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PubMed2002

Short-course rifamycin and pyrazinamide treatment for latent tuberculosis infection in patients with HIV infection: the 2-year experience of a comprehensive community-based program in Broward County, Florida.

OBJECTIVES: To determine the completion rate and tolerability of short-course rifamycin and pyrazinamide treatment of latent tuberculosis infection (LTBI) in HIV-infected patients through a comprehensive community-based program. DESIGN: Prospective cohort, with comparison to a historical control group. PATIENTS: Of 3,118 patients with HIV infection screened for LTBI between February 1999 and March 2001, 135 patients were placed on rifamycin/pyrazinamide for 2 months under directly observed therapy and were compared to a historical group comprised of 93 HIV-infected patients who were placed on self-administered treatment of isoniazid for 12 months between 1996 and 1998. RESULTS: Of 135 patients receiving rifamycin/pyrazinamide, 124 patients (92%) completed treatment; 5 patients had to discontinue treatment due to side effects (allergic skin reactions [n = 4], hepatitis [n = 1]). The completion rate of the historical group who received isoniazid therapy was 61% (57 of 93 patients; p < 0.001); none of those who received isoniazid experienced significant side effects. CONCLUSION: In our experience, a comprehensive, community-based program of rifamycin/pyrazinamide for LTBI achieved significantly higher adherence than that of traditional isoniazid therapy, and thus may provide improved tuberculosis prevention in a community with high prevalence of HIV-infected patients.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

[Epidemiological study of a tuberculosis case in a large manufacturing enterprise in Quebec].

OBJECTIVES: To determine the prevalence of tuberculosis infection related to a case of pulmonary and laryngeal tuberculosis in a workplace and to study PPD predictors. METHODS: The Mantoux skin test (PPD) was offered to all potentially infected contacts. Participants were asked to answer a questionnaire. RESULTS: Among 112 exposed employees, 92 (82.1%) were tested. At the 5 mm level, 65.2% of employees had positive tuberculin skin test (PPD). By controlling prior BCG and the degree of exposure, it showed a positive association between age and PPD (RC: 3.5; 95% CI: 1.25-10.03). When age and BCG were controlled, high exposure was statistically associated with PPD results (RC: 5.6; 95% CI: 1.25-24.68). CONCLUSION: The observed prevalence rate is probably related to the fact that the index case was very infectious and had contact in an enclosed area over a long period of time before withdrawal from work.

Adult↗

PubMed2004

Cytokine production and lymphocyte proliferation in patients with Nocardia brasiliensis actinomycetoma.

IFN-gamma, TNF-alpha, IL-4, IL-10 and IL-12 concentrations in the supernatant of peripheral blood mononuclear cell (PBMC) cultures and the in vitro proliferation of PBMC were studied in 25 patients with actinomycetoma caused by Nocardia brasiliensis and in 10 healthy controls from endemic zones. Cell cultures were stimulated by a N. brasiliensis crude cytoplasmic antigen (NB) and five semi-purified protein fractions (NB2, NB4, NB6, NB8, and NB10) separated by isoelectric. Phytohemagglutinin (PHA) and purified protein derivative (PPD) of Mycobacterium tuberculosis were used as control antigens. Skin tests were performed by injecting 0.1 ml of candidin and PPD intradermally (ID). Patients showed a poor response to tuberculin, while their response to candidin was more than two fold greater than that observed in the controls. Cell proliferation showed no statistically significant differences in either group. IFN-gamma production was higher in the healthy controls than in the patients, whereas TNF-alpha secretion was slightly higher in the patients' cultures. IL-4 was detected in the patients' cultures but not in the controls. IL-10 and IL-12 were present at low concentrations in both groups. These results suggest that patients with actinomycetoma show normal antigen recognition, but with low IFN-gamma production, and higher concentrations of IL-4, IL-10 and TNF-alpha in the patients' PBMC cultures, indicating that they probably have a Th2 type of immune response.

Adolescent↗

PubMedDate not supplied

Multidrug-resistant tuberculosis versus drug-sensitive tuberculosis in human immunodeficiency virus-negative patients: computed tomography features.

OBJECTIVES: To compare the computed tomography (CT) features of patients with multidrug-resistant tuberculosis with those of patients with drug-sensitive tuberculosis in a country not associated with the human immunodeficiency virus (HIV) epidemic. METHODS: The CT images of 47 patients with multidrug-resistant tuberculosis were compared with those of 47 patients with drug-sensitive tuberculosis as a control group. Each multidrug-resistant tuberculosis patient was age (decade) and gender matched to a drug-sensitive tuberculosis patient. All patients were seronegative to HIV. This study evaluated the presence of centrilobular nodules, consolidation, emphysema, bronchiectasis, lung destruction, calcified granuloma, cavitation, pleural effusion, and lymphadenopathy. A statistical comparison was performed by using the Fisher exact test for univariate analysis and a multiple logistic regression method for multivariate analysis. RESULTS: In univariate analysis, bronchiectasis, lung destruction, a calcified granuloma, and cavitation were more frequently observed in multidrug-resistant tuberculosis than in drug-sensitive tuberculosis. Multivariate analysis showed that cavity formation was the only significant difference between multidrug-resistant tuberculosis and drug-sensitive tuberculosis. In patients with cavitary tuberculosis, multiple cavities (>3 cavities) were observed only in patients with multidrug-resistant tuberculosis. CONCLUSIONS: Most patients with multidrug-resistant tuberculosis had cavity formation on CT. Although the presence of a cavity does not mean multidrug resistance, multiple cavities suggest the possibility of multidrug-resistant tuberculosis.

Adolescent↗

PubMed2004

Intracellular expression of interleukin-4 and interferon-gamma by a Mycobacterium tuberculosis antigen-stimulated CD4+ CD57+ T-cell subpopulation with memory phenotype in tuberculosis patients.

In some chronic pathological conditions, antigen persistence activates and expands the CD4+ CD57+ T-cell subset. The host immune response against tuberculosis infection is maintained through the continuous presence of antigen-stimulated effector/memory helper T cells. To determine whether CD4+ CD57+ T cells were also expanded in human tuberculosis, we analysed (by flow cytometry) the phenotype of peripheral blood CD4+ T cells from 30 tuberculosis patients and 30 healthy controls. We observed a significant increase in the CD4+ CD57+ T-cell subset in tuberculosis patients in comparison to healthy controls (P < 0.001). Most CD4+ CD57+ T cells exhibited a CD28- CD45RO+ CD62L- phenotype, which is associated with memory cells. In vitro, a higher number of antigen-stimulated CD4+ CD57+ T cells produced intracellular interferon-gamma and interleukin-4 compared with antigen-stimulated CD4+ CD57- T cells (P < 0.001). These findings suggest that the majority of CD4+ CD57+ T cells correspond to a phenotype of activated memory T cells.

Adult↗

PubMed2006

[Interleukin-2 in the correction of T-cell anergy in patients with pulmonary tuberculosis].

The clinical and immunomodulating effects of lymphotropic administration of interleukin-2 (IL-2) were studied in the combine treatment of patients with pulmonary tuberculosis. The patients with tuberculosis were shown to have the low levels of monocytes with the intracellular expression of tumor necrosis factor-alpha (TNF-alpha) and the high count of CD14+ CD16+ monocytes with the intracellular expression of IL-10. The changes in the monocytic link were most pronounced in patients with PPD-induced anergy appeared as the low proliferation and production of alpha-interferon (alpha-INF). During clinical trials, 19 patients received tuberculostatic therapy in combination with IL-2 (Roncoleukin) (a study group) whereas 16 patients had tuberculostatic therapy alone (a control group). The administration of Roncoleukin statistically significant increased a proliferative response to PPD and normalized the count of CD14+ CD16+ monocytes with anti-inflammatory and immunosuppressive activities. The restoration of a PPD response was recorded more frequently in the study group than in the control one (75% vs 30%; p = 0.045). The magnitude of positive X-ray changes was also higher in the study group than in the control one (63% vs 25%; p = 0.026). The findings suggest the clinical and immunomodulating effects of IL-2 (Roncoleukin) in the combined therapy for tuberculosis.

Adolescent↗

PubMed1989

The combined toxicity of azidothymidine and antimycobacterial agents. A retrospective study.

Eight patients being treated for tuberculosis prior to starting azidothymidine therapy (study group) were compared with 56 patients who were treated with azidothymidine but not with antimycobacterial agents (control group). Toxicity was assessed 12 wk after the initiation of treatment with azidothymidine. Study group patients were more likely than control subjects to be either black or Hispanic (75% versus 30%, p = 0.02). There were no other statistically significant demographic differences. Seven study patients, and 20 control subjects experienced a fall in leukocyte count greater than 10% (88% versus 36%, p = 0.01). Within each group, patients with acquired immune deficiency syndrome (AIDS) were more likely to experience this degree of hematologic toxicity than were patients with AIDS-related complex (p = 0.03). However, analysis of covariance showed no significant differences between the groups after 12 wk of azidothymidine with regard to mean leukocyte or platelet counts, hemoglobin levels, or values for tests of liver function. The groups were similar in transfusion requirements and frequency of changes in azidothymidine dosage. Although this study was limited in power by the number of patients and the nonrandomized, retrospective design, the data suggest that patients can tolerate concurrent therapy with azidothymidine and antimycobacterial agents without unacceptable toxicity.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Bactericidal activity of increasing daily and weekly doses of moxifloxacin in murine tuberculosis.

Moxifloxacin (MXF) is a new 8-methoxyquinolone with potent activity against Mycobacterium tuberculosis and a half-life of 9 to 12 h in humans. Previous in vivo studies using daily doses of 100 mg/kg of body weight have demonstrated bactericidal activity comparable to that of isoniazid (INH) in a murine model of tuberculosis (TB). Recent pharmacokinetic data suggest that MXF may have been underadministered in these studies and that a 400-mg/kg dose in mice better approximates the area under the concentration-time curve obtained in humans after a 400-mg oral dose. Therefore, the bactericidal activity of MXF in doses up to 400 mg/kg given daily or weekly for 28 days was assessed in mice infected intravenously with 5 x 10(6) CFU of M. tuberculosis. INH was used as a positive control. After 3 days of daily therapy, the CFU counts from splenic homogenates for mice treated with MXF in doses of 100 to 400 mg/kg/day were lower than those from pretreatment controls. No significant differences in CFU counts were seen when mice receiving INH or MXF at 50 mg/kg/day were compared to pretreatment controls. After 28 days of therapy, dose-dependent reductions in CFU counts in splenic homogenates were seen for daily MXF therapy. The maximum bactericidal effect was seen with daily doses of 400 mg/kg, which resulted in a reduction in CFU counts of 1 log(10) greater than that with INH treatment, although the difference was not statistically significant. CFU counts from lung homogenates after 28 days of therapy were significantly lower in all treatment groups than in untreated controls. The weekly administration of MXF in doses ranging from 50 to 400 mg/kg resulted in no significant bactericidal activity. Mice receiving daily MXF doses of 200 and 400 mg/kg/day failed to gain weight and appeared ill after 28 days of therapy, findings suggestive of drug toxicity. In conclusion, MXF has dose-dependent bactericidal activity against M. tuberculosis in the mouse when given in doses up to 400 mg/kg, where its pharmacokinetic profile better approximates that of standard human dosages. Combination regimens which take advantage of the enhanced pharmacodynamic profile of MXF at these doses have the potential to shorten the course of antituberculous therapy or allow more intermittent (i.e., once-weekly) therapy and should be evaluated in the mouse model of TB.

Animals↗

PubMed1998

[An analysis of the care for a tubercular patient. Problem detection].

OBJECTIVE: Make a epidemiological and descriptive analysis of the tuberculosis patients care, researching problems which may be the etiology of the increase of illness. DESIGN: Descriptive observing retrospective study. SETTING: Soria County. PATIENTS: 186 cases with positive Mycobacterium tuberculosis culture, since January 1, 1983 until December 31, 1993. RESULTS: The 65.4% of patients were hospitalized to make the diagnostic and/or to begin treatment. We found delayed diagnostics much as 5.5 years. The mean was 120.9 +/- 244.7 days until the diagnostic was performed, 1991 y 1992 were the highest delayed time to diagnostic years of the study. The diagnostic and control of the 99.5% of patients was done at hospital. Only a 64% of patients could be considered as healthy at the onset of his control. CONCLUSIONS: Most of physicians consider the tuberculosis as a hospital illness, so there are delayed diagnostic and therapeutics and worse control of evolution, therapy compliance and contacts study.

Antitubercular Agents↗

PubMed1978

Controlled clinical trial of five short-course (4-month) chemotherapy regimens in pulmonary tuberculosis. First report of 4th study. East African and British Medical Research Councils.

Five 4-mo regimens of chemotherapy for tuberculosis are compared. The two regimens in which rifampicin was given throughout the 4 mo were associated with bacteriological-relapse rates of 8% in the first 6 mo after stopping chemotherapy, but the three regimens in which rifampicin was given for only the first 2 mo had relapse-rates of 24-32%. There was no evidence that the addition of pyrazinamide in the second 2 mo of chemotherapy reduced the bacteriological-relapse rate. Removal of the streptomycin from the first 2 mo appeared to reduce the bactericidal and sterilising activity of the regimen, although the differences were not statistically significant. The incidence of adverse reactions was very low with all five regimens.

Adolescent↗

PubMed1998

Bronchopulmonary aspergilloma: a reappraisal.

BACKGROUND: Classically, most complications observed after operations for aspergilloma occurred in patients with sequelae of tuberculosis. Because the incidence of tuberculosis has declined over the past two decades, aspergilloma is expected to develop with increasing frequency in patients without previous tuberculosis. Therefore, our hypothesis was that operative outcome should have improved during the most recent years in comparison with our previous experience. METHODS: Operative outcome of 12 recently accrued patients was evaluated and compared with a historic control group of 55 patients, previously reported by the same center. RESULTS: As expected, only 17% of patients of the present series had a history of tuberculosis, compared with 57% in the former series. Postoperatively, there was no mortality. Major morbidity has decreased, although this difference is not statistically significant: bleeding decreased from 44% to 9% of patients; space problems decreased from 47% to 18%; and prolonged hospital stay (>30 days) decreased from 32% to 9%. CONCLUSIONS: Our results support a trend toward improved postoperative outcome of operations for aspergilloma owing to a decreased incidence of aspergilloma growing in tuberculous cavitations.

Adolescent↗

PubMed2004

Smear-negative pulmonary tuberculosis and lymphocyte subsets.

OBJECTIVE: To correlate and quantitate lymphocyte subsets with clinically diagnosed smear-negative pulmonary tuberculosis and severity of disease. DESIGN: Case-control study. PLACE AND DURATION OF STUDY: Military Hospital and Armed Forces Institute of Pathology Rawalpindi. 1999-2000. SUBJECTS AND METHODS: Freshly diagnosed, well-characterized smear-negative patients (n=15) of pulmonary tuberculosis were selected. Non-induced three-consecutive negative smears of sputum with simultaneous culture for AFB for 6-8 weeks, positive Mauntoux test (Z10 mm), blood complete picture with ESR and chest x-rays were done. Selected panel of monoclonal antibodies against specific CD markers were used. Statistical analysis done by student t-test or Mann-Whitney rank-sum test with the help of Sigma State software. RESULTS: Hemoglobin and total lymphocyte counts were significantly reduced whereas total leukocyte counts with absolute neutrophil counts were increased. Fraction of CD4+ and CD8+ T lymphocytes with HLA-DR expression was reduced while no significant change in rest of the TB and NK lymphocytes. CONCLUSION: Low hemoglobin level, high neutrophil count and low total lymphocytes suggest possible direct relationship with extent of disease. The number of activated CD4+, CD8+, ab and gd TCR T cells have tendency to increase during Mycobacterium infection. This seems to have a potential of being a good, non-invasive prognostic indicator for patients with pulmonary tuberculosis.

Adult↗

PubMed1998

Pulmonary bovine-type tuberculosis in rabbits: bacillary virulence, inhaled dose effects, tuberculin sensitivity, and Mycobacterium vaccae immunotherapy.

This report elucidates four aspects of the immunology of pulmonary tuberculosis produced in rabbits: (i) the virulence of bovine-type tubercle bacilli, strain Ravenel S, (ii) systemic factors influencing the generation of visible primary pulmonary tubercles, (iii) differences in tuberculin sensitivity of rabbits and humans, and (iv) the effect of Mycobacterium vaccae immunotherapy on cavitary tuberculosis. Laboratory strain Ravenel S (ATCC 35720) was not fully virulent. Fully virulent strains produce one visible primary pulmonary tubercle for each three bacillary units inhaled. Strain ATCC 35720 produced one such tubercle for each 18 to 107 bacillary units inhaled, indicating that its virulence was reduced by 6- to 36-fold. When a low dose of this Ravenel S strain was inhaled, the host resistance (measured by the number of inhaled bacilli needed to generate one visible primary pulmonary tubercle) was increased at least 3.5-fold compared to the host resistance when a high dose was inhaled. Rabbits and humans differ in the degree and in the maintenance of their dermal sensitivities to tuberculin. Compared to rabbits, humans are 100 times more sensitive to tuberculin. Also, at 33 weeks rabbits with well-controlled cavitary tuberculosis usually showed a decrease in their tuberculin reactions of about 50% from peak values, whereas humans with such well-controlled tuberculosis are thought to maintain strong reactions for many years. These species differences may be due to desensitization to group II mycobacterial antigens in the rabbits because they have a different diet and a different type of digestive tract. M. vaccae immunotherapy of rabbits with cavitary tuberculosis produced no statistically significant effects. Experiments with many more rabbits would be required to prove whether or not such immunotherapy is beneficial.

Animals↗

PubMed1991

Socioeconomic development, health interventions and mortality decline in Costa Rica.

Costa Rica, whose life expectancy was 74 years by 1985, has reached a health level comparable to a developed country. The health achievements of this country are product of political and socioeconomic circumstances as well as of right public health policies. Until about 1970 the features of Costa Rica mortality, although somewhat better than the Latin American average, evolved in a similar way to the rest of the region. In particular, the decades of 1940s and 1950s saw dramatic improvements in life expectancy, thanks mainly to the import of low-cost, high-effectiveness health technologies. In the 1970s, however, Costa Rica departed from a regional pattern of stagnation and managed to close the gap with developed countries in terms of mortality levels. A dramatic decline in the infant mortality rate from 60 to 19 per 1,000 took place in this decade. The main determinants of this breakthrough were health interventions, notably a primary health care program, even though favorable socioeconomic conditions and a reduced fertility also played a role. Ecological data and other evidence suggest that up to three fourths of the mortality decline was accounted for contemporary improvements in public health services, with about 40 percent attributable to primary health care interventions. Furthermore, by targeting interventions on the less privileged population, these interventions had the merit of reducing geographic and socioeconomic differentials in child mortality.

Cause of Death↗

PubMed1977

Absorption of rifampicin in gastrectomized patients. Effect of meals.

Rifampicin absorption was studied in six gastrectomized and six non-gastrectomized tuberculous patients who had been on continuous rifampicin therapy for more than 4 weeks. A dose of 450 mg was given on two occasions, first immediately after breakfast and, 2 days later, 1 h before breakfast. In all the gastrectomized and control patients a serum level well above the MIC for M. tuberculosis (0.2-0.5 microgram/ml) was achieved irrespective of whether rifampicin was administered after the meal or during fasting. Gastrectomized patients tended to have more delayed serum concentration peaks postprandially than when fasting. The differences in absorption were not statistically significant, and the serum concentrations remained above the MIC for M. tuberculosis for similar lenghts of time. Individual serum concentrations varied greatly, and this variation may represent a greater problem in the routine monitoring of rifampicin serum levels than administration of the drug with food.

Adult↗

PubMed1998

Preventive therapy for tuberculosis in Western Australia.

SETTING: State Tuberculosis Control Programme, Western Australia. OBJECTIVE: To ascertain baseline information, applicability and efficacy of preventive therapy for tuberculosis (TB) under indirectly supervised treatment in Western Australia. DESIGN: Retrospective analyses of records of persons with TB infection who were prescribed preventive therapy for the period 1993-1996 inclusive, using simple descriptive statistics. RESULTS: Preventive therapy was given to 411 persons after screening for TB due to on-arrival migrant surveillance (269), contact tracing (59), tuberculin surveys (59) and other reasons (24). Six-month isoniazid monotherapy (HMT) was prescribed for 403 and multidrug regimens for the remaining eight. Excepting 34 whose compliance was unknown, varying degrees of treatment non-adherence were found in 90 (24%) of the remaining 369 persons given HMT, including 36 (10%) with under five months of total medication. Minor adverse drug effects occurred in 32 (9%) subjects and contributed to the non-adherence in 23 of these. One person has since developed active TB. CONCLUSIONS: Preventive therapy in Western Australia conformed to generally accepted guidelines. Varying degrees of non-adherence to HMT occurred in 24% of persons, but 90% completed adequate therapy under indirect supervision. Non-adherence is significantly related to adverse drug effects.

Adolescent↗

PubMed2005

[Study on the molecular epidemiology of Mycobacterium tuberculosis in Shanghai].

OBJECTIVE: To explore the molecular-epidemiology of Mycobacterium tuberculosis in Shanghai. METHODS: Drug-resistant and drug-susceptible strains of M. tuberculosis were randomly selected from the bank of M. tuberculosis of Shanghai Municipal Center for Disease Control and Prevention and were genotyped by mycobacterial interspersed repetitive units(MIRU) and Spoligotyping methods. The genotyping results were analyzed and combined with epidemiological data. RESULTS: The Spoligotyping results demonstrated that 89 % (81/91) of the strains belonged to the Beijing genotype. Of the patients who had received BCG-vaccination,88.5% (54/61) infected with strains of Beijing genotype and 90.0% (27/30) of the patients were not BCG-vaccinated. However, the difference was not statistically significant. Drug-resistant rate from those strains of Beijing genotype was 45.7 (37/81), lower than that of non-Beijing genotype (60.0% ,6/10). Again,the difference was not statistically significant. The MIRU results showed that 62.6 % (57/91) were strains of clusters. CONCLUSION: The Beijing genotype of M. tuberculosis were found to be the dominant strains in Shanghai. The associations between Beijing genotype strains and BCG vaccination or drug-resistant were not found. Results from cluster analysis suggested that some cases might belong to the newly developed cases.

Adolescent↗

PubMedDate not supplied

[Efficacy and efficiency of antitubercular treatment in health jurisdictions of Morelos].

OBJECTIVE: To evaluate the efficacy and efficiency of tuberculosis treatment administered by the Secretaría de Salud (SSA) in the sanitary jurisdictions of Cuernavaca and Cuautla, Morelos, for the 1992-1996 period by retrospectively reviewing tuberculosis treatment control cards. MATERIAL AND METHODS: Official Norm for Tuberculosis Prevention and Control in Primary Care Units outcome definitions were used. Data was collected on standardized forms and analyzed with SAS and Epi Info programs; 149 primary care units and 4 hospitals in the study area were visited. RESULTS: There were found 288 patients cards, of which 260 were new cases. These patients received 311 treatments of which 85% were directly observed. Reviewed cards represented 60% of SSA notified cases for this period. There were analyzed 246 treatments of which 32% were bacteriological cures, 26% probable cures, 18% dropouts, 1% failures and 3% deaths. In 20% of treatments the outcome was unknown. Cure rate was better in new cases (61%) than in retreatments (38%), p < 0.01. Efficacy of treatment was 71% and efficiency 58%. Patients receiving retreatment abandoned it more frequently (32%) than new cases (16%), p < 0.01. A statistically significant association was found between abandoned treatment and being retreated (OR = 3.3, CI 95% 1.3-8.5, p = 0.01) or belonging to a lower socioeconomic level (OR = 2.3, CI 95% 1.0-4.9, p = 0.04). In the 34 retreatment programs, 22 were initiated after abandonment, failure or relapse. CONCLUSIONS: Proportion of cure rate (58%) compares unfavorably with WHO recommendations (85%). Implications of a high dropout rate and probability of circulation of resistant strains of M tuberculosis are discussed. Creative strategies to reinforce patient compliance which take into account the patient and not only the health services, extension of cultures to known M. tuberculosis drug resistance and evaluation of modifications to drug regimens are proposed. Review of treatment control cards is a useful tool for program evaluation.

Adult↗