International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

The epidemiologic relationship between tuberculosis and non-tuberculous mycobacterial disease: a systematic review.

SETTING: Tuberculosis (TB) rates are decreasing in many areas, while non-tuberculous mycobacteria (NTM) infection rates are increasing. The relationship between the epidemiology of TB and NTM infections is not well understood. OBJECTIVE: To understand the epidemiologic relationship between TB and NTM disease worldwide. DESIGN: A systematic review of Medline (1946-2014) was conducted to identify studies that reported temporal trends in NTM disease incidence. TB rates for each geographic area included were then retrieved. Linear regression models were fitted to calculate slopes describing changes over time. RESULTS: There were 22 studies reporting trends in rates of NTM disease, representing 16 geographic areas over four continents: 75% of areas had climbing incidence rates, while 12.5% had stable rates and 12.5% had declining rates. Most studies (81%) showed declining TB incidence rates. The proportion of incident mycobacterial disease caused by NTM was shown to be rising in almost every geographic area (94%). CONCLUSION: We found an increase in the proportion of mycobacterial disease caused by NTM in many parts of the world due to a simultaneous reduction in TB and increase in NTM disease. Research into the interaction between mycobacterial infections may help explain this inverse relationship.

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis.

OBJECTIVE: To evaluate the early bactericidal activity (EBA) of the new fluoroquinolones levofloxacin, gatifloxacin and moxifloxacin in patients with pulmonary tuberculosis (PTB). DESIGN: Randomized, open-label trial. Forty adults with newly diagnosed smear-positive PTB (10 per arm) were assigned to receive isoniazid (INH) 300 mg, levofloxacin 1000 mg, gatifloxacin 400 mg, or moxifloxacin 400 mg daily for 7 days. Sputum for quantitative culture was collected for 2 days before and daily during 7 days of monotherapy. Bactericidal activity was estimated by measuring the decline in bacilli during the first 2 days (EBA 0-2) and last 5 days of monotherapy (extended EBA, EBA 2-7). Laboratory staff were blinded to treatment assignment. RESULTS: The EBA 0-2 of INH (0.67 log10 cfu/ml/day) was greater than that of moxifloxacin and gatifloxacin (0.33 and 0.35 log10 cfu/ml/day, respectively), but not of levofloxacin 1000 mg daily (0.45 log10 cfu/ml/day) (P = 0.14). Bactericidal activity between days 2 and 7 was similar for all three fluoroquinolones. In a pooled comparison, the EBA 2-7 of the fluoroquinolones was greater than for INH. CONCLUSION: Moxifloxacin, gatifloxacin, and high-dose levofloxacin have excellent EBA, only slightly less than for INH, and greater extended EBA. These drugs warrant further study in the treatment of drug-susceptible TB.

A 13-year molecular epidemiological analysis of tuberculosis in San Francisco.

BACKGROUND: We examined the molecular epidemiology of tuberculosis (TB) in San Francisco during a 13-year period encompassing the peak of TB resurgence and subsequent decline to historic low levels. OBJECTIVE: To compare rates of TB caused either by rapid progression of recent Mycobacterium tuberculosis infection or by reactivation of latent infection. METHODS: All TB cases reported from 1991 to 2003 were included. Genotyping was performed to identify clustered cases. RESULTS: The annual TB case rate decreased significantly from 50.8 to 28.8 cases/100000 persons from 1992 to 1999 (P < 0.0001). After 1999, no significant decrease was observed for the population as a whole or in any subgroup examined. Similarly, the rate of clustered cases decreased significantly from 1992 to 1999 (11.4 to 3.1 cases/100000, P < 0.0001). Although the rate of non-clustered cases also declined significantly (25.6 to 17.6 cases/100,000, P < 0.0001), there was a disproportionate reduction in clustered cases (94.7% vs. 50.8%, P < 0.0001). Neither clustered nor non-clustered cases decreased significantly after 1999. CONCLUSIONS: TB case rates reached a plateau despite ongoing application of control measures implemented in 1993. These data suggest that intensification of measures designed to identify and treat persons with latent TB infection will be necessary to further reduce TB incidence.

The role of molecular epidemiology in contact investigations: a US perspective.

Preventing tuberculosis (TB) transmission through treatment of active cases and contact investigation is the highest priority of TB control programs in the United States. The role of contact investigation is becoming increasingly important as the number of TB cases declines nationally. However, the effectiveness of contact investigation has been difficult to assess because, prior to the availability of molecular genotyping techniques, levels of transmission were crudely measurable. Epidemiological links within and outside the traditional concentric circle approach are limited by the quality of the contact investigation, the skill and knowledge of the investigator and the information provided by the patient. Molecular epidemiology has added a new dimension by enabling the recognition of unsuspected transmission, likely locations of transmission, and quantification of the extent of transmission that is occurring within a given population. In the future, as real-time genotyping becomes more available, the role of molecular epidemiology is likely to expand.

Problems and solutions for the Stop TB partnership.

Recent international efforts for global control of tuberculosis have resulted in a new movement: the Stop TB partnership. One of the operational goals of this movement is based on WHO-determined targets to detect, by 2005, 70% of new smear-positive cases under DOTS, and to successfully treat 85% of these cases. In a paper in the Bulletin of the World Health Organization, Dye and colleagues present data that show the current case-detection rate to be low (only 27%), and that in many areas treatment-success rates are still below the WHO target level. Dye and colleagues predict, by linear extrapolation of these data, that the WHO target of a 70% case detection rate will be achieved by 2013. Here, we discuss why it is unlikely that the WHO global targets for either case detection or treatment success will be reached by 2013, and we also offer some potential solutions.

Comparison of a whole-blood interferon gamma assay with tuberculin skin testing for detecting latent Mycobacterium tuberculosis infection.

CONTEXT: Identifying persons with latent tuberculosis infection (LTBI) is crucial to the goal of TB elimination. A whole-blood interferon gamma (IFN-gamma) assay, the QuantiFERON-TB test, is a promising in vitro diagnostic test for LTBI that has potential advantages over the tuberculin skin test (TST). OBJECTIVES: To compare the IFN-gamma assay with the TST and to identify factors associated with discordance between the tests. DESIGN AND SETTING: Prospective comparison study conducted at 5 university-affiliated sites in the United States between March 1, 1998 and June 30, 1999. PARTICIPANTS: A total of 1226 adults (mean age, 39 years) with varying risks of Mycobacterium tuberculosis infection or documented or suspected active TB, all of whom underwent both the IFN-gamma assay and the TST. MAIN OUTCOME MEASURE: Level of agreement between the IFN-gamma assay and the TST. RESULTS: Three hundred ninety participants (31.8%) had a positive TST result and 349 (28.5%) had a positive IFN-gamma assay result. Overall agreement between the IFN-gamma assay and the TST was 83.1% (kappa = 0.60). Multivariate analysis revealed that the odds of having a positive TST result but negative IFN-gamma assay result were 7 times higher for BCG-vaccinated persons compared with unvaccinated persons. The IFN-gamma assay provided evidence that among unvaccinated persons with a positive TST result but negative IFN-gamma assay result, 21.2% were responding to mycobacteria other than M tuberculosis. CONCLUSIONS: For all study participants, as well as for those being screened for LTBI, the IFN-gamma assay was comparable with the TST in its ability to detect LTBI, was less affected by BCG vaccination, discriminated responses due to nontuberculous mycobacteria, and avoided variability and subjectivity associated with placing and reading the TST.

Early therapy for latent tuberculosis infection.

The risk of developing active tuberculosis is highest within the first 2 years of infection. Therefore, an intervention that targets persons with recent infection, such as identifying contacts of active cases, could be particularly effective as an epidemic control measure. A mathematical model of a tuberculosis epidemic is formulated and used to evaluate the strategy of targeting therapy to persons with recently acquired latent tuberculosis infection. The model is used to quantify the effectiveness of therapy for early latent tuberculosis infection in reducing the prevalence of active tuberculosis. The model is also used to demonstrate how effective therapy for early latent tuberculosis infection has to be to eliminate tuberculosis, when used in conjunction with therapy for active tuberculosis. Analysis of the model suggests that programs such as contact investigations, which identify and treat persons recently infected with Mycobacterium tuberculosis, may have a substantial effect on controlling tuberculosis epidemics.

Comparison of sputum induction with fiberoptic bronchoscopy in the diagnosis of tuberculosis: experience at an acquired immune deficiency syndrome reference center in Rio de Janeiro, Brazil.

Many patients with suspected pulmonary tuberculosis (PTB) do not produce sputum spontaneously or are smear-negative for acid-fast bacilli (AFB). We prospectively compared the yield of sputum induction (SI) and fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) for the diagnosis of PTB in a region with a high prevalence of tuberculosis and human immunodeficiency virus (HIV) infection. Fifty seven percent (143 of 251) of patients had diagnoses of PTB, of whom 17% (25 of 143) were HIV seropositive. There were no significant differences in the yields of AFB smears or cultures whether obtained via SI or BAL. Among 207 HIV-seronegative patients, the AFB smear and mycobacterial culture results from specimens obtained by SI and BAL were in agreement in 97% (202 of 207) (kappa test = 0.92) and 90% (186 of 207) (kappa test = 0.78), respectively. Among HIV-seropositive patients the agreements between AFB smear and culture results for SI and BAL specimens were 98% (43 of 44) (kappa test = 0.93) and 86% (38 of 44) (kappa test = 0.69), respectively. We conclude that SI is a safe procedure with a high diagnostic yield and high agreement with the results of fiberoptic bronchoscopy for the diagnosis of PTB in both HIV-seronegative and HIV-seropositive patients.

Twelve months of isoniazid compared with four months of isoniazid and rifampin for persons with radiographic evidence of previous tuberculosis: an outcome and cost-effectiveness analysis.

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.

Tuberculosis in the homeless. A prospective study.

We set out to determine tuberculosis incidence and risk factors in the homeless population in San Francisco. We also examined the transmission of tuberculosis by molecular methods. We followed a cohort of 2,774 of the homeless first seen between 1990 and 1994. There were 25 incident cases during the period 1992 to 1996, or 270 per 100,000 per year (350/100,000 in African Americans, 450/100,000 in other nonwhites, 60/100,000 in whites). Ten cases were persons with seropositive HIV. Independent risk factors for tuberculosis were HIV infection, African American or other nonwhite ethnicity, positive tuberculin skin test (TST) results, age, and education; 60% of the cases had clustered patterns of restriction fragment length polymorphism, thought to represent recent transmission of infection with rapid progression to disease. Seventy-seven percent of African-American cases were clustered, and 88% of HIV-seropositive cases. The high rate of tuberculosis in the homeless was due to recent transmission in those HIV-positive and nonwhite. African Americans and other nonwhites may be at high risk for infection or rapid progression. Control measures in the homeless should include directly observed therapy and incentive approaches, treatment of latent tuberculous infection in those HIV-seropositive, and screening in hotels and shelters.

A molecular epidemiologic analysis of tuberculosis trends in San Francisco, 1991-1997.

BACKGROUND: 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. OBJECTIVE: To describe trends in rates of tuberculosis cases and clustered cases in San Francisco from 1991 through 1997. DESIGN: Population-based study. SETTING: San Francisco, California. PATIENTS: Persons with tuberculosis diagnosed between 1 January 1991 and 31 December 1997. MEASUREMENTS: 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. RESULTS: 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). CONCLUSIONS: 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.

The epidemiology of tuberculosis diagnosed after death in San Francisco, 1986-1995.

SETTING: San Francisco, California. OBJECTIVES: To identify the characteristics of persons in whom tuberculosis was diagnosed after death, and determine whether secondary cases of tuberculosis resulted from them. DESIGN: Retrospective review of all cases of tuberculosis reported in San Francisco from 1986 through 1995, combined with a prospective evaluation of the molecular epidemiology of tuberculosis. RESULTS: Four per cent of the reported 3102 tuberculosis cases were diagnosed after death. The rate of tuberculosis cases diagnosed after death was 1.63 per 100000 population. Age 43 years or older, male sex, white race, and birth in the United States were characteristics independently associated with a diagnosis of tuberculosis after death. During 1993-1995, injecting drug use was also independently associated with a diagnosis of tuberculosis after death (odds ratio 9.24, 95% confidence interval 1.77-39.38). Cases of tuberculosis diagnosed after death do not appear to be significant sources of undetected tuberculosis transmission causing new secondary tuberculosis cases in the community. CONCLUSIONS: Health care providers in San Francisco, and probably other urban areas, should maintain a high index of suspicion for tuberculosis in ageing, white, US-born males, and injecting drug users.

Simultaneous infection with two strains of Mycobacterium tuberculosis identified by restriction fragment length polymorphism analysis.

Simultaneous infection with two different strains of Mycobacterium tuberculosis has been demonstrated using phage typing. We report here the first case of mixed infection identified using IS6110-based genotyping of M. tuberculosis. The patient was diagnosed with pulmonary tuberculosis in February, 1991. The initial isolate of M. tuberculosis had two different genotype patterns (dark 7-band and light 14-band patterns). However, in a repeat isolate obtained several months later, only the 14-band pattern was visible. Exogenous reinfection and laboratory cross-contamination were unlikely because both genotype patterns were unique in the San Francisco database which includes over 1300 isolates of M. tuberculosis. This case demonstrates the importance of identifying mixed infections in the study of the molecular epidemiology of tuberculosis. Mixed infections could be confused with exogenous reinfection or laboratory cross-contamination, and important epidemiologic connections could be missed.

Preventing tuberculosis among HIV-infected persons: a survey of physicians' knowledge and practices.

BACKGROUND: Guidelines exist for screening, diagnosing, and preventing tuberculosis (TB) among HIV-infected persons, but their application and utility are unknown. METHODS: We conducted a survey of knowledge and practices among 1,300 physicians in the San Francisco Bay area to assess their practices towards TB among HIV-infected persons. RESULTS: Of 630 respondents, 350 (56%) provided care for HIV-infected persons. Thirty-four percent of the respondents had seen the most recent guidelines for preventing tuberculosis among HIV-infected persons; 65% routinely provide information to HIV-infected patients about the risks of exposure to Mycobacterium tuberculosis; 39% provide annual tuberculin skin testing (TST) to HIV-infected patients without a history of a positive test; 86% knew that >/=5-mm induration is considered a positive TST result in HIV-infected persons; and 47% provide a 12-month regimen of chemoprophylaxis for HIV-infected persons who have a positive TST but not active tuberculosis. Physician specialty and experience with HIV-infected persons were not strongly correlated; experience was a better predictor of correct knowledge and practices. CONCLUSIONS: Many physicians were not aware of the standards of care for preventing tuberculosis among HIV-infected patients, even in a geographic area with a high prevalence of M. tuberculosis and HIV.

Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli.

BACKGROUND: The microscopic examination of sputum for acid-fast bacilli, is a simple and rapid test that is used to provide a presumptive diagnosis of infectious tuberculosis. While patients with tuberculosis with sputum smears negative for acid-fast bacilli are less infectious than those with positive smears, both theoretical and empirical evidence suggest that they can still transmit Mycobacterium tuberculosis. We aimed to estimate the risk of transmission from smear-negative individuals. METHODS: As part of an ongoing study of the molecular epidemiology of tuberculosis in San Francisco, patients with tuberculosis with mycobacterial isolates with the same DNA fingerprint were assigned to clusters that were assumed to have involved recent transmission. Secondary cases with tuberculosis, whose mycobacterial isolates had the same DNA, were linked to their presumed source case to estimate transmission from smear-negative patients. Sensitivity analyses were done to assess potential bias due to misclassification of source cases, unidentified source cases, and HIV-1 co-infection. FINDINGS: 1574 patients with culture-positive tuberculosis were reported and DNA fingerprints were available for 1359 (86%) of these patients. Of the 71 clusters of patients infected with strains that had matching fingerprints, 28 (39% [95% CI 28-52]) had a smear-negative putative source. There were 183 secondary cases in these 71 clusters, of whom a minimum of 32 were attributed to infection by smear-negative patients (17% [12-24]). The relative transmission rate of smear-negative compared with smear-positive patients was calculated as 0.22 (95% CI 0.16-0.32). Sensitivity analyses and stratification for HIV-1 status had no impact on these estimates. INTERPRETATION: In San Francisco, the acid-fast-bacilli smear identifies the most infectious patients, but patients with smear-negative culture-positive tuberculosis appear responsible for about 17% of tuberculosis transmission.