Treatment of Tuberculosis Horsburgh, C. Robert; Barry, Clifton E; Lange, Christoph
The New England journal of medicine,
11/2015, Letnik:
373, Številka:
22
Journal Article
Recenzirano
Tuberculosis is often a difficult infection to treat. This review article summarizes the many manifestations of the disease and the major treatment options in the various contexts in which the ...disease occurs.
Tuberculosis, a scourge since prehistoric times, affects more than 9 million people and causes the death of 1.5 million people each year. Effective treatment has been available for 60 years, but such treatment takes at least 6 months, and resistance to the drugs, which is increasing throughout the world, threatens the effectiveness of treatment.
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This review summarizes the theoretical principles of tuberculosis treatment, current therapeutic approaches, areas of uncertainty, and persistent challenges.
Principles of Tuberculosis Treatment
A series of clinical trials conducted by the U.K. Medical Research Council and the U.S. Public Health Services between 1948 and 1986 showed that . . .
Treatment of latent TB is an important public-health strategy, but 9 months of daily isoniazid (270 doses) poses challenges for compliance. In this study, 3 months of weekly isoniazid plus ...rifapentine (12 doses) was found to be noninferior to 9 months of isoniazid alone.
Tuberculosis results in nearly 2 million deaths annually worldwide.
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More than 2 billion persons are infected with
Mycobacterium tuberculosis,
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and from this reservoir active tuberculosis will develop in millions of persons in coming decades. Treatment of latent
M. tuberculosis
infection among the persons at highest risk for progression to active disease is an important strategy for tuberculosis control and elimination.
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The current standard regimen for the treatment of latent
M. tuberculosis
infection is 9 months of daily isoniazid.
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The efficacy for isoniazid was found to be 69 to 93% in a study that was published in 1982 (before the . . .
Management of drug-resistant tuberculosis Lange, Christoph; Dheda, Keertan; Chesov, Dumitru ...
The Lancet (British edition),
09/2019, Letnik:
394, Številka:
10202
Journal Article
Recenzirano
Drug-resistant tuberculosis is a major public health concern in many countries. Over the past decade, the number of patients infected with Mycobacterium tuberculosis resistant to the most effective ...drugs against tuberculosis (ie, rifampicin and isoniazid), which is called multidrug-resistant tuberculosis, has continued to increase. Globally, 4·6% of patients with tuberculosis have multidrug-resistant tuberculosis, but in some areas, like Kazakhstan, Kyrgyzstan, Moldova, and Ukraine, this proportion exceeds 25%. Treatment for patients with multidrug-resistant tuberculosis is prolonged (ie, 9–24 months) and patients with multidrug-resistant tuberculosis have less favourable outcomes than those treated for drug-susceptible tuberculosis. Individualised multidrug-resistant tuberculosis treatment with novel (eg, bedaquiline) and repurposed (eg, linezolid, clofazimine, or meropenem) drugs and guided by genotypic and phenotypic drug susceptibility testing can improve treatment outcomes. Some clinical trials are evaluating 6-month regimens to simplify management and improve outcomes of patients with multidrug-resistant tuberculosis. Here we review optimal diagnostic and treatment strategies for patients with drug-resistant tuberculosis and their contacts.
Abstract
Many persons with immunological tests indicating Mycobacterium tuberculosis infection, such as tuberculin skin tests or interferon-γ release assays, are at risk of progression to ...tuberculosis disease. Persons whose tests revert to negative may no longer be at such risk. Therefore, identifying the rate of test reversion, potentially indicating cure of M. tuberculosis infection, is an important area of investigation. In their accompanying article (Am J Epidemiol. 2023;192(12):1937–1943), Schwalb et al. extract data on test reversion from prechemotherapy literature and construct a model to predict the rate of reversion, and thus the likely cure of infection. Unfortunately, the incompleteness of the historical data and the use of imprecise definitions of test positivity and reversion lead to substantial misclassification and limit the usefulness of the model. Better definitions and improved tests will be needed in order to develop a clear picture of this aspect of the natural history of tuberculosis.
Cape Town has one of the highest TB burdens of any city in the world. In 1900 the City of Cape Town, New York City and London had high mortality of tuberculosis (TB). Throughout the 20th century ...contemporaneous public health measures including screening, diagnosis and treatment were implemented in all three settings. Mandatory notification of TB and vital status enabled comparison of disease burden trajectories.
TB mortality, notification and case fatality rates were calculated from 1912 to 2012 using annual TB notifications, TB death certifications and population estimates. Notification rates were stratified by age and in Cape Town by HIV status (from 2009 onwards).
Pre-chemotherapy, TB mortality and notification rates declined steadily in New York and London but remained high in Cape Town. Following introduction of combination chemotherapy, mean annual case fatality dropped from 45-60% to below 10% in all three settings. Mortality and notification rates subsequently declined, although Cape Town notifications did not decline as far as those in New York or London and returned to pre-chemotherapy levels by 1980. The proportional contribution of childhood TB diminished in New York and London but remained high in Cape Town. The advent of the Cape Town HIV-epidemic in the 1990s was associated with a further two-fold increase in incidence. In 2012, notification rates among HIV-negatives remained at pre-chemotherapy levels.
TB control was achieved in New York and London but failed in Cape Town. The TB disease burden trajectories started diverging before the availability of combination chemotherapy in 1952 and further diverged following the HIV epidemic in 1990. Chemotherapy impacted case fatality but not transmission, evidenced by on-going high childhood TB rates. Currently endemic TB results from high on-going transmission, which has been exacerbated by the HIV epidemic. TB control will require reducing transmission, which is inexorably linked to prevailing socio-economic factors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, the lifetime risk of reactivation tuberculosis among persons in the United States who have had a positive tuberculin skin test was estimated from published data. The lifetime risk is ...20 percent or higher among persons with skin-test induration of 10 mm or greater and either human immunodeficiency virus infection or evidence of old, healed tuberculosis.
The lifetime risk of reactivation tuberculosis is 20 percent or higher among some groups.
Once the transmission of
Mycobacterium tuberculosis
from persons with active tuberculosis has been controlled in a population, the focus of tuberculosis control shifts to the prevention of active tuberculosis among persons with latent tuberculosis infection — those who have a positive tuberculin skin test but no evidence of active disease. Tuberculosis in this subpopulation results from the reactivation of previously controlled infection and is termed reactivation tuberculosis. The prevention of reactivation tuberculosis through the treatment of latent tuberculosis infection is a major goal of the national strategy for eliminating tuberculosis in the United States.
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Unfortunately, the treatment of latent . . .
Noninvasive markers of liver fibrosis correlate with the stage of liver fibrosis, but have not been widely applied to predict liver-related mortality.
We assessed the ability of two indices of liver ...fibrosis, aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fib-4, and two markers of extracellular matrix metabolism, hyaluronic acid (HA) and YKL40, to predict liver mortality in a prospective cohort of hepatitis C virus (HCV)-infected individuals with and without HIV coinfection. These were compared with two established prognostic scores, the Child-Pugh-Turcotte (CPT) and model of end-stage liver disease (MELD) scores.
A total of 303 subjects, of whom 207 were HIV positive at study entry, were followed up for a mean period of 3.1 years. There were 33 deaths due to liver disease. The ability of each test and score to predict 3-year liver mortality was expressed as the area under the receiver operator curve. The area under the receiver operator curve 95% confidence intervals were: HA 0.92 (0.86-0.96), CPT 0.91 (0.79-0.96), APRI 0.88 (0.80-0.93), Fib-4 0.87 (0.77-0.92), MELD 0.84 (71-0.91). In multivariate analyses HA, APRI, and fib-4 were independent predictors of mortality when included in models with MELD or CPT.
Noninvasive markers of liver fibrosis are highly predictive of liver outcome in HCV-infected individuals with and without HIV coinfection. These markers seem to have a prognostic value independent of CPT and MELD.
The relationship between malnutrition and tuberculosis (TB) severity is understudied. We investigated the effect of malnutrition on radiographic findings and mycobacterial burden.
Subjects included ...newly diagnosed, smear-positive, culture-confirmed, pulmonary TB cases enrolled in the Regional Prospective Observational Research for TB (RePORT) cohort. Multivariate regression models were used to evaluate the relationship at start of treatment between body mass index (BMI) and chest radiograph (CXR) findings of cavitation and percentage of lung affected and mycobacterial growth indicator tube (MGIT) time to positive (TTP). Severe malnutrition was defined as BMI<16 kg/m2, moderate malnutrition as 16-18.4kg/m2, and "normal"/overweight as ≥18.5 kg/m2.
Of 173 TB cases with chest x-ray data, 131 (76%) were male. The median age was 45 years (range 16-82); 42 (24%) had severe malnutrition and 58 (34%) moderate malnutrition. Median percentage of lung affected was 32% (range 0-95), and 132 (76%) had cavitation. Individuals with severe malnutrition had, on average, 11.1% 95% CI: 4.0-13.3 more lung affected, compared to those with normal BMI, controlling for diabetes and cavitation. In multivariable analyses, cases with severe malnutrition had a 4.6-fold 95% CI, 1.5-14.1 increased odds of cavitation compared to those with normal BMI, controlling for smoking. Median MGIT TTP was 194.5 hours. Neither severe (aRR 0.99; 95% CI, 0.9-1.2) nor moderate (aRR 0.97; 95% CI, 0.8-1.1) malnutrition was associated with MGIT TTP.
We found that malnutrition was associated with increased extent of disease and cavitation on CXR. These findings may reflect the immunomodulatory effect of malnutrition on pulmonary pathology.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
High mortality rates have been reported for patients co-infected with extensively drug-resistant tuberculosis (XDR-TB) and HIV, but treatment outcomes have not been reported. We report treatment ...outcomes for adult XDR TB patients in KwaZulu-Natal Province, South Africa. Initial data were obtained retrospectively, and outcomes were obtained prospectively during 24 months of treatment. A total of 114 XDR TB patients were treated (median 6 drugs, range 3-9 drugs); 82 (73%) were HIV positive and 50 (61%) were receiving antiretroviral therapy. After receiving treatment for 24 months, 48 (42%) of 114 patients died, 25 (22%) were cured or successfully completed treatment, 19 (17%) withdrew from the study, and 22 (19%) showed treatment failure. A higher number of deaths occurred among HIV-positive patients not receiving antiretroviral therapy and among patients who did not show sputum culture conversion. Culture conversion was a major predictor of survival but was poorly predictive (51%) of successful treatment outcome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline ...on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB.
Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.
Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided.
New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.
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