XDR-TB patients in South Africa often released without cure, still infectious

Many patients with extensively drug-resistant and totally resistant tuberculosis in South Africa are being discharged from the hospital and potentially exposing their communities to infection, researchers reported in The Lancet.

“These patients can survive for months or even years, and are contributing to the community-based spread of XDR-TB,” Keertan Dheda, PhD, of the department of medicine at the University of Cape Town in South Africa, said in a press release. “Alarmingly, we have shown for the first time that, in contrast to sporadic and isolated cases of treatment failure and near total or totally drug-resistant cases that have been reported in several countries, treatment failure, and discharge of such patients into the wide community, is occurring systematically on a country-wide level in South Africa.”

Dheda and colleagues prospectively followed 107 patients from three provinces in South Africa who were diagnosed with XDR-TB from August 2002 to February 2008. Fifty-six patients had isolates available that were genotyped to identify the TB strain. The isolates also were tested for susceptibility to 10 anti-TB drugs. All participants were treated as inpatients with directly observed therapy, and median treatment duration was 22.1 months. Forty-four patients (41%) had HIV.

After 60 months, only 12 patients (11%) had favorable outcomes, either cure or treatment completion. Seventy-nine patients (74%) had died, four had defaulted on treatment and 11 (10%) had failed treatment. Thirty-six (64%) of the 56 isolates tested were resistant to at least eight drugs. There was one patient who was resistant to all 10 drugs. The Beijing genotype was associated with resistance to more drugs.

Forty-five patients were released from the hospital and into the community, and 26 of those (58%) had achieved sputum culture conversion. The remaining patients were treatment failures who were still culture-positive for TB despite 12 months of treatment. One-third of those patients were also smear-positive and at high risk for transmitting the disease. Among those who had failed treatment, the median survival from time of discharge was 19.8 months. There was confirmed evidence that one patient who failed treatment had transmitted XDR-TB to his brother.

“Many patients who fail treatment are being discharged back into the community because little bed space is available in designated TB hospitals, and alternative long-term residential and palliative care facilities are scarce,” Dheda said. “Testing of new combined regimens and tough community infection control plans to minimize disease spread by patients who fail treatment, including the building of modernized sanatoriums and funding comprehensive home-based care, are urgently needed.”

In an accompanying comment, Max R. O’Donnell, MD, of Albert Einstein College of Medicine and Neil W. Schluger, MD, of Columbia University College of Physicians and Surgeons, said this study raises an urgent alarm for the need for global TB control.

“[Multidrug-resistant TB] in all its forms is an out-of-control problem with potentially vast and devastating consequences for global public health,” they wrote. “Major new investments in drug development, diagnostics and operational research are sorely needed. Unfortunately, as a recent report from Treatment Action Group indicates, global TB research budgets are shrinking, not growing. The situation regarding MDR and XDR-TB is bleak.”

For more information:

O’Donnell M. Lancet. 2014;doi:10.1016/S0140-6736(14)60043-X.

Pietersen E. Lancet. 2014;doi:10.1016/S0140-6736(13)62675-6.

Disclosure: Dheda, O’Donnell and Schluger report no relevant financial disclosures.