Occurrence of human infection with Salmonella Typhi in sub-Saharan Africa.

Typhoid fever, caused by Salmonella enterica serovar Typhi, results in over 1.2 million cases and 29 thousand deaths annually from sub-Saharan Africa. Combating this disease requires various intervention approaches, such as typhoid conjugate vaccines and improving water, sanitation, and hygiene. Enhancing the effectiveness of these strategies necessitates a deeper understanding of the variation of the typhoid fever across the target region. Although the magnitude and variation of typhoid fever at the country level have been studied globally, sub-national variation remains underexplored. To address this gap, we collected data from 229 published reports on typhoid fever occurrences in sub-Saharan Africa between January 2000 and December 2020. The dataset includes information on the year and geographical location of observation, diagnostic tests used, and the type of studies in which typhoid fever was reported. By analyzing this dataset, we can gain insights into the sub-national heterogeneity of typhoid fever's burden in the region. This knowledge will be instrumental in designing more effective intervention strategies to combat the disease.

Association Between Median Household Income and Perioperative Outcomes of Lumbar Spinal Fusion: An Analysis of the National Inpatient Sample (2009-2020).

BACKGROUND: Relationships between low socioeconomic status and surgical outcomes are well established for certain procedures. However, scant literature has focused on relationships between median household income and lumbar fusion outcomes. METHODS: Patients who underwent fusion procedures between January 1, 2009 and December 31, 2020 were identified from the National Inpatient Sample database. They were categorized into 4 quartiles, from lowest to highest, based on median household incomes in respective zip codes. We applied univariable and multivariable linear and logistic regression models to analyze perioperative data according to income quartiles. RESULTS: We included 2,826,396 patients. In multivariable regression, patients in the 3 lowest income quartiles exhibited higher rates of in-hospital cardiac events perioperatively, with odds ratios (ORs) of 1.19 (95% confidence interval [CI]1.13-1.26, P < 0.001), 1.10 (95% CI 1.05-1.16, P < 0.001), and 1.06 (95% CI 1.01-1.12, P = 0.011) for the first, second, and third quartiles, respectively. Patients in the lowest income (first) quartile had a higher occurrence of perioperative urinary complications (OR = 1.07, 95% CI 1.03-1.12, P = 0.001), systemic infectious complications (OR = 1.17, 95% CI 1.04-1.32, P = 0.006), neurological deficit (OR = 1.17, 95% CI 1.06-1.30, P = 0.002), and wound infections (OR = 1.22, 95% CI 1.12-1.34, P < 0.001). Those in the 3 lowest income quartiles were less likely to experience respiratory, gastrointestinal, and venous thrombotic complications (P < 0.05). The lowest income quartile had protective associations for dural tears (OR 0.93, 95% CI 0.89-0.99, P = 0.038) and postprocedure anemia across all 3 lower quartiles, with OR < 1 and P < 0.001. CONCLUSIONS: Reduced household income significantly affected perioperative outcomes after lumbar fusion and should be taken into consideration during the perioperative period.

Spatial and temporal clustering of typhoid fever in an urban slum of Dhaka City: Implications for targeted typhoid vaccination.

BACKGROUND: Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans are the only reservoir, inadequate water, sanitation, and hygiene infrastructure increases risk of typhoid. High-quality data to assess spatial and temporal relationships in disease dynamics are scarce. METHODS: We analyzed data from a prospective cohort conducted in an urban slum area of Dhaka City, Bangladesh. Passive surveillance at study centers identified typhoid cases by microbiological culture. Each incident case (index case) was matched to two randomly selected index controls, and we measured typhoid incidence in the population residing in a geographically defined region surrounding each case and control. Spatial clustering was evaluated by comparing the typhoid incidence in residents of geometric rings of increasing radii surrounding the index cases and controls over 28 days. Temporal clustering was evaluated by separately measuring incidence in the first and second 14-day periods following selection. Incidence rate ratios (IRRs) were calculated using Poisson regression models. RESULTS: We evaluated 141 typhoid index cases. The overall typhoid incidence was 0.44 per 100,000 person-days (PDs) (95% CI: 0.40, 0.49). In the 28 days following selection, the highest typhoid incidence (1.2 per 100,000 PDs [95% CI: 0.8, 1.6]) was in the innermost cluster surrounding index cases. The IRR in this innermost cluster was 4.9 (95% CI: 2.4, 10.3) relative to the innermost control clusters. Neither typhoid incidence rates nor relative IRR between index case and control populations showed substantive differences in the first and second 14-day periods after selection. CONCLUSION: In the absence of routine immunization programs, geographic clustering of typhoid cases suggests a higher intensity of typhoid risk in the population immediately surrounding identified cases. Further studies are needed to understand spatial and temporal trends and to evaluate the effectiveness of targeted vaccination in disrupting typhoid transmission.

American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator as a Predictor of Postoperative Outcomes After Adult Spinal Deformity Surgery: A Retrospective Cohort Analysis.

BACKGROUND AND OBJECTIVES: In recent years, there has been an outpouring of scoring systems that were built to predict outcomes after various surgical procedures; however, research validating these studies in spinal surgery is quite limited. In this study, we evaluated the predictability of the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator (ACS NSQIP SRC) for various postoperative outcomes after spinal deformity surgery. METHODS: A retrospective chart review was conducted to identify patients who underwent spinal deformity surgery at our hospital between January 1, 2014, and December 31, 2022. Demographic and clinical data necessary to use the ACS NSQIP SRC and postoperative outcomes were collected for these patients. Predictability was analyzed using the area under the curve (AUC) of receiver operating characteristic curves and Brier scores. RESULTS: Among the 159 study patients, the mean age was 64.5 ± 9.5 years, mean body mass index was 31.9 ± 6.6, and 95 (59.7%) patients were women. The outcome most accurately predicted by the ACS NSQIP SRC was postoperative pneumonia (observed = 5.0% vs predicted = 3.2%, AUC = 0.75, Brier score = 0.05), but its predictability still fell below the acceptable threshold. Other outcomes that were underpredicted by the ACS NSQIP SRC were readmission within 30 days (observed = 13.8% vs predicted = 9.0%, AUC = 0.63, Brier score = 0.12), rate of discharge to nursing home or rehabilitation facilities (observed = 56.0% vs predicted = 46.6%, AUC = 0.59, Brier = 0.26), reoperation (observed 11.9% vs predicted 5.4%, AUC = 0.60, Brier = 0.11), surgical site infection (observed 9.4% vs predicted 3.5%, AUC = 0.61, Brier = 0.05), and any complication (observed 33.3% vs 19%, AUC = 0.65, Brier = 0.23). Predicted and observed length of stay were not significantly associated (ß = 0.132, P = .47). CONCLUSION: The ACS NSQIP SRC is a poor predictor of outcomes after spinal deformity surgery.

Comparative analysis of patient demographics, perioperative outcomes, and adverse events after lumbar spinal fusion between urban and rural hospitals: an analysis of the National Inpatient Sample (NIS) database.

OBJECTIVE: Rural location of a patient's primary residence has been associated with worse clinical and surgical outcomes due to limited resource availability in these parts of the US. However, there is a paucity of literature investigating the effect that a rural hospital location may have on these outcomes specific to lumbar spine fusions. METHODS: Using the National Inpatient Sample (NIS) database, we identified all patients who underwent primary lumbar spinal fusion in the years between 2009 and 2020. Patients were separated according to whether the operative hospital was considered rural or urban. Univariable and multivariable regression models were used for data analysis. RESULTS: Of 2,863,816 patients identified, 120,298 (4.2 %) had their operation at a rural hospital, with the remaining in an urban hospital. Patients in the urban cohort were younger (P < .001), more likely to have private insurance (39.81 % vs 31.95 %, P < .001), and fewer of them were in the first (22.52 % vs 43.00 %, P < .001) and second (25.96 % vs 38.90 %, P < .001) quartiles of median household income compared to the rural cohort. The urban cohort had significantly increased rates of respiratory (4.49 % vs 3.37 %), urinary (5.25 % vs 4.15 %), infectious (0.49 % vs 0.32 %), venous thrombotic (0.57 % vs 0.24 %, P < .001), and neurological (0.79 % vs 0.36 %) (all P < .001) perioperative complications. On multivariable analysis, the urban cohort had significantly increased odds of the same perioperative complications: respiratory (odds ratio[OR] = 1.48; 95 % confidence interval [CI], 1.26-1.74), urinary (OR = 1.34; 95 %CI, 1.20-1.50), infection (OR = 1.63; 95 %CI, 1.23-2.17), venous thrombotic (OR = 1.79; 95 %CI, 1.32-2.41), neurological injury (OR = 1.92; 95 %CI, 1.46-2.53), and localized infection (OR = 1.65; 95 %CI, 1.25-2.17) (all P < .001). CONCLUSIONS: Patients undergoing lumbar fusions experience significantly different outcomes based on the rural or urban location of the operative hospital.

Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): a population-based study.

BACKGROUND: Typhoid Fever remains a major cause of morbidity and mortality in low-income settings. The Severe Typhoid in Africa programme was designed to address regional gaps in typhoid burden data and identify populations eligible for interventions using novel typhoid conjugate vaccines. METHODS: A hybrid design, hospital-based prospective surveillance with population-based health-care utilisation surveys, was implemented in six countries in sub-Saharan Africa. Patients presenting with fever (≥37·5°C axillary or ≥38·0°C tympanic) or reporting fever for three consecutive days within the previous 7 days were invited to participate. Typhoid fever was ascertained by culture of blood collected upon enrolment. Disease incidence at the population level was estimated using a Bayesian mixture model. FINDINGS: 27 866 (33·8%) of 82 491 participants who met inclusion criteria were recruited. Blood cultures were performed for 27 544 (98·8%) of enrolled participants. Clinically significant organisms were detected in 2136 (7·7%) of these cultures, and 346 (16·2%) Salmonella enterica serovar Typhi were isolated. The overall adjusted incidence per 100 000 person-years of observation was highest in Kavuaya and Nkandu 1, Democratic Republic of the Congo (315, 95% credible interval 254-390). Overall, 46 (16·4%) of 280 tested isolates showed ciprofloxacin non-susceptibility. INTERPRETATION: High disease incidence (ie, >100 per 100 000 person-years of observation) recorded in four countries, the prevalence of typhoid hospitalisations and complicated disease, and the threat of resistant typhoid strains strengthen the need for rapid dispatch and implementation of effective typhoid conjugate vaccines along with measures designed to improve clean water, sanitation, and hygiene practices. FUNDING: The Bill & Melinda Gates Foundation.

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.

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.

Cervical Vertebral Bone Quality Score Independently Predicts Distal Junctional Kyphosis After Posterior Cervical Fusion.

BACKGROUND AND OBJECTIVE: Posterior cervical fusion is the surgery of choice when fusing long segments of the cervical spine. However, because of the limited presence of this pathology, there is a paucity of data in the literature about the postoperative complications of distal junctional kyphosis (DJK). We aimed to identify and report potential associations between the preoperative cervical vertebral bone quality (C-VBQ) score and the occurrence of DJK after posterior cervical fusion. METHODS: The authors retrospectively reviewed records of patients who underwent posterior cervical fusion at a single hospital between June 1, 2010, and May 31, 2020. Patient data were screened to include patients who were >18 years old, had baseline MRI, had baseline standing cervical X-ray, had immediate postoperative standing cervical X-ray, and had clinical and radiographic follow-ups of >1 year, including a standing cervical X-ray at least 1 year postoperatively. Univariate analysis was completed between DJK and non-DJK groups, with multivariate regression completed for relevant clinical variables. Simple linear regression was completed to analyze correlation between the C-VBQ score and total degrees of kyphosis angle change. RESULTS: Ninety-three patients were identified, of whom 19 (20.4%) had DJK and 74 (79.6%) did not. The DJK group had a significantly higher C-VBQ score than the non-DJK group (2.97 ± 0.40 vs 2.26 ± 0.46; P < .001). A significant, positive correlation was found between the C-VBQ score and the total degrees of kyphosis angle change (r 2 = 0.26; P < .001). On multivariate analysis, the C-VBQ score independently predicted DJK (odds ratio, 1.46; 95% CI, 1.27-1.67; P < .001). CONCLUSION: We found that the C-VBQ score was an independent predictive factor of DJK after posterior cervical fusion.

Comparative Analysis of the 3 Cervical Vertebral Bone Quality (C-VBQ) Score Methodologies and Their Correlations to the Lumbar Vertebral Bone Quality (VBQ) Score.

OBJECTIVE: Common complications after spinal fusion, such as pseudoarthrosis, cage subsidence, or instrumentation failure, are affected by patients' bone quality. The cervical-vertebral bone quality (C-VBQ) score, a magnetic resonance imaging (MRI)-based adaption of the lumbar vertebral bone quality (VBQ) score, was developed by 3 separate research groups simultaneously to evaluate bone quality in cervical spinal fusion patients. We present the first analysis comparing these scoring methods to the well-validated VBQ score. METHODS: A retrospective analysis of data for consecutive patients who underwent spine surgery at a single institution was completed. The VBQ score was calculated using the Ehresman et al. METHOD: The C-VBQ scores, named according to placement of the region of interest within the cerebral spinal fluid, were calculated separately using the methods of Soliman et al. (C2-VBQ), Razzouk et al. (C5-VBQ), and Huang et al. (T1-VBQ). Linear regression models were utilized to evaluate correlations to the VBQ score. RESULTS: A total of 105 patients were identified (mean age, 57.0 ± 11.9 years; women, 50.5%). Mean scores were C2-VBQ, 2.37 ± 0.55; C5-VBQ, 2.36 ± 0.61; and T1-VBQ, 2.64 ± 0.68. The C-VBQ scores for the C2 level were significantly higher than those for the C3-C6 levels (3.18 ± 0.96 vs. 2.63 ± 0.77, P < 0.001), whereas the C7 level was found to have significantly lower C-VBQ scores (2.42 ± 0.78 vs. 2.63 ± 0.77, P = 0.04). The C2-VBQ (r = 0.63) score had the strongest correlation to the VBQ score, compared to C5-VBQ (r = 0.41) and T1-VBQ (r = 0.43) (P < 0.001). CONCLUSIONS: This study demonstrates that the C2-VBQ had the strongest correlation to the lumbar VBQ score among all C-VBQ scores.

Invasive non-typhoidal Salmonella from stool samples of healthy human carriers are genetically similar to blood culture isolates: a report from the Democratic Republic of the Congo.

Invasive non-typhoidal Salmonella (iNTS) (serotypes Typhimurium and Enteritidis) are major causes of bloodstream infections in sub-Saharan Africa, but their reservoir is unknown. Aiming to demonstrate human carriers as a reservoir, we assessed an iNTS disease endemic rural community (Kikonka health area, Democratic Republic of the Congo) for intestinal carriage of iNTS. After a census, healthy subjects from randomly selected households provided three successive stool samples for Salmonella culture. We next compared the stool isolates for genetic relatedness with time and health area-matched blood culture isolates obtained from hospitalized patients by multiple locus variable-number tandem repeat analysis (MLVA) and performed whole genome sequencing (WGS) on a subset of stool and blood isolates. Among 2,354 eligible subjects, 2,234 (94.9%) consented and provided at least one stool sample, and 2,219 (94.3%) provided three stool samples. The cumulative proportion of Salmonella carriers after 3 days was 4.4% (n = 98). S. Typhimurium and Enteritidis were found in 26 and 3 carriers, respectively, representing 1.3% (29 out of 2,234) of participants living in 6.0% (26 out of 482) of households. MLVA types of all 26 S. Typhimurium stool isolates matched with the corresponding MLVA types of blood isolates. The MLVA type of one out of three Enteritidis stool isolates matched the single MLVA type of the five Enteritidis blood isolates. WGS analysis of S. Typhimurium (n = 20) and S. Enteritidis (n = 4) isolates revealed Typhimurium multilocus sequence type (ST)313 Lineage 2 and Enteritidis ST11 Central/Eastern African and Outlier clades and confirmed the MLVA clustering. More than three-quarters of Typhimurium isolates showed combined multidrug resistance, ceftriaxone resistance, and fluoroquinolone non-susceptibility. In conclusion, the present study demonstrated iNTS carriage among healthy community members, with stool isolates that were genetically similar to blood culture isolates obtained in patients from the same community. These findings contribute to the evidence of a human reservoir of iNTS.

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.

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.

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.

Characterization of Typhoid Intestinal Perforation in Africa: Results From the Severe Typhoid Fever Surveillance in Africa Program.

Background: Typhoid intestinal perforation (TIP) remains the most serious complication of typhoid fever. In many countries, the diagnosis of TIP relies on intraoperative identification, as blood culture and pathology capacity remain limited. As a result, many cases of TIP may not be reported as typhoid. This study demonstrates the burden of TIP in sites in Burkina Faso, Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Methods: Patients with clinical suspicion of nontraumatic intestinal perforation were enrolled and demographic details, clinical findings, surgical records, blood cultures, tissue biopsies, and peritoneal fluid were collected. Participants were then classified as having confirmed TIP, probable TIP, possible TIP, or clinical intestinal perforation based on surgical descriptions and cultures. Results: A total of 608 participants were investigated for nontraumatic intestinal perforation; 214 (35%) participants had surgically-confirmed TIP and 33 participants (5%) had culture-confirmed typhoid. The overall proportion of blood or surgical site Salmonella enterica subspecies enterica serovar Typhi positivity in surgically verified TIP cases was 10.3%. TIP was high in children aged 5-14 years in DRC, Ghana, and Nigeria. We provide evidence for correlation between monthly case counts of S. Typhi and the occurrence of intestinal perforation. Conclusions: Low S. Typhi culture positivity rates, as well as a lack of blood and tissue culture capability in many regions where typhoid remains endemic, significantly underestimate the true burden of typhoid fever. The occurrence of TIP may indicate underlying typhoid burden, particularly in countries with limited culture capability.

The interplay between WASH practices and vaccination with oral cholera vaccines in protecting against cholera in urban Bangladesh: Reanalysis of a cluster-randomized trial.

The current global initiative to end Cholera by 2030 emphasizes the use of oral cholera vaccine (OCV) combined with feasible household Water-Sanitation-Hygiene (WASH) interventions. However, little is known about how improved WASH practices and behaviors and OCV interact to reduce the risk of cholera. We reanalyzed two arms of a cluster-randomized trial in urban Bangladesh, to evaluate the effectiveness of OCV given as a 2-dose regimen. One arm (30 clusters, n = 94,675) was randomized to vaccination of persons aged one year and older with OCV, and the other arm (30 clusters, n = 80,056) to no intervention. We evaluated the prevention of cholera by household WASH, classified at baseline using a previously validated rule, and OCV over 2 years of follow-up. When analyzed by assignment to OCV clusters rather than receipt of OCV, in comparison to persons living in "Not Better WASH" households in the control clusters, reduction of severe cholera (the primary outcome) was similar for persons in "Not Better WASH" households in vaccine clusters (46%, 95% CI:24,62), for persons in "Better WASH" households in the control clusters (48%, 95% CI:25,64), and for persons in "Better WASH" households in the vaccine clusters (48%, 95% CI:16,67). In contrast, when analyzed by actual receipt of a complete OCV regimen, , in comparison to persons in "Not Better WASH" households in the control clusters, protection against severe cholera increased steadily from 39% (95% CI:13,58) in residents of "Better WASH" households in the control clusters to 57% (95% CI:35,72) in vaccinated persons in "Not Better WASH" households to 63% (95% CI:21,83) in vaccinated persons in "Better WASH" households. This analysis suggests that improved household WASH and OCV received may interact to provide greater protection against cholera. However, the divergence between findings related to intent to vaccinate versus those pertaining to actual receipt of OCV underscores the need for further research on this topic.

Health itinerary-related survival of children under-five with severe malaria or bloodstream infection, DR Congo.

BACKGROUND: Prompt appropriate treatment reduces mortality of severe febrile illness in sub-Saharan Africa. We studied the health itinerary of children under-five admitted to the hospital with severe febrile illness in a setting endemic for Plasmodium falciparum (Pf) malaria and invasive non-typhoidal Salmonella infections, identified delaying factors and assessed their associations with in-hospital death. METHODOLOGY: Health itinerary data of this cohort study were collected during 6 months by interviewing caretakers of children (>28 days - <5 years) admitted with suspected bloodstream infection to Kisantu district hospital, DR Congo. The cohort was followed until discharge to assess in-hospital death. PRINCIPAL FINDINGS: From 784 enrolled children, 36.1% were admitted >3 days after fever onset. This long health itinerary was more frequent in children with bacterial bloodstream infection (52.9% (63/119)) than in children with severe Pf malaria (31.0% (97/313)). Long health itinerary was associated with in-hospital death (OR = 2.1, p = 0.007) and two thirds of deaths occurred during the first 3 days of admission. Case fatality was higher in bloodstream infection (22.8% (26/114)) compared to severe Pf malaria (2.6%, 8/309). Bloodstream infections were mainly (74.8% (89/119)) caused by non-typhoidal Salmonella. Bloodstream infections occurred in 20/43 children who died in-hospital before possible enrolment and non-typhoidal Salmonella caused 16 out of these 20 bloodstream infections. Delaying factors associated with in-hospital death were consulting traditional, private and/or multiple providers, rural residence, prehospital intravenous therapy, and prehospital overnight stays. Use of antibiotics reserved for hospital use, intravenous therapy and prehospital overnight stays were most frequent in the private sector. CONCLUSIONS: Long health itineraries delayed appropriate treatment of bloodstream infections in children under-five and were associated with increased in-hospital mortality. Non-typhoidal Salmonella were the main cause of bloodstream infection and had high case fatality. TRIAL REGISTRATION: NCT04289688.

Cost of oral cholera vaccine delivery in a mass immunization program for children in urban Bangladesh.

Cholera poses a substantial health burden in the developing world due to both epidemic and endemic diseases. The World Health Organization recommends oral cholera vaccines for mass vaccination campaigns in addition to traditional prevention practices and treatments in resource-poor settings. In many developing countries like Bangladesh, the major challenge behind implementing mass vaccination campaigns concerns the affordability of the oral cholera vaccine (OCV). Vaccination of children with OCV is not only an impactful approach for controlling cholera at the population level and reducing childhood morbidity but is also considered more cost-effective than vaccinating all ages. The aim of the study was to estimate the cost of an OCV campaign for children from a societal perspective using empirical study. A total of 66,311 children aged 1 to 14 years old were fully vaccinated with two doses of the OCV Shanchol while 9,035 individuals received one dose of this vaccine. The estimated societal cost per individual for full vaccination was US$ 6.11, which includes the cost of vaccine delivery estimated at US$ 1.95. The cost per single dose was estimated at US$ 2.86. The total provider cost for full vaccination was estimated at US$ 6.01 and the recipient cost at US$ 0.10. Our estimation of OCV delivery costs for children was relatively higher than what was found in a similar mass OCV campaign for all age groups, indicating that there may be additional cost factors to consider in targeted vaccine campaigns. This analysis provides useful benchmarks for the possible costs related to delivery of OCV to children and future OCV cost-effectiveness models should factor in these possible cost disparities. Attempts to reduce the cost per dose are likely to have a greater impact on the cost of similar vaccination campaigns in many resource-poor settings.

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.

OBJECTIVE: To 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 PARTICIPANTS: We 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 MEASURE: First severe cholera episode detected during follow-up period. METHODS: We 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. RESULTS: The '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. CONCLUSIONS: Salutary 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 NUMBER: This article is a re-analysis of data from a cluster randomized trial; can be found on ClinicalTrials.gov NCT01339845.

Serology as a Tool to Assess Infectious Disease Landscapes and Guide Public Health Policy.

Understanding the local burden and epidemiology of infectious diseases is crucial to guide public health policy and prioritize interventions. Typically, infectious disease surveillance relies on capturing clinical cases within a healthcare system, classifying cases by etiology and enumerating cases over a period of time. Disease burden is often then extrapolated to the general population. Serology (i.e., examining serum for the presence of pathogen-specific antibodies) has long been used to inform about individuals past exposure and immunity to specific pathogens. However, it has been underutilized as a tool to evaluate the infectious disease burden landscape at the population level and guide public health decisions. In this review, we outline how serology provides a powerful tool to complement case-based surveillance for determining disease burden and epidemiology of infectious diseases, highlighting its benefits and limitations. We describe the current serology-based technologies and illustrate their use with examples from both the pre- and post- COVID-19-pandemic context. In particular, we review the challenges to and opportunities in implementing serological surveillance in low- and middle-income countries (LMICs), which bear the brunt of the global infectious disease burden. Finally, we discuss the relevance of serology data for public health decision-making and describe scenarios in which this data could be used, either independently or in conjunction with case-based surveillance. We conclude that public health systems would greatly benefit from the inclusion of serology to supplement and strengthen existing case-based infectious disease surveillance strategies.

Antibiotic use from formal and informal healthcare providers in the Democratic Republic of Congo: a population-based study in two health zones.

OBJECTIVE: In the Democratic Republic of Congo and other low-resource countries, community-acquired pathogens are increasingly resistant to most locally available antibiotics. To guide efforts to optimize antibiotic use to limit antibiotic resistance, we quantified healthcare provider-specific and community-wide antibiotic use. METHODS: From household surveys, we estimated monthly healthcare visit rates by provider. From healthcare visit exit surveys, we estimated prevalence, defined daily doses, and access/watch/reserve distribution of antibiotic use by provider. Combining both, we estimated community-wide antibiotic use rates. RESULTS: Of 88.7 (95% CI 81.9-95.4) healthcare visits per 1000 person-months (n = 31221), visits to private clinics (31.0, 95% CI 30.0-32.0) and primary health centres (25.5, 95% CI 24.6-26.4) were most frequent. Antibiotics were used during 64.3% (95% CI 55.2-73.5%, 162/224) of visits to private clinics, 51.1% (95% CI 45.1-57.2%, 245/469) to health centres, and 48.8% (95% CI 44.4-53.2%, 344/454) to medicine stores. Antibiotic defined daily doses per 1000 inhabitants per day varied between 1.75 (95% CI 1.02-2.39) in rural Kimpese and 10.2 (95% CI 6.00-15.4) in (peri) urban Kisantu, mostly explained by differences in healthcare utilisation (respectively 27.8 versus 105 visits per 1000 person-months), in particular of private clinics (1.23 versus 38.6 visits) where antibiotic use is more frequent. The fraction of Watch antibiotics was 30.3% (95% CI 24.6-35.9%) in private clinics, 25.6% (95% CI 20.2-31.1%) in medicine stores, and 25.1% (95% CI 19.0-31.2%) in health centres. Treatment durations <3 days were more frequent at private clinics (5.3%, 9/169) and medicine stores (4.1%, 14/338) than at primary health centres (1.8%, 5/277). DISCUSSION: Private healthcare providers, ubiquitous in peri-urban settings, contributed most to community-wide antibiotic use and more frequently dispensed Watch antibiotics and shortened antibiotic courses. Efforts to optimize antibiotic use should include private providers at community level.