Transcript Tuberculin skin test

Pediatrics
Tuberculosis in children
Zhi-min Chen
Dept. Pediatric Pulmonology，Children’s Hospital
Email: [email protected]
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 dust
By alimentary tract
raw milk
contaminated food
By 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 BW35
Environmental 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
Pediatrics
Primary Pulmonary Tuberculosis
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
Chloride
<40mg/dl，or CSF/blood <50%
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 Intube (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
+++
: >=20mm strong-positive
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
Tuberculosis control programs
BCG (Bacillus Calmette-Guerin)
involve case finding and treatment.
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
Recommended treatment regime
Pediatrics
Pertussis and
Pertussis 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 wellappearing 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.
Q&A
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