Which clinical parameters predict a CSF diagnosis of meningitis in a population with high HIV prevalence?

Background. The HIV epidemic has changed the aetiology of meningitis in sub-Saharan Africa, and frontline clinicians are faced with a variety of meningitic presentations. Doctors working in resource-limited settings have the challenge of appropriately selecting patients for lumbar puncture (LP), a potentially risky procedure that requires laboratory analysis.Methods. In a rural South African hospital, the practice of performing LPs was audited against local guidelines. Data were collected retrospectively between February and June 2013. Symptoms and signs of meningitis, HIV status, investigations performed prior to LP and cerebrospinal fluid (CSF) results were recorded. With the aim of determining statistically significantclinical predictors of meningitis, parameters were explored using univariate and multivariate logistic regression analyses.Results. A total of 107 patients were included, of whom 43% had an  abnormal CSF result. The majority (76%) of patients were HIV-positive (CD4+ cell count <200 cells/ìl in 46%). Cryptococcal meningitis (CCM) was the most prevalent microbiological diagnosis, confirmed in 10 out of 12 patients. Of the non-microbiological diagnoses, lymphocytic predominance was the most common abnormality, present in 17 out of 33 patients. Confusion (p=0.011) was the most statistically significant predictor of anabnormal CSF result. Headache (p=0.355), fever (p=0.660) and  photophobia (p=0.634) were not statistically predictive.Conclusion. The high incidence of CCM correlates with previous data from sub-Saharan Africa. In populations with high HIV prevalence, the classic meningitic symptoms of headache, fever and photophobia, while common presenting symptoms, are significantly less predictive of a meningitis diagnosis than confusion

Clinical outcomes and outcome measurement tools reported in randomised controlled trials of treatment for snakebite envenoming: A systematic review

Background: Snakebite is a priority neglected tropical disease and causes a range of complications that vary depending on the snake species. Randomised clinical trials have used varied outcome measures that do not allow results to be compared or combined. In accordance with the Core Outcomes Measurements in Effectiveness Trials (COMET) initiative, this systematic review aims to support the development of a globally relevant core outcome set for snakebite. // Methods: All randomised controlled trials, secondary analyses of randomised controlled trials and study protocols investigating the efficacy of therapeutics for human snakebite envenoming were eligible for inclusion. Study screening and data extraction were conducted in duplicate by two independent reviewers. All primary and secondary outcome measures were extracted and compiled, as were adverse event outcome measures. Similar outcome measures were grouped into domains. The study was prospectively registered with PROSPERO: CRD42020196160.// Results: This systematic review included 43 randomised controlled trials, two secondary analyses and 13 study protocols. A total of 382 outcome measures were extracted and, after duplicates were merged, there were 153 unique outcomes. The most frequently used outcome domain (‘venom antigenaemia’) was included in less than one third of the studies. The unique outcomes were classified into 60 outcome domains. Patient-centred outcomes were used in only three of the studies. // Discussion: Significant heterogeneity in outcome measures exists in snakebite clinical trials. Consensus is needed to select outcome measures that are valid, reliable, patient-centred and feasible. The results of this systematic review strongly support the development of a core outcome set for use in snakebite clinical trials

Treatment outcomes of patients on Second-line Antiretroviral Therapy in resource-limited settings: A Systematic Review and Meta-Analysis

A growing proportion of patients on antiretroviral therapy in resource-limited settings have switched to second-line regimens. We carried out a systematic review in order to summarize reported rates and reasons for virological failure among people on second-line therapy in resource-limited settings

Clinical outcomes and outcome measurement tools reported in randomised controlled trials of treatment for snakebite envenoming: A systematic review

Background Snakebite is a priority neglected tropical disease and causes a range of complications that vary depending on the snake species. Randomised clinical trials have used varied outcome measures that do not allow results to be compared or combined. In accordance with the Core Outcomes Measurements in Effectiveness Trials (COMET) initiative, this systematic review aims to support the development of a globally relevant core outcome set for snakebite. Methods All randomised controlled trials, secondary analyses of randomised controlled trials and study protocols investigating the efficacy of therapeutics for human snakebite envenoming were eligible for inclusion. Study screening and data extraction were conducted in duplicate by two independent reviewers. All primary and secondary outcome measures were extracted and compiled, as were adverse event outcome measures. Similar outcome measures were grouped into domains. The study was prospectively registered with PROSPERO: CRD42020196160. Results This systematic review included 43 randomised controlled trials, two secondary analyses and 13 study protocols. A total of 382 outcome measures were extracted and, after duplicates were merged, there were 153 unique outcomes. The most frequently used outcome domain (‘venom antigenaemia’) was included in less than one third of the studies. The unique outcomes were classified into 60 outcome domains. Patient-centred outcomes were used in only three of the studies. Discussion Significant heterogeneity in outcome measures exists in snakebite clinical trials. Consensus is needed to select outcome measures that are valid, reliable, patient-centred and feasible. The results of this systematic review strongly support the development of a core outcome set for use in snakebite clinical trials

A long-term observational study of paediatric snakebite in Kilifi County, south-east Kenya

Introduction Estimates suggest that one-third of snakebite cases in sub-Saharan Africa affect children. Despite children being at a greater risk of disability and death, there are limited published data. This study has determined the: population-incidence and mortality rate of hospital-attended paediatric snakebite; clinical syndromes of snakebite envenoming; and predictors of severe local tissue damage. Methods All children presenting to Kilifi County Hospital, Kenya with snakebite were identified through the Kilifi Health and Demographic Surveillance System (KHDSS). Cases were prospectively registered, admitted for at least 24-hours, and managed on a paediatric high dependency unit (HDU). Households within the KHDSS study area have been included in 4-monthly surveillance and verbal autopsy, enabling calculation of population-incidence and mortality. Predictors of severe local tissue damage were identified using a multivariate logistic regression analysis. Results Between 2003 and 2021, there were 19,606 admissions to the paediatric HDU, of which 584 were due to snakebite. Amongst young children (≤5-years age) the population-incidence of hospital-attended snakebite was 11.3/100,000 person-years; for children aged 6–12 years this was 29.1/100,000 person-years. Incidence remained consistent over the study period despite the population size increasing (98,967 person-years in 2006; and 153,453 person-years in 2021). Most cases had local envenoming alone, but there were five snakebite associated deaths. Low haemoglobin; raised white blood cell count; low serum sodium; high systolic blood pressure; and an upper limb bite-site were independently associated with the development of severe local tissue damage. Conclusion There is a substantial burden of disease due to paediatric snakebite, and the annual number of cases has increased in-line with population growth. The mortality rate was low, which may reflect the species causing snakebite in this region. The identification of independent predictors of severe local tissue damage can help to inform future research to better understand the pathophysiology of this important complication

Where do those data go? Reuse of screening results from clinical trials to estimate population prevalence of HBV infection in adults in Kilifi, Kenya

Chronic hepatitis B infection (CHB) is a significant problem worldwide with around 300 million people infected. Ambitious goals have been set towards its elimination as a public health threat by 2030. However, accurate seroprevalence estimates in many countries are lacking or fail to provide representative population estimates, particularly in the WHO African Region (AFRO). This means the full extent of HBV infection is not well described, leading to a lack of investment in diagnostics, treatment and disease prevention. Clinical trials in the WHO AFRO region have been increasing over time and many test for infectious diseases including hepatitis B virus (HBV) to determine baseline eligibility for participants, however these screening data are not reported. Here we review data from six clinical trials completed at the KEMRI-Wellcome Trust Research Programme between 2016 and 2023 that screened for HBV using hepatitis B surface antigen (HBsAg) as part of the trial exclusion criteria. 1727 people had HBsAg results available, of which 60 tested positive. We generated a crude period HBV prevalence estimate of 3.5% (95% CI 2.6–4.5%), and after standardisation for sex and age to account for the population structure of the Kilifi Health Demographics Surveillance System (KHDSS), the prevalence estimate increased to 5.0% (95% CI 3.4–6.6%). The underrepresentation of women in these trials was striking with 1263/1641 (77%) of participants being male. Alanine aminotransferase (ALT) was significantly higher in the HBsAg positive group but was not outside the normal range. We argue that routine collation and publishing of data from clinical trials could increase precision and geographical representation of global HBV prevalence estimates, enabling evidence-based provision of clinical care pathways and public health interventions to support progress towards global elimination targets. We do acknowledge when using clinical trials data for seroprevalence estimates, that local population structure data is necessary to allow standardisation of results, and the point of care tests used here are limited in sensitivity and specificity

Which clinical parameters predict a CSF diagnosis of meningitis in a population with high HIV prevalence?

Background. The HIV epidemic has changed the aetiology of meningitis in sub-Saharan Africa, and frontline clinicians are faced with a variety of meningitic presentations. Doctors working in resource-limited settings have the challenge of appropriately selecting patients for lumbar puncture (LP), a potentially risky procedure that requires laboratory analysis. Methods. In a rural South African hospital, the practice of performing LPs was audited against local guidelines. Data were collected retrospectively between February and June 2013. Symptoms and signs of meningitis, HIV status, investigations performed prior to LP and cerebrospinal fluid (CSF) results were recorded. With the aim of determining statistically significant clinical predictors of meningitis, parameters were explored using univariate and multivariate logistic regression analyses. Results. A total of 107 patients were included, of whom 43% had an abnormal CSF result. The majority (76%) of patients were HIV-positive (CD4 + cell count <200 cells/µl in 46%). Cryptococcal meningitis (CCM) was the most prevalent microbiological diagnosis, confirmed in 10 out of 12 patients. Of the non-microbiological diagnoses, lymphocytic predominance was the most common abnormality, present in 17 out of 33 patients. Confusion (p=0.011) was the most statistically significant predictor of an abnormal CSF result. Headache (p=0.355), fever (p=0.660) and photophobia (p=0.634) were not statistically predictive. Conclusion. The high incidence of CCM correlates with previous data from sub-Saharan Africa. In populations with high HIV prevalence, the classic meningitic symptoms of headache, fever and photophobia, while common presenting symptoms, are significantly less predictive of a meningitis diagnosis than confusion

Where do those data go? Reuse of screening results from clinical trials to estimate population prevalence of HBV infection in adults in Kilifi, Kenya

Chronic hepatitis B infection (CHB) is a significant problem worldwide with around 300 million people infected. Ambitious goals have been set towards its elimination as a public health threat by 2030. However, accurate seroprevalence estimates in many countries are lacking or fail to provide representative population estimates, particularly in the WHO African Region (AFRO). This means the full extent of HBV infection is not well described, leading to a lack of investment in diagnostics, treatment and disease prevention. Clinical trials in the WHO AFRO region have been increasing over time and many test for infectious diseases including hepatitis B virus (HBV) to determine baseline eligibility for participants, however these screening data are not reported. Here we review data from six clinical trials completed at the KEMRI-Wellcome Trust Research Programme between 2016 and 2023 that screened for HBV using hepatitis B surface antigen (HBsAg) as part of the trial exclusion criteria. 1727 people had HBsAg results available, of which 60 tested positive. We generated a crude period HBV prevalence estimate of 3.5% (95% CI 2.6-4.5%), and after standardisation for sex and age to account for the population structure of the Kilifi Health Demographics Surveillance System (KHDSS), the prevalence estimate increased to 5.0% (95% CI 3.4-6.6%). The underrepresentation of women in these trials was striking with 1263/1641 (77%) of participants being male. Alanine aminotransferase (ALT) was significantly higher in the HBsAg positive group but was not outside the normal range. We argue that routine collation and publishing of data from clinical trials could increase precision and geographical representation of global HBV prevalence estimates, enabling evidence-based provision of clinical care pathways and public health interventions to support progress towards global elimination targets. We do acknowledge when using clinical trials data for seroprevalence estimates, that local population structure data is necessary to allow standardisation of results, and the point of care tests used here are limited in sensitivity and specificity

Is continuous positive airway pressure (CPAP) a new standard of care for type 1 respiratory failure in COVID-19 patients? A retrospective observational study of a dedicated COVID-19 CPAP service

The aim of this case series is to describe and evaluate our experience of continuous positive airway pressure (CPAP) to treat type 1 respiratory failure in patients with COVID-19. CPAP was delivered in negative pressure rooms in the newly repurposed infectious disease unit. We report a cohort of 24 patients with type 1 respiratory failure and COVID-19 admitted to the Royal Liverpool Hospital between 1 April and 30 April 2020. Overall, our results were positive; we were able to safely administer CPAP outside the walls of a critical care or high dependency unit environment and over half of patients (58%) avoided mechanical ventilation and a total of 19 out of 24 (79%) have survived and been discharged from our care

The 20-minute whole blood clotting test (20WBCT) for snakebite coagulopathy—A systematic review and meta-analysis of diagnostic test accuracy

Background The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of the 20WBCT was conducted to evaluate the accuracy of the 20WBCT to detect coagulopathy, indicative of systemic envenoming. Methods and findings Databases were searched from inception up to 09/12/2020 to identify studies that compared the 20WBCT and INR/fibrinogen on five or more subjects. Data was extracted from full-text articles by two reviewers using a predetermined form. Authors of 29 studies that lacked sufficient details in the manuscript were contacted and included if data meeting the inclusion criteria were provided. Included studies were evaluated for bias using a tailored QUADAS-2 checklist. The study protocol was prospectively registered on PROSPERO database (CRD42020168953). The searches identified 3,599 studies, 15 met the inclusion criteria and 12 were included in the meta-analysis. Data was reported from 6 countries and included a total of 2,270 patients. The aggregate weighted sensitivity of the 20WBCT at detecting INR >1.4 was 0.84 (CI 0.61 to 0.94), the specificity was 0.91 (0.76 to 0.97) and the SROC AUC was 0.94 (CI 0.91 to 0.96). The aggregate weighted sensitivity of the 20WBCT at detecting fibrinogen <100 mg/dL was 0.72 (CI 0.58 to 0.83), the specificity was 0.94 (CI 0.88 to 0.98) and the SROC AUC was 0.93 (0.91 to 0.95). Both analyses that used INR and fibrinogen as the reference test displayed considerable heterogeneity. Conclusions In the absence of laboratory clotting assays, the 20WBCT remains a highly specific and fairly sensitive bedside test at detecting coagulopathy following snakebite. However, clinicians should be aware of the importance of operator training, standardized equipment and the lower sensitivity of the 20WBCT at detecting mild coagulopathy and resolution of coagulopathy following antivenom