Background Probiotics may be effective in reducing the duration of acute infectious diarrhoea. Objectives To assess the effects of probiotics in proven or presumed acute infectious diarrhoea. Search methods We searched the trials register of the Cochrane Infectious Diseases Group, MEDLINE, and Embase from inception to 17 December 2019, as well as the Cochrane Controlled Trials Register (Issue 12, 2019), in the Cochrane Library, and reference lists from studies and reviews. We included additional studies identified during external review. Selection criteria Randomized controlled trials comparing a specified probiotic agent with a placebo or no probiotic in people with acute diarrhoea that is proven or presumed to be caused by an infectious agent. Data collection and analysis Two review authors independently applied inclusion criteria, assessed risk of bias, and extracted data. Primary outcomes were measures of diarrhoea duration (diarrhoea lasting ≥ 48 hours; duration of diarrhoea). Secondary outcomes were number of people hospitalized in community studies, duration of hospitalization in inpatient studies, diarrhoea lasting ≥ 14 days, and adverse events. Main results We included 82 studies with a total of 12,127 participants. These studies included 11,526 children (age < 18 years) and 412 adults (three studies recruited 189 adults and children but did not specify numbers in each age group). No cluster‐randomized trials were included. Studies varied in the definitions used for "acute diarrhoea" and "end of the diarrhoeal illness" and in the probiotic(s) tested. A total of 53 trials were undertaken in countries where both child and adult mortality was low or very low, and 26 where either child or adult mortality was high. Risk of bias was high or unclear in many studies, and there was marked statistical heterogeneity when findings for the primary outcomes were pooled in meta‐analysis. Effect size was similar in the sensitivity analysis and marked heterogeneity persisted. Publication bias was demonstrated from funnel plots for the main outcomes. In our main analysis of the primary outcomes in studies at low risk for all indices of risk of bias, no difference was detected between probiotic and control groups for the risk of diarrhoea lasting ≥ 48 hours (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.91 to 1.09; 2 trials, 1770 participants; moderate‐certainty evidence); or for duration of diarrhoea (mean difference (MD) 8.64 hours shorter, 95% CI 29.4 hours shorter to 12.1 hours longer; 6 trials, 3058 participants; very low‐certainty evidence). Effect size was similar and marked heterogeneity persisted in pre‐specified subgroup analyses of the primary outcomes that included all studies. These included analyses limited to the probiotics Lactobacillus rhamnosus GG and ...

Background: Major infectious disease outbreaks are a constant threat to human health. Clinical research responses to outbreaks generate evidence to improve outcomes and outbreak control. Experiences from previous epidemics have identified multiple challenges to undertaking timely clinical research responses. This scoping review is a systematic appraisal of political, economic, administrative, regulatory, logistical, ethical and social (PEARLES) challenges to clinical research responses to emergency epidemics and solutions identified to address these. Methods: A scoping review. We searched six databases (MEDLINE, Embase, Global Health, PsycINFO, Scopus and Epistemonikos) for articles published from 2008 to July 2018. We included publications reporting PEARLES challenges to clinical research responses to emerging epidemics and pandemics and solutions identified to address these. Two reviewers screened articles for inclusion, extracted and analysed the data. Results: Of 2678 articles screened, 76 were included. Most presented data relating to the 2014-2016 Ebola virus outbreak or the H1N1 outbreak in 2009. The articles related to clinical research responses in Africa (n = 37), Europe (n = 8), North America (n = 5), Latin America and the Caribbean (n = 3) and Asia (n = 1) and/or globally (n = 22). A wide range of solutions to PEARLES challenges was presented, including a need to strengthen global collaborations and coordination at all levels and develop pre-approved protocols and equitable frameworks, protocols and standards for emergencies. Clinical trial networks and expedited funding and approvals were some solutions implemented. National ownership and community engagement from the outset were a key enabler for delivery. Despite the wide range of recommended solutions, none had been formally evaluated.

Scabies is known to be a public health problem in many settings but the majority of recent data is from rural settings in the Pacific. There is a need for high quality data from sub-Saharan Africa and peri-urban settings to inform scale up of scabies control efforts. There have been anecdotal reports of scabies being a public health problem in Liberia but robust data are lacking. We conducted a cross-sectional cluster-randomised prevalence survey for scabies in a peri-urban community in Monrovia, Liberia in February-March 2020. Participants underwent a standardised examination conducted by trained local health care workers. Health related quality of life (HRQoL) was assessed using age-appropriate versions of the dermatology life quality index (DLQI). Prevalence estimates were calculated accounting for clustering at community and household levels and associations with key demographic variables assessed through multivariable random-effects logistic regression. 1,318 participants from 477 households were surveyed. The prevalence of scabies was 9.3% (95% CI: 6.5–13.2%), across 75 (19.7%) households; impetigo or infected scabies prevalence was 0.8% (95% CI: 0.4–1.9%). The majority (52%) of scabies cases were classified as severe. Scabies prevalence was lower in females and higher in the youngest age group; no associations were found with other collected demographic or socio-economic variables. DLQI scores indicated a very or extremely large effect on HRQoL in 29% of adults and 18% of children diagnosed with scabies. Our study indicates a substantial burden of scabies in this peri-urban population in Liberia. This was associated with significant impact on quality of life, highlighting the need for action to control scabies in this population. Further work is needed to assess the impact of interventions in this context on both the prevalence of scabies and quality of life.

Background The International Alliance for the Control of Scabies (IACS) recently published expert consensus criteria for scabies diagnosis. Formal validation of these criteria is needed to guide implementation. We conducted a study to provide detailed description of the morphology and distribution of scabies lesions as assessed by dermatologists and validate the IACS criteria for diagnosis by both expert and non-expert examiners. Methods Participants from a community in Monrovia, Liberia, were independently assessed by two dermatologists and six non-expert examiners. Lesion morphology and distribution were documented based on the dermatologist examination. Diagnoses were classified by IACS criteria and the sensitivity and specificity of non-expert examiner assessments calculated. Results Papules were the most common lesions (97.8%). Burrows were found in just under half (46.7%) and dermatoscopy was positive in a minority (13.3%). Scabies lesions were found in all body regions but more than 90% of patients could have been diagnosed by an examination of only the limbs. Severity of itch was associated with lesion number (p = 0.003). The sensitivity of non-expert examiners to detect typical scabies ranged between 69-83% and specificity 70-96%. The sensitivity of non-expert examiners was higher in more extensive disease (78-94%).

Background Scabies is known to be a public health problem in many settings but the majority of recent data is from rural settings in the Pacific. There is a need for high quality data from sub-Saharan Africa and peri-Urban settings to inform scale up of scabies control efforts. There have been anecdotal reports of scabies being a public health problem in Liberia but robust data are lacking. Methods We conducted a cross-sectional cluster-randomised prevalence survey for scabies in a peri-urban community in Monrovia, Liberia in February-March 2020. Participants underwent a standardised examination conducted by trained local health care workers. Health related quality of life (HRQoL) was assessed using age-appropriate dermatology life quality indices (DLQIs). Prevalence estimates were calculated accounting for clustering at community and household levels and associations with key demographic variables assessed through multivariable random-effects logistic regression. Results 1,318 participants from 477 households were surveyed. The prevalence of scabies prevalence was 9.3% (95% CI: 6.5-13.2%), across 75 (19.7%) households; impetigo or infected scabies prevalence was 0.8% (95% CI: 0.4-1.9%). The majority (52%) of scabies cases were classified as severe. Scabies prevalence was lower in females and higher in the youngest age group; no associations were found with other collected demographic or socio-economic variables. DLQI scores indicated a very or extremely large effect on HRQoL in 29% of adults and 18% of children diagnosed with scabies. Conclusions Our study indicates a substantial burden of scabies in this peri-Urban population in Liberia. This was associated with significant impact on quality of life, highlighting the need for action to control scabies in this population. Further work is needed to assess the impact of interventions in this context on both the prevalence of scabies and quality of life.

Background The International Alliance for the Control of Scabies (IACS) recently published expert consensus criteria for scabies diagnosis. Formal validation of these criteria is needed to guide implementation. We conducted a study to provide detailed description of the morphology and distribution of scabies lesions as assessed by dermatologists and validate the IACS criteria for diagnosis by both expert and non-expert examiners. Methods Participants from a community in Monrovia, Liberia, were independently assessed by two dermatologists and six mid-level healthcare workers. Lesion morphology and distribution were documented based on the dermatologist examination. Diagnoses were classified by IACS criteria and the sensitivity and specificity of MLHW assessments calculated. Results Papules were the most common lesions (97.8%). Burrows were found in just under half (46.7%) and dermatoscopy was positive in a minority (13.3%). Scabies lesions were found in all body regions but more than 90% of patients could have been diagnosed by an examination of only the limbs. Severity of itch was associated with lesion number (p=0.003). The sensitivity of MLHWs to detect typical scabies ranged between 69-83% and specificity 70-96%. The sensitivity of MLHWs was higher in more extensive disease (78-94%). Conclusions The IACS criteria proved a valid tool for scabies diagnosis. For the purposes of implementation papules and burrows represent truly typical scabies lesions. MLHWs are able to diagnose scabies with a high degree of accuracy, demonstrating they could form a key component in population-level control strategies.

BackgroundBuruli ulcer is a chronic ulcerating skin condition, with the highest burden found in Central and West Africa where it disproportionately affects the most vulnerable populations. Treatment is demanding, comprising eight-weeks of daily antibiotics, regular wound care and possible surgical intervention. Treatment completion is key to optimising outcomes, however the degree of and barriers to this are not well understood. Recent change from injectable treatment (SR8) to oral treatment (CR8) has made it feasible to further decentralise care, potentially improving treatment access and completion. However, the impact of this and of other demographic and clinical influences on treatment completion must be explored first to ensure appropriate models of care are developed. Methodology/Principal findingsA retrospective clinical notes review and secondary data analysis of records from patients diagnosed between 1 January 2006-31 December 2018 at four district hospital clinics in the Ashanti and Central Regions, Ghana. Univariable analyses and multivariable logistic regression were performed to assess the association between explanatory variables and treatment completion.There were 931 patient episodes across the four clinics with overall treatment completion of 84.4%. CR8 was associated with higher treatment completion compared to SR8 (OR 4.1, P = 0.001). There was no statistically significant association found between distance from patient residence to clinic and treatment completion. Conclusions/SignificanceImproved treatment completion with CR8 supports its use as first line therapy and may enable decentralisation to fully community-based care. We did not find an association between distance to care and treatment completion, though analyses were limited by data availability. However, we did find evidence that distance to care continues to be associated with more severe forms of disease, which may reflect the higher costs of accessing care PLOS NEGLECTED TROPICAL DISEASES

Background Clinical research generates evidence for improving clinical management and control of emerging epidemics. However, experiences from previous disease outbreaks have identified multiple challenges to undertaking necessary clinical research in a timely way. We aimed to identify how political, economic, administrative, regulatory, logistical, ethical, and social (PEARLES) challenges can be overcome to advance clinical research preparedness and responses to emerging epidemics by searching the literature.Methods In this systematic review, we searched six databases (MEDLINE, Embase, Ovid Global Health, PsycINFO, Scopus, and Epistemonikos) for English language articles published between Jan 1, 2008, and July 31, 2018. We included articles about clinical research responses (ie, responses regarding the safety and effectiveness of medications, treatment regimens [including supportive care], devices, or diagnostic products intended for human use) to epidemics that were declared a public health emergency of international concern and that contained up-to-date information. We did not include studies that only focused on public health responses. Two reviewers screened records for inclusion and extracted and summarised the data using a narrative approach. We included publications reporting PEARLES challenges of, and solutions to, the instigation of clinical research responses to emerging epidemics, or solutions identified through research with health system stakeholders. FindingsOf 2678 articles screened for inclusion, 76 articles were included. Most presented clinical research experiences from the 2014-16 Ebola virus disease outbreak (58 [76%]) or the 2009 H1N1 pandemic (20 [26%]), or both. The articles related to studies set in Africa (n=37), Europe (n=8), North America (n=5), Latin America and the Caribbean (n=3), and Asia (n=1); 22 articles covered a global perspective. The publications presented a range of challenges to delivering clinical research. Some were universal, others depended on the context and nature of the outbreak. International agreed frameworks, research protocols and standards, data sharing agreements, ethical publication standards, and incentivised, primed, global clinical research networks were among the solutions recommended, together with national ownership and community engagement from the outset and strengthening of country research capacity. Despite the wide range of recommended solutions, none had been formally evaluated.Interpretation To strengthen global preparedness to emerging epidemics, solutions for rapid clinical research deployment, delivery, and dissemination must be developed, implemented, and evaluated. Improvements are urgently needed to develop and strengthen collaborations, funding mechanisms, global and national research capacity, preapproved protocols, tools, and frameworks for various contexts and scenarios. Clinical research communities globally need to evaluate their activities and refine and rehearse outbreak research response plans in between epidemics.