Podcast: The accuracy of rapid diagnostic tests for detecting typhoid and paratyphoid (enteric) fever

Point-of-care rapid diagnostic tests which use a small amount of blood are available for infectious diseases such as malaria and HIV, and make an important contribution to patient management. Cochrane Reviews of the accuracy of such tests have influenced World Health Organization (WHO) policy and, in May 2017, they were added to with a new Cochrane Diagnostic Test Accuracy review of rapid tests for typhoid and paratyphoid fevers. Lalith Wijedoru from the Alder Hey Children's Hospital in Liverpool in UK tells us more in this podcast.

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John: Hello, I'm John Hilton, editor of the Cochrane Editorial unit.  Point-of-care rapid diagnostic tests which use a small amount of blood are available for infectious diseases such as malaria and HIV, and make an important contribution to patient management. Cochrane reviews of the accuracy of such tests have influenced WHO policy and, in May 2017, they were added to with a new Cochrane Diagnostic Test Accuracy review of rapid tests for typhoid and paratyphoid fevers. Lalith Wijedoru from the Alder Hey Children's Hospital in Liverpool in UK tells us more in this podcast.

Lalith: Typhoid and paratyphoid fevers are infectious diseases, collectively known as ‘enteric fever’, which are common in areas with poor hygiene and sanitation in sub-Saharan Africa, and across Asia. Patients have fever but few other specific signs and symptoms and the disease is often confused with other infectious diseases which cause fever. Rapid, accurate diagnostic tests would widen access to testing in regions where laboratory testing might not be accessible, and individual patients would benefit, by obtaining their test results during a single clinic visit. However, as I’ll explain, our examination of the up-to-date evidence does not support the use of the rapid, point-of-care tests that are currently available.
The WHO recommends blood culture as the best test for enteric fever but, even in the best settings, this only confirms the diagnosis in about two thirds of patients who have it. The necessary laboratories are also costly, and usually unavailable in the resource-limited settings where enteric fever is common. The Widal Test is a simple and widely-used test, but it’s known to over-estimate the number of actual cases, which can lead to unnecessary treatment and the development of antibiotic resistance. The lack of a robust test for enteric fever makes it difficult to manage patients with fever and for governments and policy makers to understand the true burden of the disease, and make decisions about national vaccination.
In the past two decades, several commercially available typhoid rapid diagnostic tests have appeared and we wanted to examine the evidence to see if the WHO could recommend them as a replacement for blood culture and if they could be used as a diagnostic test when patients with fever present to a healthcare facility in areas where enteric fever is suspected to be common.
A total of thirty-seven diagnostic accuracy studies met our criteria and all of the rapid diagnostic tests evaluated were for diagnosing typhoid fever. Most of the studies were from the Asia-Pacific region, with five done in sub-Saharan Africa. The tests were mainly used on patients thought to have enteric fever, rather than on all patients with fever.
Three main commercially available rapid diagnostic tests, Typhidot, TUBEX and Test-It-Typhoid tests were evaluated, each in several thousand patients, but we found that the accuracy of these three rapid diagnostic test groups was only moderate and there was too little evidence for other tests to draw conclusions about them. There was no statistical evidence to show that one test was better than another.
The overall quality of the studies was low. Most did not use the most accurate reference standard of blood and bone marrow culture, and there were few high quality studies where multiple rapid diagnostic tests were evaluated in a single study. Many studies used a case-control design which tends to over-estimate diagnostic test accuracy.
In summary, these rapid diagnostic tests are not accurate enough to replace blood culture as the best current test for typhoid. We hope our review inspires more research into alternative point-of-care diagnostic tests, as well as a more robust reference standard for this important but neglected disease.

John: If you would like to read more about the tests and the studies that evaluated them, the full version of this Cochrane Review is available free to all online. If you got to Cochrane Library dot com and search 'Rapid diagnostic tests for typhoid', you’ll find it easily.

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