Data_Sheet_1_Prevalence, Risk Factors, and Genetic Characterization of Extended-Spectrum Beta-Lactamase Escherichia coli Isolated From Healthy Pregnant Women in Madagascar.PDF

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.

抗菌耐药性是全球范围内的重大公共卫生问题，影响人类、动物和环境。然而，尤其是在发展中国家，相关数据匮乏。因此，世界卫生组织开发了一项名为“Tricycle”的一体化健康监测项目，专注于人类、动物和环境中的ESBL产生性大肠杆菌的流行情况。在此，我们展示了马达加斯加Tricycle项目人类社区部分的首次研究结果。从2018年7月到2019年4月，对来自安塔那那利佛、马哈贾加、安巴托纳扎卡和塔马塔夫的492名孕妇的直肠拭子进行了ESBL-E. coli携带情况的检测。调查了人口统计学、社会学和环境风险因素，并对大肠杆菌分离株进行了特征描述（抗生素敏感性、耐药性和致病基因、质粒和基因组多样性）。孕妇中ESBL-E. coli的携带流行率为34%，从12%（塔马塔夫）到65%（安巴托纳扎卡）不等。与ESBL-E. coli携带相关的最主要风险因素是雨季（OR = 2.9，95% CI 1.3–5.6，p = 0.009）。对144名参与者中的168个分离株进行了全基因组测序。blaCTX–M–15是最常见的ESBL基因（86%）。一个分离株对碳青霉烯类抗生素具有耐药性，并携带blaNDM–5基因。大多数分离株属于与共生相关的系统发育组A、B1和C（90%），以及与肠外致病性相关的系统发育组B2、D和F（10%）。多位点序列分型显示67种不同的序列型，聚集在17个克隆复合体（STc）中，其中最常见的是STc10/系统发育组A（35%），其次是新兴的STc155/系统发育组B1（7%）、STc38/系统发育组D（4%）和STc131/系统发育组B2（3%）。尽管观察到了广泛的克隆多样性，但SNP分析揭示了多个遗传上紧密相关的分离株（n = 34/168），这表明存在人传人的传播。IncY质粒的流行率异常（23%），所有携带blaCTX–M–15。其中大多数（85%）显示出高度同源性（≥85%），这表明IncY ESBL质粒在马达加斯加的传播。这项大规模研究揭示了马达加斯加四个城市孕妇中ESBL-E. coli的高流行率，与温暖和降雨有关。它展示了全国范围内大肠杆菌的广泛多样性，以及特定克隆的传播和质粒的扩散。这突显了在该国控制抗生素耐药性的公共卫生干预的紧迫需求。