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Oxford Centre for Tropical Medicine and Global Health
Epidemiology of Burkholderia pseudomallei, Streptococcus suis, Salmonella spp., Shigella spp. and Vibrio spp. infections in 111 hospitals in Thailand, 2022
The information on notifiable diseases in low- and middle-income countries is often incomplete, limiting our understanding of their epidemiology. Our study addresses this knowledge gap by analyzing microbiology laboratory and hospital admission data from 111 of 127 public referral hospitals in Thailand, excluding Bangkok, from January to December 2022. We evaluated factors associated with the incidence of notifiable bacterial diseases (NBDs) caused by 11 pathogens; including Brucella spp., Burkholderia pseudomallei, Corynebacterium diphtheriae, Neisseria gonorrhoeae, Neisseria meningitidis, non-typhoidal Salmonella spp. (NTS), Salmonella enterica serovar Paratyphi, Salmonella enterica serovar Typhi, Shigella spp., Streptococcus suis, and Vibrio spp.. We used multivariable Poisson random-effects regression models. Additionally, we compared their yearly incidence rates in 2022 with those from 2012-2015 in hospitals where paired data were available. In 2022, the NBD associated with the highest total number of deaths was B. pseudomallei (4,407 patients; 1,219 deaths) infection, followed by NTS (4,501 patients; 461 deaths), S. suis (867 patients, 134 deaths) and Vibrio spp. (809 patients, 122 deaths) infection. The incidence rates of B. pseudomallei, S. suis and Vibrio spp. infections were highest in the northeast, upper central and west, respectively. The incidence rate of NTS infection was generally high across all geographical regions. The yearly incidence rates of B. pseudomallei and S. suis infections in 2022 were higher than those between 2012-2015, while those of fecal-oral transmitted NBDs including NTS infection, typhoid, shigellosis and vibriosis were lower. Overall, B. pseudomallei and S. suis infections are emerging and associated with a very high number of deaths in Thailand. Although the incidence of NTS infection and vibriosis are decreasing, they are still associated with a high number of cases and deaths. Specific public health interventions are warranted.
Prediction of PaO2 from SpO2 values in critically ill invasively ventilated patients: rationale and protocol for a patient-level analysis of ERICC, LUNG SAFE, PRoVENT and PRoVENT-iMiC (PRoPERLy II).
INTRODUCTION: In patients with acute respiratory distress syndrome (ARDS), mortality risk is typically assessed using the arterial partial pressure of oxygen (PaO2) divided by the fraction of inspired oxygen (FiO2), known as the PaO2/FiO2 ratio. Recently, the SpO2/FiO2 ratio, which uses peripheral oxygen saturation (SpO2) instead of PaO2, has been suggested as a reasonable alternative when there is little access to arterial blood gas analyses. Additionally, equations that predict PaO2 from SpO2 values could offer another viable method for assessment. AIM: To evaluate the accuracy of methods for predicting PaO2 from SpO2 values and compare risk stratification based on measured versus predicted PaO2/FiO2 ratios using a large database that harmonizes the individual data of patients included in four observational studies. METHODS AND ANALYSIS: The individual data from four observational studies ('Epidemiology of Respiratory Insufficiency in Critical Care study' [ERICC], 'Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure' [LUNG SAFE], 'PRactice of VENTilation in critically ill patients without ARDS' [PRoVENT], and 'PRactice of VENTilation in critically ill patients in Middle-income Countries' [PRoVENT-iMiC]) were harmonized and pooled into a database named 'PRoPERLy II'. The primary endpoint of this planned analysis will be the accuracy of currently available methods to predict PaO2 from SpO2 values. The secondary endpoint will be the accuracy of classification based on SpO2/FiO2 ratio and the predicted PaO2/FiO2 ratio. DISSEMINATION: Our planned analysis addresses a clinically important research question by comparing different equations for predicting PaO2 from SpO2 values.
Simplifying medicine dosing for children by harmonising weight bands across therapeutic areas.
Generally, dose recommendations for children are expressed as fixed dosing increments related to bodyweight, known as weight bands. The weight bands recommended in WHO treatment guidelines vary between diseases, leading to complexity and potential dosing errors when treating children for multiple diseases simultaneously. The introduction of a harmonised weight banding approach for orally administered drugs across disease areas could streamline dosing for young children, but implementing such an approach would require changes in current dosing recommendations. In this Health Policy, we describe the process we conducted to: identify therapeutic areas for harmonisation of weight bands; propose a harmonised weight-banding system to align with current use of weight bands in antibiotic guidance; and simulate the expected effect of dose adjustments due to weight-band harmonisation. Each step of this process, along with the effect and feasibility of weight-band harmonisation was discussed with clinical, policy, and pharmacology experts convened by WHO, representing four therapeutic areas: tuberculosis, HIV, malaria, and hepatitis C. Dosing according to harmonised weight bands across the targeted therapeutic areas was found to be feasible and should be considered for implementation by WHO disease programmes through their appropriate normative processes.
Using Dried Blood Spots to Quantitatively Detect Anti–SARS-CoV-2 IgG Antibodies by ELISA: A Validation Study
ABSTRACT. SARS-CoV-2 serological testing is useful to determine seroprevalence, epidemiological trends, and the extent of transmission. The collection and transport of serum samples can be logistically challenging, especially in remote underserved areas. Dried blood spots (DBSs) would allow easier sample collection and logistical handling compared with standard serum collection, particularly for extensive and repeated SARS-CoV-2 serosurveys. We evaluated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the IgG ELISA (Wantai, Beijing, China) using DBSs against sera for the quantitative detection of SARS-CoV-2 IgG antibody. The IgG ELISA was used to test paired sera and DBSs obtained from individuals with recent virologically confirmed COVID-19 illness and banked paired sera and DBSs collected before the COVID-19 pandemic. We found that 100/100 (100%) seropositive samples were positive using DBSs, and 193/194 (99%) seronegative samples were negative using DBSs. Compared with sera, the DBS method had a 100% sensitivity, 99% specificity, 99% PPV, and 100% NPV. Use of DBSs for SARS-CoV-2 household or population serosurveys may be considered in situations with limitations in sample collection, shipment, and storage.
Do Oral Cholera Vaccine and Water, Sanitation, and Hygiene Combine to Provide Greater Protection Against Cholera? Results From a Cluster-Randomized Trial of Oral Cholera Vaccine in Kolkata, India
Abstract Background Oral cholera vaccine (OCV) and incremental improvements in household water, sanitation, and hygiene (WASH) within cholera-endemic areas can reduce cholera risk. However, we lack empiric evaluation of their combined impact. Methods We evaluated a cluster-randomized, placebo-controlled trial of OCV (Shanchol) in Kolkata, India. The study population included 108 777 individuals, and 106 879 nonpregnant individuals >1 year of age were eligible to receive 2 doses of OCV or placebo. We measured cholera risk in all household members assigned to OCV vs placebo and in all members of households with “Better” vs “Not Better” WASH, where WASH was classified according to validated criteria. Protection was measured by Cox proportional hazard models. Results Residence in an OCV household was associated with protective effectiveness (PE) of 54% (95% CI, 42%–64%; P < .001) and was similar regardless of Better (PE, 57%; 95% CI, 26%–75%; P = .002) or Not Better (PE, 53%; 95% CI, 40%–64%; P < .001) household WASH. Better WASH household residence was associated with PE of 30% (95% CI, 5%–48%; P = .023) and was similar in OCV (PE, 24%; 95% CI, −26% to 54%; P = .293) and placebo (PE, 29%; 95% CI, −3% to 51%; P = .069) households. When assessed conjointly, residence in OCV households with Better WASH was associated with the greatest PE against cholera at 69% (95% CI, 49%–81%; P < .001). Conclusions These findings suggest that the combination of a vaccine policy and improved WASH reduces cholera risk more than either would alone, although the magnitude of either intervention was not affected by the other. Future randomized trials investigating OCV and WASH interventions separately and together are recommended to further understand the interaction between OCV and WASH.
Association Among Household Water, Sanitation, and Hygiene (WASH) Status and Typhoid Risk in Urban Slums: Prospective Cohort Study in Bangladesh
Background Typhoid fever, or enteric fever, is a highly fatal infectious disease that affects over 9 million people worldwide each year, resulting in more than 110,000 deaths. Reduction in the burden of typhoid in low-income countries is crucial for public health and requires the implementation of feasible water, sanitation, and hygiene (WASH) interventions, especially in densely populated urban slums. Objective In this study, conducted in Mirpur, Bangladesh, we aimed to assess the association between household WASH status and typhoid risk in a training subpopulation of a large prospective cohort (n=98,087), and to evaluate the performance of a machine learning algorithm in creating a composite WASH variable. Further, we investigated the protection associated with living in households with improved WASH facilities and in clusters with increasing prevalence of such facilities during a 2-year follow-up period. Methods We used a machine learning algorithm to create a dichotomous composite variable (“Better” and “Not Better”) based on 3 WASH variables: private toilet facility, safe drinking water source, and presence of water filter. The algorithm was trained using data from the training subpopulation and then validated in a distinct subpopulation (n=65,286) to assess its sensitivity and specificity. Cox regression models were used to evaluate the protective effect of living in “Better” WASH households and in clusters with increasing levels of “Better” WASH prevalence. Results We found that residence in households with improved WASH facilities was associated with a 38% reduction in typhoid risk (adjusted hazard ratio=0.62, 95% CI 0.49-0.78; P<.001). This reduction was particularly pronounced in individuals younger than 10 years at the first census participation, with an adjusted hazard ratio of 0.49 (95% CI 0.36-0.66; P<.001). Furthermore, we observed an inverse relationship between the prevalence of “Better” WASH facilities in clusters and the incidence of typhoid, although this association was not statistically significant in the multivariable model. Specifically, the adjusted hazard of typhoid decreased by 0.996 (95% CI 0.986-1.006) for each percent increase in the prevalence of “Better” WASH in the cluster (P=.39). Conclusions Our findings demonstrate that existing variations in household WASH are associated with differences in the risk of typhoid in densely populated urban slums. This suggests that attainable improvements in WASH facilities can contribute to enhanced typhoid control, especially in settings where major infrastructural improvements are challenging. These findings underscore the importance of implementing and promoting comprehensive WASH interventions in low-income countries as a means to reduce the burden of typhoid and improve public health outcomes in vulnerable populations.
Better Existing Water, Sanitation, and Hygiene Can Reduce the Risk of Cholera in an Endemic Setting: Results From a Prospective Cohort Study From Kolkata, India
Abstract Background Global cholera control efforts rely heavily on effective water, sanitation, and hygiene (WASH) interventions in cholera-endemic settings. Methods Using data from a large, randomized controlled trial of oral cholera vaccine conducted in Kolkata, India, we evaluated whether natural variations in WASH in an urban slum setting were predictive of cholera risk. From the control population (n = 55 086), baseline WASH data from a randomly selected “training subpopulation” (n = 27 634) were analyzed with recursive partitioning to develop a dichotomous (“better” vs “not better”) composite household WASH variable from several WASH features collected at baseline, and this composite variable was then evaluated in a mutually exclusive “validation population” (n = 27 452). We then evaluated whether residents of better WASH households in the entire population (n = 55 086) experienced lower cholera risk using Cox regression models. Better WASH was defined by a combination of 4 dichotomized WASH characteristics including safe source of water for daily use, safe source of drinking water, private or shared flush toilet use, and always handwashing with soap after defecation. Results Residence in better WASH households was associated with a 30% reduction in risk of cholera over a 5-year period (adjusted hazard ratio, 0.70 [95% confidence interval, .49–.99]; P = .048). We also found that the impact of better WASH households on reducing cholera risk was greatest in young children (0–4 years) and this effect progressively declined with age. Conclusions The evidence suggests that modest improvements in WASH facilities and behaviors significantly modify cholera risk and may be an important component of cholera prevention and elimination strategies in endemic settings. Clinical Trials Registration. NCT00289224.
Prevention of Typhoid by Vi Conjugate Vaccine and Achievable Improvements in Household Water, Sanitation, and Hygiene: Evidence From a Cluster-Randomized Trial in Dhaka, Bangladesh
AbstractBackgroundTyphoid fever contributes to approximately 135 000 deaths annually. Achievable improvements in household water, sanitation, and hygiene (WASH) combined with vaccination using typhoid conjugate vaccines (TCVs) may be an effective preventive strategy. However, little is known about how improved WASH and vaccination interact to lower the risk of typhoid.MethodsA total of 61 654 urban Bangladeshi children aged 9 months to <16 years, residing in 150 clusters with a baseline population of 205 760 residents, were randomized 1:1 by cluster to Vi-tetanus toxoid TCV or Japanese encephalitis (JE) vaccine. Surveillance for blood culture–confirmed typhoid fever was conducted over 2 years. Existing household WASH status was assessed at baseline as Better or Not Better using previously validated criteria. The reduction in typhoid risk among all residents associated with living in TCV clusters, Better WASH households, or both was evaluated using mixed-effects Poisson regression models.ResultsThe adjusted reduced risk of typhoid among all residents living in the clusters assigned to TCV was 55% (95% confidence interval [CI], 43%–65%; P < .001), and that of living in Better WASH households, regardless of cluster, was 37% (95% CI, 24%–48%; P < .001). The highest risk of typhoid was observed in persons living in households with Not Better WASH in the JE clusters. In comparison with these persons, those living in households with Better WASH in the TCV clusters had an adjusted reduced risk of 71% (95% CI, 59%–80%; P < .001).ConclusionsImplementation of TCV programs combined with achievable and culturally acceptable household WASH practices were independently associated with a significant reduction in typhoid risk.Clinical Trials RegistrationISRCTN11643110.
Are better existing WASH practices in urban slums associated with a lower long-term risk of severe cholera? A prospective cohort study with 4 years of follow-up in Mirpur, Bangladesh
ObjectiveTo investigate the association between existing household water quality, sanitation and hygiene (WASH) practices and severe cholera risk in a dense urban slum where cholera is highly endemic.Design, setting and participantsWe assembled a large prospective cohort within a cluster randomised trial evaluating the effectiveness of oral cholera vaccine. Our dynamic cohort population (n=193 576) comprised individuals living in the ‘non-intervention’ clusters of the trial, and were followed over 4 years. This study was conducted in a dense urban slum community of Dhaka, Bangladesh and cholera surveillance was undertaken in 12 hospitals serving the study area.Primary outcome measureFirst severe cholera episode detected during follow-up period.MethodsWe applied a machine learning algorithm on a training subpopulation (n=96 943) to develop a binary (‘better’, ‘not better’) composite WASH variable predictive of severe cholera. The WASH rule was evaluated for performance in a separate validation subpopulation (n=96 633). Afterwards, we used Cox regression models to evaluate the association between ‘better’ WASH households and severe cholera risk over 4 years in the entire study population.ResultsThe ‘better’ WASH rule found that water quality and access were the most significant factors associated with severe cholera risk. Members of ‘better’ WASH households, constituting one-third of the population, had a 47% reduced risk of severe cholera (95% CI: 29 to 69; p<0.001), after adjusting for covariates. The protective association between living in a ‘better’ WASH household and severe cholera persisted in all age groups.ConclusionsSalutary existing household WASH practices were associated with a significantly reduced long-term risk of severe cholera in an urban slum of Dhaka. These findings suggest that WASH adaptations already practised in the community may be important for developing and implementing effective and sustainable cholera control programmes in similar settings.Trial registration numberThis article is a re-analysis of data from a cluster randomized trial; can be found on ClinicalTrials.govNCT01339845