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HomeInfectious DiseasesWorld TB Day – Simple tests to diagnose TB

World TB Day – Simple tests to diagnose TB

A study published by researchers from the University of Cape Town shows that among hospitalised patients with HIV infection, a simple and inexpensive urine test identified more TB diagnoses in the first 24 hours of admission than rapid sputum-based tests.

This urine test (the Determine TB-LAM assay, similar to a pregnancy test) detects components of the cell wall of the TB bacterium in the urine and takes about 20 minutes to undertake without need for special infrastructure.

One of the researchers on the study, Professor Graeme Menthes, said: “The results of this study build on findings of other UCT researchers that this urine test can reduce mortality among HIV-infected patients admitted to hospital by speeding up the diagnosis of TB.

“The findings of these studies challenge the dogma that the first place to look for TB is in the sputum. Among a select group of patients (HIV-infected patients with very weak immune systems admitted to hospital) a combination of tests is required, including urine and sputum tests, to facilitate a quick diagnosis of TB thereby allowing doctors to start patients with TB on appropriate treatment rapidly.”

Historically, the laboratory examination of sputum samples has been the method used to diagnose most cases of TB. However, it is well recognised that this approach often fails in patients with HIV infection. In many of these patients, TB spreads from the lungs to the blood and other organs in the body due to poor immunity.

Additionally, there may be few or no TB bacteria found in their sputum, either because they are too weak or ill to produce a good sputum sample or because of less TB cavity formation in their lungs.

The difficulty of diagnosing TB is particularly true for patients with HIV who are sick enough to be admitted to hospital. Notably, in such patients, it is critically important to make a rapid diagnosis of TB so that treatment may be initiated promptly to avoid deaths.

The study was conducted at GF Jooste Hospital prior to it being decommissioned. A total of 427 consecutive patients with HIV infection admitted to the medical wards were screened for TB using sputum, urine and blood tests. In total, one in three (33%) of these patients were diagnosed with active TB disease.

Among patients with TB, sputum microscopy and sputum Xpert diagnosed TB within 24 hours of admission in 19% and 27%, respectively, compared to 38% using the urine Determine TB-LAM assay. The urine test was particularly useful for diagnosing TB in the patients with the lowest CD4 counts or weakest immune systems as well as those who were anaemic.

The main reason that the urine test outperformed the sputum test was because of how difficult it was to obtain a sputum specimen from many patients on admission. Whereas almost all patients, even those were very ill, could provide a urine sample.

The study was led by Professor Steve Lawn, who passed away in September 2016, after a long battle with brain cancer. Lawn, originally from the UK, conducted research in Cape Town from 2004 until the time of his death. He made seminal contributions to understanding the interactions between HIV and TB, the role of antiretroviral therapy in preventing TB in HIV-infected people and the important role of new diagnostic tests in improving the diagnosis of TB in HIV-infected people. Lawn published over 100 papers with UCT colleagues on HIV and TB in leading international journals.

Abstract
Background: We previously reported that one-third of HIV-positive adults requiring medical admission to a South African district hospital had laboratory-confirmed tuberculosis (TB) and that almost two-thirds of cases could be rapidly diagnosed using Xpert MTB/RIF-testing of concentrated urine samples obtained on the first day of admission. Implementation of urine-based, routine, point-of-care TB screening is an attractive intervention that might be facilitated by use of a simple, low-cost diagnostic tool, such as the Determine TB-LAM lateral-flow rapid test for HIV-associated TB.
Methods: Sputum, urine and blood samples were systematically obtained from unselected HIV-positive adults within 24 hours of admission to a South African township hospital. Additional clinical samples were obtained during hospitalization as clinically indicated. TB was defined by the detection of Mycobacterium tuberculosis in any sample using Xpert MTB/RIF or liquid culture. The diagnostic yield, accuracy and prognostic value of urine-lipoarabinomannan (LAM) testing were determined, but urine-LAM results did not inform treatment decisions.
Results: Consecutive HIV-positive adult acute medical admissions not already receiving TB treatment (n = 427) were enrolled regardless of clinical presentation or symptoms. TB was diagnosed in 139 patients (TB prevalence 32.6%; median CD4 count 80 cells/μL). In the first 24 hours of admission, sputum (spot and/or induced) samples were obtained from 37.0% of patients and urine samples from 99.5% of patients (P < 0.001). The diagnostic yields from these specimens were 19.4% (n = 27/139) for sputum-microscopy, 26.6% (n = 37/139) for sputum-Xpert, 38.1% (n = 53/139) for urine-LAM and 52.5% (n = 73/139) for sputum-Xpert/urine-LAM combined (P < 0.01). Corresponding yields among patients with CD4 counts Conclusions: Routine testing for TB in newly admitted HIV-positive adults using Determine TB-LAM to test urine provides major incremental diagnostic yield with very high specificity when used in combination with sputum testing and has important utility among those without respiratory TB symptoms and/or unable to produce sputum. The assay also rapidly identifies individuals with a poor prognosis.

Authors
Stephen D Lawn, Andrew D Kerkhoff, Rosie Burton, Charlotte Schutz, Andrew Boulle, Monica Vogt, Ankur Gupta-Wright, Mark P Nicol, Graeme Meintjes

 

A test done with blood obtained from a finger prick and can make a TB diagnosis in less than an hour is being developed by a multinational team of scientists led by researchers at Stellenbosch University and by Professor Gerhard Walzl. The diagnostic test is a hand-held, battery-operated instrument that will measure chemicals in the blood of people with possible TB. This test will not have to be done in a laboratory and health-care workers will be able to perform it with minimal training.

Walzl said in a report in The Conversation that it is a low-cost screening test and has the potential to significantly speed up TB diagnosis in resource-limited settings.

Walzl said: “The test is still in development. We have patented the bio-signature, which identifies the levels of chemicals in the blood of a patient. A bio-signature consists of a combination of chemicals and indicates a disease state. This signature was discovered by African scientists. The inventors included South African, Cameroonian and Ethiopian scientists.

“The test’s accuracy and efficacy will be tested in five African countries over the next three years. We will recruit 800 people who have TB symptoms from Namibia, the Gambia, Uganda, Ethiopia and South Africa.

“Clinical research sites will be set up or strengthened in all five countries. And participating countries will be able to use the data generated from this project.

“We are still trying to improve the signature by adding additional markers. In addition, we would like to optimise and fine tune the device to enable it to measure the signature on a strip similar to a pregnancy test or a glucose test strip.

“One of the challenges in South Africa is that people in remote areas with high TB incidence still do not benefit from newer developments in TB testing. As a result they face long diagnostic delays and often need to come back to clinics on several occasions before they are diagnosed.

“This test will mean that health-care workers with minimal training can use the test at grassroots level and get immediate access to screening test results.

“It would also reduce the cost of testing for TB. Our test would initially cost US$2.50 per test. With commercialisation that price could drop significantly. Currently the culture test costs $45 per test while the DNA sample test costs $12 per test.

“The test would be used best as a screening test. This is because it can identify people who need further investigation and can screen out those who don’t. So far we have been able to identify 70% of patients who do not need further testing.”

“The World Health Organisation has identified a screening test as important for high-prevalence areas, for those who are in contact with people who have TB, those living with HIV, homeless people, immune-compromised people and those living in areas with poor access to diagnostic services.”

[link url="http://www.polity.org.za/article/uct-uct-study-shows-that-urine-test-is-better-for-diagnosing-tb-rapidly-among-hospitalised-hiv-infected-patients-2017-03-22"]University of Cape Town material[/link]
[link url="http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0822-8"]BMC Medicine abstract[/link]
[link url="https://theconversation.com/african-scientists-a-step-closer-to-testing-for-tb-in-a-matter-of-minutes-59285"]The Conversation report[/link]

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