Basic facts about TB TB is an infectious disease caused by the bacillus Mycobacterium

tuberculosis. It typically afects the lungs (pulmonary TB) but can also afect other sites
(extrapulmonary TB). The disease is spread when people who are sick with pulmonary TB
expel bacteria into the air, for example by coughing. Overall, a relatively small proportion (5–
15%) of the estimated 1.7 billion people infected with M. tuberculosis will develop TB
disease during their lifetime. However, the probability of developing TB disease is much
higher among people infected with HIV, and also higher among people afected by risk
factors such as under-nutrition, diabetes, smoking and alcohol consumption. Diagnostic tests
for TB disease include the following: ! Rapid molecular tests – The only rapid test for
diagnosis of TB currently recommended by WHO is the Xpert® MTB/RIF assay (Cepheid,
USA). It can provide results within 2 hours, and was initially recommended (in 2010) for
diagnosis of pulmonary TB in adults. Since 2013, it has also been recommended for use in
children and to diagnose specific forms of extrapulmonary TB. The test has much better
accuracy than sputum smear microscopy; ! Sputum smear microscopy –Developed more
than 100 years ago, this technique requires the examination of sputum samples using a
microscope to determine the presence of bacteria. In the current case definitions
recommended by WHO, one positive result is required for a diagnosis of smear-positive
pulmonary TB; ! Culture-based methods – The current reference standard, they require
more developed laboratory capacity and can take up to 12 weeks to provide results.
Globally, use of rapid molecular tests is increasing, and many countries are phasing out the
use of smear microscopy for diagnostic purposes (although microscopy and culture remain
necessary for treatment monitoring). Despite advances in diagnostics, a considerable
proportion of the TB cases reported to WHO are still clinically diagnosed rather than
bacteriologically confirmed. In 2016, for example, only 57% of the pulmonary cases reported
to WHO were bacteriologically confirmed. There are also tests for TB that is resistant to first-
line and second-line anti-TB drugs. They include Xpert MTB/ RIF, which simultaneously tests
for TB and resistance to rifampicin (the most efective first-line anti-TB drug); rapid line probe
assays (LPAs) that test for resistance to rifampicin and isoniazid (referred to as first-line
LPAs); a rapid LPA that tests for resistance to fluoroquinolones and injectable anti-TB drugs
(referred to as a second-line LPA); and sequencing technologies. First-line LPAs were first
recommended by WHO in 2008; the second-line LPA was first recommended in May 2016.
Culture-based methods currently remain the reference standard for drug susceptibility
testing. Without treatment, the mortality rate from TB is high. Studies of the natural history
of TB disease in the absence of treatment with anti-TB drugs (conducted before drug
treatments became available) found that about 70% of individuals with sputum smear-
positive pulmonary TB died within 10 years of being diagnosed, as did about 20% of people
with culture-positive (but smear-negative) pulmonary TB.a Efective drug treatments were
first developed in the 1940s. The currently recommended treatment for cases of drug-
susceptible TB is a 6-month regimen of four first-line drugs: isoniazid, rifampicin, ethambutol
and pyrazinamide. The Global TB Drug Facility supplies a complete 6-month course for about
US$ 40 per person. Treatment success rates of at least 85% for cases of drug-susceptible TB
are regularly reported to WHO by its 194 Member States. Treatment for rifampicin-resistant
TB (RR-TB) and multidrug-resistant TB (MDR-TB)b is longer, and requires more expensive
and more toxic drugs. Until early 2016, the treatment regimens recommended by WHO
typically lasted for 20 months, and cost about US$ 2000–5000 per person. As a result of new
evidence from several countries, WHO issued updated guidance in May 2016. Shortened
regimens of 9–12 months are now recommended for patients (other than pregnant women)
with pulmonary RR-TB or MDR-TB that is not resistant to second-line drugs. The cost of a
shortened drug regimen is about US$ 1000 per person. The latest data reported to WHO
show a treatment success rate for MDR-TB of 54%, globally, reflecting high rates of loss to
follow-up, unevaluated treatment outcomes and treatment failure. There are 17 TB drugs in
clinical trials and combination regimens that include new compounds as well as other drugs
are also being tested in clinical trials. The bacille Calmette-Guérin (BCG) vaccine, which was
developed almost 100 years ago and has been shown to prevent severe forms of TB in
children, is still widely used. However, there is currently no vaccine that is efective in
preventing TB disease in adults, either before or after exposure to TB infection. There are 12
TB vaccines in Phase I, Phase II or Phase III trials.