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.

Highlights

  • Antimicrobial resistance (AMR) has become a tremendous global public health issue, which affects humans, animals and the environment

  • Rectal swabs were collected at the last prenatal consultation in three maternity wards in the capital city Antananarivo [Joseph Raseta Befelatanana Hospital (JRB) – July–August 2018, MèreEnfant Tsaralalana Hospital (TSA) – July–October 2018, and Joseph Ravoahangy Andrianavalona Hospital (JRA) – March– April 2019] as well as three in provincial cities [Mahajanga Androva Hospital (MAH) – September–November 2018], Toamasina [Morafeno Hospital (TOA) – August–November 2018] and Ambatondrazaka [Alaotra Mangoro Hospital (AMB)

  • To analyze more precisely extended-spectrum beta-lactamase (ESBL)-E. coli dissemination we focused on isolates differing by less than 10 SNPs, a cut-off used in the literature to define closely related isolates (Schürch et al, 2018)

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Summary

Introduction

Antimicrobial resistance (AMR) has become a tremendous global public health issue, which affects humans, animals and the environment. A meta-analysis conducted in 2016 estimated that 14% of healthy individuals worldwide were carriers of ESBL-E (Karanika et al, 2016). An important cornerstone in the control of AMR is the implementation and monitoring of AMR surveillance indicators [World Health Organization [WHO], 2015]. In this context, the World Health Organization (WHO) proposed a surveillance protocol called Tricycle aiming to provide a simplified, integrated and trans-sectoral surveillance system. The proposed surveillance focuses on a single key indicator, the prevalence of ESBLEscherichia coli, in the three major settings that are the human (community carriage and hospital infection), the food-chain (poultry) and the environment (water). For the human component of the Tricycle protocol, the population targeted as representative of the community was healthy pregnant women approaching or at delivery

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