Biology subjects

Kotloff, K. L.

Publications and source records attributed to Kotloff, K. L..

3 recordsLinked to original sources

bioRxiv2024

Genetic diversity and antimicrobial resistance of Campylobacter jejuni isolates from Gambian children under five with moderate-to-severe diarrhoea and healthy Controls

IntroductionCampylobacter is a leading cause of bacterial gastroenteritis globally, but its molecular epidemiology remains poorly understood in sub-Saharan Africa. This study investigates the genotypic population structure of Campylobacter jejuni isolates from children with moderate-to-severe diarrhoea (MSD) and healthy controls in The Gambia. Additionally, we determined the antimicrobial susceptibility levels of the isolates. MethodsAs part of the Global Enteric Multicenter Study (GEMS) in The Gambia, a total of 49 C. jejuni isolates were collected from the stools of children under 5 years old, including 22 with MSD and 27 healthy controls. These isolates were subjected to multilocus sequence typing (MLST) and antimicrobial susceptibility testing using the disc-diffusion method. ResultsThe C. jejuni isolates belonged to 22 sequence types (STs), ten of which were novel. The most common STs were ST-353 (19.1%, 9/47), ST-7784 (12.7%, 6/47), and ST-1038 (10.6%, 5/47). All isolates were fully susceptible to erythromycin, tetracycline, gentamicin and chloramphenicol, with two isolates (4.4%, 2/45) resistant to ciprofloxacin and nalidixic acid. Antimicrobial resistance or intermediate susceptibility to trimethoprim-sulfamethoxazole, cefotaxime and ampicillin was observed in 91.1% (41/45), 90.9% (40/44), and 44.4% (20/45) of the isolates, respectively. There was no strong evidence linking C. jejuni antimicrobial susceptibility or MLST genotype to MSD status. ConclusionThis study provides the first overview of the high genotypic diversity of human C. jejuni isolates in The Gambia and reveals low-level resistance among the isolates to antibiotics commonly used to treat campylobacteriosis. The study contributes to understanding the epidemiology and resistance patterns of C. jejuni in this region.

microbiology↗

bioRxiv2019

The seasonality of diarrheal pathogens: A retrospective study of seven sites over three years

BackgroundPediatric diarrhea can be caused by a wide variety of pathogens, from bacteria to viruses to protozoa. Pathogen prevalence is often described as seasonal, peaking annually and associated with specific weather conditions. Although many studies have described the seasonality of diarrheal disease, these studies have occurred predominantly in temperate regions. In tropical and resource-constrained settings, where nearly all diarrhea-associated mortality occurs, the seasonality of many diarrheal pathogens has not been well characterized. As a retrospective study, we analyze the seasonal prevalence of diarrheal pathogens among children with moderate-to-severe diarrhea (MSD) over three years from the seven sites of the Global Enteric Multicenter Study (GEMS), a case-control study. Using data from this expansive study on diarrheal disease, we characterize the seasonality of different pathogens, their association with site-specific weather patterns, and consistency across study sites. Methodology/Principal FindingsUsing traditional methodologies from signal processing, we found that certain pathogens peaked at the same time every year, but not at all sites. We also found associations between pathogen prevalence and weather or "seasons", which are defined by applying modern machine-learning methodologies to site-specific weather data. In general, rotavirus was most prevalent during the drier "winter" months and out of phase with bacterial pathogens, which peaked during hotter and rainier times of year corresponding to "monsoon", "rainy", or "summer" seasons. Conclusions/SignificanceIdentifying the seasonally-dependent prevalence for diarrheal pathogens helps characterize the local epidemiology and inform the clinical diagnosis of symptomatic children. Our multi-site, multi-continent study indicates a complex epidemiology of pathogens that does not reveal an easy generalization that is consistent across all sites. Instead, our study indicates the necessity of local data to characterizing the epidemiology of diarrheal disease. Recognition of the local associations between weather conditions and pathogen prevalence suggests transmission pathways and could inform control strategies in these settings.

epidemiology↗

bioRxiv2017

Drivers of antimicrobial resistance amongst intestinal Escherichia coli isolated from children in South Asia and sub-Saharan Africa

Antimicrobial resistance (AMR) dynamics are poorly understood in developing countries, where data on the prevalence of AMR in enteric bacteria are sparse, particularly among children and in the community setting. Here we use a combination of phenotyping, genomics and antimicrobial usage data to investigate patterns of AMR amongst atypical enteropathogenic E. coli (aEPEC) strains isolated from children <5 years old in seven countries (four in sub-Saharan Africa and three in South Asia) over a three-year period. We detected very high rates of AMR, with 65% of isolates displaying resistance to [≥]3 drug classes; the rates of AMR were the same amongst strains associated with diarrhea and strains that were carried asymptomatically. Whole genome sequencing identified a diversity of genetic mechanisms for AMR, which could explain >95% of observed phenotypic resistance. Analysis of AMR gene co-occurrence revealed clusters of acquired AMR genes that were frequently co-located on small plasmids and transposons, providing opportunities for acquisition of multidrug resistance in a single step. We used discriminant analysis to investigate potential drivers of AMR within the bacterial population, and found that genetic determinants of AMR were associated with geographical location of isolation but not with phylogenetic lineage of the E. coli strain or disease status of the human host. Comparison with antimicrobial usage data showed that the prevalence of resistance to newer drugs (fluoroquinolones and third-generation cephalosporins) was correlated with usage, which was generally higher in South Asia than Africa. In particular, fluoroquinolone resistance-associated mutations in gyrA were significantly associated with use of these drugs for treatment of diarrheic children. Notably resistance to older drugs such as trimethoprim, chloramphenicol and ampicillin, which are conferred by acquired AMR genes that were frequently clustered together in mobile genetic elements, were common in all locations despite differences in usage; this suggests that reversion to sensitivity is unlikely to occur even if these drugs are removed from circulation. This study provides much-needed insights into the frequencies of AMR in intestinal E. coli in community-based children in developing countries and to antimicrobial usage for diarrhea where the burden of infections is greatest.

microbiology↗