A VIEW ON TB CONTROL

Presented by :
HMN, AL JAHRA CENTER
 Tuberculosis (TB) is caused by a bacterium calledMycobacterium
tuberculosis. The bacteria usually attack the lungs, but TB bacteria
can attack any part of the body such as the kidney, spine, and
brain. If not treated properly, TB disease can be fatal.

Under a high magnification of 15549, this colorized scanning electron micrograph (SEM)
depicted some of the ultrastructural details seen in the cell wall configuration of a number of
Gram-positiveMycobacterium tuberculosisbacteria. As an obligate aerobic organismM.
tuberculosiscan only survive in an environment containing oxygen. This bacterium ranges in
length between 2 - 4m, and a width between 0.2 - 0.5m.
Mode of Transmission
 TB Symptoms
Symptoms of TB disease include:
a bad cough that lasts 3 weeks or longer
pain in the chest
coughing up blood or sputum
weakness or fatigue
weight loss
no appetite
chills
fever
sweating at night
How the Mycolic Acid in their cell wall served as a
Virulence Factor to the Host?
Infection, Containment, Persistence of the Bacilli in Bio-
Molecular Cell Phases
 TB Testing if Exposed or Infected
Two Types: the tuberculin skin test and TB blood tests.
.A positive TB skin test or TB blood test only tells that a person has been infected with TB bacteria. It does not tell
whether the person haslatent TB infection(LTBI) or has progressed toTB disease. Other tests, such as a chest x-
ray and sputum sample,needed to see whether the person has TB disease
1.Tuberculin skin test: The TB skin test (also called the Mantoux tuberculin skin test) is performed by injecting a
small amount of fluid (called tuberculin) into the skin in the lower part of the arm. A person given the tuberculin
skin test must return within 48 to 72 hours to have a trained health care worker look for a reaction on the arm. The
health care worker will look for a raised, hard area or swelling, and if present, measure its size using a ruler.
Redness by itself is not considered part of the reaction.
The skin test result depends on the size of the raised, hard area or swelling. It also depends on the persons risk of
being infected with TB bacteria and the progression to TB disease if infected.
Positive skin test:Thismeans the persons body was infected with TB bacteria. Additional tests are needed to
determine if the person has latent TB infection or TB disease. A health care worker will then provide treatment as
needed.
Negative skin test:This means the persons body did not react to the test, and that latent TB infection or TB
disease is not likely.

2.TB blood tests:TB blood tests (also called interferon-gamma release assays or IGRAs) measure how the
immune system reacts to the bacteria that cause TB. An IGRA measures how strong a persons immune system
reacts to TB bacteria by testing the persons blood in a laboratory.
Two IGRAs are approved by the U.S. Food and Drug Administration (FDA) and are available in the United States:
QuantiFERONTB Gold In-Tube test (QFT-GIT)
T-SPOT.TB test (T-Spot)
Positive IGRA:This means that the person has been infected with TB bacteria. Additional tests are needed to
determine if the person has latent TB infection or TB disease. A health care worker will then provide treatment as
needed.
Negative IGRA:This means that the persons blood did not react to the test and that latent TB infection or TB
disease is not likely.
IGRAs are the preferred method of TB infection testing for the following:
People who have receivedbacille CalmetteGurin (BCG). BCG is a vaccine for TB disease.
People who have a difficult time returning for a second appointment to look for a reaction to the TST.
There is no problem with repeated IGRAs.
 Who Should Get Tested for TB
TB tests are generally not needed for people
with a low risk of infection with TB
bacteria.
Certain people should be tested for TB bacteria
because they are more likely to get TB disease,
including:
1. People who have spent time with someone
who has TB disease
2. People with HIV infection or another medical
problem that weakens the immune system
3. People who have symptoms of TB disease
(fever, night sweats, cough, and weight loss)
4. People from a country where TB disease is
common (most countries in Latin America,
the Caribbean, Africa, Asia, Eastern Europe,
and Russia)
5. People who live or work somewhere in the
United States where TB disease is more
common (homeless shelters, prison or jails,
or some nursing homes)
6. People who use illegal drugs
 Sputum Culture, Lowenstein Jensen Agar, 37,1week

Identification ofMycobacterium tuberculosis

Slow growing mycobacteria(growth of isolated colonies in more than 7 days)
Nonpigmented, rough, dry colonieson Lwenstein-Jensen medium
Acid-fast(Ziehl-Neelsen or Kinyoun stain)
Nonphotochromogenic
The niacin test:positive
The nitrate reduction test:positive
Growth on TCH (thiophene-2-carboxylic acid hydrazide); 10g/ml:positive, TCH
resistant (unlikeM.bovis)
Growth on pyrazinamidase agar (PZA); 25g/ml:negative
The arylsulfatase test (3-Day test):negative
 4 AFB TESTING
1. An AFB smear Mycobacteriaare called acid-fast bacilli because they are rod-shapedbacteria(bacilli) that can be
seen under the microscope following a staining procedure in which the bacteria retain the color of the stain after an
acid wash (acid-fast).Used as a rapid test , sputum is spread thinly onto a glass slide, treated with a special stain, and
examined under a microscope for "acid-fast" bacteria. AFB smears can providepresumptiveresults within a few hours
and are valuable in helping to make decisions about treatment whilecultureresults are pending. However, this rapid
test is lesssensitivethan culture.

2.NAATA ,nucleic acid amplification test- molecular test for TB called ) may be done in conjunction with an AFB
smear. NAAT detects the genetic components of mycobacteria by amplifying/replicating pieces of the microorganisms'
genetic material. These tests can help decrease the amount of time necessary for a presumptive diagnosis of
tuberculosis to less than 24 hours. The testing can narrow the identification to a complex of mycobacteria (a
combination, of whichM. tuberculosisis the most common). They are fairly sensitive andspecificwhen they are
performed on specimens where acid-fast bacteria were seen on the smear. When they are done on samples that are
AFB-negative by smear, they tend to be less sensitive. The test methods are approved for respiratory samples but
must be confirmed with an AFB culture. They provide the health practitioner with a quick answer, allowing him or her
to isolate potentially infectious people and minimize the spread of the disease. Guidelines from the Centers for
Disease Control and Prevention recommend that people with signs and symptoms of TB have at least one sample
tested using nucleic acid amplification in conjunction with AFB smear and culture.

3. AFB cultures are used to diagnose activeM. tuberculosisinfections, infections due tonontuberculous
mycobacteria, or to determine whether TB-like symptoms are due to another cause. They are used to help determine
whether the TB is confined to the lungs (pulmonary disease) or has spread to organs outside the lungs
(extrapulmonary disease). AFB cultures can also be used to monitor the effectiveness of treatment and can help
determine when a person is no longer infectious. Though this test is more sensitive than an AFB smear, it takes longer
for results to become available. Mycobacteria grow more slowly than other types of bacteria so positive identification
may take days to several weeks, while negative results (no mycobacterial growth) can take up to 6 to 8 weeks to
confirm.

4.Susceptibility testingis usually ordered in conjunction with an AFB culture to determine the most effective
antibiotic to treat the mycobacterial infection.M. tuberculosismay be resistant to one or more drugs commonly used
to treat TB. In addition to routine susceptibility testing, there are now some molecular tests available that can identify
thegenesin bacteria that confer resistance to the most commonly prescribed drugs.
 Latent TB Infection and TB Disease
Not everyone infected with TB bacteria becomes sick. As a result, two TB-
related conditions exist: latent TB infection and TB disease.
Latent TB Infection
TB bacteria can live in the body without making you sick. This is called latent
TB infection. In most people who breathe in TB bacteria and become infected,
the body is able to fight the bacteria to stop them from growing. People with
latent TB infection do not feel sick and do not have any symptoms. People
with latent TB infection are not infectious and cannot spread TB bacteria to
others. However, if TB bacteria become active in the body and multiply, the
person will go from having latent TB infection to being sick with TB disease.
TB Disease
TB bacteria become active if the immune system can't stop them from
growing. When TB bacteria are active (multiplying in your body), this is called
TB disease. People with TB disease are sick. They may also be able to spread
the bacteria to people they spend time with every day.
Many people who have latent TB infection never develop TB disease. Some
people develop TB disease soon after becoming infected (within weeks)
before their immune system can fight the TB bacteria. Other people may get
sick years later when their immune system becomes weak for another
reason.
 TB Risk Factors
Once a person is infected with TB
bacteria, the chance of
developing TB disease is higher if
the person:
Has HIV infection;
Has been recently infected with
TB bacteria (in the last 2 years);
Has other health problems, like
diabetes, that make it hard for the
body to fight bacteria;
Abuses alcohol or uses illegal
drugs; or
Was not treated correctly for TB
infection in the past
Testing for TB Infection
There are two kinds of tests that are used to
detect TB bacteria in the body: the TB skin test (TST) and TB blood
tests. These tests can be given by a health care provider or local
health department. If you have a positive reaction to either of the
tests, you will be given other tests to see if you have latent TB
infection or TB disease.
 Treatment for Latent TB Infection
People withlatent TB infectionhave TB bacteria in their bodies, but they are
not sick because the bacteria are not active. People with latent TB infection
do not have symptoms, and they cannot spread TB bacteria to others.
However, if TB bacteria become active in the body and multiply, the person
will go from having latent TB infection to being sick with TB disease. For this
reason, people with latent TB infection are often prescribed treatment to
prevent them from developing TB disease. Treatment of latent TB infection is
essential for controlling and eliminating TB in the United States.
Because there are less bacteria in a person with latent TB infection,
treatment is much easier.Four regimensare approved for the treatment of
latent TB infection. The medications used to treat latent TB infection include:
isoniazid (INH)
rifampin (RIF)
rifapentine (RPT)
Certain groups of people (such as people with weakened immune systems)
are at veryhigh risk of developing TB diseaseonce infected with TB bacteria.
Every effort should be made to begin appropriate treatment and to ensure
completion of the entire course of treatment for latent TB infection.
 LTBI

Latent Tuberculosis Infection

Priftin is indicated in adults and children 2 years and older for the treatment of latent
tuberculosis infection caused by Mycobacterium tuberculosis in patients at high risk of
progression to tuberculosis disease (including those in close contact with active tuberculosis
patients, recent conversion to a positive tuberculin skin test, HIV-infected patients, or those with
pulmonary fibrosis on radiograph).
Limitations of Use
Active tuberculosis disease should be ruled out before initiating treatment for latent tuberculosis
infection.
Priftin must always be used in combination with INH as a 12-week once-weekly regimen for
the treatment of latent tuberculosis infection.
Priftin in combination with INH is not recommended for Individuals presumed to be exposed to
 Treatment for TB Disease

TB bacteria become active (multiplying in the body) if the immune system

can't stop them from growing. When TB bacteria are active, this is called
TB disease. TB disease will make a person sick. People with TB disease may
spread the bacteria to people with whom they spend many hours.
TB disease can be treated by taking several drugs for 6 to 9 months. There
are 10 drugs currently approved by the U.S. Food and Drug Administration
(FDA) for treating TB. Of the approved drugs, the first-line anti-TB agents that
form the core of treatment regimens include:
isoniazid (INH)
rifampin (RIF)
ethambutol (EMB)
pyrazinamide (PZA)
Regimens for treating TB disease have an initial phase of 2 months, followed
by a choice of several options for thecontinuation phaseof either 4 or 7
months (total of 6 to 9 months for treatment).
 QA

1. Once I complete treatment for TB infection, can I get TB infection again?

Yes. The treatment you receive for TB infection only treats the TB
germs in your body now. There is a chance that you can be around
someone else with TB and get new TB germs. Yetmost healthy
people wont need to be treated ever again.
2. After I complete treatment for TB infection, does that mean I will not get
TB disease? The medicine does not work for everyone, but works
really well for most people. Most people who complete treatment
for TB infection will not get TB disease

3. Why treated in combination therapy for over fifty years? Drugs are not
used singly (except inlatent TBor chemoprophylaxis), and regimens
that use only single drugs result in the rapid development of
resistance and treatment failure.[5][6]The rationale for using multiple
drugs to treat TB are based on simple probability. The frequency of
spontaneous mutations that confer resistance to an individual drug
are well known: 1 in 107for EMB, 1 in 108for STM and INH, and 1 in
1010for RMP.[7]
Patients with extensive pulmonary TB have approximately
1012bacteria in their body, and therefore will probably be harboring
approximately 105EMB-resistant bacteria, 104STM-resistant
bacteria, 104INH-resistant bacteria and 10 RMP-resistant bacteria.
Resistance mutations appear spontaneously and independently, so
 QA
Can I have a tuberculosis (TB) infection and not be sick?
Yes. There are many people in the United States and worldwide who have alatent
form ofTB infection. They have been exposed to the bacteria, but their body's
immune system has confined it to a localized area in their lungs, in an inactive form.
People with latent TB infections are not sick and they are not infectious, but the
bacteria are still there and still alive. If those with latent infections are tested, most
would have a positiveTB skin test. The majority of people with latent TB infection,
about 90%, will never progress to active tuberculosis disease.

Those who do have active TB may not feel ill at first. Early symptoms may be subtle
and, if the TB is extrapulmonary (outside of the lungs in organs such as the kidney
and bone), the tuberculosis may be fairly advanced by the time it causes noticeable
symptoms.
 Why Combination Therapy?
Other theoretical reasons for supporting combination therapy
The different drugs in the regimen have different modes of action. I
INH are bacteriocidal against replicating bacteria.
EMB is bacteriostatic at low doses, but is used in TB treatment at
higher, bactericidal doses. RMP is bacteriocidal and has a
sterilizing effect.
PZA is only weakly bactericidal, but is very effective against
bacteria located in acidic environments, inside macrophages, or in
areas of acute inflammation.

All TB regimens in use were 18 months or longer until the appearance of rifampicin.

In 1953, the standard UK regimen was 3SPH/15PH or 3SPH/15SH 2.

Between 1965 and 1970, EMB replaced PAS. RMP began to be used to treat TB in 1968 and the
BTSstudy in the 1970s showed that 2HRE/7HR was efficacious.

In 1984, a BTS study showed that 2HRZ/4HR was efficacious, [8]with a relapse rate of less than
3% after two years.

In 1995, with the recognition that INH resistance was increasing, the British Thoracic Society
recommended adding EMB or STM to the regimen: 2HREZ/4HR or 2SHRZ/4HR,which are the
regimens currently recommended.

The WHO also recommend a six-month continuation phase of HR if the patient is still
culture positive after 2 months of treatment (approximately 15% of patients with fully
sensitive TB) and for those patients who have extensive bilateral cavitation at the
. What is DOT or Direct Observed Therapy
It is the practice of taking TB medications in the presence of a health practitioner is known as direct observed
therapy (DOT). DOT ensures that people are taking their medications and continuing their therapy for the
required length of time. Unlike other bacterial infections that can be cured in 7-10 days, TB must be treated with
two or more drugs for several months. People tend to forget to take their medication when they are feeling better.
Since TB medications must be taken for many months, the risk of non-compliance is high. Having a health
practitioner administer the medications weekly increases the likelihood that the entire regimen will be completed
and decreases the likelihood that someone will relapse with a more resistant strain of TB.

.Besides TB, what other types of mycobacteria can be identified with AFB testing?
Examples of othermycobacteriathat can cause infections and are detected using AFB tests include:
Mycobacterium avium-intracellularecomplex (MAC)can cause a lung infection in people with weakened
immune systems, such as those with AIDS; this infection is not contagious but it can be difficult to treat as it
tends to be highly resistant to antibiotics.
Mycobacterial species, such asMycobacterium marinum, grow in water, such as fish tanks, and can cause skin
infections.
Mycobacterium fortuitumandMycobacterium chelonae, and other rapidly growing mycobacteria, cause skin
and wound infections following cosmetic surgery, prosthetic device implantation, and visits to nail salons.
A few mycobacteria, such asMycobacterium bovis, can sometimes be transferred from animals to humans.
See the article onNontuberculous Mycobacteriafor more examples and details.
Nocardiaspecies are not a type of mycobacteria but can be detected using some AFB laboratory
tests.Nocardiacan cause infections of the lungs
 MRD TB (Multi Resistant Drug
Tuberculosis)
Treatment of MDR-TB must be done on the basis of sensitivity testing: it is impossible to treat such patients
without this information. If treating a patient with suspected MDR-TB, the patient should be started on SHREZ+
MXF+cycloserinepending the result of laboratory sensitivity testing.
A gene probe forrpoBis available in some countries and this serves as a useful marker for MDR-TB, because
isolated RMP resistance is rare (except when patients have a history of being treated with rifampicin alone). [76]If
the results of a gene probe (rpoB) are known to be positive, then it is reasonable to omit RMP and to use SHEZ+
MXF+cycloserine. The reason for maintaining the patient on INH despite the suspicion of MDR-TB is that INH is so
potent in treating TB that it is foolish to omit it until there is microbiological proof that it is ineffective.
There are also probes available for isoniazid-resistance (katG[77]andmabA-inhA[78]), but these are less widely
available.
resistant to both INH and RMP
five drugs should be chosen in the following order (based on known sensitivities):
anaminoglycoside(e.g.,amikacin,kanamycin) or polypeptide antibiotic (e.g.,capreomycin)
PZA
EMB
afluoroquinolones:moxifloxacinis preferred (ciprofloxacinshould no longer be used[79]);
rifabutin
cycloserine
athioamide:prothionamideorethionamide
PAS
amacrolide: e.g.,clarithromycin
linezolid
high-doseINH(if low-level resistance)
interferon-[80]
thioridazine
meropenemandclavulanic acid[81][82]
Drugs are placed nearer the top of the list because they are more effective and less toxic; drugs are placed
nearer the bottom of the list because they are less effective or more toxic, or more difficult to obtain.
Resistance to one drug within a class generally means resistance to all drugs within that class, but a notable
exception is rifabutin: rifampicin-resistance does not always mean rifabutin-resistance and the laboratory should
be asked to test for it.
What is the difference between
multidrug-resistant TB (MDR-TB) and
extensively-resistant TB (XDR-TB)?
Both indicate strains ofMycobacteria
tuberculosisthat can be difficult to treat,
but XDR-TB is resistant to more drug
therapies.
MDR-TB is resistant to the two most
powerful drugs, isoniazid and
rifampin

. XDR-TB is currently defined by the

Centers for Disease Control and
Prevention and the World Health
Organization asM. tuberculosisthat
is resistant to isoniazid and rifampin
plus resistant to any fluoroquinolone
and to at least one of three injectable
"second-line" drugs (amikacin,
kanamycin, or capreomycin).

The emergence of XDR-TB is being closely

watched by the world medical community
and measures are being taken in hopes of
 REFERENCES
1. http://www.cdc.gov.us/
2. https://labtestsonline.org/
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