Pulmonary Tuberculosis

Introduction
• Tuberculosis is an infectious disease that has been
known for centuries. Traditionally, the term
tuberculosis has been used to indicate infections
caused by Mycobacterium tuberculosis and
Mycobacterium bovis; however, a multitude of
causative mycobacteria are recognized.
• Mycobacterium tuberculosis (MTB) is the etiological
agent of tuberculosis in humans. Humans and cows
are the only reservoirs for the bacterium.
• M. bovis is the etiological agent of TB in cows and
rarely in humans. Humans can be infected by
unpasteurized milk consumption
• Other human pathogens include M. avium which
causes a TB-like disease especially prevalent in AIDS
patients, and M. leprae, the causative agent of
leprosy.
• The Mycobacterium tuberculosis complex includes
M tuberculosis, M bovis, and M africanum, all
closely related species or subspecies that may cause
the disease tuberculosis (TB) in humans.
• Tuberculosis may involve multiple organs such as
the lung, liver, spleen, kidney, brain, and bone.
• In endemic regions, the normal host immune
response may be sufficient to contain the infection
and prevent clinical presentation.
• Uncontrolled or uncontained infection may result in
great morbidity and mortality.
Colonies of Mycobacterium tuberculosis on
Lowenstein-Jensen medium.
 6
• Chains of cells in smears made from in vitro-grown
colonies often form distinctive serpentine cords.
This observation was first made by Robert Koch
who associated cord factor with virulent strains of
the bacterium.
• M.TB. is not classified as either Gram-positive or
Gram-negative because it does not have the
chemical characteristics of either, although the
bacteria do contain peptidoglycan (murein) in their
cell wall.
• Mycobacterium species, along with a related genus
Nocardia, are classified as acid-fast bacteria due to
their impermeability to certain dyes and stains.
Despite this, once stained, acid-fast bacteria will
retain dyes when heated and treated with acidified
organic compounds.
• One acid-fast staining method for Mycobacterium
tuberculosis is the Ziehl-Neelsen stain. Acid-fast
bacilli appear pink in a contrasting background in
this method.
Mycobacterium tuberculosis. Acid-
fast stain
• Mycolic acids are strong hydrophobic molecules
that form a lipid shell around the organism and
affect permeability properties at the cell surface.
Mycolic acids are thought to be a significant
determinant of virulence in M.TB.
• Probably, they prevent attack of the mycobacteria
by cationic proteins, lysozyme and oxygen radicals
in the phagocytic granule. They also protect
extracellular mycobacteria from complement
deposition in serum.
• In summary, the high concentration of lipids in the
cell wall of Mycobacterium tuberculosis has been
associated with these properties of the bacterium:
• • Impermeability to stains and dyes
• Resistance to many antibiotics
• Resistance to killing by acidic and alkaline
compounds
• Resistance to osmotic lysis via complement
deposition
• Resistance to lethal oxidations and survival inside
of macrophages
 Pathophysiology
• Bacteriological recognition of a
mycobacterial infection is a protracted
process that may delay appropriate medical
therapy.
• The advent of polymerase chain reaction
(PCR) techniques has increased the rapidity
with which tuberculous infection is
diagnosed.
• TB infection occurs as a consequence of the
inhalation of bacillus-laden droplets expelled from
an infected host.
• Given the stringent growth requirements of the
organism, the development of an infection depends
on prolonged exposure to an individual with active
pulmonary tuberculosis.
• After inhalation, it travels via the airways to the
pulmonary parenchyma where it is deposited. It has
a predilection for the lower lobes.
• The organism is ingested by alveolar macrophages.
As a result of the natural defenses of the tubercle
bacillus, alveolar macrophages may be unsuccessful
in attempting to completely destroy the bacilli,
which then lie dormant within the macrophage.
• Subsequently, bacilli may travel via the pulmonary
lymphatics, or they may enter the vascular system
and seed distant sites such as the liver, spleen, or
bone marrow.
• In most immunocompetent individuals,
macrophages are successful in containing the bacilli,
and the infection is self-limited and often
subclinical. The contained infection in
immunocompetent hosts is called primary
tuberculosis.
• Primary tuberculosis is seen most often in children
in endemic regions. Since the advent of the AIDS
era, adults may present with radiographic findings
similar to those of primary tuberculosis.
• In some patients, pulmonary macrophages are
unable to contain the bacilli and are overwhelmed,
leading to a clinically apparent infection. This is
more common in HIV/AIDS.
• This form of tuberculosis is called progressive
primary tuberculosis. Patients with progressive
primary tuberculosis may present with pulmonary
manifestations (often with miliary tuberculosis) or
with manifestations of systemic or disseminated
disease.
• Postprimary (reactivation) tuberculosis is seen in
patients in whom the initial infection was contained
successfully by the pulmonary macrophages, with
bacilli remaining viable within the macrophages.
• Infection results when the host's immune status (T
cells) is compromised.
• This form may appear in the elderly population, for
example.
 Stages of the Disease
• The following stages that will be explained are for a
M.TB. sensitive host. It should be realized that, only
a small percent of M.TB. infections progress to
disease and even a smaller percent progress all the
way to stage 5.
• Disease progression depends on:
• • Strain of M.TB.
• Prior exposure
• Vaccination
• Infectious dose
• Immune status of the host
 Stage 1
• Droplet nuclei are inhaled. One droplet nucleus contains no
more than 3 bacilli. Droplet nuclei are so small that they can
remain air-borne for extended periods of time. The most
effective (infective) droplet nuclei tend to have a diameter
of 5 µm. Droplet nuclei are generated by during talking,
coughing and sneezing. Coughing generates about 3000
droplet nuclei. Talking for 5 minutes generates 3000 droplet
nuclei but singing generates 3000 droplet nuclei in one
minute. Sneezing generates the most droplet nuclei by far,
which can spread to individuals up to 10 feet away.
• After droplet nuclei are inhaled, the bacteria are
nonspecifically taken up by alveolar macrophages. However,
the macrophages are not activated and are unable to
destroy the intracellular organisms.
• Tuberculosis begins when droplet nuclei reach the alveoli.
When a person inhales air that contains droplets most of the
larger droplets become lodged in the upper respiratory tract
(the nose and throat), where infection is unlikely to develop.
However, the smaller droplet nuclei may reach the small air
sacs of the lung (the alveoli), where infection begins.
Spread of droplet nuclei from one
individual to another
Tuberculosis begins when droplet
nuclei reach the alveoli
 Stage 2
• Begins 7-21 days after initial infection. M.TB.
multiplies virtually unrestricted within
unactivated macrophages until the
macrophages burst.
• Other macrophages begin to extravasate
from peripheral blood.
• These macrophages also phagocytose M.TB.,
but they are also unactivated and hence can
not destroy M.TB
 Stage 3
• At this stage lymphocytes begin to infiltrate. The
lymphocytes, specifically T-cells, recognize
processed and presented M.TB. antigen in context
of MHC molecules.
• This results in T-cell activation and the liberation of
cytokines including gamma interferon (IFN). The
liberation of IFN causes the activation of
macrophages. These activated macrophages are
now capable of destroying M.TB.
• It is at this stage that the individual becomes
tuberculin-positive. This positive tuberculin
reaction is the result of the host developing a
vigorous cell mediated immune (CMI) response.
• A CMI response must be mounted to control an
M.TB. infection. An antibody mediated immune
(AMI) will not aid in the control of a M.TB. infection
because M.TB. is intracellular and if extracellular, it
is resistant to complement killing due to the high
lipid concentration in its cell wall.
• Although a CMI response is necessary to control an
M.TB. infection, it is also responsible for much of
the pathology associated with tuberculosis.
Activated macrophages may release lytic enzymes
and reactive intermediates that facilitate the
development of immune pathology.
• Activated macrophages and T-cells also secrete
cytokines that may also play a role in the
development of immune pathology, including
Interleukin 1 ( IL-l), tumour necrosis factor (TNF),
and gamma IFN.
• It is also at this stage that tubercle formation
begins.
• The center of the tubercle is characterized by
"caseation necrosis" meaning semi-solid or
"cheesy" consistency.
• M.TB. cannot multiply within these tubercles
because of the low pH and anoxic environment.
• M.TB. can, however, persist within these tubercles
for extended periods.
 Stage 4
• Although many activated macrophages can be
found surrounding the tubercles, many other
macrophages present remain unactivated or poorly
activated. M.TB. uses these macrophages to
replicate and hence the tubercle grows.
• The growing tubercle may invade a bronchus. If this
happens, M.TB. infection can spread to other parts
of the lung, artery or other blood supply line.
• The hematogenous spread of M.TB. may result in
extrapulmonary tuberculosis otherwise known as
milliary tuberculosis.
• The name "milliary" is derived from the fact
that metastasizing tubercles are about the
same size as a millet seed, a grain commonly
grown in Africa.
• The secondary lesions caused by milliary TB
can occur at almost any anatomical location,
but usually involve the genitourinary system,
bones, joints, lymph nodes, and peritoneum.
These lesions are of two types:
• 1. Exudative lesions result from the
accumulation of PMN's around M.TB. Here
the bacteria replicate with virtually no
resistance. This situation gives rise to the
formation of a "soft tubercle".
• 2. Productive or granulomatous lesions occur
when the host becomes hypersensitive to
tuberculoproteins. This situation gives rise to
the formation of a "hard tubercle".
 Stage 5
• For unknown reasons, the caseous centers of the
tubercles liquify. This liquid is very conducive to
M.TB. growth and hence the organism begins to
rapidly multiply extracellularly. After sometime, the
large antigen load causes the walls of nearby
bronchi to become necrotic and rupture. This
results in cavity formation.
• This also allows M.TB. to spill into other airways
and rapidly spread to other parts of the lung.
• As stated previously, only a very small percent of
M.TB. infections result in disease, and even a
smaller percentage of M.TB. infections progress to
an advanced stage.
• Usually the host will begin to control the infection
at some point. When the primary lesion heals, it
becomes fibrous and calcifies. When this happens
the lesion is referred to as the Ghon complex.
• Depending on the size and severity, the Ghon
complex may never subside.
• Typically the Ghon complex is readily visible
upon chest X-ray.
• Small metastatic foci containing low numbers of
M.TB. may also calcify. However, in many cases
these foci will contain viable organisms.
• These foci are referred to as Simon foci.
• The Simon foci are also visible upon chest X-ray and
are often the site of disease reactivation.
Virulence Mechanisms and Virulence
Factors
• M. tuberculosis does not possess the classical
bacterial virulence factors such as toxins, capsules
and fimbriae.
• M.TB. has special mechanisms for cell entry. The
tubercle bacillus can bind directly to mannose
receptors on macrophages
• M.TB. grows intracellularly. In particular, antibodies
and complement are ineffective. Once M.TB. is
phagocytosed, it can inhibit phagosome-lysosome
fusion.
• The exact mechanism used by M.TB. to accomplish
this is not known but it is thought to be the result of
a protein secreted by bacterium that modifies the
phagosome membrane.
• The bacterium may remain in the phagosome or
escape from the phagosome, in either case finding a
protected environment for growth in the
macrophage.
• M.TB. interferes with the toxic effects of
reactive oxygen intermediates produced in
the process of phagocytosis
• Antigen 85 complex: These proteins may aid in
walling off the bacteria from the immune system
• Slow generation time: Because of M.TB's slow
generation time, the immune system may not
readily recognize the bacteria or may not be
triggered sufficiently to eliminate them.
• Many other chronic diseases are caused by bacteria
with slow generation times, for example, slow-
growing M. leprae causes leprosy, T.pallidum
causes syphilis, and Borrelia burgdorferi causes
Lyme disease.
• High lipid concentration in cell wall, as mentioned
previously, accounts for impermeability and
resistance to antimicrobial agents, resistance to
killing by acidic and alkaline compounds in both the
intracellular and extracellular environment, and
resistance to osmotic lysis via complement
deposition and attack by lysozyme.
• The cord factor is primarily
associated with virulent strains of
M.TB. It is known to be toxic to
mammalian cells and to be an
inhibitor of PMN migration.
However, its exact role in M.TB.
virulence is unclear.
 Mortality/Morbidity
• In immunocompetent patients in endemic regions,
the primary infection is contained, and the patients
remain asymptomatic.
• In some patients with relative immune
compromise, primary infection may lead to
fulminant pulmonary infection, with pulmonary
necrosis leading to death.
• This is called progressive primary tuberculosis.
Pulmonary manifestations of progressive
P/tuberculosis may be radiographically
indistinguishable from manifestations of
postprimary tuberculosis.
• Postprimary tuberculosis is a significant cause of
worldwide morbidity and mortality. Morbidity may
result from any affected organ system.
• Pulmonary morbidity may result from a chronic
cough, haemoptysis (which may be fatal), fibrosis,
superinfection , bronchial stenosis, repeated
pulmonary infections from tuberculous
bronchiectasis, or emphysema.
• Significant morbidity also may arise from chronic
tuberculous osteomyelitis, chronic renal
insufficiency, or neurological changes related to
central nervous system (CNS) tuberculosis.
• Race and Sex
• Race: Tuberculosis is a worldwide infection.
Endemic areas include India, Southeast Asia, and
sub-Saharan Africa.
• Sex: No sex predilection exists for tuberculosis.
 Age
• Infection may occur at any age and is most
significant at the extremes of age.
• Primary tuberculosis is usually seen in young
children in endemic regions.
• The incidence is increasing in individuals in
nonendemic regions who are
immunocompromised.
Clinical Identification and Diagnosis of
Tuberculosis
• The diganosis of tuberculosis requires detection of
acid-fast bacilli in sputum via the Ziehl-Neelsen
method.
• The organisms must then be cultured from sputum.
First, the sputum sample is treated with NaOH.
• This kills other contaminating bacteria but does not
kill the M.TB. present because M.TB. is resistant to
alkaline compounds by virtue of its lipid layer.
• However, methods of culturing can take 4-6 weeks
to yield visible colonies. As a result, another
method is commonly used and is called the BACTEC
System.
• The media used in the BACTEC system contains
radio-labelled palmitate as the sole carbon source.
• As M.TB. multiplies, it breaks down the palmitate
and liberates radio-labelled CO2. Using the BACTEC
system, M.TB. growth can be detected in 9-16 days
vs 4-6 weeks using conventional media.
 Skin Testing
• This is performed as the tuberulin or Mantoux test.
PPD (purified protein derivative) is employed as the
test antigen in the Mantoux test.
• PPD is generated by boiling a culture of M.TB.,
specifically Old Tuberculin (OT). 5 TU (tuberculin
units), which equals 0.0001mg of PPD, in a 0.1 ml
volume is intracutaneously injected in the forearm.
The test is read within 48-72 hours
Administering the Mantoux test. CDC
•
• The test is considered positive if the diameter of the
resulting lesion is 10 mm or greater. The lesion is
characterized by erythema (redness) and swelling
and induration (raised and hard). 90% of people
that have a lesion of 10 mm or greater are currently
infected with M.TB. or have been previously
exposed to M.TB. 100% of people that have a lesion
of 15 mm or greater are currently infected with
M.TB. or have been previously exposed to M.TB.
• False +ve tests usually manifest as lesser reactions.
These could indicate prior exposure, infection with
other Mycobacteria or vaccination with BCG. In
places where the vaccine is not used, lesser
reactions should be regarded as highly suspicious.
• False negatives are more rare than false positives
but are especially common in AIDS patients as they
have an impaired CMI response. Other conditions
such as malnutrition, steroids, etc., can rarely result
in a false negative reaction.
 Radiographic findings
• In primary TB, a lobar or segmental infiltrate, with
ipsilateral hilar adenopathy, is seen on chest films.
Adenitis may cause hilar adenopathy, leading to
compression of the bronchus and displacement of
the great vessels and trachea.
• Resolution of primary M tuberculosis may be
associated with development of a parenchymal
nodule or Ghon focus, which typically becomes
calcified with time. When a Ghon focus is
associated with calcified hilar lymph nodes, it is
termed a primary or Ranke's complex.
• Primary M tuberculosis infection may
progress in a small percentage of
patients, resulting in pleurisy and
pleural effusion, progressive caseous
pneumonia, extensive
bronchopneumonia, or haematogenous
spread that leads to disseminated
disease.
• Some studies have indicated that primary M
tuberculosis is not recognized initially on chest
radiographs from more than half of cases among
hospitalized adults subsequently diagnosed with TB
• The chest radiograph in patients with secondary TB
may show fibronodular changes, most often in the
upper lobes. Cavity formation or volume loss may
also be apparent. Active disease should be
suspected even if calcifications are present.
• One of the more common reasons for missed
diagnoses of active TB is ascribing granulomatous
changes to "old granulomatous disease," without
ruling out M tuberculosis.
• Other unusual presentations of reactivation disease
include lower-lobe infiltrates, adenopathy,
pulmonary masses, isolated or associated pleural
effusion, pneumothorax, alveolar filling pattern, or
presentation resembling adult respiratory distress
syndrome.
Young male patient with fever and cough has a focal opacity in
the left lower lobe that looks like a pneumonia. This is a case of
primary tuberculosis in an adult.
 Posteroanterior chest radiograph in a young patient shows a
right upper lobe and right lower lobe consolidation and a small
pleural effusion on the right side
 Imaging techniques
• Computed tomography (CT) is more sensitive than
chest radiography for detection of cavities,
lymphadenopathy, miliary disease, bronchiectasis,
bronchial stenosis, bronchopleural fistula, and
pleural effusion.
• The increased sensitivity of CT also is valuable when
findings on chest films are absent or inconsistent
and for guiding diagnostic evaluations, such as
bronchoscopy.
• High-resolution CT may reveal occult abscesses,
cavities, and the extent of pleural disease. CT is also
useful in patients with extensive fibrosis, scarring,
or postsurgical changes.
• Magnetic resonance imaging is preferred for
diagnosis of extrapulmonary disease, such as
skeletal and intracranial TB.
• A number of tests, ranging from acid-fast smears to
complex serologic studies, are available or under
development for identifying TB infections.
 Acid-fast smear
• The Ziehl-Neelsen carbolfuchsin or Kinyoun
carbolfuchsin stains have been essential in TB
diagnosis for nearly 100 years. Although less
sensitive than culture, the acid-fast smear is a rapid
and inexpensive test that can be performed with a
minimum of equipment and is very specific for
mycobacteria.
• Depending on the bacterial load, a single sputum
smear has sensitivity between 22% and 80%, but the
yield is improved when multiple sputum specimens
are examined.
 Fluorochrome stains & Nucleic acid
amplification
• Most laboratories in the US use fluorochrome
stains, such as auramine-rhodamine stain. With
these techniques, mycobacteria fluoresce with a
bright orange colour and can be easily seen on low-
power microscopy, increasing the sensitivity of the
smears.
• Direct tests of nucleic acid amplification are rapid,
widely available, and can be performed in a day.
The US Food and Drug Administration has approved
only the first two of the three methods described
here.
 Gene probes
• The Amplified M. Tuberculosis Direct Test (Gene-
Probe) targets mycobacterial ribosomal RNA by
transcription-mediated amplification.
• It is best used (and only approved for use) in
patients in whom acid-fast bacilli smears are
positive and cultures are in process.
• Since specificity is less than 100%, even in patients
with positive smears, occasional false-positive
results do occur, usually in patients with
nontuberculous mycobacterial infections.
 PCR testing
• This technique amplifies even very small portions of
a predetermined target region of M tuberculosis-
complex DNA.
• The test uses an automated system that can rapidly
detect as few as one organism from sputum,
bronchoalveolar lavage, blood, cerebrospinal fluid,
pleural fluid, or other fluid and tissue samples and
has shown sensitivity and specificity of nearly 90%
in pulmonary disease.
 Serological assays
• Development of a sensitive and specific serological
assay for M tuberculosis has been attempted for
several decades but remains elusive.
• However, newer procedures using enzyme
immunoassay may make serological testing possible
in the future.
• Such a procedure would be particularly helpful in
detection of M. tuberculosis in children or in
patients who have extrapulmonary infection and
when obtaining specimens is a problem
 Signs & Symptoms
• Chronic cough of over several weeks
• Haemoptysis Plueral effusion
• Fever Malaise
• Weariness Emphysema
• Weight loss
• Night sweats
• Anorexia
• Chest pain
• Dyspnoea
 Tuberculosis Treatment
• Because administration of a single drug often leads
to the development of a bacterial population
resistant to that drug, effective regimens for the
treatment of TB must contain multiple drugs to
which the organisms are susceptible.
• When two or more drugs are used, each helps
prevent the emergence of tubercle bacilli resistant
to the others.
• When the in vitro susceptibility of a patient's isolate
is not known, improper selection of drugs may
result in the development of drug-resistant
organisms.
• Hence, tuberculosis is usually treated with four
different antimicrobial agents. The course of drug
therapy usually lasts from 6-9 months.
• The most commonly used drugs are rifampicin (RIF),
isoniazid (INH), pyrazinamide (PZA ) and
ethambutol (EMB) or streptomycin (SM).
• When adherence with the regimen is assured, this
four-drug regimen is highly effective .
• Based on the prevalence and characteristics of
drug-resistant organisms, at least 95% of patients
will receive an adequate regimen (at least two
drugs to which their organisms are susceptible) if
this four-drug regimen is used at the beginning of
therapy.
• Furthermore, a patient who is treated with the
four-drug regimen, but who defaults therapy, is
more likely to be cured and not relapse when
compared with a patient treated for the same
length of time with a three-drug regimen.
TB is treated in two phases:
• An Initial Phase using at least three drugs and
• A Continuation Phase using two drugs in fully sensitive cases;
requiring specialized knowledge esp. in resistant or non-
respiratory TB.
Either the unsupervised or the supervised regimen should be
used but not concurrently.
In Initial Phase, at least 3 drugs are concurrently used for two
months:
 to reduce the bacterial population rapidly
 To prevent emergence of drug-resistant bacteria.
 They are best given as Combination preparations
unless b/c of resistance and intolerance.
Best choice of drugs includes daily use of :
INH,RIF,PYZ and ETH.ETH can be omitted if the risk of
resistance to INH is low.

Streptomycin can be used if resistance has been

established b/4 commencing therapy.

Treatment wt PYZ and (ETH if appropriate) should be

continued until full susceptibility is confirmed, even if
longer than two months.
• In Continuation Phase, treatment is continued for a
further 4 months after the initial phase wt INH and
RIF(preferably in combination preparation). Longer
treatment is required for resistant organisms and
meningitis, perhaps wt regimen modification.

• Unsupervised Treatment is given to patients likely to

adhere to the daily anti-TB treatment for 6 months
as follows:
• Rifater® (INH,RIF and PYZ) for 2 months initial
phase only.
• Adults under 40 kg 3 tabs daily, 40- 49 kg 4
tabs daily,50-64kg 5tabs daily, over 65kg 6tabs
daily.
• ETH is for 2 months initial phase only.
• Adult and child 15mg/kg daily.
• Rifinah® or Rimactazid® (RIF and INH) (for 4 months
Continuation Phase) following initial treatment with
Rifater®.

• Adult under 50kg 3tabs daily of Rifinah-150 or

Rimactazid-150, 50kg and over, 2tabs daily of
Rifinah-300 or Rimactazid-300 or if combination
preparations are not appropriate we use:

• INH for 2-month initial & 4-month continuation

phases.

• Adult 300mg daily, Child 5-10mg/kg(max. 300mg)

daily.
• RIF for 2-month initial & 4-month continuation phases.
• Adult under 50kg 450mg daily, 50kg & over 600mg
daily;Child10mg/kg(max. 600mg daily).

• PYZ for 2-month initial phase only.

• Adult under 50kg 1.5g daily, 50kg & over 2g daily; Child
35mg/kg daily.
• ETH for 2-month initial phase only .

• Adult & Child 15mg/kg daily

• Streptomycin: By deep IM injection in a dose of
15mg/kg (max. 1g) daily;
• the dose is reduced in those under 50kg, those
over 40 years or those with renal impairment.
• Plasma drug conc. shld. be measured in patients
wt. impaired renal fxn. In whom strep. must be
used wt. great care.
• Side effects increase after a cumulative dose of
100mg, which shld. only be exceeded in
exceptional circumstances.
• Pregnancy and Breastfeeding: Std. regimen may be
used but Streptomycin is contraindicated in
pregnancy.

• Children: INH,RIF and PYZ can be given in both the

Initial & Continuation Phases.

• ETH should be included in the first 2 months with a

high risk of resistant infection though care is needed
b/c of difficulty in testing eyesight and getting
reports of visual symptoms.
• One-hour (‘peak’) conc. shld. be
15-40mg/litre;

• Predose (‘trough’) conc. shld. be less than

5mg/litre (less than 1mg in renal impairment
or in those over 50 years).
• Supervised Treatment (DOTS): Here, drug
treatment should be fully supervised i.e.,
Directly Observed Treatment Shortcourse in
patients likely not to comply with the treatment
regimen.
• They are given INH,RIF,PYZ and ETH ( or Strep) 3
times a week under supervision for the Ist 2
months followed by INH and RIF 3 times a week
for another 4 months as :
• INH for 2-month initial & 4-month continuation phases.

• Adult & Child 15mg/kg( max. 900mg ) 3 times a week.

• RIF for 2-month initial & 4-month continuation phases.

• Adult 600-900mg 3 times a week; Child 15mg/kg (max. 900mg) 3

times a week.

• PYZ for 2-month initial phase only

• Adult under 50kg 2g 3 times a week, 50kg and over 2.5g 3 times a
week; Child 50mg/kg 3 times a week.

• ETH for 2-month initial phase only.

• Adult and Child 30mg/kg 3 times a week.

• Immunocompromised Patients:
• Always culture the organism for confirmation b/c the
organism may be multi-resistant.

• Confirmed M.TB sensitive to Ist line drugs shld. be

treated wt a std. 6-month regimen.

• Patients to be closely monitored after completing

treatment or treatment modified if caused by
resistant bacteria and specialist advice sought for
treatment or chemoprophylaxis in a HIV positive
person and care taken to choose his regimen to
avoid hazardous interactions.
 Prevention
Chemoprophylaxis may be required in those who
have evidence of latent TB and under treatment wt
immunosuppressants or fear of developing
reactivation of previously latent TB or in
susceptible close contacts or those who have
become tuberculin positive, INH is used for 6
months, longer chemoprophylaxis is not
recommended.
 Chemoprophylaxis dose
Dose: INH 300mg daily for 6 months;
Child 5-10mg/kg daily (max. 300mg daily)
• Or INH 300mg daily + RIF 600mg daily(450mg
daily if less than 50kg) for 3 months; Child INH
5-10mg /kg daily (max. 300mg daily) + RIF
10mg/kg daily (max. 600mg daily)
 Prevention contd.
• A vaccine against M.TB. is available. It is called BCG
(Bacillus of Calmette and Guerin, after the two
Frenchmen that developed it).
• BCG consists of a live attenuated strain derived
from Mycobacterium bovis. This strain of
Mycobacterium has remained avirulent for over 60
years.
• The vaccine is not 100% effective. Studies suggest a
60-80% effective rate in children.
 Disadvantages of the vaccine
• The vaccine cannot circumvent disease reactivation
in previously exposed individuals.
• The vaccine does not prevent infection, only
disease. Therefore, the entire population would
have to be vaccinated if the vaccine was to be
considered efficacious.
• Vaccination may complicate the way the tuberculin
skin test is read.
• In places that do not vaccinate, the skin test may be
used to monitor the effectiveness of antibiotic
therapy.
 MONITORING
Liver Fxn Test should be done b/4 initiating the
therapy and done frequently in the Ist 2 months in
those wt liver dx or dependent on alcohol.
Further checks to be done when there are signs of
liver dx during therapy and medical attention
immediately sought.
Renal fxn shld. also be checked b/4 the therapy starts
and appropriate dosage adjustment done. ETH
&STREP are avoided in renal dx.
 CAUSES OF TREATMENT FAILURE
• Major causes of treatment failure are
incorrect prescribing by the physician and
inadequate compliance by the patient.
Monthly tablet counts and urine examination
(rifampicin imparts orange-red colouration)
may be useful indicators of compliance with
treatment. Avoid both excessive and
inadequate dosage. Treatment should be
supervised by a specialist physician.
 SIDE EFFECTS
INH:
• Peripheral neuropathy; treated wt 10mg- 20mg of
pyridoxine daily.
• Hepatitis
• Psychosis.
RIF:
• Transient disturbance of LF wt elevated serum
transaminases; change if severe.
• 6 toxicity syndromes on intermittent treatment
such as influenza-like, abdominal, and respiratory
symptoms, shock, renal failure and
thrombocytopenic purpura in 20-30% of patients.
• Induces hepatic enzymes and can cause
therapeutic failures in oestrogens,
corticosteroids, phenytoin, sulphonylureas
and anticoagulants.
• PYZ:
• Occasional liver toxicity.
ETH:
• Visual disturbances in the form of loss of
acuity, colour blindness and restriction of
visual fields.
STREP:
• Vestibular and auditory damage,
nephrotoxicity, nausea, vomiting and rash.
• Drug resistant TB shld. be treated by a specialist
physician wt. experience in such cases and where
appropriate facilities for infection-control exist.
• Second line drugs available for infections caused by
resistant organisms or when Ist line drugs cause
unacceptable side effects are:
• Amikacin
• Capreomycin
• Cycloserine.
Newer macrolides such as:
• Azithromycin
• Clarithromycin.
Quinolones:
• Ciprofloxacin
• Ofloxacin.

Protionamide (prothionamide) no longer

used in the UK.
 End
• Thank you for your time and
attention.
• End