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The Agent:: Mycobacterium Tuberculosis

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The Agent:Mycobacterium Tuberculosis

 Tubercle bacilli
 Non-motile,non-sporing, non-capsulated rods.
 They may be straight or slightly curved

 3 x 0.3µm size

 Obligate anaerobes, slow growing.

 Destroyed by direct sunlight, UV light and

pasteurization of milk
Pathogenesis
 Mode of transmission: Droplet infection
 Portal of entry:
 Inhalation, ingestion or inoculation.
 Primary site of infection
 Lung, tonsils, mucous membrane, intestine, skin
Droplet Nuclei
 "Droplet nuclei" spread via the airborne route -
primary means of transmission of M.T.B
 Bacilli containing droplets - expelled by talking,
coughing, sneezing- from patients with pulmonary
tuberculosis.
 These desiccate to 2-5 u in diameter, - inhalation
to the level of the alveolus.
Pathogenesis
 Bacilli multiply and cause inflammation
 Macrophage engulf bacilli
 Formation of granulomatous lesion
(Tubercle)
 Some tissue within dies - caseation
 Scar tissue around tubercle – isolation of
bacilli
Post-primary TB:Genesis
 Reactivation of quiescent focus
 Direct progression of primary

 Hematogenous spread

 Re-infection
Organs affected
 Pulmonary disease: Most common (85%
of disease).
 Pulmonary tuberculosis is the only infectious
form.
 Extrapulmonary disease occur alone or with
pulmonary involvement.
 Most common sites: Lymph nodes, pleura,
bones, meninges, genitourinary tract and
hematogenous (miliary) spread.
History: Risk factors for TB
 HIV infection
 H/o +ve purified protein derivative (PPD) test
 H/o of prior TB treatment
 Exposure to an active case of TB
 Travel to/immigration from, an endemic area
 Homelessness, shelter-dwelling, incarceration
SYMPTOMS
 Cough/expectoration
 Hemoptysis
 Dyspnea
 Chest pain
 Weight loss/anorexia
 Fever
 Night sweats
 Malaise & Fatigue
SIGNS
 Pyrexia
 Tachycardia
 Tachypnoea
 Wasting/emaciation
 Signs of
 Effusion
 Consolidation
 Other
Physical Examination
 Depend on the organs involved.
 Pulmonary TB - abnormal breath sounds,
especially over the upper lobes or involved
areas. Rhonchi or bronchial breath sounds
may be noted.
Collar-stud abscess
Diagnosis
• Clinical

• Radiological

• Mycobacteriogical

• Immunological

• Hematological

• Molecular-biological
Radiology & imaging
➢ Not diagnostic

➢ Contributory evidence

➢ Differential diagnoses

➢ Judicious use of CT scans

➢ USG thorax and Abdomen

➢ Bimonthly reviews
Image Challenge

Q: This 20-year-old man was evaluated for fever. What is the diagnosis?

1. Allergic bronchopulmonary aspergillosis


2. Cystic fibrosis
3. Primary hyperparathyroidism
4. Sarcoidosis
NEWER TESTS FOR DIAGNOSIS
Microscopy
1. LED Fluorescent microscopy:
Auramine-rhodamine staining –
more sensitive than ZN staining.
2. Induce sputum :
(a) Nebulized saline
(b) Post-broncodialator
(b) Bronchoscopic specimen
3. FNAC specimen
NEWER TESTS FOR DIAGNOSIS

Interferon Gamma Release Assay (IGRA)

Blood test

QuantiFERON–TB Gold In-Tube test (QFT–GIT) is
an approved test of IGRA.

Positive IGRA means that the person has been
infected.

If negative, latent TB infection or TB disease is not
likely.
NEWER TESTS FOR DIAGNOSIS
Culture

Traditional: – Löwenstein-Jensen’s, Kirchner, or
Middlebrook media culture – 6-8 weeks time.

Newer:- MB/BacT, BACTEC 9000, VersaTREK, & the
Mycobacterial Growth Indicator Tube (MGIT).

Microscopic Observation Drug Susceptibility assay
(MODS) - more sensitive, faster and cheaper test for
TB. Direct observation of M.TB & also simultaneously
yields drug-resistance.
NEWER TESTS FOR DIAGNOSIS
Nucleic acid amplification tests (NAAT)
Uses the polymerase chain reaction (PCR) technique or
transcription-mediated amplification to detect
mycobacterial nucleic acid.

Cartridge Based NAAT (CB NAAT)

MTB direct test (MTD, Gen-Probe)

Truenat MTB, Truenat MTB Plus, & Truenat
MTB-Rif Dx - tests made in India.

Xpert XDR for drug resistant TB
Immunological diagnosis


Mantoux test

National Sample Survey

Background reactivity

False positive / False negative

Realize limitations :
An adjunct
OTHER NEWER TESTS
➢ Fluorodeoxy Glucose PET/CT useful in
detection of active TB lesions,
differentiation from latent disease, staging
& monitoring the disease
➢ Antibody in Lymphocyte Supernatant or
ALS Assay - immunologically detects active
disease.
➢ Detection of LAM, mycobacterial
lipoarabinomannan antigen in urine - activity
Chemotherapy

Rx only after confirmation

Never use a single drug

Initial Attack phase +

Continuation phase

Attack Phase : 8 weeks

Continuation phase : 16 weeks

Never add single drug to a failing regimen

Use sterilizing drugs wherever possible
Common drugs
 Rifampicin (R) 450/600 10mg/kg
o Rifacilin
o Rifamycin
o Rifampila
o Rimpin
o Zucox
 INH (H) 300 5mg/kg
o Isokin
o Isonex
o Solonex

 Use sterilizing drugs wherever possible


Common drugs
 Ethambutol (E) 800/1200 25mg/kg
o Combutol
o Ebutol
o Ecox
o Myambutol
o Mycobutol
 Pyrazinamde (Z) 1500/2000 35mg/kg
o PZA-CIBA
o P-Zide
o Piraldina

 Use sterilizing drugs wherever possible


DOTS

Directly observed treatment, short-course, also
known as TB-DOTS)

Control strategy recommended by the World
Health Organization.

WHO: The most cost-effective way to stop the
spread of TB in communities with a high
incidence is by curing it.
DOTS

Patients receive TB drugs under OBSERVATION

Must take the TB drug in front of a DOTS agent.

The DOTS agent - a volunteer from the patient’s
community, OR a family member.

DOTS applies when TB drugs are taken with the patient
being observed by a DOTS volunteer.
Regimen

Thrice weekly (earlier), now daily.

Attack phase: 8 wks x EHRZ

Continuation phase: 24 wks x HR

For relapse and discontinued :

EHRZ + Inj. Streptomycin x 8 weeks

After 8 wks, EHRZ x 4 wks, thereafter for 5 m HRE

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