London School of Hygiene & Tropical Medicine

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    Geographical Differences in SARS-CoV-2 Antibody Response Dynamics and Neutralisation Profiles to Mild COVID-19: Lessons from a UK-Uganda Comparison.

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    Background: The global SARS-CoV-2 pandemic revealed stark variability in clinical outcomes across populations, underscoring the need for region-tailored vaccination strategies. To inform standardised global immunisation efforts, this study compared longitudinal binding antibody responses and neutralisation capacities in mild COVID-19 cases from Uganda and the United Kingdom (UK). Methods: IgG responses to spike (S) and nucleocapsid (N) proteins, along with IgM responses to S and receptor-binding domain (RBD) proteins, were assessed in 29 Ugandan and 14 UK participants over 84 and 82 days, respectively. Antibody levels were quantified using a validated enzyme-linked immunosorbent assay (ELISA), alongside pseudovirus neutralisation assays targeting the D614G variant. Results: Ugandan participants exhibited higher early IgG and IgM levels, particularly against spike and RBD, with a rapid onset of responses that waned quickly. UK participants showed a slower but sustained increase in IgG and IgM levels. Neutralisation titres revealed elevated responses in 16.4% of Ugandan participants (>2000) compared to 4.5% of UK participants, suggesting a greater sensitivity to viral neutralisation. Conversely, 31.8% of UK participants exhibited low titres (<25) compared to 14.8% of Ugandan participants, indicating differences in resistance mechanisms. Neutralisation correlated strongly with spike and receptor-binding domain IgG in the UK cohort but showed weaker correlations in Ugandan participants. Conclusions: These findings highlight distinct population-level immune responses, suggesting that geographic factors shaped the quality and durability of SARS-CoV-2 immunity. Tailored vaccination strategies are essential to optimise immunity across diverse populations and improve global epidemic preparedness

    The future of nephrology in 2050.

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    As medicine advances at an unprecedented pace, the field of nephrology is poised for transformative change. By 2050, breakthroughs in kidney disease prevention, dialysis, transplantation, and omics-driven precision medicine could redefine patient care and outcomes. Here, we share our perspectives on the challenges faced and how changes in health policy, emerging technologies, novel therapies, and data-driven approaches might shape the future of nephrology. From innovative dialysis solutions to xenotransplantation and AI-powered diagnostics, we explore the possibilities that could revolutionise kidney health in the decades to come

    Barriers to Skin Cancer Diagnosis and Treatment in Low- and Middle-Income Countries and Solutions: A Literature Review.

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    Skin cancer mortality disproportionately affects low- and lower-middle-income regions despite the prevalence being lower than in high-income countries. Considering the need to diagnose it early for the best outcomes, this review addresses the barriers preventing it from being diagnosed and treated promptly and proposes possible solutions. Some of the barriers we found include the low number of dermatologists and pathologists, inadequate facilities, lack of education, the cost of healthcare, the denial of needing professional help, the fear and stigmatization of a skin cancer diagnosis, and the reliance on non-medical therapies. Meanwhile, solutions we identified are training programs for healthcare professionals and the public, technological advancements (including nanotechnology-based treatments, telemedicine, and social media use, the development and implementation of artificial intelligence programs), international collaborations, research, and increasing the number of cancer registries and national cancer control plans. Despite these solutions not being foolproof, they will lead to earlier cancer diagnosis, more individuals seeking skin check-ups, better knowledge of skin cancer, improving the quality of life of vulnerable populations, and decrease in mortality

    Foetal growth in pregnant women with HIV.

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    OBJECTIVE: 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

    Distribution, Risk Factors and Epidemiological Trends of Pancreatic Cancer Across Countries' Income Levels: A Comprehensive Analysis.

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    BACKGROUND: Globally, pancreatic cancer poses a significant concern for public health. AIMS: The objective of this study was to assess the burden of pancreatic cancer on varying income levels. METHODS AND RESULTS: Data from the Global Burden of Disease Study (GBD) 2021 and Gross Domestic Product Per Capita data were utilised in this study. All countries were categorised into four groups based on their income levels. Age-standardised incidence, mortality and disability-adjusted life years (DALYs) rates were the primary parameters to analyse the burden of pancreatic cancer. The associations between pancreatic cancer burden and countries' economic levels were analysed with linear regression models. High-income-level countries generally had a higher burden compared to other income levels in 2021. Greenland had the highest rate of age-standardised DALYs at 374.93 per 100 000, followed by Uruguay (297.06) and Monaco (290.87). A higher gross domestic product (GDP) per capita was linked to a higher age-standardised incidence (β = 0.77, 95% CI = 0.63, 0.90, p < 0.001), mortality (β = 0.72, 95% CI = 0.59, 0.86, p < 0.001) and DALYs (β = 14.59, 95% CI = 11.38, 17.80, p < 0.001). From 1990 to 2021, the pancreatic cancer burden increased across all income levels, with the most pronounced rise seen in lower-middle-income countries. Smoking-related age-standardised DALYs have decreased since 1990. However, there was a notable increase in males in upper-middle-income countries during the same period. CONCLUSION: In conclusion, the pancreatic cancer burden has been increasing globally. The burden of pancreatic cancer varies significantly among countries with different income levels. Effective preventions are needed to control the burden of pancreatic cancer

    A global living systematic review and meta-analysis hub of emerging vaccines in pregnancy and childhood.

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    The COVID-19 pandemic accelerated vaccine development and generated a rapidly evolving body of evidence before and after the vaccine rollout. We developed a robust online platform to efficiently synthesize this emerging information for current and future challenges. Expanding upon our interactive living systematic review-initially focused on COVID-19- we now include chikungunya and Lassa fever (with protocols presented in this issue), Mpox, and Disease X ( https://www.safeinpregnancy.org ). We aim to continuously monitor and periodically update and disseminate high-quality data on vaccine safety, efficacy, effectiveness, and immunogenicity in pregnancy and childhood. This platform computes real-time meta-analyses and features a visualization tool to present findings in a clear and accessible manner, supporting decision-making, vaccine development pipelines, and implementation strategies worldwide. It is also designed to integrate data on a hub of emerging vaccines in pregnancy and childhood and reflects a collaborative effort among multiple organizations

    The association between residential segregation and stillbirths in Brazil-a cross-sectional study.

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    BACKGROUND: Segregation is the degree to which two or more groups live separately. While US research has linked segregation to increased stillbirth risk, studies from Latin America have yet to explore this. This study investigated the association between the racial and income segregation index (SI) and stillbirth prevalence in Brazil. METHODS: We used nationwide birth data from Brazil in 2018 (live births from Live Birth Information System, SINASC, and stillbirths from Mortality Information System, SIM). Income and racial SI were calculated using the 2010 national census and analyzed as quintiles with the least segregated group as the reference. Odds ratios were calculated using a logistic regression model, adjusting for infant sex, maternal age, education, previous fetal loss, and the municipal level percentage of the population earning less than half the minimum wage. The sub-analysis was stratified by city size, area-level stillbirth prevalence, and stillbirth type (intrapartum or antepartum). RESULTS: Two million seven hundred seventy-one thousand two hundred seventy-two live-born and stillborn in 2018 were included in the analysis. Women in municipalities with high income and racial SI were older, had more education, and had more previous fetal loss. Women in municipalities with the highest income SI had a 25.1% higher risk of delivering a stillbirth (95% CI: 1.202-1.303). Those in the highest racial SI municipalities had a 5.5% lower risk of delivering a stillbirth compared to those in the quintile with the lowest racial SI (95% CI: 0.908-0.984). In regions with low stillbirth prevalence, a dose-response relationship was observed between income segregation and stillbirth, with the risk of stillbirth among those with the highest income SI being more than twice that of the least segregated (OR 2.086, 95% CI: 1.494-2.911). In larger cities, racial and income segregation were associated with reduced odds of stillbirth. The effect of income SI was larger for intrapartum stillbirths. CONCLUSIONS: We observed that income segregation increases the odds of stillbirth, especially in municipalities with low stillbirth prevalence, while the association for racial segregation was less consistent

    Consensus on Adolescent and Young Adult HIV Research Consent in Low- and Middle-Income Countries.

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    IMPORTANCE: Many adolescents and young adults (AYAs) in low- and middle-income countries (LMICs) are excluded from HIV research because of challenges with informed consent for study participation, which makes it difficult to understand and improve the lives of AYAs living with HIV and AIDS in a wide variety of settings. OBJECTIVE: To help increase the inclusion of AYAs in HIV research, we developed a consensus statement on practical strategies for improving AYA consent in HIV research in LMICs. EVIDENCE REVIEW: The VOICE (HIV Youth Informed Consent & Ethics in Research) Working Group included AYAs, researchers, community organizers, advocates, research ethics committee members, parents of AYAs, and bioethicists who drafted initial statement items using data from a global open call and scoping review. An adapted Delphi process was then used to develop consensus statement items. The process involved 3 rounds of online Likert-scale questionnaires and a hybrid (online and in-person) consensus summit in Lagos, Nigeria, in 2022, with the total study period lasting from August 23, 2021, to February 10, 2023. FINDINGS: Thirty-five people participated in the final round of the Delphi process, including 14 individuals younger than 35 years (40.0%), 25 HIV researchers (71.4%), and 32 people who worked in an LMIC (91.4%). Twenty-five items reached a predefined threshold for consensus (≥80% agreement). Strong consensus emerged for formal mechanisms (eg, cocreation, crowdsourcing, or youth advisory boards) for AYA engagement in and education about research as well as for strategies to enhance parental and guardian involvement in HIV research when safe and appropriate. Capacity strengthening can allow AYAs to review research protocols, join ethical review committees, and advocate for regulatory change. Two items in the statement (alternatives to parental consent and raising awareness among research ethics committees about AYA-independent consent) required further refinement to reach the agreement threshold for inclusion. CONCLUSIONS AND RELEVANCE: Greater engagement of both AYAs and parents may help to enhance consent processes and increase the inclusion of AYAs in LMIC HIV research studies. The resulting consensus statement provides practical strategies for implementing improved consent processes for AYA research participation at the organizational, community, and policy levels, which may help foster greater inclusion of AYAs in HIV research and address existing data gaps

    Effect of a novel house design (star home) on indoor malaria mosquito abundance in rural Tanzania: secondary outcomes of an open-label, household, randomised controlled trial.

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    BACKGROUND: Screening houses can reduce malaria transmission in sub-Saharan Africa. Our study evaluated whether a novel screened house design (star home) with bedrooms on the second storey reduced indoor mosquito abundance compared with traditional houses in Mtwara, Tanzania. METHODS: In this open-label, household, randomised controlled trial, indoor mosquito abundance was assessed in 110 star homes and 110 neighbouring traditional houses in 59 villages from Jan 5, 2022, to Dec 20, 2023. Mosquitoes were collected using US Centers for Disease Control light traps every 7 weeks. Anopheles gambiae and Anopheles funestus species were identified using PCR and Plasmodium falciparum sporozoites detected using ELISA. Nightly temperature, CO2 concentrations, and duration of door opening was recorded. Differences between study groups were analysed using generalised linear mixed-effects models. The trial is registered with ClinicalTrials.gov (NCT04529434). FINDINGS: Of 9290 mosquitoes collected, 1899 were A gambiae, 69 were A funestus, and 7322 Culex species, mainly Culex quinquefasciatus. Star homes had 51% less A gambiae (adjusted risk ratio [RR] 0·49, 95% CI 0·35 to 0·69; p<0·0001) and 61% less Culex species (RR 0·39, 0·32 to 0·48; p<0·0001) than traditional houses. At night, star homes were 0·5°C cooler (95% CI 0·2 to 0·9; p=0·010), with similar concentrations of CO2 (-7 ppm, 95% CI -19 to 6; p=0·285) and had external doors open 53% less time than traditional houses (7·5 min/h vs 16·2 min/h; p<0·0001). INTERPRETATION: Star homes reduced indoor mosquito abundance and malaria transmission risk compared with traditional houses, demonstrating the protective efficacy of houses that are well screened and air permeable in rural Africa. FUNDING: Hanako Foundation, Singapore

    First referral hospitals in low-resource settings: a narrative review of expectations for clinical service provision.

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    First referral hospitals (FRHs) have an important role to play in helping many countries achieve 'Health for All'. However, their specific role and the clinical services they are expected to provide to achieve this are evolving. To explore this issue further, we undertook a narrative review to examine the clinical service expectations of FRHs outlined in academic and policy literature, which identified a total of 404 FRH service expectations. At a global level, some categories of services provide extensive specific service recommendations, likely resulting from historical priorities and the influence of vertical programming and professional interests. However, in several important areas we identified few or no recommendations. At the level of individual country case studies undertaken through this review, FRH clinical service recommendations within available policy documents vary considerably. Our findings suggest a disconnect between the ambition for FRH and the difficult, context-specific decision-making needed at the national level on the role of FRHs as a service delivery platform within integrated health systems helping countries achieve universal health coverage

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