Outbreaks Of Multidrug-resistant Tuberculosis Research Articles

Nosocomial outbreak of multidrug-resistant tuberculosis caused by a strain of Mycobacterium tuberculosis W-Beijing family in St. Petersburg, Russia.

A molecular epidemiologic study of 35 Mycobacterium tuberculosis isolates from 19 patients was conducted to define a nosocomial outbreak of multidrug-resistant tuberculosis in St. Petersburg, Russia. IS 6110-restriction fragment length polymorphism (RFLP) fingerprinting, together with investigations to detect mutations conferring drug resistance, revealed relationships between the isolates and links between the cases. Three patients and a nurse exposed to active tuberculosis were proved to be involved in the outbreak; the source case was identified. The outbreak strain possessed a 17-band RFLP pattern and a spoligoprofile (signals 35-43) characteristic of the W-Beijing family as well as distinctive mutations in katG315, rpoB531, embB306 and rpsL43. This specific RFLP pattern has previously been identified among Mycobacterium tuberculosis W-Beijing strains isolated across the former Soviet Union and in the St. Petersburg area of Russia. The spread of multidrug-resistant strains of W-Beijing genotype in the general population and in hospital settings presents a serious threat for public health in Russia. Specific pathogenic properties of W-Beijing genotype strains, such as enhanced transmissibility and the ability to cause reinfection and to readily acquire drug resistance to major antituberculosis drugs, along with special features of host response, have yet to be investigated.

Multidrug-resistant tuberculosis and HIV infection.

In the 1990s, outbreaks of multidrug-resistant tuberculosis (MDR TB) among HIV-positive patients ultimately led to the establishment in the developed world of a comprehensive TB control strategy for these patients that is effective. The treatment regimen for HIV and MDR TB is complicated by the fact that most of the drugs used have not been studied for interactions with antivirals. Hence, overlapping toxicities require intensive management and monitoring of these patients. Good public health policy is essential to preventing MDR TB outbreaks among immunosuppressed patients.

Molecular approaches to tuberculosis.

Molecular approaches to tuberculosis.

Use and efficacy of tuberculosis infection control practices at hospitals with previous outbreaks of multidrug-resistant tuberculosis.

To evaluate the implementation and efficacy of selected Centers for Disease Control and Prevention guidelines for preventing spread of Mycobacterium tuberculosis. Analysis of prospective observational data. Two medical centers where outbreaks of multidrug-resistant tuberculosis (TB) had occurred. All hospital inpatients who had active TB or who were placed in TB isolation and healthcare workers who were assigned to selected wards on which TB patients were treated. During 1995 to 1997, study personnel prospectively recorded information on patients who had TB or were in TB isolation, performed observations of TB isolation rooms, and recorded tuberculin skin-test results of healthcare workers. Genetic typing of M tuberculosis isolates was performed by restriction fragment-length polymorphism analysis. We found that only 8.6% of patients placed in TB isolation proved to have TB; yet, 19% of patients with pulmonary TB were not isolated on the first day of hospital admission. Specimens were ordered for acid-fast bacillus smear and results received promptly, and most TB isolation rooms were under negative pressure. Among persons entering TB isolation rooms, 44.2% to 97.1% used an appropriate (particulate, high-efficiency particulate air or N95) respirator, depending on the hospital and year; others entering the rooms used a surgical mask or nothing. We did not find evidence of transmission of TB among healthcare workers (based on tuberculin skin-test results) or patients (based on epidemiological investigation and genetic typing). We found problems in implementation of some TB infection control measures, but no evidence of healthcare-associated transmission, possibly in part because of limitations in the number of patients and workers studied. Similar evaluations should be performed at hospitals treating TB patients to find inadequacies and guide improvements in infection control.

Investigation and control of a large outbreak of multi-drug resistant tuberculosis at a central Lisbon hospital

An increase in the number of new cases of tuberculosis (TB) combined with poor clinical outcome was identified among HIV-infected injecting drug users attending a large HIV unit in central Lisbon. A retrospective epidemiological and laboratory study was conducted to review all newly diagnosed cases of TB from 1995 to 1996 in the HIV unit. Results showed that from 1995 to 1996, 63% (109/173) of the Mycobacterium tuberculosis isolates from HIV-infected patients were resistant to one or more anti-tuberculosis drugs; 89% (95) of these were multidrug-resistant, i.e., resistant to at least isoniazid and rifampicin. Eighty percent of the multidrug-resistant strains (MDR) available for restriction fragment length polymorphism (RFLP) DNA fingerprinting clustered into one of two large clusters. Epidemiological data support the conclusion that the transmission of MDR-TB occurred among HIV-infected injecting drug users exposed to infectious TB cases on open wards in the HIV unit. Improved infection control measures on the HIV unit and the use of empirical therapy with six drugs once patients were suspected to have TB, reduced the incidence of MDR-TB from 42% of TB cases in 1996 to 11% in 1999.

Molecular epidemiology of uberculosis among eight hospitals in New York City, 1996–1997

Objective: To determine the molecular epidemiology of tuberculosis isolated from patients cared for at eight hospitals scattered throughout New York City. Materials and Methods: Cases of tuberculosis occurring in 1996 and 1997 at collaborating hospitals were identified, and demographic data were extracted from patient charts. All available isolates were analyzed by IS 6110 for genetic relatedness. The molecular fingerprints were compared both to each other and to the larger repository of strains from New York City developed and maintained at the Public Health Research Institute. Results: One hundred and eighty cases were fully characterized. Compared with New York City cases, study patients were more likely to be Asian and less likely to be non-Hispanic blacks. Overall, 97 (54%) of the cases were clustered with respect to other study strains or with respect to the other New York City isolates. Clustered strains were significantly more likely to be from non-Hispanic blacks or patients born in the United States. The largest cluster (n = 17) was the “W” strain previously associated with an outbreak of multidrug-resistant tuberculosis in New York City. In the current study, the majority of W strain isolates were fully drug-susceptible. Conclusions: High rates of genetically related tuberculosis continue to occur among patients in New York City, in spite of improved control of nosocomial outbreaks and dramatic decreases in the overall case rates. The use of molecular techniques to suggest patterns of transmission has become essential in developing and assessing routine tuberculosis control strategies.

The Analysis of Risk Factors of Treatment Failure in MDR-TB

Background Outbreaks of multidrug-resistant tuberculosis(MDR-TB) are caused by the low rate of treatment response due to limitation in number of available drugs and high rates of adverse drug side-effects. This study analysed the risk factors for MDR-TB patients, who did not respond to treatment, with an aim to improve the rate of treatment response. Methods Retrospective study of 111 MDR-TB patients at National Mokpo Tuberculosis Hospital from Jan. 1996 to Dec. 1998 was made. The patients were separated into tow groups ; group I comprised of patients who were treated successfully and group II comprised of those were not treated successfully. In order to analyze the risk facotrs for treatment faulure, differences between the two groups were compared and the confidence limit regarding the results were tested using an independent t-test, chi-square test and a Fisher's exact tets. Results The treatment failure rate of MDO-TB patients was 32% (36 patients), and treatment success rate 68%(75 patients). This study found no significant difference between two groups in terms of age, sex, family history, extent of the disease on the chest X-ray, the number of sensitive drugs in the treatment regimen, and the number of sensitive bactericidal drugs in the treatement regimen (p>0.05). However, a past history of pulmonary tuberculosis, cavitary lesions on the chest X-ray, the number of tretaments, the number of resistant drugs and the number of drugs used showed a significant difference(p<0.05). Conclusion The rate of treatment failure in MDR-TB was increased by a past history of pulmonary tuberculosis, cavitary lesions on the chest X-ray, the number of treatments, the number of resistant drugs and the number of drugs used. For improving the treatment response of MDR-TB, every effort should be made to reduce the drug resistance caused by failure of the first treatment.

High rate of tuberculosis reinfection during a nosocomial outbreak of multidrug-resistant tuberculosis caused by Mycobacterium bovis strain B.

We present a study of a nosocomial outbreak of multidrug-resistant tuberculosis caused by Mycobacterium bovis in 31 patients, 30 of whom were infected with human immunodeficiency virus; all 31 died of progressive tuberculosis. All M. bovis strains had identical spoligotyping patterns and showed resistance to 12 antituberculosis drugs. Reinfection was suggested in 11 cases and confirmed in 4 by molecular typing methods. The causative strain was named "B strain."

Criteria for the control of drug-resistant tuberculosis.

Antibiotic resistance is a growing impediment to the control of infectious diseases worldwide, tuberculosis (TB) being among them. TB kills two million people each year and foci of multidrug-resistant TB (MDR-TB) have been identified in Eastern Europe, Africa, Asia, and Latin America. A critical question for health policy is whether standardized short-course chemotherapy for TB, based on cheap first-line drugs, can prevent and reverse the spread of drug resistance. Here we use mathematical modeling, in conjunction with treatment results from six countries, to show that best-practice short-course chemotherapy is highly likely to bring strains resistant to either of the two key drugs isoniazid and rifampicin under control and to prevent the emergence of MDR-TB. However, it is not certain to contain MDR-TB once it has emerged, partly because cure rates are too low. We estimate that approximately 70% of prevalent, infectious MDR-TB cases should be detected and treated each year, and at least 80% of these cases should be cured, in order to prevent outbreaks of MDR-TB. Poor control programs should aim to increase case detection and cure rates together for three reasons: (i) these variables act synergistically; (ii) when either is low, the other cannot succeed alone; and (iii) the second-line drugs needed to raise MDR-TB cure rates are few and extremely costly. We discuss the implications of these results for World Health Organization policy on the management of antibiotic resistance.

Transmission of a multidrug-resistant Mycobacterium tuberculosis strain resembling "strain W" among noninstitutionalized, human immunodeficiency virus-seronegative patients.

Since 1990, several outbreaks of multidrug-resistant tuberculosis (MDR-TB) have been described among institutionalized patients infected with human immunodeficiency virus (HIV). We describe a community MDR-TB outbreak among HIV-seronegative patients in Cape Town, South Africa. Isolates were characterized by restriction fragment length polymorphism (RFLP) analysis and dot-blot hybridization analysis of mutations conferring resistance for isoniazid, rifampin, streptomycin, and ethambutol. All isolates were identical on RFLP analysis. In 2 patients, RFLP analysis showed exogenous reinfection during or after treatment for drug-susceptible TB. Mutation analysis confirmed the genotypic identity of the isolates. The infecting strain was genotypically related to strain W, which is responsible for the majority of MDR-TB outbreaks in New York City. Transmission of MDR-TB is thus not limited to HIV-seropositive patients in an institutional setting but occurs within a community.

A multidrug-resistant tuberculosis microepidemic caused by genetically closely related Mycobacterium tuberculosis strains.

IS6110 DNA fingerprinting was used to characterize an outbreak of multidrug-resistant tuberculosis in 21 individuals (17 males and 4 females) living in or roaming among four distantly separated areas in the Czech Republic. The restriction fragment length polymorphism (RFLP) analysis separated the collected Mycobacterium tuberculosis strains into group A, including 14 patients with six IS6110 copies, and group B, with 7 patients displaying highly similar RFLP patterns but with two additional IS6110 bands. A switch from pattern A to pattern B was observed in one patient, and the subsequent detection of subclone B in seven more individuals has been explained by the instability of DNA genotypes caused by transposition of IS6110 elements.

The return of tuberculosis

At the end of the 20th century, tuberculosis remains a major public health issue. In developing countries tuberculosis is a leading cause of morbidity and mortality, and the spread of the HIV epidemic contributes significantly to the worsening of the situation. Coinfection with tuberculosis and HIV results in special diagnostic and therapeutic problems and uses up larger amounts of medical resources in developing countries. Outbreaks of multidrug resistant tuberculosis (MDR-TB) were first reported from US-American centers caring for HIV patients, but have now been observed in many other countries. In Western Europe the tuberculosis epidemic is under control, but increasing incidence rates in migrants raise new problems in these countries. Tuberculosis is uncontrolled in large parts of the former Soviet Union due to the socio-economic break-down in these countries. Only rigorous infection control measures on a world-wide scale will prevent further detoriation of this situation. Therefore, the extension of surveillance systems, and sufficient funding for the prevention, diagnosis, and treatment of tuberculosis by national governments and international organizations are all urgently needed.

An outbreak of multidrug-resistant tuberculosis involving HIV-infected patients of two hospitals in Milan, Italy

To describe an outbreak of multidrug-resistant tuberculosis (MDR-TB), amongst HIV-infected patients, spread from one hospital in Milan to another. Descriptive epidemiological investigation and molecular typing. All cases identified by intensive case-finding were described in terms of clinical characteristics, previous nosocomial exposure to an infectious MDR-TB patient, previous stays in other institutional settings where exposure to MDR-TB could have occurred, and restriction fragment length polymorphism (RFLP) pattern. Between October 1991 and July 1995, 116 cases of MDR-TB were identified (85 at hospital A and 31 at hospital B). A single case patient, infected at hospital A, introduced the strain into hospital B. Eighty-two of the 92 strains available for fingerprinting revealed an identical pattern; 10 strains had unique RFLP patterns. Nosocomial exposure to an infectious MDR-TB patient was ascertained for 39 of the 56 patients with the 'outbreak' RFLP strain at hospital A (69.6%) and for 24 of the 26 patients at hospital B (92.3%). The median duration of exposure was 32 days at hospital A and 40 days at hospital B. For eight patients with the outbreak strain, exposure was determined to have probably occurred in other hospitals, in the community or in prison. This is the largest nosocomial outbreak of MDR-TB reported in Europe. Exposure to MDR-TB cases in other institutions caring for HIV-infected patients probably contributed to the spread of this epidemic. Strict control measures should be immediately adopted in order to prevent the spread of TB amongst HIV-infected patients in institutional settings in Europe.

A continuing outbreak of multidrug-resistant tuberculosis, with transmission in a hospital nursery.

We investigated an increase in cases of multidrug-resistant tuberculosis (MDRTB) at a large urban facility where a prior nosocomial outbreak of MDRTB had occurred. Nosocomial transmission appeared to account for this outbreak as well, including a cluster of cases in a newborn nursery. Seven of 24 patients (29%) described in this investigation may have been exposed in the hospital nursery during an approximately 2-week period. We believe this to be the first documented outbreak of MDRTB in a hospital nursery. The transmission in the nursery demonstrates that the possibility of exposure to unrecognized active tuberculosis in nursery and hospital personnel is always present. Infection and active disease in the infants developed after a relatively short period of exposure. These findings underscore the need for adherence to published infection control guidelines in health care settings.

Nosocomial transmission of Mycobacterium bovis resistant to 11 drugs in people with advanced HIV-1 infection

Since 1990, several nosocomial outbreaks of multidrug-resistant (MDR) tuberculosis have occurred, none of which have involved Mycobacterium bovis. We describe an epidemic of nosocomial and primary MDR M bovis tuberculosis from December, 1993, to February, 1995, among HIV-1-infected patients in a district of Madrid. We undertook genetic characterisation of the M bovis strain and investigated its presence in a tuberculosis epidemic in a Madrid hospital in a case-controlled study. We assessed 19 cases diagnosed with MDR tuberculosis due to M bovis during the study period. For the control group, we randomly selected 33 patients with HIV-1 infection and isolation of a strain of M tuberculosis susceptible to isoniazid, rifampicin, or both, who were treated in Ramón y Cajal Hospital. Infection-control policies and practices were implemented. We detected 19 cases in HIV-1-infected patients of primary MDR tuberculosis produced by M bovis resistant to 11 antituberculosis drugs. We found phenotypic and genotypic similarities in the strains of M bovis. In the case group, the index case and two other cases had had previous contact with another hospital that had had an MDR tuberculosis outbreak. All patients died after a mean of 44 days (range 2-116), despite multidrug treatment with first-line and second-line antituberculosis drugs. The cases with M bovis MDR tuberculosis were significantly more likely than controls to have been admitted to a hospital ward at the same time as patients already infected with MDR tuberculosis during the 10 months before their diagnosis (adjusted odds ratio 94.6 [95% CI 9.4-956.3], p < 0.0001). Advanced HIV-1 immunosuppression was associated with the development of MDR tuberculosis. Implementation of control measures stopped the epidemic. An M bovis primary MDR tuberculosis epidemic that cannot be treated effectively and with high mortality has emerged in Europe and has been transmitted between hospitals.

Occupational risk ofMycobacterium tuberculosis infection in hospital workers

We conducted a 4-year (1/89-12/92) retrospective cohort study among employees at a large metropolitan hospital where a nosocomial outbreak of multidrug-resistant tuberculosis (TB) had occurred. We compared the risk of tuberculin skin test (TST) conversion among employees who worked on wards where patients with culture-confirmed TB were cared for ("exposed") with the risk among employees who worked on wards with no such patients ("unexposed"). Exposed employees had a higher 4-year risk of TST conversion (14.5%) than unexposed employees (1.4%) (adjusted relative risk 13.4; 95 percent confidence interval 5.1-35.2). Exposed employees had significantly higher risks of conversion than unexposed employees during 1989-91, but not for 1992. Among the exposed, ward clerks had a risk of conversion (15.6%) only slightly lower than nurses (18.2%). We conclude that employees who worked in areas where patients with active M. tuberculosis infection were cared for, including workers who did not provide direct patient care, had a higher risk of TST conversion than employees who did not work in these areas. Reasons for the decline in risk over time include outbreak termination, fewer admissions of patients with TB, implementation of effective infection control measures, and possible resistance to infection in some members of the study population.

Investigation of an outbreak of multidrug resistant tuberculosis among renal patients using rpo B genes sequencing and IS 6110 inverse PCR

A cluster of cases of tuberculosis among five patients receiving treatment for renal failure was investigated. Insertion sequence (IS6110) fingerprinting and antibiotic resistance profiling of the Mycobacterium tuberculosis isolates from four of the patients (A-D), who had been on the same ward, showed that three of these cases (A-C) were related, but that the fourth (D) was distinct. An isolate from the fifth patient (E), who had been on a separate ward, was indistinguishable from the outbreak strain by IS6110 profile. However, the isolate from patient E and a second isolate from patient A differed from the previous strains in being rifampicin resistant. Sequence analysis of the rpo B genes of the two rifampicin-resistant strains demonstrated the presence of different mutations, showing that they had evolved independently from the same source strain. IS6110 and rpo B gene analyses are invaluable for the accurate investigation of outbreaks of multidrug resistant tuberculosis.

The Epidemiology and Control of Tuberculosis in the United States

After a dramatic increase in the incidence of tuberculosis from 1985 to 1992 due in part to the AIDS epidemic and an increase in immigration, the tuberculosis incidence rate and the number of cases reported in the United States has declined and continued through 1996. The reasons for this decline have been attributed to the increase in government funding for tuberculosis control efforts and treatment with directly observed therapy. Although the overall incidence has declined since 1992, 31 states and the District of Columbia reported in 1996 case rates greater than 3.5 per 100,000 population, which is the target for the year 2000. Along with the overall decline, the case rates remain high among minorities and in foreign-born persons. Also, several outbreaks of multidrug-resistant tuberculosis have occurred in some areas. In order to ensure containment of such outbreaks and to sustain the decline of tuberculosis in the United States, the control efforts must remain high priorities for public and private health agencies.

Transmission between HIV-infected patients of multidrug-resistant tuberculosis caused by Mycobacterium bovis.

To investigate outbreaks of multidrug-resistant tuberculosis (TB) by using DNA fingerprint databases. Investigation of two outbreaks of multidrug-resistant TB in separate hospitals in Spain by restriction fragment length polymorphism (RFLP) and spoligotyping. Outbreak strains were compared with more than 1500 RFLPs of Mycobacterium tuberculosis complex strains isolated in Spain and 6000 RFLPs from 30 different countries. Standardized IS6110 DNA fingerprinting and 'spoligotyping' was used to type multidrug-resistant isolates belonging to the M. tuberculosis complex amongst the outbreak cases. The DNA types were matched against DNA fingerprint databases in Spain and The Netherlands. The DNA typing analysis indicated that a single multidrug-resistant Mycobacterium bovis strain was responsible for a nosocomial outbreak in a hospital in Spain involving at least 16 HIV-infected patients with non-treatable to multidrug-resistant TB. Introduction of the fingerprint type of this strain to the international database revealed a single matching strain. This strain was also isolated from an HIV-infected patient in The Netherlands who had died from multidrug-resistant TB. This patient had previously been hospitalized in Spain, where a multidrug-resistant TB nosocomial outbreak involving 20 HIV-infected patients was ongoing. The strains causing this outbreak were also identified as M. bovis with an identical DNA pattern to those strains isolated in the Spanish hospital and the patient in The Netherlands. The use of centralized DNA databases can help to identify rapidly the origin and transmission routes of multidrug-resistant TB across international boundaries and the potential use of such an early warning surveillance system for investigation of nosocomial multidrug-resistant TB outbreaks between HIV-infected patients. To our knowledge this is the first report of transmission of multidrug-resistant M. bovis between hospitals.

A model for interval-censored tuberculosis outbreak data.

As the incidence of tuberculosis (TB) has increased in the United States, occupationally acquired TB has increased among the health care workers (HCWs). This paper describes a model developed in response to the needs of an outbreak of multidrug-resistant TB. One of the goals of the outbreak investigation was to estimate the risk of tuberculin skin test (TST) conversion as a function of HCW job type and the period during which persons were employed over the study period. TST conversions were evaluated at periodic examinations and data are interval-censored. We present a generalized linear model that extends Efron's survival model for censored survival data to the case of interval-censored data.