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Community views on mass drug administration for soil-transmitted helminths: a qualitative evidence synthesis
No full textBackground: Soil-transmitted helminth (STH) infections are amongst the most common infectious diseases worldwide, with an estimated 24% of the world's population currently infected. Mass drug administration (MDA) is the periodic medicinal treatment, without prior individual diagnosis, of at-risk people living in endemic areas. The World Health Organization currently recommends MDA for STHs. MDA programmes are complex health interventions; achieving adherence is important to their success. Adherence is influenced by the target population's perceptions of the drug, the programme, and those delivering it.Objectives: To synthesize qualitative research evidence about community experiences and perceptions of mass drug administration programmes for soil-transmitted helminths. To assess whether our findings confirm, extend, enrich, or conflict with those of a 2022 Cochrane qualitative evidence review of mass drug administration programmes for lymphatic filariasis.Search methods: We searched CENTRAL, MEDLINE, Embase, and four other databases up to 11 November 2024, together with reference checking, and citation searching.Selection criteria: We synthesized qualitative and mixed-methods studies. We included studies exploring community experiences and perceptions of MDA programmes for STHs in any country, conducted between 2001 and 2024. We included all participants of MDA programmes, regardless of disease status, individual participation, or other demographic information. We also included lay healthcare workers and formally qualified healthcare workers, if their perspectives were clearly separated from those of the general population.Data collection and analysis: We collected data on study characteristics and programme delivery, including country, endemicity, drug regimen, how the drugs were delivered, use of health education and sensitization, and adherence monitoring. We conducted thematic analysis using a 'best-fit' framework synthesis based on a framework developed in a 2022 Cochrane review exploring community views on mass drug administration for filariasis (a parasitic infection caused by filarial worms). We conducted a deductive phase, accommodating our data within the existing model, followed by an inductive phase, during which we explored data not accommodated by the framework. We used the GRADE-CERQual approach to assess our confidence in the findings, and updated the filariasis review's conceptual model to display our findings.Main results: We included 17 studies, conducted in Bangladesh, Benin, India, Kenya, Malawi, Nigeria, the Philippines, and Turkey. Four themes emerged, three of which were identified in the review of MDA for lymphatic filariasis. People weigh up the benefits and harms in their decision to participate in MDA, though some may not have a choice. Outcomes of individual participation in MDA may be positive, negative, or both. The decision to partake is a careful balance of risk, benefit, and feasibility (high confidence). Unpleasant associations become part of the narrative and spread rapidly through the community (moderate confidence). Physical and social barriers prevent some people from being able to access MDA even if they want to participate (moderate confidence). Many people are suspicious of MDA programmes, although trust may be built over time. Factors such as historical legacies, rumours, and mistrust of people involved in the programme affect overall trust in drug distribution and influence whether people choose to participate. Past experiences can have a profound effect on people, and negative experiences are likely to deter people from future participation (high confidence). Careful management of the relationships between people implementing the programme and people receiving the programme is important to building trust over time (moderate confidence). The drug distributor's status in the community is often low, and they are not well-equipped to answer the communities' questions. People employed to distribute the drugs during STH treatment campaigns often lack a healthcare background and in-depth training around the drug or the disease itself (moderate confidence). Some community members prefer distribution from people they know or trust (high confidence). However, others place value on the knowledge or status of the drug distributors, and may not participate if the community drug distributors (CDDs) cannot answer their programme-related questions (moderate confidence). Many community members have ideas to improve delivery and want more involvement in the programme. Although some programmes conduct education and sensitization activities prior to drug distribution, many community members still lack awareness of the timing and purpose of the distribution (high confidence). People value distribution strategies that make it easy for everyone to participate, and express a desire for adults in the community to be included in the programme (moderate confidence). Many community members believe a more comprehensive health campaign, which includes improved sanitation, is necessary to tackle STH burden (moderate confidence). One theme that the filariasis review identified was not substantiated by the findings in this review (Programmes expect compliance: this can result in coercion and blame).Authors' conclusions: Despite the prevalence and undoubted impact of MDA programmes over the past 10 years, endemic hotspots and continued transmission are common, due in part to poor community adherence. The 2022 Cochrane review outlined several key community concerns and doubts that hinder the effective implementation of MDA for lymphatic filariasis. This review shows that most of these concerns and doubts are shared by communities targeted for MDA for STHs, indicating that there are fundamental challenges in the overall conceptualization and design of MDA programmes that need to be addressed.Funding: TF, MT, RK, and the Cochrane Infectious Diseases Group editorial base were funded by UK aid from the UK Government for the benefit of low- and middle-income countries (project number 300342-104). The views expressed do not necessarily reflect the UK Government's official policies.Registration: The protocol for this review was published in January 2024 on the Cochrane Database of Systematic Reviews. Available at doi.org/10.1002/14651858.CD015794
Interventions to support parents, families and caregivers in caring for preterm or low birth weight infants at home: A systematic review and meta-analysis
Full text linkThe aim of this study was to determine what interventions, approaches, or strategies to support mothers/fathers/caregivers and families in caring for preterm (<37 gestational weeks) or low birthweight (<2,500g) infants in the home have been effective in improving outcomes. We conducted a systematic review and meta-analysis. A comprehensive search of relevant electronic databases, including MEDLINE, Embase, CINAHL and Cochrane Central Register of Controlled Trials was completed in September 2024. Studies were included if they utilised interventions which focused on providing support to participants (mother/father/parents, families or caregivers) to care for their infants in the home. Two reviewers independently screened papers in Covidence and extracted data. Random effects meta-analyses were undertaken. Quality of studies and certainty of evidence were assessed using CASP and GRADE, respectively. Critical outcomes based on WHO preterm and low birthweight criteria comprised infant mortality, morbidity, growth and neurodevelopment. Priority outcomes comprised breastfeeding, care seeking, parent-infant interaction, mother-child attachment and parental health and wellbeing. Forty-seven studies were included. There is some evidence that support interventions may improve outcomes related to infant mortality, improvements in infant growth, exclusive breastfeeding, infant cognitive development, immunisation uptake, and reduction in maternal stress and depression. However, the overall certainty of evidence is low or very low in the majority of studies. We conclude that interventions providing support for parents to care for infants in the home may improve outcomes for this population. There is a need for well-considered large scale support interventions, prioritised and developed with women and families.</p
Molnupiravir for treating COVID-19
No full textRATIONALE: Five years from the start of the COVID-19 pandemic, morbidity and mortality have subsided. Vaccines have contributed to reducing the risk of infection and severe disease. However, new COVID-19 variants continue to emerge, and the role of oral antivirals such as molnupiravir in preventing progression of disease or hospitalisation must be assessed. OBJECTIVES: To assess the effects of molnupiravir in people with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mild to moderate symptoms. SEARCH METHODS: We identified all relevant randomised controlled trials (RCTs) by searching the Cochrane COVID-19 Study Register, Science Citation Index Expanded, the World Health Organization (WHO) Global Literature on Coronavirus Disease database, and the COVID Network Meta-Analysis database with no language restrictions up to 26 April 2024. ELIGIBILITY CRITERIA: We considered full-text articles, preprints, abstracts, trial registry records, and reports of ongoing trials. Cluster-RCTs were eligible for inclusion, but cross-over trials were ineligible. Participants had confirmed SARS-CoV-2 infection with or without risk factors for severe disease. The intervention was molnupiravir 800 mg taken orally every 12 hours for five days, and control was no treatment, placebo, or standard of care, as defined by the study authors. We excluded studies comparing molnupiravir with treatment strategies that included molnupiravir. OUTCOMES: Our critical outcomes were all-cause mortality and hospitalisation. Our important outcomes were change in clinical status, viral clearance, quality of life, adverse events, and serious adverse events. RISK OF BIAS: Two review authors independently assessed the risk of bias in each included study using the Cochrane risk of bias tool (RoB 2). Disagreements were resolved through discussion. SYNTHESIS METHODS: We conducted a meta-analysis where two or more studies with reasonably similar clinical and methodological characteristics reported the same outcome. We used data from intention-to-treat analysis where available. We analysed all outcomes at the participant level using the generic inverse variance method, applying a random-effects model. We used the GRADE approach to assess the certainty of evidence. INCLUDED STUDIES: This review included 11 studies (31,272 participants). Eight studies recruited outpatients and three recruited inpatients. We did not meta-analyse inpatient studies, as characteristics varied widely. All outpatient studies included participants with mild to moderate COVID-19, with a mean age ranging from 35 years to 57 years and variable prevalences of comorbidities and COVID-19 vaccination. We excluded suboptimal molnupiravir dosing arms in four outpatient studies and one inpatient study. SYNTHESIS OF RESULTS: Outpatients Molnupiravir compared to placebo or usual care probably results in little to no difference in all-cause mortality at 28 to 30 days (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.04 to 0.65; 7 RCTs, 29,238 participants; moderate-certainty evidence). The absolute reduction in mortality is nine fewer deaths per 10,000 people treated (95% CI 10 fewer to four fewer per 10,000), which we consider clinically insignificant. Molnupiravir may result in little to no difference in hospitalisation (RR 0.70, 95% CI 0.43 to 1.12; 6 RCTs, 29,228 participants; low-certainty evidence), symptom resolution by day 14 (RR 1.20, 95% CI 0.84 to 1.71; 3 RCTs, 22,400 participants; low-certainty evidence), and symptom resolution by day 28 (RR 1.06, 95% CI 0.89 to 1.26; 3 RCTs, 24,728 participants; low-certainty evidence). Four studies reported viral clearance by day 5, which was higher in people receiving molnupiravir compared with those receiving placebo or usual care (RR 3.40, 95% CI 2.15 to 5.36; 3067 participants). The effect size decreased by day 10 (RR 1.58, 95% CI 1.07 to 2.34; 2 RCTs, 2438 participants) and indicated little to no difference between molnupiravir and control by day 14 to 15 (RR 1.05, 95% CI 0.98 to 1.13; 4 RCTs, 3062 participants). The results at day 28 to 30 again showed higher virus clearance in the molnupiravir arm (RR 1.11, 95% CI 1.03 to 1.19; 3 RCTs, 397 participants), although there were few participants in this analysis. Molnupiravir probably results in little to no difference in adverse events (RR 1.00, 95% CI 0.87 to 1.15; 7 RCTs, 4304 participants; moderate-certainty evidence). Molnupiravir results in little to no difference in serious adverse events (RR 0.86, 95% CI 0.62 to 1.21; 8 RCTs, 30,009 participants; high-certainty evidence). Inpatients The effect of molnupiravir in inpatients is unclear; substantial heterogeneity precluded meta-analysis. Risk of bias and certainty of the evidence We assigned high risk of bias judgements to one of seven RCTs for all-cause mortality, one of six RCTs for hospitalisation, two of three RCTs for symptom resolution at 14 days and 28 days, three of seven RCTs for adverse events, and three of eight RCTs for serious adverse events. We downgraded the certainty of the evidence for serious indirectness as well as risk of bias, as the populations across trials differed by vaccination status. There was no serious imprecision identified for any outcome. Publication bias is likely high in this review, as we identified 16 unpublished trials. Six were listed as complete, but only one had available data. AUTHORS' CONCLUSIONS: In outpatients with mild to moderate COVID-19, molnupiravir 800 mg taken orally every 12 hours for five days probably results in little to no difference in all-cause mortality and may result in little to no difference in rates of hospitalisation and symptom resolution. There is evidence of increased viral clearance by day 5, but the clinical relevance of this finding is unclear. There is probably little to no difference in adverse events, and there is little to no difference in serious adverse events, with molnupiravir versus placebo or standard care. Inpatient data are lacking, and there is no evidence of benefit of molnupiravir in this population. Further research involving inpatients may change this. FUNDING: The editorial base of the Cochrane Infectious Diseases Group is funded by UK aid from the UK Government for the benefit of low- and middle-income countries (project number 300342-104). The views expressed herein do not necessarily reflect the UK Government's official policies. REGISTRATION: Protocol available at https://doi.org/10.1002/14651858.CD015381.</p
Attention to menarche, puberty education, and menstrual health monitoring are essential
No full textIn August, 2025, Maria Lohan and colleagues reported on the 30 sexual and reproductive health and rights (SRHR) research priorities identified for young adolescents (age 10–14 years), the output of a collaborative global exercise intended to bolster investment and research for this overlooked group.1 We commend their emphasis on young adolescents’ developmental needs, the perspectives of their caregivers, and the underlying determinants of positive SRHR. Among the highlighted areas, strengthening menstrual health programming (priority 11) is especially urgent to promote health and address ongoing gender inequality in this age group. The menstrual cycle typically begins during young adolescence, and early and holistic intervention in menstrual health is an entry point for SRHR throughout the life course
PoolSeq Genome-Wide Association Studies and Microbial Signature Analyses Identify Novel Candidates Associated With Pyrethroid Resistance Evolution in Anopheles funestus in Cameroon
Full text linkIntensification of insecticide resistance in malaria vectors is undermining efforts to sustain control strategies. The evolutionary features underlying such exacerbation in major vector such as Anopheles funestus are only partially understood. PoolSeq whole genome analysis of Anopheles funestus from Mibellon (Cameroon), (alive and dead at 1×, 5× and 10× concentrations), failed to identify hits associated with resistance escalation. However, stronger signals emerge at the rp1 and CYP9 loci when comparing these phenotypes to the susceptible reference strain FANG, with genomic analysis using F3 crosses implicating these regions in resistance evolution. Temporal genomic between 2014 and control unexposed 2021 populations confirmed substantial genomic changes largely confined to these two regions with evidence of selective sweeps linked to the presence of multiple novel replacement polymorphisms and signatures of complex genomic evolution emerging from major cytochrome P450 genes within the CYP9 and rp1 regions at increasing allelic frequencies in field individuals and alive genetic crosses, indicating that those variants are potentially driving resistance evolution. Combined genotyping of the rp1-based 4.3 kb SV and CYP9K1 (G454A) in alive and dead genetic crosses underscores their significant contribution to super-resistant phenotype in Anopheles funestus population in Mibellon. On the other hand, microbial composition changes, notably Elizabethkingia anophelis was associated with resistance evolution, suggesting their potential role in shaping the resistance phenotype while Serratia marcescens and Asaia bongorensis correlate with susceptibility. Genetic events and microbial symbionts associated with resistance evolution offer promising avenues for developing molecular markers to manage insecticide resistance.</p
Research capacity strengthening in fragile and shock-prone settings: Insights from a research consortium
No full textIntroductionResearch capacity strengthening (RCS) is acknowledged as a critical element for improving health systems through contextually-embedded research findings and recommendations. However, RCS remains a critical gap in the field of Health Policy and Systems Research (HPSR), especially in fragile and shock-prone settings facing unique challenges that further constrain research capacity. The ReBUILD for Resilience (ReBUILD) consortium, operating in Lebanon, Myanmar, Nepal, and Sierra Leone, sought to strengthen HPSR capacity across individual, organizational, and community levels. This paper reflects on the RCS approaches of the ReBUILD consortium, analyzing strategies and lessons learned.MethodsA mixed-methods approach was applied including surveys, discussions, progress reports, and meeting minutes. Data was collected iteratively at different stages of the RCS design and implementation.ResultsBased on needs and assets assessment, the RCS strategy was embedded in the consortium’s operations and adapted to local needs. Southern partners and early career researchers increasingly led initiatives, while mentorship and practical learning were emphasized. Efforts focused on strengthening individual skills and knowledge and expanded to the organizational level. Community members were trained and actively contributed to research design and implementation. Gender, equity and safeguarding were systematically integrated. The consortium’s work led to increased research outputs, policy influence, and improved local processes.ConclusionsFindings from ReBUILD’s RCS approach demonstrate that context-specific, values-driven, and multi-level strategies can effectively strengthen resilient research ecosystems in fragile and shock-prone settings. This study proposes an adapted conceptual framework for RCS that emphasizes flexibility, equity, and shared leadership as key to sustainable research capacity development
Genetic divergence and lower frequencies of insecticide resistance markers in the novel Anopheles gambiae Bissau molecular form in The Gambia
Full text linkThe members of Anopheles gambiae species complex are ubiquitous in Afro-tropics. They have been exposed continuously to insecticides, contributing to evolution of resistance within the complex. This study used whole genome sequence data from phase 3 of the An. gambiae 1000 Genomes Project to investigate the population structure and resistance mechanisms of a newly identified species, An. gambiae Bissau molecular form (Bissau) in The Gambia. Bissau exhibited subtle divergence from sister taxa An. coluzzii (Fixation index (FST) of 0.013) and An. gambiae s.s. (FST of 0.023), suggesting ongoing geneflow among them. It also displayed a low but evident level of sub-clustering correlating with geographical location, contrary to sister taxa whose populations were not spatially structured. Additionally, Bissau displayed a higher number of substitutions, though at very low frequencies, in target site regions (specifically Vgsc and Ace-1) of the genome compared to its sister taxa. The well-established Vgsc-L995F mutation, normally associated with dichloro-diphenyl-trichloroethane (DDT) and pyrethroid resistance, was detected in all taxa. Also present, but at a lower frequency (< 20%) was N1570Y allele, normally associated with increased level of pyrethroid resistance when it co-occurs with L995F. Additionally, variants T791M and A1746S were found to occur alongside L995F in Bissau population at an elevated linkage disequilibrium (LD r2 = 0.7). These findings accentuate the critical role this novel species could play on the emergence and spread of insecticide resistance in The Gambia.</p
Differential effects of dual and synergist-based insecticide-treated bed nets on pyrethroid resistance and L995F/S knockdown resistance mutation dynamics in Anopheles gambiae s.l. populations in south-western Burkina Faso
Full text linkBackground: The introduction of next-generation insecticide-treated nets (ITNs) in Burkina Faso aims to mitigate pyrethroid resistance in malaria vectors. This study evaluated the impact of different ITN types on phenotypic resistance and kdr mutation frequencies in Anopheles gambiae sensus lacto (s.l.) populations across three health districts over 3 years. Methods: Annual mosquito collections were conducted in Banfora (where pyrethroid–chlorfenapyr nets had been distributed), Gaoua (pyrethroid-only ITNs) and Orodara (pyrethroid–piperonyl butoxide [PBO] ITNs). Two populations were analysed: adult females collected directly from the field and those reared from field-collected larvae. World Health Organization (WHO) susceptibility bioassays measured 24-h mortality after exposure to 1×, 5× and 10× concentrations of deltamethrin and alphacypermethrin, with and without pre-exposure to piperonyl butoxide. Frequencies of kdr mutations L995F and L995S were determined by polymerase chain reaction (PCR). Results: High-intensity resistance was observed in each study district, with mortality consistently below 45% and not reaching WHO thresholds even at 10× doses. PBO increased mortality, indicating metabolic resistance, but failed to restore full susceptibility. L995F predominated across all districts, years and mosquito populations. L995S remained low and variable. Pyr-only nets were associated with rising L995F frequencies and lower mortality in resistance assays. Pyrethroid (Pyr)–chlorfenapyr (CFR) nets improved mortality in resistance assays without increasing kdr prevalence. Pyr–PBO nets showed partial and inconsistent efficacy, with mosquitoes having mixed patterns in resistance assays. Similar patterns between field and laboratory-reared populations were observed. Conclusions: ITN type strongly influenced resistance dynamics. Dual-active ingredient (AI) nets, particularly Pyr–CFR, appear more effective in managing resistance. Integrated resistance management combining ITN rotation, routine monitoring and complementary interventions is essential to preserve vector control efficacy.</p
Extra-pulmonary TB: a comparison between migrants and populations born in a low-incidence country
Full text linkThe proportion of TB cases attributable to extra-pulmonary TB (EPTB) is increasing in high-income countries, including England. We sought to describe the burden of EPTB in East London, an area with a large migrant population and high TB incidence.A retrospective analysis of individuals with TB was conducted and compared to national data.1,262 patients were diagnosed with TB between 2016 and 2019. 52.7% had EPTB, 32.6% isolated pulmonary TB (PTB), and 14.7% concurrent disease. This compares to 43.8% of individuals nationally with isolated EPTB. In our cohort, of those with EPTB, 83.6% were non-UK-born (migrants). Multivariate analysis demonstrated that migrants had significantly higher odds of EPTB compared to UK-born individuals after adjusting for age and sex (adjusted odds ratio: 1.55, 95% confidence interval: 1.16–2.09, P = 0.003). Median time since entry to the UK among migrants who were diagnosed with EPTB was 11 years (interquartile range: 5–21). Treatment outcomes were worse in migrants with EPTB, mainly due to higher mortality.Our data reports a higher proportion of EPTB compared to national data. EPTB was more common in migrants than UK-born individuals.<p/
Medical haematology: Repositioning haematology at the centre of medicine
Full text linkHaematology is at a crossroads, divided between haemato-oncology and the disparate disciplines collectively known as ‘non-malignant’ haematology. This latter term is a misnomer that devalues a spectrum of complex, life-threatening conditions and contributes to workforce shortages and research inequities. This article argues for the formal adoption of the term Medical Haematology to redefine this domain. We chart its central role across medicine, from guiding anticoagulation, transfusion and thrombosis care across specialties to addressing global health challenges. We highlight its pioneering contributions to molecular medicine and immunotherapy, exemplified by gene therapy for haemophilia and the repurposing of chimeric antigen receptor T cells for autoimmune disease. Finally, we present a forward-looking blueprint involving establishment of ‘Blood Teams’, revamping educational curricula and championing equity to secure the speciality's future. Embracing Medical Haematology is a strategic imperative to reflect the life-threatening nature of many conditions within the speciality, attract trainees, rebalance research priorities and firmly re-establish haematology's indispensable role at the heart of modern medical practice.</p