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Background: The PRECISE (PREgnancy Care Integrating translational Science, Everywhere) Network is a new and broadly-based group of research scientists and health advocates based in the UK, Africa and North America. Methods: This paper describes the protocol that underpins the clinical research activity of the Network, so that the investigators, and broader global health community, can have access to 'deep phenotyping' (social determinants of health, demographic and clinical parameters, placental biology and agnostic discovery biology) of women as they advance through pregnancy to the end of the puerperium, whether those pregnancies have normal outcomes or are complicated by one/more of the placental disorders of pregnancy (pregnancy hypertension, fetal growth restriction and stillbirth). Our clinical sites are in The Gambia (Farafenni), Kenya (Kilifi County), and Mozambique (Maputo Province). In each country, 50 non-pregnant women of reproductive age will be recruited each month for 1 year, to provide a final national sample size of 600; these women will provide culturally-, ethnically-, seasonally- and spatially-relevant control data with which to compare women with normal and complicated pregnancies. Between the three countries we will recruit ≈10,000 unselected pregnant women over 2 years. An estimated 1500 women will experience one/more placental complications over the same epoch. Importantly, as we will have accurate gestational age dating using the TraCer device, we will be able to discriminate between fetal growth restriction and preterm birth. Recruitment and follow-up will be primarily facility-based and will include women booking for antenatal care, subsequent visits in the third trimester, at time-of-disease, when relevant, during/immediately after birth and 6 weeks after birth. Conclusions: To accelerate progress towards the women's and children's health-relevant Sustainable Development Goals, we need to understand how a variety of social, chronic disease, biomarker and pregnancy-specific determinants health interact to result in either a resilient or a compromised pregnancy for either mother or fetus/newborn, or both. This protocol has been designed to create such a depth of understanding. We are seeking funding to maintain the cohort to better understand the implications of pregnancy complications for both maternal and child health. [ABSTRACT FROM AUTHOR]

Background: The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) focus is on randomized trials of different approaches to mass drug administration (MDA) in endemic countries in Africa. Because their studies provided an opportunity to evaluate the effects of mass treatment on Schistosoma-associated morbidity, nested cohort studies were developed within SCORE's intervention trials to monitor changes in a suite of schistosomiasis disease outcomes. This paper describes the process SCORE used to select markers for prospective monitoring and the baseline prevalence of these morbidities in four parallel cohort studies.Methods: In July 2009, SCORE hosted a discussion of the potential impact of MDA on morbidities due to Schistosoma infection that might be measured in the context of multi-year control. Candidate markers were reviewed and selected for study implementation. Baseline data were then collected from cohorts of children in four country studies: two in high endemic S. mansoni sites (Kenya and Tanzania), and two in high endemic S. haematobium sites (Niger and Mozambique), these cohorts to be followed prospectively over 5 years.Results: At baseline, 62% of children in the S. mansoni sites had detectable eggs in their stool, and 10% had heavy infections (≥ 400 eggs/g feces). Heavy S. mansoni infections were found to be associated with increased baseline risk of anemia, although children with moderate or heavy intensity infections had lower risk of physical wasting. Prevalence of egg-positive infection in the combined S. haematobium cohorts was 27%, with 5% of individuals having heavy infection (≥50 eggs/10 mL urine). At baseline, light intensity S. haematobium infection was associated with anemia and with lower scores in the social domain of health-related quality-of-life (HRQoL) assessed by Pediatric Quality of Life Inventory.Conclusions: Our consensus on practical markers of Schistosoma-associated morbidity indicated that height, weight, hemoglobin, exercise tolerance, HRQoL, and ultrasound abnormalities could be used as reference points for gauging treatment impact. Data collected over five years of program implementation will provide guidance for future evaluation of morbidity control in areas endemic for schistosomiasis.Trial Registration: These cohort studies are registered and performed in conjunction with the International Standard Randomised Controlled Trial Registry trials ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 , and ISRCTN32045736 . [ABSTRACT FROM AUTHOR]

Background: A major unresolved safety concern for malaria case management is the use of artemisinin combination therapies (ACTs) in the first trimester of pregnancy. There is a need for human data to inform policy makers and treatment guidelines on the safety of artemisinin combination therapies (ACT) when used during early pregnancy. Methods: The overall goal of this paper is to describe the methods and implementation of a study aimed at developing surveillance systems for identifying exposures to antimalarials during early pregnancy and for monitoring pregnancy outcomes using health and demographic surveillance platforms. This was a multi-center prospective observational cohort study involving women at health and demographic surveillance sites in three countries in Africa: Burkina Faso, Kenya and Mozambique [(ClinicalTrials.gov Identifier: NCT01232530)]. The study was designed to identify pregnant women with artemisinin exposure in the first trimester and compare them to: 1) pregnant women without malaria, 2) pregnant women treated for malaria, but exposed to other antimalarials, and 3) pregnant women with malaria and treated with artemisinins in the 2nd or 3rd trimesters from the same settings. Pregnant women were recruited through community-based surveys and attendance at health facilities, including antenatal care clinics and followed until delivery. Data from the three sites will be pooled for analysis at the end of the study. Results are forthcoming. Discussion: Despite few limitations, the methods described here are relevant to the development of sustainable pharmacovigilance systems for drugs used by pregnant women in the tropics using health and demographic surveillance sites to prospectively ascertain drug safety in early pregnancy. Trial registration: NCT01232530 [ABSTRACT FROM AUTHOR]

Background: Residual malaria transmission is the result of adaptive mosquito behavior that allows malaria vectors to thrive and sustain transmission in the presence of good access to bed nets or insecticide residual spraying. These behaviors include crepuscular and outdoor feeding as well as intermittent feeding upon livestock. Ivermectin is a broadly used antiparasitic drug that kills mosquitoes feeding on a treated subject for a dose-dependent period. Mass drug administration with ivermectin has been proposed as a complementary strategy to reduce malaria transmission. Methods: A cluster randomized, parallel arm, superiority trial conducted in two settings with distinct eco-epidemiological conditions in East and Southern Africa. There will be three groups: human intervention, consisting of a dose of ivermectin (400 mcg/kg) administered monthly for 3 months to all the eligible population in the cluster (>15 kg, non-pregnant and no medical contraindication); human and livestock intervention, consisting human treatment as above plus treatment of livestock in the area with a single dose of injectable ivermectin (200 mcg/kg) monthly for 3 months; and controls, consisting of a dose of albendazole (400 mg) monthly for 3 months. The main outcome measure will be malaria incidence in a cohort of children under five living in the core of each cluster followed prospectively with monthly RDTs Discussion: The second site for the implementation of this protocol has changed from Tanzania to Kenya. This summary presents the Mozambique-specific protocol while the updated master protocol and the adapted Kenya-specific protocol undergo national approval in Kenya. BOHEMIA will be the first large-scale trial evaluating the impact of ivermectin-only mass drug administration to humans or humans and cattle on local malaria transmission Trial registration: ClinicalTrials.govNCT04966702. Registered on July 19, 2021. Pan African Clinical Trials Registry PACTR202106695877303. [ABSTRACT FROM AUTHOR]

Background: While there is increasing evidence on the safety of artemisinin-based combination therapy (ACT) for the case management of malaria in early pregnancy, little is known about the association between exposure to ACT during the first trimester and the effect on fetal growth. Methods: Data were analysed from prospective studies of pregnant women enrolled in Mozambique, Burkina Faso and Kenya designed to determine the association between anti-malarial drug exposure in the first trimester and pregnancy outcomes, including low birth weight (LBW) and small for gestational age (SGA). Exposure to anti-malarial drugs was ascertained retrospectively by record linkage using a combination of data collected from antenatal and adult outpatient clinic registries, prescription records and self-reported medication usage by the women. Site-level data synthesis (fixed effects and random effects) was conducted as well as individual-level analysis (fixed effects by site). Results: Overall, 1915 newborns were included with 92 and 26 exposed to ACT (artemether–lumefantrine) and quinine, respectively. In Burkina Faso, Mozambique and Kenya at recruitment, the mean age (standard deviation) was 27.1 (6.6), 24.2 (6.2) and 25.7 (6.5) years, and the mean gestational age was 24.0 (6.2), 21.2 (5.7) and 17.9 (10.2) weeks, respectively. The LBW prevalence among newborns born to women exposed to ACT and quinine (QNN) during the first trimester was 10/92 (10.9%) and 7/26 (26.9%), respectively, compared to 9.5% (171/1797) among women unexposed to any anti-malarials during pregnancy. Compared to those unexposed to anti-malarials, ACT and QNN exposed women had the pooled LBW prevalence ratio (PR) of 1.13 (95% confidence interval (CI) 0.62–2.05, p-value 0.700) and 2.03 (95% CI 1.09–3.78, p-value 0.027), respectively. Compared to those unexposed to anti-malarials ACT and QNN-exposed women had the pooled SGA PR of 0.85 (95% CI 0.50–1.44, p-value 0.543) and 1.41 (95% CI 0.71–2.77, p-value 0.322), respectively. Whereas compared to ACT-exposed, the QNN-exposed had a PR of 2.14 (95% CI 0.78–5.89, p-value 0.142) for LBW and 8.60 (95% CI 1.29–57.6, p-value 0.027) for SGA. The level of between sites heterogeneity was moderate to high. Conclusion: ACT exposure during the first trimester was not associated with an increased occurrence of LBW or SGA. However, the data suggest a higher prevalence of LBW and SGA for children born to QNN-exposed pregnancies. The findings support the use of ACT (artemether–lumefantrine) for the treatment of uncomplicated malaria during the first trimester of pregnancy. [ABSTRACT FROM AUTHOR]

Background: African annual killifishes (Nothobranchius spp.) are adapted to seasonally desiccating habitats (ephemeral pools), surviving dry periods as dormant eggs. Given their peculiar life history, geographic aspects of their diversity uniquely combine patterns typical for freshwater taxa (river basin structure and elevation gradient) and terrestrial animals (rivers acting as major dispersal barriers). However, our current knowledge on fine-scale inter-specific and intra-specific genetic diversity of African annual fish is limited to a single, particularly dry region of their distribution (subtropical Mozambique). Using a widespread annual killifish from coastal Tanzania and Kenya, we tested whether the same pattern of genetic divergence pertains to a wet equatorial region in the centre of Nothobranchius distribution. Results: In populations of Nothobranchius melanospilus species group across its range, we genotyped a part of mitochondrial cytochrome oxidase subunit 1 (COI) gene (83 individuals from 22 populations) and 10 nuclear microsatellite markers (251 individuals from 16 populations). We found five lineages with a clear phylogeographic structure but frequent secondary contact. Mitochondrial lineages were largely congruent with main population genetic clusters identified on microsatellite markers. In the upper Wami basin, populations are isolated as a putative Nothobranchius prognathus, but include also a population from a periphery of the middle Ruvu basin. Other four lineages (including putative Nothobranchius kwalensis) coexisted in secondary contact zones, but possessed clear spatial pattern. Main river channels did not form apparent barriers to dispersal. The most widespread lineage had strong signal of recent population expansion. Conclusions: We conclude that dispersal of a Nothobranchius species from a wet part of the genus distribution (tropical lowland) is not constrained by main river channels and closely related lineages frequently coexist in secondary contact zones. We also demonstrate contemporary connection between the Ruvu and Rufiji river basins. Our data do not provide genetic support for existence of recently described cryptic species from N. melanospilus complex, but cannot resolve this issue. [ABSTRACT FROM AUTHOR]

Background: Resistance and tolerance to Plasmodium falciparum can determine the progression of malaria disease. However, quantitative evidence of tolerance is still limited. We investigated variations in the adverse impact of P. falciparum infections among African pregnant women under different intensities of malaria transmission.Methods: P. falciparum at delivery was assessed by microscopy, quantitative PCR (qPCR) and placental histology in 946 HIV-uninfected and 768 HIV-infected pregnant women from Benin, Gabon, Kenya and Mozambique. Resistance was defined by the proportion of submicroscopic infections and the levels of anti-parasite antibodies quantified by Luminex, and tolerance by the relationship of pregnancy outcomes with parasite densities at delivery.Results: P. falciparum prevalence by qPCR in peripheral and/or placental blood of HIV-uninfected Mozambican, Gabonese and Beninese women at delivery was 6% (21/340), 11% (28/257) and 41% (143/349), respectively. The proportion of peripheral submicroscopic infections was higher in Benin (83%) than in Mozambique (60%) and Gabon (55%; P = 0.033). Past or chronic placental P. falciparum infection was associated with an increased risk of preterm birth in Mozambican newborns (OR = 7.05, 95% CI 1.79 to 27.82). Microscopic infections were associated with reductions in haemoglobin levels at delivery among Mozambican women (-1.17 g/dL, 95% CI -2.09 to -0.24) as well as with larger drops in haemoglobin levels from recruitment to delivery in Mozambican (-1.66 g/dL, 95% CI -2.68 to -0.64) and Gabonese (-0.91 g/dL, 95% CI -1.79 to -0.02) women. Doubling qPCR-peripheral parasite densities in Mozambican women were associated with decreases in haemoglobin levels at delivery (-0.16 g/dL, 95% CI -0.29 to -0.02) and increases in the drop of haemoglobin levels (-0.29 g/dL, 95% CI -0.44 to -0.14). Beninese women had higher anti-parasite IgGs than Mozambican women (P < 0.001). No difference was found in the proportion of submicroscopic infections nor in the adverse impact of P. falciparum infections in HIV-infected women from Kenya (P. falciparum prevalence by qPCR: 9%, 32/351) and Mozambique (4%, 15/417).Conclusions: The lowest levels of resistance and tolerance in pregnant women from areas of low malaria transmission were accompanied by the largest adverse impact of P. falciparum infections. Exposure-dependent mechanisms developed by pregnant women to resist the infection and minimise pathology can reduce malaria-related adverse outcomes. Distinguishing both types of defences is important to understand how reductions in transmission can affect malaria disease.Trial Registration: ClinicalTrials.gov NCT00811421 . Registered 18 December 2008. [ABSTRACT FROM AUTHOR]

Background: Female sex workers (FSWs) are extremely vulnerable to adverse sexual and reproductive health (SRH) outcomes. To mitigate these risks, they require access to services covering not only HIV prevention but also contraception, cervical cancer screening and sexual violence. To develop context-specific intervention packages to improve uptake, we identified gaps in service utilization in four different cities. Methods: A cross-sectional survey was conducted, as part of the baseline assessment of an implementation research project. FWSs were recruited in Durban, South Africa (n = 400), Mombasa, Kenya (n = 400), Mysore, India (n =458) and Tete, Mozambique (n = 308), using respondent-driven sampling (RDS) and starting with 8-16 'seeds' identified by the peer educators. FSWs responded to a standardised interviewer-administered questionnaire about the use of contraceptive methods and services for cervical cancer screening, sexual violence and unwanted pregnancies. RDS-adjusted proportions and surrounding 95% confidence intervals were estimated by non-parametric bootstrapping, and compared across cities using post-hoc pairwise comparison tests with Dunn--Šidák correction. Results: Current use of any modern contraception ranged from 86.2% in Tete to 98.4% in Mombasa (p = 0.001), while non-barrier contraception (hormonal, IUD or sterilisation) varied from 33.4% in Durban to 85.1% in Mysore (p < 0.001). Ever having used emergency contraception ranged from 2.4% in Mysore to 38.1% in Mombasa (p < 0.001), ever having been screened for cervical cancer from 0.0% in Tete to 29.0% in Durban (p < 0.001), and having gone to a health facility for a termination of an unwanted pregnancy from 15.0% in Durban to 93.7% in Mysore (p < 0.001). Having sought medical care after forced sex varied from 34.4% in Mombasa to 51.9% in Mysore (p = 0.860). Many of the differences between cities remained statistically significant after adjusting for variations in FSWs' sociodemographic characteristics. Conclusion: The use of SRH commodities and services by FSWs is often low and is highly context-specific. Reasons for variation across cities need to be further explored. The differences are unlikely caused by differences in socio-demographic characteristics and more probably stem from differences in the availability and accessibility of SRH services. Intervention packages to improve use of contraceptives and SRH services should be tailored to the particular gaps in each city. [ABSTRACT FROM AUTHOR]

Background: Estimating the size of forcibly displaced populations is key to documenting their plight and allocating sufficient resources to their assistance, but is often not done, particularly during the acute phase of displacement, due to methodological challenges and inaccessibility. In this study, we explored the potential use of very high resolution satellite imagery to remotely estimate forcibly displaced populations. Methods: Our method consisted of multiplying (i) manual counts of assumed residential structures on a satellite image and (ii) estimates of the mean number of people per structure (structure occupancy) obtained from publicly available reports. We computed population estimates for 11 sites in Bangladesh, Chad, Democratic Republic of Congo, Ethiopia, Haiti, Kenya and Mozambique (six refugee camps, three internally displaced persons' camps and two urban neighbourhoods with a mixture of residents and displaced) ranging in population from 1,969 to 90,547, and compared these to "gold standard" reference population figures from census or other robust methods. Results: Structure counts by independent analysts were reasonably consistent. Between one and 11 occupancy reports were available per site and most of these reported people per household rather than per structure. The imagery-based method had a precision relative to reference population figures of <10% in four sites and 10-30% in three sites, but severely over-estimated the population in an Ethiopian camp with implausible occupancy data and two post-earthquake Haiti sites featuring dense and complex residential layout. For each site, estimates were produced in 2-5 working person-days. Conclusions: In settings with clearly distinguishable individual structures, the remote, imagery-based method had reasonable accuracy for the purposes of rapid estimation, was simple and quick to implement, and would likely perform better in more current application. However, it may have insurmountable limitations in settings featuring connected buildings or shelters, a complex pattern of roofs and multi-level buildings. Based on these results, we discuss possible ways forward for the method's development. [ABSTRACT FROM AUTHOR]

Background: Qualitative research networks (QRNs) bring together researchers from diverse contexts working on multi-country studies. The networks may themselves form a consortium or may contribute to a wider research agenda within a consortium with colleagues from other disciplines. The purpose of a QRN is to ensure robust methods and processes that enable comparisons across contexts. Under the Self-Testing Africa (STAR) initiative and the REACHOUT project on community health systems, QRNs were established, bringing together researchers across countries to coordinate multi-country qualitative research and to ensure robust methods and processes allowing comparisons across contexts. QRNs face both practical challenges in facilitating this iterative exchange process across sites and conceptual challenges interpreting findings between contexts. This paper distils key lessons and reflections from both QRN experiences on how to conduct trustworthy qualitative research across different contexts with examples from Bangladesh, Ethiopia, Kenya, Indonesia, Malawi, Mozambique, Zambia and Zimbabwe., Methods: The process of generating evidence for this paper followed a thematic analysis method: themes initially identified were refined during several rounds of discussions in an iterative process until final themes were agreed upon in a joint learning process., Results: Four guiding principles emerged from our analysis: a) explicit communication strategies that sustain dialogue and build trust and collective reflexivity; b) translation of contextually embedded concepts; c) setting parameters for contextualizing, and d) supporting empirical and conceptual generalisability. Under each guiding principle, we describe how credibility, dependability, confirmability and transferability can be enhanced and share good practices to be considered by other researchers., Conclusions: Qualitative research is often context-specific with tools designed to explore local experiences and understandings. Without efforts to synthesise and systematically share findings, common understandings, experiences and lessons are missed. The logistical and conceptual challenges of qualitative research across multiple partners and contexts must be actively managed, including a shared commitment to continuous 'joint learning' by partners. Clarity and agreement on concepts and common methods and timelines at an early stage is critical to ensure alignment and focus in intercountry qualitative research and analysis processes. Building good relationships and trust among network participants enhance the quality of qualitative research findings.