Published ahead of print on June 29, 2006, doi:10.1164/rccm.200510-1667OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200510-1667OC
Predicting Non-Completion of Treatment for Latent Tuberculous InfectionA Prospective SurveyPulmonary Center, Boston University School of Medicine; and Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts Correspondence and requests for reprints should be addressed to Jussi J. Saukkonen, M.D., Pulmonary Center, 80 East Concord Street, R-304, Boston, MA 02118. E-mail: jsaukk{at}bu.edu
Treatment of latent tuberculosis (TB) infection (LTBI) is essential for the elimination of TB in the United States, but treatment is often not completed. Little is known about patients' reasons for not completing treatment. We hypothesized that certain health beliefs, lifestyle, and clinic- and regimen-related barriers to provision of care could predict non-completion of LTBI treatment.
Methods: We administered a survey in English, Chinese, or Spanish to patients with LTBI at the first TB clinic visit. Using Results: 217 patients, 90% foreign-born, completed the survey, and 28.6% of which finished at least 6 mo of isoniazid under usual clinic conditions. Multivariate analysis identified two independent predictors of non-completion: low risk perception of progressing to active TB without LTBI treatment (odds ratio [OR], 0.31 [0.13–0.72], 95% confidence interval [CI]), p = 0.007, accounting for 20% of non-completers, and not wanting venipuncture (OR, 0.43 [0.22–0.85], 95% CI), p = 0.015, accounting for 37% of non-completers. Another 18% shared both predictors; thus these two predictors accounted for 75% of non-completers in total. Conclusions: Patients assess LTBI treatment risks and inconveniences relative to low perceived benefits at treatment outset. Predictors of LTBI treatment non-completion are identifiable at the first visit. Targeting TB high-risk individuals, minimizing inconveniences, further education, and use of diagnostic tests with improved specificity for TB may address these concerns.
Key Words: isoniazid • latent tuberculosis infection • prospective survey As the incidence of tuberculosis (TB) disease has decreased in the United States, the diagnosis and treatment of latent TB infection (LTBI) has assumed increasing importance. Standard LTBI treatment is daily isoniazid for 6 to, preferably, 9 mo, with completion rates often ranging from 20 to 60% for 6 mo of isoniazid (1, 2). Limited objective information is available regarding factors influencing adherence to LTBI treatment. We hypothesized that barriers to the provision of TB care, related to regimen or clinic, or in beliefs regarding tuberculosis or health and lifestyle in general, could be identified at the outset of treatment. We have presented preliminary findings from this study previously in the form of an abstract (3).
Human Studies Approval The Institutional Review Board of Boston University Medical Campus approved this study and the surveys employed. Participation in the study was voluntary and not linked to treatment.
TB Clinic Usual Procedures
Study Enrollment
Survey Administration
Data Analysis
Respondent Demographics and TB Risk Factors Surveys were completed by a total of 217 individuals: 148 in English, 22 in Spanish, and 47 in Chinese. The respondents were 90% foreign-born and included a substantial proportion of racial minorities (Table 1). There were more women among survey participants (54.4%, versus 44.2% men). A majority of participants were under the age of 35 (52%), with a median age of 34 yr. Participant demographics were similar to those of patients with LTBI who were offered treatment at this clinic (4). The most common TB risk factor was foreign-birth in a TB endemic country. Approximately one third of participants received their follow-up at neighborhood health centers.
Completion of LTBI Treatment A total of 29.0% completed at least 6 mo of isoniazid, with 19.4% completing the full 9-mo course and 9.2% completing between 6 and 9 mo of treatment. Nearly two-thirds (65.9%) of the participants self-discontinued treatment either by declaration or by not returning to the clinic within 3 mo. Another 5.3% had treatment discontinued by a TB provider due to adverse events, including itching, rash, fatigue, malaise, headache, dizziness, nausea, abdominal discomfort, and diarrhea.
Predictors of LTBI Treatment Non-Completion
Regimen and Clinic-related Barriers to Care
Health Beliefs Univariate predictors of treatment non-completion included not having a primary care physician (RR, 0.48 [0.25–0.87], p = 0.013) and not valuing regular visits to a health care professional for health maintenance (RR, 0.27 [0.07–0.85], p = 0.019) (Table 3). Patients who perceived a low risk for developing active TB without LTBI treatment were significantly less likely to complete LTBI treatment (RR, 0.35 [0.18–0.67], p = 0.001). This was also true for those who completed only the English version of the survey (RR, 0.26 [0.10–0.62], 95% CI, p = 0.001). Multivariate analysis also identified low TB risk perception as a significant predictor of treatment non-completion (OR, 0.31 [0.13–0.72], 95% CI, p = 0.007). This view alone accounted for 37% of non-completers and was a shared predictor among 18% of all non-completers. The majority of respondents felt that they were not infected with TB, and believed that BCG vaccine would prevent the development of TB, but these views did not predict failure to complete treatment. Reluctance to have venipuncture, and perception of low TB risk, as both independent and shared predictors, accounted for 75% of non-completers.
From a broad array of patients' health-related concerns, we identified two predictors of non-completion of 6 mo of isoniazid for treatment of LTBI by multivariate analysis, which together accounted for 75% of non-completers. Patients who perceived a low risk of progressing from LTBI to TB disease were significantly less likely to complete 6 mo of isoniazid. Patients with LTBI may perceive the threat, or severity of illness, from TB disease as potentially high, but their risk of disease incidence as low (5). Low risk perception alone was a predictor of non-completion among 37% of non-completers. This view is likely related to the finding that only 25% of our survey participants (Table 3) unequivocally accepted the diagnosis of LTBI. Non-acceptance of LTBI diagnosis may also reflect fear of therapeutic consequences: adverse effects, follow-up visits, hidden costs, or stigma (6–8). BCG vaccination, likely received by the majority of our foreign-born study population, is often thought to cause or confound a positive tuberculin skin test (TST) result (8, 9), although considerable epidemiologic evidence is available to enhance the interpretation of TST results in those vaccinated (1, 9–12). Furthermore, only 6.3% of survey participants categorically doubted the protective efficacy of BCG (Table 3), likely further contributing to the perception of low TB disease risk. Patients who perceive low risk of progressing to TB disease are likely to see little benefit in LTBI treatment. The most significant patient concern associated with LTBI treatment was reluctance to have venipuncture, expressed by approximately half of the survey participants. This alone was a predictor of non-completion in 20% of non-completers . This view was expressed before actually having venipuncture, which was performed in the Clinical Laboratory at a separate location. Venipuncture seems to have been a greater issue for patients than concern about isoniazid toxicity, which, although held by the majority of survey participants, was not associated with failure to complete treatment (Table 3). Historically, a significant proportion of our TB clinic patients have been considered at risk for isoniazid hepatotoxicity, leading to the transaminase-monitoring regime described. Current CDC/ATS recommendations suggest that clinical rather than biochemical monitoring may be employed in most patients without risk factors for hepatotoxicity undergoing LTBI treatment (1). This practice, rather than a wider-ranging biochemical monitoring policy, may enhance adherence to treatment of LTBI. There were several potential limitations to our study. Other reasons for failure to complete may have emerged after treatment initiation and were not detected in this study. Among those who did not return for follow-up visits, there might have been some with adverse events associated with non-adherence to treatment of LTBI (8, 14, 15). The threshold for stopping isoniazid due to adverse events is likely to differ between providers and patients. Adverse events have been reported to occur in 14 to 18% (14, 16), but in our study were relatively infrequent and rarely treatment limiting. Patient education may have varied among multiple clinic providers. Three languages were used for the performance of this study, with small accrual in two of the three groups. A larger study may have permitted the identification of language group–specific risks for non-completion. While some studies have found demographic associations (8, 14) with failure to complete isoniazid LTBI treatment, we did not, and this appears to be an inconsistent finding (1).
We have shown that at the first clinic visit patients have specific views regarding the risks, inconveniences, and benefits of LTBI treatment, which are associated with treatment non-adherence. Further studies are needed to determine whether the identified predictors can be generalized, or if others emerge. The overall treatment completion rate was low in this study and was no better for the highest TB risk groups, although similar rates have been reported elsewhere (2, 8, 14, 17, 18). Efforts to treat LTBI are more likely to succeed in patients who perceive a greater risk from TB than the risks and inconveniences of the treatment regimen, necessitating lucid LTBI patient education addressing these concerns. Our findings also reinforce current recommendations to target individuals at high risk of TB for testing and treatment (1). Improved diagnostic tests are now becoming available, which can more accurately draw a distinction between BCG-vaccinated individuals and TB-infected individuals, for example, such as assays of in vitro IFN-
The authors thank members of the Centers for Disease Control's TB Trials Consortium Recruitment & Retention Committee, and Richard Menzies, M.D., for suggestions regarding survey development; they also appreciate the help of Susan Yoon, R.N., N.P., in implementing this project.
This study was funded by Boston University Medical School Summer Research Program. Originally Published in Press as DOI: 10.1164/rccm.200510-1667OC on June 29, 2006 Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. Received in original form October 25, 2005; accepted in final form June 27, 2006
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ABSTRACT
METHODS
2 and logistic regression analysis, we assessed demographics, TB risk factors, and survey responses as predictors of non-completion of 6 mo of isoniazid. 
release in response to Mycobacterium tuberculosis–specific antigens (
