[Show abstract][Hide abstract] ABSTRACT: We describe a microevolutionary event of a prevalent strain of Mycobacterium tuberculosis that caused two outbreaks in San Francisco. During the second outbreak, a direct variable repeat was lost. We discuss the
mechanisms of this change and the implications of analyzing multiple genetic loci in this context.
[Show abstract][Hide abstract] ABSTRACT: Treatment of patients with multidrug-resistant tuberculosis requires prolonged therapy, often involving long hospital stays. Despite intensive and costly therapy, cure rates are relatively low.
We reviewed the outcomes for all patients with multidrug-resistant tuberculosis treated in San Francisco, California, during 1982-2000 and identified billing charges for patients treated during 1995-2000. Mycobacterium tuberculosis isolates were genotyped by IS6110-based restriction fragment-length polymorphism analysis.
Forty-eight cases were identified with resistance to a median of 3 drugs (range, 2-9 drugs). The median age of the patients was 49.5 years (range, 22-78 years); 36 (75%) of 48 patients were foreign born, 11 (23%) were human immunodeficiency virus (HIV) seropositive, and 45 (94%) had pulmonary tuberculosis. Thirty-two (97%) of the 33 HIV-seronegative patients were cured, with only 1 relapse occurring 5 years after treatment. All 11 HIV-seropositive patients died during observation. Twenty-one patients (44%) required hospitalization, with a median duration of stay of 14 days (range, 3-74 days). The estimated inpatient and outpatient aggregate cost for the 11 patients treated after 1994 was $519,928, with a median cost of $27,752 per patient. No secondary cases of multidrug-resistant tuberculosis were identified through population-based genotyping.
Treatment of multidrug-resistant tuberculosis in HIV-seronegative patients largely on an outpatient basis was feasible and was associated with high cure rates and lower cost than in other published studies. Patients with underlying HIV infection had very poor outcomes.
[Show abstract][Hide abstract] ABSTRACT: Many epidemiologic studies of tuberculosis are being conducted worldwide. Fingerprinting with a secondary marker in strains with fewer than six IS6110-hybridizing bands enhances the tracking of strains, but its impact on population-level inferences has not been well studied.
To investigate the effects of secondary genotyping for low-copy Mycobacterium tuberculosis isolates with polymorphic guanine-cytosine-rich repetitive sequence (PGRS) on epidemiologic inferences in population-based research settings.
For San Francisco tuberculosis cases (1991-1996), clusters were defined by IS6110 alone and by PGRS/IS6110 to 1) estimate recent transmission, 2) evaluate the theoretical influence of bacterial population parameters on these estimates, and 3) assess risk factors for recent transmission.
Secondary typing on low-copy strains (20.3% of all isolates) decreased the estimate of recent transmission from 29.1% to 25.3% (P = 0.03). The most influential parameters in determining whether supplemental genotyping results in different estimates were the proportion of low-copy strains and the amount of clustering. Risk factors for recent transmission were identical for both definitions of clustering.
The statistical and inferred effects of secondary genotyping of M. tuberculosis seem to depend on the proportion of low-copy strains in the population. When this proportion is low or when few secondary patterns match, supplemental genotyping may yield minimal insight into population-level investigations.
The International Journal of Tuberculosis and Lung Disease 01/2001; 4(12):1111-9. · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Isoniazid taken daily for 12 mo and isoniazid and rifampin taken daily for 4 mo are both recommended options for patients with radiographic evidence of previous tuberculosis and positive tuberculin skin tests who have not had prior treatment. We compared the completion rates, number of adverse effects, and cost effectiveness of these two regimens. Patients were treated at the San Francisco Tuberculosis Clinic from 1993 through 1996. A Markov model was developed to assess impact on life expectancy and costs. One thousand twenty-two patients, with a mean age of 52 yr, and > 90% foreign born, were treated; 545 received isoniazid and 477 received isoniazid and rifampin. For isoniazid, 79.8% completed 12 mo of therapy and 4.9% had adverse effects versus 83.6% completion, 6.1% adverse effects for isoniazid and rifampin (p > 0.05 for all between-group comparisons). Both regimens increased life expectancy by 1.4-1.5 yr. Compared with isoniazid, isoniazid and rifampin produced net incremental savings of $135 per patient treated. In patients with radiographic evidence of prior tuberculosis who have not been previously treated, isoniazid for 12 mo and isoniazid and rifampin for 4 mo have similar rates of completion and adverse effects, and both increase life expectancy compared with no treatment. Isoniazid and rifampin for 4 mo is cost saving compared with isoniazid alone. This advantage was maintained even when compared with 9 mo of isoniazid, the new American Thoracic Society/Centers for Disease Control (ATS/CDC) recommendation for treatment with isoniazid alone.
American Journal of Respiratory and Critical Care Medicine 12/2000; 162(5):1648-52. DOI:10.1164/ajrccm.162.5.2003028 · 13.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the effectiveness and cost-effectiveness of a program to provide screening for tuberculosis infection and directly observed preventive therapy (DOPT) in methadone maintenance clinics, we determined completion rates of screening for tuberculosis infection, medical evaluation, and preventive therapy, as well as the number of active tuberculosis cases and tuberculosis-related deaths prevented, in five clinics in San Francisco, California. Between 1990 and 1995, a total of 2,689 clients (of whom 18% were HIV-seropositive) were screened at least once. Of eligible clients, 99% received tuberculin skin tests, 96% received a medical examination, 91% began isoniazid preventive therapy, and 82% completed preventive therapy. Program effectiveness was enhanced by close collaboration between public health and methadone maintenance programs and the use of incentives and enablers. Over a 3-yr follow-up period, only one verified case of tuberculosis was reported among clients with a positive tuberculin skin test, thereby preventing as much as 95% of expected tuberculosis cases. Over 10 yr, we estimate the program would prevent 30.0 (52%) of 57.7 expected cases of tuberculosis, and 7.6 (57%) of 13.4 expected tuberculosis-related deaths. The program cost $771,569, but averted an estimated $876,229, for a net savings of $104,660 (average of $3, 724 per case prevented). Our study demonstrates that when effectively implemented, screening for tuberculosis infection and DOPT in methadone maintenance clinics is a highly cost-effective approach to prevent tuberculosis.
American Journal of Respiratory and Critical Care Medicine 08/1999; 160(1):178-85. DOI:10.1164/ajrccm.160.1.9810082 · 13.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To decrease tuberculosis case rates and cases due to recent infection (clustered cases) in San Francisco, California, tuberculosis control measures were intensified beginning in 1991 by focusing on prevention of Mycobacterium tuberculosis transmission and on the use of preventive therapy.
To describe trends in rates of tuberculosis cases and clustered cases in San Francisco from 1991 through 1997.
San Francisco, California.
Persons with tuberculosis diagnosed between 1 January 1991 and 31 December 1997.
DNA fingerprinting was performed. During sequential 1-year intervals, changes in annual case rates per 100,000 persons for all cases, clustered cases (cases with M. tuberculosis isolates having identical fingerprint patterns), and cases in specific subgroups with high rates of clustering (persons born in the United States and HIV-infected persons) were examined.
Annual tuberculosis case rates peaked at 51.2 cases per 100,000 persons in 1992 and decreased significantly thereafter to 29.8 cases per 100,000 persons in 1997 (P < 0.001). The rate of clustered cases decreased significantly over time in the entire study sample (from 10.4 cases per 100,000 persons in 1991 to 3.8 cases per 100,000 persons in 1997 [P < 0.001]), in persons born in the United States (P < 0.001), and in HIV-infected persons (P = 0.003).
The rates of tuberculosis cases and clustered tuberculosis cases decreased both overall and among persons in high-risk groups. This occurred in a period during which tuberculosis control measures were intensified.
Annals of internal medicine 07/1999; 130(12):971-8. · 17.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
American Journal of Respiratory and Critical Care Medicine 01/1999; 158(6):1797-803. DOI:10.1164/ajrccm.158.6.9804029 · 13.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
American Journal of Respiratory and Critical Care Medicine 08/1998; 158(2):465-9. DOI:10.1164/ajrccm.158.2.9801062 · 13.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: San Francisco, California.
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.
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.
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.
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.
The International Journal of Tuberculosis and Lung Disease 01/1998; 1(6):536-41. · 2.32 Impact Factor