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TB Notes 1, 2005

No. 1, 2005

International Updates

Factors Associated with Default from Multidrug-Resistant Tuberculosis Treatment, South Africa, 1999-2001

In the past decade, South Africa has experienced a rapid escalation of TB incidence, with new cases rising from less than 100 per 100,000 persons in 1990 to 558 per 100,000 in 2003. In the 2002 Report on Global TB Control, the World Health Organization (WHO) ranked South Africa third in the world in terms of reported TB incidence for 1999 and seventh in terms of absolute number of persons with active TB.1 Health services are currently burdened by more than 200,000 new TB patients per year, of whom 60% are estimated to be infected with HIV.2

At present, the estimated proportion of TB cases in South Africa identified as multidrug-resistant TB (MDR TB) ranges from 1% to 2% among new cases and 4% to 14% among retreatment cases, depending on the province. Treatment default has been identified as a significant problem in these patients. Failure to adhere to MDR TB therapy may result in primary transmission of MDR TB in the community, amplify resistance to second-line drugs, and increase the chance of failure in subsequent treatment attempts.3

CDC technical assistance was requested to assist in conducting an evaluation of factors associated with treatment default among patients receiving treatment for MDR TB. This case-control investigation to identify patient-level and provider-level factors for default to MDR TB treatment was conducted in 2003 and 2004. These results will assist the South Africa National TB Control Program in strengthening existing strategies for improving adherence among all TB patients and introduce new strategies to maintain adherence among the growing pool of MDR TB patients being treated under the national standardized MDR TB treatment guidelines.

We conducted an unmatched, questionnaire-based, case-control study among adult persons aged 18 years and older diagnosed with MDR TB between October 1, 1999, and September 30, 2001, and for whom MDR TB treatment was initiated. Data was collected from sites in five provinces. We selected all patients from MDR TB treatment register lists generated by each province’s MDR TB referral hospital. We defined cases as MDR TB patients 18 years or older who initiated standardized MDR TB therapy but subsequently defaulted. We defined controls as MDR TB patients who initiated MDR TB treatment and were considered to have completed a full treatment course (either cure or completion or failure). Owing to logistical limitations, we restricted our interviewers to look for patients living within 200 kilometers of the hospital.

A questionnaire was developed in English and translated into the other common South African languages (Xhosa, Zulu, Tswana, and Afrikaans) and back-translated into English to evaluate the quality of translation. This study was conducted using a face-to-face, administered questionnaire. The questionnaire consisted of a mixture of open-ended, multiple choice, and yes/no questions. Questions were asked to establish demographic and social characteristics, health service experience, clinical characteristics, TB/MDR TB knowledge, and self-reported reasons for defaulting (if applicable).

Our study provided multiple layers of information about patient, provider, and health system-level factors that may influence patients’ adherence to MDR TB treatment. First, we discovered that 13% of treatment defaulters (our cases) and 10% of treatment completers were improperly classified in the MDR TB registers we examined. The proper recording of treatment outcome is of enormous importance in a country like South Africa, with an emerging problem of MDR TB in the midst of a large human immunodeficiency virus (HIV) epidemic. Misclassification bias, even on the order of 10% seen here, can markedly skew “good outcomes” (treatment success of 70%-75%) to “modest” outcomes (treatment success of 60%-65%).

Second, not surprisingly, our investigators uncovered a significant death rate among defaulters and those completing MDR TB treatment in our sampling cohort. More than one in four patients who were classified as defaulters were in fact found to have died after the last contact with their MDR TB clinic. Twenty percent of those for whom we found death dates had died within 2 months after stopping treatment, and were thus “true deaths.”

We were also unable to contact another one third of treatment defaulters, likely due to internal migration or death. Therefore the “true death rate” among those undergoing treatment for MDR TB may not be known, but it is likely higher than the 25% reported in recent MDR TB outcome studies in South Africa.

We identified four major areas associated with treatment default in the patients we interviewed. The most significant factors we found associated with treatment default were related to the quality of the patient-provider relationship. Our multivariate model showed that defaulters were nearly ten times more likely to report dissatisfaction with health care worker attitudes. They were also ten times more likely to report missing treatment due to health care worker attitudes. Though it is possible that a small proportion of defaulters went into treatment with preconceived negative feelings about the health care services, this bias is unlikely to account for such an overwhelming disparity of opinion.

Lack of support from family and friends during treatment also appears to be crucial. Our multivariate model showed that cases were twice as likely to report feeling ashamed about having MDR TB. Twice as many cases reported a lack of social support from family or friends during treatment. This is often reflective of the stigma they feel is attached to TB, the amount of support they feel in disclosing their disease to others, and of being seen as a TB patient by friends and family.

Importantly, our model showed that the use of illegal substances during treatment, such as marijuana or mandrax, was more than ten times more likely to be reported by cases than controls. The use of alcohol on an occasional or regular basis was also more commonly reported by cases. Cases were four times more likely to report having spent time in prison during MDR TB treatment than controls.

When cases were asked directly why they defaulted treatment, the most common response was that side effects were too common. It is possible that patients’ discomfort in having MDR TB, the associated stigma of having TB, and a poor experience in the health care setting may translate into a lowered tolerance to side effects from medication. The outward expression of these difficulties in treatment could be perceived by patients to be medication side effects.

Based on our findings, we are able to recommend that the National TB Control Programme consider strengthening the training, supervision, and support of health care providers of MDR TB patients to avoid burnout and overwork. We also feel it is necessary for the programme to provide continuing education for health professionals on the importance of the patient-provider relationship, and the importance of the health care provider attitude. Given that support from family and friends is a crucial component of completing treatment, the programme should consider supporting patients’ treatment and care package with family support sessions, treatment counseling, and substance abuse counseling.

—Submitted by Timothy Holtz, MD, MPH
Div of TB Elimination


  1. World Health Organization. Global Tuberculosis Control: Surveillance, Planning, Financing. WHO Report 2003. Geneva, Switzerland: World Health Organization, 2003; report no. WHO/CDS/TB/2003.316.
  2. World Health Organization. Tuberculosis control in South Africa: joint programme review 1996. Geneva: World Health Organization, 1996. WHO/TB/96.208.
  3. World Health Organization. Anti-tuberculosis drug resistance in the world. The WHO/IUATLD global project on anti-tuberculosis drug resistance surveillance. Geneva, World Health Organization, 1997 (WHO/CDS/TB/1997.229).


Released October 2008
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
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