Tuberculosis
Kolářová M., EPI Autumn 2019
The most important causative agent of tuberculosis is
Mycobacterium tuberculosis.
M. 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 of which M. leprae and
M. avium are best known.
Tuberculosis – Case definition
Clinical Criteria
◼ Any person with the following two:
◼ — Signs, symptoms and/or radiological findings consistent with active tuberculosis in any site
◼ AND
◼ — A clinician’s decision to treat the person with a full course of anti-tuberculosis therapy
◼ OR
◼ A case discovered post-mortem with pathological findings consistent with active tuberculosis that would have indicated anti-tuberculosis
antibiotic treatment had the patient been diagnosed before dying
Laboratory Criteria
◼ — Laboratory criteria for case confirmation
◼ At least one of the following two:
◼ — Isolation of Mycobacterium tuberculosis complex (excluding Mycobacterium bovis-BCG) from a clinical specimen
◼ — Detection of Mycobacterium tuberculosis complex nucleic acid in a clinical specimen AND positive microscopy for acid-fast bacilli or
equivalent fluorescent staining bacilli on light microscopy
◼ — Laboratory criteria for a probable case
◼ At least one of the following three:
◼ — Microscopy for acid-fast bacilli or equivalent fluorescent staining bacilli on light microscopy
◼ — Detection of Mycobacterium tuberculosis complex nucleic acid in a clinical specimen
◼ — Histological appearance of granulomata
Epidemiological Criteria NA
Case Classification
◼ A. Possible case
◼ Any person meeting the clinical criteria
◼ B. Probable case
◼ Any person meeting the clinical criteria and the laboratory criteria for a probable case
◼ C. Confirmed case
◼ Any person meeting the clinical and the laboratory criteria for case confirmation
TB notification rate over time
◼The TB notification rate has decreased from 19.3 per 100
000 population in 2004 to 12.7 in 2013.
◼
4
Figure 2: TB notification rate per 100 000 population in EU/EEA
2004−2013
0
5
10
15
20
25
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
cases/100000
Year of reporting
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.
◼ Clinical features and sequelae
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.
In the pre-chemotherapy era, case-fatality from tuberculous meningitis
approached 100 per cent. Pulmonary TB accounted for the majority of
deaths. Sputum smear-positive TB has a much higher fatality than sputum
smear-negative TB. Untreated sputum smear-positive TB leads to death in
about 30–40 per cent of cases within one year and cumulatively kills about
50–70 per cent of cases within 5 to 7 years5.
◼ Epidemiology
◼ The average notification rate in the European Union
(EU) and European Economic Area (EEA) region is
16.7 per 100 000 population (2008 data).
◼ In low-incidence countries (reporting a notification rate
below 20 per 100 000), TB is predominant in
vulnerable populations. Examples of vulnerable
populations include individuals from high incidence
countries, prisoners, contacts of contagious patients,
persons who have previous had TB, drug addicts,
alcoholics, illegal immigrants and the homeless. In
some of these risk groups the incidence is increased
due of ongoing transmission (e.g. prisoners, drug
addicts and homeless people)7-10.
◼ Transmission
◼ Humans are the main reservoir 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.
◼ The lifetime risk of developing TB for people outside of the risk
groups is approximately ten per cent11. For HIV-infected
persons this risk is much higher, amounting to 8–10 per cent
per year.
◼ Patients with a negative culture of sputum (‘closed’ TB) and
cases of extrapulmonary TB are not considered to be
contagious.
◼ 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.
Transmission II
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 infected14.
◼ 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 BCGvaccination
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.
◼ 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.
◼ Prevention II
◼ Practising cough hygiene will decrease the spread of all types
of infections that are spread through the air.
◼ 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.
◼ Management and treatment
◼ Notification of TB cases is compulsory in most EU countries6.
◼ Cases of respiratory TB require infection control precautions until infectivity
has been eliminated by effective chemotherapy; this often requires two
weeks treatment with drugs to which the infecting strain is sensitive19,20.
◼ Contact investigation can be performed as soon as a contagious patient with
TB has been diagnosed. The aim of this activity is to identify secondary
cases of TB and/or newly infected persons. If a secondary case is identified
through the contact investigation, this patient can be diagnosed early which
then reduces the chance of further transmission21.
◼ Newly infected persons can be offered prophylactic treatment in order to
reduce their chance of progression from latent to active disease1.
◼ The treatment of active TB has two phases: an initial intensive phase and a
continuation phase. The recommended standard regimen by the WHO for all
new cases is an intensive phase of two months with isoniazid, rifampicin,
pyrazinamide and ethambutol and a continuation phase of four months with
isoniazid and rifampicin.
◼ Drug resistance is increasing in many countries, and treatment failure and
relapse are strongly associated with initial drug resistance23. Individual risk
factors include history of previous treatment for TB, recent contact with drugresistant
case and HIV infection24.
◼ Persons at a high risk for developing TB (cases with recent M. tuberculosis
infection and those with clinical conditions associated with progression to
active TB like HIV, for example) will be given prophylactic treatment25,26.
◼ Areas of uncertainty
◼ Use of interferon gamma-release assays (IGRA): IGRA, a new diagnostic
tool, is gradually being introduced in circumstances in which the tuberculin
skin test is currently used.
◼ Caution is necessary when testing certain populations because of limited
data in the use of IGRAs. More data are necessary on their use in younger
age groups, among persons recently exposed to M. tuberculosis, and in
immunocompromised persons (e.g. cases of HIV, users of
immunosuppressive drugs, selected haematological disorders, those with
specific malignancies along with cases of diabetes, silicosis and chronic
renal failure). Limited data are available on the use of IGRA to determine
who is at risk for developing active TB.
◼ Treatment and prophylaxis of MDR TB and XDR TB cases: There is little
evidence regarding the treatment of MDR TB and XDR TB. In the absence
of controlled trials, expert opinions prevail and perspectives differ according
to personal experience. As a result, significant discrepancies are found in
the guidelines published by scientific societies29,30. Success rates for the
treatment of MDR TB patients vary between 50–80 per cent, depending on
the treatment setting.
◼ Also, evidence for the effects of latent TB infection treatment in people
exposed to MDR TB is extremely limited both in quantity and quality. For the
treatment of MDR TB at present, we see a great variety in recommended
treatment.
◼ Further studies are required on the level of recurrence of TB following
successful treatment from real-life directly observed treatment, short-course
(DOTS) programmes.
Key conclusions for the European Region
In 2011, the countries of the WHO European Region
reported 295 968 new episodes (new and relapses)
of TB (33 per 100 000 population) out of an estimated
380 000 (range 321–437 000), which would correspond
to 42 cases per 100 000 population (range 36–49).
More than 85% of them were in the 18 high priority
countries (HPC) of the WHO European Region.
• The Region maintained a relatively high case detection
rate for all cases: 78% (range 67–92%).
TB notifications by country◼In 2013, 64 844 TB cases were reported in the EU/EEA.
◼The notification rate was 12.7 per 100 000 population (range 3.4–83.5).
16
Figure 1: TB
notification rate
per 100 000
population by
country, EU/EEA,
2013
Not included or 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
Zdroj: www.czso.cz
Vývoj počtu hlášených TBC/100 tis.obyvatel,ČR
Struktura hlášené TBC podle dg., rok
2012
TBC – in Slovakia - 2013
number of cases/100 000 residents
16,15
8,06
4,81
4,79
4,89
4,31
5,71
BA TT
TN
NI
ZA
BB
5,62
PO
KE
Source: Doc. MUDr. Ivan Solovič, CSc.
Key conclusions for the European Region
More than 44 000 (44–46 000) deaths were estimated
to have been caused by TB in the Region (4.9 per
100 000 population) (range 4.7–5.3).
Overall, 92% of deaths occurred in the 18 HPC.
The notification shows a 24% decrease compared to
2005, however there is a significant difference in TB
notification rates among the countries, from 2 to 119
per 100 000 population.
• In ten countries of the Region (all in EU/EEA), the
under-fives accounted for more than half of the cases
detected among children.
Key conclusions for the European Region
• In 2011, there were 12 751 (56.5%) TB cases with
HIV co-infection detected from the 22 500 (range
18–27 000) estimated in the WHO European Region.
Estimated prevalence of HIV infection among incident
TB patients was 6% (range 5.6–6.2%), with 3.6% of
these cases occurring in the EU/EEA countries and
6.5% in the non-EU/EEA countries.
Due to the low reporting coverage of HIV testing (60%), only 12
751 (6.2%) of the 205 578 new TB and previously treated
cases were found to have HIV co-infections.
◼ Three countries reported higher rates of HIV positivity
among TB patients: Ukraine (18.5%), Malta (16.7%)
and Estonia (15%).
Key conclusions for the European Region
• Of the 78 000 estimated MDR-TB cases in the
Region, around 30 000 (38%) were detected in
2011.
In all, 98% of them were reported by 18 HPC.
The prevalence of MDR among new TB cases
in the Region amounted to 14% and 7.7%
among previously treated cases.
Although testing coverage for XDR has almost
doubled in the Region, it is still only at 9%,
documenting that 11% of MDR-TB patients are
XDR-TB.
In response to the alarming problem of MDR-TB,
all 53 Member States have fully endorsed the
Consolidated Action Plan to Prevent and Combat
Multidrug- and Extensively Drug-Resistant
Tuberculosis in the WHO European Region
2011–2015 and its accompanying Resolution
EUR/RC61/R7 from the sixty-first session of the
WHO Regional Committee for Europe in 2011.
The Action Plan includes a set of activities for
countries, WHO and partners in order to achieve
universal access to prevention and treatment of
M/XDR-TB. WHO is currently preparing a
detailed report on progress with the
implementation of the Consolidated Action Plan
to Prevent and Combat Multidrug- and
Extensively Drug-Resistant Tuberculosis in 2013.