Predominance of multidrug-resistant Salmonella Typhi genotype 4.3.1 with low-level ciprofloxacin resistance in Zanzibar

PLoS Negl Trop Dis. 2024 Apr 17;18(4):e0012132. doi: 10.1371/journal.pntd.0012132. eCollection 2024 Apr.


Background: Typhoid fever is a common cause of febrile illness in low- and middle-income countries. While multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) has spread globally, fluoroquinolone resistance has mainly affected Asia.

Methods: Consecutively, 1038 blood cultures were obtained from patients of all age groups with fever and/or suspicion of serious systemic infection admitted at Mnazi Mmoja Hospital, Zanzibar in 2015-2016. S. Typhi were analyzed with antimicrobial susceptibility testing and with short read (61 strains) and long read (9 strains) whole genome sequencing, including three S. Typhi strains isolated in a pilot study 2012-2013.

Results: Sixty-three S. Typhi isolates (98%) were MDR carrying blaTEM-1B, sul1 and sul2, dfrA7 and catA1 genes. Low-level ciprofloxacin resistance was detected in 69% (43/62), with a single gyrase mutation gyrA-D87G in 41 strains, and a single gyrA-S83F mutation in the non-MDR strain. All isolates were susceptible to ceftriaxone and azithromycin. All MDR isolates belonged to genotype 4.3.1 lineage I (, with the antimicrobial resistance determinants located on a composite transposon integrated into the chromosome. Phylogenetically, the MDR subgroup with ciprofloxacin resistance clusters together with two external isolates.

Conclusions: We report a high rate of MDR and low-level ciprofloxacin resistant S. Typhi circulating in Zanzibar, belonging to genotype, which is widespread in Southeast Asia and African countries and associated with low-level ciprofloxacin resistance. Few therapeutic options are available for treatment of typhoid fever in the study setting. Surveillance of the prevalence, spread and antimicrobial susceptibility of S. Typhi can guide treatment and control efforts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Bacterial Agents* / pharmacology
  • Child
  • Child, Preschool
  • Ciprofloxacin* / pharmacology
  • Drug Resistance, Multiple, Bacterial* / genetics
  • Female
  • Genotype*
  • Humans
  • Infant
  • Male
  • Microbial Sensitivity Tests*
  • Middle Aged
  • Salmonella typhi* / classification
  • Salmonella typhi* / drug effects
  • Salmonella typhi* / genetics
  • Salmonella typhi* / isolation & purification
  • Tanzania / epidemiology
  • Typhoid Fever* / epidemiology
  • Typhoid Fever* / microbiology
  • Whole Genome Sequencing
  • Young Adult


  • Ciprofloxacin
  • Anti-Bacterial Agents

Grants and funding

The study received funding from the Norwegian National Centre on Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway. Vestre Viken Hospital Trust, Drammen, Norway supported the study including a salary to AO. Western Norway Regional Health Authority, University of Bergen, Norway supported AO by a PhD scholarship (Project Number 912277). CAMRIA - Combatting Anti-Microbial Resistance with Interdisciplinary Approaches, Centre for Antimicrobial Resistance in Western Norway, funded by Trond Mohn Foundation, supported the study (grant number TMS2020TMT11). SM has received a salary from STRESST - Antimicrobial Stewardship in Hospitals, Resistance Selection and Transfer in a One Health Context, University of Bergen, Norway (JPIAMR grant number NFR333432). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.