Abstract
ObjectiveTo determine the diagnostic accuracy of three rapid diagnostic tests (RDTs) for typhoid fever in febrile hospitalised patients in Bangladesh.MethodsFebrile adults and children admitted to Chittagong Medical College Hospital, Bangladesh, were investigated with Bact/Alert® blood cultures and real‐time PCR to detect Salmonella enterica Typhi and Paratyphi A and assays for Rickettsia, leptospirosis and dengue fever. Acute serum samples were examined with the LifeAssay (LA) Test‐it™ Typhoid IgM lateral flow assay detecting IgM antibodies against S. Typhi O antigen, CTKBiotech Onsite Typhoid IgG/IgM Combo Rapid‐test cassette lateral flow assay detecting IgG and IgM antibodies against S. Typhi O and H antigens and SD Bioline line assay for IgG and IgM antibodies against S. Typhi proteins.ResultsIn 300 malaria smear‐negative febrile patients [median (IQR) age of 13.5 (5–31) years], 34 (11.3%) had confirmed typhoid fever: 19 positive by blood culture for S. Typhi (three blood PCR positive) and 15 blood culture negative but PCR positive for S. Typhi in blood. The respective sensitivity and specificity of the three RDTs in patients using a composite reference standard of blood culture and/or PCR‐confirmed typhoid fever were 59% and 61% for LifeAssay, 59% and 74% for the CTK IgM and/or IgG, and 24% and 96% for the SD Bioline RDT IgM and/or IgG. The LifeAssay RDT had a sensitivity of 63% and a specificity of 91% when modified with a positive cut‐off of ≥2+ and analysed using a Bayesian latent class model.ConclusionsThese typhoid RDTs demonstrated moderate diagnostic accuracies, and better tests are needed.
Highlights
Typhoid fever is a common infection in adults and children in Bangladesh [1,2,3]
Blood culture sensitivity is limited by low number of bacteria circulating in the blood, small volumes of blood taken for culture and prior antimicrobial therapy [7]
In the light of this, the LifeAssay rapid diagnostic tests (RDTs) results were re-analysed with a threshold of ≥2+ rather than ≥1+ to indicate a positive result and the sensitivity fell from 59% to 41% but the specificity rose from 61% to 87%
Summary
Typhoid (enteric) fever is a common infection in adults and children in Bangladesh [1,2,3]. Antimicrobial resistance to standard treatments for Salmonella enterica serovars Typhi and Paratyphi A infections is widespread. R. Maude et al Rapid diagnostic tests for typhoid fever volume 20 no 10 pp 1376–1384 october 2015. A diagnosis of typhoid fever is rarely confirmed as diagnostic tests are unavailable or have limited diagnostic accuracy. Blood culture sensitivity is limited by low number of bacteria circulating in the blood, small volumes of blood taken for culture and prior antimicrobial therapy [7]. Bone marrow culture is more sensitive than blood culture, because of the higher number of bacteria present, and can remain positive several days after effective antimicrobial treatment has started, yet is rarely used except in a research context [8, 9]. The Widal test is still used but as it is based on cross-reactive antigens, it lacks sensitivity and specificity [11, 12]
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