London School of Hygiene & Tropical Medicine

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    Identification of Burkholderia cepacia strains that express a Burkholderia pseudomallei-like capsular polysaccharide.

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    Burkholderia pseudomallei and Burkholderia cepacia are Gram-negative, soil-dwelling bacteria that are found in a wide variety of environmental niches. While B. pseudomallei is the causative agent of melioidosis in humans and animals, members of the B. cepacia complex typically only cause disease in immunocompromised hosts. In this study, we report the identification of B. cepacia strains isolated from either patients or soil in Laos and Thailand that express a B. pseudomallei-like 6-deoxyheptan capsular polysaccharide (CPS). These B. cepacia strains were initially identified based on their positive reactivity in a latex agglutination assay that uses the CPS-specific monoclonal antibody (mAb) 4B11. Mass spectrometry and recA sequencing confirmed the identity of these isolates as B. cepacia (formerly genomovar I). Total carbohydrates extracted from B. cepacia cell pellets reacted with B. pseudomallei CPS-specific mAbs MCA147, 3C5, and 4C4, but did not react with the B. pseudomallei lipopolysaccharide-specific mAb Pp-PS-W. Whole genome sequencing of the B. cepacia isolates revealed the presence of genes demonstrating significant homology to those comprising the B. pseudomallei CPS biosynthetic gene cluster. Collectively, our results provide compelling evidence that B. cepacia strains expressing the same CPS as B. pseudomallei co-exist in the environment alongside B. pseudomallei. Since CPS is a target that is often used for presumptive identification of B. pseudomallei, it is possible that the occurrence of these unique B. cepacia strains may complicate the diagnosis of melioidosis.IMPORTANCEBurkholderia pseudomallei, the etiologic agent of melioidosis, is an important cause of morbidity and mortality in tropical and subtropical regions worldwide. The 6-deoxyheptan capsular polysaccharide (CPS) expressed by this bacterial pathogen is a promising target antigen that is useful for rapidly diagnosing melioidosis. Using assays incorporating CPS-specific monoclonal antibodies, we identified both clinical and environmental isolates of Burkholderia cepacia that express the same CPS antigen as B. pseudomallei. Because of this, it is important that staff working in melioidosis-endemic areas are aware that these strains co-exist in the same niches as B. pseudomallei and do not solely rely on CPS-based assays such as latex-agglutination, AMD Plus Rapid Tests, or immunofluorescence tests for the definitive identification of B. pseudomallei isolates

    Association between tuberculosis and pregnancy outcomes: a retrospective cohort study of women in Cape Town, South Africa

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    BACKGROUND: Tuberculosis (TB) remains a leading cause of mortality among women of childbearing age and a significant contributor to maternal mortality. Pregnant women with TB are at high risk of adverse pregnancy outcomes. This study aimed to determine risk factors for an adverse pregnancy outcome among pregnant women diagnosed with TB. METHODS: Using TB programmatic data, this retrospective cohort analysis included all women who were routinely diagnosed with TB in the public sector between October 2018 and March 2020 in two health subdistricts of Cape Town, and who were documented to be pregnant during their TB episode. Adverse pregnancy outcome was defined as either a live birth of an infant weighing <2500 g and/or with a gestation period <37 weeks or as stillbirth, miscarriage, termination of pregnancy, maternal or early neonatal death. Demographics, TB and pregnancy characteristics were described by HIV status. Logistic regression was used to determine risk factors for adverse pregnancy outcome. RESULTS: Of 248 pregnant women, half (52%) were living with HIV; all were on antiretroviral therapy at the time of their TB diagnosis. Pregnancy outcomes were documented in 215 (87%) women, of whom 74 (34%) had an adverse pregnancy outcome. Being older (35-44 years vs 25-34 years (adjusted OR (aOR): 3.99; 95% CI: 1.37 to 11.57), living with HIV (aOR: 2.72; 95% CI: 0.99 to 4.63), having an unfavourable TB outcome (aOR: 2.29; 95% CI: 1.03 to 5.08) and having presented to antenatal services ≤1 month prior to delivery (aOR: 10.57; 95% CI: 4.01 to 27.89) were associated with higher odds of an adverse pregnancy outcome. CONCLUSIONS: Pregnancy outcomes among women with TB were poor, irrespective of HIV status. Pregnant women with TB are a complex population who need additional support prior to, during and after TB treatment to improve TB treatment and pregnancy outcomes. Pregnancy status should be considered for inclusion in TB registries

    Ozone-related acute excess mortality projected to increase in the absence of climate and air quality controls consistent with the Paris Agreement

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    Short-term exposure to ground-level ozone in cities is associated with increased mortality and is expected to worsen with climate and emission changes. However, no study has yet comprehensively assessed future ozone-related acute mortality across diverse geographic areas, various climate scenarios, and using CMIP6 multi-model ensembles, limiting our knowledge on future changes in global ozone-related acute mortality and our ability to design targeted health policies. Here, we combine CMIP6 simulations and epidemiological data from 406 cities in 20 countries or regions. We find that ozone-related deaths in 406 cities will increase by 45 to 6,200 deaths/year between 2010 and 2014 and between 2050 and 2054, with attributable fractions increasing in all climate scenarios (from 0.17% to 0.22% total deaths), except the single scenario consistent with the Paris Climate Agreement (declines from 0.17% to 0.15% total deaths). These findings stress the need for more stringent air quality regulations, as current standards in many countries are inadequate

    The Royal College of Ophthalmologists' National Ophthalmology Database Study of Cataract Surgery: Report 13, monitoring post-cataract surgery endophthalmitis rates-the rule of X

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    BACKGROUND: Cataract surgical safety has improved over recent decades, with endophthalmitis rates before 2006 typically 0.13-0.15% compared with the most recent UK national estimate of 0.02%. There remains, however, substantial variation in reported rates from different centres. Due to the low event rate, this disparity may not be noticed and opportunities to improve therefore be missed. We propose a method of monitoring post-cataract endophthalmitis rates that would help centres with higher rates identify this. METHODS: A statistical tool, available to download or use online, permits comparison of local endophthalmitis rate with the estimated UK rate of 0.02%. Centres are encouraged to maintain a register of endophthalmitis cases, and when the number reaches a threshold (X cases), either in a certain time period or in a fixed number of procedures, then the centre can consider itself as an outlier and trigger local investigations to improve infection control. RESULTS: Example outputs are offered, such as for a unit doing 5000 cataracts annually, a value of X is suggested such that the third case of endophthalmitis (X = 3) in a 12-month period would give 85% confidence, the fourth case 90% confidence and the fifth case 95% confidence that the true endophthalmitis rate for that unit was higher than the national average. CONCLUSIONS: This statistical tool provides a basis for units to set a threshold number of cases of endophthalmitis within a given period that would trigger local processes, thus helping inform local monitoring processes for this rare but potentially catastrophic complication of cataract surgery

    Convergence and divergence in mortality: A global study from 1990 to 2030

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    An empirical question that has motivated demographers is whether there is convergence or divergence in mortality/longevity around the world. The epidemiological transition is the starting point for studying a global process of mortality convergence. This manuscript aims to provide an update on the concept of mortality convergence/divergence. We perform a comprehensive examination of nine different mortality indicators from a global perspective using clustering methods in the period 1990-2030. In addition, we include analyses of projections to provide insights into prospective trajectories of convergence clubs, a dimension unexplored in previous work. The results indicate that mortality convergence clubs of 194 countries by sex resemble the configuration of continents. These five clubs show a common steady upward trend in longevity indicators, accompanied by a progressive reduction in disparities between sexes and between groups of countries. Furthermore, this paper shows insights into the historical evolution of the convergence clubs in the period 1990-2020 and expands their scope to include projections of their expected future evolution in 2030

    Coping Strategies and Help-Seeking Behaviors among Survivors of Intimate Partner Violence: A Qualitative Study of Spouses of Men with Heavy Drinking in India

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    Background. Despite the high prevalence of intimate partner violence (IPV) against women in India (33%), there are persistently low rates of disclosure and help-seeking amongst survivors. The aim of this study was to explore both coping strategies employed by survivors and the perceived barriers and facilitators to seeking support from informal and formal resource networks. Methods. We conducted semistructured, in-depth qualitative interviews with thirty-five women survivors of IPV in Goa, India, in secure, private locations, utilizing flipcharts and vignettes to elicit deeper insights into efficacies of support resources. The data were transcribed, translated, and analyzed utilizing qualitative content analysis. Results. The most common coping mechanisms cited by survivors involved passive resistance, such as self-distraction, keeping quiet during violent outbursts, and leaving the home temporarily. Generally, survivors sought support from informal support networks (the natal family, in-laws, neighbors/community members, and close friends) before approaching formal support structures (medical/legal professionals, professors, police, and nongovernment organizations). In fact, informal structures were often facilitators of formal help-seeking. Survivors sought help at various stages of their marital relationship. Primary deterrents to help-seeking included the normalization of IPV by survivors and providers alike, resulting in the stigmatization of disclosing experiences of IPV and ostracism of survivors and close relatives; another barrier was a general lack of awareness of existing support resources. Conclusion. Our findings reveal that there are numerous barriers to help-seeking and shortcomings of support resources. Survivors’ evaluations of support resources reveal that robust, community-level, and meso-level structural changes are required to promote help-seeking behaviors, including the destigmatization of IPV amongst providers and broader society and raising awareness of available support resources

    Improving access to family planning for women with disabilities in Kaduna city, Nigeria: study protocol for a pragmatic cluster-randomized controlled trial with integrated process evaluation.

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    BACKGROUND: Globally, women with disabilities are less likely to have access to family planning services compared to their peers without disabilities. However, evidence of effective interventions for promoting their sexual and reproductive health and rights remains limited, particularly in low- and middle-income settings. To help address disparities, an inclusive sexual and reproductive health project was developed to increase access to modern contraceptive methods and reduce unmet need for family planning for women of reproductive age with disabilities in Kaduna city, Nigeria. The project uses demand-side, supply-side and contextual interventions, with an adaptive management approach. This protocol presents a study to evaluate the project's impact. METHODS: A pragmatic cluster-randomized controlled trial design with surveys at baseline and endline will be used to evaluate interventions delivered for at least 1 year at health facility and community levels in comparison to 'standard' state provision of family planning services, in the context of state-wide and national broadcast media and advocacy. Randomization will be conducted based on the health facility catchment area, with 19 clusters in the intervention arm and 18 in the control arm. The primary outcome measure will be access to family planning. It was calculated that at least 950 women aged 18 to 49 years with disabilities (475 in each arm) will be recruited to detect a 50% increase in access compared to the control arm. For each woman with disabilities enrolled, a neighbouring woman without disabilities in the same cluster and age group will be recruited to assess whether the intervention has a specific effect amongst women with disabilities. The trial will be complemented by an integrated process evaluation. Ethical approval for the study has been given by the National Health Research Ethics Committee of Nigeria and London School of Hygiene & Tropical Medicine. DISCUSSION: Defining access to services is complex, as it is not a single variable that can be measured directly and need for family planning is subjectively defined. Consequently, we have conceptualized 'access to family planning' based on a composite of beliefs about using services if needed. TRIAL REGISTRATION: ISRCTN registry ISRCTN12671153. Retrospectively registered on 17/04/2023

    Knowledge and use of voluntary food and drink guidelines in English nurseries? Results from a nationally representative cross-sectional study

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    Good nutrition in early life is vital for healthy development, and sets the stage for good health throughout the life-course. Most children aged 0–4 years old in the UK spend at least some time each week in an early years’ setting (EYS), such as a nursery or childminder. Unlike schools which serve older children, there are no statutory standards for the food and drinks served to the youngest children in EYS, despite the potential for greater public health gains due to early intervention. Two comprehensive, age-appropriate voluntary guidelines were developed, one called the Example Menus for Early Years Settings in England by the government and another, called Eat Better, Start Better by a charity. Both are seen as standard across the sector. To assess nurseries’ awareness and use of voluntary guidelines, including how they are used and how they can be improved upon, and examine how these vary by socioeconomic deprivation and setting types (private nurseries and voluntary, community and charity nurseries), we conducted the first nationally representative cross-sectional survey of nurseries in England via an online survey. Using frequency distributions and binomial multivariate logistic regression models, considerable discrepancies between awareness (82.6 %) and use (48.8 %) of available EYS dietary guidelines were found. A key reason for not using guidelines was ‘I know what is healthy without them.’ The question about whether following food and drink guidelines should be voluntary or statutory generated mixed findings. More research is required to understand the factors influencing nurseries’ views on whether guidelines should be voluntary or statutory

    Comparing the Performance of Three Models Incorporating Weather Data to Forecast Dengue Epidemics in Reunion Island, 2018-2019.

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    We developed mathematical models to analyze a large dengue virus (DENV) epidemic in Reunion Island in 2018-2019. Our models captured major drivers of uncertainty including the complex relationship between climate and DENV transmission, temperature trends, and underreporting. Early assessment correctly concluded that persistence of DENV transmission during the austral winter 2018 was likely and that the second epidemic wave would be larger than the first one. From November 2018, the detection probability was estimated at 10%-20% and, for this range of values, our projections were found to be remarkably accurate. Overall, we estimated that 8% and 18% of the population were infected during the first and second wave, respectively. Out of the 3 models considered, the best-fitting one was calibrated to laboratory entomological data, and accounted for temperature but not precipitation. This study showcases the contribution of modeling to strengthen risk assessments and planning of national and local authorities


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