Prevalence, Risk Factors, and Genetic Characterization of Extended-Spectrum Beta-Lactamase Escherichia coli Isolated From Healthy Pregnant Women in Madagascar

Abstract

Antimicrobial resistance is a major public health concern worldwide affecting humans, animals and the environment. However, data is lacking especially in developing countries. Thus, the World Health Organization developed a One-Health surveillance project called Tricycle focusing on the prevalence of ESBL-producing Escherichia coli in humans, animals, and the environment. Here we present the first results of the human community component of Tricycle in Madagascar. From July 2018 to April 2019, rectal swabs from 492 pregnant women from Antananarivo, Mahajanga, Ambatondrazaka, and Toamasina were tested for ESBL-E. coli carriage. Demographic, sociological and environmental risk factors were investigated, and E. coli isolates were characterized (antibiotic susceptibility, resistance and virulence genes, plasmids, and genomic diversity). ESBL-E. coli prevalence carriage in pregnant women was 34% varying from 12% (Toamasina) to 65% (Ambatondrazaka). The main risk factor associated with ESBL-E. coli carriage was the rainy season (OR = 2.9, 95% CI 1.3–5.6, p = 0.009). Whole genome sequencing was performed on 168 isolates from 144 participants. blaCTX–M–15 was the most frequent ESBL gene (86%). One isolate was resistant to carbapenems and carried the blaNDM–5 gene. Most isolates belonged to commensalism associated phylogenetic groups A, B1, and C (90%) and marginally to extra-intestinal virulence associated phylogenetic groups B2, D and F (10%). Multi locus sequence typing showed 67 different sequence types gathered in 17 clonal complexes (STc), the most frequent being STc10/phylogroup A (35%), followed distantly by the emerging STc155/phylogroup B1 (7%), STc38/phylogroup D (4%) and STc131/phylogroup B2 (3%). While a wide diversity of clones has been observed, SNP analysis revealed several genetically close isolates (n = 34/168) which suggests human-to-human transmissions. IncY plasmids were found with an unusual prevalence (23%), all carrying a blaCTX–M–15. Most of them (85%) showed substantial homology (≥85%) suggesting a dissemination of IncY ESBL plasmids in Madagascar. This large-scale study reveals a high prevalence of ESBL-E. coli among pregnant women in four cities in Madagascar associated with warmth and rainfall. It shows the great diversity of E. coli disseminating throughout the country but also transmission of specific clones and spread of plasmids. This highlights the urgent need of public-health interventions to control antibiotic resistance in the country.

Tricycle surveillance in Antananarivo, Madagascar: circulation of both extended-spectrum beta-lactamase producingEscherichia colistrains and plasmids among humans, chickens and the environment

“…We have already reported a correlation between ESBL- E. coli prevalence carriage in humans and the wet season in a previous study in Madagascar, as well as other studies. 7,14,15 In contrast, we did not find any publications reporting a positive correlation between seasonality and ESBL- E. coli carriage in farm animals. The rainy period is well known for favouring faecal-oral transmission of enteric bacteria.…”

“…3 Human isolates are part of a larger collection of ESBL- E. coli strains from Malagasy pregnant women, described previously. 7 In brief, healthy pregnant women were enrolled from July 2018 to April 2019, after having provided written informed consent. Rectal swabs were collected in three maternity wards in Antananarivo (Joseph Raseta Befelatanana hospital [JRB], Mère-Enfant Tsaralalana hospital [TSA], and Joseph Ravoahangy Andrianavalona hospital [JRA]) and sent to each hospital laboratory.…”

Recurrent bacteremia with a hypermucoviscous Escherichia coli isolated from a patient with perihilar cholangiocarcinoma: insights from a comprehensive genome-based analysis

“…E. coli of phylogenetic group C have been described as of commensal bacteria in humans and birds, but have been also reported in the clinical context [ 45 , 46 ]. Serotype O8 has been commonly identified in clinical E. coli , but also in strains isolated from animals and sewage.…”

Faecal carriage of ESBL-producingEscherichia coliin a remote region of Niger

“…The pronounced diversity among A strains and the low prevalence of B2 strains supports the hypothesis that the strains described here are almost individual-specific, and aligns with the expected composition of commensal E. coli strains from humans living in developing countries. Along the same line, a recent study performed in healthy pregnant women in Madagascar showed a high prevalence of ESBL- E. coli (34%), composed mostly of isolates belonging to various phylogroup A clones (72%)[33].…”

“…This rate increases to 8.3% and 14.6%, respectively, in clinical isolates recovered from hospitals in Zambia [36] and China [37]. In the study from Madagascar cited above [33], the bla CTX-M gene was located on the chromosome in 31% of strains. The highest incidence of chromosomal bla CTX-M gene described so far was observed in Japan, where bla CTX-M-14 was found on the chromosome in 45.9% of cases, and in 16.2% both on chromosome and plasmid in community commensal strains [38].…”