Childhood Tuberculosis

Mehretie Kokeb, MD
Asst.Professor of Pediatrics and Child Health
• Epidemiology
• Etiology
• Transmission and Pathogenesis
• C/ms
• Diagnosis
• Management
 Epidemiology
• Worldwide:
Eight million (3million children) new cases each
Three million(1.3million children) deaths year
95% occurs in developing countries with high
HIV/AIDS ,limited Dxtic and therapeutic facilities
One third of the world population is infected with M.TB
• Latent TB infection(LTBI)-occurs after
inhalation of infected droplet nuclei with
M.TB
 This stage is characterized by:
Reactive Tuberculin skin test
Absence of clinical and
Radiological evidence of active TB
 TB(Disease)-refers to apparent S/Sx or radiologic changes
active TB
 Untreated infants with LTBI have 40% liklihood of
developing disease compared with only 5-10% in adults
 The greatest risk of progression occurs during the 1st 2yr after
infection
• Risk for progression to TB from LTBI increases in:
Infants & children below 5yrs of age (especially <2yrs)
Co-infected with HIV
Persons with skin conversion in the past 1-2yr
Immunocompromization(malignancy,drugs,DM,malnutrition)

• Key risk factors for TB:

Strong contact with newly diagnosed smear +ve caase
Age below 5yrs
HIV infection
Severe malnutrition
• The global burden of TB is increasing due to:
o HIV epidemics
o Poverty
o Crowding
o Inefficient TB control programs
o Inadequate health coverage & poor access to health services
 Etiology
• Mycobacterium Tuberculous complex:
 M.TB
 M.Bovis
 M.Africanum
 M.Microti
 M.Canetti
• All belong to the order Actinomycetales and family Mycobacteriaceae
M.TB
o most important cause
o Non-spore forming
o Non-motile
o Obligate aerobe
o Slow-growing
o Grow best at 37-41oC
o Cell wall with high lipid content which gives “acid-fast” staining
properties (resistance to decolorization with acid alcohol)
 Transmission & Pathogenesis
• Incubation period from infection to development of +ve
tuberculin test is 2-6wks
• Transmission is person to person (usually by air borne
mucus droplet nuclei)
• Risk of transmission is dependent on :
• Index case;
Smear positive TB
Extensive upper lobe infiltrate & cavity
Copious production of sputum
Severe & forceful cough
Not treated
• Environment:
Poor ventilation
Overcrowding
Intimacy

• Young children (<7yrs) rarely infect others b/c:

– Sparse bacilli
– Cough is often absent or lacks the tussive force to suspend
infectious particles of correct size
• M.bovis may penetrate the GI mucosa or invade the
lymphatic tissue of oropharynx when large numbers are
ingested
 Immunity
• Cell-mediated immunity develops 2-12wk after infection,along
with tissue hypersensitivity
• After inhalation into the alveolus,bacillus is ingested by
macrophages but may not be killed
• Alveolar macrophages present the antigen to T-lymphocytes,
producing DTH, which together with newly activated
macrophages causes IC killing of bacilli & granuloma formation
• Bacilli multiply, from granulomas, spread to local LNs, &
disseminate to extrathoraxic organs lymphohematogenously.
• The pathologic events in the initial tuberculous infection
depend on the balance between:
Mycobacterial antigen load
Cell-mediated immunity(enhance IC killing)
Tissue hypersensitivity(promotes extracellular killing)

• When Ag load is small & tissue hypersensitivity is high

granuloma formation (from organization of lymphocytes,
macrophages and fibroblasts)
• When both (Ag & sensitivity) are high:

– granuloma is less organized

– Tissue necrosis is incomplete
– Results in formation of caseous material
• When degree of tissue sensitivity is low (infants,low immunity)
– Diffuse reaction
– Infection is not well contained
– Results in local tissue damage and dissemination
• Factors that predispose to serious disease:
– Young age
– Geneticfactors
– Immunosuppresion (AIDS,malnutrition, measles, pertussis,
malignancy,steroids)
 Tuberculin Skin Test (Mantoux Test)
• Id, 0.1ml, 5TU of PPD, volar surface of arms
• T-cells sensitized by prior infection are recruited to the skin;
release lymphokines that induce indurations through local
vasodilatation, edema, fibrin deposition and recruitment of other
inflammatory cells to the area
• Amount of induration is measured 48-72hrs after administration
• Positive test:
> 10mm (immunocompetent)
> 5mm (immunocompromised)
• False positive result:
o Cross-sensitization to Ags of NTM (usually below 10mm)
o BCG
50% never develop the reaction
Reactivity usually wanes in 2-3yrs
If > 10mm , it is taken as +ve
BCG is not a contraindication to PPD test
• False Negative:
Young age(below 3months)
Malnutrition
Immunosupression
Viral infections (measles, mumps, varicella, influenza)
Vaccination with live-viruses (within 6wks)
Overwhelming TB
 Pathogenesis
• The 1o complex of TB includes local infection at the portal of
entry & regional LNs
• Lung is portal of entry in more than 98% of cases
• Bacilli multiply initially within alveoli & alveolar ducts
• Most are killed, some survive within inactivated macrophages
• Macrophages carry the bacilli to regional LNs by lymphatic
vessels
• If lung is portal of entry, hilar LNs are often involved but
paratracheal LNs may be involved(upper lobe)
• Tissue reaction in the lung parenchyma & LNs intensifies over
the next 2-12wks
The parenchymal lesion of 1o complex often heals completely
by fibrosis or calcification
Occasionally may continue to enlarge & result in focal
pneumonitis & pleuritis
If caseation is intense, center of the lesion liquefies & empties
into the bronchus leaving a residual cavity
The infection of regional LNS develop some fibrosis &
encapsulation, but healing is usually incomplete
Viable M.TB can persist for decades within parenchymal or LN
foci
• If hilar & Para tracheal LNs enlarge(as part of host inflammatory
reaction), they may ecroach on a regional LN bronchus
partial obstruction bronchus distal hyperinflation
complete obstruction results in atelectasis
 Inflamed caseos nodes can attach to the bronchial wall & erode
through it, causing endobronchial TB or a fistula tract
 During the development of 1o complex,bacilli are carried to most
tissues of the body through the blood & lymphatic vessels;
common seeding is in the organs of Reticuloendothelial System
 Bacterial replication occurs in organs with conditions that
favor their growth:
Lung apices
Brain
Kidneys
Bones
• Disseminated TB occurs if:
o Circulating number of bacilli is large and
o Host immune response is inadequate
• The time b/n initial infection & clinically apparent disease is variable:
Disseminated & meningeal TB are early manifestations (2-6mo after
infection)
TB LAP & endobronchial TB(3-9mo)
Bones & joints take several years
Renal TB takes decades after infection

 Pulmonary TB that occurs more than a year after 1o infection is usually due
to endogenous regrpwth of bacilli persisting in partially encapsulated lesions
 Common site of reactivation is the apex of upper lobes(oxygen & blood
flow good)
 C/ms
Pulmonary
Extrapulmonary-occurs in 25-30% 0f children
-increases in HIV infection
• Primary Pulmonary Disease
– 70% of lung foci are subpleural & localized pleurisy is common
– All lobar segments of the lung are at equal risk of initial infection
– Enlarged LNs obstruction& compression of regional bronchus
– Usual sequence: hilar LAP focal hyperinflation atelectasis

• Subcarinal LAP may cause esophageal compression & rarely

bronchoesophageal
• May have lobar pneumonia without impressive hilar LAP
• Erosion of a parechymal lesion into blood or lymphatic vessel may result
in dissemination of bacilli & a military pattern (small nodules distributed
on CXR)
 S/Sx of Primary Pulmonary Disease:
• Surprisingly minimal out of proportion of X-ray findings
• More than 50% with moderate –severe CXR findings have no physical
signs
• Infants are more likely to experience S/Sx
• Systemic (fever, night sweat, anorexia, decreased activity)
• Failure to thrive
• If bronchial obstruction, localized wheezes or decreased breath sounds
• In yong children (<3yr), milliary TB may occur
• Dx of primary pulmonary TB:
– Most specific is isolation of M.TB
• Sputum (>7yr) for AFB stainig & culture
• Early morning gastric aspirate (young age)
 Yield is low (25-50% positive with 3cultures)
 Negative culture never exclude pulmonary TB
 If PPD is reactive,abnormal CXR & contact Hx,
adequate evidence
 Progressive primary pulmonary TB
• Occurs when the primary infection is not contained &
produces bronchopneumonia or lobar pneumonia (usually
middle, lower) & cavitations
• HGF, severe cough with sputum, weight, night sweats
• Reduced breath sounds, rales, dullness or egophony over the
cavity
• TST is reactive
 Reactivation pulmonary TB
• Rare in children
• Most frequent site are the original parenchymal focus,LNS or
the apical segments (Simon foci) established during the
hematogenous phase of early infection
• Usually there is little/no LAP & no extathoracic TB b/c of the
established immune response preventing spread
 S/Sx: related with cavitation & endobronchial spread
• Fever, night sweat, malaise, weight loss
• Productive cough, heomptysis
• CXR (commonly)- extensive infiltrates or thick-walled cavities
in the upper lobes
 Upper Respiratory Tract TB
• Rare
• Laryngeal TB (cough, sore throat, hoarseness, dysphagia)
– Most have extensive upper lobe pulmonary disease
– Occasionally primary laryngeal disease with normal CXR
o Middle ear TB
• painless unilateral otorrhea,
• tinnitus,
• decreased hearing,
• perforation of tympanic membrane
• Due to aspiration of infected pulmonary secretion or hematogenous
• Preauricular & cervical LAP may be accompanied with it
 Milliary TB
• Wide spread hematogenous dissemination with infection of
multiple organs
• Diagnosed when > 2organs are involved
• Commonly involved organs are: lungs,liver, spleen & BM
• Choroid tubercles are specific for Dx of milliary TB
• Lesions are of roughly same size as that of a millet seed
• Development of disseminated TB depends on:
– Number of bacilli released from primary focus
– Adequacy of immune response
• S/Sx:
– Fever, weakness,
– malaise, anorexia,
– weight loss, LAP,
– night sweats & Hepatosplenomegally
– Diffuse bilateral pneumonitis & meningitis may be
noted
– Anemia, monocytosis, thrombocytopenia & abnormal
LFT are common
– TST is positive in only 60% of cases
 Liver & BM Bx may be needed for DX
• TODAY?
 Extrapulmonary Tuberculosis (EPTB)
• Every organ can be affected by tuberculosis
• Common forms of extra pulmonary TB in children:

TB Lymphadenitis
• TB of Superficial LNs (Scrofula) is most common form of EPTB
• Tonsilar, anterior cervical, submandibular & supraclavicular nodes are
involved secondary to extension of lesions of upper lung lobes & abdomen
• Inguinal, epitrochlear or axillary are associated with skin or bone TB
Disease is usually unilateral
Initially firm, discrete, non-tender multiple nodes
involved and mass of matted nodes will be formed
Systemic symptoms (except fever) are rare

TST is usually reactive

CXR is normal in 70% of cases
may resolve spontaneously
If untreated
progress to caseation & necrosis (common)
Capsule will be ruptured & spread to adjacent nodes
Rupture usually results in draining sinus tract
• Dx of Tb lymphadenitis is histiologic/bacteriologic
confirmation (excisional Bx)
• Culture yield is 50%

• Pleural Disease
• TB effusion can be localized or generalized
• Usually is a hypersensitivity response to TB antigens
• May result from discharge of bacilli into the pleural space from a
subpleural pul. Focus or caseated LN
• Asymptomatic local pleural effusion is so frequent in primary
TB which is basically a component of the primary complex
• Large effusions occur months-yrs after primary infection
• TB effusion is infrequent in children below 6yrs
• Usually unilateral
• Rare in disseminated TB
• S/Sx:
• Radiologic finding is more extensive than physical findings
• Onset is usually sudden (fever, SOB, chest pain during
inspiration, reduced breath sounds)
• TST is positive in 70-80% of cases
• Scoliosis is one of the complications
• Prognosis is excellent
• Dx;
• pleural fluid & membrane examination
• Pleural tap (Thoracentesis)
-fluid is usually yellow (sometimes tinged with blood)
-Sp.gr is 1.02-1.025
-Glucose is low
-AFB is rarely positive
-culture is positive only in 30%
• Pleural membrane Bx- has high yield of AFB & culture
-granuloma formation can be demonstrated
 Pericardial TB
• Rare
• Most common form of cardiac TB
• Usually arises from direct inoculation or lymphatic drainage from
subcarinal LNs
• S/Sx:
– fever, malaise, wt.loss
– Chest pain (not common in children)
– Pericardial friction rub
– Distant heart sounds
– Pulsus paradoxus
• Pericardicentesis: AFB staining is rarely positive
- culture is positive in 30-70% of cases
• pericardial Bx-culture yield is higher
-granulomas are suggestive
 CNS TB
• Most serious complication of dissemination (fatal if no Rx)
• TB meningitis
• Usually arises from the formation of a metastatic caseous lesions (cerebral
cortex or meninges) that develop during the lymphohematogenous of
primary infection
• Initial lesion enlarges & discharges small no. of bacilli into subarachnoid
space
• The resulting gelatinous exudate infiltrates corticomeningeal vessels
inflammation & obstruction cerebral cortex infarction
 Brain stem is often the site of greatest involvement
 Commonly involved Cranial nerves are III, VI, and VII
• The exudate also interferes with the CSF flow in & out of the ventricle
(at the level of basilar cisterns) Communocating Hydrocephalus
• The combination of vasculitis, infarction, cerebral edema,
and hydrocephalus results in severe damage (gradual,rapid)
• Electrolyte abnormalities (abnormal metabolism, SIADH)
also contributes to the pathogenesis of TB meningitis
• Most common b/n 6mo-4yrs
• C/ms:
– Rapid or slowly progressing
– Mostly slow progression having 3 stages;
Stage I (1-2wks):
 non-specific symptoms (fever, headache,irritability, malaise)
 Focal neurologic deficits are rare
 Stagnation or loss of developmental milestones

Stage II:
 Lethargy
 Nuchal rigidity
 Seizures
 Hypertonia
 Vomiting
 Cranial nerve palsies
 Positive Kernig & Brudzinski sign
 Stage III:
 Coma

 Hemi-or para-plegia

 Hyperetension

 Decerebration

 Deterioration of vital signs

Prognosis is dependent on stage of TB meningitis

 Stage I almost all survive without sequelae
 Stage II 10-20% mortality and sequelae
 Stage III 50% mortality and almost all remain with sequelae
• Common permanent disabilities:
– Blindness
– Deafness
– Paraplegia
– Diabetes Insipides
– Mental retardation
 Prognosis is worse in infants
• Dx: high degree of supicion
 TST is positive in 50%
 CXR is normal in 20-50%
 CSF- WBC(10-500/mm3)
-increased protein (400-5,000mg/dl)
- glucose is usually < 40mg/dl
- AFB & culture yield is dependent on volume of CSF
(if 5-10ml: AFB is +ve in 30%, cultture –50-70%)
 CT/MRI of the brain
• Tubeculoma
• Presents as brain tumor
• In children most common infratentorially (base of the
brain near the cerebellum)
• Lesions are most often singular
• S/Sx:
– headache, seizure, fever
– TST is usually reactive
– CXR is usually normal
• Dx: CT/MRI- discrete lesions with significant surrounding
edema and ring enhancement
 GI/Peritoneal TB
• GI TB
– Oral cavity or pharynx is rare
– Esophageal Tb is rare (may be associated with traceesophageal fistula)
• TB Enteritis
– Caused by hematogenous route or swallowing of bacilli from their own
lungs or ingestion of raw milk (M.bovis)
– Most common sites of involvement; ileum, jejunum & appendix
 C/ms
– Pain, diarrhea/contipation, wt.loss, fever due to shallow ulcer
– Mesentric adenitis is common
– Enlarged nodes may cause intestinal obstruction or erode through the
omentum to cause generalized peritonitis
 Renal TB
• Rare in children (longer incubation period)
• Usually due to lymphohematogenous spread
• Disease is usually unilateral
• Bacilli are often seen from urine in case of milliary TB
• Fistula into the renal pelvis and spread locally to ureters,
prostate, epididymis
• Usually silent early being marked by mic. Hematuria &
sterile pyuria
• As diseases progresses, dysuria, flank/abdominal pain &
gross hematuria develop
• Urine culture is positive in 80-90% of cases
• AFB (large volume of urine) is +ve in 50-70% of cases
• IVP- may show mass lesion,dilatation of proximal ureters,
multiple small filling defects & hydronephrosis
 Bone & Joint TB
• Vertebrae is commonly involved with gibbus deformity &
kyphosis and paralysis
• Other sites: long & flat bones; hip, knee

 Cutaneous TB
 Common with HIV,malnutrition and poor hygiene
 Sites of predilection: face, lower limbs & genitals
o Tubercolous chancre
o Scrofuloderma
o Erythema nodosum
o Tb verruca cutis (warty TB)
o Tuberculids
 Perinatal TB
• Can be congenital
• Commonly acquired postnatal
• C/ms;
– similar to sepsis & other neonatal problems
– May manifest early but common time is 2-3wks of age (RD,
poor feeding, fever, HSM, FTT, abdominal distension)
• Dx and Mx of Perinatal TB
If mother has active TB:
 Screen the newborn (S/Sx, gastric aspirate, CXR)
If positive,antiTB
If negative,INH for 3months
 At 3months, PPD
o if +ve, continue for 6-9mon
o If non-reactive, give BCG and DIC INH
 Isolation of the newborn:
 Seriously sick mother
 Previous Rx for TB
 Suspected drug resistant TB
 Dx of TB in Children

• Acid Fast Staining/culture (sputum, gastric aspirate,LN, fluid) is definitive

 Smear +ve TB:
The criteria are:
• two or more initial sputum smear examinations positive for acid fast
bacilli; or
• one sputum smear examination positive for acidfast bacilli plus
• CXR abnormalities consistent with active pulmonary TB, as determined
by a clinician; or
• one sputum smear examination positive for acid fast bacilli plus sputum
culture positive for M. tuberculosis.
 Smear -ve TB:
• Pulmonary TB, sputum smear negative
A case of pulmonary TB that does not meet the definition for smear positive
pulmonary TB; Such cases include :
 cases without smear results, which should be exceptional in adults but
relatively more frequent in children.
 In keeping with good clinical and public health practice,
diagnostic criteria for sputum smear negative pulmonary TB
should include:
• at least three sputum specimens negative for acid fast bacilli;
and
• radiological abnormalities consistent with active pulmonary
TB; and
• no response to a course of broad spectrum antibiotics; and
• decision by a clinician to treat with a full course of antiTB
chemotherapy.
• If AFB is negative, Dx is based on:
Contact with patient(adult) with pulmonary TB
S/Sx suggestive of TB
X-Ray finding consistent with TB
Positive TST
• If 3 are fullfilled, TB is likely Dx
• If severe malnutrition or immunosupresion, 2 criteria are enough
 Mx of Childhood TB
• Principles :
 Chemotherapy/AntiTB drugs
 Nutritional rehabilitation
 Screening of the family(index case, other contacts)
 Follow up (Adherence,response, drug side effect)
  AntiTB Drugs
• The main objectives of antiTB treatment are to:
1. cure the patient (by rapidly eliminating most of the bacilli);
2. prevent death from active TB or its late effects;
3. prevent relapse of TB (by eliminating the dormant bacilli);
4. prevent the development of drug resistance (by using a combination of
drugs);
5. decrease TB transmission to others.
 Category I
o newly Dxed smear positive

o Smear –ve extensive pulmonary TB

o Severe extrapulmonary (meningitis, pericarditis, adrenal,laryngeal)

 HRZS/2months-------HR/4months
Category II
o Rx failure
o Defaulter
o Relapse
 2HRZES/1HRZE -----5HRE
Category III
o Smear –ve less severe form of pulmonary
o Less severe form of extrapulmonary TB
 2HRZ -----4HR or 6HE
Category IV
o Chronic (i.e treated as category II but failed)
Second line antiTB drugs for treatment of MDRTBin children

• Ethionamide or prothionamide
• Fluoroquinolones
– Ofloxacin
– Levofloxacin
– Moxifloxacin
– Gatifloxacin
– Ciprofloxacin
• Aminoglycosides
– Kanamycin
– Amikacin
– Capreomycin
• Cycloserine or terizidone

• paraAminosalicylic acid
 Steroids in TB
Meningitis
Pericarditis
Adrenal insufficiency
Airway obstruction (LAP, laryngeal TB)
Bilateral pleural effusion with respiratory problem
• Indications for prescribing steroids in renal TB:
– Severe bladder symptoms
– Tubular structure involvement (eg, ureter, fallopian
tubes, spermatic cord)