TUBERCULOSIS

:: Box 1.1
Basic facts about TB
TB is an infectious disease caused by the bacillus
Mycobacterium tuberculosis. It typically affects the
lungs (pulmonary TB) but can also affect 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 2–3 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.
Diagnostic tests for TB disease include:
sputum smear microscopy. This was developed more than
100 years ago. Sputum samples are examined under a
microscope to see if bacteria are present. In the current
case definitions recommended by WHO, one positive result
is required for a diagnosis of smear-positive pulmonary TB;
rapid molecular tests. The only rapid test for diagnosis
of TB currently recommended by WHO is the Xpert®
MTB/RIF assay (Cepheid, Sunnyvale USA). It was initially
recommended (in 2010) for diagnosis of pulmonary TB
in adults. Since 2013, it has also been recommended for
children and specific forms of extrapulmonary TB. The test
has much better accuracy than microscopy; and
culture methods. These are the current reference standard
but 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 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 2015, for example, 57% of the
pulmonary cases reported to WHO were bacteriologically
confirmed.
There are also tests for TB that is resistant to first and
second-line anti-TB drugs. They include Xpert MTB/RIF,
which simultaneously tests for TB and resistance to rifampicin
(the most effective 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 death rate from TB is high. Studies
of the natural history of TB disease in the absence of
treatment with anti-TB drugs (that were conducted before
drug treatments became available) found that about 70% of
people with sputum smear-positive pulmonary TB died within
10 years, as did about 20% of people with culture-positive
(but smear-negative) pulmonary TB. a
Effective drug treatments were first developed in the 1940s.
The currently recommended treatment for new 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 new 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. A standardised shorter
MDR-TB regimen of 9–12 months is now recommended for all
patients (excluding pregnant women) with pulmonary MDR/
RR-TB that is not resistant to second-line drugs. The cost of a
shortened drug regimen is about US$ 1000 per person.
New TB drugs have begun to emerge from the pipeline, and
combination regimens that include new compounds are 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
widely used. However, there is currently no vaccine that is
effective in preventing TB disease in adults, either before or
after exposure to TB infection. There are 13 TB vaccines in
Phase I, Phase II or Phase III trials.
a
Tiemersma EW, van der Werf MJ, Borgdorff MW, Williams BG, Nagelkerke
NJ. Natural history of tuberculosis: duration and fatality of untreated
pulmonary tuberculosis in HIV negative patients: a systematic review. PLoS
One. 2011;6(4):e17601 (http://www.ncbi.nlm.nih.gov/pubmed/21483732,
accessed 27 July 2016).
b
Defined as resistance to isoniazid and rifampicin, the two most powerful
anti-TB drugs.
4 :: GLOBAL TUBERCULOSIS REPORT 2016