The clinical and microbiological characteristics of enteric fever in Cambodia, 2008-2015

PLoS Negl Trop Dis. 2017 Sep 20;11(9):e0005964. doi: 10.1371/journal.pntd.0005964. eCollection 2017 Sep.

Abstract

Background: Enteric fever remains a major public health problem in low resource settings and antibiotic resistance is increasing. In Asia, an increasing proportion of infections is caused by Salmonella enterica serovar Paratyphi A, which for a long time was assumed to cause a milder clinical syndrome compared to Salmonella enterica serovar Typhi.

Methodology: A retrospective chart review study was conducted of 254 unique cases of blood culture confirmed enteric fever who presented at a referral adult hospital in Phnom Penh, Cambodia between 2008 and 2015. Demographic, clinical and laboratory data were collected from clinical charts and antibiotic susceptibility testing was performed. Whole genome sequence analysis was performed on a subset of 121 isolates.

Results: One-hundred-and-ninety unique patients were diagnosed with Salmonella Paratyphi A and 64 with Salmonella Typhi. In the period 2008-2012, Salmonella Paratyphi A comprised 25.5% of 47 enteric fever cases compared to 86.0% of 207 cases during 2013-2015. Presenting symptoms were identical for both serovars but higher median leukocyte counts (6.8 x 109/L vs. 6.3 x 109/L; p = 0.035) and C-reactive protein (CRP) values (47.0 mg/L vs. 36 mg/L; p = 0.034) were observed for Salmonella Typhi infections. All but one of the Salmonella Typhi isolates belonged to haplotype H58 associated with multidrug resistance (MDR) (i.e. resistance to ampicillin, chloramphenicol and co-trimoxazole).;42.9% actually displayed MDR compared to none of the Salmonella Paratyphi A isolates. Decreased ciprofloxacin susceptibility (DCS) was observed in 96.9% (62/64) of Salmonella Typhi isolates versus 11.5% (21/183) of Salmonella Paratyphi A isolates (all but one from 2015). All isolates were susceptible to azithromycin and ceftriaxone.

Conclusions: In Phnom Penh, Cambodia, Salmonella Paratyphi A now causes the majority of enteric fever cases and decreased susceptibility against ciprofloxacin is increasing. Overall, Salmonella Typhi was significantly more associated with MDR and DCS compared to Salmonella Paratyphi A.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Cambodia / epidemiology
  • Drug Resistance, Bacterial
  • Female
  • Humans
  • Male
  • Paratyphoid Fever / epidemiology
  • Paratyphoid Fever / microbiology
  • Paratyphoid Fever / pathology
  • Retrospective Studies
  • Salmonella paratyphi A / classification
  • Salmonella paratyphi A / isolation & purification
  • Salmonella typhi / classification
  • Salmonella typhi / drug effects
  • Salmonella typhi / isolation & purification
  • Typhoid Fever / epidemiology
  • Typhoid Fever / microbiology*
  • Typhoid Fever / pathology*

Substances

  • Anti-Bacterial Agents

Grants and funding

The surveillance of bloodstream infections at the Sihanouk Hospital Center of HOPE is supported by the Belgian Directorate of Development Cooperation (DGD) (https://diplomatie.belgium.be/en/policy/development_cooperation/who_we_are/our_organisation/dgd) through project 2.08 of the Third Framework Agreement between the Belgian DGD (Ministry of Development Cooperation) and the Institute of Tropical Medicine (ITM). This study was further supported by the Strategic Network Laboratory Quality Management (LQM) project (http://www.labquality.be/) (Belgian Development Cooperation), the Institut Pasteur and the French government’s Investissement d’Avenir programme, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (http://www.agence-nationale-recherche.fr/?ProjetIA=10-LABX-0062) (grant number ANR-10-LABX-62-IBEID). LMFK is supported by the Flemish Ministry of Sciences (EWI, SOFI project IDIS) (http://www.ewi-vlaanderen.be/en) and received additional travel grants (grant numbers K2.060.16N and K2.065.17N) from the Fund for Scientific Research Flanders (F.W.O.-Vlaanderen, Belgium) (http://www.fwo.be/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.