Health

In a 2020 JAMA Viewpoint, Lawrence Summers and I guessed at the possible economic costs of long COVID.1 At the time, we thought the cost might be $2.6 trillion. With more data, that estimate can be updated. I do so here.

Der beliebte zuckerfreie Süßstoff Xylitol erhöht Risiko für Herzinfarkte und Schlaganfälle deutlich.

In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard ...

This cohort study compares overall survival, treatment adherence, and patient characteristics among patients with cancer receiving conventional cancer treatment with vs without complementary medicine.

Background Accessible, accurate screening tests are necessary to advance tuberculosis (TB) case finding and early detection in high-burden countries. We compared the diagnostic accuracy of available TB triage tests. Methods We prospectively screened consecutive adults with ≥2 weeks of cough presenting to primary health centers in the Philippines, Vietnam, South Africa, Uganda, and India. All participants received the index tests: chest-X-ray (CXR), venous or capillary Cepheid Xpert TB Host Response (HR) testing, and point-of-care C-reactive protein (CRP) testing (Boditech iChroma II). CXR images were processed using computer-aided detection (CAD) algorithms. We assessed diagnostic accuracy against a microbiologic reference standard (sputum Xpert Ultra, culture). Optimal cut-points were chosen to achieve sensitivity ≥90% and maximize specificity. Two-test screening algorithms were considered, using two approaches: 1) sequential negative serial screening in which the second screening test is conducted only if the first is negative and positive is defined as positive on either test and 2) sequential positive serial screening, in which the second screening test is conducted only if the first is positive and positive is defined as positive on both tests. Results Between July 2021 and August 2022, 1,392 participants with presumptive TB had valid results on index tests and the reference standard, and 303 (22%) had confirmed TB. In head-to-head comparisons, CAD4TB v7 showed the highest specificity when using a cut-point that achieves 90% sensitivity (70.3% vs. 65.1% for Xpert HR, difference 95% CI 1.6 to 8.9; 49.7% for CRP, difference 95% CI 17.0 to 24.3). Among the possible two-test screening algorithms, three met WHO target product profile (TPP) minimum accuracy thresholds and had higher accuracy than any test alone. At 90% sensitivity, the specificity was 79.6% for Xpert HR-CAD4TB [sequential negative], 75.9% for CRP-CAD4TB [sequential negative], and 73.7% for Xpert HR-CAD4TB [sequential positive]. Conclusions CAD4TB achieves TPP targets and outperforms Xpert HR and CRP. Combining screening tests further increased accuracy. Cost and feasibility of two-test screening algorithms should be explored. Registration NCT04923958 ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the United States National Institute of Allergy and Infectious Diseases [U01AI152087]. POC CRP test kits and ichroma II machines were donated by Boditech Med Inc, and Xpert HR test kits were donated by Cepheid. CAD was performed by FIND at no cost to the study. The installation and use of the CAD4TB software evaluated in this manuscript was provided free of charge by Delft Imaging to FIND. Study funders and product developers had no role in study design, data collection, data analysis, data interpretation, or writing. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was registered with [ClinicalTrials.gov][1] ([NCT04923958][2]). Study procedures were approved by the institutional review board (IRB) of the University of California San Francisco, the University of Heidelberg, and by local IRBs at each enrollment site. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are available from the corresponding author, CD, upon reasonable request. [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04923958&atom=%2Fmedrxiv%2Fearly%2F2024%2F06%2F21%2F2024.06.20.24308402.atom

Chicago – Erhalten Personen mit einem Body-Mass-Index (BMI) von ≥ 35 kg/m² einen Glucagon-like Peptide-1 Rezeptoragonisten (GLP-1-RA), reduziert das im...

Ja, auch Männer kommen in die Wechseljahre. Diese sind aber meist deutlich weniger beschwerlich als der weibliche Gegenpol. Ein kurzer Überblick.

This cohort study examines the association between melatonin supplementation and the risk of development or progression of age-related macular degeneration in older US adults.

Nature Immunology - Immunosuppression is regulated by the circadian clock and can be leveraged to promote the efficacy of immune checkpoint inhibitor therapy.

Effective antiviral drugs prevent hospitalisation and death from COVID-19. Antiviral efficacy can be efficiently assessed in vivo by measuring rates of SARS-CoV-2 clearance estimated from serial viral genome densities quantitated in nasopharyngeal or oropharyngeal swab eluates. We conducted an individual patient data meta-analysis of unblinded arms in the PLATCOV platform trial to characterise changes in viral clearance kinetics and infer optimal design and interpretation of antiviral pharmacometric evaluations. Methods Serial viral density data were analysed from symptomatic, previously healthy, adult patients (within 4 days of symptom onset) enrolled in a large multicentre, randomised, adaptive, pharmacodynamic, platform trial (PLATCOV) comparing antiviral interventions for SARS-CoV-2. Viral clearance rates over 1 week were estimated under a hierarchical Bayesian linear model with B-splines used to characterise temporal changes in enrolment viral densities and clearance rates. Bootstrap re-sampling was used to assess the optimal duration of follow-up for pharmacometric assessment, where optimal was defined as maximising the expected Z score when comparing effective antivirals with no treatment. PLATCOV is registered at ClinicalTrials.gov, NCT05041907. Findings Between Sept 29, 2021, and Oct 20, 2023, 1262 patients were randomly assigned in the PLATCOV trial. Unblinded data were available from 800 patients (who provided 16 818 oropharyngeal viral quantitative PCR [qPCR] measurements), of whom 504 (63%) were female. 783 (98%) patients had received at least one vaccine dose and 703 (88%) were fully vaccinated. SARS-CoV-2 viral clearance was biphasic (bi-exponential). The first phase (α) was accelerated by effective interventions. For all the effective interventions studied, maximum discriminative power (maximum expected Z score) was obtained when evaluating serial data from the first 5 days after enrolment. Over the 2-year period studied, median viral clearance half-lives estimated over 7 days shortened from 16·6 h (IQR 15·3 to 18·2) in September, 2021, to 9·2 h (8·0 to 10·6) in October, 2023, in patients receiving no antiviral drugs, equivalent to a relative reduction of 44% (95% credible interval [CrI] 19 to 64). A parallel reduction in viral clearance half-lives over time was observed in patients receiving antiviral drugs. For example, in the 158 patients assigned to ritonavir-boosted nirmatrelvir (3380 qPCR measurements), the median viral clearance half-life reduced from 6·4 h (IQR 5·7 to 7·3) in June, 2022, to 4·8 h (4·2 to 5·5) in October, 2023, a relative reduction of 26% (95% CrI –4 to 42). Interpretation SARS-CoV-2 viral clearance kinetics in symptomatic, vaccinated individuals accelerated substantially over 2 years of the pandemic, necessitating a change to how new SARS-CoV-2 antivirals are compared (ie, shortening the period of pharmacodynamic assessment). As of writing (October, 2023), antiviral efficacy in COVID-19 can be efficiently assessed in vivo using serial qPCRs from duplicate oropharyngeal swab eluates taken daily for 5 days after drug administration.

Nature - Lolamicin, a novel antibiotic developed from a pyridinepyrazole precursor, exhibits potent activity against a broad range of Gram-negative multidrug-resistant clinical isolates, and good...

A small study with big implications.

DMZ – WIRTSCHAFT / MM ¦ AA ¦ Der Anteil der Personen, die sich bei der Arbeit gestresst fühlen, ist in den letzten zehn Jahren von 18% auf 23% gestiegen. Stress am Arbeitsplatz hat in den letzten Jahren stark zugenommen. Laut einer neuen Publikation des Bundesamtes für Statistik (BFS) zu Arbeit und Gesundheit hat sich der Anteil der Personen, die sich bei der Arbeit gestresst fühlen, von 18% im Jahr 2012 auf 23% im Jahr 2022 erhöht. Stress stellt inzwischen das am stärksten wachsende physische und psychosoziale Risiko für die Gesundheit am Arbeitsplatz dar. Mehr als die Hälfte (53%) der gestressten Personen geben zudem an, sich emotional erschöpft zu fühlen, was ihr Risiko für ein Burnout erheblich erhöht. Stress im Gesundheits- und Sozialwesen besonders verbreitet Die Ergebnisse der Schweizerischen Gesundheitsbefragung (SGB) zeigen, dass insbesondere im Gesundheits- und Sozialwesen ein hoher Stresspegel herrscht. Im Jahr 2022 gaben 25% der erwerbstätigen Frauen und 21% der erwerbstätigen Männer an, dass sie regelmäßig oder ständig Stress bei der Arbeit erleben. Diese Anteile sind seit 2012, insbesondere bei Frauen, deutlich gestiegen. Vor zehn Jahren berichteten 17% der Frauen und 18% der Männer von hohem Arbeitsstress. Besonders betroffen ist das Gesundheits- und Sozialwesen, wo 29% der Beschäftigten unter Stress leiden. Hier ist jede vierte Erwerbstätige eine Frau. Anstieg des Burnout-Risikos bei Frauen Der Anteil der Frauen, die sich bei der Arbeit emotional erschöpft fühlen und somit einem höheren Burnout-Risiko ausgesetzt sind, ist von 20% im Jahr 2012 auf 25% im Jahr 2022 gestiegen. Bei den Männern blieb der Anteil stabil bei 19%. Am höchsten ist das Risiko der emotionalen Erschöpfung bei Personen, die Stress am Arbeitsplatz erleben: Über die Hälfte von ihnen (53%) fühlen sich emotional verbraucht. Diese Personen zeigen auch häufiger Anzeichen einer Depression (27% gegenüber 5% bei weniger gestressten Personen). Zunahme von sexueller Belästigung und Diskriminierung Frauen berichten 2022 häufiger von Diskriminierung oder Gewalt am Arbeitsplatz als Männer (21% gegenüber 16%). Besonders auffällig ist der höhere Anteil von Frauen, die in den letzten zwölf Monaten wegen ihres Geschlechts diskriminiert wurden (8,4% gegenüber 1,5% bei Männern). Auch sexuelle Belästigung ist häufiger ein Thema: 1,7% der Frauen und 0,4% der Männer gaben an, davon betroffen zu sein. Bei den 15- bis 29-jährigen Frauen lag der Anteil sogar bei 4,1%. Der Anteil der Frauen, die sexuelle Belästigung erlebt haben, ist von 0,6% im Jahr 2012 auf 1,7% im Jahr 2022 gestiegen. Leichter Rückgang physischer Risiken Während psychosoziale Risiken zugenommen haben, ist der Anteil der Erwerbstätigen, die physischen Risiken ausgesetzt sind, leicht gesunken. 2022 waren 47% der Männer und 43% der Frauen bei ihrer Arbeit mindestens drei von zehn möglichen physischen Risiken ausgesetzt. Bei den Männern ging dieser Anteil von 50% im Jahr 2012 auf 47% zurück. Insbesondere die Exposition gegenüber giftigen oder schädlichen Stoffen verringerte sich bei den Männern deutlich von 28% auf 23%. Frauen gaben häufiger als Männer an, unter schmerzhaften und ermüdenden Körperhaltungen zu leiden (50% gegenüber 45%) sowie Personen tragen oder bewegen zu müssen (15% gegenüber 8%). Hohe Risiken in Gast- und Baugewerbe sowie Gesundheitswesen In der Landwirtschaft und im Baugewerbe überwiegen physische Risiken deutlich gegenüber psychosozialen Risiken. Über 80% der Beschäftigten in diesen Branchen sind mindestens drei physischen Risiken ausgesetzt. Im Gesundheitswesen, Gastgewerbe, Handel und Verkehr treten psychosoziale Risiken ebenso häufig auf wie physische Risiken. In diesen Sektoren sind mehr als die Hälfte der Erwerbstätigen mindestens drei physischen oder psychosozialen Risiken ausgesetzt. Junge Erwerbstätige besonders betroffen Erwerbstätige unter 30 Jahren sind häufiger physischen Risiken ausgesetzt als ältere Altersklassen. Insbesondere junge Männer sind betroffen: 61% der unter 30-Jährigen berichten von mindestens drei physischen Risiken, im Vergleich zu 46% bei den 30- bis 49-Jährigen und 41% bei den 50- bis 64-Jährigen. Junge Frauen sind zudem häufiger psychosozialen Risiken ausgesetzt, wie Stress (32% gegenüber 26% bei den 30- bis 49-Jährigen bzw. 19% bei den 50- bis 64-Jährigen) und Gewalt oder Diskriminierung (32% gegenüber 20% bzw. 16%). Diese Entwicklungen unterstreichen die Notwendigkeit, Maßnahmen zum Schutz der Gesundheit am Arbeitsplatz zu verstärken und insbesondere psychosoziale Risiken stärker in den Fokus zu rücken. Herausgeber Bundesamt für Statistik http://www.statistik.admin.ch

Vor allem Senior-Level-Arbeitskräfte mit viel Berufserfahrung wechseln laut einer Studie zur Konkurrenz. Und nehmen dabei wertvolles Fachwissen mit

Eine Studie der Universität hat untersucht wie unterschiedlich sich Homeoffice und Präsenzarbeit auf die Gesundheit auswirken. Das Ergebnis: Homeoffice ist gesünder.

This cohort study evaluates the risk of death in patients hospitalized for COVID-19 or seasonal influenza following the emergence of the JN.1 variant in winter 2023.

Schwacher Harnstrahl, Schmerzen beim Wasserlassen, häufige Harnwegsinfekte – mögliche Symptome einer Harnröhrenenge. Hier erfahren Sie wie sie entsteht, wie man sie erkennt und wie sie behandelt wird

As an avian influenza virus panzootic is underway, the threat of a human pandemic is emerging. Infections among mammalian species in frequent contact with humans should be closely monitored. One mammalian family, the Felidae, is of particular concern. Felids, known as felines or cats, are susceptible to avian influenza virus infection. Felines prey on wild birds and may serve as a host for avian influenza virus adaptation to mammals. Feline-to-feline transmission has been demonstrated experimentally [[1][1]], and real-world outbreaks have been reported [[2][2],[3][3]]. Domestic cats are a popular human companion animal and thus provide a potential pathway for zoonotic spillover of avian influenza viruses to humans. Here, we provide a systematic review of the scientific literature to describe the epidemiology and global distribution of avian influenza virus infections in felines reported from 2004 – 2024. We aim to provide a comprehensive background for the assessment of the current risk, as well as bring awareness to the recurring phenomenon of AIV infection in felines. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement We acknowledge the support of the University of Maryland Baltimore, Institute for Clinical & Translational Research (ICTR) and the University of Maryland Strategic Partnership: MPowering the State (MPower). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3

Early after the start of the COVID-19 pandemic, the detection of influenza B/Yamagata cases decreased globally. Given the potential public health implications of this decline, in this Review, we systematically analysed data on influenza B/Yamagata virus circulation (for 2020–23) from multiple complementary sources of information. We identified relevant articles published in PubMed and Embase, and data from the FluNet, Global Initiative on Sharing All Influenza Data, and GenBank databases, webpages of respiratory virus surveillance systems from countries worldwide, and the Global Influenza Hospital Surveillance Network.

Far-right media figures are promoting the purported health benefits of raw, unpasteurized milk even though the Food and Drug Administration and Centers for Disease Control and Prevention warn that it could cause serious illness and even death. Some of those figures championed raw milk, calling it “real milk,” claiming it could “reverse serious health issues,” and accusing the government of attempting to keep it away from people.

Warum man Reisgerichte lieber gleich aufessen oder schnell kühlen sollte

Analyzing anatomic shapes of tissues and organs is pivotal for accurate disease diagnostics and clinical decision-making. One prominent disease that depends on anatomic shape analysis is osteoarthritis, which affects 30 million Americans. To advance osteoarthritis diagnostics and prognostics, we introduce ShapeMed-Knee, a 3D shape dataset with 9,376 high-resolution, medical imaging-based 3D shapes of both femur bone and cartilage. Besides data, ShapeMed-Knee includes two benchmarks for assessing reconstruction accuracy and five clinical prediction tasks that assess the utility of learned shape representations. Leveraging ShapeMed-Knee, we develop and evaluate a novel hybrid explicit-implicit neural shape model which achieves up to 40% better reconstruction accuracy than a statistical shape model and implicit neural shape model. Our hybrid models achieve state-of-the-art performance for preserving cartilage biomarkers; they are also the first models to successfully predict localized structural features of osteoarthritis, outperforming shape models and convolutional neural networks applied to raw magnetic resonance images and segmentations. The ShapeMed-Knee dataset provides medical evaluations to reconstruct multiple anatomic surfaces and embed meaningful disease-specific information. ShapeMed-Knee reduces barriers to applying 3D modeling in medicine, and our benchmarks highlight that advancements in 3D modeling can enhance the diagnosis and risk stratification for complex diseases. The dataset, code, and benchmarks will be made freely accessible. ### Competing Interest Statement AAG is a shareholder of NeuralSeg Ltd., and GeminiOV. ### Funding Statement This work was supported in part by the National Institutes of Health R01 AR077604, R01 EB002524, R01 AR079431, P41 EB027060, the Wu Tsai Human Performance Alliance, and a CIHR Postdoctoral Fellowship. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Data were acquired from the Osteoarthritis Initiative (OAI). https://nda.nih.gov/oai I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced are available online at https://huggingface.co/datasets/aagatti/ShapeMedKnee

Nature - Scientists identify the brain cells that regulate inflammation, and pinpoint how they keep tabs on the immune response.

Sometimes something happens that takes your breath away, in a good way. Those who read my stuff know I’m not someone who gets carried away by optimism, to say the least. But a new paper by scientists at Columbia has blown me away. Researchers have made a discovery, which, if it holds up, has the potential to transform treatments for autoimmune diseases and post-viral illness like long covid and myalgic encephalomyelitis.

Highly pathogenic avian influenza (HPAI) viruses cross species barriers and have the potential to cause pandemics. In North America, HPAI A(H5N1) viruses related to the goose/Guangdong 2.3.4.4b hemagglutinin phylogenetic clade have infected wild birds, poultry, and mammals. Our genomic analysis and epidemiological investigation showed that a reassortment event in wild bird populations preceded a single wild bird-to-cattle transmission episode. The movement of asymptomatic cattle has likely played a role in the spread of HPAI within the United States dairy herd. Some molecular markers in virus populations were detected at low frequency that may lead to changes in transmission efficiency and phenotype after evolution in dairy cattle. Continued transmission of H5N1 HPAI within dairy cattle increases the risk for infection and subsequent spread of the virus to human populations.

Although latent infection with Toxoplasma gondii is among the most prevalent of human infections, it has been generally assumed that, except for congenital transmission, it is asymptomatic. The demonstration that latent Toxoplasma infections can alter ...

Objective: To determine whether vitamin D supplementation influences grip strength, explosive leg power, cardiorespiratory fitness and risk of exercise-induced bronchoconstriciton (EIB) in South African schoolchildren. Methods: Sub-study (n=450) in Cape Town schoolchildren aged 8-11 years, nested within a phase 3 randomised placebo-controlled trial (ViDiKids). The intervention was weekly oral doses of 10,000 IU vitamin D3 (n=228) or placebo (n=222) for 3 years. Outcome measures were serum 25-hydroxyvitamin D3 (25[OH]D3) concentrations, grip strength, standing long jump distance, peak oxygen uptake (VO2peak, determined using 20-metre multi-stage shuttle run tests) and the proportion of children with EIB, all measured at end-study. Results: 64.7% of participants had serum 25(OH)D3 concentrations 75 nmol/L at baseline. At 3-year follow-up, children randomised to vitamin D vs. placebo had higher mean serum 25(OH)D3 concentrations (97.6 vs. 58.8 nmol/L respectively; adjusted mean difference [aMD] 39.9 nmol/L, 95% CI 36.1 to 43.6) and long jump distance (128.3 vs. 122.1 cm; aMD 3.6 cm, 95% CI 0.0 to 7.2). No end-study differences in grip strength, VO2peak, or spirometric lung volumes were seen, but administration of vitamin D vs. placebo was associated with a borderline-significant increased risk of EIB (14.5% vs. 8.6%; adjusted odds ratio 1.92, 95% CI 0.99 to 3.73). Conclusion: A 3-year course of weekly oral supplementation with 10,000 IU vitamin D3 elevated serum 25(OH)D3 concentrations in South African schoolchildren and induced a small increase in long jump distance, but had no effect on grip strength or VO2 peak. Potential effects of vitamin D on risk of EIB require further research. ### Competing Interest Statement ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd and Hyphens Pharma Ltd. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd; support for attending meetings from Pharma Nord Ltd and Abiogen Pharma Ltd; receipt of consultancy fees from DSM Nutritional Products Ltd and Qiagen Ltd; receipt of a speaker fee from the Linus Pauling Institute; participation on Data and Safety Monitoring Boards for the VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology, Pan African Clinical Trials Registry ref PACTR20200989766029) and the Trial of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India (ClinicalTrials.gov ref [NCT04641195][1]); and unpaid work as a Programme Committee member for the Vitamin D Workshop. All other authors declare that they have no competing interests. ### Clinical Trial NCT02880982 ### Funding Statement This research was funded by the UK Medical Research Council (refs MR/R023050/1 and MR/M026639/1, both awarded to ARM). RJW was supported by Wellcome (104803, 203135). He also received support from the Francis Crick Institute which is funded by Cancer Research UK (FC2112), the UK Medical Research Council (FC2112) and Wellcome (FC2112). NCH and CC are supported by the UK Medical Research Council [MC\_PC\_21003; MC\_PC\_21001]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The trial was approved by the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee (Ref: 796/2015) and the London School of Hygiene and Tropical Medicine Observational/Interventions Research Ethics Committee (Ref: 7450-2). Participants and their parents/guardians provided written informed assent and consent, respectively, to take part in the trial before any study procedures were conducted. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Anonymised data are available from corresponding authors upon reasonable request, subject to terms of IRB and regulatory approval. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04641195&atom=%2Fmedrxiv%2Fearly%2F2024%2F03%2F27%2F2024.03.26.24304912.atom