Validation of genotype cluster investigations for Mycobacterium tuberculosis: application results for 44 clusters from four heterogeneous United States jurisdictions.

BACKGROUND: Tracking the dissemination of specific Mycobacterium tuberculosis (Mtb) strains using genotyped Mtb isolates from tuberculosis patients is a routine public health practice in the United States. The present study proposes a standardized cluster investigation method to identify epidemiologic-linked patients in Mtb genotype clusters. The study also attempts to determine the proportion of epidemiologic-linked patients the proposed method would identify beyond the outcome of the conventional contact investigation. METHODS: The study population included Mtb culture positive patients from Georgia, Maryland, Massachusetts and Houston, Texas. Mtb isolates were genotyped by CDC's National TB Genotyping Service (NTGS) from January 2006 to October 2010. Mtb cluster investigations (CLIs) were conducted for patients whose isolates matched exactly by spoligotyping and 12-locus MIRU-VNTR. CLIs were carried out in four sequential steps: (1) Public Health Worker (PHW) Interview, (2) Contact Investigation (CI) Evaluation, (3) Public Health Records Review, and (4) CLI TB Patient Interviews. Comparison between patients whose links were identified through the study's CLI interviews (Step 4) and patients whose links were identified earlier in CLI (Steps 1-3) was conducted using logistic regression. RESULTS: Forty-four clusters were randomly selected from the four study sites (401 patients in total). Epidemiologic links were identified for 189/401 (47 %) study patients in a total of 201 linked patient-pairs. The numbers of linked patients identified in each CLI steps were: Step 1 - 105/401 (26.2 %), Step 2 - 15/388 (3.9 %), Step 3 - 41/281 (14.6 %), and Step 4 - 28/119 (30 %). Among the 189 linked patients, 28 (14.8 %) were not identified in previous CI. No epidemiologic links were identified in 13/44 (30 %) clusters. CONCLUSIONS: We validated a standardized and practical method to systematically identify epidemiologic links among patients in Mtb genotype clusters, which can be integrated into the TB control and prevention programs in public health settings. The CLI interview identified additional epidemiologic links that were not identified in previous CI. One-third of the clusters showed no epidemiologic links despite being extensively investigated, suggesting that some improvement in the interviewing methods is still needed.

Mortality hazard and survival after tuberculosis treatment.

OBJECTIVES: We compared mortality among tuberculosis (TB) survivors and a similar population. METHODS: We used local health authority records from 3 US sites to identify 3853 persons who completed adequate treatment of TB and 7282 individuals diagnosed with latent TB infection 1993 to 2002. We then retrospectively observed mortality after 6 to 16 years of observation. We ascertained vital status as of December 31, 2008, using the Centers for Disease Control and Prevention's National Death Index. We analyzed mortality rates, hazards, and associations using Cox regression. RESULTS: We traced 11 135 individuals over 119 772 person-years of observation. We found more all-cause deaths (20.7% vs 3.1%) among posttreatment TB patients than among the comparison group, an adjusted average excess of 7.6 deaths per 1000 person-years (8.8 vs 1.2; P < .001). Mortality among posttreatment TB patients varied with observable factors such as race, site of disease, HIV status, and birth country. CONCLUSIONS: Fully treated TB is still associated with substantial mortality risk. Cure as currently understood may be insufficient protection against TB-associated mortality in the years after treatment, and TB prevention may be a valuable opportunity to modify this risk.

The health-system benefits and cost-effectiveness of using Mycobacterium tuberculosis direct nucleic acid amplification testing to diagnose tuberculosis disease in the United States.

BACKGROUND: The utility of Mycobacterium tuberculosis direct nucleic acid amplification testing (MTD) for pulmonary tuberculosis disease diagnosis in the United States has not been well described. METHODS: We analyzed a retrospective cohort of reported patients with suspected active pulmonary tuberculosis in 2008-2010 from Georgia, Hawaii, Maryland, and Massachusetts to assess MTD use, effectiveness, health-system benefits, and cost-effectiveness. RESULTS: Among 2140 patients in whom pulmonary tuberculosis was suspected, 799 (37%) were M. tuberculosis-culture-positive. Eighty percent (680/848) of patients having acid-fast-bacilli-smear-positive specimens had MTD performed; MTD positive-predictive value (PPV) was 98% and negative-predictive value (NPV) was 94%. Nineteen percent (240/1292) of patients having smear-negative specimens had MTD; MTD PPV was 90% and NPV was 88%. Among patients suspected of tuberculosis but not having MTD, smear PPV for lab-confirmed tuberculosis was 77% and NPV 78%. Compared with no MTD, MTD significantly decreased time to diagnosis in patients with smear-positive/MTD-positive specimens, decreased respiratory isolation for patients having smear-positive/MTD-negative/culture-negative specimens, decreased outpatient days of unnecessary tuberculosis medications, and reduced resources expended on contact investigation. While MTD generally cost more than no MTD, incremental cost savings occurred in patients with human immunodeficiency virus (HIV) or homelessness to diagnose or to exclude tuberculosis, and in patients with substance abuse having smear-negative specimens to exclude tuberculosis. CONCLUSIONS: MTD improved diagnostic accuracy and timeliness and reduced unnecessary respiratory isolation, treatment, and contact investigations. It was cost saving in patients with HIV, homelessness, or substance abuse, but not in others.

Risk of progression to active tuberculosis among foreign-born persons with latent tuberculosis.

BACKGROUND: Increased risk for tuberculosis (TB) disease has been identified in foreign-born persons in the United States, particularly during the first 5 years after their arrival in the United States. This could be explained by undetected TB disease at entry, increased prevalence of latent TB infection (LTBI), increased progression from LTBI to TB, or a combination of these factors. METHODS: We performed a cluster analysis of TB cases in Boston and a case-control study of risk factors for TB with an unclustered isolate among Boston residents with LTBI to determine whether such persons have an increased risk for reactivation of disease. RESULTS: Of 321 case patients with TB seen between 1996 and 2000, 133 isolates were clustered and 188 were not. In multivariate analysis, foreign birth was associated with an unclustered isolate (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2 to 3.8; p < 0.01), while being a close contact of a TB case was negatively associated (OR, 0.22; 95% CI, 0.07 to 0.73; p = 0.02). When 188 TB patients with unclustered isolates were compared to 188 age-matched control subjects with LTBI, there was no association between the occurrence of TB and foreign birth (OR, 0.71; 95% CI, 0.42 to 1.3); among foreign-born persons, there was no association between the occurrence of TB and being in the United States

Civil Surgeon Tuberculosis Evaluations for Foreign-Born Persons Seeking Permanent U.S. Residence.

Foreign-born persons in the United States seeking to adjust their status to permanent resident must undergo screening for tuberculosis (TB) disease. Screening is performed by civil surgeons (CS) following technical instructions by the Centers for Disease Control and Prevention. From 2011 to 2012, 1,369 practicing CS in California, Texas, and New England were surveyed to investigate adherence to the instructions. A descriptive analysis was conducted on 907 (66%) respondents. Of 907 respondents, 739 (83%) had read the instructions and 565 (63%) understood that a chest radiograph is required for status adjustors with TB symptoms; however, only 326 (36%) knew that a chest radiograph is required for immunosuppressed status adjustors. When suspecting TB disease, 105 (12%) would neither report nor refer status adjustors to the health department; 91 (10%) would neither start treatment nor refer for TB infection. Most CS followed aspects of the technical instructions; however, educational opportunities are warranted to ensure positive patient outcomes.

Predictors of failure to complete treatment for latent tuberculosis infection.

OBJECTIVE: Low rates of completion of treatment for latent tuberculosis infection (LTBI) limit its usefulness as a strategy for elimination of tuberculosis (TB) in the United States. This retrospective cohort study assessed predictors of completion of LTBI treatment among patients seen at an urban United States TB clinic in 1998. METHODS: A retrospective cohort study of acceptance and completion of LTBI treatment among patients first seen in a TB clinic in 1998 was performed. RESULTS: Of 2621 persons with a positive tuberculosis skin test (TST), 1723 were offered treatment and 1572 (91.2%) accepted. Of the 1572 who accepted, treatment was completed by 607 (38.6%). Of those persons who failed to complete treatment, 517/965 (54%) dropped out before the end of the first month of the course. Among 1375 persons under 35 years of age who initiated LTBI treatment, failure to complete was associated with birth in Haiti (OR=2.17, CI(95%) 1.49-3.17) or the Dominican Republic (OR=1.93, CI(95%) 1.08-3.43). CONCLUSION: These results suggest that country-specific cultural and behavioral factors may contribute to failure to complete LTBI treatment, and that interventions to increase completion should focus on the first month after initiation.

Health department costs of managing persons with suspected and noncounted tuberculosis in New York City, Three Texas counties, and Massachusetts.

OBJECTIVES: To describe persons with suspected (did not meet the national tuberculosis [TB] surveillance case definition) and noncounted TB (met the TB case definition but transferred and were counted by another jurisdiction) and estimate costs incurred by public health departments for managing them. METHODS: We reviewed TB registry, medical records, budgets, bills, salaries, organizational charts, and travel/activity logs from the year 2000 at health departments in New York City (NYC), three Texas (TX) counties (El Paso, Hidalgo, and Webb), and Massachusetts (MA). We also interviewed or observed personnel to estimate the time spent on activities for these patients. RESULTS: In 2000, NYC and MA had more persons with suspected (n = 2,996) and noncounted (n = 163) TB than with counted (n = 1,595) TB. TX counties had more persons with counted TB (n = 179) than with suspected (n = 55) and noncounted (n = 15) TB. Demographic and clinical characteristics varied widely. For persons with suspected TB, NYC spent an estimated $1.7 million, with an average cost of $636 for each person; TX counties spent $60,928 ($1,108 per patient); and MA spent $1.1 million ($3,330 per patient). For persons with noncounted TB, NYC spent $303,148 ($2,180 per patient), TX counties spent $40,002 ($2,667 per patient), and MA spent $84,603 ($3,525 per patient). CONCLUSIONS: Health departments incurred substantial costs in managing persons with suspected and noncounted TB. These costs should be considered when allocating TB program resources.

Genotyping analyses of tuberculosis cases in U.S.- and foreign-born Massachusetts residents.

We used molecular genotyping to further understand the epidemiology and transmission patterns of tuberculosis (TB) in Massachusetts. The study population included 983 TB patients whose cases were verified by the Massachusetts Department of Public Health between July 1, 1996, and December 31, 2000, and for whom genotyping results and information on country of origin were available. Two hundred seventy-two (28%) of TB patients were in genetic clusters, and isolates from U.S-born were twice as likely to cluster as those of foreign-born (odds ratio [OR] 2.29, 95% confidence interval [CI] 1.69 to 3.12). Our results suggest that restriction fragment length polymorphism analysis has limited capacity to differentiate TB strains when the isolate contains six or fewer copies of IS6110, even with spoligotyping. Clusters of TB patients with more than six copies of IS6110 were more likely to have epidemiologic connections than were clusters of TB patients with isolates with few copies of IS6110 (OR 8.01, 95%; CI 3.45 to 18.93).

Impact of genotyping of Mycobacterium tuberculosis on public health practice in Massachusetts.

Massachusetts was one of seven sentinel surveillance sites in the National Tuberculosis Genotyping and Surveillance Network. From 1996 through 2000, isolates from new patients with tuberculosis (TB) underwent genotyping. We describe the impact that genotyping had on public health practice in Massachusetts and some limitations of the technique. Through genotyping, we explored the dynamics of TB outbreaks, investigated laboratory cross-contamination, and identified Mycobacterium tuberculosis strains, transmission sites, and accurate epidemiologic links. Genotyping should be used with epidemiologic follow-up to identify how resources can best be allocated to investigate genotypic findings.

Estimated costs of false laboratory diagnoses of tuberculosis in three patients.

We estimated direct medical and nonmedical costs associated with a false diagnosis of tuberculosis (TB) caused by laboratory cross-contamination of Mycobacterium tuberculosis cultures in Massachusetts in 1998 and 1999. For three patients who received misdiagnoses of active TB disease on the basis of laboratory cross-contamination, the costs totaled U.S. dollars 32618. Of the total, 97% was attributed to the public sector (local and state health departments, public health hospital and laboratory, and county and state correctional facilities); 3% to the private sector (physicians, hospitals, and laboratories); and <1% to the patient. Hospitalizations and inpatient tests, procedures, and TB medications accounted for 69% of costs, and outpatient TB medications accounted for 18%. The average cost per patient was dollars 10873 (range, dollars 1033-dollars 21306). Reducing laboratory cross-contamination and quickly identifying patients with cross-contaminated cultures can prevent unnecessary and potentially dangerous treatment regimens and anguish for the patient and financial burden to the health-care system.