1. Sings and symptoms
• A person came to the clinic. She told the
doctor that she had cough over 3 weeks,
sometime with blood, and mucus. She lost
weight and always felt tired. She got fever
frequently and sweating at night. She also felt
pain in the chest area when she cough or
sometime while she was breathing. She was
losing her appetite.
3. Diagnosis Test
• Blood test
• A chest X ray
• Pulmonary function test ( PFTs)
• Gram positive/ negative/ acid fast strain test
• IGRA ( interferon Gamma Release Assay)
• TST ( Tuberculin Skin Test )
• AFB smear Microscopy
• ELISA
• Molecular Line Probe Assay
4. Tuberculosis ( Pandemic Infection)
• One of the top 10 causes of death worldwide.
• In 2015, 10.4 million people fell ill with TB and 1.8 million died from
the disease (including 0.4 million among people with HIV.
• In 2015, an estimated 1 million children became ill with TB and 170
000 children died of TB (excluding children with HIV).
• TB is a leading killer of HIV-positive people: in 2015, 35% of HIV
deaths were due to TB.
• Globally in 2015, an estimated 480 000 people developed
multidrug-resistant TB (MDR-TB).
• TB is spread from person to person through the air. (fast infection
spread)
• Direct costs, mostly covered by the public sector,
averaged $134,000 per MDR TB and$430,000 per XDR TB patient; in
comparison, estimated cost per non-MDR TB patient is $17,000.
7. Antitubercular Treatment or ATT
General treatment –combination of multiple
drugs for at least 4 months
– More than 20 drugs available for TB
– Some drugs are effective on certain
circumstances such as drug resistance TB cases
8. New TB patients or first time TB patients
treatment
• cured by combination of ‘first line’ drugs in 6 months
• ‘First line’ TB drugs
– Isoniazid
– Rifampicin
– Pyrazinamide
– Ethambutol
– Streptomycin
( New TB patients include only those who have not had
TB treatment before, or they have received less than
one month of anti TB drugs.)
Rifampicin –
C43H58N4O12
C6H7N3O - Isoniazid
9. 6 Months Treatment
• For the two month intensive TB treatment
phase they should receive:
• Isoniazid + rifampicin + pyrazinamide + ethambutol
drugs
• followed by ( for the continuation 4 months
TB treatment)
• Isoniazid + rifampicin drugs
• recommended to take drugs everyday for 6 months
10. TB resistant patients treatment
• Can be cured by drugs such as bedaquiline and
delamanid
• The drugs for TB resistant cases are more expensive
and have more side effects than susceptible TB drugs.
• These resistant drugs treatment given to-
– patients who have is a high level of isoniazid resistance
locally
– patients who have developed active TB disease after
known contact with a patient who is documented as
having drug resistant TB
– patients who already got the ‘first line’ treatment and
still not cured after 6 months period
11. A Few Examples of Drugs Mechanisms
• Rifampicin - inhibits the gene transcription of mycobacteria by blocking
the DNA-dependent RNA polymerase, which prevents the bacteria from
synthesizing messenger RNA and protein, causing cell death.
• Response from bacteria - Resistance to rifampin occurs due to mutations
in the rpoBgene, which encodes the RNA polymerase beta chain
• Isoniazid - It comprises a pyridine ring and a hydrazine group. Isoniazid is a
prodrug and must be activated by the M. tuberculosis catalase-peroxidase
enzyme KatG; the activation of isoniazid produces oxygen-derived free
radicals (superoxide, hydrogen peroxide, and peroxynitrite) and organic
free radicals that inhibit the formation of mycolic acids of the bacterial cell
wall, causing DNA damage and, subsequently, the death of the bacteria.
• Response from bacteria - KatG mutations, which decrease the activity of
isoniazid and prevent the prodrug from being converted into its active
metabolite
12. ???????????
• “ TB vaccine is not working anymore”
– Why? Antibody? Immune system? HIV? Side
effects?
Drugs resistant Bacteria growth rate is increasing
very fast. ( Drugs treatment failure)
_ Doctor? Patients? Drugs quality? Bacteria’s
adaption?
Initial infection, bacteria will be ingested by the alveolar macrophages of the lungs.
the majority of these bacilli are destroyed or inhibited.
A small number may multiply intracellularly and are released when the macrophages die.
When release, these bacteria may spread by way of lymphatic channels or through the bloodstream to more distant tissues and organs (including areas of the body in which TB disease is most likely to develop: regional lymph nodes, apex of the lung, kidneys, brain, and bone).
