London School of Hygiene & Tropical Medicine

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    Acute kidney injury does not explain sex differences in kidney replacement therapy initiation or death amongst individuals with chronic kidney disease reported to the UK Renal Registry.

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    BACKGROUND: Why more males than females start kidney replacement therapy (KRT) is incompletely understood. Acute kidney injury (AKI) is a possible factor underlying sex differences in chronic kidney disease (CKD) progression, but previous studies regarding this have been inconclusive. We investigated sex differences in the association between AKI and CKD progression in UK nephrology care. METHODS: This cohort study uses UK Renal Registry data. Adults with CKD stages 4/5 in 14 nephrology centres in England were followed from January 2018 to December 2021. We compared their baseline characteristics by sex and calculated cause specific hazard ratio (HR) for outcomes: time to AKI stage 2/3 (AKI2/3), initiation of chronic KRT and death by all causes. RESULTS: A total of 15 547 patients were included. Fewer females (43.8%) were seen in renal centres than males (56.2%). During follow-up, 3909 (25.1%) AKI2/3 episodes, 3510 (22.6%) KRT initiations, and 7293 (46.9%) deaths were observed. Males were more likely than females to experience each outcome: AKI2/3 [adjusted HR 1.39, 95% confidence interval (CI) 1.31-1.49], KRT initiation (adjusted HR 1.51, 95% CI 1.39-1.65) and death (adjusted HR 1.11, 95% CI 1.05-1.16). Adjustment for AKI2/3 did not change the association between being male and the higher risk of KRT initiation. CONCLUSION: Being male was associated with a higher risk of AKI2/3, KRT initiation and death. Fewer females appeared in nephrology care data than expected from population CKD prevalence. However, no evidence was found to support the hypothesis that AKI2/3 explains the higher KRT initiation rates seen amongst males

    Urban Aedes aegypti suitability indicators: a study in Rio de Janeiro, Brazil.

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    BACKGROUND: Controlling Aedes aegypti stands as the primary strategy in curtailing the global threat of vector-borne viral infections such as dengue fever, which is responsible for around 400 million infections and 40 000 fatalities annually. Effective interventions require a precise understanding of Ae aegypti spatiotemporal distribution and behaviour, particularly in urban settings where most infections occur. However, conventionally applied sample-based entomological surveillance systems often fail to capture the high spatial variability of Ae aegypti that can arise from heterogeneous urban landscapes and restricted Aedes flight range. METHODS: In this study, we aimed to address the challenge of capturing the spatial variability of Ae aegypti by leveraging emerging geospatial big data, including openly available satellite and street view imagery, to locate common Ae aegypti breeding habitats. These data enabled us to infer the seasonal suitability for Ae aegypti eggs and larvae at a spatial resolution of 200 m within the municipality of Rio de Janeiro, Brazil. FINDINGS: The proposed microhabitat and macrohabitat indicators for immature Ae aegypti explained the distribution of Ae aegypti ovitrap egg counts by up to 72% (95% CI 70-74) and larval counts by up to 74% (72-76). Spatiotemporal interpolations of ovitrap counts, using suitability indicators, provided high-resolution insights into the spatial variability of urban immature Ae aegypti that could not be captured with sample-based surveillance techniques alone. INTERPRETATION: The potential of the proposed method lies in synergising entomological field measurements with digital indicators on urban landscape to guide vector control and address the prevailing spread of Ae aegypti-transmitted viruses. Estimating Ae aegypti distributions considering habitat size is particularly important for targeting novel vector control interventions such as Wolbachia. FUNDING: German Research Foundation and Austrian Science Fund

    Malaria parasites undergo a rapid and extensive metamorphosis after invasion of the host erythrocyte.

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    Within the human host, the symptoms of malaria are caused by the replication of malaria parasites within erythrocytes. Growth inside the erythrocyte exposes the parasites to the normal surveillance of erythrocytes by the host organism, in particular the clearance of erythrocytes in the spleen. Here we show that the malaria parasite Plasmodium falciparum undergoes a rapid, multi-step metamorphosis that transforms the invasive merozoite into an amoeboid-shaped cell within minutes after invading erythrocytes. This transformation involves an increase in the parasite surface area and is mediated by factors already present in the merozoite, including the parasite phospholipid transfer protein PV6. Parasites lacking PV6 do not assume an amoeboid form and instead are spherical and have a smaller surface area than amoeboid forms. Furthermore, erythrocytes infected with P. falciparum parasites lacking PV6 undergo a higher loss of surface area upon infection, which affects the traversal of infected erythrocytes through the spleen. This is the first evidence that after invasion, the parasite undergoes a rapid, complex metamorphosis within the host erythrocyte that promotes survival in the host

    Why the growth of arboviral diseases necessitates a new generation of global risk maps and future projections.

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    Global risk maps are an important tool for assessing the global threat of mosquito and tick-transmitted arboviral diseases. Public health officials increasingly rely on risk maps to understand the drivers of transmission, forecast spread, identify gaps in surveillance, estimate disease burden, and target and evaluate the impact of interventions. Here, we describe how current approaches to mapping arboviral diseases have become unnecessarily siloed, ignoring the strengths and weaknesses of different data types and methods. This places limits on data and model output comparability, uncertainty estimation and generalisation that limit the answers they can provide to some of the most pressing questions in arbovirus control. We argue for a new generation of risk mapping models that jointly infer risk from multiple data types. We outline how this can be achieved conceptually and show how this new framework creates opportunities to better integrate epidemiological understanding and uncertainty quantification. We advocate for more co-development of risk maps among modellers and end-users to better enable risk maps to inform public health decisions. Prospective validation of risk maps for specific applications can inform further targeted data collection and subsequent model refinement in an iterative manner. If the expanding use of arbovirus risk maps for control is to continue, methods must develop and adapt to changing questions, interventions and data availability

    Disentangling the contributions of anthropogenic climate change, greenhouse gases, and aerosols to heat-related mortality in Great Britain: a climate change impact attribution study.

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    BACKGROUND: Anthropogenic aerosols are a critical contributor to climate change and their net cooling effects can partially counter the warming effects of greenhouse gases, but they are rarely considered in health impact attribution studies of climate change. The aim of this study was to attribute heat-related deaths in Great Britain to anthropogenic climate change and individual forcings of greenhouse gases and aerosols. METHODS: Using a special suite of climate simulations, past and future heat-related deaths in Great Britain attributable to the relative contributions of anthropogenic greenhouse gas and aerosol forcings were estimated under the Shared Socioeconomic Pathway SSP2-4.5. Empirical confidence intervals were quantified combining uncertainties from climate models and health risk functions. FINDINGS: Emergence of heat-related mortality associated with anthropogenic climate change was partially counteracted by the cooling effects of aerosols, with the time of emergence being approximately four decades later compared with the greenhouse gas-only simulation. We estimate that around 700 annual heat-related deaths during 1961-1980 were masked by the cooling effects of aerosols. There was a sharp increase in heat-deaths between 1980 and 2020 due to the combined effects of greenhouse gas increases and large aerosol reductions. By the end of the 21st century, a 2-6-fold increase in heat-related deaths due to greenhouse gases is projected, with a negligible counteracting contribution of aerosols. INTERPRETATION: In addition to greenhouse gases, the potential contributions of aerosols should be considered when assessing climate change risks and mitigation pathways. This is crucial due to their opposing temperature effects, diverging future emission trajectories, and varying geographical scales. Separate attribution of climate change impacts to the global effects of greenhouse gases and local effects of aerosols can enhance transparency and equity, and can inform loss and damage funding models. Such impact attribution assessments can help to optimise health co-benefits and prevent unintended negative consequences of environmental policies on heat-related and air pollution-related health outcomes. FUNDING: Health Protection Research Unit in Environmental Change and Health, National Institute for Health and Care Research

    The impact of violence and COVID-19 on Mexico's life-expectancy losses and recent bounce-back, 2015-22.

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    BACKGROUND: Before the COVID-19 pandemic, life expectancy in Mexico stagnated from the early 2000s, mainly due to increased homicides. During the pandemic, Mexico experienced sizable excess mortality. We aimed to assess the contribution of violence, COVID-19, and causes of death that were amenable to healthcare to life-expectancy changes between 2015 and 2022 in Mexico. METHODS: We used administrative mortality and adjusted population estimates to construct life tables. We applied demographic methods to untangle contributions of causes of death to life-expectancy changes by year and sex at the subnational level. RESULTS: Between 2015 and 2019, life expectancy declined from 71.8 to 71.1 years for males and stagnated at 77.6 years for females. Violence among young males explains most of the decline (54.3%). Between 2019 and 2020, life expectancy decreased by 7.1 and 4.4 years for males and females, respectively. COVID-19 accounted for 55.4% of that change for males and 57.7% for females. In 2021, male life expectancy stagnated but continued to decline for females by 0.44 years due to COVID-19 deaths. In 2022, we observed unequal recovery patterns in life expectancy across regions, as northern states experienced larger improvements than central and southern states. CONCLUSION: We documented large variations in life-expectancy losses across Mexican states before, during, and after the COVID-19 pandemic. Before the pandemic, violence accounted for most of the male life-expectancy losses. During the pandemic, following COVID-19 deaths, mortality due to diabetes and causes that were amenable to healthcare contributed considerably to observed losses, with an uneven impact on the sexes

    Point-of-care ultrasound reveals extensive pathology in Gabonese preschool-age children with urogenital schistosomiasis.

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    BACKGROUND: Historically, urinary tract pathology caused by S. haematobium infection was thought to affect predominantly school-age children (SAC) and adults. Increasing availability of ultrasound data from endemic areas demonstrates that even younger children develop potentially irreversible pathology. METHODOLOGY/PRINCIPAL FINDINGS: Point-of-care ultrasound for urinary schistosomiasis and urine microscopy were performed across age groups in 105 patients with symptomatic urogenital schistosomiasis in Lambaréné, Gabon. Of 96 ultrasound scans with sufficient image quality, bladder wall thickening > 5mm was found in 9/20 (45%) preschool-age children (PSAC), 29/51 (57%) SAC and 7/25 (28%) adults. Upper urinary tract pathology was found in 19/90 (21%) patients across age groups, up from three years of age. Urine egg counts were highest in PSAC, with high-intensity infection (≥ 50 eggs/10 ml urine) in 19/24 (79%) and hyper-infection (≥ 500 eggs/10 ml urine) in 10/24 (42%). Bladder wall thickening > 5mm and upper urinary tract pathology correlated significantly with high-intensity infection with crude odds ratios of 8.6 (95% CI 3.1-23.8; p<0.001) and 6.6 (95% CI 1.4-30.7; p=0.02), respectively. Three months after praziquantel treatment, parasitology showed a cure rate of 51% and egg reduction rate of 95%, while bladder wall thickening and upper urinary tract pathology persisted in 12/41 (29%) and 7/12 (58%) patients. CONCLUSIONS/SIGNIFICANCE: A high proportion of PSAC in areas endemic for urogenital schistosomiasis already have detectable urinary tract pathology. Our findings highlight the urgent need to include this age group in mass drug administration programs, as recommended now by WHO. Further, particular attention should be paid to individual patient care

    The Association Between Women's Perception of Birth During the Pandemic, Companion of Choice and Support From Health Professionals: A Cross-Sectional Study in 20 Countries in the WHO European Region.

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    BACKGROUND: Mitigation measures implemented in response to the COVID-19 pandemic led to significant changes in maternity care across Europe, including restrictions on companions during labor and birth. This cross-sectional study explores the association between the presence of a companion of choice and a positive perception of the birth experience. Additionally, it explores the association between health professionals' attention, assistance, and availability during labor and birth and a positive perception of birth. METHODS: We utilized a structured, validated online questionnaire, available in 25 languages, to assess the quality of maternal care during the COVID-19 pandemic from women's perspectives. We conducted logistic regression to explore associations between variables related to the presence of a companion of choice, health professionals' attention, assistance, and availability, and positive perceptions of birth, when controlled for confounders, including birth mode and medical interventions. RESULTS: Responses from 48,039 women across 20 countries in the WHO European Region were included. Always having a companion of choice during birth (aOR: 2.11) and always receiving adequate care from health professionals (assistance aOR: 2.12, attention aOR: 36.64, availability aOR: 2.12) were associated with positive birth perception. Instrumental births (aOR: 0.76), episiotomies (aOR: 0.74), fundal pressure (aOR: 0.52), and cesarean births (planned aOR: 0.80, unplanned prelabor aOR: 0.60, unplanned in-labor aOR: 0.52) were associated with less positive birth perceptions. DISCUSSION: This study highlights the critical role of having a chosen companion and receiving adequate attention, assistance, and availability from health professionals in promoting positive birth perceptions, even in times of crisis such as the COVID-19 pandemic. Ensuring the presence of a companion of choice and comprehensive professional support is crucial for delivering high-quality, respectful maternity care

    Preferential transmission of minority and drug-resistant clones in polyclonal infections in Mali.

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    BACKGROUND: In polyclonal human malaria infections, the roles of individual clones in human-to-mosquito transmission and their relative transmissibility remain poorly understood. In addition, mutations conferring drug resistance can result in a transmission advantage or disadvantage. METHODS: Amplicon sequencing of complexity of infection and drug resistance markers was used to analyse post-treatment stage-specific malaria parasite dynamics in human blood infections and in the midguts of mosquitoes that became infected after direct membrane feeding assays (DMFAs). Blood samples originated from 50 asymptomatic Plasmodium falciparum gametocyte-carrying participants. These were collected prior to treatment and at five timepoints over 28 days following a three-day artemisinin-based combination therapy (ACT) regimen of dihydroartemisinin-piperaquine or pyronaridine-artesunate at the Ouélessébougou Clinical Research Unit of the Malaria Research and Training Centre of the University of Bamako (Bamako, Mali). At each study visit, DMFAs were conducted. RESULTS: A total of 57 Pfcsp haplotypes and 53 Pftrap haplotypes were identified, indicating high genetic diversity among parasite clones. Prior to treatment, human infections were more often polyclonal and had a higher median multiplicity of infection (MOI; 3 (IQR 2-5)), compared to mosquito midgut infections (1 (IQR 1-2)). At this timepoint, it is likely that some clones detected in human blood are not producing gametocytes and are, therefore, not contributing to mosquito transmission. Minority clones preferentially transmitted, and these same clones often persisted in the human blood samples post-treatment. These observations mirror the rapid decline in asexual parasite density that occurs after ACT initiation, and the more persistent circulation of gametocytes. The data, therefore, suggests that asexual gametocyte-non-producing clones outnumber the gametocyte-producing clones at baseline, yet it is these gametocyte-producing minority clones that are transmitted to and surviving in mosquitoes. Certain haplotypes were also found to be more prevalent in human samples compared to mosquito infections, and vice versa, with 12.6% of haplotypes at baseline exclusively observed in mosquitoes. Along with this, varying odds of transmission for different parasite clones were observed, indicating that there are inherent clonal differences in gametocyte productivity or viability. To assess the transmission of drug-resistant clones, the overall prevalence of molecular markers of drug resistance was determined in both human and mosquito hosts, followed by a pairwise comparison between human blood infections and paired infected midguts. This showed that Asn51Ile in Pfdhfr and Lys540Glu in Pfdhps may have a transmission advantage under ACT, while Ala613Ser in Pfdhps may confer a transmission disadvantage. CONCLUSIONS: Overall, these findings indicate that parasite dynamics and clonal transmissibility are highly complex, even after ACT. This complexity may have important epidemiological implications, as it suggests the transmission of minority clones and highlights the impact of drug resistance markers on transmissibility

    A multifaceted menstrual health intervention to improve psychosocial outcomes and menstrual practices among secondary schoolgirls in Northwest Tanzania: a pilot intervention study.

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    INTRODUCTION: Schools provide an important opportunity to sustainably reach and improve menstrual experiences and outcomes among adolescent girls. This study examined changes in psychosocial outcomes and menstrual practices after a pilot menstrual health intervention in schools in Northwest Tanzania. METHODS: We conducted a pre/post evaluation of a pilot menstrual health intervention in four schools in Mwanza region. The intervention included: (i) 10-hours comprehensive menstrual sexual and reproductive health (MSRH) education curriculum delivered over 5 days, (ii) distribution of menstrual management kits, (iii) improvement of school WASH facility guided by needs, and (iv) training on menstrual pain management strategies, supply of pain killers and training a specific teacher on dispensing. The primary outcome was measured using the Menstrual Practices Need Scale (MPNS). We assessed seven secondary outcomes: menstrual pain management practice; self-efficacy in managing menstruation; menstrual-related anxiety; self-reported urogenital infection symptoms; MSRH knowledge; participation in school during menstruation; and school climate score. We used linear (for MPNS, and school climate score), and logistic (for remaining secondary outcomes) random-effect regression models to examine changes in outcomes between baseline and endline. RESULTS: A total of 486 schoolgirls (mean age 15.6 years [SD 1.3]) were recruited for the baseline survey; of these 396 participated in the endline survey. At 12-months follow up, menstrual experience improved for MPNS-36 subscales of transport and menstrual material needs, (mean difference (MD), 0.52; 95% CI 0.38-0.66), and menstrual material reuse needs, (MD 0.32; 0.14-0.50), while menstrual materials reuse insecurity did not change, (MD -0.08; -0.27-0.11). For the secondary outcomes, there was an increased use of analgesics for menstrual pain management, (OR 2.21; 95% CI 1.33-3.67); improved self-efficacy for managing menstruation, (OR 2.02; 1.35-3.04); MSRH knowledge, (OR 5.23; 3.25-8.39), participation in school (OR 2.80; 1.89-4.16) and reduced menstrual-related anxiety, (OR 0.38; 0.25-0.59). There was no evidence of change in self-reported urogenital symptoms, (OR 0.71; 0.49-1.01) or school climate, (MD 0.05; -0.19-0.28). CONCLUSION: The pilot intervention showed improvements in menstrual practices, psychosocial outcomes and school participation among schoolgirls but had no effect on school climate or self-reported urogenital symptoms. Stronger evidence from rigorously designed trials is needed to confirm the effectiveness of the intervention and scalability of these findings

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