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Background Clinicians have limited therapeutic options for enteric as a result of increasing antimicrobial resistance, and therefore typhoid vaccination is recommended as a preventive measure. As a part of the Surveillance for Enteric Fever in Asia Project (SEAP), we investigated the extent measured the burden of antimicrobial resistance (AMR) among confirmed enteric fever cases in Bangladesh, Nepal, and Pakistan. Methods From September 2016–September 2019, SEAP recruited study participants of all age groups from its outpatient, inpatient, hospital laboratory, laboratory network, and surgical sites who had a diagnosis of febrile illness that was either suspected or blood culture confirmed for enteric fever. Antimicrobial resistance of isolates was determined by disc diffusion using Clinical and Laboratory Standard Institute cut-off points. We reported the frequency of multidrug resistance (MDR)(resistance to ampicillin, cotrimoxazole, and chloramphenicol), extensive drug resistance (XDR) (MDR plus non-susceptible to fluoroquinolone and any 3rd generation cephalosporins), and fluoroquinolone (FQ) and azithromycin non-susceptibility. Results We enrolled 8,705 blood culture confirmed enteric fever cases: 4,873 (56%) from Bangladesh, 1,602 (18%) from Nepal and 2,230 (26%) from Pakistan. Of these, 7,591 (87%) were Salmonella Typhi and 1114 (13%) were S. Paratyphi. MDR S. Typhi was identified in 17% (701/4065) of isolates in Bangladesh, and 1% (19/1342) in Nepal. In Pakistan, 16 % (331/2084) of S. Typhi isolates were MDR, and 64% (1319/2074) were XDR. FQ nonsusceptibility among S. Typhi isolates was 98% in Bangladesh, 87% in Nepal, and 95% in Pakistan. Azithromycin non-susceptibility was detected in 77 (2%) in Bangladesh, 9 (.67%) in Nepal and 9 (.59%) isolates in Pakistan. In Pakistan, three (2%) S. Paratyphi isolates were MDR; no MDR S. Paratyphi was reported from Bangladesh or Nepal. Conclusions Although AMR against S. Paratyphi was low across the three countries, there was widespread drug resistance among S. Typhi, including FQ non-susceptibility and the emergence of XDR S. Typhi in Pakistan, limiting treatment options. As typhoid conjugate vaccine (TCV) is rolled out, surveillance should continue to monitor changes in AMR to inform policies and to monitor drug resistance in S. Paratyphi, for which there is no vaccine.

Building on previous multicountry surveillance studies of typhoid and others salmonelloses such as the Diseases of the Most Impoverished program and the Typhoid Surveillance in Africa Project, several ongoing blood culture surveillance studies are generating important data about incidence, severity, transmission, and clinical features of invasive Salmonella infections in sub-Saharan Africa and South Asia. These studies are also characterizing drug resistance patterns in their respective study sites. Each study answers a different set of research questions and employs slightly different methodologies, and the geographies under surveillance differ in size, population density, physician practices, access to healthcare facilities, and access to microbiologically safe water and improved sanitation. These differences in part reflect the heterogeneity of the epidemiology of invasive salmonellosis globally, and thus enable generation of data that are useful to policymakers in decision-making for the introduction of typhoid conjugate vaccines (TCVs). Moreover, each study is evaluating the large-scale deployment of TCVs, and may ultimately be used to assess post-introduction vaccine impact. The data generated by these studies will also be used to refine global disease burden estimates. It is important to ensure that lessons learned from these studies not only inform vaccination policy, but also are incorporated into sustainable, low-cost, integrated vaccine-preventable disease surveillance systems.