Sequence of the Presentation History of TB TB Transmission
Drug-Resistant TB TB Pathogenesis Progression from LTBI to TB
disease Sites of TB disease TB Classification System Laboratory and
Physical examination of TB
History of TB
History of Tubercluosis TB has affected humans for millennia
Historically known by a variety of names, including: Consumption
Wasting disease White plague TB was a death sentence for many
History of TB Scientific Discoveries in 1800s Until mid 1800s,
many believed TB was hereditary 1865 Jean Antoine-Villemin proved
TB was contagious 1882 Robert Koch discovered M. tuberculosis, the
bacterium that causes TB
Germany issued a Postal stamp to give tribute to Robert
Koch
History of TB Sanatoriums Before TB antibiotics, many patients
were sent to sanatoriums Patients followed a regimen of bed rest,
open air, and sunshine TB patients who could not afford sanatoriums
often died at home Sanatorium patients resting outside
Famous personalities affected with TB
Breakthrough in the Fight Against TB Drugs that could kill TB
bacteria were discovered in 1940s and 1950s Streptomycin (SM)
discovered in 1943 Isoniazid (INH) and paminosalicylic acid (PAS)
discovered between 1943 and 1952 TB death rates in U.S. began to
drop dramatically Each year, fewer people got TB Most TB
sanatoriums in U.S. had closed by mid 1970s
TB Resurgence Increase in TB in mid 1980s Contributing factors:
Inadequate funding for TB control programs HIV epidemic Increased
immigration from countries where TB is common Spread in homeless
shelters and correctional facilities Increase and spread of multi
drug-resistant TB March 16, 1992 Newsweek Magazine Cover
TB History Timeline 1993: TB cases decline due to increased
funding and enhanced TB control efforts 1865: JeanAntoine Villemin
proved TB is contagious 1840 1860 1884: First TB sanatorium
established in U.S. 1880 1900 1882: Robert Koch discovers M.
tuberculosis 1943: Streptomycin (SM) a drug used to treat TB is
discovered Mid-1970s: Most TB sanatoriums in U.S. closed 1920 1960
1940 1943-1952: Two more drugs are discovered to treat TB: INH and
PAS 1980 2000 Mid-1980s: Unexpected rise in TB cases
TB Transmission
TB Transmission Transmission is defined as the spread of an
organism, such as M. tuberculosis, from one person to another.
TB Transmission Types of Mycobacteria There are different types
of Mycobacterium M. tuberculosis causes most TB cases in the world
Mycobacteria that can cause TB: M. tuberculosis M. bovis (the
bovine tubercle bacillus) M. africanum (isolated from cases in
West, Central, and East Africa) M. microti (the "vole" bacillus, a
less virulent and rarely encountered organism) M. pinnipedii (a
bacillus infecting seals and sea lions in the southern hemisphere
and recently isolated from humans) Mycobacteria that do not cause
TB e.g., M. avium complex
TB Transmission TB is spread person to person through the air
via droplet nuclei M. tuberculosis may be expelled when an
infectious person: Coughs Sneezes Speaks Sings Transmission occurs
when another person inhales droplet nuclei
TB Transmission Dots in air represent droplet nuclei containing
M. tuberculosis
TB Transmission Probability that TB will transmitted depends
on: be Infectiousness of person with TB disease Environment
occurred in which exposure Length of exposure Virulence (strength)
of the tubercle bacilli The best way to stop transmission is to:
Isolate infectious persons Provide effective treatment to
infectious persons as soon as possible
Etiological Agent M. tuberculosis is a rod-shaped,
non-spore-forming, thin aerobic bacterium measuring 0.5 um to 3 um
the bacilli cannot be decolorized by acid alcohol; this
characteristic justifies their classification as acid-fast bacilli.
Acid fastness is due mainly to the organisms' high content of
mycolic acids, long-chain crosslinked fatty acids, and other
cellwall lipids It grows slowly . It cant tolerate heat, but It can
live in humid or dry or cold surroundings.
Symptoms associated with the TB Cough (2-3 weeks or more)
Coughing up blood Chest pains Fever Night sweats Feeling weak and
tired Losing weight without trying Decreased or no appetite If you
have TB outside the lungs, you may have other symptoms
Pathological changes of TB Following are the different
pathological changes associated with TB. Infiltration Hyperplasia
Calcification These changes happen in different stages of the
tuberculosis When defense system is predominant, there are less
number of bacteria and only hyperplasia and calcification would
happen. When defense system is weak, there are large number of
bacteria and only calcification would happen. As a result of
infection, infected areas are enlarged and deteriorated.
Clinical Manifestations of TB Systemic signs: Most patients
present as cases of pulmonary tuberculosis with fever, weight loss,
anorexia, fatigue, night sweats wasting. Respiratory signs: Cough
may vary from mild to severe, and sputum may be scant and mucoid or
copious and purulent. Hemoptysis may be due to cough of a caseous
lesion or bronchial ulceration chest pain, tachypenea ect. Physical
signs: nonspecific.
Drug-Resistant TB
Drug-Resistant TB Caused by M. tuberculosis organisms resistant
to at least one TB treatment drug Isoniazid (INH) Rifampin (RIF)
Pyrazinamide (PZA) Ethambutol (EMB) Resistant means drugs can no
longer kill the bacteria
Drug-Resistant TB Primary Resistance Caused by person-to-person
transmission of drug-resistant organisms Secondary Resistance
Develops during TB treatment: Patient was not given appropriate
treatment regimen OR Patient did not follow treatment regimen as
prescribed
Drug-Resistant TB Mono-resistant Resistant to any one TB
treatment drug Poly-resistant Resistant to at least any 2 TB drugs
(but not both isoniazid and rifampin) Multidrug resistant (MDR TB)
Resistant to at least isoniazid and rifampin, the 2 best first-line
TB treatment drugs Extensively drug resistant (XDR TB) Resistant to
isoniazid and rifampin, PLUS resistant to any fluoroquinolone AND
at least 1 of the 3 injectable second-line drugs (e.g., amikacin,
kanamycin, or capreomycin)
TB infection and the World
TB Pathogenesis Pathogenesis is defined as how an infection or
disease develops in the body.
TB Pathogenesis Occurs when tubercle bacilli are in the body,
but the immune system is keeping them under control Develops when
immune system cannot keep tubercle bacilli under control May
develop very soon after infection or many years after infection
About 10% of all people with normal immune systems who have LTBI
will develop TB disease at some point in their lives People with TB
disease are often infectious
TB Pathogenesis Droplet nuclei containing tubercle bacilli are
inhaled, enter the lungs, and travel to small air sacs
(alveoli)
TB Pathogenesis 2 b r o n c h io le b lo o d v e s s e l t u b
e r c le b a c illi a lv e o li Tubercle bacilli multiply in
alveoli, where infection begins
TB Pathogenesis 3 b r a in bone lu n g k id n e y A small
number of tubercle bacilli enter bloodstream and spread throughout
body
TB Pathogenesis LTBI 4 s p e c ia l im m u n e c e lls fo r m a
b a r r ie r s h e ll (in th is e x a m p le , b a c illi a r e in
th e lu n g s ) Within 2 to 8 weeks the immune system produces
special immune cells called macrophages that surround the tubercle
bacilli These cells form a barrier shell that keeps the bacilli
contained and under control (LTBI)
TB Pathogenesis 5 s h e ll b r e a k s dow n and tu b e r c le
b a c illi e s c a p e a n d m u lt ip ly (in th is e x a m p le ,
T B d is e a s e d e v e lo p s in th e lu n g s ) If the immune
system CANNOT keep tubercle bacilli under control, bacilli begin to
multiply rapidly and cause TB disease This process can occur in
different places in the body
TB Pathogenesis
LTBI vs. TB Disease Latent TB Infection (LTBI) TB Disease (in
the lungs) Inactive, contained tubercle bacilli in Active,
multiplying tubercle bacilli in the body the body TST or blood test
results usually positive TST or blood test results usually positive
Chest x-ray usually normal Chest x-ray usually abnormal Sputum
smears and cultures negative Sputum smears and cultures may be
positive No symptoms Symptoms such as cough, fever, weight loss Not
infectious Often infectious before treatment Not a case of TB A
case of TB
TB Pathogenesis Progression from LTBI to TB Disease
Progression to TB Disease Risk of developing TB disease is
highest the first 2 years after infection People with LTBI can be
given treatment to prevent them from developing TB disease
Detecting TB infection early and providing treatment helps prevent
new cases of TB disease
Progression to TB Disease Some conditions increase probability
of LTBI progressing to TB disease Infection with HIV Organ
transplant Chest x-ray findings suggestive of previous TB Silicosis
Diabetes mellitus Severe kidney disease Certain types of cancer
Certain intestinal conditions Low body weight Substance abuse
Recent TB infection Prolonged therapy with corticosteroids and
other immunosuppressive therapy, such as prednisone and tumor
necrosis factor-alpha [TNF-] antagonists
Progression to TB Disease People Exposed to TB Not TB Infected
Latent TB Infection (LTBI) Not Infectious Not Infectious Negative
TST or QFT-G test result Positive TST or QFT-G test result No TB
Infection Latent TB Infection May go on to develop TB disease
Progression to TB Disease TB and HIV In an HIV-infected person,
TB can develop in one of two ways: Person with LTBI becomes
infected with HIV and then develops TB disease as the immune system
is weakened Person with HIV infection becomes infected with M.
tuberculosis and then rapidly develops TB disease Image credit:
Mississippi State Department of Health
TB Pathogenesis Sites of TB Disease
Sites of TB Disease Bacilli may reach any part of the body, but
common sites include: B r a in L a ry n x Bone Lym ph node P le u r
a Lung K id n e y S p in e
TB Pathogenesis TB Classification System
TB Classification System Based on pathogenesis of TB Class Type
Description 0 No TB exposure Not infected No history of TB exposure
Negative result to a TST or IGRA 1 TB exposure No evidence of
infection History of TB exposure Negative result to a TST (given at
least 810 weeks after exposure) or IGRA 2 TB infection No TB
disease Positive result to a TST or IGRA Negative smears and
cultures (if done) No clinical or x-ray evidence of active TB
disease
TB Classification System Based on pathogenesis of TB Class Type
Description 3 TB, clinically active Positive culture (if done) for
M. tuberculosis Positive result to a TST or IGRA, and clinical,
bacteriological, or x-ray evidence of TB disease 4 Previous TB
disease (not clinically active) Medical history of TB disease
Abnormal but stable x-ray findings Positive result to a TST or IGRA
Negative smears and cultures (if done) No clinical or x-ray
evidence of active TB disease 5 TB suspected Signs and symptoms of
TB disease, but evaluation not complete
Laboratory and Physical examination of TB
Laboratory and Physical Examination Following methods are used
for laboratory and physical examination of TB Chest radiography
Sputum examination Tuberculin testing PCR test to detect TB TB
antibody testing Bronchoscopy
Radiology
Radiology Chest radiography is the most important method to
detect TB TBs characteristics of a chest radiograph favor the
diagnosis of tuberculosis as following shadows mainly in the upper
zone patchy or nodular shadows the presence of a cavity or
cavities, although these, of course, can also occur in lung
abscess, carcinoma, etc the presence of calcification, although a
carcinoma or pneumonia may occur in an areas of the lung where
there is calcification due to tuberculosis bilateral shadows,
especially if these are in the upper zones the persistence of the
abnormal shadows without alteration in an x-ray repeated after
several weeks this helps to exclude a diagnosis of pneumonia or
other acute infection
Primary Complex
Milliary Tuberculosis
Secondary Pulmonary TB infiltrate
Sputum examination There are direct smear and culture methods.
Direct smear examination is only positive when a large no of
bacilli begin to excrete
Tuberculin testing A tuberculin skin test is done to see if you
have ever had tuberculosis (TB). The test is done by putting a
small amount of TB protein (antigens) under the top layer of skin
on your inner forearm. If you have ever been exposed to the TB
bacteria (Mycobacteriumtuberculosis), your skin will react to the
antigens by developing a firm red bump at the site within 2 days.
The TB antigens used in a tuberculin skin test are called purified
protein derivative (PPD). A measured amount of PPD in a shot is put
under the top layer of skin on your forearm. This is a good test
for finding a TB infection. It is often used when symptoms,
screening, or testing, such as a chest Xray, show that a person may
have TB. A tuberculin skin test cannot tell how long you have been
infected with TB. It also cannot tell if the infection is latent
(inactive) or is active and can be passed to others.
Tuberculin testing A reaction of less then 05nm is considered
as negative. 5-9mm is considered positive (+) 10-19mm is considered
positive (++) More then 20mm is considered positive (+++) A
positive tuberculin test indicates TB infection with or without
disease.
PCR to detect Tuberculosis
Bronchoscopy Bronchoscopy is a technique of visualizing the
inside of the airways for diagnostic and therapeutic purposes. An
instrument (bronchoscope) is inserted into the airways, usually
through the nose or mouth. This allows the practitioner to examine
the patient's airways for abnormalities such as foreign bodies,
bleeding, tumors, or inflammation. Specimens may be taken from
inside the lungs. The construction of bronchoscopes ranges from
rigid metal tubes with attached lighting devices to flexible
optical fiber instruments with real time video equipment.
White blood cells and ESR The white blood count is usually
normal. In practice the white blood count is only useful in a
minority of cases, When the patient is less ill and the
radiological shadowing less extensive the count is often normal or
high normal ESR is often elevate