tuberculosis in children zhi-min chen dept. pediatric pulmonology ， children’s hospital email:...
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Tuberculosis in children
Zhi-min Chen
Dept. Pediatric Pulmonology ， Children’s Hospital
Email: [email protected]
Pediatrics
Tubercle bacillus
Oder Actinomycetales
Family mycobacteriaceae
Genus Mycobacterium(M.)
Species M. tuberculosis M. bovis Non-TB M.
Chronicle of Tuberculosis
1882 Discovery of TB(Robert Koch)
1921 BCG development
1944 Invention of streptomycin
1952 Invention of Isoniazid
1966 Invention of Rifampin
………
Characteristics
Acid-fastness
ziehi-Neelsen
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
From TB infection to TB disease
Light J ,et al. Curr Probl Pediatr adolesc Health Care,2009; 39:61
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
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
isolation of M. tuberculosis: most specific
• 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
biopsy and histology : pathognomonic
• 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
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
Case report
6-month-old girl
Born in San Francisco, but her parents immigrated to
USA from China 8 yrs ago.
Chief Complaint
cough and fever for 3 weeks and tachypnea for 1 week.
No response to routine antibiotic therapy
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: helpful
Therapeutic trial
Diagnosis
Laboratory Study
Clinical diagnosis
History
Clinical manifestation
Tuberculin test
Roentgenographic examination
Therapeutic trial: final
Prevention of TB
Avoiding contact with those with open
pulmonary tuberculosis
BCG (Bacillus Calmette-Guerin)
vaccination
Chemoprophylaxis
Prevention of TB
Avoiding contact with those with open
pulmonary tuberculosis
BCG (Bacillus Calmette-Guerin)
vaccination
Chemoprophylaxis
Tuberculosis control programs
involve case finding and treatment.
Treatment
Antituberculosis therapy:
early, dosage, combination, regular, whole course
intensification stage and consolidate stage
directly observing therapy shortcourse (DOTS)
Corticosteroids
Symptomatic management
Supportive care
Recommended treatment regime
Pediatrics
Pertussis andPertussis syndrome
Definition
Pertussis (whooping cough)
caused by Bordetella pertussis,
The pertussis syndrome
includes disease caused by Bordetella pertussis
and certain other infectious agents
Etiology
Bordetella pertussis
tiny, Gram-negative, coccobacilli
Other infectious agents
Bordetella parapertussis
Adenovirus
Dual infection (of above)
Other common pathogens of protracted cough:
mycoplasma, chlamydia, RSV, parainfluenza virus
Epidemiology
Infect only humans and transmitted person
to person by coughing
Most contagious during the earliest stage
The peak incidence <4 m
The annual rate--100 to 200/100,000, higher
in developing countries
Clinical manifestation
The mean incubation period is 6 days.
The progression of pertussis
Catarrhal stage
Paroxysmal stage
Convalescent stage
Clinical manifestation
Catarrhal stage
nonspecific signs
• Injection
• increased nasal secretions
• low-grade fever
last 1 to 2 weeks
Clinical manifestation
The paroxysmal stage
approximately 2 to 4 weeks.
as catarrhal symptoms wane, coughing begins first
as a dry, intermittent, irritative hack;
then evolve into coughing in paroxysms during
expiration, causing young children to lose their
breath (machine-gun burst of uninterrupted
coughs).
Clinical manifestation
The paroxysmal stage After the most insignificant startle from a draught,
light, sound, sucking or stretching, a well-appearing young infant begins to choke, gasp, and flail extremities, eyes watering and bulging, face reddened or purple, tongue protruding maximally until at the seeming last moment of consciousness.
Characteristic whoop follows this paroxysm of cough (the forceful inhalation against a narrowed glottis).
Others: post-tussive emesis, conjunctival hemorrages and petechiae on the upper body
Clinical manifestation
The Convalescent stage
gradual resolution of symptoms over
1 to 2 weeks.
residual cough may persist for
months, especially with physical
stress or respiratory irritants
Clinical manifestation
Young infants may not display the classic
pertussis syndrome: the first signs may be episodes of apnea
unlikely to have the classic whoop
more likely to have CNS damage as a result of
hypoxia
more likely to have secondary bacterial
pneumonia.
Laboratory studies
The diagnosis depends on isolation of B. pertussis Culture of nasopharyngeal swabs
Direct fluorescent antibody staining
Serologic tests are not useful for diagnosis of acute infection.
Leucocytosis (20,000~ 50,000/mm3) with lymphocytosis is characteristic beyond the neonatal age
Imaging study
NOT specific
Segmental lung atelectasis
not unusual during pertussis, especially during the
paroxysmal stage.
Perihilar infiltrates
common and similar to what is seen in viral
pneumonia.
Diagnosis and differential diagnosis
the diagnosis based on recognition of the
pattern of illness is quite accurate
Respiratory viruses such as RSV, parainfluenza
virus, and C. pneumoniae among infants and
M. pneumoniae in older children may produce a
bronchitic illness that is not distinguished
easily from pertussis.
Complications
Major complications:hypoxia, apnea, pneumonia,
seizures, encephalopathy, and malnutrition.
The most frequent complication is pneumonia
caused by B. pertussis itself or resulting from
secondary bacterial infection from S.
pneumoniae, Hib, and S. aureus.
Complications
Other complications
atelectasis, pneumomediastinum,
pneumothorax, or interstitial or
subcutaneous emphysema; epistaxis;
hernias; and retinal and subconjunctival
hemorrhages, otitis media and sinusitis .
Goal of therapy
Limit the number of paroxysms
Observe the severity of cough to provide
assistance when necessary
Maximize nutrition, rest, and recovery
without sequelae
Treatment
Erythromycin given early, eradicates nasopharyngeal carriage
of organisms within 3 to 4 days and ameliorates the effects of the infection.
not effective in the paroxysmal stage.
Azithromycin and clarithromycin
TMP-SMZ
Pertussis-specific immunoglobulin ( effective)
Prevention
Active immunization
acellular pertussis vaccine, given in
combination with the toxoids of tetanus
and diphtheria (DTaP with an efficacy of
70% to 90%;
Compared with older, whole cell pertussis
vaccines, acellular vaccines have fewer
adverse effects and local reactions.
Prevention
Erythromycin and other macrolides
effective in preventing disease in
contacts exposed to pertussis.
Prevention
Close contact <7y should be given a macrolide antibiotic.
should receive a booster dose of DTaP, unless a
booster dose has been given within the preceding
3 years.
Close contact > 7y prophylactic macrolide antibiotic for 10 to 14 days
NOT the vaccine.
Thank you for your attention