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 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isoniazid (INH) has been the mainstay of treatment of latent tuberculosis infection for almost 50 years. The currently recommended preferred regimen is 9 months daily self-administered INH (9H); this has efficacy of more than 90% if completed properly. Unfortunately, INH is associated with serious adverse events, including hepatotoxicity. Although risk factors for this complication are well established, allowing for better selection of candidates for therapy, this complication still occurs, and is occasionally fatal. Hence close follow up of patients is necessary, increasing the cost and complexity of treatment. This problem, plus the lengthy duration, results in poor acceptance by patients and providers, and poor adherence by patients. As a result, many preventable cases of tuberculosis continue to occur, and the public health impact of latent tuberculosis infection treatment is suboptimal. These problems have spurred interest in finding shorter, safer and cheaper alternative regimens, with similar efficacy. Of the many regimens that have been examined, 2 months of rifampin and pyrazinamide has excellent efficacy-in experimental studies in mice and randomized trials, largely in HIV-infected persons. However, while the safety of 2 months of rifampin and pyrazinamide appears acceptable in HIV-infected persons and children, in non-HIV-infected adults this regimen is associated with an unacceptably high rate of severe liver toxicity. Three to four months of INH and rifampin has had equivalent effectiveness as 6 months INH in several randomized trials. However, completion of therapy and toxicity has been the same as with INH-possibly because two drugs are taken rather than one. The fourth commonly studied regimen is 4 months rifampin. This has been found to have significantly better completion than 9H, with significantly less toxicity, especially hepatotoxicity. However, only one trial has evaluated efficacy and effectiveness of mono-rifampin therapy. In this trial, 3 months rifampin had somewhat better efficacy than either 3 months of isoniazid and rifampin (3HR) or 6 months isoniazid. Two large scale trials are ongoing; one is comparing efficacy and effectiveness of 9H with 4 months rifampin (both daily and self-administered), while the second, which is nearing completion, compares daily self-administered 9H with 3 months directly observed once weekly INH combined with rifapentine. The results of these two trials will likely shape future recommendations substantially.
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PMID:Treatment of latent tuberculosis infection: An update. 2040 26

Much remains unknown about latent infection with Mycobacterium tuberculosis. Existing immunodiagnostic tools for this condition have various limitations, most importantly in their ability to predict disease. Randomised controlled trials have established protective efficacy of isoniazid therapy for 6-12 months among non-HIV-infected and HIV-infected subjects. While efficacy may reach 90%, acceptance and adherence to prolonged therapy are less than desired. Rifampicin plus pyrazinamide for 2 months, though efficacious, has been associated with excess hepatotoxicity in non-HIV-infected persons. Isoniazid plus rifampicin for 3 months has proven efficacy, but adverse effects may be more frequent than isoniazid or rifampicin monotherapy. Rifampicin monotherapy for 3-4 months is well tolerated, but efficacy data are currently limited, and concerns remain over possible selection of rifampicin-resistant mutants. For contacts of patients with multidrug-resistant tuberculosis, expert opinions differ on whether to treat with at least two drugs or just a fluoroquinolone, and for how long. With the existing diagnostic and treatment tools, efficacy of preventive therapy does not necessarily translate into field effectiveness. A targeted approach is required to maximise cost-effectiveness. Each geographic region needs to set its own priority after taking into account available scientific data and local circumstances.
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PMID:Treatment of latent infection with Mycobacterium tuberculosis: update 2010. 2069 57

Despite dramatic advances in diagnosis and treatment, tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide. World Health Organization (WHO) reports that one-third of the global population is infected by M. tuberculosis. Direct identification of individuals who are latently infected with live M. tuberculosis without active disease is currently not possible (Latent TB Infection, LTBI). Available immunodiagnostic tests, i.e. Tuberculin Skin Testing and Interferon-gamma Release Assay, ascertain a state of M. tuberculosis specific immune response; they have several limitations in their ability to predict the risk of developing TB disease. Protective efficacy of isoniazid preventive treatment for 6 to 12 months was proved among non-HIV-infected and HIV-infected individuals. The frequency of symptomatic hepatitis due to isoniazid has been estimated to be 1 to 3 per 1,000 persons. The protection of isoniazid treatment in HIV-infected persons appears to be short-lasting (1-2.5 years), in areas with a high incidence of TB. Isoniazid plus rifampicin for 3 months has proven efficacy. There are not sufficient data on preventive treatment for contacts of patients with drug-resistant TB; existing recommendations are based on expert opinions. Rifampicin for 4 months is a choice for the treatment of individuals exposed to an index case with isoniazid-resistant TB. WHO does not recommend anti-TB second-line drugs for preventive therapy.
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PMID:[Diagnosis and treatment of latent tubercular infections]. 2106 7

Approximately 10% of new cases of tuberculosis (TB) in the United States occur in HIV-infected persons. HIV infection dramatically increases the risk of TB, and this increased risk is present throughout the course of HIV infection. TB and HIV coinfection complicates the course and treatment of both diseases. Isoniazid preventive therapy and antiretroviral therapy both substantially reduce the risk of developing active disease in persons with latent TB infection. Antiretroviral therapy should be given during treatment for active TB, as mortality was reduced by 56% with initiation of antiretroviral therapy before the completion of TB therapy. In addition, for patients with low CD4+ cell counts (less than 200/microm3), starting antiretroviral therapy during the intensive phase of TB treatment reduced mortality by 34% compared with delaying antiretroviral therapy until 8 weeks after TB treatment initiation.
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PMID:Current issues in the diagnosis and management of tuberculosis and HIV coinfection in the United States. 2110 14

Tuberculosis (TB) was declared a public health emergency by WHO in 2005. The disease is a significant contributor to maternal mortality and is among the three leading causes of death among women aged 15-45 years in high burden areas. The exact incidence of tuberculosis in pregnancy, though not readily available, is expected to be as high as in the general population. Diagnosis of tuberculosis in pregnancy may be challenging, as the symptoms may initially be ascribed to the pregnancy, and the normal weight gain in pregnancy may temporarily mask the associated weight loss. Obstetric complications of TB include spontaneous abortion, small for date uterus, preterm labour, low birth weight, and increased neonatal mortality. Congenital TB though rare, is associated with high perinatal mortality. Rifampicin, INH and Ethambutol are the first line drugs while Pyrazinamide use in pregnancy is gaining popularity. Isoniazid preventive therapy is a WHO innovation aimed at reducing the infection in HIV positive pregnant women. Babies born to this mother should be commenced on INH prophylaxis for six months, after which they are vaccinated with BCG if they test negative. Successful control of TB demands improved living conditions, public enlightenment, primary prevention of HIV/AIDS and BCG vaccination.
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PMID:Tuberculosis in pregnancy: a review. 2213 39

HIV-associated tuberculous meningitis (TBM) has high mortality. Aside from the devastating impact of multidrug resistance (MDR) on survival, little is understood about the influence of other bacterial factors on outcome. This study examined the influence of Mycobacterium tuberculosis drug resistance, bacterial lineage, and host vaccination status on outcome in patients with HIV-associated TBM. Mycobacterium tuberculosis isolates from the cerebrospinal fluid of 186 patients enrolled in two studies of HIV-associated TBM in Ho Chi Minh City, Vietnam, were tested for resistance to first-line antituberculosis drugs. Lineage genotyping was available for 122 patients. The influence of antituberculosis drug resistance and M. tuberculosis lineage on 9-month mortality was analyzed using Kaplan-Meier survival analysis and Cox multiple regression models. Isoniazid (INH) resistance without rifampin resistance was associated with increased mortality (adjusted hazard ratio [HR], 1.78, 95% confidence interval [CI], 1.18 to 2.66; P = 0.005), and multidrug resistance was uniformly fatal (n = 8/8; adjusted HR, 5.21, 95% CI, 2.38 to 11.42; P < 0.0001). The hazard ratio for INH-resistant cases was greatest during the continuation phase of treatment (after 3 months; HR, 5.05 [95% CI, 2.23 to 11.44]; P = 0.0001). Among drug-susceptible cases, patients infected with the "modern" Beijing lineage strains had lower mortality than patients infected with the "ancient" Indo-Oceanic lineage (HR, 0.29 [95% CI, 0.14 to 0.61]; P = 0.001). Isoniazid resistance, multidrug resistance, and M. tuberculosis lineage are important determinants of mortality in patients with HIV-associated TBM. Interventions which target these factors may help reduce the unacceptably high mortality in patients with TBM.
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PMID:Influence of antituberculosis drug resistance and Mycobacterium tuberculosis lineage on outcome in HIV-associated tuberculous meningitis. 2247 Jan 17

Toxic epidermal necrolysis (TEN) is a potentially life-threatening disorder characterized by widespread erythema, necrosis, and bullous detachment of the epidermis and mucous membranes. Without proper management,TEN can cause sepsis leading to death of the patient. Though TEN is commonly drug induced, Isoniazid (INH) has been uncommonly associated with TEN. As INH is one of the first line drugs in treatment of tuberculosis, TEN induced INH needs modification of antitubercular therapy (ATT) with withdrawal of INH from the treatment regime along with other supportive treatments. Patients with HIV infection and disseminated tuberculosis need to be urgently initiated on an effective ATT on diagnosis of tuberculosis. However, if the patient develops potential life-threatening toxicity to first line antitubercular drugs like INH, an alternative effective ATT combination needs to be started as soon as the condition of the patient stabilizes as most of these patients present in advanced stage of HIV infection and this is to be followed by antiretroviral therapy (ART) as per guidelines. The present case reports the effectiveness of an ATT regime comprising Rifampicin, Pyrazinamide, Ethambutol, and Levofloxacin along with ART in situations where INH cannot be given in disseminated tuberculosis in HIV patients.
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PMID:Response to Modified Antitubercular Drug Regime and Antiretroviral Therapy in a Case of HIV Infection with Disseminated Tuberculosis with Isoniazid Induced Toxic Epidermal Necrolysis. 2325 95

Tuberculosis (TB) is a public health problem in many large cities. We retrospectively studied the clinical characteristics and treatment outcomes of patients with active TB at 6 hospitals in Bangkok and Nonthaburi, Thailand during 2008-2009. Eight hundred thirteen patients were included in the study. The mean age of subjects +/- SD was 41 +/- 14 years and mean body weight +/- SD was 53 +/- 11 kilograms. The three leading co-morbid conditions were HIV infection (40%), diabetes (6%) and chronic liver disease (2%). Two-thirds of subjects had isolated pulmonary TB. Isoniazid, rifampicin and multi-drug resistance were seen in 13, 7 and 5%, respectively. After 1 year, 52% were cured or completed treatment, 19% transferred out, 12% defaulted, 9% were still on-going TB treatment, 7% had died and 1% had failed treatment. Survival rates at 2, 6 and 12 months were 93, 85 and 81% among HIV seropositive subjects; 96, 94 and 92% among HIV seronegative subjects and 98, 97 and 97% among subjects with unknown HIV status (p < 0.001). On multivariate analysis, death was associated with: TB/HIV co-infection (HR 2.8; 95% CI 1.6-5.0), low body weight (HR 1.6; 95% CI 1.2-2.3), being elderly (HR 1.4; 95% CI 1.1-1.8) and having extrapulmonary/disseminated TB (HR 2.2; 95% CI 1.1-4.2). HIV infection and diabetes were the most common co-morbidities among TB subjects in our study. The percent of patients with unfavorable outcomes was relatively high, particularly among HIV co-infected and elderly subjects. Further effort needs to be made to improve these unfavorable TB outcomes in Nonthaburi and Bangkok, Thailand.
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PMID:Clinical characteristics and treatment outcomes among patients with tuberculosis in Bangkok and Nonthaburi, Thailand. 2341 6

Background. Tuberculosis is a major public health problem, and its control has been facing a lot of challenges with emergence of HIV. The occurrence of multidrug-resistant strain has also propounded the problem especially in children where diagnosis is difficult to make. Multidrug-resistant tuberculosis (MDR-TB) is in vitro resistant to isoniazid (H) and rifampicin (R). Paediatric multi-drug resistant tuberculosis with HIV coinfection is rare, and there is no documented report from Nigeria. Objective. To report a case of paediatric MDR-TB in Nigeria about it. Methods. The case note of the patient was retrieved, and relevant data were extracted and summarized. Results. A 9-year-old female HIV-positive pupil with a year history of recurrent cough, 3 months history of recurrent fever, and generalized weight loss was diagnosed and treated for tuberculosis but failed after retreatment. She was later diagnosed with MDR-TB and is presently on DOT-Plus regimen. Conclusion. Paediatric MDR-TB with HIV co-infection is rare. Early diagnosis and treatment is important to prevent spread of the disease. The use of Isoniazid preventive therapy is recommended for children who come in contact with patients with active tuberculosis and also for HIV patients without active tuberculosis.
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PMID:Paediatric Multidrug-Resistant Tuberculosis with HIV Coinfection: A Case Report. 2342 97

Drug-resistant tuberculosis, including drug-resistant tuberculous meningitis, is an emerging health problem in many countries. An association with Beijing strains and drug resistance-related mutations, such as mutations in katG and rpoB genes, has been found. The pathology, clinical features and neuroimaging characteristics of drug-resistant tuberculous meningitis are similar to drug-responsive tuberculous meningitis. Detection of mycobacteria in cerebrospinal fluid (CSF) by conventional methods (smear examination or culture) is often difficult. Nucleic acid amplification assays are better methods owing to their rapidity and high sensitivity. The Xpert MTB/RIF assay (Cepheid, CA, USA) is a fully-automated test that has also been found to be effective for CSF samples. Treatment of multidrug-resistant tuberculous meningitis depends on the drug susceptibility pattern of the isolate and/or the previous treatment history of the patient. Second-line drugs with good penetration of the CSF should be preferred. Isoniazid monoresistant disease requires addition of another drug with better CSF penetration. Drug-resistant tuberculous meningitis is associated with a high mortality. HIV infected patients with drug-resistant tuberculous meningitis have severe clinical manifestations with exceptionally high mortality. Prevention of tuberculosis is the key to reduce drug-resistant tuberculous meningitis.
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PMID:Drug-resistant tuberculous meningitis. 2375 Jul 32


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