Limitations of typhoid fever diagnostics and the need for prevention

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Author: Henk L Smits
Date: Mar. 2013
From: Expert Review of Molecular Diagnostics(Vol. 13, Issue 2)
Publisher: Expert Reviews Ltd.
Document Type: Report
Length: 2,298 words
Lexile Measure: 1660L

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Author(s): Henk L Smits 1



diagnostic accuracy; gold standard; point-of-care test; prevention; typhoid

During the last decades of the 20th century, a marked transition was seen in the incidence of typhoid fever in Papua New Guinea (PNG) from sporadic, isolated cases with epidemic outbreaks to the endemic presence of the disease throughout most of the country [1] . The increased number of typhoid cases was thought to be due to an increased population along with migration, introducing new infectious disease to the immunologically naive indigenous population and presenting new challenges to healthcare services. The clinical presentation of patients with typhoid fever is nonpathognomonic and laboratory testing is essential for confirmation [2] . With the increased exposure to the pathogen, a notable rise in seroprevalence of antibodies agglutinating in the Widal test, the test still most commonly used for the serodiagnosis of typhoid fever, was observed in samples collected from the general population of PNG [3] . As a consequence, the diagnostic accuracy of the Widal test dropped considerably, and in order to maintain a high specificity, it was judged necessary to increase the cutoff value by two dilution steps from 1:40 to 1:160. Typhoid fever is an acute disease, with symptoms and signs developing rapidly and patients' condition often deteriorating quickly early on in the disease at a stage when the immune response is still developing [4,5] . Since specific antibodies tend to develop slowly in typhoid fever, the use of a higher cutoff value in the Widal test inevitably leads to a fall in sensitivity and a much reduced diagnostic value during the first week of illness when medical intervention is essential and most effective [6] . In endemic areas, the interpretation of the Widal test result is particularly cumbersome, as titers tend to be low with a high percentage of the samples agglutinating at or around the cutoff value [7,8] . The limited diagnostic value of the Widal test has triggered the development of new serodiagnostics in various formats and using more defined antigens. The study by Siba et al. evaluated three rapid diagnostic tests on patients from PNG and used, in addition to blood culture, real-time PCR based on the detection of the Salmonella enterica serovar Typhi H1-d flagellin gene as a surrogate reference test [9] . However, the diagnostic characteristics and clinical utility of PCR is ill-defined and requires validation against the gold standard. Moreover, the diagnostic yield of PCR, similar to that of blood culture, is likely to drop with the onset of the immune response when the pathogen starts to disappear from the blood. Hence, with disease progression, the diagnostic sensitivity of PCR and blood culture, and antibody detection tests will show opposing trends. Therefore, using blood culture or PCR as a reference test in the evaluation of a serological assay requires stratification according to the duration of illness, and the analysis of paired samples is advised.

Summary of methods & results

In the study by Siba et al ., the diagnostic value of the Widal test (cutoff value [greater than or...

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Gale Document Number: GALE|A321864203