Background. The diagnosis of typhoid fever based on the Widal slide agglutination test remains a major hurdle in developing countries due to varied perceptions of the value of the Widal test in determining clinical decision-making. We undertook a study to evaluate the diagnostic performance of the Widal test and the Typhidot immunoassay in patients suspected of having typhoid fever in the Menoua division, West Region of Cameroon. Methods. Blood and stool samples were collected from 558 consenting febrile patients on the basis of suspicion of typhoid fever. These patients attended three district health services of the Menoua division between April 2018 and September 2019. These patients had clinical symptoms suggestive of typhoid fever as determined by their consultant. Serum was used for the Widal slide agglutination test and for the Typhidot rapid immunoassay test based on manufacturer’s guidelines. A composite reference of fever plus positive coproculture for Salmonella typhi and Salmonella paratyphi was used as the reference. The sensitivity, specificity, and predictive values of the positive and negative tests were calculated as well as Cohen’s kappa for agreement between the two tests. Results. Of 558 patients, 12.90% tested positive for the reference method, 57.17% tested positive for the Widal slide agglutination test, while 15.59% were positive for Typhidot-IgM. The overall sensitivity, specificity, and predictive values of the positive and negative tests were 80.56%, 94.03%, 66.6%, and 97.03% for Typhidot-IgM and 94.44%, 48.35%, 21.32%, and 98.33% for the Widal slide agglutination test, respectively. Cohen’s kappa estimates were 0.1660 (0.121–0.211) and 0.386 (0.312–0.460) for the Widal test and Typhidot immunoassay for 53.6% and 76.16% agreements of all observations, respectively. Conclusion. The Widal test was found to have a lower predictive value for the diagnosis of typhoid fever in our setting. However, the Typhidot test, although better, was not ideal. Diagnosis of typhoid fever should therefore rely on adequate clinical suspicion and a positive Typhidot test to improve the clinical management of typhoid fever in our setting.
Enteric fever caused by Salmonella typhi and Salmonella paratyphi remains a major burden in developing countries due to varied perceptions of the value of the Widal test in determining clinical decision-making. The burden of typhoid fever, worldwide, shows that it causes 16.6 million new infections and about 600,000 deaths each year . However, the incidence of typhoid fever has dropped to about 10/100,000 population/year in developed countries due to improved living standard, proper hygiene and sanitation, and better healthcare systems, but the incidence is still higher, 100/100,000 population/year, in less developed countries . A key challenge to the effective control of typhoid fever is related to poor diagnosis. Diagnosis of typhoid fever in clinical settings is complicated because of overlapping symptoms with other common infections such as malaria, dengue, and viral enteritis [3–5]. For proper diagnosis, a test with a good diagnostic performance, especially in children with febrile diseases [6, 7], is of great importance. In addition, the misuse of antibiotics via automedication makes diagnosis difficult on a clinical basis . The gold standard for the diagnosis of enteric fever is blood culture, but this test not only has a poor sensitivity in clinical settings but also is time consuming and expensive for patients and clinics in remote settings where culture facilities may not be always available and the population is poor . The main diagnostic in such settings is based on the Widal slide agglutination test which is difficult to interpret for several reasons: cross-reactivities, time lag between infection and production of antibodies, and persistence of target antibodies long after treatment with very low correlation with active disease [10, 11]. The tube dilution technique enables a quantification of specific antibodies, and a change in titer can indicate active disease, but it is not very accessible. Many studies suggest that the Typhidot test, a plausible alternative based on the detection of antibody production against the outer membrane preparation common to Salmonella typhi and Salmonella paratyphi, has better performance characteristics. However, variations in sensitivity and specificity in the diagnosis of enteric fever among adults and children have also been noted [12–14]. The assay gives good results during early infections with a sensitivity of 68–95% and a specificity of 75–95% [15, 16]. An increase in the negative predictive value is important in endemic areas . Recommendations from the World Health Organization for typhoid rapid antibody testing  and some studies that have evaluated the Typhidot ability to detect antibodies have shown variations in sensitivity and specificity  in different settings. Although comparative studies have relied on the use of imperfect gold standard tests, a composite reference has been suggested to improve diagnostic values, but no agreement has been reached on which combinations can form a good composite reference standard, Storey et al. . In this study, we undertook to evaluate the diagnostic performance of the Widal and Typhidot tests against a composite reference made of a combination of fever (≥37.50 C), 3–7 days or more, and a positive stool culture test for Salmonella typhi and/or paratyphi in combination with one or more of the following clinical symptoms: persistent headache, abdominal discomfort, vomiting, and nausea. The choice of this combination was based on the feasibility and independence of the tests conditional to the disease, and although less specific, measures were taken to exclude other common febrile conditions such as malaria and respiratory tract infections. This was done in a bid to find a local strategy to better diagnose typhoid fever.
2.1. Study Area and Period
The Menoua division, one of the six divisions of the West Region of Cameroon, covers a surface area of 1380 km²; it is divided into six subdivisions (Figure 1) as follows: Dschang, Santchou, Nkong-Ni, Penka-Michel, Fokoue, and Fongo-Tongo. The altitude ranges from 600 to 800 m in Santchou through Dschang at 1500 m and Djuititsa at an altitude of 2200 m. The division has an average rainfall of about 1717.7 mm, and temperature ranges from 13.6°C to 25.35°C. About four in every five indigenes practice subsistence and/or smallholder farming, and the most important food stuffs grown include cabbage, carrot, onion, maize, banana, tomato, plantain, and beans. As of 2005, the division had a total population of 285,764. The capital of this division is Dschang.