Rapid diagnostic tests for typhoid and paratyphoid (enteric) fever


Wijedoru L, Mallett S, Parry CM



Differentiating both typhoid (Salmonella Typhi) and paratyphoid (Salmonella Paratyphi A) infection from other causes of fever in endemic areas is a diagnostic challenge. Although commercial point-of-care rapid diagnostic tests (RDTs) for enteric fever are available as alternatives to the current reference standard test of blood or bone marrow culture, or to the widely used Widal Test, their diagnostic accuracy is unclear. If accurate, they could potentially replace blood culture as the World Health Organization (WHO)-recommended main diagnostic test for enteric fever.


To assess the diagnostic accuracy of commercially available rapid diagnostic tests (RDTs) and prototypes for detecting Salmonella Typhi or Paratyphi A infection in symptomatic persons living in endemic areas.


We included diagnostic accuracy studies of enteric fever RDTs in patients with fever or with symptoms suggestive of enteric fever living in endemic areas. We classified the reference standard used as either Grade 1 (result from a blood culture and a bone marrow culture) or Grade 2 (result from blood culture and blood polymerase chain reaction, or from blood culture alone).


Two review authors independently extracted the test result data. We used a modified QUADAS-2 extraction form to assess methodological quality. We performed a meta-analysis when there were sufficient studies for the test and heterogeneity was reasonable.


Thirty-seven studies met the inclusion criteria and included a total of 5080 participants (range 50 to 1732). Enteric fever prevalence rates in the study populations ranged from 1% to 75%. Meta-analyses showed an average sensitivity of 78% and specificity of 87% for TUBEX; and an average sensitivity of 69% and specificity of 90% for all Test-It Typhoid and prototype tests (KIT). Across all forms of the Typhidot test, the average sensitivity was 84% and specificity was 79%. In the 700 people without enteric fever, the number of people incorrectly diagnosed with enteric fever would be 161 with Typhidot tests, 91 with TUBEX, and 70 with Test-It Typhoid and prototype (KIT) tests. The CIs around these estimates were wide, with no difference in false positive results shown between tests. The quality of the data for each study was evaluated using a standardized checklist called QUADAS-2. Overall, the certainty of the evidence in the studies that evaluated enteric fever RDTs was low.


In 37 studies that evaluated the diagnostic accuracy of RDTs for enteric fever, few studies were at a low risk of bias. The three main RDT tests and variants had moderate diagnostic accuracy. There was no evidence of a difference between the average sensitivity and specificity of the three main RDT tests. More robust evaluations of alternative RDTs for enteric fever are needed.

Click here to view the article, published in Cochrane Database for Systemic Reviews