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The World Mosquito Program posted the results of a 3-year randomised controlled trial in Yogyakarta, Indonedia, providing compelling gold standard evidence for the efficacy of the Wolbachia method in controlling dengue. The deployment of Wolbachia-carrying Aedes aegypti mosquitoes lead to a reduction of 77% in dengue incidence in Wolbachia-treated versus untreated areas.
Safety and efficacy of single-dose primaquine to interrupt Plasmodium falciparum malaria transmission in children compared with adults: a systematic review and individual patient data meta-analysis.
BackgroundAdding a single dose of primaquine to artemisinin-based combination therapy (ACT) for the treatment of falciparum malaria can reduce the transmission of Plasmodium falciparum and could limit the spread of artemisinin partial resistance, including in Africa, where the disease burden is greatest. We aimed to compare the safety and efficacy of single-dose primaquine plus ACT between young children (aged <5 years) and older children (aged 5 years to <15 years) and adults (aged ≥15 years), and between low and moderate-to-high transmission areas.MethodsFor this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, WHO Global Index Medicus, OpenGrey.eu, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform, from database inception to April 3, 2024, with no language restrictions. We included prospective studies on efficacy against falciparum malaria that enrolled at least one child younger than 15 years and involved a study group given a single dose of primaquine (≤0·75 mg/kg) plus ACT. Studies involving mass drug administration, healthy volunteers, or patients with severe malaria or mixed (with non-falciparum) infections were excluded. For inclusion in the efficacy analysis, data on transmission potential (as determined by gametocytaemia, infectivity, or both) at enrolment and follow-up (day 3, day 7, or day 14) were required; the safety analysis required data on haemoglobin concentrations or haematocrit values at enrolment and at one or more follow-up visits by day 7, any data on adverse events, or both. After independent screening of the search results by two reviewers, the investigators of eligible studies were invited to contribute individual patient data. We quantified day 7 gametocyte carriage, probability of infecting a mosquito, decreases (>25%) in haemoglobin concentration associated with anaemia, and adverse events until day 28 using regression analyses, with random study-site intercepts to account for clustered data. These analyses were registered with PROSPERO, CRD42021279363 (safety) and CRD42021279369 (efficacy).FindingsOf 5697 records identified by the search, 30 studies were eligible for analysis. Of these, individual patient data were shared for 23 studies, including 6056 patients from 16 countries: 1171 (19·3%) young children (aged <5 years), 2827 (46·7%) older children (aged 5 years to <15 years), and 2058 (34·0%) adults (aged ≥15 years). Adding a single low dose of primaquine (0·2-0·25 mg/kg) to ACTs reduced day 7 gametocyte positivity (adjusted odds ratio [aOR] 0·34, 95% CI 0·22-0·52; p<0·001) and infectivity to mosquitoes over time (aOR per day 0·02, 0·01-0·07, p<0·001). No difference was found in the effect of single low-dose primaquine both on gametocyte positivity in young children compared with older children (1·08, 0·52-2·23; p=0·84) and adults (0·50, 0·20-1·25; p=0·14) and between low-transmission and moderate-to-high transmission settings (1·07, 0·46-2·52; p=0·86), and on infectivity to mosquitoes in young children compared with older children (1·36, 0·07-27·71; p=0·84) and adults (0·31, 0·01-8·84; p=0·50) and between low-transmission and moderate-to-high transmission settings (0·18, 0·01-2·95; p=0·23). Gametocyte clearance was also similar for different ACTs (dihydroartemisinin-piperaquine vs artemether-lumefantrine) when combined with a primaquine target dose of 0·25 mg/kg (1·56, 0·65-3·79; p=0·32 at day 7). However, patients given a primaquine dose of less than 0·2 mg/kg with dihydroartemisinin-piperaquine were more likely to have gametocytaemia than those treated with artemether-lumefantrine (5·68, 1·38-23·48; p=0·016 at day 7). There was no increase in anaemia-associated declines in haemoglobin concentration (>25%) at a primaquine dose of 0·25 mg/kg, regardless of age group, transmission setting, and glucose-6-phosphate dehydrogenase status. The risks of adverse events of grade 2 or higher and of serious adverse events were similar between primaquine and no-primaquine groups, including in young children.InterpretationRegardless of malaria transmission intensity and age group, a single dose of 0·25 mg/kg primaquine is safe and efficacious for reducing P falciparum transmission. These findings underscore the need for primaquine formulations suitable for young children, and also provide supportive evidence to expand the use of single low-dose primaquine in regions with a moderate-to-high transmission rate that are threatened by artemisinin partial resistance.FundingThe EU and the Bill & Melinda Gates Foundation.
Creating different global health futures: mapping the health research ecosystem and taking decolonial action.
This paper promotes reflexive consideration of health research practices using a decolonisation lens. We propose both incremental and more radical action in five domains: knowledge production, funding and programmes, dissemination, uptake, and education and training. We suggest four steps towards transformation and share a reflexive tool to operationalise these steps.
Infant-level and child-level predictors of mortality in low-resource settings: the WHO Child Mortality Risk Stratification Multi-Country Pooled Cohort
Background: Despite impressive reductions in overall global child mortality, the rate of decline has slowed during the past decade. Current guidelines for the care of paediatric patients in low-resource settings mostly focus on broad clinical syndromes or undernutrition rather than children's individual contextualised risk. We aimed to identify readily assessable child-level characteristics that can predict mortality risk in a range of community and health-care settings in high-burden settings. Methods: The WHO Child Mortality Risk Stratification Multi-Country Pooled Cohort (WHO-CMRS) included pooled data from individual children enrolled in observational or randomised controlled trials in low-income and middle-income countries. The criteria for inclusion of a dataset were documentation of age, weight, vital status, and date of death, and at least two observations per participant younger than 60 months. To calculate odds ratios, we built generalised linear mixed effects regression (glmer) models with each child and each study as random intercepts and time interval as the offset. In all analyses, the outcome was defined as death within the respective observation period of the child. From the glmer models, we predicted absolute risk of death per child-month associated with risk exposures separately and combined with anthropometry according to the following age groups: 0–5 months, 6–11 months, 12–23 months, and 24–59 months. Studies were grouped according to population types studied: the general population, populations selected based on anthropometric criteria, and populations selected based on the presence of illness. Findings: We analysed pooled data from WHO-CMRS, including 75 287 children from 33 studies done in 17 countries between Jan 1, 2001, and Dec 31, 2021. During a total of 69 085 child-years of follow-up, 2805 (3·7%) children died. Age younger than 24 months, low anthropometry, preterm birth, low birthweight, and absence of breastfeeding (either was breastfeeding not offered or an underlying illness interfered with breastfeeding practices) were each associated with increased mortality: risks declined with increasing age. The highest absolute mortality risk was among the youngest children (age 0−5 months), with a weight-for-age Z score of less than −3 (ie, a predicted absolute risk of 11·0 [95% CI 6·2−19·5] per 1000 child-months in general population studies). Risks were additive: underlying risk exposures such as low birthweight and preterm birth added to the mortality risks in children with anthropometric deficit. For example, children aged 0−5 months with a weight-for-age Z score of less than −3 and a history of preterm birth had a predicted absolute mortality risk of 40·1 (95% CI 22·0−72·1). However, overall mortality and the association between child-level characteristics and mortality differed according to the type of study population and child age. Interpretation: Risk assessments combining individual child-level characteristics including anthropometry can enable programmes to identify children at high and lower risk of mortality and, thereafter, differentiate care accordingly. Such a strategy could reduce mortality and optimise health system efficiency and effectiveness. Funding: US Agency for International Development. Translations: For the Spanish and French translations of the abstract see Supplementary Materials section.
Putting health facilities on the map: a renewed call to create geolocated, comprehensive, updated, openly licensed dataset of health facilities in sub-Saharan African countries.
BackgroundHealthcare service provision, planning, and management depend on the availability of a geolocated, up-to-date, comprehensive health facility database (HFDB) to adequately meet a population's healthcare needs. HFDBs are an integral component of national health system infrastructure forming the basis of efficient health service delivery, planning, surveillance, and ensuring equitable resource distribution, response to epidemics and outbreaks, as well as for research. Despite the value of HFDBs, their availability remains a challenge in sub-Saharan Africa (SSA). Many SSA countries face challenges in creating a HFDB; existing facility lists are incomplete, lack geographical coordinates, or contain outdated information on facility designation, service availability, or capacity. Even in countries with a HFDB, it is often not available open-access to health system stakeholders. Consequently, multiple national and subnational parallel efforts attempt to construct HFDBs, resulting in duplication and lack of governmental input, use, and validation.Main bodyIn this paper, we advocate for a harmonized SSA-wide HFDB. To achieve this, we elaborate on the steps required and challenges to overcome. We provide an overview of the minimum attributes of a HFDB and discuss past and current efforts to collate HFDBs at the country and regional (SSA) levels. We contend that a complete HFDB should include administrative units, geographic coordinates of facilities, attributes of service availability and capacity, facilities from both public and private sectors, be updated regularly, and be available to health system stakeholders through an open access policy. We provide historical and recent examples while looking at key issues and challenges, such as privacy, legitimacy, resources, and leadership, which must be considered to achieve such HFDBs.ConclusionA harmonized HFDB for all SSA countries will facilitate efficient healthcare planning and service provision. A continental, cross-border effort will further support planning during natural disasters, conflicts, and migration. This is only achievable if there is a regional commitment from countries and health system stakeholders to open data sharing. This SSA-wide HFDB should be a government-led initiative with contributions from all stakeholders, ensuring no one is left behind in the pursuit of improved health service provision and universal health coverage.
Wrangling Real-World Data: Optimizing Clinical Research Through Factor Selection with LASSO Regression.
Data-driven approaches to clinical research are necessary for understanding and effectively treating infectious diseases. However, challenges such as issues with data validity, lack of collaboration, and difficult-to-treat infectious diseases (e.g., those that are rare or newly emerging) hinder research. Prioritizing innovative methods to facilitate the continued use of data generated during routine clinical care for research, but in an organized, accelerated, and shared manner, is crucial. This study investigates the potential of CURE ID, an open-source platform to accelerate drug-repurposing research for difficult-to-treat diseases, with COVID-19 as a use case. Data from eight US health systems were analyzed using least absolute shrinkage and selection operator (LASSO) regression to identify key predictors of 28-day all-cause mortality in COVID-19 patients, including demographics, comorbidities, treatments, and laboratory measurements captured during the first two days of hospitalization. Key findings indicate that age, laboratory measures, severity of illness indicators, oxygen support administration, and comorbidities significantly influenced all-cause 28-day mortality, aligning with previous studies. This work underscores the value of collaborative repositories like CURE ID in providing robust datasets for prognostic research and the importance of factor selection in identifying key variables, helping to streamline future research and drug-repurposing efforts.
A comparison of national seasonal influenza treatment guidelines across the Asia Pacific region.
Seasonal influenza leads to 2-3 million infections and up to 650,000 global deaths annually, with particularly high mortality in Asia and relatively low annual vaccination rates for prevention. Relatively lower attention is paid to antiviral treatment as a facet of influenza response strategy both in research and national policy. This study compares national influenza treatment guidelines across countries in the Asia Pacific region, and assesses the antiviral recommendations, comprehensiveness, availability, and quality, compared with World Health Organisation (WHO) guidelines. Ministry of Health websites were searched, and key stakeholders were contacted to obtain national influenza treatment guidelines. Official guidelines detailing pharmacologic treatment for seasonal influenza were included. Key data for comparison were extracted and quality appraisal was conducted using the AGREE II instrument. Out of 49 countries and areas in the World Health Organisation Western Pacific and South-East Asia regions, under half (14/49; 28.6%) had established national influenza treatment guidelines. Nine (9/49; 18.4%) reported no seasonal flu guidelines at all, and information could not be obtained for 25 (51.0%). All guidelines recommend oseltamivir in line with WHO recommendations, although rationale and evidence reviews were often missing. There was variation in recommendations for other antivirals, indications for treatment, definitions of severity and recency of publication. The AGREE II tool quality assessments revealed the highest average scores were observed in the 'presentation' domain and lowest scores in 'editorial independence' and 'rigour of development' domains, demonstrating limited evidence-based guideline development. The variability in recommendations and definitions highlight the need for a stronger evidence base with direct comparisons of antiviral treatment for hard and soft endpoints, and improvements in systematic guideline development. Established treatment guidelines are a key component of national influenza response strategy and in the post-covid pandemic era, renewed attention to seasonal influenza management is surely warranted.
Hide and seek with falsified medicines: Current challenges and physico-chemical and biological approaches for tracing the origin of trafficked products.
The criminal trafficking of falsified medical products is a worldwide, yet still largely overlooked, public health problem. A falsified medicine fraudulently misrepresents its identity, composition and/or source, often being ineffective or toxic for patients. Although techniques have been developed to detect falsified medicines, it remains a challenge to trace where- and by whom- the products are manufactured. We aim to discuss plausible biological and physico-chemical analytical techniques that could reveal information about the origin of medical falsifications. We first provide a brief overview on the prevalence, criminal activities, health impacts and (bio)chemical features of falsified medical products. We then explore diverse laboratory approaches, that are used in food fraud, illicit drug and wildlife trafficking investigations, and discuss how they could be combined and redirected towards tracing falsified medicine origin and hence empowering enforcement to counter this pernicious but neglected global health problem.
When health data go dark: the importance of the DHS Program and imagining its future.
BACKGROUND: The suspension and/or termination of many programmes funded through the United States Agency for International Development (USAID) by the new US administration has severe short- and long-term negative impacts on the health of people worldwide. We draw attention to the termination of the Demographic and Health Surveys (DHS) Program, which includes nationally representative surveys of households, DHS, Malaria Indicator Surveys [MIS]) and health facilities (Service Provision Assessments [SPA]) in over 90 low- and middle-income countries. USAID co-funding and provision of technical support for these surveys has been shut down. MAIN BODY: The impact of these disruptions will reverberate across local, regional, national, and global levels and severely impact the ability to understand the levels and changes in population health outcomes and behaviours. We highlight three key impacts on (1) ongoing data collection and data processing activities; (2) future data collection and consequent lack of population-level health indicators; and (3) access to existing data and lack of support for its use. CONCLUSIONS: We call for immediate action on multiple fronts. In the short term, universal access to existing data and survey materials should be restored, and surveys which were planned or in progress should be completed. In the long term, this crisis should serve as a tipping point for transforming these vital surveys. We call on national governments, regional organisations, and international partners to develop sustainable alternatives that preserve the principles (standardised questionnaires, backward compatibility, open access data with rigorous documentation) which made the DHS Program an invaluable global health resource.
Influence of context on engagement with COVID-19 testing: a scoping review of barriers and facilitators to testing for healthcare workers, care homes and schools in the UK.
ObjectiveThe UK government's response to the COVID-19 pandemic included a 'test, trace and isolate' strategy. Testing services for healthcare workers, care homes and schools accounted for the greatest spend and volume of tests. We reviewed relevant literature to identify common and unique barriers and facilitators to engaging with each of these testing services.DesignScoping review.Search strategyPubMed, Scopus and the WHO COVID-19 Research Database were searched for evidence published between 1 January 2020 and 7 November 2022. This was supplemented by evidence identified via free-text searches on Google Scholar and provided by the UK Health Security Agency (UKHSA).Data extraction and synthesisData were extracted by a team of reviewers and synthesised thematically under the broad headings of perceptions, experiences, barriers and facilitators to engaging with the COVID-19 testing programme.ResultsThis study included 40 sources, including 17 from projects that informed UKHSA's decisions during the pandemic. Eight themes emerged and were used to categorise barriers and facilitators to engaging with the testing services for healthcare workers, care homes and schools: (1) perceived value, (2) trust in the tests and public bodies, (3) importance of infrastructure, (4) impact of media and social networks, (5) physical burden of the test, (6) perceived capability to undertake testing, (7) importance of relevant information and 8) consequences of testing.ConclusionsUniversal barriers and facilitators to engagement with the testing programme related to the core elements of each testing service, such as uncomfortable specimen collection and the influence of media and peers; these could be mitigated or leveraged to increase engagement across settings. However, the individuals involved, perceptions of value and available resources differed across services, leading to unique experiences between settings. Thus, consideration of context is crucial when designing and implementing a testing programme in response to a pandemic.
The latency time of SARS-CoV- 2 Delta variant in infection- and vaccine-naive individuals from Vietnam
Abstract Background The latency time (from infection to infectiousness) guides the choice of measures required to control an infectious disease. Estimates of the SARS-CoV- 2 latency time are sparse due to lack of appropriate and representative data. Infection time is rarely known exactly and exposure information may be subject to several biases. Information on the endpoint requires repeated testing. Moreover, estimation is challenging because both the starting point and endpoint are typically interval censored and data may be subject to length-biased sampling (truncation). Methods We collected detailed information on exposure from public health reports produced during an outbreak with the SARS-CoV- 2 Delta variant in Ho Chi Minh City, Vietnam, in May-July 2021. Using a custom digital form and application facilitated reliable choices on exposure window. This comprehensive data set on exposure and test results from 1951 individuals, collected in the absence of large-scale vaccination or earlier infection, is the first of its kind outside of China. We accounted for the doubly interval censored nature of the observations and went beyond the standard assumption of a constant infection risk over calendar time (exponential growth) and allowed for flexibility regarding the latency time (generalized gamma distribution). We addressed right truncation due to a cutoff in data collection and a finite quarantine length. Employing a Bayesian approach, using the program , made the analyses relatively straightforward. Results Assuming exponential growth, our estimate of SARS-CoV- 2 Delta variant’s mean latency time was 3.22 (95% Credible Interval 2.89 - 3.55) days; the median was 1.81 (95% CrI 1.44- 2.16) days; the 95 th percentile was 10.98 (95% CrI 9.91 - 12.41) days. These values were much larger if a uniform infection risk was assumed. Conclusions Using a Bayesian approach with the program, we were able to estimate the SARS-CoV- 2 latency time distribution of the Delta variant in infection-naive and vaccine-naive individuals. Estimates were sensitive to the assumptions made regarding the risk of infection within the exposure window. Compared to earlier studies, the median latency time was shorter, while the 95 th percentile was larger. Our results stress the importance of thoughtful data collection and analysis for evidence-based control of an infectious disease.
Understanding the primary healthcare context in rural South and Southeast Asia: a village profiling study
Abstract Background Understanding contextual factors is critical to the success of health service planning and implementation. However, few contextual data are available at the village level in rural South and Southeast Asia. This study addressed the gap by profiling representative villages across seven sites in Thailand (n=3), Cambodia, Laos, Myanmar and Bangladesh. Methods Key informant surveys supplemented by other information sources were used to collect data from 687 villages on four key indicators (literacy rate, and percentages of attended deliveries, fully immunised children and latrine coverage), as well as access to various services. Data were analysed descriptively. Results Sites varied considerably. Five were highly diverse ethno-culturally and linguistically, and all relied on primary health centres and village health/malaria workers as the main providers of primary healthcare. These were generally bypassed by severely ill patients for urban first-level referral hospitals and private sector facilities. While >75% of villages were near primary schools, educational attainment was generally low. Over 70% of villages at each site had mobile phone coverage and availability of electricity was high (≥65% at all sites bar Myanmar). Conclusion These results illustrate the similarities and differences of villages in this region that must be considered in public health research and policymaking.
Progression of lymphatic filariasis antigenaemia and microfilaraemia over 4.5 years in antigen-positive individuals, Samoa 2019-2023
Objectives: The first round of triple-drug mass drug administration (MDA) for lymphatic filariasis (LF) in Samoa was in 2018. This study aims to i) examine progression of LF antigen (Ag) and microfilaria (Mf) in Ag-positive individuals from 2019-2023; and ii) compare Ag/Mf prevalence in household members of Mf-positive vs Mf-negative participants. Methods: In 2023, we tested Ag-positive participants (indexes) from a 2019 survey in Samoa, and their household members. We tested for Ag (Alere/Abbott Filariasis Test Strip) and Mf. We examined changes in Ag/Mf status in index participants and compared Ag/Mf prevalence between household members of Mf-positive and Mf-negative indexes. Results: We recruited 91 indexes and 317 household members. In 2023, all 17 Mf-positive indexes remained Ag-positive and 11/15 with Mf results (73.3%) were Mf-positive. Of 74 Mf-negative indexes, 79.7% remained Ag-positive in 2023 and 31.1% became Mf-positive. Household members of Mf-positive indexes were more likely to be Ag-positive (odds ratios 3.3, 95% CI 1.0-10.3) compared to those of Mf-negative indexes. Conclusion: Our results raise concerns regarding long-term effectiveness of a single-dose of triple-drug MDA for sustained clearance of Mf in Samoa. Guidelines for follow-up and treatment of Ag/Mf-positive people and household members are urgently required.
The respiratory syncytial virus vaccine and monoclonal antibody landscape: the road to global access.
Respiratory syncytial virus (RSV) is the second most common pathogen causing infant mortality. Additionally, RSV is a major cause of morbidity and mortality in older adults (age ≥60 years) similar to influenza. A protein-based maternal vaccine and monoclonal antibody (mAb) are now market-approved to protect infants, while an mRNA and two protein-based vaccines are approved for older adults. First-year experience protecting infants with nirsevimab in high-income countries shows a major public health benefit. It is expected that the RSV vaccine landscape will continue to develop in the coming years to protect all people globally. The vaccine and mAb landscape remain active with 30 candidates in clinical development using four approaches: protein-based, live-attenuated and chimeric vector, mRNA, and mAbs. Candidates in late-phase trials aim to protect young infants using mAbs, older infants and toddlers with live-attenuated vaccines, and children and adults using protein-based and mRNA vaccines. This Review provides an overview of RSV vaccines highlighting different target populations, antigens, and trial results. As RSV vaccines have not yet reached low-income and middle-income countries, we outline urgent next steps to minimise the vaccine delay.