Gates Open Research最新文献

Background: Vitamin B12 is an essential cofactor for two enzymes that have critical functions in pregnancy, both for maternal health and fetal development. However, the optimal supplemental dosage and its correlation with vitamin B12 status during pregnancy remain inadequately understood due to limited data.

Methods: This is a single-blinded, stratified, dose-ranging trial of vitamin B12 supplementation that will be conducted at the Ifakara Health Institute Bagamoyo Clinical Trial Unit in Bagamoyo, Tanzania. We will enroll 40 pregnant participants (gestational age 25-28 weeks) and 10 non-pregnant participants, stratified based on baseline vitamin B12 status (sufficient and insufficient). Pregnant participants are sequentially assigned to one of three doses: 2.6, 10, and 50 µg for four weeks. At the highest dose, pregnant participants are randomized to receive 50 µg once a day (Q24H) or 25 µg twice a day (Q12H). The two lower doses (2.6 and 10 µg) are given Q24H. Non-pregnant participants will receive 2.6 µg Q24H. The trial includes a four week in-patient phase for daily assessment and controlled feeding, with pregnant participants assessed once postpartum. Primary endpoints include serum B12 concentrations, holotranscobalamin concentrations, and their ratio after four weeks of daily supplementation.

Discussion: This study aims to deepen our understanding of nutrient requirements in pregnancy by generating high-quality, high dimensional data. We will answer questions about how pre supplementation vitamin B12 status and dosage impact vitamin B12 saturable absorption and steady-state over the course of four weeks. Limitations include our inability to assess pharmacokinetic changes across gestation, the impact of vitamin B12 status or supplementation on pregnancy and fetal/newborn health, comparing vitamin B12 effects between pregnant and non-pregnant individuals above the recommended dietary allowance (2.6 µg), and comparing Q12H and Q24H dosing at 50 µg. This is the first controlled feeding study to be conducted in sub-Saharan Africa.

Registration: ClinicalTrials.gov ( NCT05426395, 16/06/2022).

Population distributions across countries and regions exhibit significant spatial and temporal variability. This variation highlights the need for high-resolution, small-area demographic data to address the challenges posed by shifting population dynamics, urbanization, and migration. Small area population modelling, particularly the production of gridded population estimates, has advanced rapidly over the past decade. Gridded population estimates rely heavily on the availability of detailed geospatial ancillary datasets to capture, inform and explain the variabilities in population densities and distributions at small area scales, enabling the disaggregation from areal unit-based counts. Here we describe an extensive geospatial collection of annual, high resolution, spatio-temporally harmonised, global datasets aimed at driving improvements in mapping small area population density variation. This article presents the spatio-temporal harmonisation process that results in an open access repository of 73 individual gridded datasets addressing topography, climate, nighttime lights, land cover, inland water, infrastructure, protected areas as well as the built-up environment on a global level at a spatial resolution of 3 arc-seconds (approximately 100 metres). Datasets are available as annual time series from 2015 up to and including at least 2020, and as recent as 2023 where source datasets allow. Such datasets not only support population modelling but also applications across environmental, economic, and health sectors, supporting informed policy-making and resource allocation for sustainable development.

In 2021, Salmonella Paratyphi A caused >2 million illnesses, resulting in >14,000 deaths, most of which occurred among children under 5 years of age in socioeconomically deprived populations. Both typhoid fever and paratyphoid fever occur in such areas, but paratyphoid fever is currently concentrated in South Asia. Typhoid conjugate vaccines are recommended for the control of enteric fever in typhoid-endemic settings; however, there are increasing demands for the development of vaccines that can address enteric fever more broadly by including protection against paratyphoid fever. The WHO preferred product characteristics (PPC) and a research and development (R&D) technology roadmap are normative documents developed with the guidance and contribution of a multidisciplinary expert group following a standard methodological framework. In this paper, we summarize the PPC and R&D roadmap presenting the key attributes for a bivalent Salmonella enterica serovar Typhi and Paratyphi A vaccine, and discuss the identified key research and data gaps needed to optimize vaccine value and to inform public health and policy decisions, with a particular focus in paratyphoid and enteric fever endemic countries.

Background: There is a concern that SARS-CoV-2 infection may drive poor outcomes after Mycobacterium tuberculosis Mtb exposure and infection. We performed an ex vivo Mtb killing assay using peripheral blood mononuclear cells (PBMC) from three groups: healthy household contacts of people with active TB with and without serologic evidence of previous SARS-CoV-2 infection (COV+HHC and COV-HHC), and participants with active TB and previous SARS-CoV-2 (COV+TB+).

Methods: Twenty participants per group from Cape Town, South Africa were classified according to SARS-CoV-2 anti-S and anti-N antibody tests. We infected PBMC from each participant at a MOI of 0.001 with Mtb strain H37Rv in a 4-day growth inhibition assay. Mycobacteria were quantified through inoculation into Bactec Mycobacteria Growth Indicator Tube (MGIT) liquid culture. PBMC from a subset of participants were infected in the presence of autologous time-matched serum and Mtb-uninfected control PBMCs were included.

Results: There was no difference in the time to detection of Mtb or the normalised Mtb growth ratio (log10CFUsample - log10CFUcontrol) between groups in the standard protocol, or when infected cells from the COV+HHC and COV+TB+ (n=10 each) groups were cultured with autologous time-matched serum. The group with active TB demonstrated the best Mtb growth control. Extracellular Mtb measured by culturing the supernatants of the infected cell cultures also did not show any difference between groups. Five (14.3%) uninfected controls were culture positive.

Conclusion: Our results show that previous SARS-CoV-2 does not affect the Mtb killing ability of circulating mononuclear immune cells in vitro. Previous SARS-CoV-2 is unlikely to affect the outcome of Mtb infection through this mechanism.

We urgently need novel, effective, and accessible vaccines to end tuberculosis (TB) as a public health crisis. The 7th Global Forum on TB Vaccines was convened from 8-10 October 2024 in Rio de Janeiro, Brazil. Under the theme of "Driving innovation from discovery to access," the program covered the breadth of TB vaccine research and development (R&D) through implementation, while underscoring the need for greater innovation and investments to advance development and ensure rapid, affordable, and equitable access. Participants shared the latest research on: approaches to diversify the TB vaccine pipeline, candidates advancing through late-stage trials toward licensure, and efforts to ensure new TB vaccines reach the populations that most need them. The forum provided a platform to learn from diverse experts across the field, including researchers, industry, funders, civil society, and affected communities. Participants examined cross-cutting enablers throughout, including opportunities to establish novel partnership and financing models, enhance open science, optimize R&D practices, and strengthen leadership and engagement with community members and high burden countries alike. In this report, we synthesize key themes and findings from the meeting, highlighting progress and priorities in the TB vaccine field.

Background: The proportion of HIV-positive individuals who present for initiation or re-initiation of antiretroviral therapy (ART) with advanced HIV disease (AHD) and are at risk for morbidity and mortality remains high throughout sub-Saharan Africa. In Zambia, where 20% of ART initiators are diagnosed with AHD, little is known about the characteristics of those starting ART with AHD, why treatment initiation is delayed, how AHD clinical management influences clinical and non-clinical outcomes, or implementation of national AHD guidelines at facility level.

Protocol: AHD-Zambia is a mixed-methods observational study to describe AHD clients and care during the first six months after starting or re-starting ART in Zambia. The study will be conducted at 24 public sector primary health facilities in four provinces. It will enroll ART clients screened for AHD during a three-month data collection period (Cohort 1), clients screened for AHD in the 12 months prior to the data collection period (Cohort 2), patients hospitalized for AHD-related conditions (Cohort 3); and clinical providers at the study sites who manage clients with AHD (Cohort 4). Data collection will include quantitative surveys, medical record review during the 12 months before and after enrollment, qualitative interviews, and focus group discussions. Facility-level indicators will also be collected. Outcomes will include detailed profiles of AHD clients and their 6 and 12-month retention in care and viral suppression, provider and client views on barriers to and preferences for AHD care, and assessment of facility fidelity to AHD guidelines.

Discussion: This study will generate a comprehensive profile of clients presenting with AHD in Zambia, including clinical, demographic, social, and behavioral characteristics, treatment outcomes, and barriers to providing guideline-compliant care. Findings will provide insight into the delivery of AHD services, identify gaps in implementation, and support improvements to retention and care during the early treatment period.

Registration: Clinicaltrials.gov NCT06904456.

Several studies have documented the persistence of economic development outcomes across space and over long periods. Other studies have argued that the reversal of fortune has also occurred over time and space. Since different areas of current Nigeria were once under the rule of states with different degrees of political centralization and later investment in Koranic, this study seeks to explore whether areas or districts under a more centralized political system are more likely to participate in large-scale school expansion programs, such as the 1976 Universal Primary Education (UPE) and 1999 Universal Basic Education (UBE). To check for evidence of the reversal of fortune, we determine whether the degree of state centralization on school participation is more or less in areas that have large investments in Koranic education. OLS results show that while an index of state centralization has a positive and significant impact on enrolment in UPE and UBE programs, the effect is negative and statistically significant for those with heavy investment in Koranic education (measured by district fraction of 1914-46 cohorts with Koranic education). The results are robust to adding an extensive range of explanatory variables and specification tests. While the structure of the economy at the onset of Islamic activities in Nigeria may have made investment in Koranic education worthwhile, the contemporary world does not require Koranic education to make either regional or national advancement possible. Thus, there is a clear case of mismatch between the demands of modern economic life and the skills possessed by a large section. Thus, well-designed policies are required to address this mismatch and accelerate inclusive economic development.

This article addresses the evolving challenges in evaluating insecticide-based tools for vector control. In response to the emergence of insecticide resistance in major malaria vectors, novel chemistries and products are coming to market, and there is a need to review the available testing methodologies. Commonly used methods for evaluating insecticides, such as the World Health Organization (WHO) cone bioassay, are inadequate for the diverse range of tools now available. Innovation to Impact (I2I) has studied the variability in laboratory methods, with the aim of identifying key factors that contribute to variation and providing recommendations to tighten up protocols. The I2I Methods Landscape is a living document which presents a review of existing methods for evaluating vector control tools, with the scope currently extending to insecticide-treated nets (ITNs) and indoor residual sprays (IRS). The review reveals a lack of validation for many commonly used vector control methods, highlighting the need for improved protocols to enhance reliability and robustness of the data that is generated to make decisions in product development, evaluation, and implementation. A critical aspect highlighted by this work is the need for tailored methods to measure endpoints relevant to the diverse modes of action of novel insecticides. I2I envisage that the Methods Landscape will serve as a decision-making tool for researchers and product manufacturers in selecting appropriate methods, and a means to prioritise research and development. We call for collective efforts in the pro-active development, validation, and consistent implementation of suitable methods in vector control to produce the data needed to make robust decisions.

This paper explores the role of Technical and Vocational Education & Training (TVET) relative to academic education in the transition of youths to the labor market in Kenya. Kenya's education system has experienced tremendous changes and diversification over the years, from replacing the old curriculum with the 8-4-4 system, and later transitioning to a competency-based curriculum, not to mention an overhaul of TVET via the Technical and Vocational Education and Training Act No. 29 of 2013. Due to these reforms, enrolment in TVET institutions has progressed upward over the past five years. The growth of the TVET sector has been promoted to help curb the rising rates of youth unemployment, but the evidence of the effectiveness of reforms to date has been sparse. The study provides evidence on two issues: (i) the effect of TVET on youth employment relative to academic education and (ii) the structure and status of the TVET sector in Kenya. We used quantitative and qualitative methodologies to generate the evidence. Findings demonstrate that youth with a TVET background have strong prospects of securing employment than those without TVET skills. However, the data from KIIs reveal gaps in the TVET sector that hinder graduates from competing effectively with their university counterparts in the labor market. The study recommends a review of the curriculum to promote holistic TVET training and match it with current technological innovations.

Background: Men living with HIV in sub-Saharan Africa have sub-optimal engagement in antiretroviral therapy (ART) programs. Generic ART counselling in Malawi does not meet men's needs.

Methods: We developed a male-specific ART counselling curriculum, adapted from the Malawi Ministry of Health curriculum, based on literature review of men's needs and motivations for treatment. We piloted the curriculum with men in six communities, with focus group discussions to assess knowledge of ART, motivators and barriers to care, and perceptions of the male-specific curriculum (n=85). We analysed data in Atlas.ti using grounded theory. We finalised the curriculum in a half-day meeting with Ministry and partner stakeholders (n=5) and implemented it in two randomized trials (IDEaL and ENGAGE). We describe the steps to develop, test and finalize the curriculum.

Results: We adapted three existing topics (status disclosure, treatment as prevention, and ART side effects) and added four new topics (how treatment contributes to men's goals, feeling healthy on treatment, navigating health systems, and self-compassion for the cyclical nature of lifelong treatment). Key motivators included: family wellbeing, having additional children, being financially stability, and earning/keeping respect. Men reported little prior understanding of how ART contributed to their personal goals, and were most interested in treatment as prevention, benefits of disclosure/social support, how to navigate health systems, and side effects with new regimens. Respondents stated that the male-specific counselling challenged the idea that men were incapable of overcoming treatment barriers to lifelong medication.

Conclusion: Men need male-specific ART counselling curriculum to address their needs and increase access to and retention in HIV care. In the Malawi context, topics should include how treatment contributes to men's goals, navigating health systems, self-compassion for lifelong treatment, and taking treatment while healthy. Other countries with high HIV burdens and limited resources could follow the steps outlined in this paper. This curriculum is being evaluated within the two randomized trials.