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      Risk factors for diarrheagenic Escherichia coli infection in children aged 6–24 months in peri-urban community, Nairobi, Kenya

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          Abstract

          Escherichia coli commonly inhabits the gut of humans and animals as part of their microbiota. Though mostly innocuous, some strains have virulence markers that make them pathogenic. This paper presents results of a cross-sectional epidemiological study examining prevalence of diarrheagenic E. coli (DEC) pathotypes in stool samples of asymptomatic healthy children (n = 540) in Dagoretti South subcounty, Nairobi, Kenya. E. coli was cultured and pathotyped using PCR to target specific virulence markers associated with Shiga-toxin, enteropathogenic, enterotoxigenic, enteroaggregative, entero-invasive and diffusely adherent E. coli. Overall prevalence of DEC pathotypes was 20.9% (113/540) with enteropathogenic E. coli being the most prevalent (34.1%), followed by enteroaggregative E. coli (23.5%) and Shiga-toxin producing E. coli (22.0%) among positive samples. We found evidence of co-infection with multiple pathotypes in 15% of the positive samples. Our models indicated that at the household level, carriage of DEC pathotypes in children was associated with age group [12–18 months] (OR 1.78; 95%CI 1.03–3.07; p = 0.04), eating matoke (mashed bananas) (OR 2.32; 95%CI 1.44–3.73; p = 0.001) and pulses/legumes (OR 1.74; 95%CI 1.01–2.99; p = 0.046) while livestock ownership or contact showed no significant association with DEC carriage (p>0.05). Our findings revealed significant prevalence of pathogenic DEC circulating among presumptive healthy children in the community. Since there has been no previous evidence of an association between any food type and DEC carriage, unhygienic handling, and preparation of matoke and pulses/legumes could be the reason for significant association with DEC carriage. Children 12–18 months old are more prone to DEC infections due to exploration and hand-to-mouth behavior. A detailed understanding is required on what proportion of positive cases developed severe symptomatology as well as fatal outcomes. The co-infection of pathotypes in the rapidly urbanizing environment needs to be investigated for hybrid or hetero-pathotype circulation that have been implicated in previous infection outbreaks.

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          Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis

          (2022)
          Summary Background Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen–drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen–drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level. Findings On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62–6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911–1·71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27·3 deaths per 100 000 (20·9–35·3), and lowest in Australasia, at 6·5 deaths (4·3–9·4) per 100 000. Lower respiratory infections accounted for more than 1·5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929 000 (660 000–1 270 000) deaths attributable to AMR and 3·57 million (2·62–4·78) deaths associated with AMR in 2019. One pathogen–drug combination, meticillin-resistant S aureus, caused more than 100 000 deaths attributable to AMR in 2019, while six more each caused 50 000–100 000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae. Interpretation To our knowledge, this study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data. AMR is a leading cause of death around the world, with the highest burdens in low-resource settings. Understanding the burden of AMR and the leading pathogen–drug combinations contributing to it is crucial to making informed and location-specific policy decisions, particularly about infection prevention and control programmes, access to essential antibiotics, and research and development of new vaccines and antibiotics. There are serious data gaps in many low-income settings, emphasising the need to expand microbiology laboratory capacity and data collection systems to improve our understanding of this important human health threat. Funding Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.
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            Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study.

            Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries. We designed the Global Enteric Multicenter Study (GEMS) to identify the aetiology and population-based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia. The GEMS is a 3-year, prospective, age-stratified, matched case-control study of moderate-to-severe diarrhoea in children aged 0-59 months residing in censused populations at four sites in Africa and three in Asia. We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three randomly selected matched community control children without diarrhoea. From patients with moderate-to-severe diarrhoea and controls, we obtained clinical and epidemiological data, anthropometric measurements, and a faecal sample to identify enteropathogens at enrolment; one follow-up home visit was made about 60 days later to ascertain vital status, clinical outcome, and interval growth. We enrolled 9439 children with moderate-to-severe diarrhoea and 13,129 control children without diarrhoea. By analysing adjusted population attributable fractions, most attributable cases of moderate-to-severe diarrhoea were due to four pathogens: rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli producing heat-stable toxin (ST-ETEC; with or without co-expression of heat-labile enterotoxin), and Shigella. Other pathogens were important in selected sites (eg, Aeromonas, Vibrio cholerae O1, Campylobacter jejuni). Odds of dying during follow-up were 8·5-fold higher in patients with moderate-to-severe diarrhoea than in controls (odd ratio 8·5, 95% CI 5·8-12·5, p<0·0001); most deaths (167 [87·9%]) occurred during the first 2 years of life. Pathogens associated with increased risk of case death were ST-ETEC (hazard ratio [HR] 1·9; 0·99-3·5) and typical enteropathogenic E coli (HR 2·6; 1·6-4·1) in infants aged 0-11 months, and Cryptosporidium (HR 2·3; 1·3-4·3) in toddlers aged 12-23 months. Interventions targeting five pathogens (rotavirus, Shigella, ST-ETEC, Cryptosporidium, typical enteropathogenic E coli) can substantially reduce the burden of moderate-to-severe diarrhoea. New methods and accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes. The Bill & Melinda Gates Foundation. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review

              The acronym ESKAPE includes six nosocomial pathogens that exhibit multidrug resistance and virulence: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. Persistent use of antibiotics has provoked the emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) bacteria, which render even the most effective drugs ineffective. Extended spectrum β-lactamase (ESBL) and carbapenemase producing Gram negative bacteria have emerged as an important therapeutic challenge. Development of novel therapeutics to treat drug resistant infections, especially those caused by ESKAPE pathogens is the need of the hour. Alternative therapies such as use of antibiotics in combination or with adjuvants, bacteriophages, antimicrobial peptides, nanoparticles, and photodynamic light therapy are widely reported. Many reviews published till date describe these therapies with respect to the various agents used, their dosage details and mechanism of action against MDR pathogens but very few have focused specifically on ESKAPE. The objective of this review is to describe the alternative therapies reported to treat ESKAPE infections, their advantages and limitations, potential application in vivo, and status in clinical trials. The review further highlights the importance of a combinatorial approach, wherein two or more therapies are used in combination in order to overcome their individual limitations, additional studies on which are warranted, before translating them into clinical practice. These advances could possibly give an alternate solution or extend the lifetime of current antimicrobials.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: SupervisionRole: Writing – review & editing
                Role: Formal analysisRole: Writing – review & editing
                Role: InvestigationRole: Validation
                Role: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: Investigation
                Role: Investigation
                Role: Investigation
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: Formal analysis
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLOS Glob Public Health
                PLOS Glob Public Health
                plos
                PLOS Global Public Health
                Public Library of Science (San Francisco, CA USA )
                2767-3375
                22 November 2023
                2023
                : 3
                : 11
                : e0002594
                Affiliations
                [1 ] Animal and Human Health Department, International Livestock Research Institute, Nairobi, Kenya
                [2 ] Department of Biochemistry, Biotechnology and Microbiology, Kenyatta University, Nairobi, Kenya
                [3 ] Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom
                [4 ] Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg C, Denmark
                [5 ] Department of Disease Control, London School of Hygiene and Tropical Medicine, London, United Kingdom
                St Paul’s Hospital Millennium Medical College, ETHIOPIA
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-5984-6444
                https://orcid.org/0000-0002-6236-2280
                https://orcid.org/0000-0002-6469-3948
                https://orcid.org/0000-0003-4576-0233
                https://orcid.org/0000-0001-6081-8363
                Article
                PGPH-D-23-01426
                10.1371/journal.pgph.0002594
                10664883
                37992040
                a65740a1-a45a-438d-bd81-8836b1d15536
                © 2023 Okumu et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 July 2023
                : 16 October 2023
                Page count
                Figures: 3, Tables: 3, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: INV-008449
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100020171, Foreign, Commonwealth and Development Office;
                Award Recipient :
                The project Development of a comprehensive intervention to address foodborne enteric disease risks among young children living in low-income informal neighbourhoods of Maputo and Nairobi is supported by the Bill & Melinda Gates Foundation (BMGF) and the Foreign, Commonwealth and Development Office (FCDO) of the UK Government (INV-008449) and the CGIAR Research Program on Agriculture for Nutrition and Health, which is led by the International Food Policy Research Institute (IFPRI).
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