背景:肠热,由肠沙门氏菌伤寒和伤寒A引起的全身性感染,仍然是低收入和中等收入国家发病率和死亡率的主要原因。通过提供干净的水和适当的卫生设施可以预防肠道热,并且可以用抗生素成功治疗。然而,高水平的抗菌素耐药性(AMR)损害了治疗的有效性。我们提供了75个流行国家中AMRS-Typhi和S-ParatyphiA的患病率的估计,包括30个没有数据的地点。
方法:我们使用贝叶斯时空建模框架来估计多药耐药(MDR)的百分比,氟喹诺酮非敏感性(FQNS),1990年至2019年,75个流行国家的1403个行政一级地区的伤寒S和副伤寒A感染的第三代头孢菌素耐药性。我们纳入了一个全面的系统评价的数据,公共卫生监测网络,以及对肠道热的大型多国研究。该国对AMR的患病率和AMR感染数量进行了估计(基于全球疾病负担研究的肠道热发病率估计),超级区域,以及每年研究的总流行区水平。
结果:我们整理了来自601个来源的数据,包括184225株伤寒沙门氏菌和副伤寒沙门氏菌,覆盖45个国家超过30年。我们发现南亚和东南亚的MDRSTyphi有所下降,而在撒哈拉以南非洲,总体患病率从1990年的6·0%(95%不确定区间4·3-8·0)上升至2019年的72·7%(67·7-77·3).从1990年的低水平开始,FQNS伤寒的患病率迅速增加,2019年南亚达到95·2%(91·4-97·7)。这相当于2019年流行国家的2·5百万(1·5-3·8)MDR伤寒S感染和7·4百万(4·7-11·3)FQNS伤寒S感染。在研究期间,在整个流行区,第三代头孢菌素耐药伤寒的患病率仍然很低,除巴基斯坦外,2019年伤寒S的第三代头孢菌素耐药率达到61·0%(58·0-63·8)。对于SParatyphiA,我们估计,在所有流行国家中,MDR和第三代头孢菌素耐药性的患病率较低,但是FQNS的急剧增加,2019年达到95·0%(93·7-96·1;3·5万[2·2-5·6]感染)。
结论:本研究对MDR的患病率进行了全面而详细的分析,FQNS,流行国家伤寒和副伤寒感染的第三代头孢菌素耐药性,跨越过去30年。我们的分析强调了这种可预防感染中AMR水平的提高,并作为指导迫切需要的公共卫生干预措施的资源。比如改善水,卫生,以及卫生和伤寒疫苗接种运动。
背景:弗莱明基金,英国卫生和社会关怀部;惠康信托基金;以及比尔和梅林达·盖茨基金会。
BACKGROUND: Enteric fever, a systemic infection caused by Salmonella enterica serovars Typhi and Paratyphi A, remains a major cause of morbidity and mortality in low-income and middle-income countries. Enteric fever is preventable through the provision of clean water and adequate sanitation and can be successfully treated with antibiotics. However, high levels of antimicrobial resistance (AMR) compromise the effectiveness of treatment. We provide estimates of the prevalence of AMR S Typhi and S Paratyphi A in 75 endemic countries, including 30 locations without data.
METHODS: We used a Bayesian spatiotemporal modelling framework to estimate the percentage of multidrug resistance (MDR), fluoroquinolone non-susceptibility (FQNS), and third-generation cephalosporin resistance in S Typhi and S Paratyphi A infections for 1403 administrative level one districts in 75 endemic countries from 1990 to 2019. We incorporated data from a comprehensive systematic review, public health surveillance networks, and large multicountry studies on enteric fever. Estimates of the prevalence of AMR and the number of AMR infections (based on enteric fever incidence estimates by the Global Burden of Diseases study) were produced at the country, super-region, and total endemic area level for each year of the study.
RESULTS: We collated data from 601 sources, comprising 184 225 isolates of S Typhi and S Paratyphi A, covering 45 countries over 30 years. We identified a decline of MDR S Typhi in south Asia and southeast Asia, whereas in sub-Saharan Africa, the overall prevalence increased from 6·0% (95% uncertainty interval 4·3-8·0) in 1990 to 72·7% (67·7-77·3) in 2019. Starting from low levels in 1990, the prevalence of FQNS S Typhi increased rapidly, reaching 95·2% (91·4-97·7) in south Asia in 2019. This corresponded to 2·5 million (1·5-3·8) MDR S Typhi infections and 7·4 million (4·7-11·3) FQNS S Typhi infections in endemic countries in 2019. The prevalence of third-generation cephalosporin-resistant S Typhi remained low across the whole endemic area over the study period, except for Pakistan where prevalence of third-generation cephalosporin resistance in S Typhi reached 61·0% (58·0-63·8) in 2019. For S Paratyphi A, we estimated low prevalence of MDR and third-generation cephalosporin resistance in all endemic countries, but a drastic increase of FQNS, which reached 95·0% (93·7-96·1; 3·5 million [2·2-5·6] infections) in 2019.
CONCLUSIONS: This study provides a comprehensive and detailed analysis of the prevalence of MDR, FQNS, and third-generation cephalosporin resistance in S Typhi and S Paratyphi A infections in endemic countries, spanning the last 30 years. Our analysis highlights the increasing levels of AMR in this preventable infection and serves as a resource to guide urgently needed public health interventions, such as improvements in water, sanitation, and hygiene and typhoid fever vaccination campaigns.
BACKGROUND: Fleming Fund, UK Department of Health and Social Care; Wellcome Trust; and Bill and Melinda Gates Foundation.