Travel-associated extensively drug-resistant typhoid fever: a case series to inform management in non-endemic regions

H Joshua Posen; Waison Wong; Daniel S Farrar; Aaron Campigotto; Tiffany Chan; Kevin R Barker; Stefan H F Hagmann; Edward T Ryan; Regina C LaRocque; Ashlee M Earl; Colin J Worby; Francesco Castelli; Victoria Pérez Fumadó; Philip N Britton; Michael Libman; Davidson H Hamer; Shaun K Morris

doi:10.1093/jtm/taac086

Travel-associated extensively drug-resistant typhoid fever: a case series to inform management in non-endemic regions

J Travel Med. 2023 Feb 18;30(1):taac086. doi: 10.1093/jtm/taac086.

Authors

H Joshua Posen¹, Waison Wong², Daniel S Farrar³, Aaron Campigotto⁴, Tiffany Chan⁵, Kevin R Barker^{6

7

8}, Stefan H F Hagmann^{9

10}, Edward T Ryan^{11

12

13}, Regina C LaRocque^{11

12}, Ashlee M Earl¹⁴, Colin J Worby¹⁴, Francesco Castelli^{15

16}, Victoria Pérez Fumadó¹⁷, Philip N Britton¹⁸, Michael Libman¹⁹, Davidson H Hamer^{20

21

22}, Shaun K Morris^{1

23

24}

Affiliations

¹ Department of Paediatrics, Division of Infectious Diseases, Hospital for Sick Children, Toronto, ON, Canada.
² Department of Paediatric Infectious Diseases and Immunology, Alder Hey Children's Hospital, Liverpool, UK.
³ Centre for Global Child Health, Hospital for Sick Children, Toronto, ON, Canada.
⁴ Department of Paediatric Laboratory Medicine, Division of Microbiology, Hospital for Sick Children, Toronto, ON, Canada.
⁵ Division of Infectious Diseases, Trillium Health Partners, Mississauga, ON, Canada.
⁶ Division of Microbiology, Department of Laboratory Medicine and Genetics, Trillium Health Partners, Mississauga, ON, Canada.
⁷ Institute for Better Health, Trillium Health Partners, Mississauga, ON, Canada.
⁸ Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁹ Division of Pediatric Infectious Diseases, Steven and Alexandra Cohen Children's Medical Center/Northwell Health, New Hyde Park, NY, USA.
¹⁰ Department of Pediatrics, Donald and Barbara Zucker School of Medicine/Hofstra Northwell, New Hempstead, NY, USA.
¹¹ Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
¹² Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹³ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁴ Infectious Disease and Microbiome Program, Broad Institute (Cambridge Massachusetts), MA, USA.
¹⁵ Department of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.
¹⁶ ASST Spedali Civili, Brescia, Italy.
¹⁷ Infectious Diseases Department, Hospital Universitari Sant Joan de Déu, Barcelona, Spain.
¹⁸ Department of Infectious Diseases and Microbiology, the Children's Hospital at Westmead, Westmead, New South Wales, Australia.
¹⁹ J.D. MacLean Centre for Tropical Diseases, McGill University, Montreal, Quebec.
²⁰ Department of Global Health, Boston University School of Public Health, Boston, MA, USA.
²¹ Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
²² Center for Emerging Infectious Diseases Research and Policy, Boston University, Boston, MA, USA.
²³ Department of Paediatrics, University of Toronto, Toronto, ON, Canada.
²⁴ Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto, ON, Canada.

PMID: 35904457
DOI: 10.1093/jtm/taac086

Abstract

Background: Extensively drug-resistant (XDR) typhoid fever is a threat to travelers to Pakistan. We describe a multicontinental case series of travel-acquired XDR typhoid fever to demonstrate the global spread of the problem and encourage preventive interventions as well as appropriate empiric antimicrobial use.

Methods: Cases were extracted from the GeoSentinel database, microbiologic laboratory records of two large hospitals in Toronto, Canada, and by invitation to TropNet sites. All isolates were confirmed XDR Salmonella enterica serovar Typhi (Salmonella typhi), with resistance to ampicillin, ceftriaxone, ciprofloxacin and trimethoprim-sulfamethoxazole.

Results: Seventeen cases were identified in Canada (10), USA (2), Spain (2), Italy (1), Australia (1) and Norway (1). Patients under 18 years represented 71% (12/17) of cases, and all patients travelled to Pakistan to visit friends or relatives. Only one patient is known to have been vaccinated. Predominant symptoms were fever, abdominal pain, vomiting and diarrhoea. Antimicrobial therapy was started on Day 1 of presentation in 75% (12/16) of patients, and transition to a carbapenem or azithromycin occurred a median of 2 days after blood culture was drawn. Antimicrobial susceptibilities were consistent with the XDR S. typhi phenotype, and whole genome sequencing on three isolates confirmed their belonging to the XDR variant of the H58 clade.

Conclusions: XDR typhoid fever is a particular risk for travelers to Pakistan, and empiric use of a carbapenem or azithromycin should be considered. Pre-travel typhoid vaccination and counseling are necessary and urgent interventions, especially for visiting friends and relatives travelers. Ongoing sentinel surveillance of XDR typhoid fever is needed to understand changing epidemiology.

Keywords: Pakistan; Typhoid fever; antimicrobial resistance; returned traveler; travel-acquired infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents
Anti-Infective Agents*
Azithromycin
Carbapenems
Humans
Pakistan / epidemiology
Salmonella typhi
Travel
Typhoid Fever* / epidemiology

Substances

Azithromycin
Anti-Bacterial Agents
Anti-Infective Agents
Carbapenems

Abstract

Publication types

MeSH terms

Substances

Grants and funding