Impact of high-dose vitamin D and calcium carbonate supplementation on bone density in adolescents living with HIV: a randomised, placebo-controlled trial.

BACKGROUND: HIV has adverse impact on skeletal development in children despite antiretroviral therapy (ART). We investigated the effect of high-dose (20 000 IU) weekly vitamin D3 and daily calcium carbonate (500 mg) supplementation for 48 weeks on bone density and muscle strength and power among peripubertal individuals (11-19 years) with perinatally acquired HIV. METHODS: We conducted an individually randomised, double-blind, placebo-controlled trial. Individuals taking ART for at least 6 months who had a defined caregiver, and knew their HIV status (in those aged >12 years) were recruited from HIV clinics in Harare, Zimbabwe and Lusaka, Zambia. The primary outcome was total body less-head bone mineral density (TBLH-BMD) Z score and secondary outcome was lumbar spine bone mineral apparent density (LS-BMAD) Z score (both measured by dual-energy x-ray absorptiometry). Linear regression was used to compare arms adjusting for country and baseline value of the measure. Pre-specified subgroup analyses by country, age-group, sex, pubertal stage, calcium intake, tenofovir disproxil fumarate use, and baseline vitamin D insufficiency (defined as 25[OH]D <75 nmol/L), and a post-hoc subgroup analysis by viral suppression, were performed. A Participant Advisory Board that included adolescents with HIV, their guardians, and health providers guided study conduct. The trial is registered with the Pan African Clinical Trials Registry, PACTR20200989766029. FINDINGS: Of 842 participants (median age 15 years [IQR 13-17], 448 [53%] female and 394 [47%] male) enrolled between Feb 4 to Nov 23, 2021, 639 (76%) were vitamin D insufficient. At 48 weeks, outcomes were available for 751 (89%) participants. There was no difference by arm in TBLH-BMD Z score (intervention vs control: mean -1·53 [SD 1·18] vs -1·56 [1·12], adjusted mean difference -0·04 [95% CI -0·01 to 0·09]) or in LS-BMAD Z score (intervention vs control: -0·64 [1·17] vs -0·71 [SD 1·16], adjusted mean difference -0·05 [95% CI -0·01 to 0·12]). However, among participants with vitamin D insufficiency at baseline, there was a significantly higher LS-BMAD Z score (adjusted mean difference 0·09 [95% CI 0·02 to 0·16], pinteraction=0·025) in the intervention arm than in the control arm. The corresponding adjusted mean difference in TBLH-BMD Z score was 0·06 (0·00-0·11), pinteraction=0·15. There was no statistical evidence of interaction in other subgroups. No drug-related severe adverse events were observed. INTERPRETATION: There was no difference in bone density between arms overall, but among those with vitamin D insufficiency the intervention improved bone density. High-dose vitamin D3 and calcium supplementation, a safe and cheap intervention, during adolescence might promote bone accrual and mineralisation in those with vitamin D insufficiency, which could increase peak bone mass. FUNDING: European Developing Country Clinical Trials Partnership

HIV testing during systematic screening for tuberculosis among household contacts in high-tuberculosis burden settings: a systematic review and meta-analysis.

BACKGROUND: Tuberculosis household contacts are at elevated risk of HIV, and systematic screening for tuberculosis is an opportunity for people to know their status. We aimed to assess the coverage and positivity of HIV testing during household systematic screening for tuberculosis. METHODS: For this systematic review and meta-analysis (PROSPERO: CRD42024471979), we searched MEDLINE, Embase, Global Health, and Africa Wide databases from Jan 1, 2000, to June 24, 2025. The primary analysis population was household contacts of people with tuberculosis without known HIV. Studies were included if HIV testing was offered to household contacts, and in the primary analysis if people known to be living with HIV were excluded from the population eligible for testing. We extracted or derived coverage (proportion of people eligible for testing who received an HIV test) and positivity (proportion of people tested with a positive result) and calculated pooled proportions using random effects meta-analysis. We narratively summarised themes from qualitative reports. Meta-regression examined the association of national HIV prevalence, time period, and participant age, with coverage and positivity of HIV testing. FINDINGS: Searches identified 31 quantitative studies (110 090 people), of which 17 (40 407 people) were included in primary analyses. Seven qualitative studies reported community or provider perspectives. The pooled proportion of eligible household contacts tested for HIV was 72·9% (95% CI 60·3-83·9), ranging from 0% to 100%. Pooled positivity of testing was 5·9% (3·6-8·8) overall. Positivity was 9·7% (5·8-14·5; ten studies) in countries with ≥10% national adult HIV prevalence. Qualitative studies highlighted context-dependent facilitators and barriers of household contacts' capability, opportunity, and motivations to engage with HIV testing. INTERPRETATION: Few studies have evaluated HIV testing for tuberculosis household contacts. Coverage of testing was reasonable but varied substantially across studies. Positivity of testing was high. Further research is needed to understand and optimise acceptability and ensure feasibility of HIV testing within screening of tuberculosis among household contacts, and tuberculosis-HIV programmes in high HIV-incidence settings should consider monitoring implementation of HIV within routine tuberculosis household contact screening. FUNDING: National Institute for Health and Care Research and Wellcome Trust

Rapid weight gain in first 2 years of life and BMI trajectories from 3 to <10 years: a population-based longitudinal study of 1.7 million Brazilian children.

BACKGROUND: Obesity is considered a disease with negative health impacts at all life stages. Changes in growth patterns, such as postnatal rapid weight gain (RWG), can be important predictors of growth trajectories in children. We investigated the association between RWG during the first two years of life and subsequent BMI trajectories from the age 3-to 9 years, and whether the association differed by birth weight group. METHODS: We used the data of a population-based cohort from the Cadastro Único (CadÚnico) of the Federal Government, the linkage of the National Live Births System (SINASC) and the National Food and Nutritional Surveillance System (SISVAN). The sample comprised 1.7 million Brazilian children aged from zero to nine years from 2008 to 2017. Mixed-effects models were used to estimate mean age-trajectories for BMI by RWG group. FINDINGS: Children who experienced RWG during the first two years of life had higher mean BMI trajectories from 3 to 9 years, compared to those who did not. The difference was seen across all birth weight groups, and was more evident for the children with high birth weight. At age 9, the BMI difference between RWG and non-RWG children was 1.31 kg/m2 (boys) and 1.43 kg/m2 (girls) for children with adequate birth weight, 1.27 kg/m2 (boys) and 1.35 kg/m2 (girls) for low birth weight, and 2.25 kg/m2 (boys) and 2.86 kg/m2 (girls) for macrosomia. INTERPRETATION: Children who experienced RWG during the first two years of life had higher BMI trajectories than children who did not. The finding highlighted the importance of monitoring child growth, which allows the early identification of potential growth deviations and the implementation of necessary interventions to ensure that children grow healthy and reach their full developmental potential. FUNDING: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES, CAPES/Print/UFBA; University College London (UCL); National Institute for Health Research (NIHR) Great Ormond Street Hospital Biomedical Research Centre; Fundação de Amparo à Pesquisa do Estado de Minas Gerais-FAPEMIG; National Council for Scientific and Technological Development-CNPq; CNPq/CGFP/DECIT/SECTICS; Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, Inovação e Complexo da Saúde do Ministério da Saúde; Wellcome Trust

Nasal microbiota and clinical features in acute flu-like illness: COVID-19 status and long COVID follow-up.

OBJECTIVES: Long COVID (LC) is a challenging medical condition. Reliable diagnostic and targetable biomarkers of LC for a proper and early diagnosis and clinical care are an unmet medical need. We aimed to evaluate targetable biomarkers for LC management. DESIGN: Comparison of nasal microbiota and clinical features in 291 individuals with acute influenzae-like illness (ILI), comparing COVID-19-positive (n=193) and negative (n=98) groups, with further stratification by long COVID (LC) outcomes (persistent symptoms >3 months). RESULTS: Clinical characteristics were balanced across groups, with upper respiratory symptoms predominating. Individuals who developed LC exhibited more cardiorespiratory symptoms during acute infection (70% vs 48%, P=0.002). Nasal microbiota analysis revealed lower alpha diversity in COVID-19-positive individuals vs other ILI (Wilcoxon: Chao2 index P=0.03305; Shannon diversity index P=0.02578; Simpson diversity index P=0.1082) but no differences in beta diversity or taxonomic composition between groups, including LC vs recovered individuals. EBV/CMV infection/reactivation was not associated with LC. Sensitivity analyses confirmed robustness to methodological and temporal biases. CONCLUSIONS: Findings suggest acute nasal microbiota disruption in individuals with COVID-19, but no LC-specific microbial profile

Cervical cancer in Bulgaria since EU accession in 2007: a struggle in the face of political instability.

BACKGROUND: Bulgaria has one of the highest cervical cancer incidence rates in the EU, driven by persistently low screening uptake and HPV vaccination coverage. Despite the preventable nature of the disease, efforts to implement effective prevention strategies have been undermined by political instability, fragmented governance, and systemic health system weaknesses. REFORM CONTENT: Since EU accession in 2007, Bulgaria has launched several initiatives, including the "Stop and Get Checked" programme and the National Program for Primary Prevention of Cervical Cancer. These efforts were supported by EU policy frameworks and funding. The 2023 National Plan for Combating Cancer aims to align with Europe's Beating Cancer Plan, proposing organised screening, expanded HPV vaccination (including boys), and improved public awareness. A new HPV prevention programme (2025-2030) sets ambitious coverage targets and introduces gender-neutral vaccination. EXPECTED RESULTS: If implemented effectively, these reforms could significantly reduce cervical cancer incidence and mortality. Key expected outcomes include increased screening coverage, higher HPV vaccination rates, improved access for underserved populations, and better data collection and monitoring. The integration of EU-supported strategies offers a pathway to more consistent and sustainable progress. CONCLUSIONS: Bulgaria's experience highlights the challenges of implementing cancer prevention in politically unstable settings. While recent reforms show promise, success depends on sustained political commitment, adequate funding, and coordinated implementation. Lessons from Bulgaria may inform other countries facing similar governance challenges, underscoring the value of external policy frameworks and targeted, system-wide approaches

Pathways to health: Reporting on health co-benefits from urban climate mitigation action varies by sector.

Well-designed city actions to reduce greenhouse gas emissions can also deliver substantial near-term health co-benefits. Improved understanding and reporting of the health benefits from climate mitigation can aid efforts by cities to design and deliver healthy, equitable solutions to the climate crisis. Using global data from the 2022 CDP-ICLEI Track cities questionnaire, we analysed factors that may influence the awareness and identification of health co-benefits from climate mitigation. Actions from the transport and AFOLU sector were five to eight times more likely to report health co-benefits than other sectors, regardless of which region the action was undertaken. There was no significant difference between actions in the pre-implementation stage compared to actions that were underway. The findings highlight the need to raise awareness about the potential health benefits linked to climate mitigation among urban policymakers across all sectors to help deliver an equitable transition to a healthy, net zero future

Burden of typhoid fever and antimicrobial resistance in India (2023): a modelling study

Background India is one of the countries with a high typhoid fever burden. In 2022, the National Technical Advisory Group on Immunisation recommended including the typhoid conjugate vaccine (TCV) in the Universal Immunisation Programme. In this study, we aimed to estimate the 2023 burden of typhoid fever and its antimicrobial resistance (AMR) to inform targeted vaccine introduction strategies. Methods We used a decision tree model to estimate typhoid cases, hospitalisations, complications, and deaths. Incidence and clinical parameters were derived from a multicentre Indian study, with state-wise AMR prevalence from a systematic review. Two co-primary and four alternative scenarios were presented to validate the robustness of the findings. Findings We estimated 4.9 million (95% UI: 4.4–5.6) typhoid cases and 7850 (4300–14,900) deaths in India in 2023. Of 730,000 (534,000–970,000) hospitalisations, 600,000 (435,000–799,000; 82%) were attributable to fluoroquinolone-resistant. Under primary scenario A, children <5 years accounted for 321,000 (235,000–427,000; 44.0%) hospitalisations and 2600 (1300–4800; 34.0%) deaths. Under primary scenario B, 5–9 years of age accounted for 265,000 (135,000–278,000; 36.0%) hospitalisations and 2900 (1500–5300; 36.0%) deaths. Delhi, Maharashtra, and Karnataka together accounted for 29% of the national burden and had the highest rates of fluoroquinolone-resistant cases and deaths among the ten highest-burden states. Deaths linked to fluoroquinolone-resistance, multidrug resistance, third-generation cephalosporins, and azithromycin resistance were 4700 (1800–10,200), 122 (45–294), 183 (69–431), and 183 (68–432), respectively. Interpretation Fluoroquinolone-resistance drives a large share of typhoid-related hospitalisations and deaths, especially in children under five and in high-burden states of India. Targeted TCV introduction, with broader age coverage among children, would maximise impact. Funding WISE programme ; Vaccine Impact Modelling Consortium ; Japan Agency for Medical Research and Development

Knowledge and acceptability of male HPV vaccination among young people and community stakeholders in northwest Tanzania: social sciences in the Add-Vacc trial.

INTRODUCTION: Human papillomavirus (HPV) and related diseases are global health concerns affecting both males and females. Tanzania introduced two-dose HPV vaccination for 14-year old girls in 2018. The Add-Vacc trial in rural northwest Tanzania is evaluating the impact of adding one-time, single-dose HPV vaccination for 14-18-year-old boys to the national programme for girls on HPV population prevalence. As this is the first time HPV vaccination has been offered to adolescent males in Tanzania, acceptability of boys' HPV vaccination among adolescents and community stakeholders was assessed. METHODS: Qualitative data were collected between July 2023-May 2024 through: 1) rapid ethnography; 2) rumours tracking using an electronic tool piloted during the study; 3) in-depth interviews with in- and out-of-school boys who accepted or declined vaccination; 4) key informant interviews with vaccination stakeholders including parents, teachers, health workers, and community leaders; and 5) focus group discussions with stakeholders and vaccination-age boys and girls. Data were coded using Nvivo12 and analysed thematically. RESULTS: Messaging on HPV-related complications beyond cervical cancer motivated parental and adolescent support for vaccinating both boys and girls. Framing male HPV vaccination as a gender equity issue and highlighting the economic burden of illness emerged as important themes. Participants emphasised the need for trusted, locally recognised messengers to convey information. Parents and peers were key influencers for adolescents, while health workers and religious/community leaders influenced parents. Some parents and adolescents who initially declined vaccination reported they later accepted it after having time to reflect and seeing vaccinated boys experienced no adverse effects. CONCLUSIONS: Single-dose HPV vaccination of males was generally acceptable across all study groups. Ongoing, dynamic community engagement and open dialogue about the full spectrum of HPV-related sequalae and HPV vaccination for both genders are essential to building trust and improving understanding and acceptability of HPV vaccination targeting boys and girls in this Tanzanian context

Eligibility for hepatitis B virus (HBV) treatment and prevalence of drug resistance in a Ugandan population cohort.

BACKGROUND: 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

Prescribing of high-cost targeted therapies in England is diverging by region

Objectives To examine regional variation in the prescribing of targeted therapies for chronic inflammatory disorders in England between 2019 and 2025. Study design Retrospective observational study. Methods This study analysed Secondary Care Medicines Data from all NHS hospitals in England to evaluate time-trends in prescribing rates of targeted therapies by Integrated Care Board (ICB). Results Substantial and increasing regional variation in prescribing rates for targeted therapies was observed between 2019 and 2025. The disparity between the highest and lowest prescribing ICBs increased over time, with rates ranging from 2.0 to 6.5 per 1000 people in 2019 and 3.4 to 14.2 per 1000 people in 2025. Conclusions There is marked and growing regional variation in the prescribing of targeted therapies across England. Further research should explore the reasons for this divergence to ensure equitable access to these highly effective treatments for patients with chronic inflammatory disorders, irrespective of geography