tuberculosis in children

Tuberculosis in children

Zhi-min Chen

Dept. Pediatric Pulmonology

Email: zmchen@zju.edu.cn

Pediatrics

Etiology: Tubercle bacillus

Oder Actinomycetales

Family mycobacteriaceae

Genus Mycobacterium(M.)

Species M. tuberculosis M. bovis Non-TB M.

Characteristics

Acid-fastness

Slow-growing

Unusual resistance

Multi-Drug Resistance strain(MDR)

Source of infection

Open Pulmonary Tuberculosis (adult)

acid-fast smear of sputum(+)

copious production of thin sputum

severe and forceful cough

extensive upper lobe infiltrate or cavity

Young children with TB rarely infect others

Route of transmission

By respiratory tract:

airbone mucus droplet nuclei

contaminated dustBy alimentary tract

raw milk

contaminated foodBy others: (Placenta,skin)

Transmission rarely occurs by direct contact with an infected discharge or contaminated fomite!

High-risk population

Genetic background:

twin

racial difference

HLA BW35Environmental factors:

socioeconomic status

overcrowding

poor nutrition

inadequate health care

TB infection and TB disease

TB infection:

inhalation of infective droplet nuclei containing

TB

A reactive tuberculin skin test and the absence

of clinical and radiographic manifestations

TB disease:

Signs and symptoms, or radiographic changes

become apparent

Infection, disease or not

Virulence of the TB strain

The size of inoculin

The hypersensitivity of the individual tissues

Nutritional or social status

Immunologic status

Genetic background

Primary Pulmonary Tuberculosis

Pediatrics

Spreading of M.tuberculosis

Initial focus (local infection at the portal of entry)

Draining lymphatic vessles

Regional lymph nodes

Blood

Other tissues of the body

Primary pulmonary tuberculosis

Clinical types Initial focus

Primary complex lymphangitis

Lymphadenitis

Bronchial lymph node tuberculosis

Primary pulmonary tuberculosis

Clinical manifestation

Surprisingly meager(subclinical)

Infants more likely to develop signs and

symptoms

Nonproductive cough and mild dyspnea as the

most common symptoms

Primary pulmonary tuberculosis

Less common symptoms

Systemic complaints

fever, night sweats, failure-to-thrive,

anorexia, etc.

Bronchial irritation or obstruction

localized wheezing

Prognosis

Improve or dissolve

Completely resolution

Induration

Calcification

Local progress

Exacerbation

Tuberculous meningitis

Most common in children of 6mo~4yr

Usually develops during the lymphohematogenous

dissemination of the primary infection

High mortality and high morbidity

Tuberculous meningitis: Clinical manifestation

Stage 1: Prodromal stage

Stage 2: Transitional stage

Stage 3: Terminal stage

Stage 1: Prodromal stage

Lasts 1~2wk

Nonspecific symptoms: character

alteration, fever, headache, malaise,

irritability, drowsiness

Focal neurologic signs absent

Stage 2: Transitional stage

Increased intracranial pressure: headache,

projectile vomiting, papilledema

Meningeal irritation: nuchal rigidity, Kernig’s

sign, Brudzinski’s sign

Toxic appearance: fever, anorexia, nausea

Others: cranial nerve palsies, convulsion

Stage 3: Terminal stage

1~3wk

Exacerbation of neurologic symptoms

Very thin with scaphoid abdomen

Electrolyte imbalance

SIADH

Cerebral salt losing syndrome

Diagnosis

Laboratory study

Clinical diagnosis

Diagnosis

Laboratory study

detection of M. tuberculosis

• Smear acid-fast staining

• Culture (BACTEC, liquid, coloricmetric)

• PCR and Gene probe

Diagnosis

Laboratory study

Isolation of M. tuberculosis

Serology: limited value

• LAM antibody

• 38kDa antibody

• 16kDa antibody

• … …

Diagnosis

Laboratory study

Isolation of M. tuberculosis

Serology

Pathology: biopsy and histology

• Caseous necrosis and encapsulation

Diagnosis

Laboratory study

Others

• INF-γ Releasing Assays( IGRAs)- promising

– INF-γ produced by T-cell responses to

M.tb-special antigens called early secreted

antigenic target 6 (ESAT-6) and culture

filtrate protein10.

– Commercial kits: Quantiferon-TB Gold In-

tube (QFT) and The T-Spot TB (T-Spot) test

Typical CSF picture of tuberculous meningitis, but NOT specific

Pressure

Appearance ground-glass

Cell counts 50~500×106/L, L. predominates

Protein

Glucose <40mg/dl ， or CSF/blood <50%

Chloride

Diagnosis

Laboratory Study

Clinical diagnosis

History

Clinical manifestation

Tuberculin test

Roentgenographic examination

Therapeutic trial

Diagnosis

Laboratory Study

Clinical diagnosis

History: usually need chest film or CT of her parents or family members

Clinical manifestation

Tuberculin test

Roentgenographic examination

Therapeutic trial

Diagnosis

Laboratory Study

Clinical diagnosis

History

Clinical manifestation: Not specific

Tuberculin test

Roentgenographic examination

Therapeutic trial

Diagnosis

Laboratory Study

Clinical diagnosis

History

Clinical manifestation

Tuberculin test: more valuable

Roentgenographic examination

Therapeutic trial

Tuberculin test ： principle & method

Based on delayed type hypersensitivity( type IV)

Two antigen preparations:

Old tuberculin, OT

Protein purified derivative, PPD

Intradermal injection of 0.1ml containing 5

tuberculin units of PPD (Mantoux test)

Tuberculin skin test:

result evaluation

The amount of induration should be measured by a trained person 48~72hours after administration

Intensity:

– or ±: <5mm negative or doubtful

+ : 5~9mm suspicious

++ : 10~19mm positive

+++ : >=20mm strong-positive

++++ : blister,ulcer,lymphangitis,double rings

What does it mean: Positive result

Previous infection with TB

Previous vaccination with BCG

Active tuberculosis

<=3 year without prior vaccination

> = 15mm

conversion occurring within 2 years

What does it mean: Negative result

Not infected with TB

False-negative :

incubation period

immunosuppression or immunodeficiency

technical error or improper reagents

Diagnosis

Laboratory Study

Clinical diagnosis

History

Clinical manifestation

Tuberculin test

Roentgenographic examination

Therapeutic trial

Diagnosis

Laboratory Study

Clinical diagnosis

History

Clinical manifestation

Tuberculin test

Roentgenographic examination

Therapeutic trial

Prevention of TB

Avoiding contact with those with open

pulmonary tuberculosis

BCG (Bacillus Calmette-Guerin)

vaccination

Chemoprophylaxis

Treatment

Antituberculosis therapy:

early, dosage, combination, regular, whole course

intensification stage and consolidate stage

directly observing therapy shortcourse (DOTS)

Corticosteroids

Symptomatic management

Supportive care