Trends in typhoid fever during the COVID-19 pandemic in Pakistan.

Pakistan has been experiencing an extensively drug-resistant (XDR) outbreak of typhoid for some years. We sought to evaluate how the COVID-19 pandemic impacted typhoid epidemiology in Pakistan, from the beginning of the pandemic in 2020 through the end of 2022, and the reduction of COVID-19 cases. We compared national public COVID-19 data with retrospectively obtained patient data of confirmed S. Typhi isolates between January 2019 and December 2022 from Shaukat Khanum Memorial Cancer Hospital and Research Centre and the hospital's extended network of laboratory collection centers across Pakistan. We observed that during the early onset of the COVID-19 pandemic and COVID-19 peaks, typhoid positivity generally decreased. This suggests that restrictions and non-pharmaceutical interventions that limited social interactions and promoted good sanitation and hygiene practices had a positive secondary effect on typhoid. This led to an overall yearly decrease in typhoid positivity between 2019 to 2021. However, the percentage of S. Typhi cases isolated that were ceftriaxone-resistant continued to increase, suggesting the continued dominance of XDR typhoid in Pakistan. In 2022, with the alleviation of pandemic restrictions, we observed increased typhoid positivity and COVID-19 and typhoid positivity started to follow similar trends. Given the continued presence of COVID-19 along with XDR typhoid in Pakistan, it will be imperative to use differential testing to ensure that the epidemiology of each reported is accurate, the spread of each it contained, and that antibiotics are not misused. The use of approved vaccinations will lessen the burden of both diseases.

Ching C ，Zaman MH ，Parveen A ，Sultan F ，Nizamuddin S ... -  《Journal of Infection in Developing Countries》

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

Nizamuddin S ，Ching C ，Kamal R ，Zaman MH ，Sultan F ... -  《-》

Emergence of an Extensively Drug-Resistant Salmonella enterica Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins.

Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel S Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant (XDR). Over 300 XDR typhoid cases have emerged in Sindh, Pakistan, since November 2016. Additionally, a single case of travel-associated XDR typhoid has recently been identified in the United Kingdom. Whole-genome sequencing of over 80 of the XDR isolates revealed remarkable genetic clonality and sequence conservation, identified a large number of resistance determinants, and showed that these isolates were of haplotype H58. The XDR S Typhi clone encodes a chromosomally located resistance region and harbors a plasmid encoding additional resistance elements, including the blaCTX-M-15 extended-spectrum β-lactamase, and carrying the qnrS fluoroquinolone resistance gene. This antibiotic resistance-associated IncY plasmid exhibited high sequence identity to plasmids found in other enteric bacteria isolated from widely distributed geographic locations. This study highlights three concerning problems: the receding antibiotic arsenal for typhoid treatment, the ability of S Typhi to transform from MDR to XDR in a single step by acquisition of a plasmid, and the ability of XDR clones to spread globally.IMPORTANCE Typhoid fever is a severe disease caused by the Gram-negative bacterium Salmonella enterica serovar Typhi. Antibiotic-resistant S Typhi strains have become increasingly common. Here, we report the first large-scale emergence and spread of a novel extensively drug-resistant (XDR) S Typhi clone in Sindh, Pakistan. The XDR S Typhi is resistant to the majority of drugs available for the treatment of typhoid fever. This study highlights the evolving threat of antibiotic resistance in S Typhi and the value of antibiotic susceptibility testing and whole-genome sequencing in understanding emerging infectious diseases. We genetically characterized the XDR S Typhi to investigate the phylogenetic relationship between these isolates and a global collection of S Typhi isolates and to identify multiple genes linked to antibiotic resistance. This S Typhi clone harbored a promiscuous antibiotic resistance plasmid previously identified in other enteric bacteria. The increasing antibiotic resistance in S Typhi observed here adds urgency to the need for typhoid prevention measures.

Klemm EJ ，Shakoor S ，Page AJ ，Qamar FN ，Judge K ，Saeed DK ，Wong VK ，Dallman TJ ，Nair S ，Baker S ，Shaheen G ，Qureshi S ，Yousafzai MT ，Saleem MK ，Hasan Z ，Dougan G ，Hasan R ... -  《mBio》

Extensively Drug-Resistant (XDR) Typhoid: Evolution, Prevention, and Its Management.

Typhoid fever is the result of a human host-restricted Salmonella enteric serotype typhi infection that causes enteric fever. Around 21 million people contract typhoid annually, with Pakistan's inhabitants at most risk amongst Asian countries where typhoid remains prevalent. Decades of indiscriminate antibiotic usage has driven the evolution of multidrug-resistant strains and more recently, extensively drug-resistant (XDR) strains of Salmonella enteric serotype typhi. Current reports of extensively drug-resistant typhoid fever outbreak in Pakistan are not only a major concern for Pakistan but also for health authorities worldwide: intercontinental transmission, spread, and replacement of native strains in neighboring countries and a major impediment to Pakistani health care management. The WHO records that there are 5274 cases of extensively drug-resistant (XDR) typhoid fever out of a total of 8188 total cases of typhoid fever reported in Pakistan. The last remaining feasible oral antibiotic that XDR typhoid remains susceptible to is azithromycin; this is a cause of major concern. Additionally, several cases of XDR typhoid fever have also been reported in patients travelling from Pakistan to the USA, UK, and Canada. This review article attempts to raise the issue of XDR typhoid with respect to its epidemiology, prevention, management, and future outlook and stresses a better understanding of antimicrobial stewardship and general surveillance of the disease. Although progress is being made to combat XDR typhoid locally, efficient, unified efforts on a national and international scale are required to contain the XDR outbreak before it is no longer manageable and leads us back to the preantibiotic era.

Akram J ，Khan AS ，Khan HA ，Gilani SA ，Akram SJ ，Ahmad FJ ，Mehboob R ... -  《-》

Whole-genome sequencing of extensively drug-resistant Salmonella enterica serovar Typhi clinical isolates from the Peshawar region of Pakistan.

Mumtaz MN ，Irfan M ，Siraj S ，Khan A ，Khan H ，Imran M ，Khan IA ，Khan A ... -  《-》