Tuberculosis

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CONTENTS

 INTRODUCTION TO TUBERCULOSIS (TB)

 BACKGROUND/ HISTORY OF EMERGENCE

 EPIDEMIOLOGY
WHAT IS TUBERCULOSIS?

 TB is one of the most common infectious disease in the world.


 Causative agent: Mycobacterium tuberculosis
 Mode of transmission: airborne spread via Respiratory droplet (produced by patients with
active infectious TB)
 Most commonly affects lungs, other organs too might be affected.
History

 Recent studies suggest, M. tuberculosis may have emerged about 70,000 years ago
in Africa
 Subsequently disseminated along with modernization and started to spread globally
during the Neolithic period, when the human density started to increase.
Epidemiology: status around the world

IN WORLD:
 It is estimated that nearly 2 billion people in the world (about one fourth of the
world’s population) are infected with M. tuberculosis.
 Every year, about 10 million people develop TB disease and 1.6 million people die of
it. In fact, TB disease is the leading cause of death due to infectious disease in the
world.

 IN USA: In 2017, the case rate was 2.8 cases per 100,000
persons.
In nepal

NEPAL NATIONAL TB PREVALENCE SURVEY BRIEF (march 24,2020)


Around 1,17,000 (88,000 – 145,000) people in Nepal are living with Tb disease today.
This is the prevalence.
NATIONAL TB PREVALENCE SURVEY, 2018-19
Around sixty-nine thousand, 69, 000 (41,000 – 103,000) people developed TB in 2018.
This is the incidence.
Also showed an estimated annual reduction of TB incidence by 3% in the last decade
Which is much better than the global annual decline rate of 1.5%–2%.
High risk for tb
 AGE> 65 y/o (poor access to heakthcare for elderly)
 Poor healthcare systems
 Spread of HIV
 Social problems: increased poverty, (Tb is also called as dz of poors),
homelessness, drug abuse, increased crowding conditions.
ACCESS TO HEALTH CARE
Among participants ( cough for 2 weeks or more)
 around 31% - seeked medical treatment in government facilities,
 around 14% in private facilities
 around 39% did not seek any care or treatment.
 good trust in government health services but may also indicate a lack
of alternative services that people can access.
 More than 80% of these patients - DOTS
Pathogenesis of
Tuberculosis
Causative agents

 Mycobacterium tuberculosis

 Mycobacterium bovis
Inhalation of droplets

Enter the periphery of lungs

Engulfed by macrophages

Cytokines produced by CD4+ lymphocytes

Recruitment of monocytes & formation of granulomas

Caseous Necrosis

Appearance of Pulmonary lesion


Appearance of pulmonary lesion- Ghon’s Focus

Combination of pulmonary lesion with regional lymph node involvement- Ghon’s


Complex
Spread of bacilli before immunity Immune response mounted
established
Secondary focus-
(formed in other organs like
lymph nodes,bones, liver, lungs
& kidneys.)

Foci resolve & viability of micro-


organisms are lost

Latent bacilli may persist


for years
ection in healthy individuals
Indicated by appearance of cell-mediated hypersensitivity reaction to tuberculin

Factors increasing risk of TB

Patient related Associsted diseases

Age: Children> adult> elderly Immunocompression


- HIV, high dose corticosteroids

Overcrowded areas Malignancy


- Lymphoma, leukemia

Close contact with TB affected person Type I DM


Primary infection Chronic renal disease
<1 year preiously

Immigrants from highly prevalent areas Deficiency of vit.D or A


Silicosis
Types of TB

1. Pulmonary TB
TB affecting the lung
alveoli
2. Extra pulmonary TB
TB affecting sites other than lungs like lymph nodes, bones,
meninges, etc.
3. Miliary TB
It is a result of acute diffused dissemination of tubercle bacilli
via blood stream.
CLINICAL FEATURES OF PULMONARY TB
 In general, clinical presentation of pulmonary tuberculosis includes:

 Chronic cough, often with haemoptysis

 Pyrexia of unknown origin

 Unresolved pneumonia

 Exudative pleural effusion

 Weight loss

 Spontaneous pneumothorax
1. PRIMARY PULMONARY TB
 Occurs soon after the initial infection with tubercle bacilli.

 Mostly asymptomatic

 May present with fever and pleuritic chest pain

 Some patients may develop erythema nodosum in legs or phlyctenular


conjunctivitis

 Regional lymphadenopathy

 Pleural effusion found in 2/3rd of cases

 Bronchiectasis may develop


2. POST-PRIMARY PULMONARY
(ADULT TYPE) TB
o May result from endogenous reactivation of distant latent infection or
recent infection

o Systemic symptoms:
-Fever
-Night sweats
-Malaise
-Loss of weight and appetite
-Fatigue

o Pulmonary symptoms:
-Cough : Initially non-productive and limited to morning and accompanied
by purulent sputum, sometimes blood streaking
-Hemoptysis
-Pleuritic chest pain sometimes develop with subpleural parenchymal
lesions or pleural disease
-Dyspnea and sometimes adult respiratory distress syndrome
CLINICAL FEATURES:
EXTRA-PULMONARY TB
Extrapulmonary TB accounts for 20%of cases in those who are HIV
negative but is more common in HIV positive patients.
Lymphadenitis

 35% of extra-pulmonary tuberculosis.

 Especially in HIV positive patients.

 Painless swelling of Cervical and Supraclavicular lymph node .


-Later become matted and fixed
-May result in fistulous tract draining caseous material
Pleural TB
 Is common and result from hypersensitivity response to mycobacterium
antigen or continuous spread from parenchymal inflammation.

 Pleural effusion may cause fever, chest pain, dyspnea and pleuritic chest
pain

 Dullness to percussion and absence of breath sounds


Genitourinary
 Patient may be asymptomatic until severe destruction of the kidney has
developed.

 Nocturia

 Hematuria.

 Dysuria.

 Abdominal or flank pain.

 Pelvic pain, menstrual abnormalities and infertility if fallopian tubes are affected

 Tubo-ovarian abscess.

 Prostatitis
Gastrointestinal
 May involve of any part of the GI tract

 Ileum and caecum most commonly affected

 Abdominal pain ,swelling and palpable mass in the abdomen

 Fever, night sweats, anorexia and weight loss

 Hematochezia

 Palpable mass in right iliac fossa

 Abdominal lymphadenopathy

 Mesenteric thickening

 Ascites
Pericardial disease
 Acute or subacute onset of fever.

 Dull retrosternal pain.

 Pericardial effusion

 Raised JVP

 Prominent ascites

 Peripheral edema
CNS
 Meningitis in young and HIV positive patients.

 Coma

 Hydrocephalus

 Intracranial HTN
Bone and joint disease
 Chronic back pain

 Kyphosis, scoliosis

 Paravertebral and psoas abscess

 Cold abscess in inguinal region

 Cord compression

 Pain and swelling of joints of insidious onset

 Fever and night sweat(uncommon)


Miliary TB

 Occurs due to haematogenous spread of tubercle bacilli.

 Clinical manifestations are non-specific and include:


-2 to 3 weeks of fever
-Night sweats
-Anorexia
- Weight loss
-Dry cough
Tuberculosis
Diagnosis
Specimens required

 PULMONARY
 Sputum
 Bronchoscopy
 Gastric washing (mainly used for children)
Specimens required
 Extrapulmonary
 Fluid examination
 Cerebrospinal – for tuberculous meningitis
 Ascitic
 Pleural – for pleural disease
 Pericardial
 Join
 Tissue biopsy
 From affected site
 Bone marrow/ liver may be diagnostic in disseminated(miliary)TB,
particularly in HIV-infected patients
Diagnostic Tests
1. AFB Microscopy

2. Mycobacterial culture

3. Radiographic procedures

4. Nucleic acid amplification

5. Drug Susceptibility testing

6. Diagnosis of Latent M. tuberculosis infection (LTBI)


a) Tuberculin Skin testing(TST)
b) IFN-γ Release Assays (IGRA)

7. Baseline blood tests


a) CBC, CRP, ESR, LFTs
1. AFB Microscopy
 Tuberculous bacilli are difficult to stain due to its lipid-rich wall.

 The most effective techniques are:

a) Ziehl-Neelsen method

b) Rhodamine-auramine staining
 a. Ziehl-Neelsen method
 b. Rhodamine-auramine staining
 This staining method causes tuberculous bacilli to fluoresce against a dark background
 Easier to use when numerous specimens need to be examined.
2. Mycobacterial culture
 It can be done is following media:
a) Solid media
1. Mycobacterium tuberculosis grows slowly (4-6 weeks) on solid
medium
2. E.g. Lowenstein-Jensen or Middlebrook
b) Liquid media
1. Faster growth (1-3 weeks)
2. E.g. BACTEC system(radioactive), Mycobacteria Growth Indicator
Tube (MGIT)
3. Radiographic procedures
 Chest X-Ray

 CT scan
4. Nucleic acid amplification tests
 Helps in diagnosis of Tuberculosis and detect the presence of rifampicin
resistance.

 WHO recommends its use worldwide as the first line diagnostic test in all
adults and children with signs or symptoms of active TB

 It is also the first choice in individuals with HIV or those suspected to have
multidrug resistant tuberculosis.
5. Drug Susceptibility testing
 This testing is important in following cases:
 Previous history of TB

 Treatment failure of TB

 Chronic disease

 Individuals who are resident in or have visited an area of high prevalence


of resistance

 HIV- positive
6. Diagnosis of Latent M. tuberculosis
infection (LTBI)

a) Tuberculin skin test

b) IFN-γ Release Assays (IGRA)


7. Baseline blood tests

 CBC, CRP, ESR, LFTs


Treatment & Management
of
Tuberculosis
Submitted by:
• Ayush Koirala
• Ayush Labh
• Pratima Gautam
• Reecha Bharkher
• Rojan Jung
Basnet
• Sudikshya Shakya
Contents
 Aims of treatment

 Drugs to treat tuberculosis

 Main adverse reactions of anituberculous drugs

 Treatment regime by WHO

 DOTS

 Tuberculosis classification for drug regime

 Drugs given to patients with TB in HIV, pregnancy, breast feeding mother


Aims of Treatment

 To cure the patient

 To prevent morbidity and mortality

 To prevent transmission of tuberculosis to others

 To prevent the development of drug resistance

 To prevent relapse of tuberculosis


Drugs to treat tuberculosis

1. First line drugs


 Streptomycin (S)
 Isoniazid (H)
 Ethambutol (E)
 Rifampicin (R)
 Pyrazinamide (Z)

These have high efficacy, low toxicity and routinely used.


2. Second line drugs
 Ethionamide

 Prothionamide

 Para–aminosalicylic acid

 Rifabutin

These have low antitubercular efficacy, higher toxicity and are reserve drugs.

3.) Newer drugs


 Fluoroquinolones : Ofloxacin, Levofloxacin, Ciprofloxacin
 Injectables : Kanamycin, Amikacin, Capreomycin
Adverse reactions
Treatment regime by WHO
 If the second month sputum smear is positive for M. tuberculosis, the intensive phase is
extended for one more month.

 During the intensive phase of treatment, every dose is administered under direct observation,
while during the continuation phase patients are asked to attend the treatment once a week,
when one dose is given under direct observation and the other two doses supplied to the patient
for self-administration.

 In Revised National Tuberculosis Control Programme (RNTCP), each patient is allotted a box of
medicines that contains drugs for the full duration of the treatment.
Directly Observed Therapy Shortcourse
(DOTS)
 Dots is a program to help cure TB.

 A DOT lay worker meets with clients to help with TB medication, and provide
support and education.

 DOT by definition means watching clients swallow each dose of anti-TB


medication.
TB classification for drug regime
A. Drug sensitive TB
- Sensitive to all 5 drugs.
- All new cases who have never taken any drug or taken for less than 1 month.

B. Multidrug resistant TB (MDR – TB )


- Resistant to at least two of the most potent first line drugs.

C. Rifampicin resistant TB (RR – TB )


- Resistant to Rifampicin (R) but not to Isoniazid (H), with/without resistance to other drugs.
- Treated like MDR – TB.
D.) Mono resistant TB
- Resistance to first line drugs but not to Rifampicin (R).
E.) Poly drug resistant TB
- Resistance to more than one first line drug but not to R and H.
F.) Extensive drug resistant TB (XDR – TB)
- Resistance to fluoroquinolone and 2nd line injectable drugs.
In HIV patients with TB
 Anti retro viral treatment should be restricted till at least the end of
intensive phase of TB treatment.

 Then Ethambutol(E) and Isoniazid(H) in continuation phase must be used.(HE


should be used in HIV)

 Use Rifambutin (if available) instead of Rifampicin.


In pregnant females with TB

 All anti-tubercular drugs are safe to use in pregnancy except Streptomycin.

 Streptomycin is ototoxic to fetus.


In breast feeding mother with TB
 Mom and baby should stay together.

 Baby can continue to breastfeed

 After active TB in baby is ruled out, the baby should be given 6 months of
Isoniazid preventive therapy followed by BCG.

 Pyridoxine supplement recommended for all pregnant and breastfeeding


mothers taking Isoniazid.
References

 Davidson’s principles and practice of medicine, 23rd edition

 API textbook of medicine, 9th edition

 KD Tripathi essentials of medical pharmacology, 8th edition


Prevention of tuberculosis
20th batch PDCH
Presentated by:-
Utsav, Sushil, Alisha, Nikita,
Ashmi, Alina
 How can we prevent tuberculosis ???
Primary prevention

Aim to block infection

Can be achieved through-

 Health education

 Specific protection
• Population strategy- BCG vaccine
• High risk strategy-
 Isoniazid preventive therapy
 Antiretroviral therapy for people with HIV
Secondary prevention

 Aims to block progression of infection to active disease

 Early diagnosis- detection of latent TB

 Specific treatment - DOT


Primary prevention
• Health education
• Specific protection
1. Population strategy - BCG VACCINE

 Bacille Calmette-Guérin vaccine

 Live attenuated vaccine derived from M. bovis

 Intradermal infection

 Recommended for routine use at birth in countries with high tuberculosis


prevalence-Tuberculin test negative
• As soon after birth or within 12 months

 Also considered for health workers with risk of exposure to multi-drug


resistant stains
Indications

 For all infants living in areas where TB is highly endemic

 For all infants and children at particular risk of TB exposure in otherwise low-
endemic areas.
Contraindication
 For persons with impaired immunity (symptomatic HIV infection, leukemia,
lymphoma or congenital immunodeficiency)

 For patient under immune suppressive treatment ( corticosteroids, alkylating


agents, antimetabolites, radiation)

 In pregnancy
2. High risk strategy

a) Isoniazid preventive therapy


 Benefit is greater in HIV – infected persons with positive tuberculin skin test

 Recommended regimen-
The standard regimen for TB preventive therapy is-
Adults : Isoniazid(INH) 5mg/kg/day( maximum 300mg/day)
Children : Isoniazid (INH) 10 mg/kg/day ( maximum 300mg/day)
o Vitamin B6 25mg/day should be given concomitantly with isoniazid to prevent
the occurrence of peripheral neuropathy.

 Recommended duration : 6 months of continuous treatment ( can be


completed over 9 months)
Contraindicated

 Patients with signs and symptoms of TB

 Patients with active liver disease or who are actively abusing alcohol because of
risk of hepatotoxicity
b. Anti Retroviral Therapy in people with HIV

 ART helps restore immune function

 ART can greatly reduce the risk of TB in a person living with HIV
Secondary prevention
Early detection- detection of latent TB
 Commonly identified using the tuberculin skin test

 For skin testing, S tuberculin units of polysorbate-stabilized PPD should be


injected intradermally into the Volar-surface of the forearm ( Mantoux
method )

 Reaction read at 48-72 hours as the transverse diameter is millimeter of


induration
The diameter of erythema is not considered.
 5mm diameter of indurations is cut off for –
 close contacts of infectious cases
 Persons with HIV infections
 Previously untreated person whose chest radiograph is consistent with
healed TB
 Cut off of 10mm for other and 15 mm for those with low risk of developing
infections

 Other tests- Interferon Gamma Release Assay ( IGRAs )


Specific treatment-Directly Observed
Therapy (DOT)

 Supervised administration of therapy thrice weekly

 Important control strategy in resource poor nation


Conclusion

TB infection can be prevented by:-


1. Involve patients and community in advisory campaigns
2. Infection control plans
3. Safe sputum collection
4. Cough etiquette and cough hygiene
5. Triage TB diagnosis and treatment
6. Improve room air ventilation
7. Protect health care workers
8. Monitor infection control practices
References

 Harrison’s Principles of Internal Medicine-15th Edition

 Davidson’s principles and practice of Medicine- 21st edition

 https://www.who.int/tb/challenges/hiv/07_tb_prevention_diagnosis_and_tre
atment_eng.pdf

 https://www.who.int/immunization/policy/schedule.pdf

 https://www.who.int/hiv/pub/guidelines/south_africa_hiv_tb.pdf

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