Open Access Highly Accessed Research article

Risk factors for the development of severe typhoid fever in Vietnam

Christopher M Parry12*, Corinne Thompson13, Ha Vinh4, Nguyen Tran Chinh4, Le Thi Phuong5, Vo Anh Ho5, Tran Tinh Hien14, John Wain16, Jeremy J Farrar13 and Stephen Baker137

Author Affiliations

1 Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 764 Vo Van Kiet, District 5, Ho Chi Minh City, Vietnam

2 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA, Liverpool, UK

3 Nuffield Department of Clinical Medicine, Centre for Tropical Medicine, Churchill Hospital, Oxford, UK

4 Hospital for Tropical Diseases, 764 Vo Van Kiet, District 5, Ho Chi Minh City, Vietnam

5 Dong Thap Provincial Hospital, Cao Lanh, Dong Thap Province, Vietnam

6 Department of Medical Microbiology, University of East Anglia, Norwich, UK

7 London School of Hygiene and Tropical Medicine, Keppel Street, WC1E 7HT, London, UK

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BMC Infectious Diseases 2014, 14:73  doi:10.1186/1471-2334-14-73

Published: 10 February 2014

Abstract

Background

Typhoid fever is a systemic infection caused by the bacterium Salmonella enterica serovar Typhi. Age, sex, prolonged duration of illness, and infection with an antimicrobial resistant organism have been proposed risk factors for the development of severe disease or fatality in typhoid fever.

Methods

We analysed clinical data from 581 patients consecutively admitted with culture confirmed typhoid fever to two hospitals in Vietnam during two periods in 1993–1995 and 1997–1999. These periods spanned a change in the antimicrobial resistance phenotypes of the infecting organisms i.e. fully susceptible to standard antimicrobials, resistance to chloramphenicol, ampicillin and trimethoprim-sulphamethoxazole (multidrug resistant, MDR), and intermediate susceptibility to ciprofloxacin (nalidixic acid resistant). Age, sex, duration of illness prior to admission, hospital location and the presence of MDR or intermediate ciprofloxacin susceptibility in the infecting organism were examined by logistic regression analysis to identify factors independently associated with severe typhoid at the time of hospital admission.

Results

The prevalence of severe typhoid was 15.5% (90/581) and included: gastrointestinal bleeding (43; 7.4%); hepatitis (29; 5.0%); encephalopathy (16; 2.8%); myocarditis (12; 2.1%); intestinal perforation (6; 1.0%); haemodynamic shock (5; 0.9%), and death (3; 0.5%). Severe disease was more common with increasing age, in those with a longer duration of illness and in patients infected with an organism exhibiting intermediate susceptibility to ciprofloxacin. Notably an MDR phenotype was not associated with severe disease. Severe disease was independently associated with infection with an organism with an intermediate susceptibility to ciprofloxacin (AOR 1.90; 95% CI 1.18-3.07; p = 0.009) and male sex (AOR 1.61 (1.00-2.57; p = 0.035).

Conclusions

In this group of patients hospitalised with typhoid fever infection with an organism with intermediate susceptibility to ciprofloxacin was independently associated with disease severity. During this period many patients were being treated with fluoroquinolones prior to hospital admission. Ciprofloxacin and ofloxacin should be used with caution in patients infected with S. Typhi that have intermediate susceptibility to ciprofloxacin.

Keywords:
Salmonella enterica serovar Typhi; Severe typhoid; Antimicrobial resistance; Multidrug resistance; Intermediate ciprofloxacin susceptibility