INTRODUCTION: these particles do not serve as effective




Tuberculosis is a
serious chronic pulmonary and systemic disease caused by infection with one of
the three members of the Myobacterium
tuberculosis, a tubercle
bacillus. Complex: Myobacterium
tuberculosis, Mycobacterium africanum or Mycobacterium bovis. Myobacterium
tuberculosis was identified and described on 1882 by a German physician
Robert Koch, which is slightly curved to straight bacillus. Myobacterium tuberculosis is obligate
aerobic, acid fast, non-motile and non-forming bacilli and contain mycolic acid
in their cell wall.

Tubercle bacilli




of Myobacterium Tuberculosis by airborne droplet nuclei which are produces when
person with pulmonary tuberculosis cough, sneeze, speak or sing. They
also may be produced through manipulation of lesion or processing of tissue or
secretions in the hospital or laboratory. Droplet nuclei are so small (1 to
5um) that air currents normally present in any indoor space can keep them
airborne for long period of time. Once released from the host, they are
dispersed throughout the room.

patients with tuberculosis also generate larger particles containing numerous
bacilli, these particles do not serve as effective vehicles for transmission of
infection because they do not remain airborne, and if inhaled, do not reach
alveoli. Organism deposited on intact mucosa or skins do not invade tissue.
When large particles are inhaled, they impact on the wall of the upper airway
or trachea, where they are trapped in the mucous blanket, carried to the
oropharynx and swallowed or expectorated.

that reduce the number of droplet nuclei in the room air are effective in
preventing the airborne transmission of tuberculosis. Ventilation with fresh
air is especially important, with six or more room-air changes an hour being
desirable. The number of viable airborne tubercle bacilli can be reduced by
ultraviolet irradiation if air in the upper part of the room. Effective
antituberculosis chemotherapy reduces the number of bacilli released into the
air by reducing the number of organisms in the sputum and the frequency of
coughing. Covering the mouth and the nose with tissues while coughing or
sneezing, or more effectively with a mask, reduce the number of organisms by
reducing the number of droplet nuclei put into air. If masks are to be used,
they should be fabricated to filter out droplet nuclei and molded to fit
tightly around the nose and mouth. Methods once thought to be important in
preventingthe transmission of tuberculosis—disposing of such personal items as
clothes and bedding, sterilizing fomites, using caps and gowns and gauze or
paper masks, boiling dishes, and washing walls—are unnecessary because they
have no bearing on airborne transmission.

M. bovis
may penetrate the gastrointestinal mucosa or invade the lymphatic tissue of the
oropharynx when ingested in milk containing large numbers of organisms. Human
infection with M.bovis has
essentially been eliminated in developed countries as a result of the
pasteurization of milk and effective tuberculosis control programs for cattle.
Airborne transmission of M.bovis can
also occur.

Humans with active TB
who release mycobacteria present in the sputum (open case) act as reservoir of
infection. The primary sites of infection are stated below:

Pulmonary tuberculosis
tract: Gastrointestinal tuberculosis
Oropharyngeal tuberculosis
Tuberculosis of the skin

and Intestinal tuberculosis contracted by drinking milk contaminated with M.bovis. Except myocardium, skeletal
muscle, pancreas and thyroid, tuberculosis can affect any organ or tissue in
the body. The factor controlling pathogenesis are the virulence of the
organism: mycosides; cord factor and hypersensitivity against the organism. The
infection by M. tuberculosis commonly
causing the development of delayed hypersensitivity to M. tuberculosis antigens, which can be detected by the tuberculin
skin test (Mantoux test).





occurs when droplet nuclei(airborne particle about 1-5 microns) are inhaled and
reach the alveoli of the lungs, via nasal passages, respiratory tract and
bronchi 2 billion people infected worldwide (1/3of the world’s population).The
number of new TB cases in the country increased from 15,000 in  2005 to 19,251 in2011 as shown in figure.










Typical TB clinical presentation

onset and chronic course

(usually productive)
Chest pain
(usually pleuritic)

constitutional symptoms (more common in children and HIV)
symptoms (if involved)

main site of Extrapulmonary disease are Miliary
or Disseminated tuberculosis and Tuberculous
meningitis. Miliary or Disseminated
tuberculosis cause by haematogenous spread of bacteria and can be due to
either primary infection or reactivation. Nonspecific signs such as fever,
night sweats, anorexia, weakness and weight loss are the presenting symptoms.
Plain chest X-ray is used to diagnose military TB although liver biopsy is
sometimes done.

Tuberculous meningitis
are seen most often in the children or immunocompromised adults and result from
haematogenous spread of pulmonary disease. Some symptoms may present with
headache and slight mental changes, weeks of low-grade fever, anorexia, malaise
and irritability. TB meningitis often diagnosed by microscopic, biochemical and
bacteriological examination which requires cerebrospinal fluid. Lymphadenitis
present in cervical, mediastinal, axillary and inguinal is most common
extrapulmonary site.















most common form of tuberculosis in adults is post-primary pulmonary tuberculosis.
It is the only form of tuberculosis which is infectious and insidious onset of
a productive cough, night sweat, anorexia and weight loss. It is not possible
to distinguish between progressive primary and “post-primary” or reactivation
TB. Signs can be subtle as in minimal cases or obvious such as consolidation,
fibrosis or stony dullness due to pleural effusion.

radiographs often reveal more disease than suggested by physical examination.  A 1.1-1.5cm grey white inflammatory
consolidation emerges-lesions (Ghon lesion) in the apical and posterior
segments of the upper lobes developed as sentilization. In most cases the
center of this focus undergoes caseating necrosis. Tubercle bacilli travel to
ipsilateral regional lymph nodes either as free bacilli or within
macrophages.This combination of parenchymal lesion and nodal involvement is
referred as Ghon complex. In 95% cases development of cell mediated immunity
controls the infection. Hence, the Ghon complex undergoe progressive fibrosis,
often followed by radiologically detectable calcification.

laboratory investigations include sputum direct smears for acid fast bacilli
which are usually positive in cavitary disease. Three specimens are collected
for diagnosis. Cultures using Lowenstein-Jensen medium take up to 8 weeks for a
final result. There are radiometric methods such as the BACTEC test which give
results within a week; subsequently sensitivity tests can be done within the
following week. The tuberculin or Mantoux test has some role in the diagnosis
of tuberculosis especially in paediatric cases and cases of extra-pulmonary
tuberculosis. The Mantoux test is used in Malaysia using the strength of 10 IU
PPD. The result is read after 72 hours.






For treatment of
adults, ant tubercular therapy (ATT) can be divided into 2 groups:

1. Primary drugs (1st-line






2. Secondary drugs (2nd –line

Ethionamide, Para-aminosalicylic acid (PAS)

Kanamycin, Capreomycin

Levofloxacin, Moxifloxacin



Rifampin is sensitive
to both gram positive and negative bacteria, sensitive mycobacterias are: M tuberculosis, M kansasi, M intracellulare,
M avium and M leper. Rifampin binds to the B subunit of bacterial
DNA-dependent RNA polymerase and thereby inhibit RNA synthesis.

Isoniazid is sensitive
to M. tuberculosis and also to M. kansasi (in high doses) atypical
myobacteia. Bacteriostatic for resting cells and bactericidal for rapidly
dividing cell, and the active form of isoniazid inhibits the synthesis of
myocolic acids which are essential components of mycobacterial cell walls.
Isoniazid is a prodrug and is activated by KatG, the mycobacterial
catalase-peroxidase enzyme. Active form of isoniazid inhibits key enzymes
involved in mycolic acids synthesis.

Pyrazinamide is a
bactericidal with excellent cerebrospinal fluid penetration. Ethambutol is
bacteriostatic which inhibits enzymes arabinasyl transferases require for cell
wall synthesis.

Short course
chemotherapy (SCC) is the combination of isoniazid, rifampin, pyrazinamide and
ethambutol or with streptomycin is given together to all patients with
pulmonary tuberculosis for the first 2 month. The second line drugs are used in




If the culture from the
source case is fully susceptible anti-tuberculosis drugs isoniazid is used in
the treatment for 6 month along with pyrazinamide for the first 2 months for
the therapy. Treatment duration will increase to 9 or 12 months due to the
possible damaged immune system in children younger than 12 months. Bacillus Calmette-Guérin
(BCG) vaccine is used for infant around the world.

By the reason difficulties
monitoring visual acuity and colour perception, ethambutol should be avoided in
treatment of children. However, studies show that ethambutol (15 mg/kg) is well
tolerated and can prevent further resistance if the child is infected with a
resistant strain.





The treatment for pregnant
women with active TB is similar to the normal patient should be treated, even
in the first stage of pregnancy. Isoniazid, rifampin, and ethambutol are used
in the standard treatment. In the Malaysia, pyrazinamide is for the standard
treatment but in US pyrazinamide is reserved for women with
suspected multidrug-resistant TB (MDR-TB). Streptomycin should not be used,
because risk of ototoxicity to the foetus.

Rifampicin is
recommended to use in pregnant patients. Tuberculosis treatment in lactating
mothers is safe as the amount of drug ingested by the nursing infant is
minimal. Breast-feeding is best avoided during this two weeks and expressed
milk should be given to the child. There is lower risk for the congenital
tuberculosis, if infant born to tuberculous mother fails to thrive.





Anti-tuberculosis drugs
such as (isoniazid, rifampicin and pyrazinamide) which consider hepatotoxic
hence patients with liver impairment, non-hepatotoxic drugs are commonly use in
the therapy. Treatment should be stopped if the liver enzymes rise more than
three times normal or if the patient becomes jaundiced clinically during
treatment drugs.

For renal impairment,
the nephrotoxicity drug (Streptomycin) should be avoided and Ethambutol should
be dosage reduced or averted in renal failure as normal dosages lead to optic
nerve damage.




The clinical situation
of the patient with HIV infection can be classified into 2 groups:

Intensive phase

Maintenance phase

During intensive phase
if there is no suspicion of drug resistance, anti-tuberculosis drugs
(isoniazid, rifampicin and pyrazinamide) are for daily treatment. If the drug
resistance the therapy should be modified by additional of ethambutol will use
in the treatment.

During the maintenance
phase, isoniazid, rifampicin, pyrazinamide (HRZ) daily for 2 months followed by
RH for 7 months biweekly or 6 months after cultures are negative for the
drug-susceptible organism. For isoniazid resistance, ethambutol,
rifampicin and pyrazinamide (ERZ) daily for 2 months followed by RE daily for
12-16 months. For rifampicin intolerance, isoniazid, Pyrazinamide, Ethambutol(EHZ)
daily for 18 -24 months.







Second line drugs such
as enviomycin, kanamycin, capreomycin, clarithromycin, ciprofloxacin,
ofloxacin, clofazamine, cycloserine and rifabutin are the drugs available in
Malaysia for treatment of tuberculosis resistant to first line drugs.

Due to ineffectiveness using
isoniazid and rifampin lead to the complexity of MDR-tuberculosis treatment.
Isoniazid has the strongest antibactericidal action and significantly
contributes to making patients rapidly noninfectious; rifampin has unique
antibacterial properties against dormant bacilli that are no longer in the
active phase of replication.




In my opinion,
prevention is better than cure which plays an important role to stop the
transmission of tuberculosis from one adult to another. The presence of
tuberculosis vaccine called Bacillus Calmette-Guerin (BCG) where it is one of
the most widely used of all current vaccines.

Besides that,
tuberculosis education is important for public, the public needs to know the basic
information about the tuberculosis for a number of reasons including reducing
the stigma still associated with tuberculosis.