Gates Open Research最新文献

{"title":"CYP2D6 Pharmacogenetics in Nigerian Sickle Cell Disease: Phase 1 of Implementing Pharmacogenomics Testing for Effective Care and Treatment in Africa (iPROTECTA) program.","authors":"Babatunde Adeagbo, Olusola Olarewaju, Ochuko Orherhe, Zedias Chikwambi, Adrian Mazhindu, Rahman Bolarinwa, Oluseye Bolaji, Collen Masimirembwa","doi":"10.12688/gatesopenres.16370.1","DOIUrl":"10.12688/gatesopenres.16370.1","url":null,"abstract":"<p><strong>Background: </strong>Sickle Cell Disease (SCD) is highly prevalent in Nigeria, with severe pain crises being a primary cause of morbidity. Codeine and tramadol are frequently used opioids, but their effectiveness and safety are significantly influenced by <i>CYP2D6</i> genetic variations. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines exist for opioid therapy based on CYP2D6 phenotypes. There's a critical need for pre-emptive pharmacogenomic (PGx) testing in African SCD patients to guide opioid selection. This study aimed to determine <i>CYP2D6</i> allele, phenotype frequencies and evaluate the feasibility of implementing pre-emptive pharmacogenomic (PGx) testing to guide opioid therapy for SCD patients in Nigeria.</p><p><strong>Methods: </strong>This prospective, multicenter implementation study recruited 503 consenting SCD patients (HbSS or HbSC) aged ≥15 years from five Nigerian sites. Blood samples were collected for DNA extraction. <i>CYP2D6</i> single-nucleotide polymorphisms and copy number variations were determined using Taqman assays based open array, GenoPharm. Phenotypes were assigned based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines using the Genomics Information Management System (GIMS). and patient-specific medication safety cards were generated.</p><p><strong>Results: </strong>We successfully genotyped 503 SCD patients with a mean age of 25.1 years, while 61.4% were female, and hydroxyurea use was less than 9.4%. Actionable <i>CYP2D6</i> variants were found in 36.6% of participants. The predicted phenotype distribution was 8.8% Ultrarapid Metabolizers (UM), 54.1% Normal Metabolizers (NM), 26.0% Intermediate Metabolizers (IM), and 1.8% Poor Metabolizers (PM), with 9.3% undetermined. Patient medication safety cards were provided to guide prescriptions.</p><p><strong>Conclusions: </strong>This study successfully established a genotyped cohort of 503 Nigerian SCD patients, demonstrating the feasibility of pre-emptive pharmacogenetic testing through a Pan-African collaborative model in a resource-limited setting. The identification of PM and UM provides direct clinical guidance, as CPIC guidelines recommend avoiding codeine and tramadol in these groups due to the high risk of diminished efficacy or serious toxicity, respectively. The high prevalence of actionable CYP2D6 variants indicates a substantial proportion of Nigerian SCD patients may experience altered opioid responses, underscoring the need for tailored prescribing to optimise pain control and minimise adverse drug reactions.</p>","PeriodicalId":12593,"journal":{"name":"Gates Open Research","volume":"9 ","pages":"101"},"PeriodicalIF":0.0,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145503534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing Research Readiness Challenges in African Institutions: Development and Application of a Modular Assessment Tool.","authors":"Patrick Amboka, H Kariuki, Nosa Orobaton, Alphonsus Neba, Julius Kirimi Sindi","doi":"10.12688/gatesopenres.16368.1","DOIUrl":"10.12688/gatesopenres.16368.1","url":null,"abstract":"<p><strong>Introduction: </strong>Historically, African research institutions have faced significant barriers to gaining recognition on a global stage due to limited infrastructure, underdeveloped governance frameworks, and low representation in high-impact publications. This underrepresentation reflects systemic barriers such as the lack of visibility of both researchers and institutions, limited funding, inadequate infrastructure, and fragmented institutional arrangements, which impede the continent's ability to contribute robustly to the global knowledge economy. To address these barriers, the Research Readiness Assessment Survey (RRAS) was developed as a modular, context-specific tool to evaluate and enhance institutional research capacity across multiple dimensions, including research infrastructure, policy and policy engagement, governance, human resources, institutional arrangements, grant management, and research outputs.</p><p><strong>Methods: </strong>The RRA was developed by integrating different global frameworks. This assessment adopted a cross-sectional design. Piloting was performed in nine institutions distributed across Kenya, Ethiopia, and Nigeria. The questionnaire used for data collection was uploaded to RedCap in English, French, and Portuguese. The tool underwent validity and reliability testing. Validity testing included piloting of nine institutions. Data from the pilot test were categorized and analyzed using STATA version 17.0. Analyses were performed at both the univariate and bivariate levels.</p><p><strong>Results: </strong>The proportion of institutions that performed, on average, in all modules, was 66.67% (n=6). None of the institutions had a strong overall institutional performance based on our scoring. The proportion of institutions that had developed overall institutional performance was 22.22% (n=2), whereas 11.11% (n=1) had limited overall institutional performance. There was a statistically significant and strong positive correlation between the following module scores and overall institutional performance: laboratory infrastructure, institutional arrangement, grant management, policy and policy engagement, project management, and human resources; [r=0.666; p-value<0.05],[r=0.916; p-value<0.001], [r=0.799; p-value<0.01], [r=0.660; p-value<0.05], [r=0.738; p-value<0.05], and [r=0.648; p <0.05], respectively.</p>","PeriodicalId":12593,"journal":{"name":"Gates Open Research","volume":"9 ","pages":"92"},"PeriodicalIF":0.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12559021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of an ultra-portable pocket-sized device for running Loop mediated isothermal amplification (LAMP) assays for rapid detection of sweetpotato viruses.","authors":"Segundo Fuentes, Kwame Ogero, Ana Perez, Jan Frederick Kreuze","doi":"10.12688/gatesopenres.16369.1","DOIUrl":"10.12688/gatesopenres.16369.1","url":null,"abstract":"<p><p>The sweetpotato ( <i>Ipomoea batatas</i>) is an important food crop in the tropical and subtropical regions of the world, but its yield and quality are heavily affected by viral diseases. Timely and precise detection of virus infections is essential for effective monitoring of seed health and disease management. We evaluated the feasibility of using a compact, ultra-portable LAMP-based diagnostic device-initially designed for human health applications-for detecting key sweetpotato viruses (SPCSV, SPFMV, and SPLCV). Field and greenhouse samples were tested, showing 100% agreement in virus detection with a larger commonly used LAMP device. Sensitivity tests confirmed consistent performance, and the use of portable power banks enabled reliable on-site use. The statistical analysis indicated high accuracy and strong correlation in time-to-positive values between methods (r > 0.89, p < 0.01). Furthermore, cost analysis demonstrated that the pocket LAMP device setup significantly reduced per-test costs-by approximately 40%-while maintaining diagnostics reliability. These findings support the potential of this tool on plant virus detection in locations with limited resources.</p>","PeriodicalId":12593,"journal":{"name":"Gates Open Research","volume":"9 ","pages":"91"},"PeriodicalIF":0.0,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12552739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145372447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Successful Multi-Component Program for Expanding Vasectomy Services by MSI Reproductive Choices Bolivia.","authors":"Alison T Hoover, Ana Cecilia Velasquez Rossi, Silvia Velasco Parihuana, Jonathan Stack, John Curington, Michel Labrecque","doi":"10.12688/gatesopenres.16366.1","DOIUrl":"10.12688/gatesopenres.16366.1","url":null,"abstract":"<p><strong>Background: </strong>Vasectomy use has historically been very low in Bolivia, constituting just 0.1% of the method mix in 2021. MSI Reproductive Choices Bolivia (MSI Bolivia), one of the major reproductive health organizations in the country, sought to increase the affordability, availability, and quality of vasectomy services in their nationwide clinics and mobile units by training in-house providers to replace contracting external providers with high fees. We describe the MSI Bolivia vasectomy program in 2021 and its results over the following two years.</p><p><strong>Methods: </strong>The program included components of the Engender Health Supply-Enabling-Environment-Demand (SEED) Programing Model™ for evidence-based vasectomy programming. First, MSI Bolivia offered free vasectomies through a social media campaign during November 2021. Second, two international No-Scalpel Vasectomy (NSV) experts trained four MSI Bolivia physicians during a week-long teaching program in La Paz, Bolivia. Third, MSI Bolivia formed partnerships and held a dissemination event to publicize the campaign. MSI Bolivia continued conducting training and marketing campaigns in 2022 and 2023.</p><p><strong>Results: </strong>During the 2021 six-week promotional campaign, 884 men signed up and over 600 were scheduled for the procedure. During the training week, the trainees performed 127 supervised vasectomies. Over the following weeks, the four trained physicians performed over 300 additional unsupervised vasectomies. Two of the newly trained physicians taught NSV to seven other colleagues in 2022 and 2023. MSI Bolivia reduced the fees for a vasectomy from Bs. 1500 (USD 215) to Bs. 850 (USD 122). The number of vasectomies performed by MSI Bolivia increased from 77 in 2019 to 643, 918, and 1,135 in 2021, 2022, and 2023, respectively.</p><p><strong>Conclusion: </strong>By training their own physicians to perform NSV, reducing costs, and advertising through social media, MSI Bolivia was able to increase the availability, quality, and acceptability of vasectomy in Bolivia.</p>","PeriodicalId":12593,"journal":{"name":"Gates Open Research","volume":"9 ","pages":"82"},"PeriodicalIF":0.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of Molecular Markers of Resistance to Antimalarial Drugs Three Years After Perennial Malaria Chemoprevention in Sierra Leone.","authors":"Haily Chen, Kwabena Owusu-Kyei, Augustin E Fombah, Julian Williams, Carla García-Fernández, Eduard Rovira-Vallbona, Andreu Bofill, Llorenç Quintó, Antía Figueroa-Romero, Falama Mac-Abdul, Mohamed Samai, Alfredo Mayor, Clara Menéndez","doi":"10.12688/gatesopenres.16367.1","DOIUrl":"10.12688/gatesopenres.16367.1","url":null,"abstract":"<p><strong>Background: </strong>Monitoring parasite resistance to antimalarial drugs is essential for detecting potential changes in drug efficacy. This study assessed the prevalence of molecular markers of resistance to sulfadoxine-pyrimethamine (SP), chloroquine, and artemisinin in Sierra Leone, where SP is used for intermittent preventive treatment in pregnancy (IPTp) and perennial malaria chemoprevention (PMC) in young children, while artemisinin is used to treat malaria episodes.</p><p><strong>Methods: </strong>A cross-sectional survey was conducted between June and August 2021 in three districts of Sierra Leone. A total of 440 febrile children aged 2-5 years attending the health facilities were screened for <i>P. falciparum</i> malaria using a rapid diagnostic test, and 300 participants with positive RDT were enrolled. Capillary blood samples were collected as dried blood spots, analyzed using quantitative PCR to confirm <i>P. falciparum,</i> and sequenced for resistance markers in <i>pfdhfr, pfdhps, pfcrt, pfmdr1,</i> and <i>pfK13.</i></p><p><strong>Results: </strong>Of 298 blood samples, 237 (79.5%) were qPCR-positive and 230 samples were successfully genotyped. The <i>pfdhfr</i> triple mutant (N51I/C59R/S108N) was detected in 99.5% of samples (217/218), while <i>pfdhps</i> mutations A437G and K540E were detected in 92.1% (211/229) and 19.1% (42/220), respectively. The <i>pfdhfr/dhps</i> quintuple mutant (triple mutant + A437G/K540E) prevalence was 4.6% (7/151), and no sextuple mutants (quintuple + <i>pfdhps</i>-A581G) were observed. Chloroquine resistance-associated mutations in <i>pfcrt</i> (CVIET haplotype) were detected in 36.6% of samples, while <i>pfmdr1</i> mutations at codon 86, 184, 1042, and 1246 occurred in 2.3%, 71.7%, 0.9% and 1.8%, respectively. No validated <i>pfK13</i> markers of artemisinin resistance were detected.</p><p><strong>Conclusion: </strong>In this study, the sustained low prevalence of <i>pfdhfr/dhps</i> quintuple mutant justifies the continued use of SP- containing IPTp and PMC, as well as its expansion in the country into the second year of life with additional SP doses. Importantly, no validated <i>pfK13</i> markers were found supporting the use of artemisinin-based combination therapies in Sierra Leone.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov NCT04235816. Registered on January 17, 2020.</p>","PeriodicalId":12593,"journal":{"name":"Gates Open Research","volume":"9 ","pages":"81"},"PeriodicalIF":0.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12508423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-blinded, stratified, dose ranging trial to assess pharmacokinetics and identify optimal dose of vitamin B12 in pregnancy in Tanzania.","authors":"Omar Lweno, Victoria S Reynolds, Matthew D Barberio, Kevin C Klatt, Sabina Mugusi, Mathangi Gopalakrishnan, Zohra Lukmanji, Fadhlun M Alwy Al-Beity, Homa K Ahmadzia, Amrita Arcot, Kelly Gallagher, Leigh A Martin, Ali Rahnavard, Alison D Gernand, Brooke Langevin, Honorati Masanja, Emily R Smith","doi":"10.12688/gatesopenres.15991.2","DOIUrl":"10.12688/gatesopenres.15991.2","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Discussion: </strong>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.</p><p><strong>Registration: </strong>ClinicalTrials.gov ( NCT05426395, 16/06/2022).</p>","PeriodicalId":12593,"journal":{"name":"Gates Open Research","volume":"8 ","pages":"95"},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12759048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WHO preferred product characteristics for bivalent Salmonella Typhi/Paratyphi A vaccine for comprehensive protection against enteric fever- key considerations and research gaps.","authors":"Ana Belen Ibarz Pavon, John Clemens, Alejandro Craviotto, John A Crump, Denise O Garrett, Melita A Gordon, Jacob John, Karen H Keddy, Matthew B Laurens, Xinxue Liu, Florian Marks, Andrew J Pollard, Senjuti Saha, Annelies Wilder-Smith","doi":"10.12688/gatesopenres.16364.1","DOIUrl":"10.12688/gatesopenres.16364.1","url":null,"abstract":"<p><p>In 2021, <i>Salmonella</i> 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 <i>Salmonella enterica</i> 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.</p>","PeriodicalId":12593,"journal":{"name":"Gates Open Research","volume":"9 ","pages":"71"},"PeriodicalIF":0.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global gridded multi-temporal datasets to support human population distribution modelling.","authors":"Dorothea Woods, Tom McKeen, Alexander Cunningham, Rhorom Priyatikanto, Andrew J Tatem, Alessandro Sorichetta, Maksym Bondarenko","doi":"10.12688/gatesopenres.16363.1","DOIUrl":"10.12688/gatesopenres.16363.1","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12593,"journal":{"name":"Gates Open Research","volume":"9 ","pages":"72"},"PeriodicalIF":0.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mycobacterium tuberculosis growth inhibition by peripheral blood mononuclear cells from household contacts is not affected by previous SARS-CoV-2 infection.","authors":"Jane A Shaw, Caleb Petersen, Andriette Hiemstra, Maynard Meiring, Osagie A Eribo, Christian Otum, Ilana van Rensburg, Ayanda Shabangu, Bronwyn Smith, Firdows Noor, Gerhard Walzl, Kevin B Urdahl, Dave Lewinsohn, Stephanus T Malherbe, Nelita du Plessis","doi":"10.12688/gatesopenres.16362.1","DOIUrl":"10.12688/gatesopenres.16362.1","url":null,"abstract":"<p><strong>Background: </strong>There is a concern that SARS-CoV-2 infection may drive poor outcomes after <i>Mycobacterium tuberculosis</i> Mtb exposure and infection. We performed an <i>ex vivo</i> 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+).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Our results show that previous SARS-CoV-2 does not affect the Mtb killing ability of circulating mononuclear immune cells <i>in vitro.</i> Previous SARS-CoV-2 is unlikely to affect the outcome of Mtb infection through this mechanism.</p>","PeriodicalId":12593,"journal":{"name":"Gates Open Research","volume":"9 ","pages":"69"},"PeriodicalIF":0.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Driving innovation from discovery to access: Meeting report of the 7 ^th Global Forum on TB Vaccines (8-10 October 2024, Rio de Janeiro, Brazil).","authors":"Shaun Palmer, Rebecca A Clark, Bridgette J Connell, Vanessa Mwebaza Muwanga, Arthur Coelho, Paul Ogongo, Carly Young","doi":"10.12688/gatesopenres.16360.1","DOIUrl":"10.12688/gatesopenres.16360.1","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12593,"journal":{"name":"Gates Open Research","volume":"9 ","pages":"65"},"PeriodicalIF":0.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144950573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}