Transmission of Mycobacterium Tuberculosis Associated with Failed Completion of Treatment for Latent Tuberculosis Infection --- Chickasaw County, Mississippi, June 1999--March 2002

During June 1999--March 2002, a total of 16 tuberculosis (TB) cases were reported from Chickasaw County, Mississippi (2000 population: 19,440), corresponding to annual TB incidences of 20.5--27.6 cases per 100,000 population. In comparison, annual TB incidences for Mississippi during the same period decreased from 7.8 to 5.4 cases per 100,000 population. This report summarizes the results of an investigation of the patients and their contacts and demonstrates the need for strategies to increase the proportion of infected contacts that successfully complete treatment for latent TB infection (LTBI).

During April--May 1, 2002, the Mississippi State Department of Health (MSDH) conducted an epidemiologic investigation of the high incidence of TB in Chickasaw County. Patients were interviewed, and health department medical records were reviewed for clinical data. Restriction fragment length polymorphism (RFLP) analysis using IS6110 was performed on all culture isolates. For contacts, LTBI was defined as infection in a patient with a tuberculin skin test (TST) >5 mm induration and no evidence of TB disease. Contact investigation logs were reviewed and health department records used to establish outcomes of treatment for LTBI.

The median age of the 16 TB patients was 31 years (range: 2--64 years); five (31%) were aged <16 years. Ten (63%) patients were male, and 15 (94%) were black. All 16 TB patients were born in the United States and were human immunodeficiency virus (HIV)-seronegative. For 11 patients from whom sputum specimens were obtained for bacteriologic examination, eight (73%) were culture-positive for Mycobacterium tuberculosis, of whom six (55%) also were sputum-smear positive for acid-fast bacilli. RFLP analysis performed on all eight culture-positive isolates showed seven (88%) with matching 10-band patterns . The contact investigations and matching RFLP patterns suggest recent transmission of M. tuberculosis. Isolates from all culture-confirmed patients were susceptible to first-line anti-TB drugs (isoniazid, rifampin, pyrazinamide, and ethambutol). All 16 patients successfully completed a CDC-recommended course of treatment.

Among the 16 TB patients, five had been diagnosed previously with LTBI as a result of TB contact investigations; patients ranged in age from 28 to 51 years, and four (80%) had a history of regular alcohol use. MSDH attempted to treat all five patients, but all had either refused or stopped treatment. The patients subsequently progressed to active TB and became sources of infection for an additional 10 TB patients, including the five patients aged <16 years.

The 16 TB patients identified 364 contacts (median: 19 contacts per case; range: 6--90). The patients, with the assistance of a health department worker, classified 350 (96%) of these contacts as either close (63%) or casual (37%). The 364 contacts represented 253 persons. As of May 1, 2002, TST screening, including if indicated a 10--12 week follow-up TST, was completed for 230 (91%) of the 253 persons. TST screening results and subsequent evaluation (including chest radiograph, and if indicated, sputum examination) detected LTBI in 67 (26%) persons. Patients with LTBI were not offered HIV testing and counseling routinely.

Adults with LTBI were offered a 9-month regimen of daily self-administered isoniazid, dispensed at 1-month increments. Directly observed treatment for LTBI was offered both to children and those adults with known HIV infection. Treatment for LTBI was defined as complete if the patient had retrieved >6 months of isoniazid and was assessed by a supervising nurse as having completed treatment. Among the 67 persons with LTBI diagnosed, treatment was initiated in 57 (85%), discontinued in nine (13%) because of side effects, and completed in 36 (54%).

As a result of this investigation, patients in Chickasaw County with untreated LTBI were again offered treatment. To enhance completion of treatment for LTBI, MSDH hired additional outreach workers and expanded the use of direct observation of treatment for LTBI. MSDH staff targeted the use of direct observation to adult patients considered at high risk for treatment default, including persons who regularly used alcohol and those who had interrupted treatment previously. MSDH also is considering the use of incentives such as grocery coupons.

To identify barriers to LTBI treatment completion, MSDH in partnership with CDC, conducted three focus groups with TB-control staff, patients adherent to treatment for LTBI, and patients nonadherent to treatment for LTBI. Focus group participants suggested that TB-control staff persistence and flexibility helped adherence to treatment for LTBI, as did participation of sex and race-matched community outreach workers. Many participants cited community and family stigma as treatment barriers and identified a need for additional information about the importance of LTBI treatment.

To address patient concerns and misconceptions, MSDH has initiated ongoing individual counseling during treatment for LTBI. Furthermore, MSDH has engaged community leaders, churches, and civic organizations to disseminate TB-related educational messages.

Reported by: T Chamblee, D Hartley, M Holcombe, MPPA, K Parham, P Upchurch, RM Webb, MD, Mississippi Dept of Health. AG Robillard, PhD, Rollins School of Public Health of Emory Univ, Atlanta, Georgia. L Diem, B Metchock, PhD, Div of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases; N DeLuca, MA, PD McElroy, PhD, T Navin, MD, W Walton, MEd, Div of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention; Div of Applied Public Health Training, Epidemiology Program Office; PK Dewan, MD, EIS Officer, CDC.

Editorial Note:

The findings in this investigation underscore the need to ensure completion of treatment for LTBI by infected contacts of TB patients. Integral components of successful contact investigations include patient interview, contact identification, and medical evaluation for active TB and LTBI (1), followed by successful initiation and completion of treatment for LTBI.

This investigation found that contact identification and evaluation were thorough and effective. For example, the median number of contacts identified and the proportion of contacts evaluated for LTBI were higher than those found in five other TB programs in a recent study of contact investigations (1,2). Despite these efforts, patients with untreated LTBI subsequently developed active TB and served as the source of ongoing TB transmission in the community. This contributed to the persistently high TB incidences in Chickasaw County.

The discovery of LTBI during contact investigation suggests recent infection. Because the risk for progression from infection to active disease is highest during the first 2 years following infection, priority should be given to treating infected contacts identified during contact investigations (3). Studies among populations at highest risk for loss to follow-up (e.g., injection-drug users, released jail inmates, and homeless persons) have shown that the use of incentives and direct observation of treatment substantially improves LTBI treatment completion rates (4--7). Among high-risk groups, these interventions might be cost-effective (8). Additional evaluation is needed to determine if patients outside these high-risk groups might benefit from incentives and direct observation of treatment. Qualitative evaluation of patient, staff, and system barriers might identify community-specific barriers to treatment initiation and completion. In Chickasaw County, focus group findings suggested that ongoing individual counseling for patients with LTBI and efforts to reduce stigma through community engagement might promote completion of treatment for LTBI. A follow-up evaluation might help determine the effectiveness of these interventions.

Completion of treatment for LTBI is the final component of an effective contact investigation. If the actual number of infected contacts substantially exceeds those identified and successfully screened, the treatment completion rate might overestimate the contact investigation effectiveness (2). To effectively interrupt M. tuberculosis transmission, successful implementation of all elements of contact investigation is necessary (8). Treating patients with LTBI increasingly challenges the response capacity of state and local TB-control programs (9). Although the decline of TB in blacks has paralleled the overall national trends, in 2001, incidence among non-Hispanic blacks remained 8.6 times higher than incidence among whites (10). TB-control programs serving black communities with high TB incidence should have the resources necessary to control TB and reduce this health disparity.

References

1. Reichler MR, Reves R, Bur S, et al. Evaluation of investigations conducted to detect and prevent transmission of tuberculosis. JAMA 2002;287:991--5.
2. Reichler MR, Reves R, Bur S, et al. Treatment of latent tuberculosis infection in contacts of new tuberculosis cases in the United States. South Med J 2002;95:414--20.
3. CDC. The use of preventive therapy for tuberculous infection in the United States: recommendations of the Advisory Committee for Elimination of Tuberculosis. MMWR 1990;39(No. RR-8):9--12.
4. Chaisson RE, Barnes GL, Hackman J, et al. A randomized, controlled trial of interventions to improve adherence to isoniazid preventative therapy to prevent tuberculosis in injection drug users. Am J Med 2001;110:610--5.
5. White MC, Gournis E, Kawamura M, et al. Effect of directly observed preventative therapy for latent tuberculosis infection in San Francisco. Int J Tuberc Lung Dis 2003;7:30--5.
6. Tulsky JP, Pilote L, Hahn J, et al. Adherence to INH prophylaxis in the homeless: a randomized controlled trial. Arch Intern Med 2000;160:697--702.
7. Snyder DC, Paz EA, Mohle-Boetani JC, et al. Tuberculosis prevention in methadone maintenance clinics: effectiveness and cost-effectiveness. Am J Respir Crit Care Med 1999;160:178--85.
8. CDC. Screening for tuberculosis and tuberculosis infection in high-risk populations. Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR 1995;44(No. RR-11):19--34.
9. CDC. Tuberculosis elimination revisited: obstacles, opportunities, and a renewed commitment. Recommendations of the Advisory Committee for Elimination of Tuberculosis. MMWR 1999;48(No. RR-9):1--13.
10. CDC. Reported tuberculosis in the United States, 2001. Atlanta, Georgia: U.S. Department of Health and Human Services, CDC, 2001.

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