Skip to main content
Premium Trial:

Request an Annual Quote

South African-led Study Supports Use of Cepheid Test for Diagnosing TB in Children

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – Cepheid's Xpert MTB/RIF molecular test can detect pediatric tuberculosis cases more accurately than smear microscopy of sputum samples, according to a study in the early, online version of The Lancet Infectious Diseases today.

Researchers from South Africa and Switzerland compared the MTB/RIF nucleic acid amplification test — which detects sequences from the tuberculosis-causing bacteria Mycobacterium tuberculosis in general as well as sequences associated with resistance to the antibiotic rifampin — with smear testing in a prospective study involving hundreds of children being treated at two Cape Town hospitals.

Although the MTB/RIF test showed lower sensitivity in children than has been previously reported in adults, the researchers reported, it was far more sensitive than smear microscopy-based tuberculosis testing, especially when two sputum samples were tested per child.

"We showed that the sensitivity of MTB/RIF for smear-negative tuberculosis is lower in children [than] it is in adults, but is twice as sensitive compared with smear microscopy in children," lead author Mark Nicol, a molecular medicine researcher at the University of Cape Town, and his co-authors wrote.

"We also showed that the incremental benefit in testing a second induced sputum specimen is substantial," they added, "suggesting that, in children, a second specimen should be tested to optimize sensitivity."

Microscopic analyses of sputum samples are widely used to find tuberculosis disease, especially in developing countries. Even so, researchers explained, the method misses many cases — particularly in children and individuals with HIV infections. And because it looks only for the presence or absence of M. tuberculosis, the smear-based test does not provide information about whether an individual is infected with a drug-sensitive or resistant form of the bug.

Late last year the World Health Organization recommended replacing smear microscopy-based tuberculosis diagnostic testing with Cepheid's Xpert MTB/RIF test, an automated sample processing and real-time PCR approach, especially for individuals who have HIV infections or are suspected of carrying drug resistant M. tuberculosis.

Nevertheless, this molecular test has not been tested specifically in children, the team explained.

"WHO recommends that Xpert MTB/RIF replace smear microscopy for initial diagnosis of suspected HIV-associated tuberculosis or multidrug-resistant pulmonary tuberculosis, but no data exist for its use in children," they wrote. "We aimed to assess the accuracy of the test for the diagnosis of pulmonary tuberculosis in children in an area with high tuberculosis and HIV prevalences."

To explore the clinical utility of the molecular test for diagnosing tuberculosis in children, researchers compared it to smear testing in 452 children 15 years old or younger who were admitted to the Red Cross War Memorial Children's Hospital or the Somerset Hospital in Cape Town between mid-February, 2009 and late-November, 2010.

Both the smear microscopy and MTB/RIF tests were compared to a mycobacterial culture testing, a reliable but time-consuming reference test. Duplicate sputum samples were tested for 385 of the children.

Overall, researchers found that the molecular test accurately detected M. tuberculosis infections, even in children who are also infected with HIV, which can complicate smear microscopy-based tests.

Of the 452 children for whom at least one sample was available, 108 children — 24 percent — were infected with HIV and 17 children were infected with both HIV and tuberculosis. The MTB/RIF test detected all 17 of these tuberculosis cases, while smear testing detected 10.

Culture testing pointed to definite tuberculosis infections in 70 of the 452 children and possible infection in 216 more. From at least one sputum test, the team found 27 smear-positive tuberculosis cases and 52 MTB/RIF-positive cases. For the cases with one sample per child, the molecular test caught all cases found by smear microscopy as well as 25 smear-negative cases.

In contrast to culture testing, which took between nine and 17 days, results from the MTB/RIF test were available in a median time of one day, researchers reported.

When the researchers tested two sputum samples for each child, meanwhile, smear testing caught 37.9 percent of tuberculosis cases, while MTB/RIF testing found 75.9 percent of cases, including all of the smear-positive cases, along with more than 60 percent of the cases missed by the smear test.

"With mycobacterial culture as the reference standard, MTB/RIF tests when done on two induced sputum samples detected twice as many cases as did smear microscopy," the study authors wrote, "detecting all of 22 smear-positive cases and 22 of 36 smear-negative cases."

The test was less sensitive for finding smear-negative cases in children than reported previously in adults, especially when researchers relied on results from a single sputum sample for each child. Adding in a second sample per child upped tuberculosis detection by almost 28 percent.

Those involved in the study say more research is needed to explore the use of the MTB/RIF test for finding rifampicin-resistant M. tuberculosis strains in children, since the current study found too few of these cases to assess this aspect of the test. They also noted that the children involved in the study likely represent more severe cases than those found in a typical clinical setting.

Even so, the researchers said the findings suggest that the MTB/RIF test is a reliable strategy for quickly diagnosing tuberculosis in children when sputum samples are available.

In an accompanying editorial in The Lancet Infectious Diseases, tropical medicine researcher Eduardo Gotuzzo from Peru's Universidad Peruana Cayetano Heredia cautioned that the use of two molecular tests per child, though increasing the test's sensitivity, is also apt to increase the cost of diagnosing tuberculosis.

"Further studies should be done in settings with different HIV and tuberculosis prevalence," he wrote, "and implementation studies and cost-effectiveness studies are needed to support the use of a second test in pediatric populations."

The Scan

Shape of Them All

According to BBC News, researchers have developed a protein structure database that includes much of the human proteome.

For Flu and More

The Wall Street Journal reports that several vaccine developers are working on mRNA-based vaccines for influenza.

To Boost Women

China's Ministry of Science and Technology aims to boost the number of female researchers through a new policy, reports the South China Morning Post.

Science Papers Describe Approach to Predict Chemotherapeutic Response, Role of Transcriptional Noise

In Science this week: neural network to predict chemotherapeutic response in cancer patients, and more.