Bacteriophage predation selects for diverse antiphage systems that frequently cluster on mobilizable defense islands in bacterial genomes. However, molecular insight into the reciprocal dynamics of ...phage-bacterial adaptations in nature is lacking, particularly in clinical contexts where there is need to inform phage therapy efforts and to understand how phages drive pathogen evolution. Using time-shift experiments, we uncovered fluctuations in
's resistance to phages in clinical samples. We mapped phage resistance determinants to SXT integrative and conjugative elements (ICEs), which notoriously also confer antibiotic resistance. We found that SXT ICEs, which are widespread in γ-proteobacteria, invariably encode phage defense systems localized to a single hotspot of genetic exchange. We identified mechanisms that allow phage to counter SXT-mediated defense in clinical samples, and document the selection of a novel phage-encoded defense inhibitor. Phage infection stimulates high-frequency SXT ICE conjugation, leading to the concurrent dissemination of phage and antibiotic resistances.
Objective
The objective of the study was to investigate potential risk factors for growth faltering among children under 5 years of age.
Method
We conducted a prospective cohort study of 553 children ...under 5 years from diarrhoea patient households in urban Dhaka, Bangladesh. Height and weight measurements were obtained at baseline and at a 12‐month follow‐up. Caregivers of young children were administered a monthly questionnaire on household sociodemographic characteristics and hygiene practices.
Results
Children with caregiver reports of mouthing soil at the majority of household visits had a significant reduction in their height‐for‐age z‐scores (HAZ) from baseline to the 12‐month follow‐up (ΔHAZ: −0.28 (95% confidence interval (CI): −0.51, −0.05)). A significant reduction in HAZ was also observed for children in households with animals in their sleeping space (ΔHAZ: −0.37 (95% CI: −0.71, −0.04)).
Conclusion
These findings provide further evidence to support the hypothesis that child mouthing of soil and the presence of animals in the child’s sleeping space are potential risk factors for growth faltering among young children. Interventions are urgently needed to provide clean play and sleeping spaces for young children to reduce exposure to faecal pathogens through child mouthing.
Objectif
L'objectif de l'étude était d'examiner les facteurs de risque potentiels de retard de croissance chez les enfants de moins de 5 ans.
Méthode
Nous avons mené une étude de cohorte prospective sur 553 enfants de moins de 5 ans provenant de ménages avec des patients diarrhéiques dans la ville de Dhaka, au Bangladesh. Les mesures de taille et de poids ont été obtenues au départ et à 12 mois de suivi. Les personnes s’occupant de jeunes enfants (les gardiens) ont reçu un questionnaire mensuel sur les caractéristiques sociodémographiques des ménages et les pratiques d'hygiène.
Résultats
Les enfants pour lesquels les gardiens ont déclaré qu'ils mâchouillaient de la terre lors de la majorité des visites à domicile présentaient une diminution du score Z de taille pour l’âge (TAZ) de manière significative de l'âge de référence au 12 mois de suivi (ΔTAZ −0,28 (intervalle de confiance (IC) à 95%: −0,51, −0,05)). Une réduction significative des TAZ a également été observée pour les enfants des ménages ayant des animaux dans leur espace de couchage (ΔTAZ −0,37 (IC95%: −0,71, −0,04)).
Conclusion
Ces résultats apportent des données supplémentaires pour appuyer l'hypothèse selon laquelle le fait que l'enfant mâchouille de la terre et la présence d'animaux dans son espace de couchage sont des facteurs de risque potentiels de retard de croissance chez les jeunes enfants. Des interventions sont urgemment nécessaires pour fournir des espaces de jeu et de sommeil sains aux jeunes enfants afin de réduire l'exposition aux agents pathogènes fécaux par le mâchouillement des enfants.
Cholera can result in the expulsion of important microbiota from the gut and result in death if left untreated. The disease transmits mainly via drinking water carrying Vibrio cholerae; and household ...contacts (HHC) of cholera patients are at elevated risk during the first week of infection. The gut microbiota profiles of HHC-children of cholera patients at Dhaka city slums were investigated before (day 0) and after (day 8) delivery of chlorinated water as part of the major study 'CHoBI7 trial (cholera-hospital-based intervention for 7 days)'.
Results of sequencing and analysis of bacterial community DNA revealed the predominance of two bacterial phyla: Bacteroidetes and Firmicutes at day 0 with a relative abundance of 62 ± 6 (mean ± SEM%) and 32 ± 7, respectively. The pattern reversed at day 8 with a decreased relative abundance of Bacteroidetes (39 ± 12; p = 0.034) and an increased abundance of Firmicutes (49 ± 12; p = 0.057). Of 65 bacterial families confirmed at day 0, six belonging to Proteobacteria including Vibrionaceae disappeared at day 8. Interestingly, the relative abundance of four Firmicutes families-Lachnospiraceae, Bifidobacteriaceae, Clostridiaceae, and Ruminococcaceae was increased in all five study children at day 8.
The observed exclusion of pathogenic Proteobacteria and enhancement of beneficial Firmicutes in the gut of children delivered with chlorinated water as part of WASH intervention reflect a great promise of the CHoBI7 program in preventing cholera and improving child health.
One of the most significant public health concerns in today's world is the persistent upsurge of infections caused by multidrug resistant bacteria. As a result, clinicians are being forced to ...intervene with either less effective backup drugs or ones with substantial side-effects. Colistin is a last resort antimicrobial agent for the treatment of infections caused by multi-drug resistant gram-negative bacteria.
(n = 65) isolated from street food (n = 20), hand rinse (n = 15), surface water (n = 10), and healthy human stool (n = 20) were tested for colistin resistance gene
and response to antimicrobial agents. Antimicrobial resistance genes and virulence genes were detected by employing polymerase chain reaction. DNA fingerprinting of the strains were determined by pulsed-field gel electrophoresis.
Screening of
allowed us to confirm colistin resistance marker gene
1 in 13 strains (street food, n = 4; hand rinse, n = 2; surface water, n = 4; and stool, n = 3); and two of these
strains carrying
-1 harbored
gene encoding extended spectrum beta lactamase. Antibiotic assay results revealed all 13
strains carrying
-1 to be multi-drug resistant (MDR), including to colistin. The minimum inhibitory concentration (MIC) for colistin ranged from 2 to 6 μg/ml. DNA sequencing confirmed homogeneity of the nucleotide sequence for
, but the
strains were heterogenous, as confirmed by pulsed-field gel electrophoresis suggesting horizontal transmission of colistin resistance in Bangladesh.
Widespread dissemination of
strains carrying
-1 encoding resistance to colistin in the present study is alarming as this is the last resort drug for the treatment of infections caused by MDR gram-negative bacteria resistant to almost all drugs used commonly.
Densely populated countries in Asia, such as Bangladesh, are considered to be major contributors to the increased occurrence of global antimicrobial resistance (AMR). Several factors make low-and ...middle-income countries vulnerable to increased emergence and spread of AMR in the environment including limited regulations on antimicrobial drug use, high volume of antimicrobials used in human medicine and agricultural production, and poor wastewater management. Previous monitoring campaigns to investigate the presence of antibiotics in the aquatic environment have employed targeted analysis in which selected antibiotics are measured using liquid chromatography with tandem mass spectrometry (LC/MS/MS). However, this approach can miss several important contaminants that can contribute to the selective pressure that promotes maintenance and dissemination of antibiotic resistance genes (ARGs) in the environment. Nontarget analysis by suspect screening and reanalysis of stored digital data of previously ran samples can provide information on analytes that were formerly uncharacterized and may be chemicals of emerging concern (CECs). In this study, surface waters in both urban and rural sites in Bangladesh were collected and analyzed for the presence of antibiotic residues and other pharmaceuticals. Utilizing targeted analysis, the antibiotics with the highest concentrations detected were ciprofloxacin (1407 ng/L) and clarithromycin (909 ng/L). In addition, using high-resolution LC/MS/MS in the first ever application of retrospective analysis in samples from Bangladesh, additional antibiotics clindamycin, lincomycin, linezolid, metronidazole, moxifloxacin, nalidixic acid, and sulfapyridine were detected. Prevalence of amoxicillin transformation products in surface waters was also confirmed. In addition, medicinal and agricultural antifungal compounds were frequently found in Bangladeshi surface waters. This later finding – the near ubiquity of antifungal agents in environmental samples – is of particular concern, as it may be contributing to the alarming rise of multi-drug resistant fungal (e.g. Candida auris) disease recently seen in humans throughout the world.
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•Urban and rural surface waters in Bangladesh were analyzed for chemicals of emerging concern.•Antibiotics that were detected at the highest concentrations were ciprofloxacin and clarithromycin.•Transformation products of amoxicillin were detected in the urban surface water samples.•Anti-fungal compounds were found to be present in Bangladesh waters including drinking water.
Objective
To characterise childhood mouthing and handling behaviours and to assess the association between hand‐to‐object and object‐to‐mouth contacts and diarrhoea prevalence in young children in ...urban Dhaka, Bangladesh.
Methods
A prospective cohort study was conducted among 494 children under 5 years of age in Dhaka, Bangladesh. This study was nested within the randomised controlled trial of the Cholera Hospital‐Based Intervention for 7 Days (CHoBI7) mobile health (mHealth) program. The CHoBI7 mHealth program focuses on promoting handwashing with soap and water treatment to diarrhoea patients and their household members through mobile messages and a single in person visit. Mouthing and handling of faeces and fomites among young children was measured by five‐hour structured observation and caregiver reports. Diarrhoea surveillance data was collected monthly for 12 months.
Results
Fifty five percent of caregivers reported that their child put a visibly dirty fomite (object or soil) in their mouth in the past week. Caregivers reported that 50% of children had mouthed visibly dirty objects, 26% had mouthed dirt, and 2% had mouthed faeces. Forty five percent of children were observed mouthing a visibly dirty fomite during structured observation, 40% of children were observed mouthing a visibly dirty object, 10% were observed mouthing soil, and one child (0.2%) was observed mouthing faeces. Mouthing of visibly dirty fomites was highest for children 12‐18 months of age with 69% of these children having caregiver reports and 54% having observed events. Children with caregiver reports of mouthing faeces had a significantly higher odds of diarrhoea over the subsequent month (Odds Ratio: 4.54; 95% Confidence Interval: 1.06, 19.48).
Conclusion
These findings demonstrate that mouthing of contaminated fomites among young children is frequent in urban environments in Bangladesh, and that mouthing faeces is associated with a significantly higher odds of diarrhoea. Interventions are urgently needed to protect young children from faecal pathogens in their play spaces.
Objectif
Caractériser les comportements de mâchouillement et de manipulation par les enfants et évaluer l'association entre les contacts main‐objet et objet‐bouche et la prévalence de la diarrhée chez les jeunes enfants dans la ville de Dhaka, au Bangladesh.
Méthodes
Une étude de cohorte prospective a été menée auprès de 494 enfants de moins de 5 ans à Dhaka, au Bangladesh. Cette étude s'inscrivait dans le cadre de l'essai contrôlé randomisé du programme CHoBI7 (Cholera‐Hospital‐Based‐Intervention‐for‐7‐days) de santé mobile (mHealth. Le programme de santé mobile CHoBI7 se concentre sur la promotion du traitement de l’eau et du lavage des mains avec à l'eau et au savon aux patients atteints de diarrhée et aux membres de leur foyer par le biais de messages mobiles et de visites de face à face. Le mâchouillement et la manipulation des excréments et des fomites chez les jeunes enfants ont été mesurés par des observations structurées de cinq heures et par les rapports des personnes s’occupant d’enfants (soignants). Les données de surveillance de la diarrhée ont été recueillies chaque mois pendant 12 mois.
Résultats
55% des soignants ont déclaré que leur enfant avait mis un fomite visiblement sale (objet ou terre) dans sa bouche au cours de la semaine précédente. Les soignants ont indiqué que 50% des enfants avaient mâchouillé des objets visiblement sales, 26% avaient mâchouillé de la terre et 2% avaient mâchouillé des excréments. 45% des enfants ont été observés en train de mâchouiller un fomite visiblement sale au cours d'une observation structurée. 40% des enfants ont été observés en train de mâchouiller un objet, 10% ont été observés en train de mâchouiller de la terre et un enfant (0,2%) a été observé en train de mâchouiller des excréments. Le mâchouillement de fomites visiblement sales était le plus fréquent chez les enfants de 12 à 18 mois; 69% de ces enfants ont été signalés par les soignants et 54% ont été observés en train de le faire. Les enfants dont les soignants avaient signalé un mâchouillement d’excréments présentaient un risque de diarrhée nettement plus élevé au cours du mois suivant (rapport de cotes: 4,54; intervalle de confiance à 95%: 1,06–19,48).
ConclusionCes résultats démontrent que le fait de mâchouiller des fomites contaminés chez les jeunes enfants est fréquent en milieu urbain au Bangladesh et que le fait de mâchouiller des excréments est associé à un risque de diarrhée nettement plus élevé. Des interventions sont urgemment nécessaires pour protéger les jeunes enfants des agents pathogènes fécaux dans leurs espaces de jeu.
Understanding the global burden of enterotoxigenic E. coli (ETEC) and Shigella diarrhea as well as estimating the cost effectiveness of vaccines to control these two significant pathogens have been ...hindered by the lack of a diagnostic test that is rapid, simple, sensitive, and can be applied to the endemic countries. We previously developed a simple and rapid assay, Rapid Loop mediated isothermal amplification based Diagnostic Test (RLDT) for the detection of ETEC and Shigella spp. (Shigella). In this study, the RLDT assay was evaluated in comparison with quantitative PCR (qPCR), culture and conventional PCR for the detection of ETEC and Shigella. This validation was performed using previously collected stool samples from endemic countries, from the travelers to the endemic countries, as well as samples from a controlled human infection model study of ETEC. The performance of RLDT from dried stool spots was also validated. RLDT resulted in excellent sensitivity and specificity compared to qPCR (99% and 99.2% respectively) ranging from 92.3 to 100% for the individual toxin genes of ETEC and 100% for Shigella. Culture was less sensitive compared to RLDT. No significant differences were noted in the performance of RLDT using samples from various sources or stool samples from moderate to severe diarrhea or asymptomatic infections. RLDT performed equally well in detection of ETEC and Shigella from the dried stool samples on filter papers. This study established that RLDT is sufficiently sensitive and specific to be used as a simple and rapid diagnostic assay to detect ETEC and Shigella in endemic countries to determine disease burden of these pathogens in the national and subnational levels. This information will be important to guide public health and policy makers to prioritize resources for accelerating the development and introduction of effective preventative and/or treatment interventions against these enteric infections.
Abstract
Background
The Cholera Hospital-Based Intervention for 7 Days (CHoBI7) mobile health (mHealth) program was a cluster-randomized controlled trial of diarrhea patient households conducted in ...Dhaka, Bangladesh.
Methods
Patients were block-randomized to 3 arms: standard message on oral rehydration solution use; health facility delivery of CHoBI7 plus mHealth (no home visits); and health facility delivery of CHoBI7 plus 2 home visits and mHealth. The primary outcome was reported diarrhea in the past 2 weeks collected monthly for 12 months. The secondary outcomes were stunting, underweight, and wasting at a 12-month follow-up. Analysis was intention-to-treat.
Results
Between 4 December 2016 and 26 April 2018, 2626 participants in 769 households were randomly allocated to 3 arms: 849 participants to the standard message arm, 886 to mHealth with no home visits arm, and 891 to the mHealth with 2 home visits. Children <5 years had significantly lower 12-month diarrhea prevalence in both the mHealth with 2 home visits arm (prevalence ratio PR: 0.73 95% confidence interval {CI}, .61–.87) and the mHealth with no home visits arm (PR: 0.82 95% CI, .69–.97). Children <2 years were significantly less likely to be stunted in both the mHealth with 2 home visits arm (33% vs 45%; odds ratio OR: 0.55 95% CI, .31–.97) and the mHealth with no home visits arm (32% vs 45%; OR: 0.54 95% CI, .31–.96) compared with children in the standard message arm.
Conclusions
The CHoBI7 mHealth program lowered pediatric diarrhea and stunting among diarrhea patient households.
Clinical Trials Registration
NCT04008134.
In this trial, young children in diarrhea patient households receiving the CHoBI7 mobile health program had less stunting and diarrhea compared with those only receiving the standard recommendation on oral rehydration solution for dehydration.
Despite the advancement in our understanding of cholera and its etiological agent, Vibrio cholerae, the prevention and treatment of the disease are often hindered due to rapid changes in drug ...response pattern, serotype, and the major genomic islands namely, the CTX-prophage, and related genetic characteristics. In the present study, V. cholerae (n = 172) associated with endemic cholera in Dhaka during the years 2015-2021 were analyzed for major phenotypic and genetic characteristics, including drug resistance patterns.
Results revealed that the V. cholerae strains belonged to serogroup O1 biotype El Tor carrying El Tor -specific genes rtxC, tcpA El Tor, and hlyA El Tor, but possessed classical-biotype cholera toxin. Serotypes of V. cholerae strains differed temporally in predominance with Inaba during 2015-2017, and again in 2020-2021, while Ogawa was the predominant serotype in 2018-2019. Also, ctxB1 was predominant in V. cholerae associated with cholera during 2015-2017, while ctxB7 was predominant in 2018, and in the subsequent years, as observed until 2021. V. cholerae strains differed in their antibiotic resistance pattern with a majority (97%) being multi-drug resistant (MDR) and belonging to six sub-groups. Notably, one of these MDR strains was resistant to eleven of the eighteen antibiotics tested, with resistance to fourth-generation cephalosporin (cefepime), and aztreonam. This extreme drug resistant (XDR) strain carried resistance-related genes namely, extended-spectrum β-lactamases (ESBL), blaOXA-1 and blaPER-3.
The observed temporal switching of serotypes, as well as the ctxB genotype, and the emergence of MDR/XDR V. cholerae and their association with endemic cholera in Dhaka underscore the need for routine monitoring of the pathogen for proper patient management.
Phage defense systems are often found on mobile genetic elements (MGEs), where they constitutively defend against invaders or are induced to respond to new assaults. Phage satellites, one type of ...MGE, are induced during phage infection to promote their own transmission, reducing phage production and protecting their hosts in the process. One such satellite in Vibrio cholerae, phage-inducible chromosomal island-like element (PLE), sabotages the lytic phage ICP1, which triggers PLE excision from the bacterial chromosome, replication, and transduction to neighboring cells. Analysis of patient stool samples from different geographic regions revealed that ICP1 has evolved to possess one of two syntenic loci encoding an SF1B-type helicase, either of which PLE exploits to drive replication. Further, loss of PLE mobilization limits anti-phage activity because of phage-mediated degradation of the bacterial genome. Our work provides insight into the unique challenges facing parasites of lytic phages and underscores the adaptions of satellites to their ever-evolving target phage.
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•Phage satellites exploit helicases of a V. cholerae lytic phage to selfishly replicate•Phylogenetically distinct helicases from patient stool samples are sensitive to hijacking•Mobilization of phage satellites is critical to avoid phage takeover of bacterial host
Phage defense systems are often found on mobile genetic elements (MGEs). McKitterick et al. discover that viral satellites in Vibrio cholerae hijack phage-encoded helicases to replicate and escape the host chromosome, which elicits robust phage defense. Mobilization to escape host takeover might explain why some resistance mechanisms cluster on MGEs.
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