Study design and rationale for the PAASIM project: a matched cohort study on urban water supply improvements and infant enteric pathogen infection, gut microbiome development and health in Mozambique.

INTRODUCTION: Despite clear linkages between provision of clean water and improvements in child health, limited information exists about the health impacts of large water infrastructure improvements in low-income settings. Billions of dollars are spent annually to improve urban water supply, and rigorous evaluation of these improvements, especially targeting informal settlements, is critical to guide policy and investment strategies. Objective measures of infection and exposure to pathogens, and measures of gut function, are needed to understand the effectiveness and impact of water supply improvements. METHODS AND ANALYSIS: In the PAASIM study, we examine the impact of water system improvements on acute and chronic health outcomes in children in a low-income urban area of Beira, Mozambique, comprising 62 sub-neighbourhoods and ~26 300 households. This prospective matched cohort study follows 548 mother-child dyads from late pregnancy through 12 months of age. Primary outcomes include measures of enteric pathogen infections, gut microbiome composition and source drinking water microbiological quality, measured at the child's 12-month visit. Additional outcomes include diarrhoea prevalence, child growth, previous enteric pathogen exposure, child mortality and various measures of water access and quality. Our analyses will compare (1) subjects living in sub-neighbourhoods with the improved water to those living in sub-neighbourhoods without these improvements; and (2) subjects with household water connections on their premises to those without such a connection. This study will provide critical information to understand how to optimise investments for improving child health, filling the information gap about the impact of piped water provision to low-income urban households, using novel gastrointestinal disease outcomes. ETHICS AND DISSEMINATION: This study was approved by the Emory University Institutional Review Board and the National Bio-Ethics Committee for Health in Mozambique. The pre-analysis plan is published on the Open Science Framework platform (https://osf.io/4rkn6/). Results will be shared with relevant stakeholders locally, and through publications.

Spatial heterogeneity of neighborhood-level water and sanitation access in informal urban settlements: A cross-sectional case study in Beira, Mozambique.

Rapid urbanization, resulting in population growth within informal settlements, has worsened exclusion and inequality in access to water and sanitation (WASH) services in the poorest and most marginalized communities. In this study, we describe the heterogeneity in water service satisfaction and WASH access in low-income, peri-urban neighborhoods of Beira, Mozambique, and examine whether this heterogeneity can be explained by distance to water distribution mains. Using spatial statistics and regression analyses, we identify spatial heterogeneity in household WASH access, as well as consumer-reported satisfaction with water services (services, pressure, quality, and sufficient quantity). We find that as distance from the water main increased, both access to an improved water source at the household and satisfaction with water pressure decreases, and water supply intermittency increases, controlling for household density and socioeconomic status. The odds of a household having access to a water source at the household or on the compound decreases with every 100-meter increase in distance from a water main pipe (odds ratio [OR] 0.87, 95% confidence interval [CI]: 0.82, 0.92). Satisfaction with water services also decreases with every 100-meter increase in distance from a water main pipe (OR: 0.80; 95% CI: 0.69, 0.94). Days of availability in the past week decreases by a factor of 0.22 for every 100-meter increase in distance from the water main (95% CI: -0.29, -0.15). Findings from this study highlight the unequal household access to water and sanitation in urban informal settlements, even within low-income neighborhoods. Describing this heterogeneity of access to water services, sanitation, and satisfaction-and the factors influencing them-can inform stakeholders and guide the development of infrastructural solutions to reduce water access inequities within urban settings.

High Prevalence of Chemical and Microbiological Drinking Water Contaminants in Households with Infants Enrolled in a Birth Cohort-Piura, Peru, 2016.

Chemical and microbiological drinking water contaminants pose risks to child health but are not often evaluated concurrently. At two consecutive visits to 96 households in Piura, Peru, we collected drinking water samples, administered health and exposure questionnaires, and collected infant stool samples. Standard methods were used to quantify heavy metals/metalloids, pesticides, and Escherichia coli concentrations in water samples. Stool samples were assayed for bacterial, viral, and parasitic enteropathogens. The primary drinking water source was indoor piped water for 70 of 96 households (73%); 36 households (38%) stored drinking water from the primary source in containers in the home. We found high prevalence of chemical and microbiological contaminants in household drinking water samples: arsenic was detected in 50% of 96 samples, ≥ 1 pesticide was detected in 65% of 92 samples, and E. coli was detected in 37% of 319 samples. Drinking water samples that had been stored in containers had higher odds of E. coli detection (adjusted odds ratio [aOR]: 4.50; 95% CI: 2.04-9.95) and pesticide detection (OR: 6.55; 95% CI: 2.05-21.0) compared with samples collected directly from a tap. Most infants (68%) had ≥ 1 enteropathogen detected in their stool. Higher odds of enteropathogen infection at the second visit were observed among infants from households where pesticides were detected in drinking water at the first visit (aOR: 2.93; 95% CI: 1.13-7.61). Results show concurrent risks of exposure to microbiological and chemical contaminants in drinking water in a low-income setting, despite high access to piped drinking water.

Effectiveness of interventions to improve drinking water, sanitation, and handwashing with soap on risk of diarrhoeal disease in children in low-income and middle-income settings: a systematic review and meta-analysis.

BACKGROUND: Estimates of the effectiveness of water, sanitation, and hygiene (WASH) interventions that provide high levels of service on childhood diarrhoea are scarce. We aimed to provide up-to-date estimates on the burden of disease attributable to WASH and on the effects of different types of WASH interventions on childhood diarrhoea in low-income and middle-income countries (LMICs). METHODS: In this systematic review and meta-analysis, we updated previous reviews following their search strategy by searching MEDLINE, Embase, Scopus, Cochrane Library, and BIOSIS Citation Index for studies of basic WASH interventions and of WASH interventions providing a high level of service, published between Jan 1, 2016, and May 25, 2021. We included randomised and non-randomised controlled trials conducted at household or community level that matched exposure categories of the so-called service ladder approach of the Sustainable Development Goal (SDG) for WASH. Two reviewers independently extracted study-level data and assessed risk of bias using a modified Newcastle-Ottawa Scale and certainty of evidence using a modified Grading of Recommendations, Assessment, Development, and Evaluation approach. We analysed extracted relative risks (RRs) and 95% CIs using random-effects meta-analyses and meta-regression models. This study is registered with PROSPERO, CRD42016043164. FINDINGS: 19 837 records were identified from the search, of which 124 studies were included, providing 83 water (62 616 children), 20 sanitation (40 799 children), and 41 hygiene (98 416 children) comparisons. Compared with untreated water from an unimproved source, risk of diarrhoea was reduced by up to 50% with water treated at point of use (POU): filtration (n=23 studies; RR 0·50 [95% CI 0·41-0·60]), solar treatment (n=13; 0·63 [0·50-0·80]), and chlorination (n=25; 0·66 [0·56-0·77]). Compared with an unimproved source, provision of an improved drinking water supply on premises with higher water quality reduced diarrhoea risk by 52% (n=2; 0·48 [0·26-0·87]). Overall, sanitation interventions reduced diarrhoea risk by 24% (0·76 [0·61-0·94]). Compared with unimproved sanitation, providing sewer connection reduced diarrhoea risk by 47% (n=5; 0·53 [0·30-0·93]). Promotion of handwashing with soap reduced diarrhoea risk by 30% (0·70 [0·64-0·76]). INTERPRETATION: WASH interventions reduced risk of diarrhoea in children in LMICs. Interventions supplying either water filtered at POU, higher water quality from an improved source on premises, or basic sanitation services with sewer connection were associated with increased reductions. Our results support higher service levels called for under SDG 6. Notably, no studies evaluated interventions that delivered access to safely managed WASH services, the level of service to which universal coverage by 2030 is committed under the SDG. FUNDING: WHO, Foreign, Commonwealth & Development Office, and National Institute of Environmental Health Sciences.

Cholera Epidemic - Lusaka, Zambia, October 2017-May 2018.

On October 6, 2017, an outbreak of cholera was declared in Zambia after laboratory confirmation of Vibrio cholerae O1, biotype El Tor, serotype Ogawa, from stool specimens from two patients with acute watery diarrhea. The two patients had gone to a clinic in Lusaka, the capital city, on October 4. Cholera cases increased rapidly, from several hundred cases in early December 2017 to approximately 2,000 by early January 2018 (Figure). In collaboration with partners, the Zambia Ministry of Health (MoH) launched a multifaceted public health response that included increased chlorination of the Lusaka municipal water supply, provision of emergency water supplies, water quality monitoring and testing, enhanced surveillance, epidemiologic investigations, a cholera vaccination campaign, aggressive case management and health care worker training, and laboratory testing of clinical samples. In late December 2017, a number of water-related preventive actions were initiated, including increasing chlorine levels throughout the city's water distribution system and placing emergency tanks of chlorinated water in the most affected neighborhoods; cholera cases declined sharply in January 2018. During January 10-February 14, 2018, approximately 2 million doses of oral cholera vaccine were administered to Lusaka residents aged ≥1 year. However, in mid-March, heavy flooding and widespread water shortages occurred, leading to a resurgence of cholera. As of May 12, 2018, the outbreak had affected seven of the 10 provinces in Zambia, with 5,905 suspected cases and a case fatality rate (CFR) of 1.9%. Among the suspected cases, 5,414 (91.7%), including 98 deaths (CFR = 1.8%), occurred in Lusaka residents.

Findings from a comprehensive diarrhoea prevention and treatment programme in Lusaka, Zambia.

BACKGROUND: The Programme for the Awareness and Elimination of Diarrhoea (PAED) was a pilot comprehensive diarrhoea prevention and control programme aimed to reduce post-neonatal, all-cause under-five mortality by 15 % in Lusaka Province. Interventions included introduction of the rotavirus vaccine, improved clinical case management of diarrhoea, and a comprehensive community prevention and advocacy campaign on hand washing with soap, exclusive breastfeeding up to 6 months of age, and the use of ORS and Zinc. This study aimed to assess the impact of PAED on under-5 mortality. METHODS: The study was a pre-post evaluation design. The Demographic and Health Survey style population-based two-stage approach was used to collect data at the beginning of the intervention and 3 years following the start of intervention implementation in Lusaka province. The primary outcome of interest was an all-cause, post-neonatal under-five mortality rate defined as the probability of dying after the 28th day and before the fifth birthday among children aged 1-59 months. The Kaplan-Meier time to event analysis was used to estimate the probability of death; multiplying this probability by 1000 to yield the post-neonatal mortality rate. Survival-time inverse probability weighting model was used to estimate Average Treatment Effect (ATE). RESULTS: The percentage of children under age 5 who had diarrhoea in the last 2 weeks preceding the survey declined from 15.8 % (95 % CI: 15.2 %, 16.4 %) in 2012 to 12.7 % (95 % CI: 12.3 %, 13.2 %) in 2015. Over the same period, mortality in post-neonatal children under 5 years of age declined by 34 %, from an estimated rate of 29 deaths per 1000 live births (95 % CI: (26, 32) death per 1000 live births) to 19 deaths per 1000 live births (95 % CI: (16, 21) death per 1000 live births). When every child in the population of children aged 1-59 months is exposed to the intervention, the average time-to-death was estimated to be about 8 months more than when no child is exposed (ATE = 7.9; 95 % CI: 4.4,11.5; P < 0.001). CONCLUSION: Well-packaged diarrhoea preventive and treatment interventions delivered at the clinic and community-level could potentially reduce probability of death among children aged 1-59 months.

Clinical Correlates of Surveillance Events Detected by National Healthcare Safety Network Pneumonia and Lower Respiratory Infection Definitions-Pennsylvania, 2011-2012.

OBJECTIVE To determine the clinical diagnoses associated with the National Healthcare Safety Network (NHSN) pneumonia (PNEU) or lower respiratory infection (LRI) surveillance events DESIGN Retrospective chart review SETTING A convenience sample of 8 acute-care hospitals in Pennsylvania PATIENTS All patients hospitalized during 2011-2012 METHODS Medical records were reviewed from a random sample of patients reported to the NHSN to have PNEU or LRI, excluding adults with ventilator-associated PNEU. Documented clinical diagnoses corresponding temporally to the PNEU and LRI events were recorded. RESULTS We reviewed 250 (30%) of 838 eligible PNEU and LRI events reported to the NHSN; 29 reported events (12%) fulfilled neither PNEU nor LRI case criteria. Differences interpreting radiology reports accounted for most misclassifications. Of 81 PNEU events in adults not on mechanical ventilation, 84% had clinician-diagnosed pneumonia; of these, 25% were attributed to aspiration. Of 43 adult LRI, 88% were in mechanically ventilated patients and 35% had no corresponding clinical diagnosis (infectious or noninfectious) documented at the time of LRI. Of 36 pediatric PNEU events, 72% were ventilator associated, and 70% corresponded to a clinical pneumonia diagnosis. Of 61 pediatric LRI patients, 84% were mechanically ventilated and 21% had no corresponding clinical diagnosis documented. CONCLUSIONS In adults not on mechanical ventilation and in children, most NHSN-defined PNEU events corresponded with compatible clinical conditions documented in the medical record. In contrast, NHSN LRI events often did not. As a result, substantial modifications to the LRI definitions were implemented in 2015. Infect Control Hosp Epidemiol 2016;37:818-824.

Candida speciation, antifungal treatment and adverse events in pediatric invasive candidiasis: results from 441 infections in a prospective, multi-national study.

A multi-national prospective study of pediatric patients with invasive candidiasis between August 2007 and September 2012 was performed and included 441 infections. Variation in infecting Candida species and antifungals used was noted between US and non-US sites. Antifungal-associated adverse events were most common with polyene use.

Toxoplasma gondii exposure affects neural processing speed as measured by acoustic startle latency in schizophrenia and controls.

The prevalence of Toxoplasma gondii (TOXO) infection in schizophrenia (SCZ) is elevated compared to controls (odds ratio=2.73). TOXO infection is associated with psychomotor slowing in rodents and non-psychiatric humans. Latency of the acoustic startle response, an index of neural processing speed, is the time it takes for a startling stimulus to elicit the reflexive response through a three-synapse subcortical circuit. We report a significant slowing of latency in TOXO seropositive SCZ vs. seronegative SCZ, and in TOXO seropositive controls vs. seronegative controls. Latency was likewise slower in SCZ subjects than in controls. These findings indicate a slowing of neural processing speed with chronic TOXO infection; the slowest startle latency was seen in the TOXO seropositive SCZ group.