The standard approach to re-treating tuberculosis (TB) in low- and middle-income settings is failing, according to research funded by the Wellcome Trust. In a study published today in the open access journal ‘PLoS Medicine’, researchers call for improved access to rapid diagnostics for drug-resistant TB, second-line TB treatment and antiretroviral HIV therapy.
Each year, between one in ten and one in five people treated for TB see their disease return after failing, interrupting or relapsing from treatment. This results in an estimated one million people in 90 countries being treated with an eight-month-long regimen of five drugs. The therapy has been in use for more than 30 years and is recommended by the World Health Organization.
A study in Kampala, Uganda, of 140 people with both HIV and TB and 148 people with TB alone found that the re-treatment TB regimen failed to work effectively in a significant proportion of people - 26 per cent of people with HIV and 20 per cent of people without HIV. Nearly a quarter (23 per cent) of patients died, and 6 per cent saw their TB disease return. Fatalities were particularly high among people with HIV.
"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," says Dr Edward Jones-López, first author of the study and Assistant Professor of Medicine at Boston University School of Medicine. "This rate is unacceptably high. It is essential that we understand why this is the case and how we might tackle this important health inequality."
The researchers believe that a number of reasons may be to blame. These include poor adherence to the drug regimen and the presence of drug-resistant forms of TB (including multidrug-resistant TB), some cases of which may have gone undiagnosed. In people with HIV, a low CD4 count - an indicator that the individual's immune system has been severely compromised - and poor access to antiretroviral therapy were significant risk factors.
The findings imply that the treatments may need to be tailored depending on whether an individual has HIV. For those who 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 people with TB. DOT combines diagnosing TB and registering each case detected, followed by standardised multi-drug treatment, individual patient outcome evaluation and cohort evaluation to monitor overall programme performance.
"It's 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," says Dr Alphonse Okwera from Makerere University, Kampala, Uganda, 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."
TB is one of the world's most deadly diseases. One-third of the world's population are believed to be infected with Mycobacterium tuberculosis, the agent that causes the disease. In many cases, the disease remains latent, but each year at least nine million people are in need of treatment for TB and more than two million people die from the disease. There are an estimated 500,000 cases of multidrug-resistant TB, the vast majority of which are undiagnosed and have limited access to effective treatment.