Common Multidrug-Resistant TB Strain in Swaziland Not Detectable by Most Advanced Rapid Diagnostic Tests

More than a quarter of multi-drug resistant tuberculosis (MDR-TB) strains isolated in a national survey in Swaziland carry a mutation that is undetectable by the advanced rapid molecular diagnostic tests currently in widespread use, according to a letter published in New England Journal of Medicine by Doctors Without Borders/Médecins Sans Frontierès (MSF) and the Research Center, Borstel, Germany. 

Rapid molecular tests such as the WHO-recommended XpertMTB/RIF assay are the first-line method for identifying cases of multidrug resistant tuberculosis (MDR-TB) and controlling the spread of the disease in Swaziland, the country with the world’s highest TB prevalence.

“Thanks to the availability of these tests, we can now find out very quickly whether patients have a drug-resistant Mycobycterium tuberculosis strain.  If so, we can start them on treatment that targets these strains, which in turn increases the chances of survival and helps curtail new drug-resistant infections,” said Alex Telnov, HIV/TB referent at MSF.  “These diagnostic tests are our front line of defense in fighting drug-resistant TB. To learn that we could be missing so many cases means there is an urgent need to adapt our detection approach to MDR-TB in Swaziland.”

Epicentre, an MSF-affiliated research center, together with the Research Center in Borstel, Germany, analyzed TB strains collected in 2009-2010 during the most recent national TB drug resistance survey in Swaziland. A genotyping analysis found that 30 percent of the 125 MDR-TB strains recovered from the survey carry a specific genetic mutation, called rpoB (1491F), that had been identified previously in rare strains from Hong Kong and Australia.

This mutation not only confers resistance to the key first-line TB drug, rifampicin (RIF), but is undetectable by the XpertMTB/RIF assay, which is used throughout most of Swaziland as the standard screening test for TB and MDR-TB as per WHO recommendation.

“The high proportion of the circulating strain with 1491F mutations poses a significant public health challenge that must not be ignored,” said Stefan Nieman, at Research Center Borstel and the German Center for Infection Research. “By missing these diagnoses of drug resistance and therefore under-treating patients, the likely consequence is further transmission of this difficult-to-treat strain.”

The results of the analysis are particularly problematic in a country where 26 percent of adults have HIV (the world’s highest prevalence), and 80 percent of TB patients are co-infected with HIV. This is especially worrying in Swaziland, where the 2009-2010 survey showed  that TB patients who are co-infected with HIV are more likely than those who are HIV-negative to be infected with MDR-TB.

As a result of this new research, MSF recommends that all patients in Swaziland who have tested positive for TB but who test negative for drug resistance by XPertMTB/RIF test undergo additional drug susceptibility testing.  It is also essential to conduct studies that can determine whether this rpoB (149B) mutation is present in neighboring countries such as South Africa of Mozambique.

“If we’re facing wide distribution of this strain in Southern Africa or elsewhere, it is imperative that the rapid molecular tests we currently use, as well as those under development, be adapted to detect a wider range of mutations,” said Elisabeth Sanchez, first author of the study.

Contact:
Prof. Dr. Stefan Niemann
Head Molecular Mycobacteriology Group / Deputy Head Priority Area Infections
Forschungszentrum Borstel
Parkallee 1
23845 Borstel, Germany
E-Mail
Phone: 04537-188 7620

Sanchez-Padilla, M. et al. (2015): Detection of Drug-Resistant Tuberculosis by Xpert MTB/RI in Swaziland, N Engl J Med. 372;12  DOI: 10.1056/NEJMc1413930
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