Continued Outbreak of Ceftriaxone-Resistant Salmonella enterica Serotype Typhi across Pakistan and Assessment of Knowledge and Practices among Healthcare Workers

Abstract

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.

Figure 1.

Distribution of Shaukat Khanum Memorial Cancer Hospital and Research Centre collection centers across Pakistan. The more collection centers within a city, the bigger the area of the circle. The four provinces (Sindh, Punjab, Balochistan, and Khyber Pakhtunkhwa [KPK]) and major cities are labeled. This figure appears in color at www.ajtmh.org.

Figure 2.

Positivity rates for Salmonella Typhi and Salmonella Paratyphi A from Shaukat Khanum Memorial Cancer Hospital and Research Centre, calculated as % of total number of blood cultures performed each year that were positive for S. Typhi or S. Paratyphi A. This figure appears in color at www.ajtmh.org.

Figure 3.

(A) % of all Salmonella Typhi isolates from blood culture samples that were XDR and (B) % of all S. Typhi isolates from blood culture samples that were from Punjab from 2017 to 2019 for Shaukat Khanum Memorial Cancer Hospital and Research Centre. For (B), there were no detected cases of XDR typhoid in 2017. XDR = extensively drug-resistant.

Figure 4.

(A) % resistant to ampicillin, chloramphenicol, co-trimoxazole, and ciprofloxacin (intermediate or resistant) of S. Typhi isolated from blood culture samples in 2017, 2018, and 2019, and (B) age distribution of all extensively drug-resistant (XDR) S. Typhi cases isolated in 2019 from Shaukat Khanum Memorial Cancer Hospital and Research Centre from Punjab (n = 682).