New strategy needed to stop tuberculosis reoccurring in poorer patients
The standard approach to re-treating tuberculosis (TB) in low and middle income settings is failing, according to new research. In a study published in the journal PLoS Medicine, scientists call for improved access to rapid diagnostics for drug-resistant TB, second-line TB treatment and antiretroviral HIV (human immunodeficiency virus) therapy. They point out that each year, between 1 in 10 and 1 in 5 patients treated for TB see their disease return after failing, interrupting or relapsing from treatment. TB patients whose disease returns typically undergo an eight-month regimen of five drugs, as advised by the World Health Organization (WHO). Although this re-treatment regimen has been used for three decades, its efficacy has never been properly evaluated in clinical trials or similar studies, and it was designed before the spread of multi-drug resistant (MDR) TB. In recent years it has become clear that this re-treatment regime all too often delivers poor outcomes, particularly for people with HIV and MDR TB. The aim of this study, by researchers in South Africa, Uganda, the UK and the US, was to investigate treatment and survival outcomes in patients who had been treated for TB in the past and identify the factors associated with poor treatment outcomes. The findings highlight the need for more effective strategies to treat people with recurring TB. 'Our study suggests that the recommended therapy for re-treating TB is failing as many as one in four people with recurrent TB in the developing world,' said Dr Edward Jones-López, first author of the study and Assistant Professor of Medicine at Boston University School of Medicine in the US. He insisted that 'this rate is unacceptably high' and said it was 'essential that we understand why this is the case and how we might tackle this important health inequality'. A study in Kampala in Uganda of 140 HIV-infected patients and 148 HIV-free patients found that the re-treatment TB regimen failed to work effectively in a significant proportion of patients; 20% of HIV-free patients and 26% of HIV-infected patients were not treated successfully (according to the team, for a successful treatment outcome the patient must be cured and have completed treatment). All MDR-TB patients had unsuccessful treatment outcomes. Nearly a quarter of the patients subsequently died, while six per cent saw their TB disease return, with fatalities being particularly high amongst HIV-infected patients. The researchers believe that a number of reasons may be to blame for these results. These include poor adherence to the drug regimen and the presence of drug-resistant forms of TB - including MDR TB - some cases of which may have gone undiagnosed. In HIV-infected individuals, a low CD4 count (an indicator that the individual's immune system has been severely compromised) and poor access to antiretroviral therapy were also significant risk factors. Other factors associated with poor treatment outcomes were increasing age and the duration of TB symptoms. 'The results of this prospective study provide evidence that the standard re-treatment approach to TB, as implemented in low- and middle-income settings, is inadequate,' the researchers conclude. 'Clinical trials of new approaches to retreatment TB in areas heavily affected by HIV and TB should be a priority. Our findings indicate the importance of a new, more effective strategy for the management of [drug-resistant] TB in low and medium-income settings with prevalent HIV infection.' The findings imply that the treatments may need to be tailored depending on whether an individual has HIV. For those that are infected, access to rapid diagnosis as well as improved second-line medication and antiretroviral therapies may provide the best outcome. The study also reinforces the need for Directly Observed Therapy (DOT) in patients with TB. DOT combines diagnosing TB and registering each patient detected, followed by standardised multi-drug treatment, individual patient outcome evaluation and cohort evaluation to monitor overall programme performance. 'It is time for us to improve our management of TB disease and in particular consider how co-infection with HIV should change the way in which we treat the disease,' commented Dr Alphonse Okwera from Makerere University in Kampala, one of the study authors. 'The lives of hundreds of thousands of people in resource-poor settings are being put at risk, so this change is long overdue.'For more information, please visit: Wellcome Trust: http://www.wellcome.ac.uk Boston University School of Medicine: http://www.bumc.bu.edu/ The article in PLoS Medicine: http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000427
Countries
Uganda, United Kingdom, United States, South Africa