The evolving relation between humans and Mycobacterium tuberculosis.
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Animals↗
Biomedical subjects
P M Small
Publications and source records attributed to P M Small.
Dissemination of Mycobacterium tuberculosis across the San Francisco Bay Area.
The propensity of Mycobacterium tuberculosis genotypes to spread across geographic boundaries was investigated by comparing the IS6110 and polymorphic GC-rich sequence patterns of M. tuberculosis isolates from San Francisco and the East Bay, two distinct regions separated by San Francisco Bay. Of 724 isolates from incident tuberculosis patients during 1992 and 1993, only 53 (7.3%) had patterns matching > or = 1 isolates from the other region. In the multivariable analysis of patient risk factors, an AIDS diagnosis (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.00-3.57) and non-Asian race (OR, 3.43; 95% CI, 1.59-7.42) were associated with having an isolate with a matching pattern. Of 375 unique IS6110 patterns among San Francisco isolates, only 9 (2.4%) matched patterns of East Bay isolates. These population-based data suggest that in the San Francisco Bay Area, M. tuberculosis does not rapidly spread across geographic boundaries, and tuberculosis control efforts should focus on transmission within defined areas.
Acquired Immunodeficiency Syndrome↗
Stability of Mycobacterium tuberculosis DNA genotypes.
To assess genotype stability in Mycobacterium tuberculosis, DNA genotypes were compared in sequential isolates from 49 patients who had sputum cultures separated by at least 90 days that grew M. tuberculosis. By use of IS6110 and the polymorphic GC-rich sequence (PGRS) as markers, it was found that paired isolates from 14 (29%) of 49 patients showed changes in their DNA genotypes between isolates (12 in IS6110 genotypes and 2 in PGRS genotypes). Changed IS6110 genotypes were confined to strains with 8-14 bands and were not related to the bacterial drug susceptibility, the patients' human immunodeficiency virus serostatus, or adherence to therapy. Although this rate of change complicates the interpretation of molecular epidemiologic studies, it can be exploited to gain additional insight into disease transmission. Furthermore, IS6110-related mutations may be a major source of genetic plasticity in M. tuberculosis and provide insights into the organism's evolution and virulence.
Antitubercular Agents↗
Simultaneous genotyping and species identification using hybridization pattern recognition analysis of generic Mycobacterium DNA arrays.
High-density oligonucleotide arrays can be used to rapidly examine large amounts of DNA sequence in a high throughput manner. An array designed to determine the specific nucleotide sequence of 705 bp of the rpoB gene of Mycobacterium tuberculosis accurately detected rifampin resistance associated with mutations of 44 clinical isolates of M. tuberculosis. The nucleotide sequence diversity in 121 Mycobacterial isolates (comprised of 10 species) was examined by both conventional dideoxynucleotide sequencing of the rpoB and 16S genes and by analysis of the rpoB oligonucleotide array hybridization patterns. Species identification for each of the isolates was similar irrespective of whether 16S sequence, rpoB sequence, or the pattern of rpoB hybridization was used. However, for several species, the number of alleles in the 16S and rpoB gene sequences provided discordant estimates of the genetic diversity within a species. In addition to confirming the array's intended utility for sequencing the region of M. tuberculosis that confers rifampin resistance, this work demonstrates that this array can identify the species of nontuberculous Mycobacteria. This demonstrates the general point that DNA microarrays that sequence important genomic regions (such as drug resistance or pathogenicity islands) can simultaneously identify species and provide some insight into the organism's population structure.
Alleles↗
Predictive value of contact investigation for identifying recent transmission of Mycobacterium tuberculosis.
Contact tracing, the evaluation of persons who have been in contact with patients having tuberculosis, is an important component of tuberculosis control. We used DNA fingerprinting to test the assumption that tuberculosis in contacts to active cases represents transmission from that person. Cases of tuberculosis in San Francisco between 1991 and 1996 with positive cultures who had been previously identified as contacts ("contact cases") to active cases ("index cases") were studied. Of 11,211 contacts evaluated, there were 66 pairs of culture-positive index and contact cases. DNA fingerprints were available for both members of these pairs in 54 instances (82%). The index and contact cases were infected with the same strain of Mycobacterium tuberculosis in 38 instances (70%; 95% CI: 56 to 82%); 16 pairs (30%) were infected with unrelated strains. Unrelated infections were more common among foreign-born (risk ratio [RR] = 5.22, p < 0.001), particularly Asian (RR = 3.89, p = 0.002) contacts. Contact investigation is an imperfect method for detecting transmission of M. tuberculosis, particularly in foreign-born persons. However, because such investigations target a group with a high prevalence of tuberculosis and tuberculous infection, these efforts remain an important activity in the control of tuberculosis.
Adult↗
Differences in contributing factors to tuberculosis incidence in U.S. -born and foreign-born persons.
To determine the factors contributing to tuberculosis incidence in the U.S.-born and foreign-born populations in San Francisco, California, and to assess the effectiveness of tuberculosis control efforts in these populations, we performed a population-based molecular epidemiologic study using 367 patients with strains of Mycobacterium tuberculosis recently introduced into the city. IS6110-based and PGRS-based restriction fragment length polymorphism (RFLP) analyses were performed on M. tuberculosis isolates. Patients whose isolates had identical RFLP patterns were considered a cluster. Review of public health and medical records, plus patient interviews, were used to determine the likelihood of transmission between clustered patients. None of the 252 foreign-born cases was recently infected (within 2 yr) in the city. Nineteen (17%) of 115 U. S.-born cases occurred after recent infection in the city; only two were infected by a foreign-born patient. Disease from recent infection in the city involved either a source or a secondary case with human immunodeficiency virus (HIV) infection, homelessness, or drug abuse. Failure to identify contacts accounted for the majority of secondary cases. In San Francisco, disease from recent transmission of M. tuberculosis has been virtually eliminated from the foreign-born but not from the U.S.-born population. An intensification of contact tracing and screening activities among HIV-infected, homeless, and drug-abusing persons is needed to further control tuberculosis in the U.S.-born population. Elimination of tuberculosis in both the foreign-born and the U.S. -born populations will require widespread use of preventive therapy.
AIDS-Related Opportunistic Infections↗
Epidemiology and clinical consequences of drug-resistant tuberculosis in a Guatemalan hospital.
STUDY OBJECTIVE: To determine the epidemiology and clinical consequences of drug-resistant TB in Guatemala. DESIGN: A prospective study conducted for 12 months. SETTING: A thoracic referral hospital in western Guatemala. PATIENTS: Three hundred and seventy-six patients with confirmed TB. RESULTS: Of 376 confirmed cases, 335 (89%) were culture-positive. Tests of drug sensitivities to four first-line antituberculous drugs were performed in 172 (51%) of the culture-positive cases. Fifty-one patients (30%) were resistant to at least one antimicrobial agent, and 26 (15%) were resistant to at least two drugs. In a multivariate model of clinically available patient characteristics, only cavitary disease (odds ratio=2.1; 95% confidence interval, 1.1-6.6) and a history of taking anti-TB medication for >2 weeks (OR=3.0; 95% CI, 1.5-10.3) were independent predictors of resistance to two or more anti-TB agents. Resistance to two or more anti-TB drugs was the single independent predictor of treatment failure (OR=6.4; 95% CI, 2.3-17.8). Twenty-four of 172 patients (14%) who denied having received prior anti-TB therapy were infected with resistant organisms, suggesting ongoing transmission of drug-resistant strains. Although 84% (69 of 82 cases) of patients with fully susceptible organisms and 89% (17 of 19 cases) with singly resistant organisms were cured, only 45% of patients (10 of 22 cases) infected with organisms resistant to two or more agents were successfully treated. CONCLUSIONS: At this sentinel site for complicated TB, a substantial subset of cases who are infected with drug-resistant bacteria cannot be easily identified or treated.
Adolescent↗
Epidemiology of Mycobacterium tuberculosis strains in San Francisco that do not contain IS6110.
IS6110 is commonly used as the basis for molecular epidemiologic and diagnostic studies of Mycobacterium tuberculosis. However, strains that do not contain IS6110 have been reported. If common, such strains would pose a limitation for molecular studies of M. tuberculosis. Analysis of a population-based sample from San Francisco of 1569 specimens submitted for fingerprinting demonstrated that the proportion of strains that lack IS6110 is less than 1%. While this low percentage permits IS6110 fingerprinting in San Francisco, it may be problematic in other settings.
Adult↗
Has BCG attenuated to impotence?
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BCG Vaccine↗
Highly drug-resistant tuberculosis.
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DNA Fingerprinting↗
Molecular fingerprinting of Mycobacterium tuberculosis: how can it help the clinician?
In just a few years, molecular fingerprinting of Mycobacterium tuberculosis has provided clinicians with significant insight into the epidemiology of tuberculosis. This methodology has allowed for a new understanding of the extent of new transmission of tuberculosis among residents of various communities and within institutions. It has also allowed for differentiation between episodes of reinfection and relapse, a task hitherto almost impossible to accomplish. In addition, molecular fingerprinting has allowed assessment of situations where laboratory cross-contamination is suspected. Thus, this technology has in many ways made clinicians reexamine many of their long-held beliefs regarding tuberculosis. In this report, Drs. Behr and Small provide a lucid description of molecular fingerprinting of M. tuberculosis, its current uses, and its future potential value.
DNA Fingerprinting↗
Tuberculosis in Mexican-born persons in San Francisco: reactivation, acquired infection and transmission.
SETTING: San Francisco, California. OBJECTIVE: To determine the relative contributions of infection acquired in San Francisco and reactivation of tuberculous infection acquired elsewhere in Mexican-born persons who developed tuberculosis in San Francisco, and to determine the frequency of transmission leading to secondary cases of tuberculosis in other persons. DESIGN: The study population consisted of all Mexican-born tuberculosis patients reported in San Francisco from 1991 through June 1995. All patients had positive cultures for Mycobacterium tuberculosis and DNA fingerprinting of isolates using IS6110 with more than two bands. Patients were classified as infected in San Francisco or infected elsewhere based on pre-defined criteria that included a second DNA fingerprinting technique (polymorphic guanine-cytosine-rich sequence), chart reviews, and selected patient interviews. RESULTS: Of the 43 Mexican-born patients studied, nine (21%) met the definition of infection acquired in San Francisco and 34 (79%) met the definition of reactivation of infection acquired elsewhere. Only one of the 43 cases resulted in two secondary cases in US-born persons. CONCLUSION: One-fifth of the Mexican-born patients who developed tuberculosis in San Francisco acquired their tuberculous infection in San Francisco; transmission from Mexican-born persons leading to tuberculosis in other persons is uncommon.
Cluster Analysis↗
Tuberculosis research. Balancing the portfolio.
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AIDS-Related Opportunistic Infections↗
The changing epidemiology of acquired drug-resistant tuberculosis in San Francisco, USA.
BACKGROUND: The increasing incidence of tuberculosis caused by drug-resistant Mycobacterium tuberculosis is thought in part to reflect inadequate implementation of standard tuberculosis control measures. However, in San Francisco, USA, which has an effective tuberculosis control programme, we have recently observed an increase in cases of acquired drug-resistance. METHODS: To explore further this observation, we analysed the secular trend of acquired drug-resistance and conducted a population-based case-control study of all reported tuberculosis cases in the city of San Francisco between 1985 and 1994. FINDINGS: We identified 14 patients with tuberculosis caused by fully susceptible M tuberculosis who subsequently developed drug-resistance. Of these acquired drug-resistance cases, two occurred between 1985 and 1989, whereas 12 occurred between 1990 and 1994 (p = 0.028). In the case-control study, AIDS (odds ratio 20.2, 95% CI 1.12-363.6), non-compliance with therapy (19.7, 1.66-234.4), and gastrointestinal symptoms (11.5, 1.23-107.0) were independently associated with acquired drug-resistance. Between 1990 and 1994, one in 16 tuberculosis patients with AIDS and either gastrointestinal symptoms or non-compliance developed acquired drug- resistance. INTERPRETATION: The substantial increase in acquired drug- resistance in San Francisco seems to be a product of the increasing prevalence of HIV/M tuberculosis coinfection. Our data suggest that the interface of the HIV and tuberculosis epidemics fosters acquired drug-resistance, and that traditional tuberculosis control measures may not be sufficient in communities with high rates of HIV infection.
AIDS-Related Opportunistic Infections↗
Control strategies for tuberculosis epidemics: new models for old problems.
Tuberculosis, although preventable and curable, causes more adult deaths than any other infectious disease. A theoretical framework for designing effective control strategies is developed and used to determine treatment levels for eradication, to assess the effects of noneradicating control, and to examine the global goals of the World Health Organization. The theory is extended to assess how suboptimal control programs contribute to the evolution of drug resistance. A new evaluation criterion is defined and used to suggest how control strategies can be improved. In order to control tuberculosis, treatment failure rates must be lower in developing countries than in developed countries.
Adult↗
A computer-assisted molecular epidemiologic approach to confronting the reemergence of tuberculosis.
Molecular epidemiologic approaches have provided important insights into the pathogenesis and epidemiology of tuberculosis. However, continued progress in this field will be reliant on the development of computerized information management systems capable of analyzing large numbers of bacterial DNA fingerprints and incorporating this with data collected as part of conventional disease surveillance. The specific attributes of these computer systems must be tailored to the nature and scope of the research question. In this article, the authors describe a system being used for the surveillance of Mycobacterium tuberculosis strains in San Francisco. The current performance characteristics are described, and potential future developmental directions are outlined. This system demonstrates several general principles of computerized molecular epidemiology that are likely to be of increasing applicability to a variety of pathogens.
Computer Simulation↗
Pulmonary complications of HIV infection in Dar es Salaam, Tanzania. Role of bronchoscopy and bronchoalveolar lavage.
To determine the pulmonary complications in HIV-1-infected patients in Dar es Salaam, Tanzania, and to evaluate the diagnostic utility of bronchoscopy and bronchoalveolar lavage, we carried out a prospective study of 237 patients with acute respiratory disease who were hospitalized at Muhimbili Medical Center (MMC). Diagnoses were made using well-defined criteria. Of the total, 127 (54%) were HIV-1-seropositive and 110 (46%) were seronegative. Tuberculosis was the most common diagnosis occurring in 95 (75%) HIV-1-seropositive and 87 (79%) seronegative patients. Bacterial pneumonia was the next most common diagnosis occurring in 18 (14%) HIV-1-seropositive and 17 (15%) seronegative patients. Pneumocystis carinii pneumonia was diagnosed in one and Kaposi's sarcoma was seen in only two HIV-1-seropositive patients. Bronchoscopy with bronchoalveolar lavage was the sole source of a diagnosis in nine (8%) seropositive and six (5%) seronegative patients. We conclude that the HIV seroprevalence rate among patients hospitalized for acute respiratory disease at MMC is extremely high. Tuberculosis was the most common cause of pulmonary disease, regardless of HIV serostatus, and other HIV-associated opportunistic pulmonary infections were unusual. Bronchoscopy with bronchoalveolar lavage added little to the diagnosis and thus should not be high-priority procedures for the routine workup in resource-poor areas where tuberculosis is endemic.
AIDS-Related Opportunistic Infections↗
The transcontinental transmission of tuberculosis: A molecular epidemiological assessment.
Many tuberculosis control activities are based on principles learned from studies of tuberculosis transmission. To date, these have largely been limited to outbreak investigations in confined geographical regions. In this report conventional and computerized DNA fingerprint- based approaches were integrated to demonstrate that the most widely prevalent strain of Mycobacterium tuberculosis from New York City was cultured from only 1 of 755 patients in San Francisco, Calif, who was a traveling salesman. Large-scale molecular epidemiologic studies may provide a better understanding of the dynamics of tuberculosis transmission between geographic regions and suggest rational measures to interrupt such transmission.
Adult↗