CHILDHOOD TUBERCULOSIS

Robert Koch

•The microorganism found in animals suffering from the disease, but not in healthy animals.
•The microorganism must be isolated from a diseased organism and grown in pure culture.
•The cultured microorganism should cause disease when introduced into a healthy animal.
•The microorganism must be reisolated from the diseased experimental host and identified as
being identical to the original specific causative agent.
 EPIDEMIOLOGY
• 95% in developing countries
• 1/3 of world population affected
• 2 billion case load
• 8 million new cases annually
• 1 million die annually
• 98% portal of entry is lung
• 8 % MDR TB – some XDR
• HIV co epidemic
 India
• 3.8 million cases
• 4,400 die every day
• 0.8 % among U5
• All age 1.6%
• 40% under 16 infected
• 105% of them develop disease
• MDR 3%
 Taxonomy of Mycobacteria
1. Tuberculous 2. NonTuberculous

• M.tuberculosis • I. Photochromogens:
– M. kansasii (Pathogen)
• M.bovis • II. Scotochromogens:
• M.africanum – M. scrofulaceum (Pathogen)
– M. aquae (Saprophyte)
• M.microti • III. Non Chromogens
• M.canetti – M.avium complex (Pathogen)
• IV. Rapid Growers
3. M. leprae – M. fortuitum (Pathogen)
 Bacteriology of Mycobacterium tuberculosis

• Non spore forming

• Non motile
• Pleomorphic
• Gram positive
• Curved rods
• Obligate aerobes
• facultative intracellular
parasite
 Clinical spectrum
Two groups
1.Infected asymptomatic – Mx +
2.Tubercular disease –
• Clinical
• Bacteriological
• Radiological
• radiological
 Clinical types
Primary:
• Latent tuberculosis
• Primary complex
• Progressive primary complex
• Disseminated tuberculosis
• Reactivation tuberculosis
Secondary:
 Secondary TB
• Very strong existing immunity
• Localization of the disease to the affected organ
• More tissue destruction due to delayed
hypersensitivity
• Apical region commonly affected due to more
Oxygen availability
• Casseation and cavitatation more pronounced
• Healing by fibrosis
 Primary TB
Pathogenesis
1. Immune host
 Pathogenesis
2. Susceptible host – progressive PC
 Pathogenesis
3.suscepible host
Reactivation TB
Disseminated TB

• Lympho hematogenous spread • varying periods of dormancy

• > 7 years of age
• Apices of lung – Simon focus
• Usually adolescents
• Brain-TBM • Upper lobe infiltration -
• Liver Simon focus
• Casseation and cavitations
• Kidney
• Pleurisy
• Bone and joints • Pericarditis
• Miliary • Tuberculoma
Time line
 Immunity
• Bacilli land on well ventilated subpleural area of
lung
• Neutrophils migarate first but could not fight due
to resistant bacterial cell wall
• Monocytes come for second line defense engulf
the bacteria but could not kill ; form epithelioid
cells- multinucelate giant cells
• Third comes T lymphocytes CD4 get sensitized
and release cytokines
 Immunity
• Cell mediated immunity

• Humeral immunity less role

• Lymphocytes recognize mycobacteria

• Produce lymphokines

• Lymphocytes and macrophages attracted to site

• Macrophage engulf and kill mycobacteria

• Delayed tissue hypersensitivity develops

• Granuloma formed
• CD4 release cytokines which activate CD8
cytotoxic cells
• CD8 lyse monocyte and release bacteria
• Activated macrophages ultimately kill the
bacteria
• After sensizitization of T lymphocytes
granuloma formation occur to prevent spread
of infection
TB granuloma
 Clinical features
Latent Tuberculosis
• Asymptomatic
• Mx + ve
• CXR normal
• No clinical signs
• 40 % develop symptomatic TB
• Maximum progression in first 2 yrs
• Reactivation during adolescence
 Clinical features
Clinical features External markers

• Fever • Wasting
• Lanugo hair
• Cough
• Long eye lashes
• Malaise
• Phlectenular conjunctivitis
• Night sweats
• Scrofuloderma
• Malaise
• Sinus ulcers
• Anorexia • Lupus vulgares
• Weight loss • Tuberculids
 Skin TB
Scrfuloderma Veruka and lupus vulgares
 TB in Prgnancy

• Prematurity

• IUGR

• Increased peri natal mortality

• Con TB in NB is rare
 Investications
Mantoux skin test
• Basis: Delayed cellular
hypersensitivity
• 0.1 ml intradermal

• 5 TU of PPD Tween 80

• Read after 48-72 hrs

• Early reaction not positive

• Delayed reaction is positive

 Mantoux
False positive: False Negative:
• Non tuberculous mycobacteria
• BCG ( up to 5 yrs; <10 mm) • Anergy
• Infant
• Malnutrition
• Suppressed immunity
• Vaccine: Measles; MMR
• Measles infection
• Miliary TB
• Technical error
 Mantoux reading
positive reaction
I. Contact history Symptoms of PC

HIV

Immuno supression > 5 mm

II. High prevalence area >10 mm

III. Low prevalence area > 15 mm

IV. Recent Mx conversion >10 mm

V. Serial Mantoux: becomes positive

 Bacterial isolation and culture

• Gastric aspirate- 3 consecutive morning

samples
• Bronchoscopy

• Negative culture and smear do not rule out TB

 AFB
Ziehl-Neelsen stain
• Heat fix
• Smear with carbol fuchsin
• Steam – 5 mts
• Rinse
• Add 3% acid – alcohol - 5
minutes
• Rinse
• Methylene blue-1 mt
• Rinse
• Dry
• Bright red purple bacilli
 Auramine-rhodamine florescent stain.

• Requires a fluorescent
microscope.
• The fluorochrome dyes
used
• The fluorescing
mycobacteria are seen
as bright yellow-orange
bacilli against a dark
background.
 Culture
Lowenstein-Jensen medium
• Egg medium

• glycerol enhances the growth of

M.tuberculosis
• also used in drug susceptibility
testing
• > 3 weeks for growth

• > 4 weeks for sensitivity

• rough, tough and buff colonies

CXR
Miliary TB
Calcified hilar adenitis
 Other tests

• Interferon release by T cells towards MT

antigens
• Quantiferon TB c-gold
• T Spot- TB

• Elispot (elliza identifies T cells specific for TB)

 Other forms of TB
• Lymphadenopathy:
• Scrofula
• More in M.bovis
• Firm, non tender, matted, fixed
• Also caused by Atypical mycobacteria; Mx positive
• FNAC
• Upper respiratory tract:
• Laryngitis
• CSOM
• Pleurisy and pericarditis
 Other forms of TB
• Miliary TB:
• Choroid tubercles
• Miliary mottling in CXR
• CNS:
• TB Meningitis
• Tuberculoma
• Abdominal Tuberculosis
• TB arthritis, osteomyelitis
• Renal and genital : rare
 TB & HIV
• 30% more in HIV
• Mx – ve
• Rapid progression
• TB induces lymphocytosis - CD4
• Lymphocytosis favours viral replication-vicious cycle
• Rifampicin toxicity increased by ART
 Treatment

• Chemoprophylaxis:
• Mx- with contact history

• Mx + 15 mm

• INH alone for 6 months or

• INH + RF for 3 months

 Treatment
• Pulmonary: 2HRZ/4HR
• INH, Rifampicin and pyrazinamide for 2 months
• INH, Rifampicin for next 4 months
• PZA kills bacilli in the macrophages
• MDR TB:
• Add ehtambutol and SM
• DOTS: “Directly Observed Therapy, Short-course“
• 2 months drugs under direct observation by health
worker
• Intermittent course
 Basis for Intermittent Chemotherapy

• In vitro experiments have shown that after a culture

of M. tuberculosis has been exposed to certain drugs
for sometimes, it takes several days (the “lag
period”), before multiplication starts again
• Higher dosing in intermittent treatment increase
peek plasma levels
 Adverse effects

• Thrombocytopenia: RMP

• Neuropathy: INH

• Hepatitis: PZA, RMP, INH

• Rash: PZA, RMP, EMB

 TB-HIV co treatmnet

• Daily tuberculosis treatment whenever possible

• DOT is not recommended

• Treatment should be started with four drugs

(typically rifampicin, isoniazid, pyrazinamide and
ethambutol) until sensitivities are known.
• 6 months treatment regimen
• Rifampicin is a powerful inducer of cytochrome
P450-3A4 and reduces levels of protease inhibitors .
This would lead to markedly decreased antiviral
activity. Rifampicin concentration will increase to
toxic levels
• It is preferred to treat TB first and then start ARV
 Paradoxical worsening

• Paradoxical worsening of TB is due to an

improvement of the host's immune response during
the course of ARV treatment, leading to more
intense inflammation at sites of TB disease. Hence it
has also been referred to as "immune restoration
syndrome"
 Corticosteroids

• TBM

• Tuberculoma

• Endobronchial TB

• Pericarditis

• Miliary TB
 Prevention
BCG
• Bacille Calmette-guerin
• Live Attenuated bovine TB bacilli
• .5 ml intradermal
• 50% effective in PT
• 80% protective in CNS TB
• No protection for adults as effect wanes after 5 years
• Contraindicated in symptomatic HIV
• Also used for diagnosis
 NB & TB Mother

Neonate:
• INH for 3 months

• Isolation of NB if mother has MDR TB

Pregnancy:
• Pyrazinamide is teratogenic

• Isoniacid, Rifampicin and ethambutol

One at risk population