Machine learning approaches for assessing moderate-to-severe diarrhea in children \u3c 5 years of age, rural western Kenya 2008-2012

Worldwide diarrheal disease is a leading cause of morbidity and mortality in children less than five years of age. Incidence and disease severity remain the highest in sub-Saharan Africa. Kenya has an estimated 400,000 severe diarrhea episodes and 9,500 diarrhea-related deaths per year in children. Current statistical methods for estimating etiological and exposure risk factors for moderate-to-severe diarrhea (MSD) in children are constrained by the inability to assess a large number of parameters due to limitations of sample size, complex relationships, correlated predictors, and model assumptions of linearity. This dissertation examines machine learning statistical methods to address weaknesses associated with using traditional logistic regression models. The studies presented here investigate data from a 4-year, prospective, matched case-control study of MSD among children less than five years of age in rural Kenya from the Global Enteric Multicenter Study. The three machine learning approaches were used to examine associations with MSD and include: least absolute shrinkage and selection operator, classification trees, and random forest. A principal finding in all three studies was that machine learning methodological approaches are useful and feasible to implement in epidemiological studies. All provided additional information and understanding of the data beyond using only logistic regression models. The results from all three machine learning approaches were supported by comparable logistic regression results indicating their usefulness as epidemiological tools. This dissertation offers an exploration of methodological alternatives that should be considered more frequently in diarrheal disease epidemiology, and in public health in general

Dengue Risk among Visitors to Hawaii during an Outbreak

Despite the high rates of dengue in many tropical destinations frequented by tourists, limited information is available on the risk for infection among short-term visitors. We retrospectively surveyed 4,000 persons who arrived in Hawaii during the peak of the 2001–2002 dengue outbreak and collected follow-up serologic test results for those reporting denguelike illness. Of 3,064 visitors who responded, 94 (3%) experienced a denguelike illness either during their trip or within 14 days of departure; 34 of these persons were seen by a physician, and 2 were hospitalized. Twenty-seven visitors with denguelike illness provided a serum specimen; all specimens were negative for anti-dengue immunoglobulin G antibodies. The point estimate of dengue incidence was zero infections per 358 person-days of exposure with an upper 95% confidence limit of 3.0 cases per person-year. Thus, the risk for dengue infection for visitors to Hawaii during the outbreak was low

Associations between Self-Reported Gastrointestinal Illness and Water System Characteristics in Community Water Supplies in Rural Alabama: A Cross-Sectional Study

Background: Community water supplies in underserved areas of the United States may be associated with increased microbiological contamination and risk of gastrointestinal disease. Microbial and health risks affecting such systems have not been systematically characterized outside outbreak investigations. The objective of the study was to evaluate associations between self-reported gastrointestinal illnesses (GII) and household-level water supply characteristics.Methods: We conducted a cross-sectional study of water quality, water supply characteristics, and GII in 906 households served by 14 small and medium-sized community water supplies in Alabama’s underserved Black Belt region.Results: We identified associations between respondent-reported water supply interruption and any symptoms of GII (adjusted odds ratio (aOR): 3.01, 95% confidence interval (CI) = 1.65– 5.49), as well as low water pressure and any symptoms of GII (aOR: 4.51, 95% CI = 2.55– 7.97). We also identified associations between measured water quality such as lack of total chlorine and any symptoms of GII (aOR: 5.73, 95% CI = 1.09–30.1), and detection of E. coli in water samples and increased reports of vomiting (aOR: 5.01, 95% CI = 1.62–15.52) or diarrhea (aOR: 7.75, 95% CI = 2.06–29.15).Conclusions: Increased self-reported GII was associated with key water system characteristics as measured at the point of sampling in a cross-sectional study of small and medium water systems in rural Alabama in 2012 suggesting that these water supplies can contribute to endemic gastro-intestinal disease risks. Future studies should focus on further characterizing and managing microbial risks in systems facing similar challenges

Evaluating four measures of water quality in clay pots and plastic safe storage containers in Kenya.

Household water treatment with chlorine can improve microbiological quality and reduce diarrhea. Chlorination is typically assessed using free chlorine residual (FCR), with a lower acceptable limit of 0.2 mg/L, however, accurate measurement of FCR is challenging with turbid water. To compare potential measures of adherence to treatment and water quality, we chlorinated recently-collected water in rural Kenyan households and measured total chlorine residual (TCR), FCR, oxidation reduction potential (ORP), and E. coli concentration over 72 h in clay and plastic containers. Results showed that 1) ORP served as a useful proxy for chlorination in plastic containers up to 24 h; 2) most stored water samples disinfected by chlorination remained significantly less contaminated than source water for up to 72 h, even in the absence of FCR; 3) TCR may be a useful proxy indicator of microbiologic water quality because it confirms previous chlorination and is associated with a lower risk of E. coli contamination compared to untreated source water; and 4) chlorination is more effective in plastic than clay containers presumably because of lower chlorine demand in plastic

In ricordo di Paolo Sylos Labini

Background: Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age. Methods/Findings: The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhiça, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged 93%) had access to a sanitation facility, while 70% of households in rural Kenya had access to a facility. Practicing open defecation was a risk factor for MSD in children <5 y old in Kenya. Sharing sanitation facilities with 1–2 or ≥3 other households was a statistically significant risk factor for MSD in Kenya, Mali, Mozambique, and Pakistan. Among those with a designated handwashing area near the home, soap or ash were more frequently observed at control households and were significantly protective against MSD in Mozambique and India. Conclusions: This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved

Methicillin-resistant Staphylococcus aureus, Hawaii, 2000–2002

Annual trends showed a significant increase in the proportion of MRSA among adult but not among pediatric patients

Sanitation and Hygiene-Specific Risk Factors for Moderate-to-Severe Diarrhea in Young Children in the Global Enteric Multicenter Study, 2007-2011: Case-Control Study.

Background: Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age. Methods/Findings: The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhiça, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged 93%) had access to a sanitation facility, while 70% of households in rural Kenya had access to a facility. Practicing open defecation was a risk factor for MSD in children <5 y old in Kenya. Sharing sanitation facilities with 1–2 or ≥3 other households was a statistically significant risk factor for MSD in Kenya, Mali, Mozambique, and Pakistan. Among those with a designated handwashing area near the home, soap or ash were more frequently observed at control households and were significantly protective against MSD in Mozambique and India. Conclusions: This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Household water treatment uptake during a public health response to a large Typhoid Fever outbreak in Harare, Zimbabwe

Locally manufactured sodium hypochlorite (chlorine) solution has been sold in Zimbabwe since 2010. During October 1, 2011–April 30, 2012, 4,181 suspected and 52 confirmed cases of typhoid fever were identified in Harare. In response to this outbreak, chlorine tablets were distributed. To evaluate household water treatment uptake, we conducted a survey and water quality testing in 458 randomly selected households in two suburbs most affected by the outbreak. Although 75% of households were aware of chlorine solution and 85% received chlorine tablets, only 18% had reportedly treated stored water and had the recommended protective level of free chlorine residuals. Water treatment was more common among households that reported water treatment before the outbreak, and those that received free tablets during the outbreak (P < 0.01), but was not associated with chlorine solution awareness or use before the outbreak (P > 0.05). Outbreak response did not build on pre-existing prevention programs.The U.S. Centers for Disease Control and Prevention Division of Global Disease Detection and Emergency Response, the U.S. Agency for International Development’s Office of U.S. Foreign Disaster Assistance, the United Nations Children’s Fund-Zimbabwe, Welthungerhilfe- Zimbabwe, and Population Services International-Zimbabwe.http://www.ajtmh.orgam201

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease