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Abstract.Typhoid remains a major cause of morbidity and mortality in endemic countries. This review analyzed typhoid burden changes in Pakistan and its association with contextual factors. A retrospective cohort study on blood culture–positive typhoid and antibiotic resistance was conducted from three tertiary hospitals and contextual factor data obtained from primary household surveys. Salmonella Typhi/Paratyphi positivity rates were estimated and trend analysis was carried out using positive cases out of total number of blood cultures performed. Contextual factors’ associations were determined through bivariate correlation analysis, using STATA (SataCorp, College Station, TX). We report a total of 17,387 S. Typhi–positive and 8,286 S. Paratyphi A and B–positive specimens from 798,137 blood cultures performed. The results suggest an overall decline in typhoid incidence as S. Typhi positivity rates declined from 6.42% in 1992 to 1.32% in 2015 and S. Paratyphi (A and B) from 1.29% to 0.39%. Subgroup analysis suggests higher S. Typhi prevalence in adults older than 18 years, whereas S. Paratyphi is greater in children aged 5–18 years. The relative contribution of S. Paratyphi to overall confirmed cases increased from 16.8% in 1992 to 23% in 2015. The analysis suggests high burden of fluoroquinolone resistance and multidrug-resistant S. Typhi strains. Statistically significant associations of water, sanitation indicators, and literacy rates were observed with typhoid positivity. Despite some progress, typhoid remains endemic and a strong political will is required for targeted typhoid control strategies. A multipronged approach of improving water, sanitation and hygiene in combination with large-scale immunization in endemic settings of Pakistan could help reduce burden and prevent epidemics.

In S. pneumoniae from Pakistan, there has been a clear reduction in susceptibility to key antibiotics since 2002, but not to amoxicillin/clavulanic acid (amoxicillin) or cefuroxime. However, susceptibility in H. influenzae has remained stable. Local antibiotic susceptibility/resistance data are essential to support informed prescribing for CA-RTIs and other infections.

Pakistan is experiencing the first known outbreak of extensively drug-resistant (XDR) Salmonella enterica serotype Typhi (resistant to third-generation cephalosporins). The outbreak originated in Hyderabad in 2016 and spread throughout the Sindh Province. Whereas focus has remained on Sindh, the burden of XDR typhoid in Punjab, the most populous province, and the rest of the country is understudied. Using laboratory data from Shaukat Khanum Memorial Cancer Hospital and Research Centre in Lahore (Punjab Province) and its network of more than 100 collection centers across the country, we determined the frequency of blood culture–confirmed XDR typhoid cases from 2017 to 2019. We observed an increase in XDR typhoid cases in Punjab, with the percent of ceftriaxone resistance among Salmonella Typhi cases increasing from no cases in 2017, to 30% in 2018, and to 50% in 2019, with children bearing the largest burden. We also observed spread of XDR typhoid to the two other provinces in Pakistan. To assess prevailing knowledge and practices on XDR typhoid, we surveyed 321 frontline healthcare workers. Survey results suggested that inappropriate diagnostic tests and antibiotic practices may lead to underdiagnosis of XDR typhoid cases, and potentially drive resistance development and spread. Of those surveyed, only 43.6% had heard of XDR typhoid. Currently, serological tests are more routinely used over blood culture tests even though blood culture is imperative for a definitive diagnosis of typhoid fever. We recommend stronger liaisons between healthcare providers and diagnostic laboratories, and increased promotion of typhoid vaccination among healthcare workers and the general population.