Transcript 10. Tüdőtuberculosis, Mycobacteriosis

Tuberculosis
Bálint Beatrix MD, PhD
SZTE, Dpt. of Pulmonology
Deszk
2015.
Tuberculosis
TB a chronic bacterial infection, causes more deaths
worldwide than any other infectious disease.
TB is spread through the air and usually infects the
lungs, although other organs are sometimes involved.
Some 2 billion people - one-third of the world's
population - are infected with the TB organism,
Tuberculosis kills 1.7 million people every year, and is
the major killer of people living with HIV.
Mycobacterium tuberculosis.
History 1.
Paleopathological evidences
- skeletal TB, bone TB
Ancient greek physisians used the word PHTYSIS
8th-9th century ¼ of the european adults died from TB.
Germ theory:
-Robert Koch (1882)-Pathogenicity of Mycobacterium tuberculosis
-Konrad Röntgen (1892)- X ray
TB in the World (number of TB cases)
Románia
Oroszország
Portugália
Szerbia
Lengyelország
Magyarország
2005
Spanyolország
Szlovénia
2004
Nagy-Britannia
2003
Szlovákia
2002
Ausztria
Belgium
2001
Csehország
Franciaország
Németország
Hollandia
Finnország
Olaszország
Dánia
Svédország
% 000
Tbc incidencia Európában az elmúlt években
TB in EUROPE
2006
160,0
140,0
120,0
100,0
80,0
60,0
40,0
20,0
0,0
Epidemiology
Region
Africa
Incidence
2,300,000
Prevalence
Deaths
2,500,000 220,000
Population
857,382,000
Americas
260,000
330,000
21,000
943,019,000
Eastern Mediterranean
660,000
1,000,000
99,000
608,628,000
Europe
380,000
500,000
45,000
899,500,000
South-East Asia
3,500,000
5,000,000 480,000
1,830,361,000
Western Pacific
1,700,000
2,500,000 130,000
1,808,797,000
Global Total
8,800,000
11,830,000 995,000
6,947,687,000
TB and HIV
People living with HIV are from 26-31 times more likely to develop
TB than persons without HIV.
TB is the most common presenting illness among people living with
HIV, including among those taking antiretroviral treatment and it is
the major cause of HIV-related death.
WHO policy on collaborative TB/HIV activities
Guidelines for national programmes and other stakeholders
http://apps.who.int/iris/bitstream/10665/44789/1/9789241503006_en
g.pdf?ua=1&ua=1
Mycobacterium tuberculosis
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The causative agents for tuberculosis
Discovered by Robert Koch in 1882
~25 % of world’s population infected
25 million is infected in USA
Mycobacterium tuberculosis: Tbc-t okozó baktérium
Robert Koch 1882-ben fedezte fel
Microbiology
Mycobacterium tuberculosis: obligate, aerobic parazite, acid-fast
slow growth, visible colonial growth: 4-6 weeks
INH resistant and sensitive strains are different
Direct examination: Ziehl-Neelsen stain:
4 m long and 0,2-0,5 m wide
10 000 organism/ml of sputumsmear positive
Culture of sputum/fluid
M. tuberculosis: growths slowly, lack of pigment, produces
Niacin:
M. bovis: niacine negative
Drug sensitivity test.
Blood test: Today's policy recommendation applies to blood tests for active TB. Blood tests
for inactive TB infection (also known as dormant or latent TB) are currently under review by
WHO.
The new recommendation comes after 12 months of rigorous analysis of evidence by WHO and
global experts. Overwhelming evidence showed that the blood tests produced an unacceptable
level of wrong results - false-positives or false-negatives - relative to tests endorsed by WHO.
WHO-approved microbiologic tests for tuberculosis
Diagnosis of active TB 1.
Test
Site
Major Findings/results of Systematic review
Sputum smear
microscopy
Pulmonary
• fluorescence microscopy is on average 10% more
nucleic acid amplification
tests (NAATs) [other than
Xpert MTB/RIF]
Pulmonary
and extrapulmonary
TB
sensitive than conventional microscopy. Specificity of
both fluorescence and conventional microscopy is
similar. Fluorescence microscopy is associated with
improved time efficiency.
•Same-day sputum smear microscopy is as accurate
as standard smear Microscopy. Compared with the
standard approach of examination of two smears with
light microscopy over 2 days, examination of 2
smears taken on the same day had much the same
sensitivity (64% for standard microscopy vs 63% for
same-day microscopy) and specificity (98% vs 98%)
Commercial, standardized NAATs have high
specificity and positive predictive value,
however, they have relatively lower (and highly
variable) sensitivity and negative predictive
value for all forms of TB, especially in smearnegative and extrapulmonary disease
WHO-approved microbiologic tests for tuberculosis Diagnosis of active TB 2.
Test
Site
Major Findings/results of Systematic review
Xpert MTB/RIF
Pulmonary TB
and
extrapulmonary
TB and RIF
resistance
Xpert MTB/RIF used as an initial diagnostic test for
detection of M. tuberculosis and rifampicin is sensitive and
specific. Xpert MTB/RIF is also valuable as an add-on test
following microscopy for patients who are smearnegative.an Xpert MTB/RIF result that is positive for
rifampicin resistance should be carefully interpreted and
take into consideration the risk of MDR TB in a given
patient and the expected prevalence of MDR TB in a given
setting.
• when used as an initial test replacing smear microscopy
Xpert MTB/RIF achieved a pooled sensitivity of 88% and
pooled specificity of 98%.
• for detection of rifampicin resistance Xpert MTB/RIF
achieved a pooled sensitivity of 94% and pooled specificity
of 98%
Automated liquid
cultures and rapid
MPt64-based
species
identification tests
Pulmonary TB
and extrapulm.
TB
specification
automated liquid cultures are more sensitive than
solid cultures; time to detection is more rapid than
solid cultures.
• mPT64-based rapid immunochromatographic tests
(ICT) for species identification has high sensitivity
and specificity
The Xpert MTB/RIF is an
automated, cartridge-based nucleic
amplification assay for the
simultaneous detection of TB and
rifampicin resistance directly from
sputum in under two hours. It can
identify Mycobacterium
tuberculosis (MTB) DNA and
resistance to rifampicin (RIF) by
nucleic acid amplification technique
(NAAT).
In 2010, the WHO endorsed it for
use in TB endemic countries and
declared it a major milestone for
global TB diagnosis.
Atípusos Mycobacterium
identifikálására is alkalmas.
Budapest OKTPI/ Corden
Laboratóriumban elérhető
Mode of spread
• TB is spread from in microscopic droplets person
to person — droplet nuclei — expelled from the
lungs when a TB sufferer coughs, sneezes, speaks,
sings, or laughs. Only people with active disease
are contagious.
• People are most likely to be contagious when their
sputum contains bacilli, when they cough
frequently and when the extent of their lung
disease, as revealed by a chest x-ray, is great.
* People who have been treated with appropriate drugs for at
least two weeks usually are not infectious.
Predisposing Factors
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Babies and young children
HIV infection
substance abuse
diabetes mellitus
silicosis
cancer
leukemia or Hodgkin's disease
severe kidney disease
low body weight
certain medical treatments
– corticosteroid treatment
– organ transplants
– chemotherapy
How Tuberculosis Affects The Body
COMMON SYMPTOMS
A bad cough that lasts
more than three weeks
Fever
TB is spread when you
inhale the bacteria in
droplets expelled then
someone infected
speaks or coughs.
Coughing up blood or sputum
Weakness or fatigue
No appetite
Weight loss
Pain in the chest
COURSE OF INFECTION
INFECTION
Can turn into either latent or active TB.
LATENT TB
In the initial stage of disease, called latent TB, TB bacteria remain alive, but
cannot spread to other tissue or people. Most infections will never get past this
stage. 10 % of latent TB infections become active.
ACTIVE TB
Active pulmonary TB
(TB in the lungs) is contagious.
Sources: CDC, PLoS One,
WHO
DEATH
Without treatment,
people who are HIV-negative have
a mean 10-year fatality rate of 70 %
RECOVERY
A full course of TB treatment takes
6 to 9 months of taking several drugs.
HOW DOES TB DISEASE DEVELOP?
There are two possible ways a person can become sick with TB
disease:
1.A person who may have been infected with TB for years and has
been perfectly healthy. The time may come when this person
suffers a change in health. The cause may be another disease like
AIDS or diabetes. Or it may be drug or alcohol abuse or a lack of
health care because of homelessness.
Whatever the cause, when the body's ability to protect itself is
damaged, the TB infection can become TB disease. In this way, a
person may become sick with TB disease months or even years
after they first breathed in the TB germs.
2. A person first breathes in the TB germs the body is unable to
protect itself against the disease. The germs then develop into
active TB disease within weeks. (This way TB disease develops
happens much more quickly.)
Symptoms
Early TB (single or multiple nodule, caseous lesion)
- no symptomes
Progresszive TB (cavitation, pneumonitis)
- nonspecific symptomes: anorexia, fatigue, weight loss,
remittent fever,
night sweets
- cough, sputum (mucopurulent)
- haemoptysis
- chest pain (inflammation of parietal pleura)
Laboratory findings
IIn advanced TB!
- RBC 
- Se albumin 
- WBC 
- Sodium 
- Calcium 
Characteristic X-ray findings
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Apical, subapical patchy infiltration
Bilateral upper lobe infiltration
Dissemination: miliary tb
Lower lobe TB
– cavitation or infiltration
– atelectesis, mass leasions, large cavitation with fluid, pneumonic-like
infiltration
• Non-specific
• Pleural effusion
• Special
– Simon foci: The initial infection leaves nodular scars in the apices of one or
both lungs, called which are the most common seeds for later active TB.
– Ghon foci: calcified scars of primary infection and residual calcified hilar
lymph nodes.
Tbc: tuberculoma
Tb pneumonia
Ghon komplex
Tb hilar adenopathy
Miliary tb
Tb: miliary
Tb: cavity
Tb: cavity
Tb: cavity
Tb:progressive
Callus pleurae, residuum
Diagnosis
• X-ray findings
• Sputum/bronchoscopic lavage fluid smear +
Negatíve tuberculin test: can not exclude the infection
• Histology: TUBERCULOMA
• epitheloid cells,
•Langhans giant cells,
•lymphocytes,
•caseous lesion (necrosis)
•Definitive diagnosis
- culture
- specification of the organism
Extrapulmonary TB
(TB can involve any organ)
-TB of the tonsils, lymph nodes, abdominal organs, bones, and joints caused
by ingestion of milk infected with M. bovis. (slaughtering cows with milk)
*GENITOURINARY TUBERCULOSIS
-kidney pyelonephritis. (chronic, "sterile" routine culture-negative)
-epididymis or prostate gland, baldder, vesicles.
-Salpingo-oophoritis
* TUBERCULOUS MENINGITIS (TB to the subarachnoid space)
* MILIARY TUBERCULOSIS (Generalized Hematogenous or
Lymphohematogenous TB) Bone marrow involvement
* TUBERCULOUS PERITONITIS
*TUBERCULOUS PERICARDITIS
*TUBERCULOUS LYMPHADENITIS
*TUBERCULOSIS OF BONES AND JOINTS (Pott's disease)
*TUBERCULOSIS OF THE LIVER
Resistant TB 1.
Drug resistant tb: resistant to one of the anti-TB drugs.
Multi-drug-resistant tuberculosis (MDR-TB): resistant to at
least isonicid(INH) and rifampicin (RMP), the 2 most
powerful first-line treatment anti-TB drugs.
The reasons why multidrug resistance continues to emerge and
spread are mismanagement of TB treatment and person-to-person
transmission.
-treatable TB when the course of antibiotics is interrupted
and the levels of drug in the body are insufficient to kill 100% of
bacteria. (Patients may feel better and halt their antibiotic course,
drug supplies may run out or become scarce, patients may forget to
take their medication from time to time or patients do not receive
effective therapy.)
-MDR-TB is spread from person to person.
Resistant TB 2.
Extensively drug resistant tb (XDR-TB). is defined as resistance
to at least isoniazid and rifampicin, and to any fluoroquinolone, and
to any of the three second-line injectables (amikacin, capreomycin,
and kanamycin).
MDR-TB and XDR-TB both take substantially longer to treat
than ordinary (drug-susceptible) TB, and require the use of
second-line anti-TB drugs, which are more expensive and have
more side-effects than the first-line drugs used for drugsusceptible TB.
In 2014, an estimated 480 000 people worldwide developed MDR-TB. It
is estimated that about 9.7% of these cases were XDR-TB.
Prevention of MDR TB
• There are several ways that drug resistance to TB, and drug
resistance in general, can be prevented:
– Rapid diagnosis & treatment
– Completion of treatment: Previous treatment of TB is an
indicator of MDR TB. If the patient does not complete his/her
antibiotic treatment, or if the physician does not prescribe the
proper antibiotic regimen, resistance can develop. Also, drugs
that are of poor quality or less in quantity, contribute to MDR
TB.
– Patients with HIV/AIDS should be identified and diagnosed as
soon as possible. They have great risk of developing drug
resistance.
– Identify contacts who could have contracted TB: i.e. family
members, people in close contact, etc.
– Research: Much research and funding is needed in the diagnosis,
prevention and treatment of TB and MDR TB.
History of chemotherapy
Streptomycin
Toxicity
Resistancy
Recidive infection
1946-1952
Isonicid
1952-1970
INH + PAS + Streptomycin
Treatment-18 months
Rifampicin
RMP + INH
RMP + INH + ETB
1970
9 months
6 months
Therapeutic agents for tb
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First line therapy
Isoniazid
Rifampin
Pyrazinamide
Streptomycin
Ethambutol
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Secund line therapy
Ethionamide
Cycloserine
Aminoglycosides
Capreomycin
PAS
Thiocetazone
Imipenem
Ampicillin
Metronidazole
Ciprofloxacin
Ofloxacin
Characteristics of 2nd line drugs
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Less effective drugs
Poor GI tolarence
Significant side effect profile
Not well studied
Some not readily available (PAS)
Treatment
All patients who have not been treated previously and do not have
other risk factors for drug resistance should receive a WHO-approved
first-line treatment regimen using quality assured drugs. The initial
phase should consist of two months of isoniazid, rifampicin,
pyrazinamide, and ethambutol.
The continuation phase should consist of isoniazid and rifampicin
given for 4 months. The doses of antituberculosis drugs used should
conform to WHO recommendations. Fixed-dose combination drugs
may provide a more convenient form of drug administration.
The principles of therapy
• Combination therapy
– kills more effectively
– Shortens therapy
• Prevents emergence of resistance:
– INH/RAMP  EMB SM  PZA
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Treatment must be for a least six month
Bactericidal phase: 1 month
Strerilizing phase: months 3 through 6
Never add a single drug
Initial therapy: four drugs
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Isoniazid (INH)
300 mg daily
Rifampin (RIF)
600 mg daily
Pyrazinamide (PZA)25-30 mg daily
Ethambutol (EMB)25 mg initially
Therapeutic Regimens
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Daily therapy
6 months
Daily treatment
180 doses
2-3 % relapse
• Short course
• 6 months
• Twice or three times
weekly
• 52-114 doses
• Equivalent relapse
Preventive therapy for
tuberculous infection
• Infection vs. active disease
• Lifetime risk for active disease
– Higher in children
– 10 % per year in HIV infected patients
• Mantoux skin test is the indicator of
infection
• Preventive therapy requires 6 months of
single drug therapy
• Isoniazid
Therapy of MDR/XDR TB
• Patients with or highly likely to have tuberculosis caused by drugresistant (especially MDR/XDR) organisms should be treated with
specialized regimens containing quality-assured second-line
antituberculosis drugs.
• The regimen chosen may be standardized or based on presumed or
confirmed drug susceptibility patterns.
• At least five drugs, pyrazinamide and four drugs to which the
organisms are known or presumed to be susceptible, including an
injectable agent, should be used in a 6–8 month intensive phase,
and at least 3 drugs to which the organisms are known or presumed
to be susceptible, should be used in the continuation phase.
• Treatment should be given for at least 18–24 months beyond
culture conversion.
TB and HIV 1.
People living with HIV are from 26-31 times more likely to develop
TB than persons without HIV.
TB is the most common presenting illness among people living with
HIV, including among those taking antiretroviral treatment and it is
the major cause of HIV-related death.
WHO-recommended collaborative TB/HIV activities
http://apps.who.int/iris/bitstream/10665/44789/1/9789241503006_en
g.pdf?ua=1&ua=1
Tuberculosis Care with TB-HIV Co-management INTEGRATED
MANAGEMENT OF ADOLESCENT AND ADULT ILLNESS
(IMAI)
http://www.who.int/hiv/pub/imai/TB_HIVModule23.05.07.pdf
TB and HIV 2.
TB and HIV co-infection is when people have both HIV infection,
and also either latent or active TB disease. When someone has both
HIV and TB, each disease speeds up the progress of the other. In
addition to HIV infection speeding up the progression from latent to
active TB, TB bacteria also accelerate the progress of HIV infection.
In 2013 of the estimated 9 million people who developed TB an
estimated 1.1 million (13%) were HIV positive. There were also in
2013 360,000 deaths from HIV associated TB equivalent to 25% of
all TB deaths, and around 25% of the estimated 1.5 million deaths
from HIV/AIDS.2
HIV infection and infection with TB bacteria are though completely
different infections
http://www.tbfacts.org/tb-hiv/#sthash.aoiSFij9.dpuf
Nontuberculous mycobacteria
• Pumonary disease
– M. avium, kansasii, abscessus, xenopi,
malmoense
• Lymphadenitis
– M. avium, scrofulaceum, malmoense
• Cutaneous disease
– M. marinum, fortuitum, chelonea, ulcerans
• Disseminated disease
– M. avium, kansasii,chelonea, haemophilum
Treatment of nontuberculous
mycobacteria
• The antituberculotic drugs are usually
not effective
• M. kansasii: INH, RIF, EMB
• M. avium: macrolide, Rifamycin, EMB
• Rapid growers: clarithromycin and 2nd
agents
History 2.
Outstanding representatives of the arts
and political life who suffered from TB
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Balzac
Brontë sisters
Chekov
Chopin
Dostoevsky
Kafka
D.H. Lawrence
Sir Walter Scott
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E. A. Poe
Voltaire
John Keats
Rembrandt’s wife
(Sashka) and his son
(Titus)
• Marquise de
Pompadur
• Napoleon II
Literature
• International standards For Tuberculosis Care 3rd
edition, 2014.
http://www.who.int/tb/publications/ISTC_3rdEd.pdf
• http://intranet.tdmu.edu.ua/data/kafedra/internal/proped
eutic_vn_des/classes_stud/en/med/lik/ptn/Phtisiology/4
/Lesson_05_%20%20secondary%20tub%2014.1.htm
• http://www.who.int/features/qa/79/en/
• http://www.who.int/tb/challenges/en/
• http://apps.who.int/iris/bitstream/10665/44789/1/97892
41503006_eng.pdf?ua=1&ua=1
Model: Simonetta Catanea died of TB at the age of 23.
Symptomes:whitish-pink colour of skin, small shoulders,
narrow thorax, low-placed and close breastssigns of phtisis