Preventive Therapy for Tuberculosis in HIV Infected Individuals

The HIV pandemic has had a major impact on the epidemiological dynamics of tuberculosis. In countries with a severe HIV epidemic, there has been a dramatic rise in the notification rates for tuberculosis (TB). The results of various studies1,2,3 have documented that persons co infected with Mycobacterium tuberculosis and HIV have a 5.8% annual risk and a 30% or greater life time risk of developing active TB, The mechanisms include reactivation of latent infection; rapid progression of primary infection3 or reinfection with Mycobacterium tubercuiosis

Clinical presentation and treatment of HIV-TB

The HIV epidemic has increased the burden of tuberculosis (TB) among young adults, especially in populations where the prevalence of TB infection is high. Infection with HIV is the most potent risk factor for progression to active tuberculosis. Individuals who are infected with Mycobacterium tuberculosis only have an approximately 10% lifetime risk of developing active tuberculosis, compared with 60% or more in persons infected with HIV and TB. This is particularly important in India where more than half the adult population harbours M. tuberculosis. It is estimated that there are about 14 million cases oftuberculosis in India, about 2 million new cases occur annually, and we are home to 1 / 4th the world’s TB prevalence. The situation is likely to get worse as the prevalence of HIV in the community increases. Therefore, it is important to understand the effect of TB and HIV on each other and take adequate measures to control this dual epidemic

Preventive therapy for tuberculosis in HIV infected individuals

The increased risk of developing tuberculosis (TB) among those infected with HIV has prompted a need to reconsider the institution of preventive therapy/chemoprophylaxis with one or more antituberculosis drugs. Prior to the initiation of preventive therapy for tuberculosis, it is essential to rule out active TB. The target population for chemoprophylaxis among HIV seropositives includes all Mantoux (PPD) positive individuals who do not have active tuberculosis and could include all PPD negative individuals living in high prevalence region for TB. The optimal duration of preventive therapy with single drug isoniazid, daily or twice weekly, should be greater than six months to provide the maximum degree of protection against tuberculosis. The effectiveness of preventive therapy should be evaluated at regular intervals by monitoring patients for drug adherence, drug toxicity and for the development of tuberculosis. Though the impact of preventive therapy on an individual basis may be rather small, widespread implementation would have substantial impact on morbidity due to tuberculosis and some impact on mortality. Till the vast majority of HIV positive individuals in the world can access antiretroviral therapy, preventive therapy for tuberculosis should be offered at voluntary counselling and testing centres, as part of a package of care that includes prophylaxis and treatment of opportunistic infections, nutritional support and counselling

HIV and tuberculosis in India

The global impact of the converging dual epidemics of tuberculosis (TB) and human immunodefi ciency virus (HIV) is one of the major public health challenges of our time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006 of whom 7.7% were HIV-infected. Tuberculosis is the most common opportunistic infection in HIV-infected patients as well as the leading cause of death. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are diffi cult to treat and contribute to increased mortality. The diagnosis of TB is based on sputum smear microscopy, a 100-year old technique and chest radiography, which has problems of specifi city. Extra-pulmonary, disseminated and sputum smear negative manifestations are more common in patients with advanced immunosuppression. Newer diagnostic tests are urgently required that are not only sensitive and specifi c but easy to use in remote and resource-poor settings. Treatment of HIV-TB co-infection is complex and associated with high pill burden, overlapping drug toxicities, risk of immune reconstitution infl ammatory syndrome (IRIS) and challenges related to adherence. From a programmatic point of view, screening of all HIV-infected persons for tuberculosis and vice-versa will help identify co-infected patients who require treatment for both infections. This requires good coordination and communication between the TB and AIDS control programs, in India

Drug-resistant tuberculosis--current dilemmas, unanswered questions, challenges, and priority needs

Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the preDOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrugresistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drugresistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and .12 years of MDR tuberculosis–specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR tuberculosis are discussed

Pediatric Tuberculosis: Global Overview and ChallengesSoumya

Tuberculosis (TB) is among the top 10 causes of death among children worldwide; however, children with TB are given low priority in most national health programs and are neglected in this epidemic. Recent technological advancements in diagnosis of TB in adults have not been validated in children. Similarly, trials of new drugs and development of pediatric formulations of standard first- and second-line drugs are lagging behind. Among human immunodeficiency virus (HIV)-coinfected children, the optimal timing for highly active antiretroviral therapy initiation and drug combinations that have minimal interactions with anti-TB drugs need further study. Although bacille Calmette-Guérin vaccine, the only vaccine available for TB, protects against disseminated and severe forms of the disease in young children, its safety in the HIV-infected population has been questioned. Multicentric trials are urgently required to help develop improved diagnostic strategies and formulate shorter, more effective, safe, and evidence-based regimens for treatment and prevention of drugsusceptible and drug-resistant TB

Role of pharmacogenomics in the treatment of tuberculosis: a review

BACKGROUND: Tuberculosis is one of the major public health problems worldwide. Modern antituberculous treatment can cure most patients; cure rates > 95% are achieved with standard short-course chemotherapy regimens containing isoniazid, rifampicin, pyrazinamide, and ethambutol among patients with drug-susceptible strains of tuberculosis; however, a small proportion do not respond to treatment or develop serious adverse events. Pharmacogenomic studies of drugs used in the treatment of tuberculosis could help us understand intersubject variations in treatment response. In this review, we compiled pharmacogenomic data on antituberculous drugs that were available from different settings that would give a better insight into the role of pharmacogenomics in the treatment of tuberculosis, thereby enhancing the efficacy and limiting the toxicity of existing antituberculosis medications. METHODS: The PubMed database was searched from 1960 to the present using the keywords “tuberculosis”, “antituberculosis treatment”, “isoniazid”, “rifampicin”, “pyrazinamide”, “ethambutol”, “pharmacogenomics”, and “polymorphism”. Abstracts from meetings and review articles were included. CONCLUSION: Studies conducted in different settings suggest that pharmacogenomics plays a significant role in isoniazid metabolism, and impacts both treatment efficacy and frequency of adverse reactions. Single nucleotide polymorphisms influencing plasma rifampicin concentrations are also reported. No data are available regarding other first-line drugs, ie, ethambutol and pyrazinamide. There is a need to incorporate pharmacogenomics into clinical trials of tuberculosis in order to understand the factors impacting therapeutic success and occurrence of adverse drug effects