Common statistical modeling methods do not necessarily produce the most relevant or interpretable effect estimates to communicate risk. Overreliance on the odds ratio and relative effect measures ...limit the potential impact of epidemiologic and public health research. We created a straightforward R package, called riskCommunicator, to facilitate the presentation of a variety of effect measures, including risk differences and ratios, number needed to treat, incidence rate differences and ratios, and mean differences. The riskCommunicator package uses g-computation with parametric regression models and bootstrapping for confidence intervals to estimate effect measures in time-fixed data. We demonstrate the utility of the package using data from the Framingham Heart Study to estimate the effect of prevalent diabetes on the 24-year risk of cardiovascular disease or death. The package promotes the communication of public-health relevant effects and is accessible to a broad range of epidemiologists and health researchers with little to no expertise in causal inference methods or advanced coding.
The spatiotemporal structure of the human microbiome
, proteome
and metabolome
reflects and determines regional intestinal physiology and may have implications for disease
. Yet, little is known ...about the distribution of microorganisms, their environment and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals
. To address these deficiencies, we developed an ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. Collection of 240 intestinal samples from 15 healthy individuals using the device and subsequent multi-omics analyses identified significant differences between bacteria, phages, host proteins and metabolites in the intestines versus stool. Certain microbial taxa were differentially enriched and prophage induction was more prevalent in the intestines than in stool. The host proteome and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Furthermore, microbially conjugated bile acid concentrations exhibited amino acid-dependent trends that were not apparent in stool. Overall, non-invasive, longitudinal profiling of microorganisms, proteins and bile acids along the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease.
Background Diarrheal disease is a leading cause of morbidity and mortality globally, especially in low- and middle-income countries. High-throughput and low-cost approaches to identify etiologic ...agents are needed to guide public health mitigation. Nanoliter-qPCR (nl-qPCR) is an attractive alternative to more expensive methods yet is nascent in application and without a proof-of-concept among hospitalized patients. Methods A census-based study was conducted among diarrheal patients admitted at two government hospitals in rural Bangladesh during a diarrheal outbreak period. DNA was extracted from stool samples and assayed by nl-qPCR for common bacterial, protozoan, and helminth enteropathogens as the primary outcome. Results A total of 961 patients were enrolled; stool samples were collected from 827 patients. Enteropathogens were detected in 69% of patient samples; More than one enteropathogen was detected in 32%. Enteropathogens most commonly detected were enteroaggregative Escherichia coli (26.0%), Shiga toxin-producing E.coli (18.3%), enterotoxigenic E. coli (15.5% heat stable toxin positive, 2.2% heat labile toxin positive), Shigella spp. (14.8%), and Vibrio cholerae (9.0%). Geospatial analysis revealed that the median number of pathogens per patient and the proportion of cases presenting with severe dehydration were greatest amongst patients residing closest to the study hospitals." Conclusions This study demonstrates a proof-of-concept for nl-qPCR as a high-throughput low-cost method for enteropathogen detection among hospitalized patients.
Microbial communities are crucial to the effectiveness and stability of bioremediation systems treating acid mine drainage (AMD); however, little research has addressed how they correlate to system ...performance under changing environmental conditions. In this study, 16S rRNA gene sequencing and quantitative PCR (qPCR) were used to characterize microbial communities within different substrate combinations of crab shell (CS) and spent mushroom compost (SMC) and their association with chemical performance in pilot-scale vertical flow ponds (VFPs) treating high risk AMD in central Pennsylvania over 643 days of operation. As compared to a control containing SMC, VFPs containing CS sustained higher alkalinity, higher sulfate-reducing rates, and more thorough metals removal (>90% for Fe and Al, >50% for Mn and Zn). Correspondingly, CS VFPs supported the growth of microorganisms in key functional groups at increasing abundance and diversity over time, especially more diverse sulfate-reducing bacteria. Through changing seasonal and operational conditions over almost two years, the relative abundance of the core phyla shifted in all reactors, but the smallest changes in functional gene copies were observed in VFPs containing CS. These results suggest that the high diversity and stability of microbial communities associated with CS are consistent with effective AMD treatment.
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•Microbial communities are critical to the bioremediation of acid mine drainage (AMD).•Pilot-scale systems in central Pennsylvania received high-risk AMD for 643 days.•Crab shell out-performed spent mushroom compost in longevity and chemical treatment.•Crab shell supported the abundance and diversity of key functional groups.•The stability of microbial communities was consistent with effective AMD treatment.
A number of studies have detected relationships between weather and diarrhea. Few have investigated associations with specific enteric pathogens. Understanding pathogen-specific relationships with ...weather is crucial to inform public health in low-resource settings that are especially vulnerable to climate change.
Our objectives were to identify weather and environmental risk factors associated with diarrhea and enteropathogen prevalence in young children in rural Bangladesh, a population with high diarrheal disease burden and vulnerability to weather shifts under climate change.
We matched temperature, precipitation, surface water, and humidity data to observational longitudinal data from a cluster-randomized trial that measured diarrhea and enteropathogen prevalence in children 6 months-5.5 years from 2012-2016. We fit generalized additive mixed models with cubic regression splines and restricted maximum likelihood estimation for smoothing parameters.
Comparing weeks with 30°C versus 15°C average temperature, prevalence was 3.5% higher for diarrhea, 7.3% higher for Shiga toxin-producing Escherichia coli (STEC), 17.3% higher for enterotoxigenic E. coli (ETEC), and 8.0% higher for Cryptosporidium. Above-median weekly precipitation (median: 13mm; range: 0-396mm) was associated with 29% higher diarrhea (adjusted prevalence ratio 1.29, 95% CI 1.07, 1.55); higher Cryptosporidium, ETEC, STEC, Shigella, Campylobacter, Aeromonas, and adenovirus 40/41; and lower Giardia, sapovirus, and norovirus prevalence. Other associations were weak or null.
Higher temperatures and precipitation were associated with higher prevalence of diarrhea and multiple enteropathogens; higher precipitation was associated with lower prevalence of some enteric viruses. Our findings emphasize the heterogeneity of the relationships between hydrometeorological variables and specific enteropathogens, which can be masked when looking at composite measures like all-cause diarrhea. Our results suggest that preventive interventions targeted to reduce enteropathogens just before and during the rainy season may more effectively reduce child diarrhea and enteric pathogen carriage in rural Bangladesh and in settings with similar meteorological characteristics, infrastructure, and enteropathogen transmission.
While low-carbohydrate and low-fat diets can both lead to weight-loss, a substantial variability in achieved long-term outcomes exists among obese but otherwise healthy adults. We examined the ...hypothesis that structural differences in the gut microbiota explain a portion of variability in weight-loss using two cohorts of obese adults enrolled in the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) study. A total of 161 pre-diet fecal samples were sequenced from a discovery cohort (n = 66) and 106 from a validation cohort (n = 56). An additional 157 fecal samples were sequenced from the discovery cohort after 10 weeks of dietary intervention. We found no specific bacterial signatures associated with weight loss that were consistent across both cohorts. However, the gut microbiota plasticity (i.e. variability), was correlated with long-term (12-month) weight loss in a diet-dependent manner; on the low-fat diet subjects with higher pre-diet daily plasticity had higher sustained weight loss, whereas on the low-carbohydrate diet those with higher plasticity over 10 weeks of dieting had higher 12-month weight loss. Our findings suggest the potential importance of gut microbiota plasticity for sustained weight-loss. We highlight the advantages of evaluating kinetic trends and assessing reproducibility in studies of the gut microbiota.
Diarrheal disease is a leading cause of childhood morbidity and mortality globally. Household water, sanitation, and handwashing (WASH) interventions can reduce exposure to diarrhea-causing ...pathogens, but meteorological factors may impact their effectiveness. Information about effect heterogeneity under different weather conditions is critical to refining these targeted interventions.
We aimed to determine whether temperature and precipitation modified the effect of low-cost, point-of-use WASH interventions on child diarrhea.
We analyzed data from a trial in rural Bangladesh that compared child diarrhea prevalence between clusters (
) that were randomized to different WASH interventions between 2012 and 2016 (NCT01590095). We matched temperature and precipitation measurements to diarrhea outcomes (
measurements, 6,921 children) by geographic coordinates and date. We estimated prevalence ratios (PRs) using generative additive models and targeted maximum likelihood estimation to assess the effectiveness of each WASH intervention under different weather conditions.
Generally, WASH interventions most effectively prevented diarrhea during monsoon season, particularly following weeks with heavy rain or high temperatures. The PR for diarrhea in the WASH interventions group compared with the control group was 0.49 (95% CI: 0.35, 0.68) after 1 d of heavy rainfall, with a less-protective effect
(95% CI: 0.60, 1.25) when there were no days with heavy rainfall. Similarly, the PR for diarrhea in the WASH intervention group compared with the control group was 0.60 (95% CI: 0.48, 0.75) following above-median temperatures vs. 0.91 (95% CI: 0.61, 1.35) following below-median temperatures. The influence of precipitation and temperature varied by intervention type; for precipitation, the largest differences in effectiveness were for the sanitation and combined WASH interventions.
WASH intervention effectiveness was strongly influenced by precipitation and temperature, and nearly all protective effects were observed during the rainy season. Future implementation of these interventions should consider local environmental conditions to maximize effectiveness, including targeted efforts to maintain latrines and promote community adoption ahead of monsoon seasons. https://doi.org/10.1289/EHP13807.
We evaluated the impact of low-cost water, sanitation, handwashing (WSH) and child nutrition interventions on enteropathogen carriage in the WASH Benefits cluster-randomized controlled trial in rural ...Bangladesh.
We analyzed 1411 routine fecal samples from children 14±2 months old in the WSH (n = 369), nutrition counseling plus lipid-based nutrient supplement (n = 353), nutrition plus WSH (n = 360), and control (n = 329) arms for 34 enteropathogens using quantitative PCR. Outcomes included the number of co-occurring pathogens; cumulative quantity of four stunting-associated pathogens; and prevalence and quantity of individual pathogens. Masked analysis was by intention-to-treat.
326 (99.1%) control children had one or more enteropathogens detected (mean 3.8±1.8). Children receiving WSH interventions had lower prevalence and quantity of individual viruses than controls (prevalence difference for norovirus: -11% 95% confidence interval CI, -5 to -17%; sapovirus: -9% 95%CI, -3 to -15%; and adenovirus 40/41: -9% 95%CI, -2 to - 15%). There was no difference in bacteria, parasites, or cumulative quantity of stunting-associated pathogens between controls and any intervention arm.
WSH interventions were associated with fewer enteric viruses in children aged 14 months. Different strategies are needed to reduce enteric bacteria and parasites at this critical young age.
Quantitative molecular diagnostic methods can effectively detect pathogen-specific nucleic acid sequences, but costs associated with multi-pathogen panels hinder their widespread use in research ...trials. Nano-liter qPCR (nL-qPCR) is a miniaturized tool for quantification of multiple targets in large numbers of samples based on assay parallelization on a single chip, with potentially significant cost-savings due to rapid throughput and reduced reagent volumes. We evaluated a suite of novel and published assays to detect 17 enteric pathogens using a commercially available nL-qPCR technology. Amplification efficiencies ranged from 88 to 98% (mean 91%) and were reproducible across four operators at two separate facilities. When applied to fecal material, assays were sensitive and selective (99.8% of DNA amplified were genes from the target organism). Due to nanofluidic volumes, detection limits were 1-2 orders of magnitude less sensitive for nL-qPCR than an enteric TaqMan Array Card (TAC). However, higher detection limits do not hinder detection of diarrhea-causing pathogen concentrations. Compared to TAC, nL-qPCR displayed 99% (95% CI 0.98, 0.99) negative percent agreement and 62% (95% CI 0.59, 0.65) overall positive percent agreement for presence of pathogens across diarrheal and non-diarrheal fecal samples. Positive percent agreement was 89% among samples with concentrations above the nL-qPCR detection limits. nL-qPCR assays showed an underestimation bias of 0.34 log
copies/gram of stool IQR -0.40, -0.28 compared with TAC. With 12 times higher throughput for a sixth of the per-sample cost of the enteric TAC, the nL-qPCR chip is a viable alternative for enteropathogen quantification for studies where other technologies are cost-prohibitive.
Anemia in young children is a global health problem. Risk factors include poor nutrient intake and poor water quality, sanitation, or hygiene.
We evaluated the effects of water quality, sanitation, ...handwashing, and nutrition interventions on micronutrient status and anemia among children in rural Kenya and Bangladesh.
We nested substudies within 2 cluster-randomized controlled trials enrolling pregnant women and following their children for 2 y. These substudies included 4 groups: water, sanitation, and handwashing (WSH); nutrition (N), including lipid-based nutrient supplements (LNSs; ages 6–24 mo) and infant and young child feeding (IYCF) counseling; WSH+N; and control. Hemoglobin and micronutrient biomarkers were measured after 2 y of intervention and compared between groups using generalized linear models with robust SEs.
In Kenya, 699 children were assessed at a mean ± SD age of 22.1 ± 1.8 mo, and in Bangladesh 1470 participants were measured at a mean ± SD age of 28.0 ± 1.9 mo. The control group anemia prevalences were 48.8% in Kenya and 17.4% in Bangladesh. There was a lower prevalence of anemia in the 2 N intervention groups in both Kenya N: 36.2%; prevalence ratio (PR): 0.74; 95% CI: 0.58, 0.94; WSH+N: 27.3%; PR: 0.56; 95% CI: 0.42, 0.75 and Bangladesh (N: 8.7%; PR: 0.50; 95% CI: 0.32, 0.78; WSH+N: 7.9%, PR: 0.46; 95% CI: 0.29, 0.73). In both trials, the 2 N groups also had significantly lower prevalences of iron deficiency, iron deficiency anemia, and low vitamin B-12 and, in Kenya, a lower prevalence of folate and vitamin A deficiencies. In Bangladesh, the WSH group had a lower prevalence of anemia (12.8%; PR: 0.74; 95% CI: 0.54, 1.00) than the control group, whereas in Kenya, the WSH+N group had a lower prevalence of anemia than did the N group (PR: 0.75; 95% CI: 0.53, 1.07), but this was not significant (P = 0.102).
IYCF counseling with LNSs reduced the risks of anemia, iron deficiency, and low vitamin B-12. Effects on folate and vitamin A varied between studies. Improvements in WSH also reduced the risk of anemia in Bangladesh but did not provide added benefit over the nutrition-specific intervention. These trials were registered at clinicaltrials.gov as NCT01590095 (Bangladesh) and NCT01704105 (Kenya).
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