Tuberculosis
Kolářová M., EPI Autumn 2017
Tuberculosis (TB) remains a common infection in EU/EEA
countries.
In 2014, 58 008 cases of TB were reported in 29 EU/EEA
countries (excluding Italy and Liechtenstein).
The EU/EEA notification rate in 2014 was 12.8 per
100 000 population.
Twenty-seven per cent of TB cases were in people of foreign
origin, most of them residing in low-incidence countries.
Multidrug-resistant TB (MDR TB) was reported for 4.0% of 36
380 cases with drug susceptibility testing results and continues
to be most prevalent in the three Baltic countries.
Of all TB cases with a known HIV status, 4.9% were co-infected
with the virus.
Ziehl-Neelsen stain of 'cords' of Mycobacterium tuberculosis isolated from a broth
culture. Tubercle bacilli aggregate end to end and side to side to form serpentine
cords, especially in broth cultures.
TUBERCULOSISThe most important causative agent of tuberculosis (TB) is Mycobacterium tuberculosis. - together
with M. bovis, M. africanum and M. microti, form the ‘M. tuberculosis complex’, which is a group within
the genus Mycobacterium. This genus also includes many different nontuberculous mycobacteria
(NTM), of which M. leprae and M. avium are best known.
M. tuberculosis is typically a slightly curved or straight rod-shaped microbe. Its length is 2–5 μm and
the generation time ranges from 12–24 hours. The bacterium is aerobic and non-spore forming 1
Humans are the main source for M. tuberculosis and M. africanum. For M. bovis, cattle
are the most important host. Cases of TB can occur sporadically in monkeys and some
other mammals.
Transmission of TB is aerogenic. After coughing, sneezing, speaking or singing, infected
sputum droplets can dry and form into droplet nuclei of approximately 6–18 μm. These
droplet nuclei can float in the air for a longer period and penetrate into the alveoli of the
host after inhalation. In moist warm air, the droplet nuclei can survive for hours
Susceptibility to BK is general. The highest susceptibility is in early childhood (under 4
years of age), puberty and in pregnant women . A higher risk of TB development exists
in immunodeficient states, silicosis, diabetes, alcoholics, malign diseases, and in the
sick with immunosuppressive treatment and HIV.
The source
of infection
Route of
transmission
Etiology:
Susceptibility
Preventive measures: is the foundation for effective TB control programmes. Preventive measures
focusing on the early diagnosis and immediate effective treatment of people with contagious TB is therefore
essential.
The vaccine currently available is the BCG-vaccine (Bacille Calmette Guérin). This is a live, weakened strain
of M. bovis. It mainly gives protection against severe forms of the disease, like meningitis TB and miliary TB,
in children under five years of age.
TUBERCULOSIS
Clinical features and diagnosis
Tuberculosis is a general chronic infectious disease mainly affecting the respiratory
tract. In approximately 10 % of cases it has extrapulmonary localization.
The disease manifestations can be classed as primary and postprimary.
 Primary TB infection is characterized by development of a primary complex
formed by a specific inflammation at the point of entry of BK (Koch´s bacillus),
peribronchial lymphangiitis and a specific inflammation of a regional lymphnode.
 A prevalent part of the primary complexes is localized in the lungs.
 An extrapulmonary primary complex usually develops due to a deglutition BK
infection.
 Primary TB infection manifests through nonspecific symptoms and clears
spontaneously. Calcification of the residual foci occurs during the further course of
TB. Mycobacteria may persist there up to several decades and cause endogenic
reactivation of TB. Only in about 10 % of infected individuals does the so-called
postprimary TB develop in the course of life. The primary infection confers
cellular immunity, its manifestation is a late-type tuberculin hypersensitivity (PPD).
TUBERCULOSIS
 Postprimary TB - all forms of tuberculosis which develop in primarily infected
persons, i.e. in humans who had a positive tuberculin reaction prior to the
disease.
 The spread of BK occurs by preformated airways, aspiration of the
metastases, and sputum expectoration (larynx TB).
 The spread may occur by a lymphatic route when the agent surpasses the
lymphatic barrier and reaches the blood. Dissemination into other organs
occurs (e.g., bones, cerebral matter, joints, kidneys).
 The symptomatology of tuberculosis is varied depending on the scope of
affection. In about 1/3 of cases the disease is long-term asymptomatic.
Infection with M. tuberculosis is asymptomatic. The
symptoms that occur when TB disease develops are
usually not very specific. Often there are complaints of
tiredness, listlessness, loss of weight, sub-febrile body
temperature and night sweating.
In the case of pulmonary TB, usually a cough has been
present for weeks or even months, possibly accompanied
by haemoptysis.
Localisation in the vertebral column (spondylitis
tuberculosa) can, apart from back pain, also present itself
as an abscess with vertebral collapse.
Lymphadenitis tuberculosa usually presents itself by
painless lymph node enlargement in the neck.
Blood in the urine (haematuria) can present as the only
symptom of TB of the kidney.

In cases of co-infection with HIV, the clinical
presentation can be less typical.
This atypical presentation is usually seen in a more
advanced stage of the HIV infection and is the result
of impaired cellular immunity.
HIV-infected patients show disseminated forms of TB
relatively often.
M. tuberculosis can develop resistance to drugs by
spontaneous chromosomal mutations.
When a case of active TB is not correctly treated, it can
result in multidrug-resistant (MDR) TB and extensively
drug-resistant (XDR) TB.
MDR TB is defined as TB bacteria that are resistant to at least isoniazid and
rifampicin.
XDR TB means that, in addition to isoniazid and rifampicin, the TB bacteria are
resistant to any fluoroquinolone and at least one of three injectable secondline
drugs (capreomycin, kanamycin and amikacin).
In general, in patients with a positive Ziehl-Neelson slide and/or positive
culture of their sputum, the start of coughing complaints is considered to
be the start of the period of infectiousness.
 The incubation period (between infection and the first signs of
illness) varies between eight weeks to a lifetime.
The greatest chance of progressing to disease is within the first two
years after infection, with half of all cases of disease occurring within five
years of the original infection.
However, a lifelong risk of progression to disease remains for all those
people with ‘dormant’ organisms.
People in whom infection progresses to disease are only a minority of all
infected persons.
People with latent TB infection are never infectious.
The risk of transmission in cases of active TB is
determined by patient factors and the type of contact
made with their surroundings.
The level of contagiousness of TB patients depends
on:
 the concentration of bacteria in the sputum,
 the severity of the cough and
 the coughing hygiene practiced by the patient.
In general, the closer and/or more frequent the
contact, the higher the chance of transmission.
Characteristics of the place of contact may also play an
important role (e.g. size of the room, ventilation). Usually,
intimate contacts (household) are at the highest risk of being
infected.
PREVENTION
The vaccine currently available is the BCG-vaccine (Bacille Calmette
Guérin).
This is a live, weakened strain of M. bovis.
It mainly gives protection against severe forms of the disease, like
meningitis TB and miliary TB, in children under five years of age.
The World Health Organization (WHO) advises BCG-vaccination for all
newborns in countries with a high incidence of TB within the framework
of the Expanded Program of Immunization (EPI).
Within the EU, the policy on BCG-vaccination varies between countries.
Low incidence countries commonly vaccinate only persons with an
increased risk of TB; for example, children whose parents come from
high incidence countries and who travel regularly to their home country
PREVENTION
 BCG-vaccination should not be given to the immunosuppressed (e.g.
HIV, leukaemia, chemotherapy) due to the increased risk for
complications.
 Also, BCG-vaccination during pregnancy should be avoided, even
though no harmful effects on the foetus have been observed.
 Practising cough hygiene will decrease the spread of all types of
infections that are spread through the air.
PREVENTION
Preventing the transmission of the disease is the foundation for effective
TB control programmes.
 Preventive measures focusing on the early diagnosis and
immediate effective treatment of people with contagious TB is
therefore essential. Many factors have been shown to be associated
with a delay in diagnosis including old age, low education/awareness,
poverty, negative sputum smear, extrapulmonary TB, female sex and
a history of immigration.

Passive case finding is defined as the detection of TB cases among
patients attending healthcare facilities because they have symptoms.
Active case finding focuses on the screening of high-risk groups
(immigrants, drug addicts, homeless people and prisoners) for TB.
It aims to identify and treat TB cases at an early stage and to provide
preventive treatment to those at the highest risk for developing active TB.
Vývoj počtu hlášených TBC/100 tis.obyvatel,ČR
Struktura hlášené TBC podle dg., rok 2012
TB Surveillance data, EU/EEA, 2014
16
TB notifications, EU/EEA, 2014
58 008 TB cases notified in 29 EU/EEA countries

Notification rate of 12.8 per 100 000 population
(range 2.5–79.7)
17
Not reporting
20 to 49 per 100 000
10 to 19 per 100 000
5 to 9 per 100 000
< 5 per 100 000
≥ 50 per 100 000
Source: European Centre for Disease Prevention and Control.
TB surveillance and monitoring in Europe, 2016.
Reported TB cases, EU/EEA, 2005 – 2014
Steady decline between 2005 and 2014:
• number of TB cases decreased by 35%
• notification rate decreased by 36%
18
0,0
2,0
4,0
6,0
8,0
10,0
12,0
14,0
16,0
18,0
20,0
10 000
20 000
30 000
40 000
50 000
60 000
70 000
80 000
90 000
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
TBcases/100000
TBcases
Year of reporting
TB cases TB cases/100 000
Source: European Centre for Disease Prevention and Control.
TB surveillance and monitoring in Europe, 2016.
TB notification rate by age group, EU/EEA, 2005 – 2014
19
0,0
5,0
10,0
15,0
20,0
25,0
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
TBcases/100000
Year of reporting
0-4 5-14 15-24 25-44 45-64 65+
Source: European Centre for Disease Prevention and Control.
TB surveillance and monitoring in Europe, 2016.
Decreased by > 25% in all age groups over the period
Notified TB in children under 15, EU/EEA, 2014
20
Not reporting
4 to 9.9 per
100 000 child population
2 to 3.9 per
100 000 child population
≥ 10 per
100 000 child population
< 2 per
100 000 child population
Source: European Centre for Disease Prevention and Control.
TB surveillance and monitoring in Europe, 2016.
2 258 TB cases reported in children under 15 years.
That is 3.9% of all TB cases (range 0-13.7%) and
2.8 notifications per 100 000 child population (range
0–20.7).
Notified TB cases in persons of foreign origin, EU/EEA,
2005 – 2014
21
* Slight decrease in the proportion of cases in persons of
foreign-origin in 2014, probably due to missing data from Italy
0
2
4
6
8
10
0
5
10
15
20
25
30
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Cases/100000
Percentage
Year of reporting
Source: European Centre for Disease Prevention and Control.
TB surveillance and monitoring in Europe, 2016.
Percentage of cases in persons of foreign origin increased from
19% in 2005 to 27% in 2014.
Rate per 100 000 total population stable* between 3.4 and 3.8
Notified extrapulmonary TB cases, EU/EEA, 2014
22
10 to 19.9%
≥ 30%
0 to 9.9%
20 to 29.9%
Not reporting
Source: European Centre for Disease Prevention and Control.
TB surveillance and monitoring in Europe, 2016.
21.8% of TB cases were extrapulmonary TB
(range 3.2–46.0%)
Multidrug-resistant TB notification rate, EU/EEA,
2010 – 2014
23
0
0,1
0,2
0,3
0,4
0,5
2010 2011 2012 2013 2014
MDRTBcases/100000
Year of reporting
Source: European Centre for Disease Prevention and Control.
TB surveillance and monitoring in Europe, 2016.
Rate was stable at 0.3 per 100 000 population between
2010 and 2014
Extensively drug-resistant TB (XDR TB), EU/EEA, 2014
24
10 to 14.9%
≥ 25%
1 to 9.9%
15 to 24.9%
< 1%
Not reporting
Source: European Centre for Disease Prevention and Control.
TB surveillance and monitoring in Europe, 2016.
* DST – drug susceptibility test
17.5% of MDR TB cases with 2nd line DST* were
extensively drug-resistant (range 0–50.0% and 5.7–
26.1% for countries reporting more than one case)
Notified TB/HIV co-infection, EU/EEA, 2014
25
10 to 14.9%
≥ 15%
1 to 9.9%
< 1%
Not reporting
* Among countries with at least 50% reporting completeness
for HIV status
Source: European Centre for Disease Prevention and Control.
TB surveillance and monitoring in Europe, 2016.
4.9% of TB cases with known HIV status* were
HIV positive (range 0–22.6%)
Tuberculosis (TB) incidence overall and among U.S.- and foreign-born persons,
by year — United States, 2000–2015.