South Africa Risks Spreading Totally Drug-Resistant Tuberculosis - The Lancet Study

South Africa risks spreading totally drug-resistant Tuberculosis: The Lancet study -- Kate Kelland Reuters London January 16, 2014 ----------------- LONDON - Patients with contagious and highly drug-resistant tuberculosis (TB) are being routinely discharged from hospitals across South Africa -- exposing others in their communities to potentially deadly infections, researchers said on Friday. In a study in the medical journal The Lancet, they said the patients, with strains of TB known as extensively-drug resistant (XDR) and totally drug resistant (TDR) TB, have exhausted all available treatment options and are sent home. "These patients can survive for months or even years and are contributing to the community-based spread of XDR-TB," said Keertan Dheda*, who led the study at the University of Cape Town's department of medicine. ---------------- BACKGROUND: Keertan Dheda* is Professor of Respiratory Medicine, Director of the Lung Infection and Immunity Unit http://www.lunginstitute.co.za/content/lung_infection.html and Head of the Division of Pulmonology, Department of Medicine, at the University of Cape Town http://www.medicine.uct.ac.za/ ================================== Tuberculosis infects the lungs and can spread through coughing and sneezing. In recent years, drug-resistant strains have spread around the world, batting off standard antibiotics and posing an increasingly urgent public health threat. Dheda's team followed 107 patients with XDR-TB from three provinces in South Africa between March 2008 and August 2012 to establish their fate. They also took samples from 56 patients and tested them to find out which and how many of 10 first- and second-line anti-TB drugs they were susceptible to. Despite being treated intensively with an average of eight anti-tuberculosis drugs, many of the patients fared poorly, with high rates of treatment failure and death. Five years after treatment initiation, only 12 of the patients had favorable outcomes and 74 percent had died. DISCHARGED WHILE INFECTIOUS TO OTHERS: The researchers found that almost two-thirds of the tested patients had resistance to at least eight drugs, and there was one case of totally drug-resistant TB that was not susceptible to any of the 10 drugs tested. More worrisome, Dheda said, was that of the XDR-TB patients discharged into the general community, some 42 percent had failed to get better on treatment and were testing positive for active TB, and of these almost a third were at high risk of transmitting the disease. The patients also survived in the community for an average of 20 months - plenty of time to infect others. When people with lung TB cough, sneeze or spit, they propel the TB germs into the air. Another person needs to inhale only a few of these germs to become infected. TREATMENT FAILURE AND DISCHARGING INFECTIOUS PATIENTS INTO WIDER COMMUNITY IS SYSTEMATIC ON A COUNTRYWIDE LEVEL IN SOUTH AFRICA "Alarmingly, we have shown for the first time that... treatment failure and discharge of such patients into the wider community is occurring systematically on a country-wide level in South Africa," Dheda said in a statement about the findings. In one case where the researchers followed a genetic trail of transmission, they found that a patient with XDR-TB who was discharged after failing treatment went on to infect his brother, who also eventually died. Dheda said the reason many TB patients are being sent away from hospitals appeared to be lack of bed space in designated tuberculosis hospitals. "And alternative long-term residential and palliative care facilities are scarce." Commenting on the findings in The Lancet, Max O'Donnell from New York's Albert Einstein College of Medicine in the United States said they should serve as an "urgent alarm". "MDR-TB (multi-drug-resistant TB) in all its forms is an out-of-control problem with potentially vast and devastating consequences for global public health," he wrote. "The situation regarding MDR and XDR-TB is bleak." (Editing by Kevin Liffey) Read more: http://www.chicagotribune.com/health/sns-rt-us-tuberculosis-southafrica-20140116,0,5067152.story#ixzz2qePWIMLe http://www.baltimoresun.com/health/sns-rt-us-tuberculosis-southafrica-20140116,0,2127229.story ------------ THE LANCET SUMMARY: Title: "Long-term outcomes of patients with extensively drug-resistant tuberculosis in South Africa: a cohort study"- Elize Pietersen MSSc, Elisa Ignatius MD, Elizabeth M Streicher PhD, Barbara Mastrapa MD, Xavier Padanilam MCFP, Anil Pooran MSc and others Jan 17, 2014 " The Lancet URL download entire article (with payment) from: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2962675-6/fulltext "January 17 2014: Long-term treatment-related outcomes in patients with extensively drug-resistant (XDR) tuberculosis are unknown. We followed up a cohort of patients to address knowledge gaps." Methods Between March, 2008, and August, 2012, we prospectively followed up a cohort of 107 patients from three provinces in South Africa, who had been diagnosed with XDR tuberculosis between August 2002, and February, 2008. Available isolates from 56 patients were genotyped to establish strain type and used for extended susceptibility testing. Findings All patients were treated empirically as inpatients with a median of eight drugs (IQR six to ten). 44 patients (41%) had HIV. 36 (64%) of 56 isolates were resistant to at least eight drugs, and resistance to an increasing number of drugs was associated with the Beijing genotype (p=0·01). After 24 months of follow-up, 17 patients (16%) had a favourable outcome (ie, treatment cure or completion), 49 (46%) had died, seven (7%) had defaulted (interruption of treatment for at least 2 consecutive months), and 25 (23%) had failed treatment. At 60 months, 12 patients (11%) had a favourable outcome, 78 (73%) had died, four (4%) had defaulted, and 11 (10%) had failed treatment. 45 patients were discharged from hospital, of whom 26 (58%) had achieved sputum culture conversion and 19 (42%) had failed treatment. Median survival of patients who had failed treatment from time of discharge was 19·84 months (IQR 4·16—26·04). Clustering of cases and transmission within families containing a patient who had failed treatment and been discharged were shown with genotypic methods. Net sputum culture conversion occurred in 22 patients (21%) and median time to net culture conversion was 8·7 months (IQR 5·6—26·4). Independent predictors of probability of net culture conversion were no history of multidrug-resistant tuberculosis (p=0·0007) and use of clofazamine (p=0·0069). Independent overall predictors of survival were net culture conversion (p<0·0001) and treatment with clofazamine (p=0·021). Antiretroviral therapy was also a predictor of survival in patients with HIV (p=0·003). Interpretation In South Africa, long-term outcomes in patients with XDR tuberculosis are poor, irrespective of HIV status. Because appropriate long-stay or palliative care facilities are scarce, substantial numbers of patients with XDR tuberculosis who have failed treatment and have positive sputum cultures are being discharged from hospital and are likely to transmit disease into the wider community. Testing of new combined regimens is needed urgently and policy makers should implement interventions to minimise disease spread by patients who fail treatment. Funding European and Developing Countries Clinical Trials Partnership, South African National Research Foundation (SARChI), and the South African Medical Research Council.