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Foetal growth in pregnant women with HIV.
Get PDFOBJECTIVE: Pregnant women with HIV (PWHIV) are at increased risk of delivering babies that are small for gestational age (SGA). We aimed to determine the foetal growth trajectories of PWHIV, compared to HIV-negative women. DESIGN: Prospective pregnancy cohort study in Soweto, South Africa, in 2013-2016. METHODS: Serial ultrasound measurements (every 5 ± 1 weeks) of foetal head circumference, biparietal diameter (BPD), abdominal circumference and femur length were obtained from less than 14 weeks' gestation to term. Multivariable linear mixed effects models were used to estimate differences in mean foetal growth measures [head circumference, BPD, abdominal circumference and femur length, and estimated foetal weight (EFW)] and mean foetal growth velocity increments (head circumference, BPD, abdominal circumference, and femur length) according to maternal HIV status. Z -scores and centiles were calculated according to the INTERGROWTH-21 st standards for foetal growth. Multivariable mixed effects logistic regression was used to examine the association of maternal HIV infection with in-utero SGA (EFW <10 th centile) and very SGA (VSGA, EFW <3 rd centile). RESULTS: Ultrasound measurements of 228 PWHIV and 384 HIV-negative pregnant women, with a median of five antenatal ultrasound scans per women, were analysed. There were no significant differences in mean foetal growth measures of head circumference [-0.37 mm, 95% confidence interval (CI) -1.46 to 0.72], BPD (0.07 mm, 95% CI -0.45 to 0.30), abdominal circumference (0.15 mm, 95% CI -1.47 to 1.17), femur length (0.04 mm, 95% CI -0.27 to 0.34) and EFW (1 g, 95% CI 0.98-1.02), and growth velocity increments for head circumference (-0.07 mm/week, 95% CI -0.24 to 0.10), BPD (-0.01 mm/week, 95% CI -0.06 to 0.04), abdominal circumference (0.19 mm/week, 95% CI -0.06 to 0.44) and femur length (0.00 mm/week, 95% CI -0.04 to 0.04) between foetuses of PWHIV and HIV-negative women. The prevalence of SGA ranged between 14.2% and 26.4% for PWHIV and between 18.5% and 24.1% for HIV-negative pregnant women during different gestation windows. There was no significant association between maternal HIV infection and in-utero SGA [adjusted odds ratio (aOR) 0.90, 95% CI 0.54-1.52] or VSGA (aOR 1.16, 95% CI 0.55-1.54). A sensitivity analysis restricted to PWHIV who received efavirenz-based antiretroviral therapy (ART) yielded results consistent with the overall analysis. CONCLUSION: Maternal HIV infection treated with ART does not appear to be associated with altered foetal growth, foetal growth velocity, or in-utero SGA, compared to HIV-negative women. Our findings support current international clinical guidelines recommending ART for PWHIV to improve maternal health and reduce vertical HIV transmission
Holistic Approaches to Zoonoses: Integrating Public Health, Policy, and One Health in a Dynamic Global Context
Get PDFZoonotic diseases pose a significant global health threat, driven by factors such as globalization, climate change, urbanization, antimicrobial resistance (AMR), and intensified human–animal interactions. The increasing interconnectedness of human, animal, and environmental health underscores the importance of the OH paradigm in addressing zoonotic threats in a globalized world. This review explores the complex epidemiology of zoonotic diseases, the challenges associated with their management, and the necessity for cross-sector collaboration to enhance prevention and control efforts. Key public health strategies, including surveillance systems, infection control measures, and community education programs, play crucial roles in mitigating outbreaks. However, gaps in governance, resource allocation, and interdisciplinary cooperation hinder effective disease management, particularly in low- and middle-income countries (LMICs). To illustrate the effectiveness of the OH approach, this review highlights successful programs, such as the PREDICT project, Rwanda’s National One Health Program, the EcoHealth Alliance, and the Rabies Elimination Program in the Philippines. These initiatives demonstrate how integrating human, animal, and environmental health efforts can enhance early detection, improve outbreak responses, and reduce public health burdens. Strengthening global health governance, enhancing surveillance infrastructure, regulating antimicrobial use, and investing in research and technological innovations are essential steps toward mitigating zoonotic risks. Ultimately, a coordinated, multidisciplinary approach is vital for addressing the dynamic challenges posed by zoonotic diseases and ensuring global health security in an increasingly interconnected world
The Use of Pictorial Recall Aids Modifies Dietary Assessment Results: Experiences from Quantitative 24-hour Dietary Recalls of Young Children in Nepal and Senegal.
Get PDFBACKGROUND: Recall bias or memory error is a known limitation of recall-based dietary assessment methods and can lead to substantial misrepresentation of diets. Pictorial recall aids have been used by various studies to mitigate recall bias, but their effect on quantitative, 4-pass 24-h dietary recall (24HR) results has not yet been measured. OBJECTIVES: This article examines uptake of pictorial recall aids among caregivers of young children in Kathmandu Valley, Nepal, and Guédiawaye Department, Senegal; describes what foods/beverages are subject to recall bias in these contexts; and assesses the effect of these recall aids on estimated dietary outcomes. METHODS: We used cross-sectional data from 24HR surveys that provided a recall aid to reduce caregiver recall bias. Young children's dietary outcomes were calculated from the 24HR data. Logistic regressions were used to compare characteristics and estimated dietary outcomes of children by recall aid uptake. McNemar's test and paired t-tests were used to compare estimated dietary outcomes in initial 24HR data with revised 24HR data that incorporated omitted items identified by the recall aid. RESULTS: Pictorial recall aids had relatively high uptake by caregivers in both contexts. Beverages, unhealthy snacks, and fruit were most subject to recall bias. Adding omitted items identified by recall aids resulted in statistically significant changes in most dietary outcomes assessed. Children of caregivers who chose to use the recall aid had significantly different estimated dietary outcomes than children of caregivers who did not use the recall aid. CONCLUSIONS: The use of pictorial recall aids modifies 24HR results in these 2 contexts. Rigorous research is needed to fully understand the impact of recall aids on 24HR methodology and results, with an aim to improve the accuracy of dietary assessment and ultimately inform evidence-based nutrition programming, policy, and recommendations
Protocol for an adaptive platform trial of intended service user-derived interventions to equitably reduce non-attendance in eye screening programmes in Botswana, India, Kenya and Nepal.
Get PDFINTRODUCTION: Only 30%-50% of people referred to clinics during community-based eye screening are able to access care in Botswana, India, Kenya and Nepal. The access rate is even lower for certain population groups. This platform trial aims to test multiple, iterative, low-risk public health interventions and simple service modifications with a series of individual randomised controlled trials (RCT) conducted in each country, with the aim of increasing the proportion of people attending. METHODS AND ANALYSIS: We will set up a platform trial in each country to govern the running of a series of pragmatic, adaptive, embedded, parallel, multiarm, superiority RCTs to test a series of service modifications suggested by intended service users. The aim is to identify serial marginal gains that cumulatively result in large improvements to equity and access. The primary outcome will be the probability of accessing treatment among the population group with the worst access at baseline. We will calculate Bayesian posterior probabilities of clinic attendance in each arm every 72 hours. Each RCT will continually recruit participants until the following default stopping rules have been met: >95% probability that one arm is best; >95% probability that the difference between the best arm and the arms remaining in the trial is <1%; or 10 000 people have been recruited. Lower thresholds may be used for RCTs testing interventions with very low risks and costs. The specific design of cluster RCTs will be determined by our research team once the intervention is known, but the population and outcome will be the same across all trials.This adaptive platform trial will be used to identify effective service modifications, driving continuous improvements in access. ETHICS AND DISSEMINATION: This trial has been approved by the research ethics committee at the London School of Hygiene & Tropical Medicine (ref: 29549). Approvals for individual interventions will be sought from UK and local ethics committees. Results will be shared via local workshops, social media and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN53970958
Durability of immunogenicity at 5 years after a single dose of human papillomavirus vaccine compared with two doses in Tanzanian girls aged 9-14 years: results of the long-term extension of the DoRIS randomised trial.
Get PDFBACKGROUND: WHO has recommended that one dose of human papillomavirus (HPV) vaccine can be given to individuals aged 9-20 years to prevent HPV infection. Estimating durability of immune responses after a single dose in the target age for vaccination is important. We report immunogenicity results in Tanzanian girls up to 5 years after receiving a dose.
METHODS: In this open-label, randomised controlled trial (the Dose Reduction Immunobridging and Safety Study of Two HPV Vaccines in Tanzanian Girls [DoRIS] trial), 930 Tanzanian schoolgirls aged 9-14 years were enrolled and randomly allocated to receive one, two, or three doses of either the two-valent vaccine (Cervarix; GSK, Wavre, Belgium) or nine-valent vaccine (Gardasil-9; Merck Sharp & Dohme, Haarlem, Netherlands). Seropositivity specific to HPV16 or HPV18, antibody geometric mean concentrations (GMCs), and antibody avidity were measured annually up to month 36. Participants in the one-dose and two-dose groups were followed annually in a long-term extension of the DoRIS trial to month 60; the primary outcome was seropositivity specific to HPV16 or HPV18 comparing one dose with two doses.
FINDINGS: Single-dose seropositivity for HPV16 IgG antibodies at month 60 with either vaccine was more than 99% and non-inferior to two doses. 98% of girls in the one-dose two-valent vaccine group and 93% in the one-dose nine-valent group were seropositive for HPV18 at month 60; however, the non-inferiority criteria for HPV18 seropositivity comparing one dose with two doses were not met. Although HPV16 and HPV18 antibody GMCs after one dose were lower than those observed after two doses, antibody GMCs in the one-dose groups remained stable from month 12 to month 60. There was no evidence of a difference between the one-dose and two-dose groups in HPV16 or HPV18 antibody avidity at month 36 for either vaccine.
INTERPRETATION: A single dose of HPV vaccine in girls aged 9-14 years continues to provide stable immune responses 5 years after vaccination, although ongoing surveillance for potential waning immunity after a single dose is needed. Participants are being followed up to 9 years after vaccination.
FUNDING: UK Department of Health and Social Care, UK Foreign, Commonwealth & Development Office, Global Challenges Research Fund, UK Medical Research Council, and the Wellcome Trust through the Joint Global Health Trials Scheme; Bill & Melinda Gates Foundation
Cardiac Troponins and Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.
No full textBACKGROUND: The extent to which high-sensitivity cardiac troponin can predict cardiovascular disease (CVD) is uncertain. OBJECTIVES: We aimed to quantify the potential advantage of adding information on cardiac troponins to conventional risk factors in the prevention of CVD. METHODS: We meta-analyzed individual-participant data from 15 cohorts, comprising 62,150 participants without prior CVD. We calculated HRs, measures of risk discrimination, and reclassification after adding cardiac troponin T (cTnT) or I (cTnI) to conventional risk factors. The primary outcome was first-onset CVD (ie, coronary heart disease or stroke). We then modeled the implications of initiating statin therapy using incidence rates from 2.1 million individuals from the United Kingdom. RESULTS: Among participants with cTnT or cTnI measurements, 8,133 and 3,749 incident CVD events occurred during a median follow-up of 11.8 and 9.8 years, respectively. HRs for CVD per 1-SD higher concentration were 1.31 (95% CI: 1.25-1.37) for cTnT and 1.26 (95% CI: 1.19-1.33) for cTnI. Addition of cTnT or cTnI to conventional risk factors was associated with C-index increases of 0.015 (95% CI: 0.012-0.018) and 0.012 (95% CI: 0.009-0.015) and continuous net reclassification improvements of 6% and 5% in cases and 22% and 17% in noncases. One additional CVD event would be prevented for every 408 and 473 individuals screened based on statin therapy in those whose CVD risk is reclassified from intermediate to high risk after cTnT or cTnI measurement, respectively. CONCLUSIONS: Measurement of cardiac troponin results in a modest improvement in the prediction of first-onset CVD that may translate into population health benefits if used at scale
Sex Differences in Acute Coronary Syndromes: A Scoping Review Across the Care Continuum.
Get PDFINTRODUCTION: Optimal diagnosis and management of acute coronary syndrome (ACS) is essential to improve clinical outcomes and prognosis. Sex disparities in ACS care have been reported in the literature, but evidence gaps remain. This review aims to map and to summarize the global evidence on sex differences in the provision of care across the ACS continuum. METHODS: A systematic literature search was conducted in Pubmed, EMBASE, and the World Health Organization Global Index Medicus. The search was restricted to original research articles published between January 1, 2013, and August 30th, 2023, and with a full-text available in English, Spanish, Dutch, or French. The search terms and key words covered five aspects of the ACS care continuum: pre-hospital care, diagnosis, treatment, in-hospital events, and discharge. RESULTS: Of the 15,033 identified articles, 446 articles (median percentage of women per study: 29%), reporting on 1,483 outcomes, were included. Most studies were conducted in high-income regions (65%). Studies reported on pre-hospital care (8%), diagnosis (9%), treatment (45%), discharge (14%) and events (24%). For 45% of outcomes, results favored men, 5% favored women, and 50% showed mixed results or no sex difference. ACS care aspects with the largest sex differences were pre-hospital care (58% of the outcomes favored men vs 7% favored women) and diagnosis (70% favored men vs 2% favored women). CONCLUSION: Studies on sex differences in ACS mainly come from high-income regions. Sex differences in ACS management are widely reported and mainly unfavorable to women, especially in the early phases of pre-hospital care and diagnosis
Challenges associated with dapsone for leprosy treatment in Indonesia - urgent need for access to alternative antimicrobial drugs.
Get PDFLeprosy is effectively treated with multi-drug therapy (MDT), a regimen containing three antibiotic drugs, including dapsone - a sulfone drug associated with potentially life-threatening adverse drug reactions. Specifically, dapsone hypersensitivity syndrome (DHS), linked to HLA-B∗13:01 polymorphism, and hemolytic anemia associated with glucose-6-phosphate dehydrogenase deficiency (G6PDd). Both of these pharmacogenetic polymorphisms can be prevented through diagnostic screening before MDT initiation averting potential complications. However, in leprosy-endemic areas like Indonesia, access to these tests often remains inaccessible due to high costs and limited laboratory capacity. Additionally, alternative dapsone-sparing treatment regimens are usually unavailable or unaffordable, restraining individuals onto suboptimal dual-therapy with rifampicin and clofazimine, which has uncertain efficacy. We raise concerns regarding the safety of dapsone-containing MDT without routine pharmacogenetic screening and the unavailability of alternative regimens. We call for action to address persisting global health inequities in care delivery, ensuring all individuals receive the safest and most effective leprosy treatment options
Effects of azithromycin in young adults with cystic fibrosis: a protocol for emulating a published randomised controlled trial using registry data.
Get PDFINTRODUCTION: Target trial emulation is a framework for evaluating the effects of treatments using observational data. The trial emulation approach involves specifying key elements of a protocol for a target trial (a randomised controlled trial designed to address the question of interest) and then describing how best to emulate the trial using observational data. Recent years have seen an uptake of target trial emulation in several disease areas, although there are limited examples in cystic fibrosis (CF). This protocol describes a study which aims to assess the applicability of target trial emulation in CF. We aim to emulate an existing trial in CF and assess to what extent the results from the trial can be replicated using registry data. METHODS AND ANALYSIS: The target trial is a published randomised controlled trial which found evidence for beneficial effects of azithromycin use on lung function in young adults with CF. Two emulated trials are planned: one using data from the UK CF Registry and one using data from the US CF Registry. The inclusion and exclusion criteria, treatment and outcome definitions, follow-up period, and estimand of interest are all designed to match the published trial as closely as possible. The analysis step of the trial emulations will use causal inference methods to control for confounding. Results obtained in the emulated trials using registry data will be compared with those from the target trial. ETHICS AND DISSEMINATION: Ethical approval has been granted by the London School of Hygiene and Tropical Medicine Ethics Committee (Ref: 29609). This study has also been approved by the UK CF Registry Research Committee and the North Star Review Board. The results of this study will be published in a peer-reviewed journal and presented at relevant scientific conferences
Effect of long-term azithromycin treatment on gut microbial diversity in children and adolescents with HIV-associated chronic lung disease.
Get PDFBACKGROUND: HIV-associated chronic lung disease (HCLD) is common in children and adolescents growing up with HIV. The use of azithromycin (AZM) reduces the rate of acute respiratory exacerbations in this population, however, impact of this treatment on the gut microbiota and associations with blood-derived inflammatory markers have not been studied. METHODS: Children and adolescents with HCLD in Harare, Zimbabwe and Blantyre, Malawi were recruited in a double-blind, placebo-controlled trial of once-weekly AZM or placebo for 48 weeks (BREATHE trial, NCT02426112). Rectal swabs were collected at inclusion (N = 346), 48 weeks (treatment end, N = 313), and 72 weeks (six months after treatment cessation, N = 244). The bacterial composition of fecal swabs was determined using 16S rRNA gene sequencing. Plasma biomarkers at inclusion and 48 weeks were measured using Luminex multiplex bead assay. FINDINGS: At 48 weeks, bacterial α-diversity was significantly lower in the AZM group, with 27 bacterial genera showing differential abundance between the study groups. The placebo group exhibited higher interconnectivity between bacterial genera at 48 weeks compared to the AZM group. Correlations between the top seven differentially abundant genera and biomarkers observed at inclusion were no longer significant at 48 weeks in both groups. Depletion of Campylobacter persisted for six months after cessation of AZM treatment. INTERPRETATION: Long-term AZM treatment in HCLD patients affects their gut bacterial composition at least 6 months after its cessation. The consequences of reduced bacterial diversity, such as altered interaction with the immune system and risk of resistance, need further investigation to understand how to optimise gut health during long-term antibiotic treatments. FUNDING: The study was funded by the Norwegian Research Council and Helse Nord (HNF 1387-17)