbeing. Methods: To understand the drivers of sexual behaviors, individual views, and socio-cultural norms, we spoke with schoolgirls, male peers, parents and teachers. The three latter groups may influence, encourage, and shape girls' views and behaviors and thus contribute to the perpetuation of cultural and societal norms. Results: One hundred and ninety-nine participants took part across 20 FGDs; 8 comprised of schoolgirl groups, and 4 each of schoolboy, parent or teacher groups. Through thematic analysis, poverty emerged as the key driver of TS and a normative behaviour amongst secondary school girls. Subthemes including parental influence, need for menstrual pads, pressure from boda boda drivers, peer pressure, and blame were part of a complex relationship linking poverty with TS. Discussion: We conclude that whilst TS is perceived as inevitable, normal and acceptable it is not really a choice for many girls. Exploring ways to encourage communication between families, including around menstruation, may help enable girls to ask for help in acquiring essential items. In addition, education at a community level may shift social norms over time and decrease the prevalence of age-disparate TS among schoolgirls and older, wealthier men in the community.

Increased reproductive tract infections among secondary school girls during the COVID-19 pandemic: associations with pandemic related stress, mental health, and domestic safety.

Background: Kenya, like many countries, shuttered schools during COVID-19, with subsequent increases in poor mental health, sexual activity, and pregnancy. We sought to understand how the COVID-19 pandemic may mediate risk of reproductive tract infections. We hypothesized that greater COVID-19 related stress would mediate risk via mental health, feeling safe inside the home, and sexual exposure, given the pandemic mitigation-related impacts of school closures on these factors. Methods: We analyzed data from a cohort of 436 girls enrolled in secondary school in rural western Kenya. Baseline, 6-, 12-, and 18- month study visits occurred April 2018 - December 2019 (pre-COVID), and 30-, 36-, and 48- month study visits occurred September 2020 - July 2022 (COVID period). At study visits, participants self-completed a survey for sociodemographics and sexual practices, and provided self-collected vaginal swabs for Bacterial vaginosis (BV) testing, with STI testing at annual visits. COVID-related stress was measured with a standardized scale and dichotomized at highest quartile. Mixed effects modeling quantified how BV and STI changed over time, and longitudinal mediation analysis quantified how the relationship between COVID-19 stress and increased BV was mediated. Findings: BV and STI prevalence increased from 12.1% and 10.7% pre-COVID to 24.5% and 18.1% during COVID, respectively. This equated to a 26% (95% CI 1.00 - 1.59) and 36% (95% CI 0.98 - 1.88) increased relative prevalence of BV and STIs, respectively, in the COVID-19 period compared to pre-COVID, adjusted for numerous sociodemographic and behavioral factors. Higher COVID-related stress was associated with elevated depressive symptoms and feeling less safe inside the home, which were each associated with increased likelihood of having a boyfriend. In longitudinal mediation analyses, the direct effect of COVID-related stress on BV was small and non-significant, indicating increased BV was due to the constellation of factors that were impacted during the COVID-pandemic. Conclusions: In this cohort of adolescent girls, BV and STIs increased following COVID-related school closures. These results highlight modifiable factors to help maintain sexual and reproductive health resiliency, such as anticipating and mitigating mental health impacts, domestic safety concerns, and maintaining sexual health services to prevent and treat reproductive tract infections.

The effectiveness of malaria camps as part of the malaria control program in Odisha, India.

Durgama Anchalare Malaria Nirakaran (DAMaN) is a multi-component malaria intervention for hard-to-reach villages in Odisha, India. The main component, malaria camps (MCs), consists of mass screening, treatment, education, and intensified vector control. We evaluated MC effectiveness using a quasi-experimental cluster-assigned stepped-wedge study with a pretest-posttest control group in 15 villages: six immediate (Arm A), six delayed (Arm B), and three previous interventions (Arm C). The primary outcome was PCR + Plasmodium infection prevalence. The time (i.e., baseline vs. follow-up 3) x study arm interaction term shows that there were statistically significant lower odds of PCR + Plasmodium infection in Arm A (AOR = 0.36, 95% CI = 0.17, 0.74) but not Arm C as compared to Arm B at the third follow-up. The cost per person ranged between US$3-8, the cost per tested US$4-9, and the cost per treated US$82-1,614, per camp round. These results suggest that the DAMaN intervention is a promising and financially feasible approach for malaria control.

The effect and control of malaria in pregnancy and lactating women in the Asia-Pacific region.

Half of all pregnancies at risk of malaria worldwide occur in the Asia-Pacific region, where Plasmodium falciparum and Plasmodium vivax co-exist. Despite substantial reductions in transmission, malaria remains an important cause of adverse health outcomes for mothers and offspring, including pre-eclampsia. Malaria transmission is heterogeneous, and infections are commonly subpatent and asymptomatic. High-grade antimalarial resistance poses a formidable challenge to malaria control in pregnancy in the region. Intermittent preventive treatment in pregnancy reduces infection risk in meso-endemic New Guinea, whereas screen-and-treat strategies will require more sensitive point-of-care tests to control malaria in pregnancy. In the first trimester, artemether-lumefantrine is approved, and safety data are accumulating for other artemisinin-based combinations. Safety of novel antimalarials to treat artemisinin-resistant P falciparum during pregnancy, and of 8-aminoquinolines during lactation, needs to be established. A more systematic approach to the prevention of malaria in pregnancy in the Asia-Pacific is required.

Menstrual cups and cash transfer to reduce sexual and reproductive harm and school dropout in adolescent schoolgirls in western Kenya: a cluster randomised controlled trial.

Background: High rates of sexual and reproductive health (SRH) harms and interrupted schooling are global challenges for adolescent girls, requiring effective interventions. We assessed the impact of menstrual cups (MCs) or cash transfers conditioned on school attendance (CCTs), or both, on SRH and schooling outcomes in western Kenya. Methods: In this cluster-randomised Cups or Cash for Girls (CCG) trial, adolescent girls in Forms two and three at 96 secondary schools in Siaya County (western Kenya) were randomised to receive either CCT, MC, combined CCT and MC, or control (1:1:1:1) for an average of 30 months. The CCT intervention comprised 1500KES (US$15 in 2016) via a cash card each school trimester. All four treatment groups received puberty and hygiene training. Assenting girls with parent or guardian consent who were post-menarche, not pregnant, area residents, not boarding, and had no disabilities precluding participation were eligible. Socio-behavioural risk factors and incidence of HIV and herpes simplex virus type 2 (HSV-2) were measured annually. School retainment and adverse events were monitored throughout. The primary outcome comprised a composite of incident HIV, HSV-2 and/or all-cause school dropout by school exit examination. The primary analysis was by intention-to-treat (ITT) using generalised linear mixed models, controlling for a priori selected baseline covariates. The trial is registered with ClinicalTrials.gov, NCT03051789. Findings: Between February 28, 2017 and June 30, 2021, 4137 girls (median age 17.1 [interquartile range (IQR): 16.3-18.0]) were enrolled and followed annually until completion of secondary school (median 2.5 years [IQR: 2.4-2.7]); 4106 (99.3%) contributed to the ITT analysis. No differences in the primary composite outcome between intervention and control groups were seen (MC: 18.2%, CCT: 22.1%, combined: 22.1%, control: 19.6%; adjusted risk ratio [aRR]: 0.97, 95% confidence interval 0.76-1.24; 1.14, 0.90-1.45; and 1.13, 0.90-1.43, respectively). Incident HSV-2 occurred in 8.6%, 13.3%, 14.8%, and 12% of the MC, CCT, combined and control groups, respectively (MC: RR: 0.67, 0.47-0.95, p = 0.027; aRR: 0.71, 0.50-1.01, p = 0.057; CCT: aRR: 1.02, 0.73-1.41, p = 0.92; combined aRR: 1.16, 0.85-2.58, p = 0.36). Incident HIV was low (MC: 1.2%, CCT: 1.5%, combined: 1.0%, and control: 1.4%; aRR: 0.88, 0.38-2.05, p = 0.77, aRR: 1.16, 0.51-2.62, p = 0.72, aRR: 0.80, 0.33-1.94, p = 0.62, respectively). No intervention decreased school dropout (MC: 11.2%, CCT: 12.4%, combined: 10.9%, control: 10.5%; aRR: 1.16, 0.86-1.57; 1.23, 0.91-1.65; and 1.06, 0.78-1.44, respectively). No related serious adverse events were seen. Interpretation: MCs, CCTs, or both, did not protect schoolgirls against a composite of deleterious harms. MCs appear protective against HSV-2. Studies of longer follow-up duration with objective measures of health impact are needed in this population. Funding: Department of Health and Social Care, the Foreign, Commonwealth & Development Office, the Medical Research Council and Wellcome.

Vaginal Microbial Network Analysis Reveals Novel Taxa Relationships among Adolescent and Young Women with Incident Sexually Transmitted Infection Compared with Those Remaining Persistently Negative over a 30-Month Period.

A non-optimal vaginal microbiome (VMB) is typically diverse with a paucity of Lactobacillus crispatus and is often associated with bacterial vaginosis (BV) and sexually transmitted infections (STIs). Although compositional characterization of the VMB is well-characterized, especially for BV, knowledge remains limited on how different groups of bacteria relate to incident STIs, especially among adolescents. In this study, we compared the VMB (measured via 16S ribosomal RNA gene amplicon sequencing) of Kenyan secondary school girls with incident STIs (composite of chlamydia, gonorrhea, and trichomoniasis) to those who remained persistently negative for STIs and BV over 30 months of follow-up. We applied microbial network analysis to identify key taxa (i.e., those with the greatest connectedness in terms of linkages to other taxa), as measured by betweenness and eigenvector centralities, and sub-groups of clustered taxa. VMB networks of those who remained persistently negative reflected greater connectedness compared to the VMB from participants with STI. Taxa with the highest centralities were not correlated with relative abundance and differed between those with and without STI. Subject-level analyses indicated that sociodemographic (e.g., age and socioeconomic status) and behavioral (e.g., sexual activity) factors contribute to microbial network structure and may be of relevance when designing interventions to improve VMB health.

Analysis of bacterial vaginosis, the vaginal microbiome, and sexually transmitted infections following the provision of menstrual cups in Kenyan schools: Results of a nested study within a cluster randomized controlled trial.

BACKGROUND: Nonhygienic products for managing menstruation are reported to cause reproductive tract infections. Menstrual cups are a potential solution. We assessed whether menstrual cups would reduce bacterial vaginosis (BV), vaginal microbiome (VMB), and sexually transmitted infections (STIs) as studies have not evaluated this. METHODS AND FINDINGS: A cluster randomized controlled trial was performed in 96 Kenyan secondary schools, randomized (1:1:1:1) to control, menstrual cup, cash transfer, or menstrual cup plus cash transfer. This substudy assessing the impact of menstrual cups on BV, VMB, and STIs, included 6 schools from the control (3) and menstrual cup only (3) groups, both receiving BV and STI testing and treatment at each visit. Self-collected vaginal swabs were used to measure VMB (16S rRNA gene amplicon sequencing), BV (Nugent score), and STIs. STIs were a composite of Chlamydia trachomatis and Neisseria gonorrhoeae (nucleic acid amplification test) and Trichomonas vaginalis (rapid immunochromatographic assay). Participants were not masked and were followed for 30 months. The primary outcome was diagnosis of BV; secondary outcomes were VMB and STIs. Intention-to-treat blinded analyses used mixed effects generalized linear regressions, with random effects term for school. The study was conducted between May 2, 2018, and February 7, 2021. A total of 436 participants were included: 213 cup, 223 control. There were 289 BV diagnoses: 162 among control participants and 127 among intervention participants (odds ratio 0.76 [95% CI 0.59 to 0.98]; p = 0.038). The occurrence of Lactobacillus crispatus-dominated VMB was higher among cup group participants (odds ratio 1.37 [95% CI 1.06 to 1.75]), as was the mean relative abundance of L. crispatus (3.95% [95% CI 1.92 to 5.99]). There was no effect of intervention on STIs (relative risk 0.82 [95% CI 0.50 to 1.35]). The primary limitations of this study were insufficient power for subgroup analyses, and generalizability of findings to nonschool and other global settings. CONCLUSIONS: Menstrual cups with BV and STI testing and treatment benefitted adolescent schoolgirls through lower occurrence of BV and higher L. crispatus compared with only BV and STI testing and treatment during the 30 months of a cluster randomized menstrual cup intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT03051789.

Fetal sex and risk of pregnancy-associated malaria in Plasmodium falciparum-endemic regions: a meta-analysis.

In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, pre-eclampsia, and gestational diabetes. One study demonstrated increased risk of placental malaria in women carrying a female fetus. We investigated the association between fetal sex and malaria in pregnancy in 11 pregnancy studies conducted in sub-Saharan African countries and Papua New Guinea through meta-analysis using log binomial regression fitted to a random-effects model. Malaria infection during pregnancy and delivery was assessed using light microscopy, polymerase chain reaction, and histology. Five studies were observational studies and six were randomised controlled trials. Studies varied in terms of gravidity, gestational age at antenatal enrolment and bed net use. Presence of a female fetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14 [95% confidence interval 1.04, 1.24]; P = 0.003; n = 11,729). Fetal sex did not associate with malaria infection when other time points or diagnostic methods were used. There is limited evidence that fetal sex influences the risk of malaria infection in pregnancy.

Prevalence of and risk factors for microscopic and submicroscopic malaria infections in pregnancy: a systematic review and meta-analysis.

BACKGROUND: Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of submicroscopic malaria infections in pregnant women in Asia, the Americas, and Africa using aggregated and individual participant data (IPD). METHODS: For this systematic review and meta-analysis, studies (published Jan 1, 1997 to Nov 10, 2021) with information on both microscopic and submicroscopic infections during pregnancy from Asia, the Americas, or Africa, identified in the Malaria-in-Pregnancy Library, were eligible. Studies (or subgroups or study groups) that selected participants on the basis of the presence of fever or a positive blood smear were excluded to avoid selection bias. We obtained IPD (when available) and aggregated data. Estimates of malaria transmission intensity and sulfadoxine-pyrimethamine resistance, matched by study location and year, were obtained using publicly available data. One-stage multivariable logit and multinomial models with random intercepts for study site were used in meta-analysis to assess prevalence of and risk factors for submicroscopic infections during pregnancy and at delivery. This study is registered with PROSPERO, number CRD42015027342. FINDINGS: The search identified 87 eligible studies, 68 (78%) of which contributed to the analyses. Of these 68 studies, 45 (66%) studies contributed IPD (48 869 participants) and 23 (34%) studies contributed aggregated data (11 863 participants). During pregnancy, median prevalence estimates were 13·5% (range 0·0-55·9, 66 substudies) for submicroscopic and 8·0% (0·0-50·6, 66 substudies) for microscopic malaria. Among women with positive Plasmodium nucleic acid amplification tests (NAATs), the median proportion of submicroscopic infections was 58·7% (range 0·0-100); this proportion was highest in the Americas (73·3%, 0·0-100), followed by Asia (67·2%, 36·4-100) and Africa (56·5%, 20·5-97·7). In individual patient data analysis, compared with women with no malaria infections, those with submicroscopic infections were more likely to present with fever in Africa (adjusted odds ratio 1·32, 95% CI 1·02-1·72; p=0·038) but not in other regions. Among women with NAAT-positive infections in Asia and the Americas, Plasmodium vivax infections were more likely to be submicroscopic than Plasmodium falciparum infections (3·69, 2·45-5·54; p<0·0001). Risk factors for submicroscopic infections among women with NAAT-positive infections in Africa included older age (age ≥30 years), multigravidity, and no HIV infection. INTERPRETATION: During pregnancy, submicroscopic infections are more common than microscopic infections and are associated with fever in Africa. Malaria control in pregnancy should target both microscopic and submicroscopic infections. FUNDING: Bill & Melinda Gates Foundation through the Worldwide Antimalarial Resistance Network.

The effectiveness of malaria camps as part of the malaria control program in Odisha, India.

Durgama Anchalare Malaria Nirakaran (DAMaN) is a multi-component malaria intervention for hard-to-reach villages in Odisha, India. The main component, Malaria Camps (MCs), consists of mass screening, treatment, education, and intensified vector control. We evaluated MC effectiveness using a quasi-experimental cluster-assigned stepped-wedge study with a pretest-posttest control group in 15 villages: six immediate (Arm A), six delayed (Arm B), and three previous interventions (Arm C). The primary outcome was PCR+ Plasmodium infection prevalence. Across all arms, the odds of PCR+ malaria were 54% lower at the third follow-up compared to baseline. A time (i.e., visit) x study arm interaction revealed significantly lower odds of PCR+ malaria in Arm A versus B at the third follow-up. The cost per person ranged between US$3-8, the cost per tested US$4-7, and the cost per treated US$82-1,614, per camp round. These results suggest that the DAMaN intervention is a promising, financially feasible approach for malaria control.

Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis.

BACKGROUND: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. METHODS: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. FINDINGS: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92). INTERPRETATION: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. FUNDING: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

Post-discharge morbidity and mortality in children admitted with severe anaemia and other health conditions in malaria-endemic settings in Africa: a systematic review and meta-analysis.

BACKGROUND: Severe anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also remain at increased risk of mortality for several months after hospital discharge. We aimed to compare the risks of morbidity and mortality among children discharged from hospital after recovery from severe anaemia versus other health conditions in malaria-endemic settings in Africa. METHODS: Following PRISMA guidelines, we searched PubMed, Scopus, Web of Science, and Cochrane Central from inception to Nov 30, 2021, without language restrictions, for prospective or retrospective cohort studies and randomised controlled trials that followed up children younger than 15 years for defined periods after hospital discharge in malaria-endemic countries in Africa. We excluded the intervention groups in trials and studies or subgroups involving children with sickle cell anaemia, malignancies, or surgery or trauma, or those reporting follow-up data that were combined with the in-hospital period. Two independent reviewers extracted the data and assessed the quality and risk of bias using the Newcastle Ottawa Scale or the Cochrane Collaboration's tool. The coprimary outcomes were all-cause death and all-cause readmissions 6 months after discharge. This study is registered with PROSPERO, CRD42017079282. FINDINGS: Of 2930 articles identified in our search, 27 studies were included. For children who were recently discharged following hospital admission with severe anaemia, all-cause mortality by 6 months was higher than during the in-hospital period (n=5 studies; Mantel-Haenszel odds ratio 1·72, 95% CI 1·22-2·44; p=0·0020; I2=51·5%) and more than two times higher than children previously admitted without severe anaemia (n=4 studies; relative risk [RR] 2·69, 95% CI 1·59-4·53; p<0·0001; I2=69·2%). Readmissions within 6 months of discharge were also more common in children admitted with severe anaemia than in children admitted with other conditions (n=1 study; RR 3·05, 1·12-8·35; p<0·0001). Children admitted with severe acute malnutrition (regardless of severe anaemia) also had a higher 6-month mortality after discharge than those admitted for other reasons (n=2 studies; RR=3·12, 2·02-4·68; p<0·0001; I2=54·7%). Other predictors of mortality after discharge included discharge against medical advice, HIV, bacteraemia, and hypoxia. INTERPRETATION: In malaria-endemic settings in Africa, children admitted to hospital with severe anaemia and severe acute malnutrition are at increased risk of mortality in the first 6 months after discharge compared with children admitted with other health conditions. Improved strategies are needed for the management of these high-risk groups during the period after discharge. FUNDING: Research Council of Norway and US Centers for Disease Control and Prevention.

'You don't have to sleep with a man to get how to survive': Girl's perceptions of an intervention study aimed at improving sexual and reproductive health and schooling outcomes.

In sub-Saharan Africa, girls suffer from high rates of morbidity and mortality, enduring high exposure to sexual and reproductive health harms. Staying in school helps protect girls from such harms. Focus group discussions were conducted in a rural, impoverished area of Kenya with adolescent girls participating in a 4-arm cluster randomised controlled trial, evaluating menstrual cups, cash transfer, or combined cups plus cash transfer against controls. To explore girls' perceptions of how trial interventions affected their SRH risks and schooling, semi-structured discussions were held at baseline, midline, and study end. Data was explored using thematic analysis. At baseline there were no discernible differences between the 4 intervention groups regarding their perceptions of relationships with boys/men, and difficulties attending or remaining in school. Midline and endline discussions found that narratives from those receiving cash transfer only, or alongside a cup were similar; girls noted fewer pregnancies and less school dropout, attributed to the cash transfer reducing the need for transactional sex. Lower absenteeism was reported by the cup only group, with perceived minimal effect on pregnancy and dropout. Girls in control and cup only groups described feeling valued through inclusion, benefitting from puberty and hygiene education. Although seemingly having little effect on reducing pregnancy or dropout, these inputs reportedly empowered girls, whilst cash transfer girls were emboldened to refuse male sexual advances. Girls noticed benefits from trial interventions, with a reduction in transactional sex and resulting pregnancy impacting on school dropout, or reduced menstrual related absenteeism. Education and study inclusion were perceived as important. Future programmes should consider alleviating material deprivation which prevents girls from attending or performing at school through schemes such as cash transfer, alongside hygiene and education packages. This will empower girls to refuse unwanted sex and understand risks, in addition to motivating academic achievement and school completion. Trial registration: ClinicalTrials.gov NCT03051789.

Quality of life and well-being problems in secondary schoolgirls in Kenya: Prevalence, associated characteristics, and course predictors.

BACKGROUND: Adolescents in sub-Saharan Africa often report low levels of quality of life (QoL) and well-being, but reliable data are limited. This study examines which sociodemographic, health, and behavioral risk factors and adverse adolescent experiences are associated with, and predictive of, QoL in Kenyan secondary schoolgirls. METHODS AND FINDINGS: 3,998 girls at baseline in a randomised controlled trial in Siaya County, western Kenya were median age 17.1 years. Subjectively perceived physical, emotional, social and school functioning was assessed using the Pediatric Quality of Life (QoL) Inventory-23. Laboratory-confirmed and survey data were utilized to assess sociodemographic, health and behavioral characteristics, and adverse adolescent experiences. We identified a group of girls with Low QoL (n = 1126; 28.2%), Average QoL (n = 1445; 36.1%); and High QoL (n = 1427; 35.7%). Significantly higher scores on all well-being indicators in the LQoL compared with HQoL group indicated good construct validity (Odds Ratio's (ORs) varying from 3.31 (95% CI:2.41-4.54, p < .001) for feeling unhappy at home to 11.88 (95%CI:7.96-17.74, p< .001) for PHQ9 defined possible caseness (probable diagnosis) of depression. Adverse adolescent experiences were independently statistically significant in the LQoL compared to the HQoL group for threats of family being hurt (aOR = 1.35,1.08-1.68, p = .008), sexual harassment out of school (aOR = 2.17,1.79-2.64, p < .001), and for menstrual problems like unavailability of sanitary pads (aOR = 1.23,1.05-1.44, p = .008) and stopping activities due to menstruation (aOR = 1.77,1.41-2.24, p < .001). After 2-years follow-up of 906 girls in the LQoL group, 22.7% persisted with LQoL. Forced sex (aOR = 1.56,1.05-2.32, p = .028) and threats of family being hurt (aOR = 1.98,1.38-2.82, p < .001) were independent predictors of persistent LQoL problems. CONCLUSIONS: Persistent QoL problems in Kenyan adolescent girls are associated with adverse physical, sexual and emotional experiences and problems with coping with their monthly menstruation. A multi-factorial integral approach to reduce the rate of adverse adolescent experiences is needed, including provision of menstrual hygiene products. TRIAL REGISTRATION: ClinicalTrials.gov:NCT03051789.

High Prevalence of Lactobacillus crispatus Dominated Vaginal Microbiome Among Kenyan Secondary School Girls: Negative Effects of Poor Quality Menstrual Hygiene Management and Sexual Activity.

The vaginal microbiome (VMB) impacts numerous health outcomes, but evaluation among adolescents is limited. We characterized the VMB via 16S rRNA gene amplicon sequencing, and its association with Bacterial vaginosis (BV) and sexually transmitted infections (STIs; chlamydia, gonorrhea, trichomoniasis) among 436 schoolgirls in Kenya, median age 16.9 years. BV and STI prevalence was 11.2% and 9.9%, respectively, with 17.6% of girls having any reproductive tract infection. Three community state types (CST) accounted for 95% of observations: CST-I L.crispatus-dominant (N=178, BV 0%, STI 2.8%, sexually active 21%); CST-III L.iners-dominant (N=152, BV 3.3%, STI 9.7%, sexually active 35%); CST-IV G.vaginalis-dominant (N=83, BV 51.8%, STI 25.3%, sexually active 43%). In multivariable adjusted analyses, sexually active girls had increased odds of CST-III and CST-IV, and use of cloth to manage menses had 1.72-fold increased odds of CST-IV vs. CST-I. The predominance of L.crispatus-dominated VMB, substantially higher than observed in prior studies of young adult and adult women in sub-Saharan Africa, indicates that non-optimal VMB can be an acquired state. Interventions to maintain or re-constitute L.crispatus dominance should be considered even in adolescents.

Exploring menstrual products: A systematic review and meta-analysis of reusable menstrual pads for public health internationally.

BACKGROUND: Girls and women need effective, safe, and affordable menstrual products. Single-use menstrual pads and tampons are regularly provided by agencies among resource-poor populations. Reusable menstrual pads (RMPs: fabric layers sewn together by an enterprise for manufacture of menstrual products) may be an effective alternative. METHODS: For this review (PROSPERO CRD42020179545) we searched databases (inception to November 1, 2020) for quantitative and qualitative studies that reported on leakage, acceptability, or safety of RMPs. Findings were summarised or combined using forest plots (random-effects meta-analysis). Potential costs and environmental savings associated with RMPs were estimated. RESULTS: A total of 44 studies were eligible (~14,800 participants). Most were conducted in low- and middle-income countries (LMIC, 78%), and 20% in refugee settings. The overall quality of studies was low. RMP uptake in cohort studies ranged from 22-100% (12 studies). One Ugandan trial among schoolgirls found leakage with RMPs was lower (44.4%, n = 72) compared to cloths (78%, n = 111, p<0.001). Self-reported skin-irritation was 23.8% after 3 months among RMP-users in a Ugandan cohort in a refugee setting (n = 267), compared to 72.8% at baseline with disposable pad use. There were no objective reports on infection. Challenges with washing and changing RMP were reported in LMIC studies, due to lack of water, privacy, soap, buckets, and sanitation/drying facilities. Among 69 brands, the average price for an RMP was $8.95 (standard deviation [sd] $5.08; LMIC $2.06, n = 10, high-income countries [HIC] $10.11), with a mean estimated lifetime of 4.3 years (sd 2.3; LMIC 2.9, n = 11; HIC 4.9 years, n = 23). In 5-year cost-estimates, in LMICs, 4-25 RMPs per period would be cheaper (170-417 US$) than 9-25 single-use pads, with waste-savings of ~600-1600 single-use pads. In HICs, 4-25 RMPs would be cheaper (33-245 US$) compared to 20 single-use tampons per period, with waste-savings of ~1300 tampons. CONCLUSION: RMPs are used internationally and are an effective, safe, cheaper, and environmentally friendly option for menstrual product provision by programmes. Good quality studies in this field are needed.

Factors associated with the prevalence of HIV, HSV-2, pregnancy, and reported sexual activity among adolescent girls in rural western Kenya: A cross-sectional analysis of baseline data in a cluster randomized controlled trial.

BACKGROUND: Adolescence is a sensitive time for girls' sexual and reproductive health (SRH), as biological changes occur concurrently with heightening pressures for sexual activity. In western Kenya, adolescent girls are vulnerable to acquiring sexually transmitted infections (STIs), such as HIV and herpes simplex virus type 2 (HSV-2), and to becoming pregnant prior to reaching adulthood. This study examines associations between individual, household, and partner-related risk factors and the prevalence of sex, adolescent pregnancy, HIV, and HSV-2. METHODS AND FINDINGS: We report baseline findings among 4,138 girls attending secondary school who were enrolled between 2017 and 2018 in the Cups or Cash for Girls (CCG) cluster randomized controlled trial in Siaya County, rural western Kenya. Laboratory confirmed biomarkers and survey data were utilized to assess the effects of girls' individual, household, and partner characteristics on the main outcome measures (adolescent reported sex, prior pregnancy, HIV, and HSV-2) through generalized linear model (GLM) analysis. Complete data were available for 3,998 girls (97%) with median age 17.1 years (interquartile range [IQR] 16.3 to 18.0 years); 17.2% were HSV-2 seropositive (n = 686) and 1.7% tested positive for HIV (n = 66). Sexual activity was reported by 27.3% girls (n = 1,090), of whom 12.2% had been pregnant (n = 133). After adjustment, orphanhood (adjusted risk ratio [aRR] 2.81, 95% confidence interval [CI] 1.18 to 6.71, p-value [p] = 0.020), low body mass index (BMI) (aRR 2.07; CI: 1.00 to 4.30, p = 0.051), and age (aRR 1.34, 1.18 to 1.53, p < 0.001) were all associated with HIV infection. Girls reporting light menstrual bleeding (aRR 2.42, 1.22 to 4.79, p = 0.012) for fewer than 3 days (aRR 2.81, 1.16 to 6.82, p = 0.023) were over twice as likely to have HIV. Early menarche (aRR 2.05, 1.33 to 3.17, p = 0.001) was associated with adolescent pregnancy and HSV-2-seropositive girls reported higher rates of pregnancy (aRR 1.62, CI: 1.16 to 2.27, p = 0.005). High BMI was associated with HSV-2 (aRR 1.24, 1.05 to 1.46, p = 0.010) and sexual activity (aRR 1.14, 1.02 to 1.28, p = 0.016). High levels of harassment were detected in the cohort (41.2%); being touched indecently conveyed the strongest association related to reported sexual activity (aRR 2.52, 2.26 to 2.81, p < 0.001). Study limitations include the cross-sectional design of the study, which informs on the SRH burdens found in this population but limits causal interpretation of associations, and the self-reported exposure ascertainment, which may have led to possible underreporting of risk factors, most notably prior sexual activity. CONCLUSIONS: Our findings indicate that adolescent girls attending school in Kenya face frequent harassment for sex and are at high risk of pregnancy and HSV-2, with girls experiencing early menarche particularly vulnerable. Targeted interventions, such as earlier sexual education programs, are warranted to address their vulnerability to SRH harms. TRIAL REGISTRATION: ClinicalTrials.gov NCT03051789.

The effectiveness of malaria camps as part of the Durgama Anchalare Malaria Nirakaran (DAMaN) program in Odisha, India: study protocol for a cluster-assigned quasi-experimental study.

The Indian state of Odisha has a longstanding battle with forest malaria. Many remote and rural villages have poor access to health care, a problem that is exacerbated during the rainy season when malaria transmission is at its peak. Approximately 62% of the rural population consists of tribal groups who are among the communities most negatively impacted by malaria. To address the persistently high rates of malaria in these remote regions, the Odisha State Malaria Control Program introduced 'malaria camps' in 2017 where teams of health workers visit villages to educate the population, enhance vector control methods, and perform village-wide screening and treatment. Malaria rates declined statewide, particularly in forested areas, following the introduction of the malaria camps, but the impact of the intervention is yet to be externally evaluated. This study protocol describes a cluster-assigned quasi-experimental stepped-wedge study with a pretest-posttest control group design that evaluates if malaria camps reduce the prevalence of malaria, compared to control villages which receive the usual malaria control interventions (e.g. IRS, ITNs), as detected by PCR.