London School of Hygiene & Tropical Medicine

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    Understanding the impact of the COVID-19 pandemic and its control measures on women and children: a Zimbabwean case study.

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    The Coronavirus Disease 2019 (COVID-19) posed significant health policy challenges, particularly for low-income countries, where policymakers faced both direct threats from the virus and social and economic harm owing to lockdown measures. We present a holistic contextualized case study of the direct and indirect impacts on women and children, highlighting disparities across socioeconomic, age, and gender groups. We utilized multiple data sources, including primary and secondary data from 28 in-depth interviews, six focus group discussions, and 40 household interviews, as well as data from government reports, District Health Information Software version 2 (DHIS2), and published research. A conceptual framework was devised to hypothesize causal pathways and guide the analysis of results. The findings indicate that the pandemic not only had direct effects, on morbidity and mortality, but also more severe indirect impacts, including job losses and limited access to healthcare, including maternal and child healthcare services, due to measures put in place to control it, which were exacerbated by well-known but inadequately considered preexisting political and economic challenges. The most severe indirect effects on healthcare services availability and wider livelihoods fell on the poorest segments of society, further widening the age and gender inequalities. Policymakers faced significant challenges in managing the direct and indirect harm of COVID-19, including short- and long-term effects and their unequal distribution across society. We conclude that the indirect effects of COVID-19 were at least as harmful, if not more so, than the direct impacts, especially for women and children. In the future, it is highly recommended to establish specific protocols and guidance for maternal and child health service access, including strategies that reduce barriers to social support

    Acceptability of self-sampling for high-risk HPV DNA testing for primary cervical cancer screening among women in Thyolo, Malawi: A qualitative study.

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    Despite the roll-out of cervical cancer screening within routine health facilities, uptake of cervical cancer screening in Malawi remains low due to factors such as privacy concerns, stigma, and distance to health facility. Self-sampling for human papillomavirus (HPV) testing offers a viable alternative to provider-delivered sampling, resolving issues with accessibility and privacy related barriers. However, there is limited understanding of the acceptability of self-sampling among women in low-income settings. We aimed to assess women's perceptions, experiences, and acceptability of self-sampling for HPV testing for primary cervical cancer screening. We conducted a qualitative phenomenological study among ten purposively sampled women screening for cervical cancer at a rural hospital in Malawi. Data collection instruments and the thematic analytical approach were guided by the Theoretical Framework of Acceptability. Key constructs that were central to this analysis included affective attitude, burden, self-efficacy, intervention coherence, and perceived effectiveness. Self-sampling emerged as a culturally and socially acceptable diagnostic practice by the women, mediated by emic values of privacy, bodily autonomy, and convenience. Women valued the ability to autonomously collect samples, which allowed them to circumvent discomfort and perceived invasiveness linked to speculum use, especially by male clinicians. Sociocultural barriers such as limited literacy levels, poor access to transport, and a lack of spousal approval restricted broader acceptability. Facilitators of acceptability included comprehension of the intervention, confidence in the self-sampling process, and the potential of the intervention to increase screening uptake, reduce cervical cancer screening-related stigma and reduce healthcare worker burden. Self-sampling for cervical cancer screening is an acceptable and promising alternative for improving the uptake of screening among women in Malawi and similar low-income countries. Scale-up of this approach will require addressing socio-cultural barriers through optimising instructional materials, engaging male partners, and leveraging community health workers for scaled community implementation via task-sharing

    Developing a mental health support package for women survivors of domestic violence and modern slavery in South Asia: a multiple methods design

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    Background Women survivors of domestic violence and modern slavery in South Asia face substantial harms to their mental health, but their advocates lack evidence-informed practice guidance on how they might support their well-being and address common mental disorders. In this synopsis, we summarise the development of a support package to help fill the gap. Our aim was to design a package of contextually appropriate interventions with which non-specialist providers could support the mental health of women survivors of domestic violence and human trafficking. Methods Our work involved a transdisciplinary group located in Afghanistan, India and Sri Lanka, with collaborators in the United Kingdom. To identify potential components of the support package, we reviewed existing guidelines, examined and undertook literature reviews and interviewed and held focus group discussions with survivors of domestic violence and human trafficking, service providers and academics. We convened multidisciplinary consultations and examined routine service data on support requirements. We considered our findings alongside published theory, developed a programme theory and articulated it in a package of support. Findings We developed a core support package and four locally adapted versions for caseworkers and field workers who support women survivors of domestic violence and human trafficking. Content areas include background information on domestic violence and modern slavery, trauma, socioecological influences, principles of counselling and ethics and confidentiality. The package includes advice on safety assessment and response to basic needs, mental health assessment, first aid, and suicide prevention, psychoeducation, crisis intervention, supporting mental health, problem-solving and goal-setting. It provides information on mental health assessment and distress reduction techniques, collaborative planning and review. Conclusions and future work We will continue to review the use of the package, networking with providers and survivors to allow iterative adaptation and improvement. We hope it will be useful, with adaptation for specific settings, for advocates and caseworkers in providing comprehensive and appropriate non-specialist support for the mental health of women survivors of violence in South Asia. Funding This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Global Health Research programme as award number 17/63/47

    Association Between Air Pollution and Monday Peak Mortality From Acute Myocardial Infarction.

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    BACKGROUND: Mortality from acute myocardial infarction (AMI) exhibits a weekly pattern, with a peak occurring on Mondays. Although several hypotheses have been proposed, the effect of air pollution on this peak has not yet been investigated. OBJECTIVES: The purpose of this study was to investigate if daily variation in major air pollutants modifies the risk of AMI mortality on Monday. METHODS: A time-series study analyzed 260,320 AMI deaths in Spain from 2004 to 2018, using records from the Spanish National Institute of Statistics. Air pollution (ie, PM2.5, PM10, nitrogen dioxide, and ozone) levels were estimated across the mainland Spain and the Balearic Islands. Regression models and multilevel meta-analysis were used to assess the weekly variation in AMI mortality and the association between air pollution and the Monday excess in AMI mortality. RESULTS: AMI mortality varied throughout the week, peaking on Monday (+3.7% above the weekly average). Particulate air pollution (PM2.5, PM10) also showed a weekly pattern, with lower levels on weekends than weekdays. A significant increase in PM2.5 and PM10 levels was observed from Sunday to Monday (12.6% and 12.0%, respectively), but not between other weekdays. After adjustment for inter-weekly baseline mortality changes, the intra-weekly pattern in AMI mortality was not modified by either the absolute level or the inter-day change in air pollutants. In addition, no association was found between air pollution and the Monday peak in AMI mortality. CONCLUSIONS: Our results suggest that the excess AMI mortality observed on Mondays in the Spanish population is not explained by concurrent variations in major air pollutants

    Unleashing the power of intelligence: revolutionizing malaria outbreak preparedness with an advanced warning system in Benin, West Africa.

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    BACKGROUND: Malaria is a significant vector-borne disease that exhibits high sensitivity to climatic variations within the West African region. In Benin, the effective prevention and mitigation of malaria pose considerable challenges, primarily due to the prevailing conditions of poverty and environmental adversities. This study endeavours to devise an advanced system for early detection and warning of malaria outbreaks in the northern part of Benin, employing monthly time series data pertaining to climatic variables. METHODS: Monthly climate data were sourced from Meteorological Agency of Benin (METEO-Benin), alongside malaria incidence data procured from the database of the Benin Ministry of Health, that covered the timeframe of 2009-2021. To ascertain the influence of climatic variables on malaria incidence, principal component analysis was applied. Subsequently, an intelligent model for forecasting malaria outbreaks was developed using support vector machine (SVM) algorithm. The developed model for malaria outbreaks was then employed to establish an intelligent system for warning and forecasting malaria incidence on a monthly basis, utilising the Meteostat platform, an online weather data service provider, in conjunction with the Streamlit framework. This application exhibits responsiveness and compatibility across all web browsers. RESULTS: Relative humidity and maximal temperature significantly influence malaria incidence in the northern region of Benin. SVM regression algorithm forecasts 80% prediction rate for malaria incidence. Consequently, the intelligent malaria outbreak warning system was successfully devised, enabling the automatic and manual prediction of monthly malaria incidence rates within the districts of northern Benin. CONCLUSIONS: This system serves as a valuable tool for stakeholders and policymakers, facilitating proactive measures to curtail malaria transmission in Benin

    Plasma Vitamin B12 May Be a Misleading Biomarker among Children with Severe Acute Malnutrition: An Observation from Mwanza, Tanzania.

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    BACKGROUND: Vitamin B12 deficiency is related to impaired neurodevelopment and anemia and is a global health concern in children with severe acute malnutrition (SAM). OBJECTIVES: We investigated vitamin B12 status in children with SAM and among non-malnourished comparisons and assessed the validity of the plasma vitamin B12 assay. METHODS: This study was part of a pilot study of a nutritional intervention. We measured plasma concentrations of vitamin B12, methylmalonic acid (MMA), total haptocorrin (HC), and total transcobalamin (TC) in children with SAM before and after 8 wk of nutritional treatment and at a single timepoint in non-malnourished children. RESULTS: We included 82 children with SAM and 82 children without acute malnutrition. Plasma vitamin B12 was higher in children with SAM at enrollment than in controls (median 647 compared with 411 pmol/L) and declined after treatment (median 469 pmol/L). Baseline plasma vitamin B12 was particularly high in children with edematous SAM compared to those without edema (P = 0.050). In contrast, plasma MMA was higher in those with SAM, reflecting lower vitamin B12 function (median 220 compared with 170 nmol/L), and declined after treatment (median 190 nmol). HC was positively correlated with vitamin B12 concentration (P < 0.001) and was also higher in children with SAM than in comparison children (median 959 compared with 789 pmol/L), decreasing after treatment (median 815 pmol/L). TC was higher in children with SAM than comparisons but did not decrease after treatment. Overall, 23% of children with SAM had MMA concentrations suggesting vitamin B12 deficiency compared to 4.5% of non-malnourished children. CONCLUSIONS: In contrast to our initial expectations, we found that plasma vitamin B12 was higher in children with SAM, especially those with edema. However, analysis of MMA revealed lower vitamin B12 function in malnourished children and improvement after treatment, warranting caution in the interpretation of plasma vitamin B12 in SAM. Elevated HC in SAM may explain high vitamin B12 concentration, but the cause of elevated HC needs further investigation

    Micro-geographic variation in antigenic diversity of PfEBA-175 region II in asymptomatic Plasmodium falciparum infections in Tanzania.

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    BACKGROUND: Malaria remains a major public health burden, and the development of effective blood-stage vaccines is complicated by extensive antigenic variation in Plasmodium falciparum antigens. PfEBA-175, a leading vaccine candidate, mediates erythrocyte invasion by binding to glycophorin A via its region II (RII), which is known to be highly polymorphic. METHODS: We examined the genetic diversity and antigenicity of PfEBA-175 region II (RII) in 172 asymptomatic P. falciparum isolates collected from Geita and Kigoma, Tanzania. Sequence diversity was assessed through nucleotide diversity (π) and analysis of selection pressure using dN-dS and Fu's Fs tests. A recombinant PfEBA-175 RII protein was expressed to evaluate antibody response in plasma samples. RESULTS: Sequence analysis revealed high nucleotide diversity (π = 0.00359 ± 0.00012), with evidence of adaptive evolution driven by immune pressure (dN-dS = 3.15, p < 0.001), and sign of recent population expansion based on Fu's Fs value (-30.614). A recombinant RII protein exhibited high antigenicity, with an average seropositivity of 84.8%, although rates varied across villages, ranging from 95.4% in Rwantaba to 50.0% in Bunyambo. The antibody response was positively correlated with age (ρ = 0.333, p < 0.001), but not with parasitemia or gender. Several important amino acids substitutions, including K478N, K481I, and L482V, were located within B-cell epitopes targeted by the invasion-inhibitory monoclonal antibody R217, and N577K, found at the dimer interface, had little effect on naturally acquired immune responses. However, several charged amino acid substitutions including D168H, T198K, K275I, K448N, and D619H influenced natural acquired antibody recognition. CONCLUSION: Despite substantial polymorphism, the glycan-binding residues of PfEBA-175 RII remain conserved, and its high antigenicity across diverse geographic and demographic contexts supports its continued evaluation as a blood-stage vaccine candidate. These findings highlight the importance of accounting for naturally occurring antigenic variation in malaria vaccine development

    Safety, tolerability, and immunogenicity of the ChAdOx1 RVF vaccine against Rift Valley fever among healthy adults in Uganda: a single-centre, single-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial.

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    BACKGROUND: Rift Valley fever (RVF) is an outbreak-prone viral zoonosis, with no vaccine available for human use. We aimed to assess the safety, tolerability, and immunogenicity of the ChAdOx1 RVF candidate vaccine among healthy adults in an RVF-endemic setting in Uganda. METHODS: We conducted a single-centre, single-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial in Masaka, southwestern Uganda. Healthy, non-pregnant adults aged 18-50 years who resided in the clinical site's service area, did not have serum antibodies against the RVF virus nucleoprotein, and had not previously received other adenovirus-vectored vaccines were eligible for inclusion. Participants were sequentially enrolled into three dose groups (group 1 [5·0 × 109 virus particles]; group 2 [2·5 × 1010 virus particles]; or group 3 [5·0 × 1010 virus particles]) and randomly assigned to vaccine or placebo in a 2:1 (group 1) or 5:1 (groups 2 and 3) ratio by use of permuted blocks. Participants received a single intramuscular dose of the ChAdOx1 RVF vaccine or saline placebo in the non-dominant deltoid. Participants were masked to the intervention administered; however, all study staff were unmasked. Coprimary outcomes were the number, proportion, and severity of local and systemic solicited reactogenicity adverse events within the first 7 days and of unsolicited adverse events within 28 days following vaccination in the vaccine and placebo groups, analysed by intention to treat. The secondary outcomes were humoral and cellular immunity to RVF virus glycoproteins. This trial is registered with ClinicalTrials.gov (NCT04672824) and is closed to recruitment. FINDINGS: Between May 5, 2022, and Sept 29, 2022, 30 participants were enrolled, of whom 24 (80%) were men and six (20%) were women (median age 25 years [IQR 22-33]). Adverse events were mostly mild or moderate and self-limiting. Local solicited adverse events were reported in 17 (71%) of 24 vaccine recipients and in no placebo recipients. The most frequently reported local solicited adverse events were injection site pain (one [25%] of four in group 1, five [50%] of ten in group 2, and seven [70%] of ten in group 3); warmth (two [50%] in group 1, three [30%] in group 2, and two [20%] in group 3); and itching (none in group 1, three [30%] in group 2, and two [20%] in group 3). Systemic solicited adverse events were reported in 20 (83%) vaccine recipients and in five (83%) of six placebo recipients. The most commonly reported systemic solicited adverse events were chills (three [75%] of four vaccine recipients vs one [50%] of two placebo recipients) in group 1; fever (two [20%] of ten vs none) and myalgia (four [40%] vs none) in group 2; and fever (four [40%] of ten vs none), headache (six [60%] vs one [50%] of two), fatigue (seven [70%] vs one [50%]), and malaise (seven [70%] vs one [50%]) in group 3. No serious adverse events were reported. By day 14, neutralising antibodies were detected in three (75%) of four individuals in group 1, nine (90%) of ten in group 2, and nine (90%) of ten in group 3. Highest antibody responses were sustained at day 28 (ten [100%]) and at day 84 (nine [90%]) in group 3. By day 14, anti-Gn and Gc immunoglobulin G responses in group 3 preceded other doses, whereas interferon-γ T-cell responses peaked for all doses, preceding the antibody peaks. INTERPRETATION: A single dose of ChAdOx1 RVF vaccine seemed to be safe, tolerable, and immunogenic in healthy adults in an RVF-endemic setting, eliciting humoral and cellular immunity. Further evaluation of the 5·0 × 1010 dose in larger and more diverse populations in areas susceptible to outbreaks is warranted. FUNDING: UK Department of Health and Social Care through the UK Vaccines Network

    Disability inclusion in Zambia's government COVID-19 policies: a framework analysis.

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    BACKGROUND: People with disabilities experienced disproportional health risks and systematic exclusion during the COVID-19 pandemic with particularly severe consequences such as poorer health outcomes and barriers to services in countries around the world. In Zambia, people with disabilities experienced income loss, stress, and additional barriers to accessing health services. This study aimed to analyse disability inclusion in national COVID-19 policies in Zambia. METHODS: We conducted content policy analysis using framework analysis. Ten documents were analysed against eight equity-relevant dimensions of a typical disability inclusive, COVID-19 crisis response. We adapted the framework from Sakellariou and used Ritchie and Spencer's five step thematic analysis. These national policies were published between March 2020 and December 2023. The documents were also scored against eight themes for policy provisions. RESULTS: Disability inclusion was generally low. Although action was provided for disability inclusion in relation to accessible information, access to healthcare and education, financial support, and considerations for the needs of people facing multiple exclusion, information was often not detailed and did not cover all people with disabilities. Several themes on disability inclusion were neglected, including reasonable accommodation and disaggregated disability data. CONCLUSION: These findings underscore persistent structural barriers to equity for people with disabilities during public health crises. It highlights shortcomings by the Government of Zambia in promoting disability inclusion during the COVID-19 pandemic. There is need for improved provisions across all stages of policy design and implementation to strengthen equity and resilience in future public health emergencies

    Diagnostic accuracy of the WHO tuberculosis treatment decision algorithms for children with presumptive tuberculosis: An individual participant data meta-analysis.

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    INTRODUCTION: In 2023, almost 200,000 children under 15 years died from tuberculosis, most without appropriate treatment. Treatment decision algorithms (TDAs), developed to facilitate rapid anti-tuberculosis treatment initiation in children, were recommended by the World Health Organization (WHO) in 2022, conditional on validation in different cohorts and settings. We performed a retrospective external evaluation of WHO TDAs using an individual participant dataset (IPD). METHODS AND FINDINGS: The IPD comprised four paediatric cohorts, restricted to children with presumptive pulmonary TB < 10 years, and including children in high-risk groups (children living with HIV "CLHIV", children with severe acute malnutrition "SAM", and children <2 years). All children in the IPD were retrospectively evaluated using both TDA A (an algorithm including chest X-ray) and TDA B (without chest X-ray), excluding the triage step. The diagnostic accuracy against a composite reference standard (confirmed and unconfirmed tuberculosis versus unlikely tuberculosis) was determined and reported as sensitivities and specificities. Of 1,886 children included (RaPaed-TB: n = 740, Umoya: n = 474, TB-Speed HIV: n = 204, TB-Speed Decentralisation: n = 468), the median age was 2.9 years (interquartile range [IQR]:1.3,5.5), 741 (39.3%) were <2 years, 382 (20.3%) were CLHIV, and 284 (15.1%) had SAM. 281 (14.9%) had confirmed tuberculosis, 672 (35.6%) were classified as unconfirmed tuberculosis (clinically diagnosed, microbiological investigations negative), and 933 (49.5%) as unlikely tuberculosis. For TDAs A and B, algorithm sensitivity was 84.3% (95% CI: 74.8, 90.6) and 90.6% (95% CI: 83.8, 94.7), respectively, with a specificity of 50.6% (95% CI: 30.4, 70.7) and 30.8% (95% CI: 21.5, 42.0), respectively. For TDA A, estimated sensitivity in children in high-risk groups was lower than those with low-risk (83.0%, 95% CI: 79.4%, 86.1%; versus 88.0%, 95% CI: 84.8%, 90.6%), while having a gain in specificity (50.0%, 95% CI: 44.9%, 55.1%; versus 36.6%, 95% CI: 32.7%, 40.7%). Trends were similar for TDA B. As for limitations, most diagnostic tuberculosis studies in children, including two of those included in the IPD, are performed at secondary or tertiary hospitals with higher levels of healthcare and thus the target population might differ somewhat from the IPD, potentially limiting the generalisability of our results. CONCLUSIONS: This retrospective external evaluation of WHO TDAs in a large IPD shows high sensitivity but sub-optimal specificity for both TDAs, in line with the meta-analyses that generated the algorithms. Prospective studies that evaluate the entire TDA, including triage step are needed. Additionally, the integration of novel diagnostic tools within the TDAs should aim to enhance the accuracy, especially the specificity

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