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1. Submitted To : Dr. Zeshan Nawaz
Subject: Advanced Epidemiology
Topic: Tuberculosis
Presented by: Iqbal Danish
Department of Microbiology 2nd Semester

2. INTRODUCTION
 Tuberculosis (TB) is a potentially fatal contagious disease that
can affect almost any part of the body but is mainly an infection
of the lungs.
 “WHO” Tuberculosis also call “TB” Is An Infectious Bacterial
Disease Caused By Mycobacterium tuberculosis, which result in
granulomatous formation in lungs and is major health problem in
developing countries.
 Historically called "consumption" due to the weight loss.
 “Tubercle” meaning Round nodule/Swelling.
 “Osis” means Condition
 In1882: Robert Koch ,a German scientist announced the
discovery of M. tuberculosis.

3. GENERAL CHARACTERISTICS
 Acid fast bacilli
 Obligate aerobe Intracellular
 Non spore forming
 Non motile
 Mesophile
 Slow generation time 15-20 hours
 Lipid rich cell wall contains mycolic acid (long chain fatty
acids) 60% of cell dry weight.
 Because the cells are hydrophobic and tend to clump
together, they are impermeable to the usual stains e.g.
Gram staining.

4. TRANSMISSION
 M. tuberculosis is transmitted from person to person by
respiratory aerosol.
 In air tiny droplets of 0.5-5 um in diameter persist when
infected person cough, sneeze or laugh and remain for
several hours.
 In developed countries, most tuberculosis is due to
reactivation in elderly, malnourished men.
 In developing countries, M. bovis is found in cow's milk,
which, unless pasteurized, can cause gastrointestinal
tuberculosis in humans.
 Only 10 percent of those infected individuals may
progress to a manifest disease.

5. PATHOGENESIS:
 Target is macrophages and reticuloendothelial cells.
 On entry in the phagosome it releases “exported repetitive protein "prevent
fusing of phagosome with lysosome so degrading enzymes have no action
on organism.
 Ghon's complex is a lesion seen in the lung that is caused by tuberculosis.
The lesions consist of a calcified focus of infection and an associated lymph
node.
 Primary infection is reactivated in apices in well oxygenated areas of
kidney, brain and bones mostly in immunocompromised patients.
 Lesions depends on presence of organism and host response.
Exudate lesion Granulomatous lesion
Formed at the initial stage of
infection mainly in lungs
Central, bacillus is surrounded by epithelial cell.
Granulomas composed of transformed
macrophages,epitheloid cells, lymphocytes .
Causes acute inflammatory
response
bacteria proliferate in pulmonary alveolar
macrophage and air spaces.

7. SPREAD OF ORGANISM
 Tubercle dissolves in
bronchus, empty in
caseous contents,
spread organism to
other parts of lungs.
 In blood stream it
disseminate if cell
mediated immunity
fails in early stage.
 Memory T cells
release cytokines try to
control outbreak of
bacteria and form
caseous necrosis.

8. CLINICAL MANIFESTATION:
1. Asymptomatic
2. Low grade fever
3. Night sweating
4. Cough
5. Dyspnea
6. Chest pain
7. Lethargy
8. Anorexia
9. Weight loss
10. Hemoptysis
11. Pneumonia

9. CLASSICATION
 Pulmonary TB
o Primary Disease
o Secondary Disease
 Extrapulmonary TB
o Lymph node TB
o Pleural TB
o TB of upper airways
o Skeletal TB
o Genitourinary TB
o Miliary TB
o Pericardial TB
o Gastrointestinal TB
o Tuberculous Meningitis
o Less common forms

10. PRIMARY TB
 Bacilli are engulfed by Alveolar Macrophages
 Multiply and give raise to Sub pleural focus
 lower lobes& lower part of upper lobes are infected called as Ghon’s
focus or Child hood TB.
 The Ghon focus together with hilary lymph node constitute the
Primary complex, leads to fibrosis after 3- 8 weeks of infection.
 Lesions forming after infection are peripheral.
 Heals in 2 – 6 months, calcified forms ranke complex.
 Some bacteria remain alive and produce latent infections.
 Infection activated in immunosuppressed conditions e.g. HIV and
AIDS
 Can lead to Meningitis, Miliary tuberculosis, other disseminated
Tuberculosis

11. SECONDARY TUBERCULOSIS
 The infection in individuals who has been previously infected
or sensitized is called secondary or post primary or reinfection
or chronic tuberculosis.
 Mainly occurs due to Reactivation of Latent infection.
 May also due to Exogenous reinfection.
 Differs from Primary Infection. Leads to;
1. Cavitation's of Lungs,
2. Enlargement of Lymph nodes,
3. Expectoration of Bacteria laden sputum.
 Dissemination into Lungs and other extra pulmonary areas.

13. EXTRA PULMONARY TB
 20% of patients of TB Patient
1) Lymph node TB ( tuberculuous lymphadenitis)
 Seen frequently in HIV infected patients.
 Painless swelling of lymph nodes most commonly at cervical
and Supraclavical (Scrofula)
2) Pleural TB
 Involvement of pleura is common in Primary TB
 results from penetration of tubercle bacilli into pleural space.
3) TB of Upper airways
 Involvement of larynx, pharynx and epiglottis.
 Dysphagia, chronic productive cough

14. 4) Genitourinary TB
 15% of all Extra pulmonary cases.
 Any part of the genitourinary tract get infected.
 Urinary frequency, Dysuria, Haematuria.
5) Skeletal TB
 Involvement of weight bearing parts like spine, hip, knee.
 Pain in hip joints n knees, swelling of knees, trauma.
6) Gastrointestinal TB
 Involvement of any part of GI Tract.
 Abdominal pain, diarrhea, weight loss
7) TB Meningitis & Tuberculoma
 5% of All Extra pulmonary TB.
 Under 5 yrs.of age are more prone, blood-brain barrier is
passed.
 Results from Hematogenous spread forming tubercules
which burst and infect meningies

15. 8) TB Pericardiatis
 1- 8% of All Extra pulmonary TB cases.
 Spreads mainly in mediastinal or hilar nodes or from
lungs.
9) Miliary or disseminated TB
 Results from Hematogenous spread through retrograde
transport of Tubercle Bacilli.
 Spread is due to entry of infection into pulmonary vein
producing lesions in different extra pulmonary sites.
10) Less common Extra Pulmonary TB
 Uveitis, painfull Hypersensitivity
 Related to phlyctenular conjuctivis.

16. TB ANNUAL REPORT WHO 2018
 Pakistan is 5TH in ranking among countries with highest incidence.
 Total registered TB patients 3,68,897 in 2017.
3%
7%
6%
54%
30%
EPIDIMEOLOGY OF TB
Balochistan
ICT
KPK
PUNJAB
SINDH

17. RISK FACTORS
(1)Poverty and poor housing
(2)Contribution of HIV and TB is deadly in 2017 300,000
people with HIV died of TB.
(3)Prisoners
(4)Alcoholism and Drug abuse.
(5)Kidney disease and diabetes.
(6)Working in healthcare.
(7)WHO stimates 8% of TB cases world wide can be linked to
smoking.
(8) Babies, children and elderly people.
(9) Malnutrition

18. MDR-TB and XDR-TB
 MDR-TB
 MDR-TB is a form of TB infection caused by bacteria that are resistant
with at least two of most powerful first line anti-TB medications/drugs
(isoniazid and rifampicin)
 Second line anti-TB drugs make it treatable and curable however,
second line is limited and require extensive chemotherapy (upto 2
years) with medicines that are expensive and toxic.
 WHO approved use of short, standardized regimen for MDR-TB
patients that included 9-12 month and less expensive than conventional
2 year medication.

19. XDR-TB
 XDR-TB is a form of TB infection caused by bacteria that are resistant
to most effective drugs of second line of anti-TB drugs.
 8.5% from MDR-TB had XDR-TB in year 2017.
 longer regimen with addition of one new drugs (bedquiline and
delamanid)
HIV and TB
 HIV weakens the immune system and increases the risk of Tuberculosis.
 HIV and TB disease risk increases when;
 HIV in endemic.
 Resources are limited.
 Latent TB could advance to TB (if HIV present).
 Treatment for HIV by “Antiretroviral Therapy (ART) decreases the chance of
occurrence of TB from latent TB.

20. DIAGNOSIS
 History and clinical examination
 Chest X-ray
 Tuberculosis creates cavities visible in x-rays
like this one in the patient's right upper lobe.
Abnormalities on chest
 Bacteriologic Evaluation
 Direct smear microscopy
 Microscopic examination of a specimen of
three morning successive sputum.
 Stained by the Ziehl-Neelsen method or
Auramine rhodamine stain (flourescent
microscopy).

21. CULTURE TEST
 Löwenstein-Jensen
 Middlebrook 7H10 & 7H11
 Acid fast bacilli (AFB) smear microscopy and culture are
still the “gold Standards” for the diagnosis of active TB.
 But conventional culture methods require (6-8) weeks for
isolation.

22. TUBERCULIN SKIN TEST (TST)
 Mantoux tuberculin skin test
 Purified Protein Derivative (PPD):
 0.1 ml is injected intradermally.
 Most people infected by M. tuberculosis are vaccinated by
BCG.
 will react to TST and develop an induration at the site of
injection.
 Diameter of this induration is measured after 48-72 hours.
 Induration of diameter 10mm or more is considered positive,
5mm or less is negative.

23. INTERPRETATION FOR TST
IN GAMMA ASSAY OR y-Interferon release assays
(GIRA)
oTest rely on the fact that T-Lymphocytes Will Release γ-
interferon.
oWhen exposed to specific antigens.
Gene expert

24. ANTI-TB DRUGS

26. Challenges to Treating TB/HIV
Latent TB/HIV:
oRifampin- Isoniazid based regimens for 12 weeks--- once
weekly
o4 months----- daily Rifampin and ART
o9 months----- daily Isoniazid, Rifampin and ART
Active TB/HIV:
oIntensive phase:
•Isoniazid, Rifamycin, Pyrazinamide, Ethambutol----- first 2
months.
oContinuous phase:
•Isoniazid and Rifamycin----- 4 months according to CDC.