Tuberculosis (TB) is a highly contagious infection caused by Mycobacterium tuberculosis, leading to significant mortality worldwide, especially among HIV-positive individuals. Multi-drug resistant TB (MDR-TB) poses a complex treatment challenge, requiring close collaboration among healthcare professionals for effective management. Diagnosis and treatment involve various approaches including skin tests, drug regimens, and adherence to therapy, with a focus on preventing transmission and managing co-infections.

1. TUBERCULOSIS
Dr. SHAIK KAREEMULLA
Associate Professor
Department of Pharmacy Practice
MMCP, (MMDU)

2. INTRODUCTION:
Tuberculosis is the most communicable and infectious disease
which is mainly caused by bacteria, Mycobacterium tuberculosis. It is an
infection, treated by anti-TB drugs. It is a global problem, with the
incidence varying across the world. An increase in reported cases of TB
in countries across all continents led the WHO to declare TB as a global
emergency. In many countries, it is compounded in those who have co-
infection with the human immune deficiency virus HIV. There has been
an increase in multi-drug resistant TB. The treatment of MDR-TB is very
complex, costlier and also have a longer duration when compared to
susceptible treated drugs.

3. TB is easily transmitted from person to person through coughing and
sneezing. Adequate and effective treatment is essential for patients to
control TB, as the BCG vaccine does not protect against the infection.
TB infection usually occurs by the respiratory route. Successful control
of TB depends on a close working collaboration between clinical,
microbiological, pharmaceutical, infection control and health care
professionals involved in TB.
EPIDEMIOLOGY:
Globally, it is estimated that TB causes 2 million deaths worldwide each
year. one-third of the population is affected with the tubercle bacillus. It
is the leading cause of death among HIV positive patients.
Over 4 million cases of TB are notified annually.

4. It is estimated that 4,40,00 people had MDR-TB world-wide and one-
third of these people die annually.
ETIOLOGY:
TB is caused by tubercle bacilli, which belongs to the genus
Mycobacterium. Among the large group, 3 species cause TB. They are
M. tuberculosis(98.6%), M. bovis(0.5%), M. africanum(0.9%). Around
15 species other than tuberculosis are recognized as pathogenic, found
in soil, milk and water. They are called as atypical bacteria. Robert
Koch discovered the microbial cause of TB. TB is highly contagious.
The greatest risk of infection is prolong contacts, mainly household
contacts. It can’t be acquired from individuals with latent TB infection.

5. Most people with active TB who have received appropriate treatment for
at least 2 weeks are non-contagious. MDR-TB is developed during the
treatment period or by transmission of MDR bacteria.
RISK FACTORS: Close contact of patient with TB, especially those
with sputum smear positive pulmonary disease. The following people are
at high risk to get active TB which have LTBI.
 HIV positive
 Drug abusers
 Organ transplantation
 Hemodialysis
 Immunocompramised people
 Receiving anti-TNF treatment


6. PATHOGENESIS:
The primary infection will be seen in individuals who were not
previously exposed. Immune compromised patients develops TB due to
activation of T- cells. This results in the development of pathological
lesions such as caseating granulomas (Tissue degeneration).
Steps include:
1) ENTRY INTO MACROPHAGES: M. tuberculosis enters the
macrophages by phagocytosis i.e., mediated by mannose binding lectin
and complement receptors.
2) REPLICATION IN MACROPHAGES: Bacteria inhibits the
maturation of phagosomes, blocks the formation of phagolysosome and
prevents the attack of lysosomal enzymes.

7. It is done by inhibiting both calcium signals and assembly of proteins
which is essential for phagolysosome formation. This stage is associated
with bacteremia at multiple sites. At this stage, most of the people are
asymptomatic or some patients may have flu like symptoms.
3) INITIATION OF IMMUNITY: Lipoproteins and glycolipids
associated with mycobacteria are recognized by innate immune
receptors. This initiates and enhances adaptive immune responses to
mycobacterium.

8. 4) THE TH1 RESPONSE: After 3 weeks of infection, TH cells are
responded and activates the macrophages, enable macrophages to act as
bactericidal. This is initiated by mycobacterial antigens after entering
into lymph nodes. IL-12 are produced by the antigen presenting cells
(APC) and dendritic cells, encounter mycobacteria by T cells
differentiation.
TH1 MEDIATED MACROPHAGES ACTIVATION AND KILLING
OF BACTERIA: TH1 cells produce interferon- gamma.
A) It stimulates infected macrophages maturation to phagolysosome and
exposing bacteria to lethal acidic environment.
B) Stimulates expression of nitric oxide synthase, produces nitric oxide,
combines with other oxidants to form reactive nitrogen intermediates

9. C) It mobilizes antimicrobial peptides against the bacteria.
D) Stimulates autophagy, it is a process that destroy damaged organelles
and intracellular bacteria.
GRANULOMATOUS INFLAMMATION AND TISSUE DAMAGE:
In addition, Macrophages stimulated by INF-gamma undergo
differentiation and aggregation to form granulomas, fuses to form giant
cells. In many people, this reaction may halt the infection, in some
patients, infection may progress further due to immuno-suppression or
advanced age. Ongoing response lead to caseation necrosis. Activated
macrophages secrete TNF and chemokines, promotes to recruit more
monocytes. Eventually, necrosis and tissue damage are seen at infected
areas.

12. CLINICAL FEATURES:
Clinically TB is separated in 2 pathophysiologic types.
1) Primary tuberculosis: It develops in previously unexposed and
un-sensitized persons. The source of organism is exogenous.
2) Secondary tuberculosis: It arises in previously sensitized host
persons. It appears after many years of primary infection.
Early warning signs: According to the Centers for Disease Control and
Prevention (CDC), the symptoms of TB include:
•Feeling sick, weak
•Loss of appetite, weight loss
•Chills, fever, night sweats
•Severe cough lasting for 3 weeks

13. SYMPTOMS:
During a latent stage, TB has no symptoms. When TB is active: cough,
fever, and other symptoms appears. TB usually affects the lungs, it also
affects other parts of the body, and symptoms will vary accordingly.
•The bones: Spinal pain and Joint destruction.
•The brain: It can lead to meningitis.
•The liver and kidneys: It impairs waste products filtration and leads to
blood in the urine.
•The heart: It impairs heart's ability to pump blood resulting in cardiac
tamponade, a condition that can be fatal.

14. Diagnosis:
 It can be diagnosed based on symptoms, medical history, assessing the
risk, and checking lung sounds.
 Most common diagnostic test for TB is a skin test where a small
injection of PPD tuberculin is administered just below forearm.
Tuberculin is an extract of the TB bacterium.
 Injection site should be checked after 2-3 days. If there is a presence
of hard, redness and swelling to a specific size, it reveals that patient
is suffering from Tuberculosis i.e., provisional diagnosis.
 Unfortunately, skin test will not give 100 percent accurate diagnosis.
 MDR TB is more difficult to diagnose when compared to regular TB.
 TB in children is also difficult to diagnose.

15.  Other tests also be performed to diagnose TB. Blood tests, chest X-
rays, and sputum tests are used to test the presence of TB bacteria and
were performed along with skin test.
TREATMENT:
In treating TB, a number of factors are important:
 Choice of drugs
 Length of the treatment
 Co-morbidity especially HIV infection, liver and renal diseases.
 Adherence to treatment by the patient.

17. DRUG TREATMENT:
DRUG NAME DOSE AND
FREQUENCY
DOSAGE DOSE
REDUCTION
IN R.F
DOSE
REDUCTION IN
L.F
Rifampicin 600 mg daily 10mg/kg No ONLY IN CLF
Isoniazid 300mg daily 5-10mg/kg Yes in severe
failure
Yes in both ALF
AND CLF
Ethambutol 400mg daily 15mg/kg Yes No
Pyrazinamide 500mg 35mg/kg Yes No
streptomycin 1g inj 15mg/kg yes No

18. RESPIRATORY TB: It affect lungs, pleural cavity, mediastinal lymph
nodes, larynx. It can be treated by the following regimen.
SIX MONTHS TREATMENT:
 Rifampicin, Isoniazid, Pyrazinamide and Ethambutol for the initial 2
months (initial phase), reduces bacterial population rapidly and
prevent the emergence of drug resistant bacteria.
 Further 4 months of Rifampicin and Isoniazid (continuation therapy)
 Combination of tablets is used to prevent accidental missing of drug
therapy and minimizing risk of MDR-TB.
 Pyridoxine in the dose of 10-15 mg should prescribe along with the
Isoniazid to reduce the incidence of CNS and peripheral neuropathic
effects.

19. LYMPH NODES TB: Previously, 9 months treatment is recommended.
Now, standard 6 months regimen is advised, since trials have shown that
6 months treatment is as effective as 9 months treatment.
MENINGEAL TB: It can be treated with Rifampicin and Isoniazid for
12 months along with Pyrazinamide, and Ethambutol for the first 2
months as it reaches CSF through inflamed meninges. Ethambutol may
cause the visual abnormalities. So care should be taken in unconscious
patients. Glucocorticoids are also recommended in management with the
initiation of anti-TB drugs. But they should be withdrawn within 2-3
weeks.
Prednisolone: 20-40 mg in adults
1-2 mg/kg in children upto maximum of 40mg.

20. BONE AND JOINT TB: Spine is the most common site for bone TB. It
is treated by 6 months regimen containing Rifampicin and Isoniazid
along with pyrazinamide and ethambutol. In some cases, surgery is done
to relieve spinal cord compression or to correct spinal deformities.
PERICARDIAL TB: It may lead to cardiac tamponade and pericarditis,
which are associated with a significant mortality and morbidity. Standard
6 months regimen is used. Glucocorticoids should also be prescribed in
dose of 60mg/day for adults or 1mg/kg/day for children. It should be
withdrawn after 2-3 weeks.

21. TREATMENT IN SPECIAL CONDITIONS:
IN CHILDREN: Doses should be reduced, prescribed should be
administered in correct volumes in appropriate strengths. Ethambutol
should not be used frequently as patients may report certain visual
disturbances.
IN PREGNANCY CONDITION: As there is a risk of TB to foetus,
treatment should be started immediately. Standard therapy should be
given. Pyridoxine supplementation should also be recommended.
RENAL DISEASES: Standard doses of Rifampicin, Isoniazid and
Pyrazinamide are prescribed. But the dose of ethambutol should be
reduced as it is eliminated through renal route.

22. DRUG-RESISTANT TB: It is considered as a worldwide problem.
Drug resistance is an important issue in the management of TB as it may
compromise the effectiveness of treatment. It is also important because
bactericidal drugs such as Isoniazid and Rifampicin become inactive.
Treatment should be individualized and requires a complex regimen that
increases the treatment costs. Drug resistance TB may developed during
treatment period.

23. DOT THERAPY: Directly Observed Therapy, in which patients taking
medications were observed by a health care professional i.e., TB patients
residing in streets or homeless patients.
RNTCP: Revised National TB Control Program was started in 1997.
Main ambition is Diagnosis and Treatment for TB are free.
The initial objectives of RNTCP are:
 To achieve and maintain a TB treatment success rate of at least 85%
among new sputum positive patients.
 To achieve and maintain detection of at least 70% of the estimated
new sputum positive people in the community.

24. PREVENTION:
 Face mask can help to lower the risk of the spreading the disease to
other people.
 Wearing a mask, covering the mouth and ventilating rooms also limits
the spread of bacteria.
 Isolate the patient from community for certain period.
 TB vaccination: BCG vaccine doesn’t protect against infection, but it
prevents from serious diseases such as miliary TB and meningeal TB.

25. Bacille Calmette Guerin Vaccination (BCG):
 The BCG vaccine contains a live attenuated strain of M.
bovis and is 70% to 80% effective against the most severe
forms of TB, such as TB meningitis in children, but is less
effective in adults.
 Public Health England, 2013 UK vaccination strategy
targets the at-risk population rather than the entire UK
population.
 In brief, BCG immunization is offered to infants at high
risk of TB exposure, children who are contacts of people
diagnosed with pulmonary TB and people younger than
35 years who are at occupational risk of TB such as

26. Case Study of Tuberculosis:
 A 50-year-old man being treated for pulmonary TB,
is reviewed in the outpatient clinic at week 4 of his
standard antituberculous treatment include
(isoniazid, rifampicin, pyrazinamide and
ethambutol). He reports feeling uneasy with some
increased nausea. Routine blood tests are
performed and his alanine transaminase (ALT) has
risen from 37 U/L to 230 U/L.

27. NICE guidelines recommendations:
National Institute for health Care and Excellence
Q1) Should the patient treatment be stopped?
Ans: Once the ALT has risen to five times the upper
limit of normal (>200 U/L), then medicines should be
discontinued.
Q2) What is the likely causative medicine?
Ans: Unfortunately, all of the drugs used can cause
liver toxicity. The least likely cause is ethambutol.

28. Q3) How should the medicines be re-introduced?
 Liver function should be monitored to ensure it is
returning to baseline. At the same time it is important to
assess for factors that increase risk of liver toxicity, such
as viral hepatitis.
 When the ALT is less than two times the upper limit of
normal (<80 U/L) reintroduction can take place in a
sequential fashion starting with ethambutol plus either
isoniazid or rifampicin.
 Pyrazinamide is reintroduced last, because it may be
the most likely drug that induces hepatotoxicity. Latest
NICE guidelines (NICE, 2016) recommend that the