Clinical and Epidemiological Features of Typhoid Fever in Pemba, Zanzibar: Assessment of the Performance of the WHO Case Definitions

Kamala Thriemer,Mohammad S Jiddawi,Na Yoon Chang,R Leon Ochiai,Jaqueline L Deen,Said M Ali,John D Clemens,Clara Jana-Lui Busch,Lorenz Von Seidlein,Mohammad Ali,Gi Deok Pak,Ramadhan Hashim,Shanette Nixon,Thomas F Wierzba ,Anne B Morrissey ,Wolfgang H Schmied ,Benedikt Ley ,Mahesh Puri ,S Shaali

doi:10.1371/journal.pone.0051823

Abstract

BackgroundThe gold standard for diagnosis of typhoid fever is blood culture (BC). Because blood culture is often not available in impoverished settings it would be helpful to have alternative diagnostic approaches. We therefore investigated the usefulness of clinical signs, WHO case definition and Widal test for the diagnosis of typhoid fever.Methodology/Principal FindingsParticipants with a body temperature ≥37.5°C or a history of fever were enrolled over 17 to 22 months in three hospitals on Pemba Island, Tanzania. Clinical signs and symptoms of participants upon presentation as well as blood and serum for BC and Widal testing were collected. Clinical signs and symptoms of typhoid fever cases were compared to other cases of invasive bacterial diseases and BC negative participants. The relationship of typhoid fever cases with rainfall, temperature, and religious festivals was explored. The performance of the WHO case definitions for suspected and probable typhoid fever and a local cut off titre for the Widal test was assessed. 79 of 2209 participants had invasive bacterial disease. 46 isolates were identified as typhoid fever. Apart from a longer duration of fever prior to admission clinical signs and symptoms were not significantly different among patients with typhoid fever than from other febrile patients. We did not detect any significant seasonal patterns nor correlation with rainfall or festivals. The sensitivity and specificity of the WHO case definition for suspected and probable typhoid fever were 82.6% and 41.3% and 36.3 and 99.7% respectively. Sensitivity and specificity of the Widal test was 47.8% and 99.4 both forfor O-agglutinin and H- agglutinin at a cut-off titre of 1∶80.Conclusions/SignificanceTyphoid fever prevalence rates on Pemba are high and its clinical signs and symptoms are non-specific. The sensitivity of the Widal test is low and the WHO case definition performed better than the Widal test.

Highlights

Diagnosing typhoid fever among the many causes of fever in sub-Saharan Africa is a huge challenge [1]
We screened a total of 142,767 patients for eligibility and 2209 (1.5%) patients were enrolled into the study
Two thirds (n = 30; 65%) of the typhoid fever patients were treated as outpatients and the remaining 16 typhoid fever cases were admitted

Summary

Introduction

Diagnosing typhoid fever among the many causes of fever in sub-Saharan Africa is a huge challenge [1]. The current gold standard for diagnosis of typhoid fever is blood culture. In the light of limited laboratory facilities in many developing countries, the diagnosis of typhoid fever remains a challenge. Specific clinical signs [3,4,5] or cheap and accurate point of care tests have remained elusive [2,6,7] and clinical algorithms are controversial because of their limited generalizability [8]. In addition to laboratory-confirmed typhoid fever the World Health Organization provides case definitions for suspected and probable typhoid fever for use during surveillance [9]. The gold standard for diagnosis of typhoid fever is blood culture (BC). We investigated the usefulness of clinical signs, WHO case definition and Widal test for the diagnosis of typhoid fever

Methods

Results

Discussion

Conclusion