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PubMed2004

Added epidemiologic value to tuberculosis prevention and control of the investigation of clustered genotypes of Mycobacterium tuberculosis isolates.

The Centers for Disease Control and Prevention established the US National Tuberculosis Genotyping and Surveillance Network to study the utility of genotyping Mycobacterium tuberculosis isolates for prevention and control. From 1998 to 2000, four sites performed conventional contact investigations and epidemiologic investigations of cases with genotypically matched M. tuberculosis isolates, called cluster investigations. The authors compared cluster pairs (two cases with M. tuberculosis isolates having identical genotypes) whose epidemiologic linkages were discovered only during cluster investigation with those whose epidemiologic linkages were discovered during conventional contact investigation. Among the 2,141 reported culture-positive tuberculosis cases, 2,055 (96%) M. tuberculosis isolates were genotyped. By itself and at a minimum, cluster investigation added 43 (38%) of the 113 total epidemiologic linkages discovered. Of the epidemiologic linkages discovered during conventional contact investigation, 29% of tuberculosis case pairs were not supported by genotyping data. The linkages discovered only during cluster investigation were more likely discovered in nontraditional settings and relationships and among larger clusters (cluster size of >5: adjusted odds ratio = 57.6, 95% confidence interval: 31.8, 104.6). Information gained from genotyping M. tuberculosis isolates should initiate cluster investigations of tuberculosis cases not previously discovered as being epidemiologically linked during conventional contact investigation. Cluster investigations will play a crucial role in predicting recent tuberculosis transmission more accurately, as we move toward tuberculosis elimination in the United States.

Arkansas↗

PubMed2005

Effect of nucleic acid amplification for Mycobacterium tuberculosis on clinical decision making in suspected extrapulmonary tuberculosis.

BACKGROUND: Laboratory-based studies have suggested the nucleic acid amplification test (NAAT) for Mycobacterium tuberculosis may be useful in diagnosing extrapulmonary tuberculosis. We sought to determine how clinicians in one hospital used results of the NAAT in clinical decision making in cases of suspected extrapulmonary tuberculosis. METHODS: We performed a retrospective analysis of all patients who underwent the NAAT on at least one nonsputum sample, excluding cerebrospinal fluid, from 1999 to 2001 in one large urban hospital. For these patients, we reviewed the hospital course, with particular attention to date of the NAAT and its influence on days treated with antituberculous medications and days to final diagnosis. RESULTS: Thirty-five patients with suspected tuberculosis who had undergone the NAAT on extrapulmonary specimens were identified. From three patients, NAAT results were nondiagnostic because of inhibitors, and they were excluded from the analysis, leaving 32 patients. Tuberculosis was ultimately diagnosed in 14 of these 32 patients. NAAT findings were positive in specimens from 12 of 14 patients with extrapulmonary tuberculosis and in 0 of 18 cases in which tuberculosis was excluded (sensitivity, 86%; specificity, 100%; positive predictive value, 100%; negative predictive value, 90%). In only 2 of 19 patients treated with antituberculous medications was the NAAT result used to determine the onset or discontinuation of therapy. In no instance was a negative NAAT result used by clinicians as definitive evidence that a patient did not have extrapulmonary tuberculosis; in all but one case, patients were continued on antituberculous therapy until final culture results were available. CONCLUSIONS: The NAAT proved to be a sensitive and specific test for detection of M tuberculosis in extrapulmonary specimens but did not weigh heavily in clinical decision making at our hospital. Judicious use of these tests may improve the accuracy and speed of diagnosis of extrapulmonary tuberculosis, while helping to eliminate unnecessary antituberculous treatment in patients without tuberculosis.

Adolescent↗

PubMed2000

[The complication with tuberculosis of the central nervous system in patients with miliary tuberculosis].

The complication with tuberculosis of the central nervous system (CNS) were studied in 16 patients with miliary tuberculosis who were admitted to our hospital during a period of two years from April, 1997 to March, 1999, and were examined by head MRI. Twelve cases (75%) were diagnosed as having tuberculosis of CNS. Six cases had tuberculosis of CNS which was found during the screening of miliary tuberculosis cases, and all had only cerebral tuberculoma. Meningeal irritative symptoms led to the discovery of tuberculosis of CNS in the remaining six cases, in which cerebral tuberculoma was complicated with tuberculous meningitis. Of these cases of meningitis, three cases showing disturbance of consciousness died, but no cases of death was found in cases by the screening. The length of time from the onset of symptoms to the diagnosis of tuberculosis was long in many of the cases complicated with tuberculosis of CNS compared with the cases without such a complication. In the cases of miliary tuberculosis, the rate of complication with tuberculosis of CNS is high, and the possibility of patients developing serious symptoms suddenly even when they were asymptomatic at the time of diagnosis and the paradoxical expansion that becomes intensified after initiation of treatment have been reported. Therefore, it is necessary to make a close checkup of CNS when the diagnosis of miliary tuberculosis has been made.

Adult↗

PubMed2006

[Study on the cause of tuberculosis recurrence by Mycobacterium tuberculosis genotyping method].

OBJECTIVE: To study the contribution of exogenous reinfection to tuberculosis recurrence. METHODS: Mycobacterium tuberculosis isolates from patients who had experienced 2 successive tuberculosis episodes during the years from January 1999 to March 2004 were genotyped by mycobacterial interspersed repetitive units (MIRU) method. The cause of tuberculosis recurrence was determined by comparing the MIRU pattern of Mycobacterium tuberculosis isolates responsible for different tuberculosis episodes from patients. RESULTS: Of 37 qualified patients with recurrent tuberculosis, the isolates from 25 patients in their two tuberculosis episodes showed different MIRU patterns, indicating that 68% recurrent patients were due to exogenous reinfection. The exogenous reinfection rate decreased with the age from 3/3 (under 30 years) to 73% (11/15, 30 to 60 years) and 58% (11/19, over 60 years). The frequency of exogenous reinfection increased with the tuberculosis recurrent interval. Within 6 months, the exogenous reinfection accounted for 58% (7/12) of all the recurrence, while for the time more than one year, the percentage increased to 79% (11/14). CONCLUSIONS: Exogenous reinfection was a major cause of tuberculosis recurrence in Shanghai. MIRU genotyping method is useful to study the cause of tuberculosis recurrence.

Adolescent↗

PubMed1995

Tuberculosis in the autopsy material: analysis of 1500 autopsies performed between 1972 and 1991 in the Institute of Tuberculosis and Chest Diseases, Warsaw, Poland.

SETTING: The present study is based on 1500 autopsies done in the Institute of Tuberculosis and Chest Diseases Warsaw, Poland during the years 1972-81 and 1982-91. OBJECTIVE: To assess the correctness of tuberculosis diagnosis before death in the above mentioned time periods. DESIGN: The autopsy reports were examined for the diagnosis of active tuberculosis proved by microscopy. The form and localisation of tuberculosis was assessed. The postmortem diagnosis was compared with clinical diagnosis. In those cases in which tuberculosis was not recognised before death the possible causes of this failure were analyzed. RESULTS: Active tuberculosis was found in 119 cases, 7.9% of all autopsies. It was localised in the lungs exclusively in 72 cases, in lungs and in extrapulmonary sites in 45 and in extrapulmonary sites only in 2. The frequency of active tuberculosis was the same for the two periods under evaluation. Tuberculosis was however not recognised before death in a much higher proportion of cases in 1982-92 (54%) than in 1972-81 (24%). The main cause of diagnostic failure was connected with atypical localisation of lesions on chest X-ray and with dissemination outside the lungs. Previous tuberculosis was a factor which facilitated the diagnosis of tuberculosis. CONCLUSIONS: In parallel with the decline of tuberculosis incidence in Poland, many doctors lack experience in diagnosing this disease, especially in cases with atypical X-ray presentation and with extrapulmonary localisation. This may lead to late or even very late diagnosis and have a significant impact on the epidemiological situation.

Adolescent↗

PubMed1993

[An epidemiological study of tuberculosis in the former coal-mining area of Chikuho. I. An analysis of newly registered tuberculosis patients in Iizuka Health Center District].

To clarify risk factors and groups at high risk of tuberculosis, a study on tuberculosis was conducted in the former coalmining area of Chikuho, where the death rate from tuberculosis was high. The authors analysed 701 newly registered tuberculosis patients during the 5 years from 1982 through 1986 in Iizuka Health Center District in the Chikuho area, studied the geographical distribution of tuberculosis incidence in Fukuoka Prefecture, and compared the trends of tuberculosis incidence in Iizuka Health Center District, all Japan and Fukuoka Prefecture. The results were as follows: 1) The incidence of tuberculosis in Iizuka Health Center District was higher than those both in all Japan and in Fukuoka Prefecture. The incidence in Iizuka Health Center District has not decreased since 1981. Therefore, the difference in tuberculosis incidence between Iizuka Health Center District, and all Japan and Fukuoka Prefecture has gradually become greater. The incidence of tuberculosis in 1986 was 81.6 (per 100,000) in Iizuka Health Center District, 58.1 in Fukuoka Prefecture, 46.6 in all Japan. 2) A specific pattern was observed in the geographical distribution of tuberculosis incidence in Fukuoka Prefecture. A high incidence was concentrated in the former coalmining area of Chikuho. 3) The positive rate of tubercle bacilli (38.8%) was the same as that in all Japan. However, the positive rate was higher in age groups 10-49 than that in all Japan. 4) A total of 83.5% of tuberculosis cases were detected when visiting doctors, mainly with complaints of cough, fever and sputum. Only 6.9% of the patients were detected by screening examinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1999

[Management of mycobacteriosis in general hospital without isolation ward for tuberculosis patients. 4. Actual status of the management of tuberculosis patients in a university hospital without isolation wards for infectious diseases].

We retrospectively evaluated clinical findings and the actual status of management of 69 tuberculosis patients admitted to the Fujita Health University Hospital, a hospital without isolation wards for infectious diseases, between 1991 and 1994. Forty-nine patients were smear-positive and 22 patients were smear-negative and culture-positive. Twenty-five cases (36.2%) were classified as type II (cavitary) and 29 cases (42.0%) as type III (non-cavitary) according to the GAKKAI classification of findings on chest X-ray films for pulmonary tuberculosis. Physicians in charge did not diagnose twenty-four patients (34.8%) as tuberculosis on admission. Physicians in charge tended not to suspect smear-negative patients of tuberculosis. Most of the patients with cavities on their chest X-ray films were strongly suspected of tuberculosis on admission, but in some of them, tuberculosis was not considered at all. Smear-positive patients with strongly suspected tuberculosis were diagnosed with the disease within three hospital days, while it took about three weeks in patients who were not considered as tuberculosis on admission to be diagnosed as tuberculosis. In the case of smear-negative patients, it took about one month and two months respectively to diagnose the case as tuberculosis. About half (51.1%) of the smear-positive patients were admitted and treated in single-bed rooms while 44.7% were attended in multiple-bed rooms for 11 days before they were transferred to single-bed rooms. When acid-fast bacilli were detected, 57.4% of the smear-positive patients were transferred to hospitals with isolation wards for infectious diseases, while the remaining smear-positive patients were treated in single-bed rooms at the university hospital. About one-third (31.7%) of the smear-negative patients had already left the hospital when specimens were found to be culture positive for tubercle bacilli. In conclusion, it is utmost important for physicians to suspect to tuberculosis for the early diagnosis of the disease.

Adult↗

PubMed1995

Epidemiological trends of tuberculosis in Spain from 1988 to 1992. Collaborative Group for the Study of Tuberculosis in Spain.

SETTING: Spain is one of the few industrialized countries in which reliable official data on the occurrence of tuberculosis are not available. OBJECTIVE: One of the purposes of the Tuberculosis and Respiratory Infection (TRI) working group established by the Spanish Society of Thoracic Surgery (Sociedad Española de Nuemología y Cirugía Torácica [SEPAR]) in 1988, was to determine the true situation of Mycobacterium tuberculosis infection and active tuberculosis disease in our country. DESIGN: A questionnaire requesting epidemiological data on tuberculosis was sent to the Departments of Public Health of all the Autonomous Communities in Spain (n = 17) and 60 members of the TRI working group (pneumologists, epidemiologists or microbiologists most actively working in the field of tuberculosis within their corresponding areas of influence). Results obtained for the period 1988 and 1992 were analyzed. RESULTS: In the 6-year-old group, annual prevalence-of-infection rates were almost 0.95%, with a slight decreasing trend over the study period. In the 14-year-old group, annual figures of around 3% have been registered. The 1992 incidence rates of new cases of tuberculosis and sputum-smear positive tuberculosis were 40 and 21.2 per 100,000, respectively. Frequently distribution by age has shown a similar trend during the study period with a clear predominance in the younger adult age groups. Reliable data in relation to the number of patients with tuberculosis and HIV infection was available in 1992. Of 5290 patients in a population of 16,954,942, there were 792 (15%) with HIV infection. CONCLUSIONS: The current epidemiological situation of tuberculosis in Spain is one of the most unfavourable as compared with epidemiological data from the remaining industrialized countries. Given the lack of a National Programme for Tuberculosis Control, each Autonomous Community should take responsibility for developing and implementing key control activities based on the cure of infectious cases and case-finding.

Adolescent↗

PubMed1996

[Detection of Mycobacterium tuberculosis in clinical specimens other than sputum by the Mycobacterium Tuberculosis Direct Test (MTD)--assessment of sample preparation methods and clinical evaluation].

The Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (MTD) has been widely used as a rapid test for the identification of Mycobacterium tuberculosis complex in clinical samples, and several research groups have verified its clinical usefulness. However, most of the specimens they tested were sputum, and there have been few reports on other specimens. In particular, there have been no reports on assessments of methods of preparing samples other than sputum for the MTD. We assessed methods of preparing samples other than sputum and the influence of a local anesthetic and an anticoagulant that may be present in samples, and also evaluated the MTD as a means of detecting M. tuberculosis in pleural fluid, bronchial lavage cerebrospinal fluid, urine and ascitic fluid. 1. Assessment of three sample preparation methods, i.e., the NALC-NaOH method GuSCN-Diatom nucleic acid extraction method, and the ultrasonication method, revealed that the combination of the NALC-NaOH method and the ultrasonication method, widely used to prepare sputum samples, is also a valid method of preparing other samples. 2. The local anesthetic and the anticoagulant used clinically and remained in specimens did not affect the results of the MTD. 3. Seven (36.8%) of 19 pleural fluid samples from patients diagnosed as tuberculous pleurisy were positive of M. tuberculosis by the MTD, while five (27.8%) of 18 pleural fluid samples cultured for bacteria were positive for M. tuberculosis complex. None of the 20 pleural fluid samples from patients diagnosed as non-tuberculous pleurisy were positive for M. tuberculosis complex either by MTD or culture. 4. Eight (32.0%) of 25 bronchial lavage samples from patients diagnosed as pulmonary tuberculosis were positive for M. tuberculosis complex by the MTD, while 3 (12.0%) were positive by culture. None of the 18 bronchial lavage samples from patients diagnosed as non-tuberculous disease were positive for M. tuberculosis complex either by the MTD or culture. Based on these results, it is concluded that the MTD is a very useful method of detecting M. tuberculosis in clinical samples other than sputum because it is more sensitive than culture on Ogawa's egg medium in detecting M. tuberculosis complex in pleural fluid samples, bronchial lavage samples, and so on, with the same preparation method as used for sputum.

Bacteriological Techniques↗

PubMed2004

[The usefulness of colonoscopic biopsy in the diagnosis of intestinal tuberculosis and pattern of concomitant extra-intestinal tuberculosis].

BACKGROUND/AIMS: Intestinal tuberculosis can be difficult to diagnose because it may mimic many other intestinal diseases. The aim of this study was to evaluate the diagnostic yield of colonoscopic biopsy and frequency of concomittent extra-intestinal tuberculosis in intestinal tuberculosis. METHODS: The medical records of 225 consecutive patients with intestinal tuberculosis (81 men, 144 women; mean age 40.6 yrs) were analyzed retrospectively. RESULTS: Histological examination of colonoscopic biopsy specimens revealed granulomas in 163 (72.4%) of the 225 patients. However, caseous necrosis was found in only 25 (11.1%) patients, and acid-fast bacilli (AFB) were noted in 39 (17.3%) of the 225 patients. Mycobacterium tuberculosis was isolated from the culture of biopsy specimens in 52 (29.3%) of 177 patients. Eighty-four patients (37.3%) had concomitant extra-intestinal tuberculosis and 67 (29.8%) showed active pulmonary tuberculosis. Histological examination of the biopsy specimens enabled the diagnosis of intestinal tuberculosis by the presence of either caseating granulomas or AFB in 52 (23.1%) patients. Combination of histological examination and Mycobacterium culture established the diagnosis in 87 (38.7%) patients. Before getting the result of Mycobacterium culture, the diagnosis could be made, by either histological examination or the presence of extra-intestinal tuberculosis in 107 (47.6%) patients. Combination of caseating granulomas, AFB staining, Mycobacterium culture, and the presence of extra-intestinal tuberculosis resulted in the diagnosis in 126 (56.0%) patients. CONCLUSIONS: To increase the diagnostic yield, AFB staining and Mycobacterium culture should be routinely performed on biopsy specimens in addition to routine histological examination for caseating granulomas.

Adolescent↗

PubMed2000

Interventions for promoting adherence to tuberculosis management.

BACKGROUND: Up to half the people with tuberculosis do not complete their treatment. Strategies to improve adherence to treatment can be targeted at the person with the disease or at health workers. OBJECTIVES: The objective of this review was to assess the effects of promoting adherence to anti-tuberculosis treatment and completion of diagnostic protocols for TB. SEARCH STRATEGY: We searched the Cochrane Collaboration Trials, the Cochrane Effective Professional Practice Group trials register, the Cochrane Infectious Diseases Group trials register, Medline, Embase, Lilacs and reference lists of articles. We contacted experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials of interventions to promote adherence with curative or preventive chemotherapy and diagnostic protocols for tuberculosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Eleven trials were included. Reminder cards sent to defaulters, a combination package of a monetary incentive and health education and more supervision of tuberculosis clinic staff increased the number of people completing their tuberculosis treatment. Direct observation by clinic nurses of people swallowing their tuberculosis drugs did not increase the likelihood of treatment success. Return to the clinic for reading of a tuberculin skin test was enhanced by monetary incentives, assistance by lay health workers, contracts and telephone prompts but not by health education. REVIEWER'S CONCLUSIONS: We have found evidence of benefit for a number of specific interventions to improve adherence to anti-tuberculous therapy and completion of diagnostic protocols. These should be implemented by health care providers where appropriate to local circumstances. Future studies in low income countries are a priority and should measure adherence as well as clinical outcomes.

Antitubercular Agents↗

PubMed2003

Longitudinal analysis of Mycobacterium tuberculosis 19-kDa antigen-specific T cells in patients with pulmonary tuberculosis: association with disease activity and cross-reactivity to a peptide from HIVenv gp120.

CD8(+) T cells play a central role in immune protection against infection with Mycobacterium tuberculosis. One of the target epitopes for anti-M. tuberculosis directed CD8(+) T cells is the HLA-A2-restricted 19-kDa lipoprotein peptide VLTDGNPPEV. T cell clones directed against this epitope recognized not only the nominal peptide ligand, but also a closely related peptide (VPTDPNPPEV) from the HIV envelope gp120 (HIV(env) gp120) protein characterized by IFN-gamma release. This cross-reactivity was confirmed in ex vivo in M. tuberculosis 19-kDa tetramer-sorted T cells from patients with tuberculosis and in HIVgp120 tetramer-reactive T cells sorted from HIV(+) patients. M. tuberculosis 19-kDa antigen-reactive T cells were present in HLA-A2(+) patients (10/10) with HIV infection with no evidence of M. tuberculosis infection, but they are absent in peripheral blood lymphocytes from healthy HLA-A2(+) individuals (10/10). M. tuberculosis 19-kDa antigen-reactive T cells were elevated in acute pulmonary tuberculosis, declined with response to therapy (7/10 patients) and resided in the terminally differentiated CD8(+) T cell subset. CD8(+) cross-reactive T cells recognizing HIV(env) or M. tuberculosis 19-kDa antigens may contribute to pathogenesis in individuals co-infected with both pathogens and may also present a marker for active tuberculosis.

Antigens, Bacterial↗

PubMed2006

Mycobacterium tuberculosis invasion and traversal across an in vitro human blood-brain barrier as a pathogenic mechanism for central nervous system tuberculosis.

BACKGROUND: Central nervous system (CNS) tuberculosis is a serious, often fatal disease that disproportionately affects young children. It is thought to develop when Mycobacterium tuberculosis breaches the blood-brain barrier (BBB), which is composed of tightly apposed brain microvascular endothelial cells. However, the mechanism(s) involved in this process are poorly understood. METHODS: To better understand these processes, we developed an in vitro model of M. tuberculosis BBB infection using primary human brain microvascular endothelial cells. RESULTS: M. tuberculosis was found to both invade and traverse the model BBB significantly more than did M. smegmatis (a nonpathogenic mycobacterium). Invasion by M. tuberculosis across the BBB required host-cell actin cytoskeletal rearrangements. By microarray expression profiling, we found 33 M. tuberculosis genes to be highly up-regulated during the early stages of invasion of the BBB by M. tuberculosis; 18 of them belong to a previously described in vivo-expressed genomic island (Rv0960-Rv1001). Defined M. tuberculosis isogenic transposon mutants for the up-regulated genes Rv0980c, Rv0987, Rv0989c, and Rv1801 were found to be deficient in their ability to invade the BBB model. CONCLUSIONS: We developed an in vitro model of M. tuberculosis BBB infection and identified M. tuberculosis genes that may be involved in CNS invasion.

Actins↗

PubMed1995

Predictive factors of Mycobacterium tuberculosis infection and pulmonary tuberculosis in prisoners.

BACKGROUND: Tuberculosis currently represents a serious problem in prison populations. METHODS: With the aim of studying the predictive factors for, and the prevalence of, Mycobacterium tuberculosis infection and pulmonary tuberculosis in a Spanish prison, all those admitted during 1991 and 1992 were included (N = 1314). The tuberculin skin test, HIV serology, chest X-ray and bacteriological examination of sputum were carried out. Statistical analysis was done by univariant tests, stratified analysis and logistic regression. RESULTS: The prevalence of M. tuberculosis infection was 55.5% (95% confidence interval [CI] 52.5-58.5). An association was found with sex, imprisonment more than once, HIV infection and age. The co-infection rate (tuberculosis plus HIV) was 9.2%. Logistic regression showed a greater risk with age (4.4% per year), time spent in prison and for males. The prevalence of pulmonary tuberculosis was 1.26% and an association was found with M. tuberculosis infection, HIV infection (odds ratio [OR] = 13.7), intravenous drug users (OR = 17.2) and imprisonment more than once (OR = 7.3). Logistic regression showed an association with HIV co-infection (OR = 20.2). CONCLUSIONS: The prevalence of M. tuberculosis infection and pulmonary tuberculosis is high when compared with similar studies. The influence of age, time spent in prison and co-infection with HIV is relevant to recommendations for specific tuberculosis prevention programmes in correctional facilities.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Rapid detection of active and latent tuberculosis infection in HIV-positive individuals by enumeration of Mycobacterium tuberculosis-specific T cells.

OBJECTIVES: An accurate test for Mycobacterium tuberculosis infection is urgently needed. The tuberculin skin test (TST) lacks sensitivity, particularly in HIV-infected individuals, and has poor specificity because of antigenic cross-reactivity with Bacillus Calmette-Guérin (BCG) vaccination. ESAT-6 and CFP-10 are antigens expressed in Mycobacterium tuberculosis, but not in Mycobacterium bovis BCG and most environmental mycobacteria. We investigated whether T cells specific for these antigens could serve as accurate markers of M. tuberculosis infection in an area of high tuberculosis and HIV prevalence. METHODS: Using the rapid ex-vivo enzyme-linked immunospot (ELISPOT) assay for IFN-gamma, we enumerated T cells specific for ESAT-6, CFP-10 and purified protein derivative (PPD) in blood samples from 50 Zambian tuberculosis patients, 75 healthy Zambian adults, and 40 healthy UK residents. TSTs were performed in 49 healthy Zambian adults. RESULTS: All (100%; n = 11) and 90% (n = 39) of HIV-negative and HIV-positive tuberculosis patients, respectively, had detectable ESAT-6- or CFP-10-specific T cells. The ESAT-6/CFP-10-based ELISPOT assay was positive in 37 out of 54 HIV-negative healthy Zambians, suggesting a 69% prevalence of latent M. tuberculosis infection. Fewer HIV-positive Zambians possessed ESAT-6/CFP-10-specific T cells, but the impact of HIV infection was less on this assay than on the PPD-based ELISPOT or TST. CONCLUSION: The ESAT-6/CFP-10-based ELISPOT assay detects active tuberculosis in HIV-positive individuals with high sensitivity. It is more specific, and possibly more sensitive, than PPD-based methods of detecting latent M. tuberculosis infection, and may potentially improve the targeting of isoniazid preventative therapy to HIV-positive individuals with latent tuberculosis infection.

Adolescent↗

PubMed2003

[A case of pulmonary tuberculosis preceded by skin tuberculosis].

We report a case of pulmonary tuberculosis, which was preceded by skin tuberculosis. 65-year old male was admitted to our hospital complaining of skin eruption which last one year. Skin biopsy proved granuloma with acid-fast bacilli. Mycobacterium tuberculosis was detected by PCR examination using skin biopsy and skin tuberculosis was confirmed. Chest roentogenography demonstrated small nodules with bilateral infiltrates compatible with pulmonary tuberculosis. M. tuberculosis was attained by culture examination using sputa sample. In this case, skin tuberculosis was a first clinical sign to suggest pulmonary tuberculosis. Peripheral blood test showed that he has developed adult T-cell leukemia and this could be an important factor for developing skin tuberculosis. Although skin tuberculosis becomes rare disease, physician should pay attention for this disease as differential diagnosis of lasting eruption.

Aged↗

PubMed2003

Inhibition of Mycobacterium tuberculosis glutamine synthetase as a novel antibiotic strategy against tuberculosis: demonstration of efficacy in vivo.

Tuberculosis remains one of humankind's greatest killers, and new therapeutic strategies are needed to combat the causative agent, Mycobacterium tuberculosis, which is rapidly developing resistance to conventional antibiotics. Using the highly demanding guinea pig model of pulmonary tuberculosis, we have investigated the feasibility of inhibiting M. tuberculosis glutamine synthetase (GS), an enzyme that plays a key role in both nitrogen metabolism and cell wall biosynthesis, as a novel antibiotic strategy. In guinea pigs challenged by aerosol with the highly virulent Erdman strain of M. tuberculosis, the GS inhibitor L-methionine-SR-sulfoximine (MSO) protected the animals against weight loss, a hallmark of tuberculosis, and against the growth of M. tuberculosis in the lungs and spleen; MSO reduced the CFU of M. tuberculosis at 10 weeks after challenge by approximately 0.7 log unit compared with that in control animals. MSO acted synergistically with isoniazid in protecting animals against weight loss and bacterial growth, reducing the CFU in the lungs and spleen by approximately 1.5 log units below the level seen with isoniazid alone. In the presence of ascorbate, which allows treatment with a higher dose, MSO was highly efficacious, reducing the CFU in the lungs and spleen by 2.5 log units compared with that in control animals. This study demonstrates that inhibition of M. tuberculosis GS is a feasible therapeutic strategy against this pathogen and supports the concept that M. tuberculosis enzymes involved in cell wall biosynthesis, including major secretory proteins, have potential as antibiotic targets.

Animals↗

PubMed1997

Drug-resistant Mycobacterium tuberculosis and atypical mycobacteria isolated from patients with suspected pulmonary tuberculosis in Honduras.

BACKGROUND: Tuberculosis is a major health problem in Central America. In Honduras, with an incidence rate of 81/100,000, it is an increasingly common cause of morbidity and hospitalization. This study was conducted to examine drug-resistant tuberculosis and prevalence of infection with atypical mycobacteria in Honduran patients with suspected pulmonary tuberculosis. METHODS: Pulmonary specimens from 235 Honduran patients with suspected tuberculosis were examined by acid-fast smears and culture. The 95 mycobacterial strains isolated were identified to species level and drug susceptibility tests were carried out. Resistant Mycobacterium tuberculosis strains were tested for susceptibility to six additional drugs. Their possible relationship was studied by DNA restriction fragment length polymorphism. RESULTS: Drug-resistant strains were found in 13 of 85 culture-verified tuberculosis patients, including 10 with isolates of multidrug-resistant bacteria. Seven of the patients with multidrug-resistant tuberculosis had smear-positive disease. Nine of them had a history of specific therapy. Two patients with drug-resistant disease were shown to be infected by identical strains. Only one of 11 HIV-positive patients had drug-resistant tuberculosis. Most resistant strains were susceptible to ciprofloxacin, amikacin, kanamycin, and pyrazinamide. Atypical mycobacteria were isolated from 10 patients with suspected tuberculosis. Seven of them were receiving antituberculosis chemotherapy and five had smear-positive samples. CONCLUSIONS: These results illustrate the importance of mycobacterial culture and subsequent species identification and in vitro susceptibility testing for identification of patients with drug-susceptible or drug-resistant tuberculosis and those infected or colonized with other mycobacteria.

Adult↗