Estimating tuberculosis cases and their economic costs averted in the United States over the past two decades.

BACKGROUND: Following a concerted public health response to the resurgence of tuberculosis (TB) in the United States in the late 1980s, annual TB incidence decreased substantially. However, no estimates exist of the number and cost savings of TB cases averted. METHODS: TB cases averted in the United States during 1995-2014 were estimated: Scenario 1 used a static 1992 case rate; Scenario 2 applied the 1992 rate to foreign-born cases, and a pre-resurgence 5.1% annual decline to US-born cases; and a statistical model assessed human immunodeficiency virus and TB program indices. We applied the cost of illness to estimate the societal benefits (costs averted) in 2014 dollars. RESULTS: During 1992-2014, 368 184 incident TB cases were reported, and cases decreased by two thirds during that period. In the scenarios and statistical model, TB cases averted during 1995-2014 ranged from approximately 145 000 to 319 000. The societal benefits of averted TB cases ranged from US$3.1 to US$6.7 billion, excluding deaths, and from US$6.7 to US$14.5 billion, including deaths. CONCLUSIONS: Coordinated efforts in TB control and prevention in the United States yielded a remarkable number of TB cases averted and societal economic benefits. We illustrate the value of concerted action and targeted public health funding.

Human tuberculosis caused by Mycobacterium bovis in the United States, Latin America and the Caribbean.

Human tuberculosis (TB) caused by Mycobacterium bovis appears to be rare in most of the region of the Americas, although some localities have reported an unusually high prevalence of M. bovis among human TB cases (e.g., San Diego, CA, USA; parts of Mexico). As surveillance data are lacking in many countries, there is substantial uncertainty regarding actual incidence. M. bovis is most often not identified, as the diagnosis of TB is made by smear microscopy alone or using egg-containing culture media lacking pyruvate. Where human M. bovis cases have been studied in the region, they appear to be associated with ingestion of unpasteurized dairy products, or with airborne acquired infection in animal keepers and meat industry workers from countries where bovine TB remains a problem. Human-to-human transmission of M. bovis does occur, but appears to account for a very small proportion of cases. Efforts to eradicate M. bovis in humans in the Americas should therefore be directed at eradicating the disease in cattle, increasing pasteurization of dairy products and providing education about the dangers of consuming unpasteurized dairy products.

Tuberculosis in humans and its epidemiology, diagnosis and treatment in the United States.

Tuberculosis (TB) is a pulmonary and systemic disease caused by Mycobacterium tuberculosis complex species. TB is spread from person to person by airborne transmission. Several factors determine the probability of transmission, including the infectiousness of the source patient and the nature of the environment where exposure occurs. This initial infection (primary TB) rapidly progresses to disease in some persons (especially children and immunocompromised persons), but resolves spontaneously in most individuals. This condition in which the organism lies dormant is known as latent TB infection (LTBI). In the United States, the diagnosis of LTBI is made with either the tuberculin skin test or an interferon-gamma release assay. LTBI is treated with isoniazid (INH; usually for 9 months) to prevent progression to TB disease. Up to 5% of immunocompetent persons will progress to TB disease at some time in the future, even decades after infection, if they are not treated for LTBI. Pulmonary TB disease is diagnosed using a combination of chest radiography and microscopic examination, culture and nucleic acid amplification testing of sputum. Treatment of drug-susceptible TB consists of at least 6 months of an INH and rifampin-containing regimen (with ethambutol and pyrazinamide for the first 2 months). In the United States, drug-resistant TB is relatively rare (approximately 1% of all patients), and is treated with an 18-24 month individualized regimen based on drug susceptibility test results.

Tuberculosis in humans and animals: an overview.

Tuberculosis (TB) is a significant disease for both humans and animals. Susceptibility to Mycobacterium tuberculosis is relatively high in humans, other primates and guinea pigs. Cattle, rabbits and cats are susceptible to M. bovis and are quite resistant to M. tuberculosis. Wild hoofed stock is generally susceptible to M. bovis, but few reports are available on the isolation of M. tuberculosis. Swine and dogs are susceptible to both M. bovis and M. tuberculosis. M. bovis accounts for only a small percentage of the reported cases of TB in humans; however, it is a pathogen of significant economic importance in wild and domestic animals around the globe, especially in countries where little information is available on the incidence of M. bovis infection in humans. Unlike transmission of M. bovis from cattle to humans, the role of human-to-human airborne transmission in the spread of M. bovis has been somewhat controversial. Investigations are needed to elucidate the relative importance of M. bovis on TB incidence in humans, especially in developing countries. Efforts should be concentrated in countries where human immunodeficiency virus (HIV) infection is widespread, as HIV-infected individuals are more susceptible to mycobacterial disease. Eradication of M. bovis in cattle and pasteurisation of dairy products are the cornerstones of the prevention of human disease.

Clinical diagnosis of tuberculosis by specialists and non-specialists.

In resource-limited settings, tuberculosis (TB) is often diagnosed by non-physicians using the acid-fast bacilli (AFB) smear only. This study examines the diagnostic accuracy of various clinicians using patient-risk history, radiography and AFB smear. A total of 321 physicians, nurses and medical students evaluated 22 profiles of TB suspects and quantified their clinical suspicion (1-99%). Culture results determined diagnostic accuracy. Overall, high-level physician training may not be required; nurses working on TB, given radiograph readings, were as accurate as TB physicians and more accurate than other physicians and clinicians. By considering clinical findings with smear results, TB specialists were significantly more accurate than smear results alone.

Isoniazid- and rifampin-resistant tuberculosis in San Diego County, California, United States, 1993-2002.

SETTING: A local tuberculosis (TB) control program. OBJECTIVES: To measure trends in isoniazid (INH) and rifampin (RMP) resistance and identify associated factors. DESIGN: Retrospective review. RESULTS: Of 2883 isolates obtained from TB patients reported between 1993 and 2002, 287 (10%) were resistant to INH, 11 (< 1%) were resistant to RMP, and 40 (1%) were resistant to both (multidrug resistance [MDR]). There were no linear trends over time. Eighty-one per cent of patients with INH resistance and 85% with MDR were born outside the United States. Sixty-three per cent of patients with drug resistance and prior TB treatment were treated outside the US. INH resistance was associated with race/ethnicity and prior treatment, RMP resistance with human immunodeficiency virus (HIV) infection, and MDR with non-US birth and prior treatment. Patients with INH- and RMP-susceptible or INH-resistant TB had higher percentages of treatment completion and sputum culture conversion than patients with RMP-resistant or MDR-TB. CONCLUSIONS: INH and RMP resistance remained stable between 1993 and 2002. Because most patients with drug resistance were infected or initially treated outside the US, future reductions in drug resistance will depend not only on local and national efforts, but also on the success of global interventions.

Treatment of Mycobacterium bovis infected tuberculosis patients: San Diego County, California, United States, 1994-2003.

SETTING: A local tuberculosis control program. OBJECTIVE: To examine treatment completion rates of patients with Mycobacterium bovis disease and compare them with those of patients with M. tuberculosis disease. DESIGN: Retrospective review of data from a tuberculosis surveillance computer database. RESULTS: Data from 167 M. bovis patients and 928 M. tuberculosis patients were examined. Rates of treatment completion were not significantly different (78% vs. 82%, chi2 = 1.60, P = 0.174), although death was more frequent among M. bovis patients (15% vs. 7%). The median time to treatment completion was 94 days longer for M. bovis patients. CONCLUSION: Overall, treatment completion rates of M. bovis and M. tuberculosis patients were comparable, although the death rate was higher for M. bovis patients. The latter finding may be related to a particularly high death rate among HIV-infected M. bovis patients. Therapy duration was longer for M. bovis patients, probably because resistance to pyrazinamide prevented the use of a short-course (6-month) regimen.

Identification of a familial cluster of pulmonary Mycobacterium bovis disease.

SETTING: Local public health department. DESIGN: Retrospective review of a cluster of three pulmonary Mycobacterium bovis cases occurring in a family, with genotyping of M. bovis strains isolated from the family members. RESULTS: The genotypes of the M. bovis isolates were identical, as determined by three different methods: IS6110 restriction fragment length polymorphism, spoligoytping and mycobacterial interspersed repetitive units-variable number tandem repeat analyses. CONCLUSION: The identification of three acid-fast bacilli (AFB) smear-positive pulmonary M. bovis cases, presenting in a single family and caused by an identical strain, suggests that person-to-person transmission of this organism may have occurred, although infection of one or more family members through ingestion of a contaminated dairy product could not be excluded.

Contact investigation for cases of pulmonary Mycobacterium bovis.

SETTING: A local tuberculosis control program in San Diego County, California. OBJECTIVE: To determine the yield of contact investigations of pulmonary Mycobacterium bovis cases. DESIGN: Retrospective review of medical records comparing tuberculin skin test (TST) conversion rates found in contact investigations of pulmonary M. bovis cases to conversion rates found in contact investigations of pulmonary M. tuberculosis cases. RESULTS: For the years 1994-2001, we identified 77 contacts of pulmonary M. bovis cases and 469 contacts of M. tuberculosis cases that met the study criteria. TST conversion rates were not significantly different based on species of the source case (13% for M. bovis, 15% for M. tuberculosis, P = 0.20). This finding was also observed when the results were stratified by presence of a cavity on chest X-ray, history of cough at diagnosis and human immunodeficiency virus (HIV) status of the source case. CONCLUSION: These results suggest that contact investigations for pulmonary M. bovis cases should be conducted in the same manner as those conducted for pulmonary M. tuberculosis cases.

Epidemiology of Mycobacterium bovis disease in San Diego County, 1994-2000.

SETTING: Local public health department. OBJECTIVE: To examine the current epidemiology of Mycobacterium bovis disease in San Diego County and to compare patient characteristics to those of patients with M. tuberculosis disease. DESIGN: Retrospective review of surveillance and epidemiologic data. RESULTS: Between 1994 and 2000, 1,931 evaluable cases of culture-positive TB were identified; 129 were infected with M. bovis and 1,802 were infected with M. tuberculosis. More than 90% of M. bovis cases occurred in Hispanic persons. About 25% of patients were children, and the main site of disease was extra-pulmonary in 53% of patients. Twenty-three per cent had concurrent HIV infection. Compared to patients with M. tuberculosis, patients with M. bovis were more likely to be Hispanic, aged 0-14 years, have extra-pulmonary disease, or have HIV co-infection in a multivariate model. They were less likely to be born in countries outside of the US or Mexico. CONCLUSION: While human disease due to M. bovis has essentially been eliminated in many parts of the US and other industrialized countries, it persists in certain demographic groups, including Hispanic children and HIV-infected adults, in San Diego County.

Management of tuberculosis in San Diego County: a survey of physicians' knowledge, attitudes and practices.

SETTING: A survey conducted in San Diego County. OBJECTIVE: To assess local physicians' knowledge, attitudes and practices regarding tuberculosis (TB). METHODS: The survey consisted of questions covering diagnosis and treatment of active disease, diagnosis and treatment of latent infection, and infection control. The survey was sent to physicians who reported a TB case or suspect to the local health department in the years 1995-1997. RESULTS: Of the 384 physicians in this group, 150 (39%) returned the survey form. The percentage of physicians whose response conformed to health department guidelines varied widely from question to question (51%-94%, median 83%). Pulmonary medicine and infectious diseases specialists, physicians educated completely in the United States (US), and physicians who treated six or more TB patients in the past 2 years were more likely to give answers in agreement with health department policies. CONCLUSIONS: Because the response rate to the survey was low, these findings may not be completely representative of the targeted group of physicians. Nevertheless, they may indicate that health care provider education about TB management standards is needed.

Comparison of a whole-blood interferon gamma assay with tuberculin skin testing for detecting latent Mycobacterium tuberculosis infection.

CONTEXT: Identifying persons with latent tuberculosis infection (LTBI) is crucial to the goal of TB elimination. A whole-blood interferon gamma (IFN-gamma) assay, the QuantiFERON-TB test, is a promising in vitro diagnostic test for LTBI that has potential advantages over the tuberculin skin test (TST). OBJECTIVES: To compare the IFN-gamma assay with the TST and to identify factors associated with discordance between the tests. DESIGN AND SETTING: Prospective comparison study conducted at 5 university-affiliated sites in the United States between March 1, 1998 and June 30, 1999. PARTICIPANTS: A total of 1226 adults (mean age, 39 years) with varying risks of Mycobacterium tuberculosis infection or documented or suspected active TB, all of whom underwent both the IFN-gamma assay and the TST. MAIN OUTCOME MEASURE: Level of agreement between the IFN-gamma assay and the TST. RESULTS: Three hundred ninety participants (31.8%) had a positive TST result and 349 (28.5%) had a positive IFN-gamma assay result. Overall agreement between the IFN-gamma assay and the TST was 83.1% (kappa = 0.60). Multivariate analysis revealed that the odds of having a positive TST result but negative IFN-gamma assay result were 7 times higher for BCG-vaccinated persons compared with unvaccinated persons. The IFN-gamma assay provided evidence that among unvaccinated persons with a positive TST result but negative IFN-gamma assay result, 21.2% were responding to mycobacteria other than M tuberculosis. CONCLUSIONS: For all study participants, as well as for those being screened for LTBI, the IFN-gamma assay was comparable with the TST in its ability to detect LTBI, was less affected by BCG vaccination, discriminated responses due to nontuberculous mycobacteria, and avoided variability and subjectivity associated with placing and reading the TST.

The role of clinical suspicion in evaluating a new diagnostic test for active tuberculosis: results of a multicenter prospective trial.

CONTEXT: In laboratory trials, nucleic acid amplification tests for the diagnosis of tuberculosis (TB) are more accurate than acid-fast bacilli (AFB) smear microscopy and are faster than culture. The impact of these tests on clinical diagnosis is not known. OBJECTIVE: To assess the performance of a nucleic acid amplification test, the enhanced Mycobacterium tuberculosis Direct (E-MTD) test, against a uniform clinical standard stratified by level of clinical suspicion. DESIGN: Prospective multicenter trial conducted between February and December 1996, documenting the clinical suspicion of TB at enrollment and using final comprehensive diagnosis as the criterion standard. SETTING: Six urban medical centers and 1 public health TB clinic. PATIENTS: A total of 338 patients with symptoms and signs consistent with active pulmonary TB and complete clinical diagnosis were stratified by the clinical investigators to be at low (< or =25%), intermediate (26%-75%), or high (>75%) relative risk of having TB. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of the E-MTD test in clinical suspicion of groups with low (n = 224); intermediate (n = 68); and high (n = 46) clinical suspicion of TB. RESULTS: Based on comprehensive clinical diagnosis, sensitivity of the E-MTD test was 83%, 75%, and 87% for low, intermediate, and high clinical suspicion of TB, respectively, and corresponding specificity was 97%, 100%, and 100% (P = .25). Positive predictive value of the E-MTD test was 59% (low), 100% (intermediate), and 100% (high) compared with 36% (low), 30% (intermediate), and 94% (high) for AFB smear. Corresponding negative predictive values were 99%, 91%, and 55% [corrected] (E-MTD test) vs 96%, 71%, and 37% (AFB smear). CONCLUSIONS: For complex diagnostic problems like TB, clinical risk assessments can provide important information regarding predictive values more likely to be experienced in clinical practice. For this series, a clinical suspicion of TB was helpful in targeting areas of the clinical spectrum in which nucleic acid amplification tests can make an important contribution.

Evaluation of a serologic test for the diagnosis of tuberculosis.

The ICT TB test, a new, simple, serologic diagnostic test for tuberculosis (TB), was performed on serum samples from individuals seen at an urban teaching hospital and a local health department clinic. The study population included cases of TB, disease with mycobacteria other than tuberculosis (MOTT), non-mycobacterial pulmonary disease, and healthy controls. In contrast to prior studies, we found the ICT TB test had little value in detection of new cases of TB (overall sensitivity was 20%). It had very low sensitivity (4%) in the first month of disease. The sensitivity improved in patients tested at least 3 months after clinical presentation, but still remained fairly low. The test was also positive in 30% cases of disease caused by MOTT demonstrating cross-reactivity. It was negative in all human immunodeficiency virus (HIV) positive cases of TB or MOTT. The overall specificity was 89%. At least part of the discrepancy between our results and those of previous investigators may be attributable to differences in the respective study populations, including incidence of HIV disease and duration of tuberculosis illness prior to testing.

Development of housing programs to aid in the treatment of tuberculosis in homeless individuals: a pilot study.

STUDY OBJECTIVES: To describe our experience with novel supervised housing programs developed to aid in the treatment of tuberculosis (TB) in homeless individuals, including a preliminary analysis of their effectiveness and estimate of potential cost savings. DESIGN: Retrospective chart review. SETTING: A county TB control program. METHODS: The San Diego County TB Control Program's computer database was used to identify homeless individuals placed in one of two supervised housing programs for treatment of TB [Young Men's Christian Association (YMCA), for noninfectious patients, or Bissell House, for infectious patients]. Charts for all these patients were reviewed and information regarding their demographics, underlying medical conditions, therapy, microbiologic markers of response to therapy, hospitalizations, and participation in supervised housing programs was recorded. MEASUREMENTS AND RESULTS: The sputum culture conversion and treatment completion rates for those housed in the YMCA were 100 and 84.6%, respectively. Of the patients in the Bissell House program, 100% had converted their smear and culture. In addition, all patients in this program completed an adequate course of supervised therapy. These rates of microbiologic conversion and treatment completion compare favorably with historical data from San Diego County and other locations. Estimated cost savings for placing medically stable infectious patients in the Bissell House for respiratory isolation and supervised treatment were estimated to be $27,034 per patient. CONCLUSIONS: Use of supervised housing to aid in treatment of TB in the homeless appears to be effective and results in substantial cost savings. A larger multicenter study should be considered to confirm these findings and better quantify the cost-effectiveness of such programs.

Effectiveness of a nosocomial tuberculosis control program at an urban teaching hospital.

STUDY OBJECTIVE: To assess the effectiveness of a nosocomial tuberculosis (TB) program at an urban teaching hospital. DESIGN: Retrospective review. SETTING: An urban teaching hospital, the University of California, San Diego Medical Center (UCSD), which cares for 25 to 30 culture-proven pulmonary TB cases (>80% of which are smear-positive) per year. STUDY POPULATION: Health-care workers. MEASUREMENTS: (1) Purified protein derivative (PPD) conversion rates. (2) Cases of active TB among health-care workers. (3) Compliance rates with isoniazid (INH) preventive therapy. RESULTS: The UCSD program was evaluated for the years 1993 to 1995. The PPD conversion rate among established employees was 0.6%. Of 556 employees who had an exposure, 494 (88.8%) were compliant with follow-up. Three hundred thirty-seven were skin-tested (the other 157 already had a known PPD >10 mm). Only 2 of 337 (0.6%) converted. One case of active TB, unrelated to any documented hospital exposure, was discovered in 3 years among approximately 5,000 employees per year (follow-up for convertors, 18 to 54 months). Only 48.4% of eligible employees completed at least 6 months of INH preventive therapy. CONCLUSIONS: UCSD's TB control measures appear to be effective in the prevention of nosocomial transmission of TB. Despite poor compliance with INH preventive therapy, cases of active TB among health-care workers were rare.