PRIMEVIEW
TUBERCULOSIS
For the Primer, visit doi:10.1038/nrdp.2016.76
M. tuberculosis
strains might have DIAGNOSIS
Tuberculosis (TB) is an airborne,
MECHANISMS varying virulence
predominantly pulmonary disease and genetic mutations can
caused by Mycobacterium tuberculosis. confer drug resistance (mono-, Diagnosis of active TB disease requires sputum
It is clinically classified as latent TB multidrug- or extensively smear microscopy (to identify the bacteria)
infection (LTBI) — an asymptomatic, drug-resistant TB). and culture-based and molecular tests, such as
contained, non-transmissible state — or GeneXpert technology. GeneXpert detects the
active TB disease, which is symptomatic presence of M. tuberculosis and can also detect
and potentially transmissible. rifampicin-resistant strains. However, implementing
this molecular assay is often not feasible in low-
income settings. Accordingly, new biomarkers are
being sought to develop simpler, non-sputum-
EPIDEMIOLOGY based, point-of-care diagnostics. New molecular
tests for universal rapid drug susceptibility testing
Approximately 9.6 million new cases of active are also required to ensure maximal efficacy of
TB disease were estimated in 2014 — 10% of which current and emerging drug regimens.
occurred in children and >1.5 million were fatal. TB
incidence is heterogeneously distributed globally,
with low-income regions, such as South Africa
(>800 cases per 100,000 population per year), having
a higher burden than higher-income regions (for
example, the United States, with 3 cases per 100,000
population per year). Only 5–15% of individuals with
LTBI will progress to active TB disease. However, this Mycobacteria
If bacteria escape ultimately migrate to
large pool of people who are
the granuloma the lung parenchyma
infected with M. tuberculosis HIV infection is a major or the draining where they form a
Complex
is an important hurdle for risk factor for developing lymph nodes, granuloma —
host–pathogen MANAGEMENT
achieving epidemic control. active TB disease: 12% of they can cause interactions a growing aggregate
new cases and 25% of all active TB disease. determine the course of cells of the
TB-related deaths occur in If they spread to of M. tuberculosis immune system Individuals with LTBI who are at increased
the bloodstream, infection: it can present that ‘walls off’ the risk of developing active TB disease should
PREVENTION patients with HIV infection
more-severe as a dynamic spectrum, bacteria, but is also a receive preventive therapy (typically, isoniazid
forms of active from LTBI to active favourable milieu for
TB disease ensue. for 6–9 months). Drug-sensitive active TB
TB disease. bacterial replication.
The only available vaccine is the Bacillus disease responds well (~85% cure rate) to
Calmette–Guérin (BCG), which was antibiotics (typically, a 6-month regimen
introduced in the 1920s. Worldwide, with isoniazid, rifampicin, pyrazinamide and
>90% of infants are vaccinated with OUTLOOK ethambutol), but drug-resistant (particularly
BCG every year, but the vaccine efficacy 2014 9.6 million multidrug-resistant and extensively drug-
in adolescents and adults — the age The goal of the WHO End The emergence of drug Investment resistant) TB needs longer treatment and is
groups that are most likely to spread TB Strategy is to decrease the resistance also needs Political will associated with poorer outcomes. The long
M. tuberculosis infection — is limited. worldwide TB incidence to to be tackled. Finally, it Biomarkers duration of treatment can cause toxicity and
New vaccines are under development, <10 per 100,000 people by will be vital to improve TB Vaccines undermine patient adherence. Antiretroviral
which are being designed to prevent 2035. Eliminating TB will require control programmes in Diagnostics therapy in HIV-positive patients can reduce the
the development of active TB disease investments in research, to high-burden settings Antimicrobials risk of concomitant TB, although drug–drug
or prevent the establishment of LTBI develop new diagnostics, through global, political 2035 interactions between antiretroviral and anti-TB
altogether upon exposure. vaccines and drugs. and financial efforts. agents might cause severe adverse effects.
<1 million
Designed
Written byby
Lucia
Laura
Brunello;
Marshalldesigned by Laura Marshall and Neil Smith Article number: 16077; doi:10.1038/nrdp.2016.77; published online 27 Oct 2016
©
2
0
1
6
M
a
c
m
i
l
l
a
n
P
u
b
l
i
s
h
e
r
s
L
i
m
i
t
e
d
,
p
a
r
t
o
f
S
p
r
i
n
g
e
r
N
a
t
u
r
e
.
A
l
l
r
i
g
h
t
s
r
e
s
e
r
v
e
d
.
