Community-based treatment of TB can save hundreds of thousands of lives

Proven Approach: 83 Percent of Study Participants In Lima, Peru Cured

Rate Exceeds Best Reported U.S. Cure Rate

Boston–January 9, 2003– Multidrug-resistant tuberculosis no longer must be considered a death sentence for infected individuals living in resource-poor nations, according to a study by a consortium of researchers led by Harvard Medical School’s Program in Infectious Disease and Social Change.

The study, which appears in this week’s New England Journal of Medicine, provides the first hard evidence that outpatient community care in poor, urban shantytowns can work for this most difficult to treat form of tuberculosis. The multidrug-resistant tuberculosis treatment model could ultimately help save hundreds of thousands of lives worldwide.

Among those who completed at least four months of therapy, the percentage with probable cures in this community-based study was 83 percent, as high as any reported to date, even in hospital settings. In contrast, the seminal report on the treatment of severe multidrug-resistant tuberculosis in a referral hospital in the United States documented a favorable response in 65 percent of patients.

“The scale of human suffering from the tuberculosis pandemic is overwhelming, and multidrug-resistant tuberculosis brings an almost indescribable helplessness,” says Carole Mitnick, ScD, the study’s lead author with the HMS Department of Social Medicine’s Program in Infectious Disease and Social Change. She and her colleagues have seen the disease, dubbed “Ebola with wings,” devastate families in urban Peru. “Finding an end to this tragedy requires high-quality ambulatory care that can be delivered in resource-poor nations,” says Mitnick. “This study reveals the effectiveness of our model against multidrug-resistant tuberculosis and offers new hope to those sick with multidrug-resistant tuberculosis and other chronic infectious diseases.”

Tuberculosis (TB) is a highly infectious bacterial disease transmitted through the air by the coughs of those who are sick. The bacterium destroys the lungs and kills approximately two million people each year, making it one of the leading infectious causes of death worldwide. The World Health Organization declared TB a global emergency in 1993 and launched an aggressive, comprehensive program known as DOTS to eliminate the epidemic. The standardized short-course treatment regimen on which the DOTS model is based, however, usually fails to cure multidrug-resistant tuberculosis (MDR-TB).

Two WHO studies, released in 1997 and 2000, found that MDR-TB strains were present in 63 of the 72 countries or regions surveyed; in some known TB hot spots, MDR-TB accounted for at least 20 percent of all previously treated TB cases. Strains of MDR-TB are resistant to the two most important drugs in the DOTS strategy and, therefore, existing therapy in poor countries for MDR-TB has been inadequate. It has been argued that drug-susceptibility testing and second-line drugs are not cost-effective in these countries due to limited resources and that intensive clinical management is impossible because of a lack of infrastructure.

The collaborative model described in this study counters these assumptions. Working in Lima, Peru, where there is a TB epidemic with a high percentage of MDR-TB patients, the consortium developed a treatment model called DOTS-Plus. In it, urban patients receive directly observed individualized therapy. Community members in northern Lima were taught to care for MDR-TB patients, who in other nations would be hospitalized. These health promoters ensure that patients continue their medications, manage adverse drug events, keep patients well nourished, and provide other support services. Drug-susceptibility testing was conducted to determine which TB drugs were likely to be effective for each patient, and cultures were performed monthly to monitor the effectiveness of the treatments.

The consortium-which includes Partners In Health, an HMS-affiliated non-governmental organization; its Peruvian sister organization, Socios En Salud; and the Peruvian Ministry of Health-enrolled 75 patients in the study between August 1, 1996 and February 1, 1999. All of them had failed treatment in the DOTS program and were diagnosed with MDR-TB, with an average resistance to six of the approximately 13 drugs used to treat TB.

Of the 75 patients originally enrolled, 66 patients completed four or more months of therapy, receiving 58 different treatment regimens lasting a median of 23 months. Of these 66, 55 (83 percent) had probable cures at the completion of therapy. Probable cure was defined as at least 12 months of consecutive negative cultures during therapy. Five patients (8 percent) withdrew from therapy; therapy failed in 1 patient; and 5 patients (8 percent) died while receiving therapy, after more than four months in the program.

“While developing a new model of care may not appear as dramatic as the discovery of a more effective drug-for those who might have otherwise been lost-this model brings similar hope,” says Mitnick, who is also with Partners In Health. “Among the hundreds of families affected by this epidemic in northern Lima alone, we found scores who had resorted to desperate measures such as selling all their land or livestock, or prostitution to buy medicines for loved ones-often two, three, or four with MDR-TB in a single household. Some had been told simply to save their money to ‘buy their own coffins.'”

“Our experience establishes that patients with chronic MDR-TB can be treated successfully as outpatients outside referral centers and in a resource-poor country,” says Paul Farmer, MD, PhD, the study’s principal investigator and HMS professor of social medicine and codirector of the Program in Infectious Disease and Social Change. “By moving treatment into the community, it is possible, without compromising the quality of therapy, to lower costs and reduce the risk of spread of MDR-TB. Successful community-based therapy for MDR-TB-and potentially HIV-provides hope for the tens of millions of patients who are suffering from chronic infectious diseases in settings with limited health infrastructure,” says Farmer, who is also the vice chair of the Division of Social Medicine and Health Inequalities at Brigham and Women’s Hospital, an HMS-affiliated teaching hospital.

The study was supported by the Bill & Melinda Gates Foundation, Thomas J. White, the Massachusetts State Laboratory Institute, the National Institute of Allergy and Infectious Diseases, and Eli Lilly.