Bayesian modelling of antimicrobial resistance in enteric fever in understudied areas
Authors: Lia Bote, Mailis Maes
Journal: The Lancet Global Health (2024)

In The Lancet Global Health, Annie J Browne and colleagues1GRAM Typhoid CollaboratorsEstimating the subnational prevalence of antimicrobial resistant Salmonella enterica serovars Typhi and Paratyphi A infections in 75 endemic countries, 1990–2019: a modelling study.Lancet Glob Health. 2024; 12: e406-e418Google Scholar inferred the percentage of drug resistance and overall incidence of enteric fever in countries that are expected to be endemic for enteric fever. To do this, they performed a comprehensive modelling analysis of antimicrobial resistance (AMR) from publicly available phenotypic data of nearly 200 000 Salmonella enterica serovar Typhi (S Typhi) and S enterica serovar Paratyphi A (S Paratyphi A) isolates, collected between 1990 and 2019 in 45 countries. S Typhi and S Paratyphi, the two pathogens that cause enteric fever, were modelled to be responsible for 14·3 million incidences and caused 135 900 deaths in 2017.2Stanaway JD Reiner RC Blacker BF et al.The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Infect Dis. 2019; 19: 369-381Summary Full Text Full Text PDF PubMed Scopus (384) Google Scholar Enteric fever can be prevented by access to clean water, adequate sanitation, and basic hygiene implementations.3Kim C Goucher GR Tadesse BT Lee WJ Abbas K Kim JH Associations of water, sanitation, and hygiene with typhoid fever in case-control studies: a systematic review and meta-analysis.BMC Infect Dis. 2023; 23: 562Crossref Scopus (1) Google Scholar The most common antibiotic treatment options for enteric fever are ampicillin or amoxicillin, chloramphenicol, co-trimoxazole, fluoroquinolones, third-generation cephalosporins, or azithromycin. During the 1960s, a multidrug-resistant (MDR) plasmid carrying resistance to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole was detected in S Typhi. By the 1990s, MDR had established itself in a subclade of the now globally dispersed H58 lineage of S Typhi.4Dyson ZA Klemm EJ Palmer S Dougan G Antibiotic resistance and typhoid.Clin Infect Dis. 2019; 68: S165-S170Crossref PubMed Scopus (85) Google Scholar, 5Anderson ES The problem and implications of chloramphenicol resistance in the typhoid bacillus.J Hygiene. 1975; 74: 289-299Crossref Scopus (84) Google Scholar Because of the rise of MDR in S Typhi, ciprofloxacin became widely used as first-line treatment, which led to the accumulation of fluoroquinolone non-susceptibility (FQNS) in another subclade of the same lineage circulating in Nepal and India.4Dyson ZA Klemm EJ Palmer S Dougan G Antibiotic resistance and typhoid.Clin Infect Dis. 2019; 68: S165-S170Crossref PubMed Scopus (85) Google Scholar Finally, extremely drug-resistant S Typhi, defined as MDR, FQNS, and third-generation cephalosporin-resistant (3GCR), emerged in Pakistan in 2016.6Klemm EJ Shakoor S Page AJ et al.Emergence of an extensively drug-resistant Salmonella enterica serovar Typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third-generation cephalosporins.mBio. 2018; (published online Feb 20.)https://doi.org/10.1128/mBio.00105-18Crossref Scopus (400) Google Scholar In 2022, the first case of extremely drug-resistant S Typhi with concurrent resistance to azithromycin—thus fully resistant to all available oral treatments—was reported, altogether highlighting the major issue of AMR in S Typhi.7Nizamuddin S Khan EA Chattaway MA Godbole G Case of carbapenem-resistant Salmonella Typhi Infection, Pakistan, 2022.Emerg Infect Dis. 2023; 29: 2395-2397Crossref Scopus (1) Google Scholar Based on the Global Burden of Disease Study, S Typhi is expected to be endemic—with an incidence of 10 per 100 000—in the super-regions of South Asia; South East Asia, East Asia, and Oceania; sub-Saharan Africa; and North Africa and the Middle East (75 countries). S Paratyphi, according to the same criteria, was only classified as endemic in the super-regions of South Asia and South East Asia, East Asia, and Oceania (18 countries).8Vos T Lim SS Abbafati C et al.Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019.Lancet. 2020; 396: 1204-1222Summary Full Text Full Text PDF PubMed Scopus (6812) Google Scholar Nevertheless, not all these endemic low-income and middle-income countries have the capacity to perform culture-based confirmation or antimicrobial susceptibility testing, and thus incidences and AMR patterns at country level are not always known. Browne and colleagues utilised data from 601 sources and employed a two-stage Bayesian spatiotemporal modelling approach, which allowed for predictions of incidence and AMR prevalence in locations without data.1GRAM Typhoid CollaboratorsEstimating the subnational prevalence of antimicrobial resistant Salmonella enterica serovars Typhi and Paratyphi A infections in 75 endemic countries, 1990–2019: a modelling study.Lancet Glob Health. 2024; 12: e406-e418Google Scholar MDR S Typhi was predicted to have decreased in South Asia, South East Asia, East Asia, and Oceania, but increased in sub-Saharan Africa. In contrast, FQNS had increased in all regions, whereas 3GCR remained low in all countries except Pakistan. Overall levels of AMR were lower in S Paratyphi across space and time. These findings demonstrate the pressing problem of AMR in S Typhi and are consistent with previously observed trends of the spread and prevalence of AMR in S Typhi in a 13 000 isolate-based global genomic collection.9Carey ME Dyson ZA Ingle DJ et al.Global diversity and antimicrobial resistance of typhoid fever pathogens: insights from a meta-analysis of 13,000 Salmonella Typhi genomes.eLife. 2023; 12e85867 Crossref Google Scholar By inferring levels of overall incidence as well as MDR, FQNS, and 3GCR in areas without data, this study emphasises the importance of using and maximising publicly available data to fill in the gaps in public health surveillance. The hope is that these detailed spatial predictions can help countries prioritise the introduction of typhoid conjugate vaccines as a preventative measure. Ultimately, the study by Browne and colleagues illustrates that we have the ability to generate significant insights on spatiotemporal patterns of AMR in S Typhi and S Paratyphi, even in areas with limited laboratory resources, through modelling approaches. This highlights the crucial need for a continued global collaborative effort to make all culture-based confirmation and antimicrobial susceptibility testing of enteric fever publicly available. Using data from such continuous global surveillance to inform and improve models such as these will ultimately increase their accuracy and granularity, further benefiting areas with limited surveillance and resources. We declare no competing interests. Estimating the subnational prevalence of antimicrobial resistant Salmonella enterica serovars Typhi and Paratyphi A infections in 75 endemic countries, 1990–2019: a modelling studyThis 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. Full-Text PDF Open Access