This document discusses tuberculosis (TB), including its risk factors, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention. It notes that TB is transmitted via airborne droplets and its major risk factors include close contact with active TB cases, immunosuppression, poverty, and smoking. Diagnosis involves sputum microscopy, culture, nucleic acid tests, chest imaging, and the tuberculin skin test. Treatment follows the DOTS (Directly Observed Treatment, Short Course) strategy to cure TB and prevent drug resistance.
2. RISK FACTORS
Close contact with someone who have active TB
Immunocompromised status
Drug abuse and alcoholism
Cigarette smoking
Poorly controlled diabetes
Poverty , Overcrowding
Healthcare personnel
Immigrants from countries with higher incidence of TB
9. 1. Elimination Of the Reservoir
Early detection of the cases.
Prompt treatment by effective medications as per the national
guidelines.
10. 2. Breaking the chain of transmission
Careful collection and management of patient sputum.
Isolation of the patient till sputum is free of bacilli.
Use of handkerchief while sneezing and coughing.
11. 3. Protecting the susceptible
Clean housing
Personal hygiene
Nutritious diet
Regular exercise and healthy lifestyle
No smoking and alcohol
Vaccination
Controlling diabetes
12. Vaccination
◦ BCG (Bacillius Calmette –Guerin) Vaccine
Live attenuated vaccine(M.bovis)
Given intradermally
Immunity lasts for 10-15 years
Given to children and adults with high risk of TB
Contraindications :HIV or immunocompromised patients
13. Vaccination in Nepal
BCG vaccine campaign started in Nepal in 1979.
Given to neonate immediately after birth
Route: Intradermal
Site: left upper arm in deltoid region
Dose : 1 (0.05ml)
15. What is DOTS therapy?
◦ DOTS (directly-observed therapy, short-course) chemotherapy means that the patient taking
the medicine should be observed by a nominated person, and the taking of the medicine
should be recorded. This ensures that the patient takes the medication regularly, which is
essential for the medicines to be effective – and to prevent the bacteria from becoming
resistant and the drug from becoming ineffective.
◦ It is a strategy to ensure cure by providing the most effective medicine and confirming that
is taken. This can be at the TB clinic, patient’s home or place of work, or any other
convenient location.
◦ DOTS plus: It refers to a DOT program that adds components for MDR-TB diagnosis,
management and treatment.
◦ Started in Nepal in September, 2005.
16. DOTS therapy
Phases of DOTS THERAPY:
1. Intensive Phase:
In DOTS, during the intensive phase of treatment a health worker or other trained
person watches as patient swallows drug in her/his presence.
2. Continuation phase:
During continuation phase, patient is issued medicine for one week in a multiblister
combipack of which the first dose is swallowed by the patient in the presence of health
worker or trained person.
The consumption of medicine in the continuation phase is also checked by return of
empty multiblister combipack, when the patient comes to collect medicine the next
week.
17. Community based DOTS
◦ Community based DOTS is an approach taken for patients who cannot attend TB
treatment centre regularly due to various reasons.
◦ Such patient will be treated in the community close to a community volunteers.
◦ Objectives of DOTS program:
◦ To increase the tubercular treatment accessibility to the patient.
◦ Treatment adherence.
◦ To raise awareness regarding disease condition in the community and decrease social
stigma.
18. Five elements of DOTS
Political commitment with increased and sustained financing.
Case detection through quality assured bacteriology.
Standardized treatment with supervision and patient support.
An effective drug supply and management system.
Monitoring and evaluation system and impact measurement system.
19. Advantages of DOTS
Increase cure rate by providing most effective drugs. Treatment success rate is upto
95%.
Cure is rapid with short course.
Decrease transmission of TB.
Decrease chance of resistance.
It is successful and effective strategy
It helps in reduction of poverty by rapid cure.
20. Disadvantages of DOTS
This isn’t rapid and reliable method of all TB treatment.
Patient compliance has to be ensured.
There is no single regimen of treatment.
Difficult in remote areas.
Spreading of MDR-PTB if volunteers don’t take precautions.
21.
22. Host factors(human)
i. Age- In developing countries, more common in young age group.
In developed countries, more common in elderly.
ii. Sex- More prevalent in males.
iii. Heredity- It is not a hereditary disease but study shows that inherited
susceptibility is important risk factor.
23. iv. Nutrition- Malnutrition is widely believed to predispose to
tuberculosis.
v. Immunity- Man has no inherited immunity against
tuberculosis. It is acquired as a result of natural infection or
BCG vaccination.
vi. Alcoholism
vii. Diabetes mellitus
viii. HIV infection
24. HIV and TB Co-infection
HIV virus damages the immune system and accelerates the progression of TB
from being a harmless infection to a life threatening condition.
patients with HIV infection are 25-30 times more likely to develop active tb.
Increased risk of recurrences and reactivation of Latent infection.
Diagnosis becomes more difficult because:
a. Co-infected people may have higher frequency of negative sputum smears and confirmation
may require sputum culture.
b. As the response of immune system is damaged in HIV, the tuberculin skin test often fails to
work.
c. In the absence of fully functioning immune system, there is less lung cavitation and Chest
radiography becomes less useful.
d. Cases of extra-pulmonary TB are more common.
25. Agent- M. tuberculosis
Non motile, non sporing, non capulated bacillus
Size- 2-3 x 0.2- 0.4 micrometers.
Is present singly or in groups
Gram staining- weakly gram positive.
Zeihl- Neel’s stain- acid fast- appears bright red.
27. Environmental factors-
D
Poor quality of life
Poor housing
Overcrowding
Population explosion
Under nutrition
Lack of education, lack of awareness of illness
Large families
Early marriages
32. Pathogenesis of TB
• Inhalation of airborne droplet containing MTB
• ↓
• Travel through respiratory tract to the alveoli/ distal airways
↓
• Engulfment by activated alveolar macrophages, dendritic cells
↓
• Replication of MTB inside macrophages
↓
• Brusting of cells, Release of bacilli and entry into other cells
↓
33. • Local pro-inflammatory response
↓
• Recruitment of mononuclear and Dendritic cells
↓
• Infected macrophages, dendritic cells spreads to lymph nodes
↓
• T cell activation in Lymph nodes
↓
• Initiation of cell mediated immunity
↓
34. • Migration of activated T cells
↓
• Formation of granulomas → containment of MTB(Dormant bacilli)
and leads to Latent TB
↓
• Liquefaction of granuloma
• Neutrophils influx
• Leads to Primary TB
35. Control of TB
• TB control:
• Reduction in prevalence and incidence of disease in the
community.
• WHO definition:
• TB control is achieved when prevalence of natural infection in the
age group 0-14 years is in order of 1%
36. Curative component of TB
A. Case findings
• Case : sputum positive cases
• Target group:
Ptx with one or more symptoms referable to chest
1. Persistent cough
2. fever
3. Hemoptysis
4. Chest pain
Ptx seeking medical advice
37. Case finding Tools
• AFB Microscopy
• Fluorescence microscopy with auramine rhodamine stain
• LED ( Fluorescent Light Emitting Diode) microscopy
38. AFB Microscopy
• Collection of sample:
• National TB Program recommends taking 2 samples on same day
with 2 hours interval.
• Previously,
• Spot sample followed by early morning sample on next day
39. Slide Reporting
• It is based on no. of bacilli seen under 1000x magnification in a
smear.
• Reflects
disease severity
patients’ infectivity
40. Slide Interpretation
No. of bacilli under ZN stain Result reported
No bacilli per 100 OIF 0
1-9 bacilli per 100 OIF Scanty
10-99 bacilli per 100 OIF +
1-10 bacilli per OIF ++
> 10 bacilli per OIF +++
41. Results:
• Smear positive:
1 out of 2 smears is positive
• Smear negative:
both the smear tested are negative
Symptomatic treatment given
Broad spectrum antibiotics except FQ, Rifampicin or streptomycin
for 10-14 days.
42. • If no improvement,
• Case I
• Repeat sputum examination
↓
if one of 2 smear +ve
↓
smear positive patient
43. • If no improvement,
• Case II
Repeat sputum examination
↓
if none of the smear +ve
↓
chest X-ray taken
↓
X-ray finding consistent with Pulmonary TB
↓
patient k/a sputum –ve pulmonary TB
44. False positive and false negative results:
• False positive results:
Technical errors
Contamination
Other acid fast particles
• False negative results:
Problem in collecting, processing or interpreting
Technical errors
45. Other tools
• Fluoresence microscopy with auramine rhodamine stain
Routinely not done → expensive
• LED ( Fluorescent Light Emitting Diode) microscopy
recommended by WHO as microscopy tool of choice.
46. Diagnostic Tools
• Nucleic Acid Amplification Test
• Mycobacterial culture
• Drug Susceptibility Testing
• Radiography
47. Nucleic Acid Amplification Technology
I. Gene X-pert MTB/ RIF (Resistance to Rifampicin)
integrates
sputum processing
DNA extraction & DNA amplification
leads to TB and MDR-TB diagnosis
Sensitivity similar to culture
Target mycobacterium Tuberculosis specifically
Enable simultaneous detection of Rifampicin resistance
Can be used as marker for MDR-TB with high accuracy
48. • Xpert MTB/RIF started in Nepal in 2011/2012
• 55 Xpert MTB/RIF centers
• 58 Gene Xpert machines
II. Xpert MTB/ RIF ultra assay
III. TB-LAMP ( Loop Mediated Isothermal Amplification)
49. Mycobacterial Culture
• Gold standard for both diagnosis and drug susceptibility testing
• Method of choice for drug resistant TB treatment monitoring
Conventional culture methods:
• Lowenstein-Jensen (LJ) media
• Takes 8 wks for –ve results
• Takes 4-6 wks after initial culture for drug susceptibility testing.
• Disadvantage: takes long duration to isolate the organism
50. Culture
Commercial Liquid Culture System:
• Mycobacterial Growth Indicator Tube (MGIT)
• Recommended by WHO as reference standard for culture
• Culture become +ve after 10 days to 2-3 weeks
• Tubes are read on weekly basis until 8th week of incubation before
result is declared to be –ve.
51. Drug Susceptibility Testing
• Recommended as current standard of care by WHO for all TB
patients
• Should consist
At least rifampicin for all initial isolates of MTB as rifampicin
resistance is excellent proxy for MDR-TB
One or more risk factors for drug resistance are identified or if
patient either fails to respond to initial therapy or has a relapse
after completion of treatment
52. expanded and rapid susceptibility for isoniazid
Rapid susceptibility test for second line anti- TB drugs especially
FQs and injectable drugs when RR-TB is found.
I. Gene Xpert MTB/RIF: detects rifampicin resistance
II. Line Probe Assay:
• PCR based test for diagnosis and determining susceptibility to anti
TB drugs
53. • 1st line LPA: isoniazid and rifampicin susceptibility
• 2nd line LPA: FQ and injectable anti TB drugs ( Aminoglycosides and
polypeptides susceptibility
• Disadvantages:
Needs higher bacterial load in sample than Xpert for +ve result
• Preferred smear +ve sample and culture over LPA.
54. • Patient eligible for LPA:
1. All previously treated patients presenting with TB should be
tested with LPA (1st line) at start of treatment.
2. All RR-TB cases should be tested with LPA (1st and 2nd line) and
culture, DST at start of treatment.
3. All treatment non- responders
III. Culture
56. Diagnosis of Latent TB infection
• Tuberculin test
• Interferon-γ Release Assay
i. Quantiferon
ii. T.spot TB test
57. Tuberculin test
• Provides evidence of past or present infection i.e. prevalence of
TB.
• Tuberculin: PPD-S and PPD-RT 23
(PPD- Purified Protein Derivatives)
• Note: 1 TU(Tuberculin Unit) of PPD-RT 23 equivalent to 5 TU of
PPD-S
58. Mantoux Test
• 1 TU of PPD in 0.1 ml taken
↓
• injected (using 26 gauge needle and tuberculin syringe)
intradermally on flexor surface of left forearm midway between elbow
and wrist
↓
• Reading taken after 72 hours (48-96 hrs)
↓
• Measured the induration transversely to the long axis of forearm
(Note: Don’t measure erythema)
↓
• Induration suggest infection not the disease
59. Interpretation
Induration in mm Significance
>20 mm Positive and high chance of disease
>10 mm Positive
6-9 mm Doubtful
<6 mm Negative
60. False positive and false negative results
• False positive results:
Caused by infection with non-tuberculous mycobacteria or by BCG
vaccination
• False negative results:
common in immunocompromised patients and in those with
overwhelming TB
61.
62. Booster Effect of Tuberculin Test
• Tuberculin sensitivity ↓es with time
• But repeated test exerts a booster effect so another tuberculin
test 1-2 weeks later gives a strong positive test (>20 mm)