Early

CHILDHOOD TUBERCULOSIS

Gopakumar Hariharan

Senior Registrar, NPICU

Royal Hobart Hospital,

Tasmania, Australia

Introduction

• Case scenario

• Mode of transmission

• Pathophysiology

• Investigations

• Treatment

• Complications

Case Scenario

• 3 months old

• Apnea and respiratory distress

• CXR- Miliary patttern suggestive of TB

• Mum- open case- cavitating lesion of lungs – AFB

positive

• Choroid Tubercles

• On ATT ; Managed in Adult ICU

Tuberculosis

• Chronic infection – Mycobacterium Tuberculosis

• Major public health problem

• Pulmonary and extrapulmonary

Russia, India, Southeast Asia, sub-

Saharan Africa, and parts of Latin America

( 95%)

Portal of entry for tuberculosis

• Inhalation of Tubercle bacilli in >95% (M.TB) – Reservoir( infected person)

• Ingestion of milk containing Bovine Tubercle bacilli (M. bovis)

• Contamination of superficial skin or mucous membrane lesion with tubercle bacilli

• Congenital infection when mother has lymphohematogenous spread during pregnancy ORtuberculous endometritis

Epidemiology

• Host Factors

• Age : all ages affected, congenital is rare

• Malnutrition : more susceptible

• Intercurrent infections : e.g. measles, whooping cough

• Environment : overcrowding, inadequate ventilation,

damp, insanitary and unhygienic conditions

Primary tuberculous infection

Primary Focus (Ghon’s focus)

• At the site of first implantation

• Usually single and Subpleural

• In most, - heals and disappears, or

- fibroses or calcifies.

Localized inflammatory Process

Primary complex

Primary Complex:

• Primary focus + Hilar lymphnodes + draining lymphatics ( Tuberculous lymphangitis)

• Complications arise more commonly from regional adenitis than from the primary focus

Progressive primary tuberculosis

• Apparently healed focus or nodes may contain viable

organisms for many years.

• During 1st 4-8 weeks, organisms are disseminated in the blood

stream directly or via lymphatic duct – involves multiple

organs

• Progression of TB depends on the age of the child, number of

tubercle bacilli, and host resistance ( HIV )

Complications of the primary

focus

1. Rupture of focus into pleural space causing serous effusion ( more than 5 years)

2. Rupture of focus into bronchus causing cavitation

3. Enlarged focus, sometimes laminated or “coin” shadow

Complications of regional nodes

1. Incomplete (ball-valve) bronchial obstruction, emphysema of middle & lower lobes

2. Complete bronchial obstruction, collapse of right lower lobe

3. Erosion of node into bronchus & segmental consolidation

4. Rupture of node into pericardium: tuberculouspericardial effusion

Bronchial complications

1. Stricture of bronchus at

site of erosion

2. Cylindrical bronchiectasis

in area of old collapse

3. Wedge shadow: contracture

& fibrosis of segmental

lesion

4. Linear scar of fibrosis

following segmental lesion

Endobronchial TB – wheeze

Fever, troublesome cough, dyspnea, wheezing and cyanosis

Symptoms

• Primary complex – mild fever, anorexia, weight

loss, decreased activity, cough

• Progressive primary complex – high grade fever,

cough.

• Expectoration and hemoptysis – usually associated

with cavity and ulceration of bronchus.

• Abnormal chest signs – decreased air entry,

dullness, creps

Miliary tuberculosis

• Most common within 1st 3 to 6 months after infection

• Due to heavy hematogenous spread of tubercle bacilli

• Onset: Insidious, with

Fever and weight loss

Palpable liver and/or spleen

Tachypnoea with normal chest findings

Miliary tuberculosis

• Hematogenous dissemination - progressive development of small lesions throughout the body, with tubercles in the

• lung, spleen, liver,

• bone marrow, heart, pancreas

• brain, choroid, skin

Radiologic diagnosis:

• “Snow storm” appearance (Multiple small lung nodules 1mm size and above in both lung fields).

Miliary TB

Millets- 1 to 3 mm

X ray

Tuberculous meningitis

Rupture of a subcortical caseous focus (Rich’s) into the subarachnoid space.

Inflammatory exudates form about base of brain and along cerebral vessels as they pass over hemispheres.

Raised intracranial pressure due to increased secretion of CSF

Adhesions along base and roof of 4th ventricles lead to obstruction to CSF flow and hydrocephalus,

.

Multiple cranial nerve involvement - III VI VII and optic chiasma.

Endarteritis – Neurological deficits

Diagnosis of TB meningitis

• Signs of meningeal irritation

• X-ray chest

• CT scan – basal exudates, inflammatory granulomas etc

• Tuberculin testing

• Retinoscopy for choroidal tubercles

• Lumbar puncture

Elevated CSF pressure(30 – 40cm h2o)

Cobweb Coagulum/ pellicle on standing

100 – 500 WBCs / cu.mm

>40 mg% protein

Low / Normal sugar

AFB smear & culture

Skin manifestations

TB verrucous cutis Erythema Nodosum

Casseous tuberculosis

Spinal tuberculosis

)

Phlyctenular conjunctivitis

Cervicitis, salpingitis, infertility

Tuberculous otitis with multiple perforations

Scrofula

Choroid Tuberculosis

Tubercles of choroid (with

miliary TB)

Panophtalmitis

Exudative retinal detachment

Responds well to treatment

Wallgren A.The time table of Tuberculosis. Tubercle 1948;29:245-251

Direct tests for tuberculosis

• Ziehl-Neelsen staining for AFB in clinical specimens (sputum, gastric juice, biopsy)

• AFB culture on Lowenstein-Jensen solid medium (4 weeks)

• PCR amplification of targeted mycobacterial DNA sequences

• DNA probes: fluorescence in situhybridization assays

Other tests

• PCR – rapid results ( antigen/ antibodies)

• Serodiagnosis – ELISA

• QuantiFERON- TB test (QFT) – for diagnosing latent TB. Based on IFN-gamma released from sensitized lymphocytes.ELISPOT

Mantoux Test

• MC used test for establishing diagnosis of TB in children

• Delayed type hypersensitivity reaction

• 0.1 ml of 5 TU PPD is injected intradermally into the volar aspect of the forearm (or 2 TU of PPD RT 23)

• A weal of 5 mm should be raised

• Reaction is read after 48 – 72 hrs

• Look for induration and erythema

Observation and Inference

• 48-72 hours later diameter of induration is measured

transversely to the long axis of the forearm.

• Induration > 10mm is suggestive of natural infection.

• 5-10 mm borderline; considered positive in

immunocompromised host

• <5mm Negative mantoux test does not rule out TB

False Negatives• Test done in incubation period of TB

• For several weeks following measles

• During Corticosteroid therapy

• Overwhelming TB infection (miliary, meningits)

• Severe Malnutrition

• If given Sub Cutaneous instead of Intra dermal

• Inactive Tuberculin

Guidelines for presumptive diagnosis of tuberculosis

Pediatr Infect Dis J 1993;12: 499-504)

A combination of at least 3 of the following:

• Symptoms/signs s/o TB: (fever > 1 mo., cough, weight loss)

• History of close contact with TB

• Positive tuberculin skin test (Mantoux > 10 mm)

• Sputum / gastric juice AFB +ve

• Lymph node / tissue biopsy positivity

• Radiologic features suggestive of TB

• Response to Anti TB Therapy

History of contact = any child who lives in a household with an adult taking ATT or has taken therapy in the past 2 years

Radiology

• In extra pulmonary TB , presence of lesions on chest radiograph supports diagnosis.

• Enlarged lymph nodes in hila, right paratracheal region

• Consolidation in progressive primary disease –heterogenous, poorly marginated with predilection to apical or posterior segments of upper lobe or superior segments of lower lobe.

• Bronchiectasis

• Pleural effusion

• Miliary TB

Treatment for TB

1st line anti-tuberculous drugs• Isoniazid H

• Rifampicin R

• Pyrazinamide Z

• Ethambutol E

• Streptomycin S

Phases of Treatment

• Intensive Phase

• Eliminate bacterial load

• Prevent emergence of drug resistant strains

• Atleast 3 Bactericidal Drugs used

• Continuation Phase

• Continue and complete therapy

• Atleast 2 Bactericidal drugs used

• Steroids

• Anti inflammatory effect – miliary, peritonitis, pericarditis

• TB meningitis

Management of Active TB

( NICE guidelines)

Progressive Pulmonary Tuberculosis and multiple LNE-

2 HRZE + 4 HR ( 6 month )

Meningeal TB

2 HRZE + 10 HR +Prednisolone /Dexamethasone

Prednisolone 1–2 mg/kg, maximum 40 mg with gradual withdrawal of the glucocorticoid considered, starting within 2–3 weeks of initiation

The 5 components of DOTS

Political & administrative commitment

Diagnosis by good quality sputum microscopy

Adequate supply of good quality drugs

Directly observed treatment

Systematic monitoring & Accountability

Prevention

Children with pulmonary TB disease are

rarely infectious due to

• Their pattern of disease,

• Low bacillary load and

• Lack of coughing force

Diagnosing latent TB

• Mantoux testing - household contacts (aged 5 years

and older) of all people with active TB and non-

household contacts (other close contacts for

example, in workplaces and schools).

• Consider Interferon-gamma testing - Mantoux

testing shows positive results, or in people for whom

Mantoux testing may be less reliable, for example

BCG-vaccinated people. ( high specificity)

Contacts – outbreak situation

• Active community surveillance

• Large numbers of people may need to be screened,

consider a single interferon-gamma test for people

aged 5 years and older.

• Preventive Therapy In Mantoux Positive : 6 HR

Healthcare workers

• Offer a Mantoux test to new employees who will be

in contact with patients or clinical materials if the

employees:

• Have not had BCG vaccination (for example, they

are without scar, other documentation or reliable

history).

• Mantoux test is positive, offer an interferon-gamma

test

BCG vaccination for

healthcare workers

• BCG vaccination should be offered to healthcare

workers, irrespective of age, who:

• are previously unvaccinated (that is, without adequate

documentation or a characteristic scar), and

• will have contact with patients or clinical

materials, and

• are Mantoux (or interferon-gamma) negative.

BCG vaccination for contacts

of people with active TB

• BCG vaccination should be offered to Mantoux-

negative contacts of people with respiratory TB if

they are previously unvaccinated and are:

• Aged 35 or younger

• aged 36 and older and a healthcare or laboratory

worker who has contact with patients or clinical

materials

Infection control

Three levels of isolation for infection control in

hospital settings:

• Negative-pressure rooms

• Single rooms - not negative pressure but are vented

to the outside of the building

• Beds on a ward

Isolation guidelines( NICE)

• Should be given a single room. Preferably not

admitted

• Visitors to a child with TB in hospital - screened

as part of contact tracing, and kept separate from

other patients until they have been excluded as the

source of infection

• Isolation for 2 weeks of treatment

Barrier nursing

Healthcare workers caring for people with TB should

not use masks, gowns or barrier nursing techniques

unless:

MDR TB is suspected

Aerosol-generating/ cough inducing(

bronchoscopy/sputum production) procedures are

being performed.

?Long term follow up

Regular follow-up clinic visits after treatment

completion were unnecessary.

Patients should be advised to watch for symptoms of

relapse and to contact the TB service rapidly if the

symptoms occur.

Multidrug resistant Tuberculosis

• A minority of cases, 6–8% in England and Wales, are

resistant to one of the antibiotics.

• Isoniazid and rifampicin are ineffective in 1% of

cases.

• These are said to be cases of multidrug-resistant

(MDR) TB, which requires special treatment and

careful monitoring.

Summary

• Pathophysiology of childhood Tuberculosis

• Various clinical manifestations

• Management

• Treatment

• Preventive measures

• Surveillance

“Nothing in life is to be feared, it is only to be

understood. Now is the time to understand more, so that

we may fear less.”

― Marie Curie