Evaluation of a newly developed ELISA against Widal, TUBEX-TF and Typhidot for typhoid fever surveillance

Abstract

Introduction: Typhoid fever is endemic in many parts of the world and represents a major cause of acute febrile illness (AFI). Rapid and accurate laboratory methods for diagnosis of this disease are needed for both patient care and surveillance situations. Methodology: Serum samples were collected from AFI patients and used to evaluate the performance of a newly developed ELISA assay that uses a mixture of somatic and flagellar antigens to detect the total antibody response against Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) infection. The levels of Ig isotype response (IgG, IgM and IgA) were also evaluated, and results were compared to those of TUBEX-TF and Typhidot commercial kits. Results: Of 234 culture-confirmed typhoid patients, the total Ig ELISA diagnosed 93% compared to 71% using Widal test. This sensitivity level (93%) is higher than that observed for the individual Ig ELISAs (IgG 75%; IgM 79%; IgA 57%) and the commercial tests TUBEX-TF (75%), Typhidot IgM (63%) and Typhidot IgG (28%). An agreement of 78% was achieved between the total Ig ELISA and Widal test. The average specificity of the ELISA was 96%. Using ELISA, up to 200 samples can be tested per run with cost per test at US$0.20. Conclusions: The developed ELISA shows superior sensitivity and specificity, when compared to Widal, TUBEX-TF and Typhidot assays, is more cost effective and allows higher throughput. This method is highly recommended for active surveillance studies or outbreak investigations of typhoid fever.

Sensitivity and specificity of typhoid fever rapid antibody tests for laboratory diagnosis at two sub-Saharan African sites

“…Furthermore, blood culture sensitivity was optimized in our study because we used modern blood culture techniques. 28 Our findings on the Widal test and the newer typhoid rapid antibody tests are similar to those from studies conducted in Asia and Egypt; [8][9][10]25,29,30 none of the rapid tests performed nearly as well as blood culture for the diagnosis of typhoid fever. Some reports suggest that the Typhidot ® test may be more useful in Asia.…”

“…While the TUBEX ® test was the most sensitive and specific in the Philippines, 6 neither TUBEX ® nor Typhidot ® was both sensitive and specific in two evaluations undertaken in Viet Nam 7,8 and performance was poor in a trial conducted in a community clinic in Bangladesh 9 and in a study in Egypt in which it was compared with a new ELISA not yet commercially available. 10 Rapid typhoid tests have not been evaluated in subSaharan Africa, where the typhoid fever burden may be smaller than in Asia. [11][12][13] The World Health Organization (WHO) has issued no recommendations on the use of typhoid rapid antibody tests.…”

Molecular Diagnosis of Enteric Fever: Progress and Perspectives

“…Much effort has been put into improving on the classic Widal test over the last twenty years specifically in order to improve the speed and reliability of serological testing (Bhutta & Mansurali, 1999;House et al, 2001;Gasem et al, 2002;Hatta et al, 2002;Jesudason et al, 2002;Olsen et al, 2004;Tam et al, 2008;Fadeel et al, 2011). Several of these assays have subsequently become commerically available; Typhidot® (Malaysian Biodiagnostic Research SDN BHD, Malaysia) and TUBEX assays (IDL Bideh, Solletuna, Sweden) are discussed in further detail below.…”

Typhoid fever: a review

“…In some studies, it has shown that for total Ig estimation ELISA has superior sensitivity when compared to other tests. 64 Recently DNA probes and polymerase-chain-reaction (PCR) have been developed to detect S. enterica serotype typhi directly in the blood. 53,58 Urine antigen detection has 65-95% sensitivity.…”