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Classified into:
a. M. tuberculosis complex (MTBC)
• M. tuberculosis: causes disease only in humans
Tuberculosis • M. bovis: causes disease in cattle, humans, other
mammals
• M. africanum
• M. microti
Ma. Anna P. Bañez, M.D. b. Nontuberculous mycobacteria (MOTT: Mycobacteria
Department of Child Health Other Than Tuberculosis)
• M. avium‐intracellulare
• M. kansasii
• Other species
Epidemiology Epidemiology
• WHO estimates that one third of the world’s • In 1998, Philippines ranked 2nd in Western
population: 2 billion are infected with M. tuberculosis pacific region next to China
• Infection rates highest in Africa, Asia, Latin America • DOH data:
• Contributory Factors:
– Impact of HIV epidemics
1995: 5th leading cause of mortality
– Population migration (39.4/100,000)
– Increasing poverty 1997: 5th leading cause of morbidity
– Social upheaval (219/100,00)
– Crowded living conditions • PPS data:
– Inadequate healthcare 1998: PTB 10th leading causes of morbidity
– Inefficient TB control programs
Extrapulmo TB 8th leading cause of mortality
Transmission of M. tuberculosis Peculiarities of Childhood TB
• Spread by droplet nuclei
• Expelled when person with infectious TB • Greater the risk of developing TB disease
coughs, sneezes, speaks, or sings • Greater risk of extrapulmonary disease e.g.
• Close contacts at highest risk of becoming miliary TB and TB meningitis
infected • Rarely develop cavitary lesions
• Transmission occurs from person with
infectious TB disease (not latent TB infection) • Lower bacillary load and bacteriologic
confirmation more difficult
• Tolerate higher doses of anti‐TB drugs per
kilogram
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TB exposure
TB TB
INH x 3 mos,
infection disease Primary
then if PPD
chemoprophylaxis
• 5 ‐ 15 % during the first 10 years following (+) + 6 mos
primary infection TB
infection
• Infants – 50% within 3‐9 months
Secondary INH x 9
• 1‐5 yr olds – 25% within 1‐2 years
chemoprophylaxis mos
• Adolescents – 15%
TB
disease
Clinical Manifestations Clinical Manifestations
• Cough / wheezing > 2 weeks • Signs and symptoms are nonspecific
• Fever > 2 weeks • ~ One‐half of children with TB disease do not
• Painless cervical and / or other have signs and symptoms
lymphadenopathy
• Thus, the need for several criteria to be met to
• Poor weight gain
prevent over diagnosis
• Failure to make a quick return to health after
an infection e.g. measles, tonsillitis or pertussis • Signs and symptoms very helpful in the case of
• Failure to respond to appropriate antibiotics as extrapulmonary TB
in AOM or pneumonia
Clinical Forms of TB Clinical Forms of TB
Pulmonary / Endothoracic Tuberculosis
Asymptomatic (Latent) TB infection (LTBI)
Pulmonary / Endothoracic Tuberculosis
Primary (Childhood) TB Progressive Primary TB
• The younger the patient, the greater risk of progressive • Primary focus develops a large caseous center, more
disease until age 5 years old cough, malaise & weight loss; cavitation on chest X‐
• Primary Complex: primary focus, lymphangitis & regional ray
lymphadenitis Endobronchial TB
• Most common signs and symptoms: non‐productive • Enlarged peribronchial LN’s, compression :
cough, mild dyspnea, cervical lymphadenopathies, failure
to gain weight – Sudden death by asphyxia
Pleurisy with Effusion – Obstructive hyperaeration of a lobar segment,
• Early complication of primary infection, localized / lobe, entire lung
generalized, unilateral or bilateral – Atelectasis specially right middle lobe, right upper
• Abrupt onset like bacterial pneumonia: fever, chest pain, lobe; maybe mistaken for asthma
short breath
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Clinical Forms of TB
Pulmonary / Endothoracic Tuberculosis Clinical Forms of TB
Miliary Tuberculosis Pulmonary / Endothoracic Tuberculosis
• A form of disseminated TB due to massive invasion of Chronic Pulmonary TB
blood stream by TB bacilli • Adult TB
• From discharge of a caseous LN into a blood vessel • With apical or infraclavicular infiltrate often with
• Most common during 1st 2– 6 months of infection cavitation, no hilar adenopathy
especially in infants • Most common in adolescent
• Acute / gravely ill; usually insidious, with low fever, Tuberculoma
weight loss, anorexia, generalized lymphadenopathy, • Can form with small caseous or granulomatous
hepatosplenomegaly develops, high fever, dyspnea, tissue surrounded by concentric fibrous tissue
cough, rales / wheezes, alveolar‐air block syndrome,
respiratory distress, hypoxia, pneumothorax sometimes with calcification
• CXR: millet seed density all over the lung fields • Often confused with cancer
• Meningitis or peritonitis in 20‐40% cases
Clinical Forms of TB Clinical Forms of TB
Pulmonary / Endothoracic Tuberculosis Extrapulmonary Tuberculosis:
Pericardial Tuberculosis Tuberculosis of the Cervical LN (Scrofula)
• Secondary to direct spread from mediastinal glands by • Most common of extrapulmonary form in children
direct invasions or lymphatic spread • Unilateral or bilateral
• Uncommon, 0.4% of untreated tuberculous infection in • Other sites: tonsillar, submandibular,
supraclavicular
children • Painless, enlarged, initially firm and movable
• Nonspecific symptoms: low fever, malaise, weight loss, become adherent to each other and anchored to
chest pain, friction rub, distant heart sounds surrounding tissues
• Pericardiocentesis: sanguinous with lymphocytic • May resolve or progress to caseation and necrosis,
predominance rupture and form draining sinus tract
• (‐) AFB, (+) pericardial fluid /biopsy culture, (+) (Scrofuloderma)
granulomas • Tuberculin test usually reactive, CXR normal in 70%
of cases
Clinical Forms of TB Clinical Forms of TB
Extrapulmonary Tuberculosis: Extrapulmonary Tuberculosis:
Tuberculosis of the CNS: Tuberculous meningitis Tuberculosis of the CNS: Tuberculous meningitis
• Most common type of TB of the CNS which may develop 3‐6 mos 3 Stages:
after an initial infection I. Early stages of irritability, behavioral changes like apathy, vomiting,
headache for 1‐2 wks.
• From a metastatic caseous lesion in the cerebral cortex / II. Pressure or convulsive seizure, meningeal signs, lethargy, neck
meninges following lymphohematogenous dissemination of stiffness, seizure, cranial nerve palsies
primary infection III. Paralytic or Terminal Stage – posturing, profound neurologic and
• Accompany miliary TB in 50% 0f cases sensorial changes with deterioration of vital signs, eventual death.
In infants, encephalitic manifestations predominate
• Brainstem – most common site, frequent dysfunction of CN 3,6, 7 • TT nonreactive in 50% of cases
• Exudate interferes with CSF flow, communicating hydrocephalus • 20‐30% with normal CXR
• (+) vasculitis, infarction, cerebral edema and hydrocephalus • CSF Analysis: lymphocyte predominance, decreased sugar,
results in severe damage markedly increased protein, AFB (+) 30%, (+) culture 50‐70%
• Most common between 6 mo‐4yr • CT Scan: basal enhancement, communicating hydrocephalus with
cerebral edema, focal ischemia
• Signs and symptoms progress slowly x weeks
Tuberculoma
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Clinical Forms of TB Clinical Forms of TB
Extrapulmonary Tuberculosis: Extrapulmonary Tuberculosis:
Tuberculosis of the Bone and Joints: Tuberculosis of the Skin:
• 1 ‐ 6% of children with untreated primary infection • Scrofuloderma
• Occurs 1 – 3 yrs after the initial infection • Erythema nodosum
• Most common sites: weight bearing bones and joint
especially vertebra causing TB of spine (Pott’s disease) Renal TB:
• Destruction of vertebrae: gibbus deformity & kyphosis • Uncommon, up to 15 – 20yrs after primary infection
Gastrointestinal TB: • Suspected if with destructive pulmonary TB w/ persistent
1. TB peritonitis due to a rupture of caseous abdominal LN painless sterile pyuria w/ associated albuminuria and
– Presents as fever, abdominal pain, weight loss, hematuria
anorexia and ascites
2. Hepatobiliary TB Others:
– Two major forms: 1. Ocular TB
a. Hard nodular liver, fever and weight loss like CA 2. Genital TB
b. Chronic recurrent jaundice 3. TB of the middle ear
Perinatal Disease
• Symptoms by 2nd‐3rd wk of life as respiratory
Tuberculosis: Classification
distress, fever, hepatosplenomegaly, poor feeding,
lethargy or irritability, lymphadenopathy, • TB exposure ‐ positive exposure
abdominal distention, failure to thrive Negative Mantoux test
• CXR: hilar and mediastinal lymphadenopathy and No signs and symptoms
lung infiltrates, miliary pattern Negative chest X‐ ray
• Signs and symptoms: similar to bacterial sepsis, • TB infection ‐ with or without exposure
other congenital infections: Syphilis,
Toxoplasmosis, CMV Positive Mantoux, but with
• Important clue: maternal or family history of TB Negative signs and symptoms and
• Tuberculin test initially negative, become (+) in 1‐3 negative chest X‐ray
mos
Tuberculosis: Classification Diagnosis: Chest X‐Ray
• TB disease ‐ has 3 or more of the following: • Primary complex (Ghon): primary focus,
• Exposure lymphangitis, lymphadenitis
• Signs and symptoms suggestive of TB • Rigor et al (1991): retrocardiac lymph nodes
• Chest X‐ray suggestive of TB (70%), hilar adenopathy with infiltrates (20%)
• Positive Mantoux • Problem: low specificity
• Laboratory findings suggestive of TB
• TB inactive – (+/‐) previous chemotherapy • May remain visible 6‐12 months or longer
• (+)radiographic evidence of calcified TB following treatment
• (+) Mantoux tuberculin test • Calcification may appear within 6 months
• (‐) signs and symptoms of TB following infection
• (‐) smear / culture for M.TB
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Diagnosis: Tuberculin Skin Test Tuberculin test
• Delayed‐type hypersensitivity Mantoux test:
• Appears 3 weeks to 3 months (usually 3‐6 weeks) •0.1 ml of solution
after an infection containing or equivalent
• Tuberculin reactivity following BCG wanes over time to 1g (5 TU PPD‐S) read at
• Unlikely to persist beyond 10 years 48‐72 hours using
ballpoint pen method
•Measure only induration
•Record reaction in
millimeters
Definitions of Positive Tubercullin Skin Test (TST)
Results In Infants, Children, and Adolescents1 Factors that Decrease Skin Test
Induration =5 mm
Children in close contact with known or suspected contagious people with tuberculosis disease.
Children suspected to have tuberculosis disease:
Reaction
‐Findings on chest radiograph consistent with active or previously tuberculosis disease
‐Clinical evidence of tuberculosis disease2
• Very young age
Children receiving immunosuppressive therapy3 or with immunosuppressive conditions, including HIV infection.
Induration = 10 mm
• Malnutrition
Children at increased risk of disseminated tuberculosis disease: • Immunosuppression by disease or drugs
‐Children younger than 4 years of age
‐Children with other medical conditions, including Hodgkin disease, lymphoma, diabetes mellitus, chronic renal
• Viral infections (measles, mumps, Varicella, influenzae)
failure, or malnutrition (see Table 3.70, p 683)
Children with increased exposure to tuberculosis disease:
• Vaccination with live‐virus vaccines
‐Children born in high‐prevalence regions of the world • Overwhelming TB
‐Children frequently exposed to adults who are HIV infected, homeless, users of illicit drugs, residents of nursing
homes, incarcerated or institutionalized, or migrant farm workers – Up to 50% with TB meningitis & disseminated
‐Children who travel to high‐prevalence regions of the world
Induration = 15 mm disease
Children 4 years of age or older without any risk factors
HIV indicates human immunodeficiency virus.
1These definitions apply regardless of previous Bacille Calmette‐Guerin (BCG) immunization erythema at TST site docs not indicate a positive test result
~10% immunocompetent children with TB disease have
Tests should be read at 48 to 72 hours after placement.
2Evidence by physical examination or laboratory assessment that would include tuberculosis in the working differential diagnosis (eg, meningitis). false negative TT
3Including immunosuppressive doses of corticosteroids (see Corticosteroids, p 692).
Other Diagnostic Tests Other Diagnostic Tests
AFB smear
• 3 early morning specimens Histologic Examination
• Sputum / gastric aspirate /other body fluids • Classic pathologic lesion: caseating granulomas
• Offers only a presumptive diagnosis; represents Newer Diagnostic Tests
either M. tuberculosis or other non‐tuberculous • Antibody detection
mycobacterium • Antigen detection
Mycobacterial Culture
• DNA probes
• Low sensitivity in children
• Not necessary if epidemiologic, tuberculin test • PCR
and x‐ray compatible with disease
• Indicated if DRTB is suspected
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Recommended Anti‐TB drugs
• Isoniazid (H) ‐ 5 to 10 mg/kg ( max 300 mg)
• Rifampicin (R) ‐ 10 to 15 mg/kg (max 600 mg)
• Pyrazinamide (Z) ‐ 15 to 30 mg/kg (max 2 gm)
• Ethambutol (E) ‐ 15 to 25 mg/kg (max 2.5 gm)
• Streptomycin (S) ‐ 20 to 30 mg/kg (max 1 gm)
Treatment Treatment
• For AFB (+) cases – monthly bacteriologic Suspect drug resistance when the following are
evaluation till negative (85% are negative present:
after 2 months, persistently + smear suggests • Previous intake of anti‐TB drugs > 1 month or
drug resistance) previous inadequate therapy
• Observe for drug adverse effects – jaundice, • Contact with drug‐resistant adult case
hepatomegaly • Residence in areas with high primary Isoniazid
• No need for liver function monitoring unless resistance (>10%)
symptoms of drug‐induced hepatitis are • Failure to improve despite compliance with
present therapy for at least 2 months
• HIV / AIDS
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Treatment
• When resistance is suspected use an initial
regimen of 4 drugs with Ethambutol or • BCG
Streptomycin as the 4th drug – Recent meta‐analysis of published BCG
• Treatment of extrapulmonary TB similar to vaccination trials suggested that BCG is 50%
PTB but use longer course (up to 12 months) effective in preventing pulmonary TB in adults and
children, and 50‐80% protective against
for TB meningitis, skeletal or joint TB and in
disseminated and meningeal TB
immunocompromised patients
• For all patients, contact assessment is
essential The End
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