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1.
Int J Tuberc Lung Dis ; 20(3): 295-303, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27046708

ABSTRACT

OBJECTIVE: To assess the 2012 served available market for tuberculosis (TB) diagnostics in China in the sector served by the China Centre for Disease Control and Prevention (CDC) and the hospital sector in China, including both designated TB hospitals and general hospitals. DESIGN: Test volumes and unit costs were assessed for tuberculin skin tests, interferon-gamma release assays (IGRAs), smear microscopy, serology, cultures, speciation tests, nucleic-acid amplification tests (NAATs), drug susceptibility tests and adenosine-deaminase tests (ADA). Data were obtained from electronic databases (CDC sector) and through surveys (hospital sector), and were estimated for the two sectors and for the country as a whole. Test costs were estimated by staff at China CDC, and using published literature. RESULTS: In 2012, the China CDC and hospital sectors performed a total of 44 million TB diagnostic tests at an overall value of US$294 million. Tests used by the CDC sector were smear microscopy, solid and liquid culture and DST, while the hospital sector also used IGRAs, NAATs, ADA and serology. The hospital sector accounted for 76% of the overall test volume and 94% of the market value. CONCLUSION: China has a very large TB diagnostic market that encompasses a wide range of diagnostic tests, with the majority being performed in Chinese hospitals.


Subject(s)
Diagnostic Tests, Routine/economics , Diagnostic Tests, Routine/methods , Tuberculosis/diagnosis , Adenosine Deaminase/analysis , China , Humans , Interferon-gamma Release Tests/economics , Interferon-gamma Release Tests/methods , Microscopy/economics , Microscopy/methods , Nucleic Acid Amplification Techniques/economics , Nucleic Acid Amplification Techniques/methods , Tuberculin Test/economics , Tuberculin Test/methods
2.
Int J Tuberc Lung Dis ; 20(3): 304-13, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27046709

ABSTRACT

BACKGROUND: India represents a significant potential market for new tests. We assessed India's market for tuberculosis (TB) diagnostics in 2013. METHODS: Test volumes and unit costs were assessed for tuberculin tests, interferon-gamma release assays, sputum smear microscopy, serology, culture, speciation testing, nucleic-acid amplification tests (i.e., in-house polymerase chain reaction, Xpert(®) MTB/RIF, line-probe assays) and drug susceptibility testing. Data from the public sector were collected from the Revised National TB Control Programme reports. Private sector data were collected through a survey of private laboratories and practitioners. Data were also collected from manufacturers. RESULTS: In 2013, India's public sector performed 19.2 million tests, with a market value of US$22.9 million. The private sector performed 13.6 million tests, with a market value of US$60.4 million when prices charged to the patient were applied. The overall market was US$70.8 million when unit costs from the ingredient approach were used for the 32.8 million TB tests performed in the entire country. Smear microscopy was the most common test performed, accounting for 25% of the overall market value. CONCLUSION: India's estimated market value for TB diagnostics in 2013 was US$70.8 million. These data should be of relevance to test developers, donors and implementers.


Subject(s)
Tuberculin Test/economics , Tuberculosis/diagnosis , Tuberculosis/economics , Humans , India , Interferon-gamma Release Tests/economics , Microscopy/economics , Mycobacterium tuberculosis/isolation & purification , Nucleic Acid Amplification Techniques/economics , Polymerase Chain Reaction/economics , Private Sector/economics , Public Sector/economics , Sensitivity and Specificity , Sputum/microbiology
3.
Int J Tuberc Lung Dis ; 14(11): 1461-7, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20937188

ABSTRACT

BACKGROUND: The Special Programme for Research and Training in Tropical Diseases established a specimen bank in 1999 to support the development and evaluation of new tuberculosis (TB) diagnostic tools. OBJECTIVE: To provide a narrative of the bank's development and discuss lessons learned, the bank's limitations and potential future applications. RESULTS: Collection sites were selected in high- and low-prevalence settings. Patients with TB symptoms, consenting to participate and to undergo human immunodeficiency virus testing were enrolled and diagnosed. Serum, sputum, saliva and urine samples were collected and sent to the bank's repositories. The bank has stocked 41,437 samples from 2524 patients at 11 sites worldwide. Ninety-five requests for specimens have been reviewed and 67 sets have been approved. Approved applicants have received sets of 20 or 200 samples. The bank allowed an evaluation of 19 commercial lateral flow tests and showed that none of them had broad global utility for TB diagnosis. CONCLUSIONS: The establishment and development of the specimen bank have provided a wealth of experience. It is fulfilling a need to provide quality specimens, but the type and number of samples may not fulfil the demands of future end-users. Plans are underway to review the mechanisms of specimen collection and distribution to maximise their impact on product development.


Subject(s)
Biological Specimen Banks/organization & administration , Specimen Handling/methods , Tuberculosis/diagnosis , Humans , Sputum/microbiology , Tropical Medicine/methods , Tuberculosis/epidemiology
4.
Int J Tuberc Lung Dis ; 14(2): 238-40, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20074417

ABSTRACT

We evaluated the diagnostic performance of the Diagnos TB AG immunoassay in 171 Tanzanians with suspected pulmonary tuberculosis (TB). The sensitivity and specificity, and positive and negative predictive values of the rapid test for the detection of pulmonary TB in this population were respectively 60.0%, 33.3%, 40.3% and 52.6%. In its current configuration, this test will not help overcome difficulties in the rapid diagnosis of TB.


Subject(s)
Antigens, Bacterial/immunology , Mycobacterium tuberculosis/immunology , Tuberculosis, Pulmonary/diagnosis , Adult , Female , Humans , Immunoassay/methods , Male , Predictive Value of Tests , Sensitivity and Specificity , Tanzania , Time Factors , Tuberculosis, Pulmonary/immunology
5.
Int J Tuberc Lung Dis ; 11(5): 485-95, 2007 May.
Article in English | MEDLINE | ID: mdl-17439669

ABSTRACT

Current international tuberculosis (TB) guidelines recommend the microscopic examination of three sputum specimens for acid-fast bacilli in the evaluation of persons suspected of having pulmonary TB. We conducted a systematic review of studies that quantified the diagnostic yield of each of three sputum specimens. By searching multiple databases and sources, we identified a total of 37 eligible studies. The incremental yield in smear-positive results (in studies using all smear-positive cases as the denominator) and the increase in sensitivity (in studies that used all culture-positive cases as the denominator) of the third specimen were the main outcomes of interest. Although heterogeneity in study methods and results presented challenges for data synthesis, subgroup analyses suggest that the average incremental yield and/or the increase in sensitivity of examining a third specimen ranged between 2% and 5%. Reducing the recommended number of specimens examined from three to two (particularly to two specimens collected on the same day) could benefit TB control programs, and potentially increase case detection for several reasons. A number of operational research issues need to be addressed. Studies examining the most effective and efficient means to utilize current technologies for microscopic examination of sputum would be most useful if they followed an internationally coordinated and standardized approach, both to strengthen the country-specific evidence base and to permit comparison among studies.


Subject(s)
Sputum/microbiology , Tuberculosis, Pulmonary/diagnosis , Humans , Sensitivity and Specificity , Specimen Handling
6.
Int J Tuberc Lung Dis ; 10(3): 256-8, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16562703

ABSTRACT

The World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (The Union) recommend direct sputum smear microscopy for tuberculosis (TB) case finding in resource-poor settings. This method is associated with poor sensitivity. Digestion of sputum with bleach prior to smear preparation has been reported to increase sensitivity. Some workers, having reviewed the relevant literature, have called for the WHO and The Union to advocate for a shift to this methodology for TB case finding. This article highlights deficiencies in the scope and detail of available evidence, and cautions against the premature, and possibly counter-productive, adoption of so-called 'bleach microscopy'. Further well-guided research is required to answer policy-relevant gaps in our knowledge about this promising technology.


Subject(s)
Hypochlorous Acid , Oxidants , Sputum/cytology , Tuberculosis/diagnosis , Tuberculosis/prevention & control , Humans , Microscopy/methods , World Health Organization
8.
Int J Tuberc Lung Dis ; 5(4): 321-8, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11334250

ABSTRACT

SETTING: Urban public teaching and referral hospital in Espirito Santo, Brazil. OBJECTIVE: To assess whether rates of infection and progression to active tuberculosis (TB) differed between household contacts of patients with multidrug-resistant (MDR) and drug susceptible (DS) pulmonary tuberculosis. DESIGN: Household contacts were assessed for evidence of TB infection and disease by purified protein derivative (PPD) skin testing, physical examination, chest X-ray, and sputum smear and culture. RESULTS: Among 133 close contacts of patients with MDR-TB, 44% were PPD-positive (> or =10 mm) compared to 37% of 231 contacts of the DS-TB cases (P = 0.18, chi2 test, OR 1.2, 95%CI 0.8-2). In a multivariate logistic regression analysis, after allowance for between-household variation in PPD responses, PPD positivity among household contacts of patients with MDR-TB remained comparable to PPD positivity in contacts of patients with DS-TB (OR 2.1, 95%CI 0.7-6.5). Respectively six (4%) and 11 (4%) contacts of the MDR- and DS-TB cases were found to have active TB at the time of initial evaluation or during follow-up (P = 0.78, chi2 test). Five of six contacts of MDR-TB cases and nine of nine contacts of DS-TB cases who developed TB, and for whom drug susceptibility test results were available, had the same bacterial susceptibility profiles as their index cases. DNA fingerprinting analysis of Mycobacterium tuberculosis isolates was identical between household contacts with active TB and the index MDR or DS-TB case for all 14 pairs compared. CONCLUSION: Our data suggest that the prevalence of tuberculous infection and progression to active TB among household contacts exposed to DS and MDR-TB cases is comparable, despite a longer duration of exposure of contacts to the index case in patients with MDR-TB.


Subject(s)
Disease Transmission, Infectious/statistics & numerical data , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/transmission , Adolescent , Adult , Age Distribution , Brazil/epidemiology , Cohort Studies , Confidence Intervals , Disease Progression , Family Characteristics , Female , Hospitals, Teaching , Humans , Infection Control , Male , Mass Chest X-Ray , Middle Aged , Odds Ratio , Physical Examination , Prevalence , Risk Factors , Sex Distribution , Sputum/microbiology , Tuberculin Test , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/transmission , Urban Population
9.
Int J Tuberc Lung Dis ; 4(11): 1074-7, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11092721

ABSTRACT

Questions have recently been raised regarding the potency of purified protein derivative (PPD) RT-23, the tuberculin most widely used world-wide for skin testing. We performed simultaneous testing with PPD RT-23 and Tubersol to compare these reagents during a tuberculin survey of 202 adult health care workers at a large teaching hospital in 1997. Individuals were tested with 2 tuberculin units (TU) PPD RT-23 and 5 TU Tubersol using the Mantoux method. Using a 10 mm cut-point for a positive PPD test, 39% of the health care workers were positive when tested with Tubersol and 35% were positive when tested with PPD RT-23. The median PPD size with Tubersol was 4 mm (interquartile range = 0-12 mm) compared to 2 mm (interquartile range = 0-12 mm) with PPD RT-23. PPD skin test reactivity with the two reagents was highly correlated (Spearman's rank coefficient, rho = 0.92; P = 0.01, two tailed). Concordance between the skin test reaction size with the two antigens did not differ based on age, sex or prior BCG vaccination. Mantoux skin test reactivity in health care workers in an area with a high prevalence of tuberculosis was comparable with PPD RT-23 and Tubersol.


Subject(s)
Personnel, Hospital , Tuberculin Test/methods , Tuberculin , Adolescent , Adult , Brazil , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Skin/pathology
11.
Am J Respir Crit Care Med ; 161(4 Pt 1): 1076-80, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10764293

ABSTRACT

Patients vary considerably in their response to treatment of pulmonary tuberculosis. Although several studies have indicated that adverse outcomes are more likely in those patients with delayed sputum sterilization, few tools are available to identify those patients prospectively. In this study, multivariate models were developed to predict the response to therapy in a prospectively recruited cohort of 42 HIV-uninfected subjects with drug-sensitive tuberculosis. The cohort included 2 subjects whose initial response was followed by drug-sensitive relapse. The total duration of culture positivity was best predicted by a model that included sputum M. tuberculosis antigen 85 concentration on Day 14 of therapy, days-to-positive in BACTEC on Day 30, and the baseline radiographic extent of disease (R = 0.63). A model in which quantitative AFB microscopy replaced BACTEC also performed adequately (R = 0.58). Both models predicted delayed clearance of bacilli in both relapses (> 85th percentile of all subjects) using information collected during the first month of therapy. Stratification of patients according to anticipated response to therapy may allow TB treatment to be individualized, potentially offering superior outcomes and greater efficiency in resource utilization, and aiding in the conduct of clinical trials.


Subject(s)
Antitubercular Agents/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Brazil/epidemiology , Cohort Studies , Culture Media , Humans , Linear Models , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/growth & development , Prospective Studies , Recurrence , Sputum/microbiology , Treatment Outcome , Tuberculosis, Pulmonary/epidemiology , Uganda/epidemiology
12.
Int J Tuberc Lung Dis ; 4(12 Suppl 2): S182-8, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11144551

ABSTRACT

Rapid and accurate diagnosis of symptomatic patients is a cornerstone of global tuberculosis control strategies. Remarkable progress has recently been made, upgrading the speed and quality of mycobacteriology diagnostic services in industrialized countries, but for most of the world where TB is a large public health burden those gains are still unrealized. Deficiencies in current case-finding tools in disease endemic countries have made it difficult to ensure access to good diagnostics at all health service levels, leaving many patients undiagnosed. Additionally, in well-established TB control programs where diagnostic access has been ensured, efforts to interrupt disease transmission have been hampered by the insensitivity and late detection of smear microscopy. Fortunately, technical progress in diagnostics is resulting in a number of improved tools, including some appropriate for low-income settings. Important work remains, however, before new diagnostic tools can be meaningfully integrated into national TB control programs of high-burden countries and before TB control strategies can take them into account. The design and quality of clinical trials evaluating new diagnostics must be improved, clinical and laboratory services that would allow rapid response to test results need to be enhanced, and basic and operational research to appraise the impact and cost-effectiveness of new diagnostic technologies must be carried out. This paper describes some of the recent advances in TB diagnostic technologies and puts them into perspective for global tuberculosis control.


Subject(s)
Bacterial Typing Techniques/trends , Mycobacterium tuberculosis/classification , Tuberculosis/diagnosis , Bacterial Typing Techniques/methods , Drug Resistance, Microbial/genetics , Drug Resistance, Multiple/genetics , Endemic Diseases , Global Health , Humans , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Sensitivity and Specificity , Tuberculosis, Multidrug-Resistant/diagnosis
13.
Antimicrob Agents Chemother ; 43(11): 2600-6, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10543735

ABSTRACT

Although Mycobacterium tuberculosis is eradicated rapidly during therapy in some patients with pulmonary tuberculosis, it can persist for many months in others. This study examined the relationship between mycobacterial drug tolerance (delayed killing in vitro), persistence, and relapse. It was performed with 39 fully drug-susceptible isolates from a prospective trial of standard short-course antituberculous therapy with sputum smear-positive, human immunodeficiency virus-uninfected subjects with pulmonary tuberculosis in Brazil and Uganda. The rate of killing in vitro was determined by monitoring the growth index (GI) in BACTEC 12B medium after addition of drug to established cultures and was measured as the number of days required for 99% sterilization. Drugs differed significantly in bactericidal activity, in the following order from greatest to least, rifampin > isoniazid-ethambutol > ethambutol (P < 0.001). Isolates from subjects who had relapses (n = 2) or in whom persistence was prolonged (n = 1) were significantly more tolerant of isoniazid-ethambutol and rifampin than isolates from other subjects (P < 0.01). More generally, the duration of persistence during therapy was predicted by strain tolerance to isoniazid and rifampin (P = 0.012 and 0.026, respectively). Tolerance to isoniazid-ethambutol and tolerance to rifampin were highly correlated (P < 0.001). Tolerant isolates did not differ from others with respect to the MIC of isoniazid; the rate of killing of a tolerant isolate by isoniazid-ethambutol was not increased at higher drug concentrations. These observations suggest that tolerance may not be due to drug-specific mechanisms. Tolerance was of the phenotypic type, although increased tolerance appeared to emerge after prolonged drug exposure in vivo. This study suggests that drug tolerance may be an important determinant of the outcome of therapy for tuberculosis.


Subject(s)
Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Tuberculosis, Pulmonary/microbiology , Carbon Dioxide/metabolism , Colony Count, Microbial , Culture Media , Drug Resistance, Microbial , Humans , Kinetics , Microbial Sensitivity Tests , Palmitic Acid/metabolism , Prospective Studies , Sputum/microbiology , Time Factors
15.
Am J Respir Crit Care Med ; 160(1): 203-10, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10390401

ABSTRACT

Effective treatment regimens for pulmonary tuberculosis are difficult to assess because of the slow growth rate of Mycobacterium tuberculosis in culture and its protracted clearance from sputum. A rapid method that reflects effective antimicrobial activity would markedly advance evaluation of treatment and promote the assessment of new antituberculosis drugs. Conventional methods measure the progressive reduction of numbers of acid-fast bacilli in the sputum smear and the clearance of organisms in sputum culture. In this study, we measured levels of M. tuberculosis 85B (alpha antigen) messenger RNA (mRNA), 16S ribosomal RNA (rRNA), and IS6110 DNA in patients' sputa to ascertain whether they could serve as potential surrogate markers of response to chemotherapy. Sputum specimens were sequentially collected for up to a year from 19 smear-positive pulmonary tuberculosis patients receiving an optimal drug treatment regimen. Nucleic acids were isolated from these specimens, and two M. tuberculosis molecular targets (mRNA, DNA) were quantified, using the ABI Prism 7700 Sequence Detection System. The Mycobacterium genus-specific 16S rRNA was quantified with a limiting dilution RT-PCR assay. Results show that levels of 85B mRNA declined after initiation of therapy, as did viable M. tuberculosis colony counts, with 90% of patients becoming negative for both markers after 2 mo of treatment. The rapid disappearance of M. tuberculosis mRNA from sputum suggests that it is a good indicator of microbial viability and a useful marker for rapid assessment of response to chemotherapy.


Subject(s)
Antitubercular Agents/therapeutic use , Mycobacterium tuberculosis/drug effects , RNA, Bacterial/drug effects , RNA, Messenger/drug effects , Sputum/microbiology , Tuberculosis, Pulmonary/drug therapy , Adult , Biomarkers/analysis , DNA, Bacterial/analysis , DNA, Bacterial/drug effects , Drug Therapy, Combination , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , RNA, Bacterial/analysis , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Treatment Outcome
16.
J Infect Dis ; 179(5): 1259-63, 1999 May.
Article in English | MEDLINE | ID: mdl-10191233

ABSTRACT

Before December 1997, in Espírito Santo, Brazil, combination antiretroviral therapy was used without routine virologic or immunologic monitoring. To examine consequences of therapy in this setting, clinical information, human immunodeficiency virus type 1 (HIV-1) RNA levels, CD4 cell counts, and protease and reverse transcriptase sequences were determined for consecutive HIV-1-infected outpatients. Of 48 treatment-naive individuals, 11 were started on therapy for HIV-related symptoms; however, 44 (92%) had an RNA level >20,000 copies/mL, a CD4 cell count <500/mm3, or symptoms. Eighteen (51%) of 35 patients on therapy had an RNA level >20,000 copies/mL. Nucleoside-resistance mutations were observed in 21 (68%) of 31 nucleoside-experienced subjects. Protease mutations necessary for high-level protease inhibitor (PI) resistance were present together with permissive mutations in 3 of 10 PI-experienced patients. Inability to identify high-risk individuals and to detect virologic failure may limit the effectiveness of antiretroviral drug programs and may promote the spread of drug resistance where virologic and immunologic monitoring are not available.


Subject(s)
Anti-HIV Agents/therapeutic use , Drug Resistance, Microbial/genetics , HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , HIV-1/genetics , Reverse Transcriptase Inhibitors/therapeutic use , Adult , Amino Acid Sequence , Anti-HIV Agents/pharmacology , Brazil , CD4 Lymphocyte Count , DNA, Viral/analysis , Drug Therapy, Combination , Female , HIV Infections/immunology , HIV Infections/virology , HIV Protease/genetics , HIV Protease Inhibitors/pharmacology , HIV Reverse Transcriptase/genetics , HIV-1/drug effects , Humans , Male , Mutation , RNA, Viral/analysis , Reverse Transcriptase Inhibitors/pharmacology , Sequence Analysis, DNA
17.
J Clin Microbiol ; 37(3): 518-23, 1999 Mar.
Article in English | MEDLINE | ID: mdl-9986805

ABSTRACT

Numerous assays have been described for the detection of DNA and rRNA sequences that are specific for the Mycobacterium tuberculosis complex. Although beneficial to initial diagnosis, such assays have proven unsuitable for monitoring therapeutic efficacy owing to the persistence of these nucleic acid targets long after conversion of smears and cultures to negative. However, prokaryotic mRNA has a typical half-life of only a few minutes and we have previously shown that the presence of mRNA is a good indicator of bacterial viability. The purpose of the present study was to develop a novel reverse transcriptase-strand displacement amplification system for the detection of M. tuberculosis alpha-antigen (85B protein) mRNA and to demonstrate the use of this assay in assessing chemotherapeutic efficacy in patients with pulmonary tuberculosis. The assay was applied to sequential, noninduced sputum specimens collected from four patients: 10 of 11 samples (91%) collected prior to the start of therapy were positive for alpha-antigen mRNA, compared with 1 of 8 (13%), 2 of 8 (25%), 2 of 8 (25%), and 0 of 8 collected on days 2, 4, 7, and 14 of treatment, respectively. In contrast, 39 of 44 samples (89%) collected on or before day 14 were positive for alpha-antigen DNA. The loss of detectable mRNA corresponded to a rapid drop over the first 4 days of treatment in the number of viable organisms present in each sputum sample, equivalent to a mean fall of 0.43 log10 CFU/ml/day. Analysis of mRNA is a potentially useful method for monitoring therapeutic efficacy and for rapid in vitro determination of drug susceptibility.


Subject(s)
Acyltransferases , Mycobacterium tuberculosis/isolation & purification , Nucleic Acid Amplification Techniques , RNA, Messenger/genetics , Sputum/microbiology , Tuberculosis/diagnosis , Antigens, Bacterial/genetics , Antitubercular Agents/therapeutic use , Bacterial Proteins/genetics , Base Sequence , DNA Primers , DNA, Bacterial/genetics , DNA, Bacterial/isolation & purification , Half-Life , Humans , Mycobacterium tuberculosis/genetics , RNA, Messenger/isolation & purification , Time Factors , Tuberculosis/drug therapy
18.
J Clin Microbiol ; 36(7): 1964-8, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9650945

ABSTRACT

Mycobacterium tuberculosis can persist in sputum for long periods of time after the initiation of antituberculosis chemotherapy. The purpose of this study was to determine whether quantitative estimates of M. tuberculosis DNA in sputum correlate with the numbers of viable bacilli and thus measure the therapeutic response of patients during treatment. Two methods of M. tuberculosis DNA quantification were examined by using DNA isolated from sputum specimens serially collected during the course of chemotherapy. A competitive PCR assay was compared to an automated system of real-time quantification with the ABI Prism 7700 Sequence Detection System (TaqMan). The ABI 7700 system uses standard PCR in conjunction with a fluorogenic probe in which the intensity of fluorescence is proportional to the amount of target DNA present. The results showed that both PCR systems are reproducible and accurate. The amounts of M. tuberculosis DNA quantified in sputum corresponded well with the numbers of acid-fast bacilli (AFB) counted by microscopy. Before initiation of antituberculosis therapy, measures of AFB, M. tuberculosis DNA, and cultivable bacilli were similar, suggesting that quantification of DNA is a good method for measuring the initial bacillary load. However, the rate of disappearance of both AFB and M. tuberculosis DNA did not correlate with the decline in cultivable bacilli in the specimen; therefore, these tests are not appropriate for monitoring treatment efficacy.


Subject(s)
DNA Transposable Elements , Mycobacterium tuberculosis/isolation & purification , Polymerase Chain Reaction/methods , Sputum/microbiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiology , Antitubercular Agents/therapeutic use , Bacteriological Techniques , Base Sequence , Binding, Competitive , Colony Count, Microbial , DNA Primers , DNA, Bacterial/analysis , Drug Therapy, Combination , Humans , Molecular Sequence Data , Mycobacterium tuberculosis/genetics , Time Factors
20.
Clin Infect Dis ; 24(6): 1139-46, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9195072

ABSTRACT

The attenuated bacille Calmette-Guérin (BCG) vaccine is administered to prevent tuberculosis. Complications of vaccination are uncommon. We report a new case of disseminated BCG disease and review 27 additional cases identified from a review of > 5,000 reports published between 1980 and 1996. Twenty-four of the 28 total cases were associated with an immune deficiency, including nine cases of AIDS. Seventy-one percent of the cases occurred in children younger than 2 years old. Sixty-eight percent of the patients were male. About one-half of the patients were vaccinated in a developed nation, but 85% of the cases were reported from a developed nation. Response to therapy was poor, with an overall mortality rate of 71%. We made two new observations. Disseminated BCG disease has historically been a disease of infants, but cases now occur in adults and older children coinfected with human immunodeficiency virus. Cases also occur after revaccination of individuals who were anergic following the initial administration of BCG vaccine. Disseminated BCG disease is an uncommon but devastating complication of vaccination that should be considered in the appropriate clinical setting. Immunocompromised infants and patients with late-stage AIDS are at greatest risk and respond poorly to standard therapies.


Subject(s)
BCG Vaccine/adverse effects , Vaccination/adverse effects , Female , HIV Infections/complications , Humans , Infant
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