Abstract and Introduction
Abstract
With nearly 9 million new active disease cases and 2 million deaths occurring worldwide every year, tuberculosis continues to remain a major public health problem. Exposure to Mycobacterium tuberculosis leads to active disease in only ~10% people. An effective immune response in remaining individuals stops M. tuberculosis multiplication. However, the pathogen is completely eradicated in ~10% people while others only succeed in containment of infection as some bacilli escape killing and remain in non-replicating (dormant) state (latent tuberculosis infection) in old lesions. The dormant bacilli can resuscitate and cause active disease if a disruption of immune response occurs. Nearly one-third of world population is latently infected with M. tuberculosis and 5%-10% of infected individuals will develop active disease during their life time. However, the risk of developing active disease is greatly increased (5%-15% every year and ~50% over lifetime) by human immunodeficiency virus-coinfection. While active transmission is a significant contributor of active disease cases in high tuberculosis burden countries, most active disease cases in low tuberculosis incidence countries arise from this pool of latently infected individuals. A positive tuberculin skin test or a more recent and specific interferon-gamma release assay in a person without overt signs of active disease indicates latent tuberculosis infection. Two commercial interferon-gamma release assays, QFT-G-IT and T-SPOT.TB have been developed. The standard treatment for latent tuberculosis infection is daily therapy with isoniazid for nine months. Other options include therapy with rifampicin for 4 months or isoniazid + rifampicin for 3 months or rifampicin + pyrazinamide for 2 months or isoniazid + rifapentine for 3 months. Identification of latently infected individuals and their treatment has lowered tuberculosis incidence in rich, advanced countries. Similar approaches also hold great promise for other countries with low-intermediate rates of tuberculosis incidence.
Introduction
Tuberculosis (TB) is a formidable public health challenge as it contributes considerably to illness and death around the world. The most common causative agent of TB in humans, Mycobacterium tuberculosis, is a member of the M. tuberculosis complex (MTBC) which includes six other closely related species: M. bovis, M. africanum, M. microti, M. pinnipedii, M. caprae and M. canettii. All MTBC members are obligate pathogens and cause TB; however, they exhibit distinct phenotypic properties and host range. Genetically, MTBC members are closely related, the genome of M. tuberculosis shows >99.9% similarity with M. bovis, the species that primarily infects cattle but can also cause TB in other mammals including man. The current TB epidemic is being sustained by two important factors; the human immunodeficiency virus (HIV) infection and its association with active TB disease and increasing resistance of M. tuberculosis strains to the most effective (first-line) anti-TB drugs. Other contributing factors include population expansion, poor case detection and cure rates in impoverished countries, wars, famine, diabetes mellitus and social decay and homelessness.
According to recent estimates, 9.4 million new active disease cases corresponding to an estimated incidence of 139 per 100,000 population occurred throughout the world in 2008. Only 5.7 million of 9.4 million cases of TB (new cases and relapse cases) were notified to national tuberculosis programs of various countries while the rest were based on assessments of effectiveness of surveillance systems. The highest number of TB cases occurred in Asia (55%) followed by Africa (30%). The highest incidence rate (351 per 100,000 population) was recorded for the African region, mainly due to high prevalence of HIV infection. An estimated 1.4 million (15%) of incident TB patients were coinfected with HIV in 2008. Globally, the total prevalent TB cases in 2008 were 11.1 million corresponding to 164 cases per 100 000 population that resulted in 1.8 million deaths (including 0.5 million TB patients coinfected with HIV). Nearly 440 000 cases of multidrug-resistant TB (MDR-TB, defined as infection with M. tuberculosis strains resistant at least to the two most important first-line drugs, rifampicin and isoniazid) occurred in 2008. By 2009, extensively drug-resistant TB (XDR-TB; defined as MDR-TB strains additionally resistant to a fluoroquinolone and a second-line anti-TB injectable agent such as kanamycin, amikacin, or capreomycin) has been found in 58 countries. While MDR-TB is difficult and expensive to treat, XDR-TB is virtually an untreatable disease in most of the developing countries.