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Azithromycin use in labour to prevent sepsis among pregnant women undergoing vaginal delivery in Nigeria (AZIN-V): a study protocol for a hybrid type 2 effectiveness-implementation trial.
No full textINTRODUCTION: Nigeria has the highest number of maternal deaths globally, and maternal peripartum sepsis is one of the leading causes of maternal mortality. A single oral dose of azithromycin (AZM; 2 g) is safe and effectively reduces 33%-60% of maternal sepsis during planned vaginal birth in low- and middle-income countries (LMICs). However, the clinical and cost-effectiveness of oral AZM during vaginal birth in Nigeria remains unknown in the context of poor antimicrobial stewardship practices, significant antimicrobial resistance and healthcare financing. Evidence is also lacking on the standard care for the prevention of maternal sepsis among pregnant women undergoing vaginal births in Nigeria. The AZIN-V trial is a hybrid type 2 effectiveness-implementation trial to determine the safety, clinical and cost-effectiveness of intrapartum oral AZM versus usual care in the prevention of peripartum maternal sepsis. The trial will also examine the impact of implementation strategies in enhancing adherence to the oral AZM protocol during planned vaginal births and identify effective strategies to improve adherence (fidelity) to the protocol in real-world LMIC settings. METHODS AND ANALYSIS: This is a multicentre hybrid type 2 trial conducted in six Nigerian states: Ebonyi, Edo, Gombe, Kano, Kwara and Lagos. The study aims to simultaneously test the clinical and cost-effectiveness of AZM (clinical trial) and the impact of implementation strategies (implementation research) in Nigeria's unique healthcare context. The clinical trial is a two-arm, cluster-randomised controlled trial conducted across 48 health facilities, randomly assigned (1:1) to either intrapartum administration of oral AZM (intervention group) or usual care-the current routine practice (control group). A total of 5040 study participants (2520 in each group) will be enrolled in the clinical trial. The implementation trial is a two-arm cluster non-randomised controlled trial conducted in 12 health facilities (1:1) allocated to either a bottom-up approach using the Plan-Do-Study-Act cycle or a usual top-down approach with a one-time training workshop and distribution of clinical guidelines, with both arms administering oral AZM during vaginal birth while assessing fidelity (primary outcome).For the clinical trial, data will be analysed using intention-to-treat statistical methods. The cost-effectiveness outcome will be analysed using the Incremental Cost-Effectiveness Ratio. Implementation outcomes will be analysed using descriptive statistics and a thematic approach. ETHICS AND DISSEMINATION: This study has been approved by the National Health Research Ethics Committee, Nigeria (NHREC/01/01/2007-30/09/2024), the ethics committees of the participating health institutions (Lagos University Teaching Hospital Research Ethics Committee: ADM/DSCST/HREC/APP/6325; University of Ilorin Teaching Hospital Health Research Ethics Committee: ERC/PAN/2025/03/0581; University of Benin Teaching Hospital Health Research Ethics Committee: ADM/E22/A/VOL. VII/483117141; Aminu Kano Teaching Hospital Research Ethics Committee: AKTH/MAC/SUB/12 A/P-3/VI/2509 and Irrua Specialist Teaching Hospital Research Ethics Committee: ISTH/HREC/20241507/605), the Ministries of Health of the six states and the National Agency for Food and Drug Administration and Control. Written informed consent will be obtained from all eligible study participants before enrolment. Results will be shared with communities and policy stakeholders and through peer-reviewed journals and will be presented at conferences. TRIAL REGISTRATION NUMBER: ISRCTN16415327
Eligibility for hepatitis B virus (HBV) treatment and prevalence of drug resistance in a Ugandan population cohort.
Full text linkBACKGROUND: The World Health Organization (WHO) 2024 Hepatitis B virus (HBV) treatment guidelines expand eligibility for nucleos(t)ide analogue treatment in individuals with chronic HBV infection. For countries to implement these guidelines, there is a critical need to understand the population who are treatment eligible. While HBV drug resistance (HBVDR) is uncommon, monitoring for any potential resistance is a relevant public health consideration. METHODS: We studied a population in rural Uganda to describe the proportion of individuals eligible for treatment based on the 2024 WHO treatment guidelines. We determined how this proportion varies according to the eligibility criteria used, comparing the performance of different assessment tools. We calculated Aspartate Aminotransferase-to-Platelet Ratio Index; APRI, Gamma-Glutamyl Transpeptidase-to-Platelet Ratio; GPR and transient elastography; TE and performed HBV sequencing using Oxford Nanopore Technology to determine the prevalence of HBVDR in treatment naive and treatment experienced individuals. RESULTS: In this cohort, 24/63 (38%) individuals with CHB were eligible for treatment. This fell to 14/63 (22%) in a hypothetical scenario where TE was not available for the assessment of liver fibrosis. We demonstrate a lack of concordance between non-invasive tests (NIT) of liver disease in treatment-naive HBV mono-infected individuals. An APRI cut-off of 0.5 had a sensitivity of 23.0% for predicting a TE score of >7 kPa (F2 fibrosis). Sensitivity for detecting F2 fibrosis was increased to 38.5% using an APRI cut off of 0.36, and to 46.2% using the GPR. We did not identify any HBVDR in the HBV mono-infected treatment-naive population (n=58). 24/210 individuals were living with HIV/HBV coinfection; HBV was sequenced in 5 of these of whom 2 had genomic evidence of nucleos(t)ide analogue resistance (rt180M/204V). CONCLUSIONS: While the WHO 2024 treatment criteria offer an opportunity to expand access to care, there is a need to determine how assessment tools differ in determination of eligibility in different settings. HBVDR remains uncommon but more research is needed to understand its prevalence and clinical impact in African populations
Acceptance of a newly introduced COVID-19 vaccine among pregnant women and their decision influencers: a qualitative study in The Gambia.
Full text linkBackground: Pregnant women infected with SARS-CoV-2 face an increased risk of severe illness and adverse maternal and neonatal outcomes. Despite the importance of the SARS-CoV-2 vaccination, acceptance among pregnant women is low in many regions, raising concerns about integrating newly introduced maternal vaccines into antenatal services. This study explored the factors shaping COVID-19 vaccine access and acceptance among pregnant women and their identified decision influencers in The Gambia.
Methods: This qualitative study was part of a larger study involving over 5000 pregnant women, both vaccinated and unvaccinated against COVID-19. Data were collected through 12 focus group discussions and 21 semi-structured interviews with decision influencers like family members and religious leaders. Thematic analysis revealed key themes interpreted using the "5-P model": perceived disease susceptibility and severity, pregnancy protection, perceived benefits, provider-patient dynamics, and perceived information sufficiency.
Results: Participants' COVID-19 vaccination decisions were shaped by their knowledge of the disease, the vaccine's benefits, and socio-cultural and religious beliefs. Key influencers, mainly husbands, played a significant role. Experiences with healthcare systems, unclear policies, and inconsistent messaging about vaccine safety during pregnancy affected choices. Misinformation from social media increased fear and hesitation, while conflicting advice from trusted sources diminished confidence. Differences in perceived risk and the quality of communication encounters further shaped how women evaluated vaccination during pregnancy.
Conclusion: This study highlights the importance of decision influencers and the impact of misinformation and inconsistent messaging on COVID-19 vaccine acceptance among pregnant women in The Gambia. By clarifying how women and their influencers navigate vaccine decisions, the findings offer practical entry points for strengthening communication and supporting the introduction of future maternal vaccines
Trial design and enrolment characteristics of LATA (Long-Acting Treatment in Adolescents): A randomised, open-label, non-inferiority, 96-week trial evaluating the virological efficacy, safety, acceptability and quality-of-life of the dual long-acting injectable regimen cabotegravir/ rilpivirine compared to daily oral therapy in virologically suppressed adolescents with HIV-1 infection, aged 12 to <20 years, in Sub-Saharan Africa.
No full textBACKGROUND: Alternatives to daily oral antiretroviral therapy (ART) are important for adolescents with HIV (AHIV) to improve adherence and outcomes. Long-Acting-injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) has demonstrated excellent efficacy and safety and strong patient preference in adults.
METHODS: LATA is an ongoing randomised, open-label, 96-week, non-inferiority trial evaluating the efficacy, safety and acceptability of LAI CAB/RPV vs. daily oral therapy with tenofovir (disoproxil fumarate or alafenamide)/lamivudine/dolutegravir (TLD). Participants are virologically suppressed AHIV aged 12- < 20 years in Kenya/South Africa/Uganda/Zimbabwe. Randomisation was 1:1 to LAI CAB/RPV given once every 8 weeks (after optional oral lead-in) or daily oral TLD. The primary outcome is viral rebound (two consecutive viral loads ≥50 copies/mL by 96-weeks). Viral loads are measured every 24 weeks. The trial employs the Smooth Away From the Expected (SAFE) non-inferiority frontier, where the non-inferiority margin depends on the observed event rate in the control arm. Secondary outcomes include confirmed viral load ≥200 copies/mL by 96-weeks, HIV resistance, safety, patient-reported outcomes and cost-effectiveness. LAI participants return to oral ART at confirmed viral load ≥200 copies/mL; LAI participants who become pregnant are given the choice to continue on LAI or to switch back to daily oral ART, with optional pharmacokinetic sampling during pregnancy and post-partum in both groups. Enrolment of 476 AHIV completed in April 2024. Results will be reported in 2026.
CONCLUSION: LATA is the first trial comparing the efficacy, safety and acceptability of LAI CAB/RPV to oral ART in AHIV, enrolled in Sub-Saharan Africa, using a programmatic approach to viral load testing.
TRIAL REGISTRATION: This trial has been registered with ClinicalTrials.gov (NCT05154747)
The Influence of Innate Immunity, Adaptive Immunity and Diet on Intestinal Microbiota Following Trichuris muris Infection
Full text linkTrichuris trichiura infects nearly 500 million people worldwide, causing intestinal inflammation, malnutrition, and growth impairment, particularly in children from low-resource settings. While host immunity is central to parasite clearance, diet and the gut microbiota may also modulate infection. Using the Trichuris muris model, we examined how immune competence and diet interact to influence worm burden, antibody responses, and gut microbiota composition. Wild-type (WT), RAG1-deficient (lacking adaptive immunity), and RAG1/γc-deficient (lacking both adaptive and innate lymphoid immunity) mice were fed either a normal diet (ND) or high-fat diet (HFD) and infected with a low dose of T. muris. WT mice on ND developed chronic infection with strong IgG2a/c responses, consistent with Th1-biased immunity. In contrast, WT mice on HFD achieved near-complete parasite clearance, accompanied by elevated IgG1 and reduced IgG2a/c titres, indicating diet-induced Th2 bias. In RAG1- and RAG1/γc-deficient mice, infection persisted under a normal diet but worm burdens were partially reduced on HFD, indicating that diet enhances parasite control through immune-independent, possibly microbiota-mediated pathways. Microbiota clustered by genotype and diet, with HFD-associated enrichment of Bacteroides, Parabacteroides, and Blautia. These findings demonstrate that diet and immune status jointly shape helminth susceptibility through coordinated effects on host immunity and the gut microbiota
Long-term safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen: a cohort study of previously vaccinated adults and children in Sierra Leone (the EBOVAC-Salone extension study)
Full text linkBACKGROUND: Evidence regarding the association between emperature and children’s nutritional status is scarce. We aimed to estimate the relationship between ambient temperature and the weight and height of Brazilian children aged 12–59 months.
METHODS: This large longitudinal cohort study from all 5570 Brazilian municipalities used data from the 100 Million Brazilians Cohort linked with data from the Information System on Live Births (SINASC), Food and Nutrition Surveillance System (SISVAN), and temperature data from the Brazilian Daily Weather Gridded Data (BR-DWGD). The study included children aged between 12–59 months with nutritional monitoring recorded by SISVAN between Jan 1, 2008 and Dec 31, 2017. We applied distributed lag non-linear models to investigate the cumulative influence of temperature over the year preceding each child’s measurement on weight and height (ie, lag: 0–51 weeks). Subgroup analyses were conducted to identify population groups facing greater risk of worse nutritional outcomes.
FINDINGS: 6 498 546 children aged between 12–59 months were included in the study. 3 226 520 (49⋅65%) participants were male, 3 272 026 (50⋅35%) were female, and 4 194 195 (64⋅54%) were Parda or Brown ethnicity. For each 1◦C increase in ambient temperature above the median (26◦C), the cumulative odds over the weekly lags 0–51 increased by 10⋅0% (odds ratio [OR] 1⋅10 [95% CI 1⋅099–1⋅103]) for underweight (low weight-for-age), 8⋅0% (OR 1⋅08 [1⋅078–1⋅081]) for wasting (low weight-for-height), and 8⋅0% (OR 1⋅08 [95% CI 1⋅078–1⋅080]) for stunting (low height-for-age) in Brazil. In stratified analyses, the odds of alnutrition associated with a 1◦C increase in ambient temperature were highest in the North (followed by the Northeast, the two poorest regions of Brazil), in municipalities with higher deprivation index, in rural areas, and among children of Indigenous mothers.
INTERPRETATION: Children experiencing high temperatures in Brazil are more likely to suffer from malnutrition, with worse outcomes observed among more vulnerable social groups. Our results highlight the deep environmental injustice in Brazilian society, with the influence of temperatures interacting with existing social and economic inequalities and exacerbating nutritional outcomes in the most vulnerable groups. Further studies are needed to investigate causal pathways and identify strategies capable of mitigating the effects of climate change on child nutrition.
FUNDING: National Council for Scientific and Technological Development (CNPq); the Department of Science and
Technology of the Secretariat of Science, Technology, Innovation and Strategic Health Inputs of the Brazilian
Ministry of Health; the Wellcome Trust
Effect of beta blockers in acute and chronic coronary syndromes without reduced ejection fraction: a landmark analysis from the REBOOT trial.
Full text linkAIMS: Current guidelines recommend beta-blocker therapy after myocardial infarction (MI) regardless of left ventricular ejection fraction (LVEF). However, recent trials question their benefit in patients with preserved LVEF. No study has yet compared beta-blocker effects during the acute coronary syndrome (ACS) phase (≤1 year post-MI) vs. the chronic coronary syndrome (CCS) phase (>1 year).
METHODS AND RESULTS: In this pre-specified landmark analysis of the REBOOT trial, we evaluated the effect of beta-blocker therapy on outcomes in two post-MI phases: the ACS period (first year; cohort 1, n = 8438) and the CCS period (>1 year, event-free patients with follow-up; cohort 2, n = 7783). The primary endpoint was all-cause death, nonfatal reinfarction, or heart failure hospitalization; secondary endpoints included individual and additional cardiovascular events. Among 623 primary outcome events, 238 occurred in the first year (28.9/1000 patient-years) and 385 thereafter (19.3/1000 patient-years). Secondary prevention use was generally high, but patients with early events had lower prescription rates than those with late events or no events. Beta-blockers were not associated with lower risk of the primary or component outcomes in either phase. A nonsignificant trend towards benefit of beta-blockers appeared during the first year in patients with mildly reduced LVEF (41-49%), whereas in the CCS phase, higher beta-blocker doses were associated with worse outcomes.
CONCLUSION: In invasively treated MI patients with LVEF >40%, beta-blockers did not reduce adverse outcomes in either the ACS or CCS phases. These findings challenge their routine use in this population and support reconsidering current guidelines. Long-term beta-blocker users after MI may be candidates for deprescription
Childhood asthma in Uganda: experiences of healthcare providers and caregivers in diagnosis and management. A FRESH AIR qualitative study.
Full text linkAsthma is the most common chronic childhood illness, however, many young children with asthma symptoms remain undiagnosed and/or misdiagnosed as pneumonia. We explored caregivers' and health care providers' understanding and practices around diagnosis and management of asthma in children less than 5 years. We conducted a cross-sectional study in primary care facilities in Uganda between June and August 2016. In-depth interviews with 25 participants, including caregivers (CGs) of young children with recurrent respiratory symptoms, healthcare workers (HCWs) and herbalists were triangulated. The findings indicated that all CGs described recurrent cough, wheeze and breathing difficulties in their children, which is suggestive of asthma, but were primarily diagnosed with pneumonia, bronchiolitis or bronchitis, and treated with antibiotics. This was in conformity with the HCWs' responses regarding their (HCWs) practices in management of children with respiratory illnesses. HCWs indicated that they did not diagnose asthma in young children but used terms like hyper-reactive airways disease or allergic cough. Caregivers were frustrated with the healthcare system due to lack of clear diagnoses and ineffective treatments. HCWs expressed frustration with unavailability of inhaled asthma medicines. The study highlighted major gaps in HCWs' practices in the management of asthma in young children leading to under-diagnosis of asthma and over-diagnosis of pneumonia., and overuse of antibiotics. Despite caregivers seeking care, their children did not get the right care, partly due to health system challenges including HCW competencies. Strategies for health system strengthening including improving HCWs' competences and availability of inhaled asthma medicines are urgently needed
Can provision of near vision glasses as an early intervention improve visual outcomes in infants at risk of perinatal brain insult? The Babies in Glasses (BiG) randomised feasibility trial.
Full text linkOBJECTIVES: We conducted a feasibility study to evaluate the feasibility of recruiting patients to examine the effect of near vision glasses in young infants at risk of cerebral visual impairment. DESIGN: A three-arm, parallel-group, open-label randomised feasibility trial. SETTING: Tertiary neonatal intensive care in London, UK. PARTICIPANTS: We included babies born before 29 weeks of gestation or at full term with hypoxic ischaemic encephalopathy. Babies who needed ongoing inpatient care, with established eye anomalies or with very high refractive errors at baseline (±8.00D) were not included. Infants with retinopathy of prematurity were not excluded. INTERVENTIONS: At 8 weeks corrected age, we allocated 18 infants to wear glasses (+3.00D over full cycloplegic refraction) immediately (intervention 1), 18 to wear the same glasses at 16 weeks (intervention 2) and 19 infants were allocated to standard treatment (no glasses). OUTCOMES: Recruitment and retention of study participants (primary), compliance wearing glasses, preferential-looking visual acuity (with glasses) and visual function as determined using A Test Battery of Child Development for Examining Functional Vision at 3-month and 6-month age post-term. RESULTS: Of 70 eligible families, 55 consented and 34 attended baseline assessments, and 28 completed the study. Non-attendance was due mainly to prolonged inpatient stay, infant health and scheduling conflicts. Glasses were worn for similar periods in each group (Intervention 1: median 2 hours/day (95% CI 1 hour to 4 hours); Intervention 2: median 2 hours/day (95% CI 1.5 hours to 3 hours)). Visual acuity improved from baseline to 6 months. Mean (SE) LogMAR (Minimum Angle of Resolution) improvements were standard care: 0.47 (0.45); intervention 1: 0.66 (0.44); intervention 2: 0.37 (0.36). Among the 29 very preterm infants, there were similar findings: standard care: 0.35 (0.35); Intervention 1: 0.67 (0.47); Intervention 2: 0.34 (0.40). As a functional measure, object permanence was present at the following rates by randomised arm: standard care: 29%; whereas intervention 1: 56%; and intervention 2: 44% (OR intervention 1 vs standard care: 3.13 (95% CI 0.38 to 25.57), ie, not statistically significant). CONCLUSIONS: We demonstrate feasibility for a definitive RCT (randomized controlled trial) with good recruitment and retention and observed potential benefits for vision and development following the dispensing of glasses at 8 weeks post-term age compared with untreated controls. We identified methodological modifications to further improve recruitment processes for a future larger study. TRIAL REGISTRATION NUMBERS: ISRCTN14646770; NCT05048550
Evaluating the broader impact of improved influenza vaccines: A full value of vaccine assessment approach.
Full text linkSeasonal influenza remains a significant global public health challenge, causing substantial morbidity and mortality each year and there remains a need for more effective and durable influenza vaccines. To direct and accelerate research efforts, a full value of vaccine assessment (FVVA) was initiated to quantify the value of next-generation, improved influenza vaccines and identify key challenges that may limit their uptake once available. The FVVA utilized a mixed-methods approach with rapid assessment of literature, stakeholder interviews, and surveys, and quantitative data analysis to estimate the full value of influenza vaccines with improved characteristics. These analyses found that if improved influenza vaccines are broadly employed, depending on their characteristics, using our demand forecast they could avert 6.6-18 billion additional influenza cases, 2.3-6.2 million additional influenza deaths, and 21-57 million disability-adjusted life years (DALYs) between 2025 and 2050 beyond those averted by current seasonal influenza vaccines. Under this scenario, introducing improved influenza vaccines could be cost-effective in 9-48 % of countries at the lowest assumed price point. However, uncertainties about price and future vaccine coverage may impact the potential cost-effectiveness. Furthermore, from the producer perspective, the FVVA highlighted the robust financial value proposition to develop and commercialize improved influenza vaccines, in both established and emerging markets. Strongly tiered prices could make these vaccines cost-effective in more countries and boost impact further. To ensure that improved influenza vaccines achieve the greatest public health benefit, effective collaboration between vaccine developers, vaccine manufacturers, donors, financiers, multilateral organisations, and policy- and decision-makers will be essential