Tuberculosis (TB) is the leading cause of death among treatable infectious diseases. TB occurs more frequently in regions of world which have greater poverty, malnutrition, general poor health, and social disruption.
Tuberculosis is caused by the gram-positive, slow-growing, intracellular bacterium, Mycobacterium tuberculosis, which was first isolated in 1882 by a German physician named Robert Koch who received a Nobel Prize for his discovery.
TB normally causes pulmonary infections, but can also affect other parts of the body. Only the pulmonary form of TB disease is infectious. Transmission occurs through inhalation of infectious droplets dispersed through coughing. TB is normally treated with a combination of specific antibiotics and Directly Observed Treatment Short-course, DOTS is the strategy recommended by the WHO for treatment of TB cases. Treatment must be continued for at least six months to be effective.
Untreated active cases of TB can infect 10-15 people per year (WHO). The emergence of new strains of drug-resistant M. tuberculosis has become a major concern especially in countries of South East Asia and within prison populations. The development of resistance has resulted mainly from poor patient-compliance, inappropriate dosing or prescribing of medication, inadequately formulated medications, and/or supply of medication. Multidrug-resistant tuberculosis (MDR-TB) refers to M. tuberculosis strains that are resistant to at least two of the first-line drugs, INH and Rifampicin. More recently, extensively drug resistant tuberculosis (XDR-TB) strains have arisen. These bacteria are also resistant to three or more of the second-line treatment drugs. XDR-TB is found most frequently in the countries of the former Soviet Union and Asia.
There are approximately 9 million new cases of TB and 2 million deaths (1.3 million in 2008) caused by TB infection each year. Tuberculosis is especially prevalent in sub-Saharan Africa and in Southeast Asia (30% and 34% of global total respectively) and incidence of the disease is higher in Eastern Europe than in Western Europe.
Approximately 70-80% of people who are given the Bacillus Calmette-Guérin (BCG) vaccine are thought to be protected against TB. However, BCG vaccination is no longer routinely given as part of the childhood immunisation schedule. Vaccinations may be recommended for people with an increased risk of developing TB infection such as health workers, people arriving from countries with high levels of TB, and people who have been in close contact with an infectious case.
Although BCG provides some protection against severe forms of paediatric TB, it has been shown to be unreliable against adult pulmonary TB, which causes the most disease worldwide. A more effective vaccine that would prevent all forms of TB, including drug resistant strains, in all age groups and among people with HIV is needed urgently.
Several new vaccines to prevent TB infection are being developed using a number of approaches including recombinant vaccines, DNA vaccines, and a TB vaccine, MVA85A, based on a genetically modified vaccinia virus (MVA) developed by the University of Oxford. This vaccine is currently undergoing phase II trials in South Africa. Other strategies being used to develop novel TB vaccines include subunit vaccines such as Hybrid-1, HyVac4, or M72, and recombinant adenoviruses such as Ad35.