title: Risk factors for the development of severe typhoid fever in Vietnam.
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.
authors: 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. cmparry@liverpool.ac.uk.
authors: Christopher M
authors: CM
authors: Parry
authors: Corinne
authors: C
authors: Thompson
authors: Ha
authors: H
authors: Vinh
authors: Nguyen Tran
authors: NT
authors: Chinh
authors: Le Thi
authors: le T
authors: Phuong
authors: Vo Anh
authors: VA
authors: Ho
authors: Tran Tinh
authors: TT
authors: Hien
authors: John
authors: J
authors: Wain
authors: Jeremy J
authors: JJ
authors: Farrar
authors: Stephen
authors: S
authors: Baker
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012307:Risk Factors; D012485:Salmonella typhi / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D012720:Severity of Illness Index; D014435:Typhoid Fever / Q000453:epidemiology / Q000382:microbiology*; D014744:Vietnam / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents