Extensively drug-resistant tuberculosis (XDR-TB) appears to be spreading in South Africa, fueled by patients who are discharged despite failing therapy, researchers reported.
In a prospective cohort of patients with XDR-TB , most patients died and only a handful were cured, according to Keertan Dheda, PhD, of University of Cape Town in South Africa, and colleagues.
About 40 percent were eventually discharged into the community and of those, almost half had failed treatment and remained alive and contagious for a median of 19.8 months, Dheda and colleagues reported online in The Lancet
Analysis showed clusters of new cases and transmission within families containing a patient who had failed therapy. Dheda said in a statement, the study shows that "treatment failure and discharge of such patients into the wider community, is occurring systematically on a countrywide level in South Africa."
The problem, he said, is that "little bed space is available in designated tuberculosis hospitals, and alternative long-term residential and palliative care facilities are scarce." The study is a "stark reminder" of the threat of drug-resistant TB, argued Max O'Donnell, MD, of Albert Einstein College of Medicine.and Neil Schluger, MD, of Columbia University College of Physicians and Surgeons, both in New York City
In an accompanying Comment article, O'Donnell and Schluger noted that global TB control efforts have resulted in modest gains in the past decade, but drug resistance threatens to reverse those improvements . Drug-resistant TB "is an out-of-control problem with potentially vast and devastating repercussions for global public health," they argued.
Most cases of TB succumb to a regimen consisting of isoniazid (Nydrazid), rifampin (Rifadin), ethambutol (Myambutol), and pyrazinamide for 8 weeks, followed by isoniazid and rifampin for another 18 weeks. But multidrug resistant-TB (MDR-TB) -- defined by resistance to [at least] isoniazid and rifampin -- is more difficult to treat. Still more difficult is XDR-TB, defined by resistance to isoniazid and rifampin, as well as any fluoroquinolone and at least one of 3 injectable 2nd-line drugs, such as amikacin (Amikin), kanamycin (Kantrex), or capreomycin (Capastat).
Between March 2008 and August 2012, Dheda and colleagues followed 107 patients from 3 provinces in South Africa who had been diagnosed with XDR-TB between August 2002 and February 2008. The study is a follow-up to a retrospective analysis, including many of the same patients, that was reported in 2010.
All were treated empirically as inpatients with a median of 8 drugs; genotypic testing of a subset of patients showed resistance to at least 8 drugs and in one case resistance to all 10 drugs that were tried.
After 60 months, the researchers reported, just 12 patients had a favorable outcome. Another 78 had died, 4 had interrupted treatment, and 11 remained alive but were considered to have failed treatment -- they remained TB culture-positive despite at least 12 months of therapy.
Patients who ran out of therapeutic options were discharged, Dheda and colleagues reported, after a median treatment duration of 22 months. All told, 56 patients died in the hospital, 6 transferred out of the region, and 45 patients were discharged.
Of those discharged, 19 had failed treatment and a third of those were smear-microscopy-positive at discharge. Their median survival was 19.84 months. "These patients can survive for months or even years, and are contributing to the community-based spread of XDR-TB," Dheda said.
Indeed, he and colleagues reported, DNA fingerprinting showed that in one instance an XDR-TB patient, who had failed treatment and been discharged, infected his brother who later died.
What's needed, O'Donnell and Schluger argued, are "major new investments in drug development, diagnostics, and operational research." But, they noted, global TB research budgets are shrinking, so that "the situation regarding MDR and XDR-TB is bleak."