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This chapter will describe the pathogen which causes tuberculosis: . It will give an overview of the historical context, the molecular and clinical epidemiology of tuberculosis in adults and children globally and describes how other epidemics, such as HIV and diabetes, influence disease control. It also summarizes the current efforts of the WHO to curtail the pandemic.

In this section the different phases of infection with will be reviewed. Starting from transmission by inhalation, to the innate and adaptive immune response and the dual role of tuberculoma formation in walling off infection, but also providing an advantageous environment for bacilli to survive and multiply. Recent data has shown the role of Tumour Necrosis Factor alpha (TNF-α) in tuberculoma maintenance and its genetic control is more complex than previously thought. The role of vitamin D in susceptibility to tuberculosis also an area which has seen a resurgence of interest and new evidence emerging that targeted vitamin D therapy may have a role in improving TB outcomes.

In this chapter we will review the clinical manifestations of tuberculosis disease.

At the turn of the century, it was widely recognized that an accurate point-of care test for TB was required to make significant reductions in the pandemic. At this time, many novel tests had been developed by research groups or small biotech companies, but had never been standardized or evaluated for scale-up and application in low-resource, high-burden settings where the need is greatest. This motivated a major drive to systematically evaluate existing tests such as commercial liquid culture and nucleic acid amplification tests (NAAT), and to develop new approaches, principally led by the Foundation for Innovative New Diagnostics (FIND ) in collaboration with industry, government and clinical partners. The evidence generated by this renewed focus on novel TB diagnostic tests, processes and algorithms has led to a substantial number of policy revisions and new WHO recommendations (Table , see also ).

In this chapter the treatment of drug sensitive and drug resistant TB and timing of antiretroviral treatment for HIV infected patients will be reviewed. Emphasis is placed on results of recent trials of fluoroquinolones for treatment shortening of drug sensitive TB. The use of two relatively novel agents in MDR-TB treatment, bedaquiline and delamanid, will be discussed.

Prevention is the key to stop transmission of TB. It consists of early diagnosis and treatment of active TB to stop infectiousness, the prevention of active disease in exposed or known latently infected individuals and vaccination. Vaccination with the Bacillus Calmette-Guerin (BCG) vaccine is unfortunately largely ineffective in interrupting transmission. However a more powerful vaccine will have the potential to cause a major shift in the management of TB. In this chapter prophylactic treatment in latently infected and HIV infected patients is reviewed. Additionally the prevention of active disease in MDR-exposed persons and vaccine development will be discussed.