Prevalence of Colonization With Antibiotic-Resistant Organisms in Hospitalized and Community Individuals in Bangladesh, a Phenotypic Analysis: Findings From the Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: Low- and middle-income countries bear a disproportionate burden of antimicrobial resistance (AMR) but often lack adequate surveillance to inform mitigation efforts. Colonization can be a useful metric to understand AMR burden. We assessed the colonization prevalence of Enterobacterales with resistance to extended-spectrum cephalosporins, carbapenems, colistin, and methicillin-resistant Staphylococcus aureus among hospital and community dwellers. METHODS: Between April and October 2019, we conducted a period prevalence study in Dhaka, Bangladesh. We collected stool and nasal specimens from adults in 3 hospitals and from community dwellers within the hospitals' catchment area. Specimens were plated on selective agar plates. Isolates underwent identification and antibiotic susceptibility testing using Vitek 2. We performed descriptive analysis and determined population prevalence estimates accounting for clustering at the community level. RESULTS: The majority of both community and hospital participants were colonized with Enterobacterales with resistance to extended-spectrum cephalosporins (78%; 95% confidence interval [95% CI], 73-83; and 82%; 95% CI, 79-85, respectively). Thirty-seven percent (95% CI, 34-41) of hospitalized patients were colonized with carbapenems compared with 9% (95% CI, 6-13) of community individuals. Colistin colonization prevalence was 11% (95% CI, 8-14) in the community versus 7% (95% CI, 6-10) in the hospital. Methicillin-resistant Staphylococcus aureus colonization was similar in both community and hospital participants (22%; 95% CI, 19-26 vs 21% (95% CI, 18-24). CONCLUSIONS: The high burden of AMR colonization observed among hospital and community participants may increase the risk for developing AMR infections and facilitating spread of AMR in both the community and hospital.

Selective Aptamer Modification of Au Surfaces in a Microelectrode Sensor Array for Simultaneous Detection of Multiple Analytes.

Aptamers have been employed as the biorecognition element in electrochemical aptamer-based (E-AB) biosensors, for the detection of a diverse range of analyte molecules, on electrodes with sizescales ranging from a few microns to several millimeters. Simultaneous detection of multiple different analytes requires the selective modification of multiple electrode surfaces with different aptamers. This process is typically achieved by incubating separate macroscale electrodes in a solution with the desired aptamer, which is unsuitable for microelectrode arrays in which the electrodes are closely spaced. In this work, we selectively modified electrode surfaces with thiolated aptamers of different single-stranded DNA sequences, by successive removal and addition of thiol monolayers. This was achieved by electrodesorption of thiol monolayers using controlled potential, to expose unmodified gold electrodes to be modified with a different thiolated aptamer, thus enabling multiple different aptamers to be used on the surfaces of closely spaced microelectrodes. All aptamers were methylene blue terminated, allowing redox currents to be measured and used to monitor aptamer probe packing density on the electrode surface and the selectivity of the sensors. Here, we demonstrate the microscale E-AB sensor multianalyte detection method using aptamers for target analytes, adenosine triphosphate, dopamine, and serotonin, which can ultimately be applied to perform localized simultaneous detection using electrode arrays.

Design and Synthesis of Kekulè and Non-Kekulè Diradicaloids via the Radical Periannulation Strategy: The Power of Seven Clar's Sextets.

This work introduces an approach to uncoupling electrons via maximum utilization of localized aromatic units, i.e., the Clar's π-sextets. To illustrate the utility of this concept to the design of Kekulé diradicaloids, we have synthesized a tridecacyclic polyaromatic system where a gain of five Clar's sextets in the open-shell form overcomes electron pairing and leads to the emergence of a high degree of diradical character. According to unrestricted symmetry-broken UCAM-B3LYP calculations, the singlet diradical character in this core system is characterized by the y0 value of 0.98 (y0 = 0 for a closed-shell molecule, y0 = 1 for pure diradical). The efficiency of the new design strategy was evaluated by comparing the Kekulé system with an isomeric non-Kekulé diradical of identical size, i.e., a system where the radical centers cannot couple via resonance. The calculated singlet-triplet gap, i.e., the ΔEST values, in both of these systems approaches zero: -0.3 kcal/mol for the Kekulé and +0.2 kcal/mol for the non-Kekulé diradicaloids. The target isomeric Kekulé and non-Kekulé systems were assembled using a sequence of radical periannulations, cross-coupling, and C-H activation. The diradicals are kinetically stabilized by six tert-butyl substituents and (triisopropylsilyl)acetylene groups. Both molecules are NMR-inactive but electron paramagnetic resonance (EPR)-active at room temperature. Cyclic voltammetry revealed quasi-reversible oxidation and reduction processes, consistent with the presence of two nearly degenerate partially occupied molecular orbitals. The experimentally measured ΔEST value of -0.14 kcal/mol confirms that K is, indeed, a nearly perfect singlet diradical.

Influence of community-level sanitation coverage and population density on environmental fecal contamination and child health in a longitudinal cohort in rural Bangladesh.

BACKGROUND: Household-level sanitation interventions have had limited effects on child health or environmental contamination, potentially due to low community coverage. Higher community-level coverage with safely managed sanitation can reduce opportunities for disease transmission. METHODS: We estimated associations between community sanitation coverage, environmental fecal contamination, and child health among 360 compounds in the control arm of the WASH Benefits trial in rural Bangladesh (NCT01590095). In each compound, we enumerated E. coli in environmental samples and recorded the 7-day prevalence of caregiver-reported diarrheal disease and acute respiratory infections (ARI) in children under five. We observed indicators of latrine access and quality among all neighboring compounds within 100 m of study compounds. We defined community coverage as the proportion of neighboring compounds with (1) at least one latrine, and (2) exclusively hygienic latrines (improved facility observed to safely contain feces), within both 50 m and 100 m of study compounds. We assessed effect modification by population density and season. RESULTS: Adjusted for confounders, study compounds surrounded by 100% coverage of at least one latrine per compound within 50 m had slightly lower log10E. coli counts in stored water (Δlog = -0.13, 95% CI -0.26, -0.01), child hand rinses (Δlog = -0.13, 95% CI -0.24, -0.02), and caregiver hand rinses (Δlog = -0.16, 95% CI -0.29, -0.03) and marginally lower prevalence of diarrheal disease (prevalence ratio [PR] = 0.82, 95% CI 0.64, 1.04) and ARI (PR = 0.84, 95% CI 0.69, 1.03) compared to compounds surrounded by <100% coverage. Effects were similar but less pronounced at 100 m. At higher population densities, community latrine coverage was associated with larger reductions in E. coli on child and caregiver hands and prevalence of diarrheal disease. Coverage with exclusively hygienic latrines was not associated with any outcome. CONCLUSION: Higher community sanitation coverage was associated with reduced fecal contamination and improved child health, with stronger effects at highly local scales (50m) and at high population densities. Our findings indicate that the relationship between community sanitation coverage, environmental contamination, and child health varies by definition of coverage, distance, and population density. This work highlights significant uncertainty around how to best measure sanitation coverage and the expected health effects of increasing sanitation coverage using a specific metric. Better understanding of community-level sanitation access is needed to inform policy for implementing sanitation systems that effectively protect community health.

Effect of sanitation improvements on soil-transmitted helminth eggs in courtyard soil from rural Bangladesh: Evidence from a cluster-randomized controlled trial.

Improved sanitation has been hypothesized to reduce soil-transmitted helminth (STH) infections by reducing the prevalence and concentration of STH eggs/larvae in soil. We evaluated the effect of a randomized sanitation program (providing households with an improved dual-pit latrine, tools for child/animal feces management, and behavioral messaging) on reducing the prevalence and concentration of STH eggs in soil from household courtyards. We collected soil samples from 1405 households enrolled in the sanitation intervention (n = 419) and control (n = 914) groups of a cluster-randomized controlled trial (WASH Benefits) in rural Bangladesh approximately 2 years after the initiation of the interventions. We analyzed samples for Ascaris lumbricoides, Trichuris trichiura, and hookworm eggs by microscopy. We estimated prevalence ratios (PR) and egg count ratio (ECR) to compare the prevalence of STH eggs and arithmetic and geometric mean egg counts for STH eggs per gram of soil in the sanitation and control arms. Among intervention households, latrines achieved high and sustained user uptake by adults while child open defecation remained common and most households did not dispose of child feces hygienically. In courtyard soil from control households, the prevalence of any STH eggs was 75.7% and the prevalence of any larvated STH eggs was 67.3%. A. lumbricoides was detected in 63.0% of control samples and T. trichiura in 55.7% of control samples; hookworm was not detected in any sample. In the control arm, the arithmetic mean egg count for any STH was 3.96 eggs/dry gram, while the geometric mean was 1.58 eggs/dry gram. There was no difference between the intervention and control groups in the prevalence of any STH eggs (PR = 0.98 (95% CI: 0.91, 1.05)) or mean egg counts (ECR = 0.08 (95% CI: -0.10, 0.26) for geometric mean and 0.07 (95% CI: -0.22, 0.37) for arithmetic mean). Adjusted models gave similar results. A compound-level sanitation intervention that provided improved latrines and tools for disposal of child and animal feces did not have an impact on STH eggs in soil. In order to effectively reduce the prevalence and concentration of STH eggs in the environment, sustained, widespread use of sanitation strategies to isolate and hygienically dispose of child and animal feces may need to complement traditional strategies for containment of adult human feces. Trial Registration: NCT01590095.

Longitudinal Effects of a Sanitation Intervention on Environmental Fecal Contamination in a Cluster-Randomized Controlled Trial in Rural Bangladesh.

Household latrine access generally is not associated with reduced fecal contamination in the environment, but its long-term effectiveness has not been measured. We conducted an environmental assessment nested within the WASH Benefits Bangladesh randomized controlled trial (NCT01590095). We quantified E. coli and fecal coliforms in samples of stored drinking water, child hands, mother hands, soil, and food among a random sample of households from the sanitation and control arms of the trial. Samples were collected during eight quarterly visits approximately 1-3.5 years after intervention initiation. Overall, there were no substantial differences in environmental fecal contamination between households enrolled in the sanitation and control arms. Statistically significant reductions were found in stored water and child hands after pooling across sampling rounds, but the effects were small and not consistent across rounds. In addition, we assessed potential effect modification of intervention effects by follow-up time, season, wealth, community-level latrine density and coverage, population density, and domestic animal ownership. While the intervention had statistically significant effects within some subgroups, there were no consistent patterns of effect modification. Our findings support a growing consensus that on-site latrines are insufficient to prevent fecal contamination in the rural household environment.

Child defecation and feces management practices in rural Bangladesh: Associations with fecal contamination, observed hand cleanliness and child diarrhea.

Child open defecation is common in low-income countries and can lead to fecal exposure in the domestic environment. We assessed associations between child feces management practices vs. measures of contamination and child diarrhea among households with children <5 years in rural Bangladesh. We visited 360 households quarterly and recorded caregiver-reported diarrhea prevalence, and defecation and feces disposal practices for children <5 years. We examined caregiver and child hands for visible dirt and enumerated E. coli in child and caregiver hand rinse and stored drinking water samples. Safe child defecation (in latrine/potty) and safe feces disposal (in latrine) was reported by 21% and 23% of households, respectively. Controlling for potential confounders, households reporting unsafe child defecation had higher E. coli prevalence on child hands (prevalence ratio [PR] = 1.12, 1.04-1.20) and in stored water (PR = 1.12,1.03-1.21). Similarly, households reporting unsafe feces disposal had higher E. coli prevalence on child hands (PR = 1.11, 1.02-1.21) and in stored water (PR = 1.10, 1.03-1.18). Effects on E. coli levels were similar. Children in households with unsafe defecation and feces disposal had higher diarrhea prevalence but the associations were not statistically significant. Our findings suggest that unsafe child feces management may present a source of fecal exposure for young children.

Agricultural Injury-Associated Chromobacterium violaceum Infection in a Bangladeshi Farmer.

Chromobacterium violaceum is an emerging environmental pathogen that causes life-threatening infection in humans and animals. In October 2017, a Bangladeshi farmer was hospitalized with high-grade fever due to an agricultural injury-related wound infection. Bacteriological and 16S rRNA gene investigation detected C. violaceum in the wound discharge. The patient recovered successfully after a combination treatment with meropenem and ciprofloxacin, followed by prolonged medication to avoid recurrence. We strongly propose to incorporate C. violaceum in the differential diagnosis of wound and skin infections occurring in tropical and subtropical regions, especially when the injury was exposed to soil or sluggish water.

Effect of Sanitation Improvements on Pathogens and Microbial Source Tracking Markers in the Rural Bangladeshi Household Environment.

Diarrheal illnesses from enteric pathogens are a leading cause of death in children under five in low- and middle-income countries (LMICs). Sanitation is one way to reduce the spread of enteric pathogens in the environment; however, few studies have investigated the effectiveness of sanitation in rural LMICs in reducing pathogens in the environment. In this study, we measured the impact of a sanitation intervention (dual-pit latrines, sani-scoops, child potties delivered as part of a randomized control trial, WASH Benefits) in rural Bangladeshi household compounds by assessing prevalence ratios, differences, and changes in the concentration of pathogen genes and host-specific fecal markers. We found no difference in the prevalence of pathogenic Escherichia coli, norovirus, or Giardia genes in the domestic environment in the sanitation and control arms. The prevalence of the human fecal marker was lower on child hands and the concentration of animal fecal marker was lower on mother hands in the sanitation arm in adjusted models, but these associations were not significant after correcting for multiple comparisons. In the subset of households with ≥10 individuals per compound, the prevalence of enterotoxigenic E. coli genes on child hands was lower in the sanitation arm. Incomplete removal of child and animal feces or the compound (versus community-wide) scale of intervention could explain the limited impacts of improved sanitation.

Microbiological contamination of young children's hands in rural Bangladesh: Associations with child age and observed hand cleanliness as proxy.

BACKGROUND: Hands are a route of transmission for fecal-oral pathogens. This analysis aimed to assess associations between hand E. coli contamination and child age and determine if observed hand cleanliness can serve as a proxy for E. coli contamination on young children's hands. METHODS: Trained field workers collected hand rinse samples from children aged 1-14 months in 584 households in rural Bangladesh and assessed the visual cleanliness of child hands (fingernails, finger pads and palms). Samples were analyzed using the IDEXX most probable number (MPN) methodto enumerate E. coli. We assessed if child age (immobile children aged 1-4 months vs. mobile children aged 5-14 months) is associated with log10 E. coli counts on hands using generalized estimating equations (GEE). We estimated the log10 difference in hand E. coli counts associated with the cleanliness of different hand parts using a multivariable GEE model.We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for dirty fingernails, fingerpads, palms and overall hands (the three observed parts combined) against binary E. coli presence on hands. RESULTS: E. coli was detected on 43% of child hands. Children in the mobile age range had 0.17 log10 MPN higher E. coli on hands than those in the immobile age range (Δlog10 = 0.17, 95% CI = 0.02, 0.32, p = 0.03). Children with visible dirt particles on finger pads had 0.46 log10 MPN higher E. coli on hands than those with clean finger pads (Δlog10 = 0.46, 95% CI = 0.05, 0.87, p = 0.03). Dirty fingernails indicated binary E. coli presence with 81% sensitivity and 26% specificity while dirty fingerpads and palms indicated E. coli presence with 29% sensitivity and 75-77% specificity. The PPV was 45-48% and NPV 59-65% for all three types of observations. CONCLUSION: Hand contamination with E. coli was prevalent among young children in rural Bangladesh, with higher levels of contamination among mobile children. Studies should assess if strategies to remove animal feces from the courtyard, provide designated hygienic play spaces for children and deliver targeted messaging to mothers to wipe or wash children's hands after contact with animals and animal feces reduce child hand contamination. Visible hand cleanliness was a poor predictor of E. coli presence on young children's hands so other low-cost field measurements are needed to accurately detect fecal contamination on hands.

Predictors of Enteric Pathogens in the Domestic Environment from Human and Animal Sources in Rural Bangladesh.

Fecal indicator organisms are measured to indicate the presence of fecal pollution, yet the association between indicators and pathogens varies by context. The goal of this study was to empirically evaluate the relationships between indicator Escherichia coli, microbial source tracking markers, select enteric pathogen genes, and potential sources of enteric pathogens in 600 rural Bangladeshi households. We measured indicators and pathogen genes in stored drinking water, soil, and on mother and child hands. Additionally, survey and observational data on sanitation and domestic hygiene practices were collected. Log10 concentrations of indicator E. coli were positively associated with the prevalence of pathogenic E. coli genes in all sample types. Given the current need to rely on indicators to assess fecal contamination in the field, it is significant that in this study context indicator E. coli concentrations, measured by IDEXX Colilert-18, provided quantitative information on the presence of pathogenic E. coli in different sample types. There were no significant associations between the human fecal marker (HumM2) and human-specific pathogens in any environmental sample type. There was an increase in the prevalence of Giardia lamblia genes, any E. coli virulence gene, and the specific E. coli virulence genes stx1/2 with every log10 increase in the concentration of the animal fecal marker (BacCow) on mothers' hands. Thus, domestic animals were important contributors to enteric pathogens in these households.

Lung Consolidation Detection through Analysis of Vocal Resonance Signals.

Consolidation of the lung is a common pathology which is sometimes life threatening. One of the primary causes is the infection of lung tissue (pneumonia). Vocal resonance and vocal fremitus are part of the routine clinical examination of the respiratory system by physicians, which although time consuming, helps in the diagnosis of consolidation of the lung. In this paper, we suggest a possible automatic lung consolidation detection system that can be used by health workers with basic training. Analysis is performed on the vocal resonance sound signals recorded using an electronic stethoscope from the chest walls of normal subjects and patients. We show that for the detection system, use of signal loudness, which is generally considered by physicians, would be infeasible and propose that signal power spectral density computed using our system be considered. Certain frequency regions in the power spectral density (periodogram) are proved to be significant indicators of lung consolidation using t-tests. These findings are then applied to design the detection system using Gaussian naive Bayes classifiers.

Do Sanitation Improvements Reduce Fecal Contamination of Water, Hands, Food, Soil, and Flies? Evidence from a Cluster-Randomized Controlled Trial in Rural Bangladesh.

Sanitation improvements have had limited effectiveness in reducing the spread of fecal pathogens into the environment. We conducted environmental measurements within a randomized controlled trial in Bangladesh that implemented individual and combined water treatment, sanitation, handwashing (WSH) and nutrition interventions (WASH Benefits, NCT01590095). Following approximately 4 months of intervention, we enrolled households in the trial's control, sanitation and combined WSH arms to assess whether sanitation improvements, alone and coupled with water treatment and handwashing, reduce fecal contamination in the domestic environment. We quantified fecal indicator bacteria in samples of drinking and ambient waters, child hands, food given to young children, courtyard soil and flies. In the WSH arm, Escherichia coli prevalence in stored drinking water was reduced by 62% (prevalence ratio = 0.38 (0.32, 0.44)) and E. coli concentration by 1-log (Δlog10 = -0.88 (-1.01, -0.75)). The interventions did not reduce E. coli along other sampled pathways. Ambient contamination remained high among intervention households. Potential reasons include noncommunity-level sanitation coverage, child open defecation, animal fecal sources, or naturalized E. coli in the environment. Future studies should explore potential threshold effects of different levels of community sanitation coverage on environmental contamination.

Fecal Indicator Bacteria along Multiple Environmental Transmission Pathways (Water, Hands, Food, Soil, Flies) and Subsequent Child Diarrhea in Rural Bangladesh.

Enteric pathogens can be transmitted through multiple environmental pathways, yet little is known about the relative contribution of each pathway to diarrhea risk among children. We aimed to identify fecal transmission pathways in the household environment associated with prospectively measured child diarrhea in rural Bangladesh. We measured the presence and levels of Escherichia coli in tube wells, stored drinking water, pond water, child hand rinses, courtyard soil, flies, and food in 1843 households. Gastrointestinal symptoms among children ages 0-60 months were recorded concurrently at the time of environmental sample collection and again a median of 6 days later. Incident diarrhea (3 or more loose stools in a 24-h period) was positively associated with the concentration of E. coli on child hands measured on the first visit (incidence rate ratio [IRR] = 1.23, 95% CI 1.06, 1.43 for a log10 increase), while other pathways were not associated. In cross-sectional analysis, there were no associations between concurrently measured environmental contamination and diarrhea. Our findings suggest higher levels of E. coli on child hands are strongly associated with subsequent diarrheal illness rates among children in rural Bangladesh.

Animal Feces Contribute to Domestic Fecal Contamination: Evidence from E. coli Measured in Water, Hands, Food, Flies, and Soil in Bangladesh.

Fecal-oral pathogens are transmitted through complex, environmentally mediated pathways. Sanitation interventions that isolate human feces from the environment may reduce transmission but have shown limited impact on environmental contamination. We conducted a study in rural Bangladesh to (1) quantify domestic fecal contamination in settings with high on-site sanitation coverage; (2) determine how domestic animals affect fecal contamination; and (3) assess how each environmental pathway affects others. We collected water, hand rinse, food, soil, and fly samples from 608 households. We analyzed samples with IDEXX Quantitray for the most probable number (MPN) of E. coli. We detected E. coli in source water (25%), stored water (77%), child hands (43%), food (58%), flies (50%), ponds (97%), and soil (95%). Soil had >120 000 mean MPN E. coli per gram. In compounds with vs without animals, E. coli was higher by 0.54 log10 in soil, 0.40 log10 in stored water and 0.61 log10 in food (p < 0.05). E. coli in stored water and food increased with increasing E. coli in soil, ponds, source water and hands. We provide empirical evidence of fecal transmission in the domestic environment despite on-site sanitation. Animal feces contribute to fecal contamination, and fecal indicator bacteria do not strictly indicate human fecal contamination when animals are present.

Macrodystrophia lipomatosa: Review of clinico-radio-histopathological features.

We report clinical, radiological, and pathological features of three cases of macrodystrophia lipomatosa, which is characterized by progressive proliferation of all mesenchymal elements, with a disproportionate increase in fibroadipose tissue. The peculiarity in our report is the involvement of contralateral hand and feet in our 1(st) case in contrast to usual presentations of this rare condition, which is often unilateral. In our 2(nd) case, the lateral aspect of foot was involved as against the usual finding of involvement of medial aspect in lower limbs, also another surprising finding in this case is increase in the size of lesion after puberty. Coming to our 3(rd) case, enlargement of almost whole of an upper extremity with profound involvement of middle, ring and little finger along with total sparing of the thumb is in itself an extremely rare occurrence as in upper limb, mainly the lateral aspect of hand and related digits bear the burnt and more over involvement of whole limb is itself an unique phenomenon.

Asymptomatic papules over central and pericentral areas of the face.

We report the case of a 24-year-old college girl, presenting with numerous acneiform papular eruptions over the central part of the face.

Automatic exact histogram specification for contrast enhancement and visual system based quantitative evaluation.

Histogram equalization, which aims at information maximization, is widely used in different ways to perform contrast enhancement in images. In this paper, an automatic exact histogram specification technique is proposed and used for global and local contrast enhancement of images. The desired histogram is obtained by first subjecting the image histogram to a modification process and then by maximizing a measure that represents increase in information and decrease in ambiguity. A new method of measuring image contrast based upon local band-limited approach and center-surround retinal receptive field model is also devised in this paper. This method works at multiple scales (frequency bands) and combines the contrast measures obtained at different scales using L(p)-norm. In comparison to a few existing methods, the effectiveness of the proposed automatic exact histogram specification technique in enhancing contrasts of images is demonstrated through qualitative analysis and the proposed image contrast measure based quantitative analysis.