Tuberculosis: what is the yield of associate investigations in non-BCG-immunized children with positive tuberculin skin tests?

SETTING: Urban county health department in Tarrant County, Texas, USA. OBJECTIVE: To determine the yield of associate investigations in non-bacille Calmette-Guerin (BCG) immunized children with positive tuberculin skin tests (TSTs). DESIGN: We compared the results of associate investigations of the contacts of 38 TST-positive, non-BCG-immunized pre-school children with the results of contact investigations of 290 culture-confirmed persons with tuberculosis (TB). RESULTS: Associate investigations were more likely than contact investigations to identify persons with culture-confirmed TB and positive TSTs. Contacts identified through associate investigation of non-BCG-immunized pre-school children were 9.4 (95%CI 4.2-22.5) times more likely to have culture-confirmed TB and 2.3 (95%CI 2.0-2.7) times more likely to have positive TSTs than contacts of persons with culture-confirmed TB. CONCLUSION: While conducting associate investigations is labor intensive, these data indicate that associate investigation of pre-school non-BCG-immunized children should be assigned priority in TB control activities, at least equal to the importance of investigating the contacts of culture-proven TB.

Tuberculosis in the foreign-born population of Tarrant county, Texas by immigration status.

The epidemiology of tuberculosis is changing in the United States as a result of immigration, yet the extent to which different classes of immigrants contribute to overall morbidity is unknown. Tuberculosis in nonimmigrant visitors is of particular interest as they are currently exempt from screening requirements. We conducted a prospective survey of all culture-positive tuberculosis patients in Tarrant County, Texas from 1/98 to 12/00. Immigration status of foreign-born patients was classified as permanent residents, undocumented, or nonimmigrant visitors. Of 274 eligible participants, 114 (42%) were foreign-born; of these, 67 (59%) were permanent residents, 28 (25%) were undocumented, and 19 (17%) were nonimmigrant visitors. Among the foreign-born, we observed significant differences by immigration status in multidrug resistance (p = 0.02), human immunodeficiency virus (HIV) infection (p = 0.0007), and hospitalization (p = 0.03 for ever/never, 0.01 for duration). Compared with other immigrants, more nonimmigrant visitors were multi-drug-resistant (16 % versus 11% of undocumented residents and 1% of permanent residents), were HIV-positive (32% versus 0% of undocumented and 5% of permanent residents), were hospitalized (47% versus 36% of undocumented and 19% of permanent residents), and had lengthy hospitalizations (median [midspread] days = 87 [25 to 153] versus 8.5 [4 to 28] for undocumented and 10 [7 to 24 d] for permanent residents). We found nonimmigrant visitors to be an important source of tuberculosis morbidity in Tarrant County. Further studies in other regions of the U.S. are needed to determine if screening and treatment recommendations of persons who spend extended periods in the U.S. should be raised to the standards set for permanent residents.

Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events.

BACKGROUND: Elevated levels of C-reactive protein, even in the absence of hyperlipidemia, are associated with an increased risk of coronary events. Statin therapy reduces the level of C-reactive protein independently of its effect on lipid levels. We hypothesized that statins might prevent coronary events in persons with elevated C-reactive protein levels who did not have overt hyperlipidemia. METHODS: The level of C-reactive protein was measured at base line and after one year in 5742 participants in a five-year randomized trial of lovastatin for the primary prevention of acute coronary events. RESULTS: The rates of coronary events increased significantly with increases in the base-line levels of C-reactive protein. Lovastatin therapy reduced the C-reactive protein level by 14.8 percent (P<0.001), an effect not explained by lovastatin-induced changes in the lipid profile. As expected, lovastatin was effective in preventing coronary events in participants whose base-line ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol was higher than the median ratio, regardless of the level of C-reactive protein (number needed to treat for five years to prevent 1 event, 47; P=0.005). However, lovastatin was also effective among those with a ratio of total to HDL cholesterol that was lower than the median and a C-reactive protein level higher than the median (number needed to treat, 43; P=0.02). In contrast, lovastatin was ineffective among participants with a ratio of total to HDL cholesterol and a C-reactive protein level that were both lower than the median (number needed to treat, 983; P=0.80). CONCLUSIONS: Statin therapy may be effective in the primary prevention of coronary events among subjects with relatively low lipid levels but with elevated levels of C-reactive protein.

Contribution of CD8(+) T cells to gamma interferon production in human tuberculosis.

The proportions of peripheral blood mononuclear cells (PBMC), CD4(+) T cells, and CD8(+) T cells that produce gamma interferon (IFN-gamma) in response to Mycobacterium tuberculosis were markedly reduced in tuberculosis patients, particularly in those with severe disease. Depletion of CD4(+) but not CD8(+) cells prior to stimulation of PBMC with M. tuberculosis abolished IFN-gamma production. These results show that (i) IFN-gamma production by CD8(+) and CD4(+) cells correlates with the clinical manifestations of M. tuberculosis infection and (ii) IFN-gamma production by CD8(+) cells depends on CD4(+) cells.

Causes and costs of hospitalization of tuberculosis patients in the United States.

OBJECTIVE: To examine the costs, lengths of stay and patient characteristics associated with tuberculosis (TB) hospitalizations. METHODS: A prospective cohort study of 1493 TB patients followed from diagnosis to completion of therapy at 10 public health programs and area hospitals in the US. The main outcome measures were the following: 1) occurrence, 2) cost, and 3) length of stay of TB-related hospitalizations. RESULTS: There were 821 TB-related hospitalizations among the study participants; 678 (83%) were initial hospitalizations and 143 (17%) were hospitalizations during the treatment of TB. Patients infected with human immunodeficiency virus (HIV) (OR 1.8, 95% CI 1.2-2.6), and homeless patients (OR, 1.7 95% CI 1.1-2.8) were at increased risk of being hospitalized at diagnosis. Homeless patients (RR 2.5, 95%CI 1.5-4.3), patients who used alcohol excessively (RR 1.9, 95% CI 1.2-3.0), and patients with multidrug-resistant TB (RR 5.7, 95% CI 2.7-11.8) were at increased risk of hospitalization during treatment. The median length of stay varied from 9 to 17 days, and median costs per hospitalization varied from $6441 to $12968 among the sites. CONCLUSION: Important social factors, HIV infection, and local hospitalization practice patterns contribute significantly to the high cost of TB-related hospitalizations. Efforts to address these specific factors are needed to reduce the cost of preventable hospitalizations.

Production of interleukin-18 in human tuberculosis.

To investigate the role of interleukin (IL)-18 in human tuberculosis, IL-18 production was evaluated in blood and at the site of disease in patients with tuberculosis. Mycobacterium tuberculosis-stimulated peripheral blood mononuclear cells (PBMC) from tuberculosis patients secreted less IL-18 and interferon-gamma (IFN-gamma) than did PBMC from healthy persons reactive to tuberculin. M. tuberculosis-induced IFN-gamma production was inhibited by anti-IL-18 and enhanced by recombinant IL-18. Alveolar macrophages secreted IL-18 in response to M. tuberculosis, and IL-18 and IFN-gamma concentrations were higher in pleural fluid of patients with tuberculosis than in pleural fluid of patients with nontuberculous diseases. These findings demonstrate that IL-18 production by PBMC correlates with IFN-gamma production and effective immunity to tuberculosis, suggesting that IL-18 contributes to a protective type 1 cytokine response in persons with mycobacterial infection.

Treatment costs of directly observed therapy and traditional therapy for Mycobacterium tuberculosis: a comparative analysis.

OBJECTIVE: Treatment of tuberculosis is a time-consuming and expensive process, often complicated by patient non-adherence. Directly observed therapy (DOT), an out-patient management strategy designed to ensure adherence, is not widely used because it is perceived to be too expensive. This study compared costs of tuberculosis treatment in DOT to the same factors in traditional therapy. DESIGN: A retrospective economic evaluation of 659 tuberculosis cases was reported to a major metropolitan county public health department between 1980 and 1994. Out-patient costs, in-patient costs and the cost impact of relapse and acquired resistance were estimated in 1995 dollars. RESULTS: Treatment costs were lower with DOT: $15,670 per case for in-patient care and $700 per case for out-patient care (P < 0.001). These cost differences resulted from shorter therapy duration (334 vs 550 days), fewer patient hospitalizations (58 vs 75%) and shorter hospital stays (26 vs 55 days per hospitalized patient). Relapse or acquired resistance occurred in 10.9% of patients and accounted for 35.7% of cost with traditional therapy, as compared to 1.2% of patients and 6.0% of cost with observed therapy. CONCLUSIONS: Directly observed therapy is less costly than traditional therapy.

Universal HIV screening at a major metropolitan TB clinic: HIV prevalence and high-risk behaviors among TB patients.

OBJECTIVES: This study assessed the outcome of implementing a policy of universal screening of patients with tuberculosis (TB) for HIV infection at a major metropolitan public health TB clinic. METHODS: HIV serologic testing was completed on 768 (93%) of 825 eligible patients. Ninety-eight HIV-positive cases (13%) were compared with 670 HIV-negative cases. The presence of adult HIV risk factors was determined by structured interview and review of medical records. RESULTS: One or more HIV risk factors were present in 93% of HIV-positive cases and 42% of HIV-negative cases. CONCLUSIONS: The metropolitan TB clinic is well suited for HIV screening, and HIV-antibody testing and counseling should be provided to all TB patients.

Diversity of DNA fingerprints of Mycobacterium tuberculosis isolates in the United States.

To investigate the diversity of IS6110 fingerprints of Mycobacterium tuberculosis isolates in the United States and to determine if matching IS6110 fingerprints represent recent interstate tuberculosis transmission, we performed restriction fragment length polymorphism analysis of M. tuberculosis isolates from 1,326 patients in three geographically separated states. Seven hundred ninety-five different IS6110 fingerprint patterns were generated, and pattern diversity was similar in each state. Ninety-six percent of the fingerprint patterns were observed in only one state, demonstrating that most IS6110 fingerprint patterns are confined to a single geographic location. Of the IS6110 fingerprint patterns that were shared by isolates from more than one state, most isolates with 1 to 5 IS6110 copies were separable by pTBN12 fingerprinting whereas those with > 15 copies were not. One high-copy-number M. tuberculosis strain had identical IS6110 and pTBN12 fingerprints and included 57 isolates from three states. Epidemiological data demonstrated significant recent transmission of tuberculosis within each city but not among the states. This suggests that identical fingerprints of isolates from geographically separate locations most likely reflect interstate tuberculosis transmission in the past, with subsequent intrastate spread of disease. Further evaluation of M. tuberculosis strains that cause outbreaks in different geographic locations will provide insight into the epidemiological and bacteriological factors that facilitate the spread of tuberculosis.

A survey of drug-resistant Mycobacterium tuberculosis and its relationship to HIV infection.

OBJECTIVE: To compare the prevalence of drug-resistant tuberculosis disease among patients with and without HIV infection. DESIGN: An historical prospective evaluation of patients with culture-proven tuberculosis reported between January 1988 and December 1995. SETTING: A major metropolitan county public health department. PATIENTS: A total of 802 consecutive culture-positive tuberculosis patients were eligible for inclusion in the study. HIV serologic testing and drug susceptibilities were completed on 741 (92%) eligible patients. Of these patients, 646 tested HIV-negative and 95 (12.8%) tested HIV-positive. Patients not tested for HIV (n = 59) and without drug susceptibilities (n = 2) were excluded from the analyses. Outpatient management was based on a policy of universal directly observed therapy. MAIN OUTCOME MEASURES: Patient HIV status, initial drug resistance and acquired drug resistance. Isolates were characterized for resistance to isoniazid, rifampin, rifabutin, ethambutol, streptomycin, capreomycin, kanamycin and ethionamide. Determination of initial resistance was based on the first available susceptibility study and acquired resistance on subsequent susceptibility studies. RESULTS: Initial drug resistance was found in 55 (8.5%) HIV-negative patients and four (4.2%) HIV-positive patients. Acquired drug resistance occurred in five (0.8%) HIV-negative patients and one (1.1%) HIV-positive patient. These differences were not statistically significant. CONCLUSIONS: HIV infection is not a risk factor for drug-resistant tuberculosis. Increased drug resistance in HIV infected tuberculosis patients reflects a failure of tuberculosis control in the underlying population.

Universal directly observed therapy. A treatment strategy for tuberculosis.

Patient adherence to prescribed tuberculosis regimens must be assured to prevent relapse, acquired resistance, and transmission. Directly observed therapy (DOT), an outpatient management strategy designed to ensure adherence, is not widely used because it is perceived to be inordinately expensive. The primary focus of this article is on using universal, as opposed to selective, DOT in the treatment of tuberculosis patients. Universal DOT is a policy where it is intended that observed therapy be used for all patients. Selective DOT is a policy where patients are observed taking medications only if certain selection criteria are satisfied. Topics addressed include cost, efficacy, nonadherence, and implementation guidelines.

The effect of directly observed therapy on the rates of drug resistance and relapse in tuberculosis.

BACKGROUND: Tuberculosis has reemerged as an important public health problem, and the frequency of drug resistance is increasing. A major reason for the development of resistant infections and relapse is poor compliance with medical regimens. In Tarrant County, Texas, we initiated a program of universal directly observed treatment for tuberculosis. We report the effect of the program on the rates of primary and acquired drug resistance and relapse among patients with tuberculosis. METHODS: We collected information on all patients with positive cultures for Mycobacterium tuberculosis in Tarrant County from January 1, 1980, through December 31, 1992. Through October 1986, patients received a traditional, unsupervised drug regimen. Beginning in November 1986, nearly all patients received therapy under direct observation by health care personnel. RESULTS: A total of 407 episodes in which patients received traditional treatment for tuberculosis (January 1980 through October 1986) were compared with 581 episodes in which therapy was directly observed (November 1986 through December 1992). Despite higher rates of intravenous drug use and homelessness and an increasing rate of tuberculosis during this 13-year period, the frequency of primary drug resistance decreased from 13.0 percent to 6.7 percent (P < 0.001) after the institution of direct observation of therapy, and the frequency of acquired resistance declined from 14.0 percent to 2.1 percent (P < 0.001). The relapse rate decreased from 20.9 percent to 5.5 percent (P < 0.001), and the number of relapses with multidrug-resistant organisms decreased from 25 to 5 (P < 0.001). CONCLUSIONS: The administration of therapy for M. tuberculosis infection under direct observation leads to significant reductions in the frequency of primary drug resistance, acquired drug resistance, and relapse.

Effect of pedal rate on cardiorespiratory responses during continuous exercise.

The role of cycle ergometer pedal rate on the gradual increase in ventilation (VE), heart rate (HR), and oxygen uptake (VO2) accompanying continuous submaximal exercise is unknown. To examine this problem, five trained males (VO2peak = 4.00 +/- 0.27 l.min-1) performed 45 min of moderate intensity (MI, 127 W) and high-moderate intensity (HMI, 166 W) cycle ergometry both at pedal rates of 60 rpm and 90 rpm. Power output and pedal rate had an additive effect on the overall mean responses for VE, HR, and VO2, producing significantly higher values as power output and pedal rate increased. During continuous exercise, VE, HR, and VO2 increased progressively from the 10th to the 45th minute for all tests. However, the rates of increase and factors modifying the VE, HR, and VO2 responses were different. HR increased during all exercise tests an average of 10.8% independent of power output and pedal rate. VE increased 7.4% during MI exercise and 10% during HMI exercise independent of pedal rate. Similar power output dependent responses were observed for rectal temperature (Tr) and blood lactate. VO2 increased 4.4% for MI and HMI exercise at 60 rpm, and 8.2% for the same power outputs at 90 rpm, respectively. Increases in Tr, the oxygen cost of pulmonary ventilation and fat oxidation, and lactate removal were estimated to account for only 31-36% of the slow rise in VO2 for any single test. This suggests that 64-69% of the rise in VO2 was due to factors related to muscle use.(ABSTRACT TRUNCATED AT 250 WORDS)