Childhood Tuberculosis

By Dr Etabezahu
Pediatrcian
Jun 2024
 MICROBIOLOGY
• M. tuberculosis belongs to the genus
Mycobacterium includes more than 50 other
species, often collectively referred to as non
tuberculous mycobacteria.
• TB is defined as a disease caused by members
of the M. tuberculosis complex, which
includes the tubercle bacillus (M.
tuberculosis), M. bovis, M. africanum, M.
microti and M. canetti
 Epidemiology
• one third of the world’s population is infected
with TB
• In countries worldwide, the reported
percentage of all TB cases occurring in
children varies from 3% - 25%.
 Epidemiology
• Untreated infants with LTBI have up to a 40%
likelihood of developing tuberculosis, adult
lifetime rates of 5–10%.
• The greatest risk (≈50%) occurs in the 1st 2 yr
after infection.
 EPIDEMIOLOGY

• Pulmonary TB (PTB): accounts for 85 % of all TB cases

Smear-positive PTB: 75 – 80% of PTB cases, worldwide
Smear-negative PTB: 20 – 25% of PTB cases, worldwide
• Extra-pulmonary TB (EPTB): represents 15% of all TB
cases in the world

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 Tb / HIV
• HIV worsened the TB situation by:
– Accelerating the progression from primary
infection to disease;
– Increasing the reactivation rate of TB;
– Increasing the re-infection rate.
• 50 to 60% of HIV infected people will develop
TB disease in their lifetime in contrast with HIV
negative persons, whose lifetime risk is only
10%.
 Risk factors
• Extremes of age: Children< 4 yrs, especially infants, and
elderly
• Poverty
• Malnutrition, including vitamin D deficiency
• Intercurrent infections (e.g.. measles)
• Immune suppression
• Recent infection: in the first 1 - 2 years after infection
• History of inadequate drug treatment
• Diabetes mellitus & End stage renal disease
• Toxic factors (e.g. alcohol and smoking)
• Low Herd immunity
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 Transmission
• Inhalation of contaminated respiratory droplets
• Prolonged close contact
• Incubation period 2-6 weeks
• Transmission increases in: Smear positive, an extensive
upper lobe infiltrate or cavity, copious production of
thin sputum, and severe and forceful cough.
Environmental factors, especially poor air circulation.
• Most adults no longer transmit the organism within
several days to 2 weeks after beginning adequate
chemotherapy, but some patients remain infectious for
many weeks.
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Tuberculous bacillus in lungs leads to one of
four possible outcomes
– Immediate clearance of the organism
– latent infection
– Rapidly progressive disease (or primary disease)
– Active disease many years after the infection
(reactivation disease)

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 Time of presentation to disease

• Disseminated and meningeal TB = 2–6 mo of

acquisition.
• lymph node or endobronchial TB within 3–9 mo.
• bones and joints take several years
• renal TB - decades after infection.

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 Clinical manifestations and diagnosis
• Infants:
– cough and mild dyspnea are the most common
symptoms.
– Fever
– night sweats
– anorexia
– decreased activity
– localized wheezing or decreased breath sounds

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 Primary pulmonary disease
• The primary complex includes the parynchymal
pulmonary focus (70% sub pleural) + the regional LN
• The hall mark in the lung is the relatively large size of
the regional LAP
• The usual sequence is hilar LAP →focal hyperinflation
→atelectasis:(collapse consolidation or segmental TB)
• Rarely, inflammed caseous LNS attach to
endobronchial wall-erosion through the wall
→endobronchial TB (fistula tract)
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Progressive primary pulmonary disease
• Rare and Serious complication
• Primary focus expansion→ large caseous
center→ liquefaction → cavity (large number of
bacilli)
• High fever, severe cough with sputum
production, weight loss, and night sweats are
common.
• Physical signs include diminished breath
sounds, rales, and dullness or egophony over
the cavity
 Reactivation tuberculosis
• Rare in childhood
• Reactivation TB results when the persistent bacteria in a host
suddenly proliferate.
• Involves the original parenchymal focus, lymph nodes, or the apical
seedings (Simon foci) established during the hematogenous phase of
the early infection.
• Occurs at the lung apices, and disseminated disease is unusual,
unless the host is severely immunosuppressed.

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 Reactivation tuberculosis

• cxr: extensive infiltrates or thick-walled cavities

in the upper lobes

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Immunosuppressive conditions associated
with reactivation TB
• Diminution in CMI associated with old
age,measeles
• Corticosteroid use
• Malignant lymphoma
• HIV infection and AIDS
• End-stage renal disease
• Diabetes mellitus

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 Pleural effusion
• It is infrequent in children <6 yr of age and rare in children <2 yr of age
• Discharge of bacilli into pleural space (pulmonary focus or caseated LN)
• Pleural fluid is usually yellow and only occasionally tinged with blood, specific gravity
1.012–1.025, protein 2–4 g/dL, and glucose may be low, (20–40 mg/dL).
• white blood cells several hundred to several thousand per cubic millimeter with an early
predominance of polymorphonuclear cells followed by a high percentage of lymphocytes.
• Acid-fast smears of the pleural fluid are rarely positive.
• Cultures of the fluid are positive in only <30% of cases.
• Biopsy of the pleural membrane is more likely to yield a positive acid-fast stain or
culture,
• The prognosis is excellent, but radiographic resolution often takes months.

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 Pericardial disease
• Rare ( 0.5-4%) of cases TB
• From Direct invasion or lymphatic drainage from subcarinal LNS
• low-grade fever, malaise, and weight loss
• Chest pain (unusual in children)
• Pericardial friction rub
• Distant heart sound
• The pericardial fluid is typically serofibrinous or hemorrhagic.
• AFB rarely positive, but cultures are positive in 30–70% of cases.
• The culture yield from pericardial biopsy may be higher.
• Complication- constrictive pericarditis

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 Disseminated disease
(lymphohematogenous)
• If the bacterial growth continues to remain unchecked, the bacilli
may spread hematogenously to produce disseminated TB.
• Miliary TB describes a disseminated disease with lesions
resembling millet seeds
• Multiple organ involvement is common
• Meningitis occurs only late in the course of the disease.

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 Milliary tuberculosis
• Milliary tuberculosis (TB) refers to clinical disease
resulting from the uncontrolled hematogenous
dissemination MTB
•most common in infants, young children and
immunosuppressed.
•Lesions are often larger and more numerous in
the lungs, spleen, liver, and bone marrow than
other tissues.

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 Milliary tuberculosis
• Signs or symptoms of meningitis or peritonitis
are found in 20–40% of patients with
advanced disease.
• corticosteroids hasten symptomatic relief.
 Lymph node disease
• most common form of extrapulmonary tuberculosis in children
• anterior cervical, submandibular, and supraclavicula
• Scrufula (TB of the superficial LNS)
• They are firm but not hard, discrete, nontender, fixed to
underlying or overlying tissue and most often unilateral; later
matted nodes
• onset of illness is occasionally more acute, with rapid
enlargement of lymph nodes, high fever, tenderness, and
fluctuance
• fine needle aspiration for culture, stain, and histology or
excisional biopsy positive≈ 50% of cases.
• chest radiograph is normal in 70% of cases
• may resolve, Rupture of the node→ draining sinus tract
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 Lymph node disease
• Differentials
– pyogenic infection.
– tumor, branchial cleft cyst,
– cystic hygroma, and
– nontuberculous mycobacteria (NTM)
– brucellosis,
– toxoplasmosis,
 CNS disease
• Most serious Complication and fatal without appropriate
treatment
• metastatic caseous lesion in the cerebral cortex or meninges
→increases in size → discharges small numbers of tubercle
bacilli into the subarachnoid space→infiltrates the
corticomeningeal blood vessels →inflammation, obstruction,
and subsequent infarction of cerebral cortex
• Commonest site is brainstem and is associated with cranial
nerves III, VI, and VII involvement.
• The exudate also interferes with CSF in & out flow→
communicative hydrocephalus.
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 TB Meningitis
• complicates about 0.3% tuberculosis infections
in children
• Common 6 mo to 4 yrs.
• occurs as part of milliary tuberculosis or many
years after the infection, when rupture of 1 or
more of the subependymal tubercles discharges
tubercle bacilli into the subarachnoid space
• Rapid progression more often in infants and
young children
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 TB Meningitis cont’d
• 20–50% of children have a normal chest radiograph.
• CSF analysis : 10 to 500 white cells/mm 3 , Polymorphonuclear
present initially, but lymphocytes predominate later, glucose is
typically <40 mg/dL but rarely <20 mg/dL, protein level is
elevated and may be markedly high (400–5,000 mg/dL)
secondary to hydrocephalus and spinal block,
• AFB ≈ 30 % positivity & culture 50-70%
• CT or MRI of the brain may show basilar enhancement and
communicating hydrocephalus with signs of cerebral edema
or early focal ischemia and cortical or thalamic silent
tuberculomas

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 Staging of TB Meningitis
• 1st stage:
▫ lasts 1–2 wk, is characterized by nonspecific symptoms,
such as fever, headache, irritability, drowsiness, and malaise.
▫ excellent outcome
• 2nd stage:
▫ The most common features are lethargy, nuchal rigidity,
seizures, positive Kernig or Brudzinski signs, hypertonia,
vomiting, cranial nerve palsies, and other focal neurologic
signs.
▫ correlates with the development of hydrocephalus,
increased intracranial pressure, and vasculitis.

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• 3rd stage:
– coma, hemiplegia or paraplegia, hypertension,
decerebrate posturing, deterioration of vital
signs, and eventually death.
– permanent disabilities, including blindness,
deafness, paraplegia, diabetes insipidus, or mental
retardation
– Poor prognosis
 Tuberculoma
• tumor-like mass resulting from aggregation of
caseous tubercles
• account for up to 40% of brain tumors
• in children they are often infratentorial, located
at the base of the brain near the cerebellum
• most often singular
• headache, fever, and convulsions

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 Tuberculoma
• CT or MRI: discrete lesions and surrounding
edema, Contrast medium enhancement may
result in a ringlike lesion
 Bone and joint disease

• The most common site is the vertebra

(tuberculos spondilitis)
• progresses to Pott disease, in which destruction
of the vertebral bodies leads to gibbus
deformity and kyphosis
• more likely to occur in children than in adults
• late complication of tuberculosis

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 Abdominal and GI disease
• TB peritonitis
– Localized peritonitis:direct extension from an
abdminal LN, intestinal focus,GU TB
– TB enteritis:hematogenous dissimination or
swallowing of tubercle bacilli from pts own lung

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 GU disease
• Rare in children:after several years or longer
• During lymphohematogenous spread
• Sterile pyuria and microscopic hematuria( early stage)
• Dysuria, flank pain,gross hematuria(late stage)
• Urine cultures for M. tuberculosis are positive in 80–
90% of cases
• The fallopian tubes are most often involved (90–100%
of cases) followed by the endometrium (50%)
• In males epididymitis or orchitis
• Complications: hydronephrosis or ureteral strictures.

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 Disease in HIV infected children
• Rate of TB disease is 30x
• Diagnosis difficult: due to absent skin test, similar
clinical conditions
• More severe
• Progressive
• Likely to occur in extrapulmonary sites
• CXR: lobar disease and lung cavitation are more
common
• Rates of drug-resistant Tb is higher
• High mortality
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 Impact of HIV/AIDS on TB

• HIV increases susceptibility to infection with

M. tuberculosis, the risk of progression to TB
disease, and the incidence and prevalence of
TB.
• increases the likelihood of re-infections and
relapses of TB.
 Impact of TB on HIV/AIDS

• TB increases HIV replication, which leads to increased

viral load.
• more rapid progression of HIV disease.
• TB increases occurrence of other OIs.
• The management of TB and HIV co-infected individual
is challenging because of:
▫ Pill burden,
▫ Increase adverse effect,
▫ Drug to drug interaction and IRIS
 Perinatal disease
• Symptoms may occur at birth but more common by the
second or 3rd week of life
• Resp distress, Fever, HSM, Poor feeding, Lethargy or
irritability
• LAP, Abdominal distension, Failure to thrive, EAR discharge,
Skin lesions
• CXR: milliary pattern
• Generalized lymphadenopathy and meningitis occur in 30–
50% of patients
• most important clue for rapid diagnosis of congenital
tuberculosis is a maternal or family history of tuberculosis.
 Pregnancy and the Newborn
• risk for prematurity, fetal growth retardation,
low birthweight, and perinatal mortality.
• Congenital tuberculosis is rare, and usually
occurs from a lesion in the placenta through
the umbilical vein then reach the fetal liver
and infect many organs.
• For the neonate it is postnatal airborne
transmission.

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 Diagnosis of TB in children

• The diagnosis of TB in children relies on careful and

thorough assessment of all the evidence derived
from a careful history, clinical examination and
relevant investigations, e.g. TST, chest X-ray
(CXR),gene xpert and sputum smear microscopy.
. microscopy for children with suspected pulmonary
TB who are old enough to produce a sputum
• Recommended approach to diagnose TB in children
• 1. Careful history (including history of TB contact and
symptoms consistent with TB)
• 2. Clinical examination (including growth assessment)
• 3. Tuberculin skin testing
• 4. Bacteriological confirmation whenever possible
• 5. Investigations relevant for suspected pulmonary TB
and suspected extrapulmonary TB
• 6. HIV testing (in high HIV prevalence areas)
 Key risk factors for TB

• The key risk factors are:

– household contact with a newly diagnosed smear-
positive case
– age less than 5 years
– HIV infection
– severe malnutrition
• The presentation in infants may be more
acute,resembling acute severe pneumonia
and should be suspected when there is a poor
response to antibiotics.
 Key features suggestive of TB

• The presence of three or more of the

following should strongly suggest a diagnosis
of TB:
– chronic symptoms suggestive of TB
– physical signs highly of suggestive of TB
– a positive tuberculin skin test
– chest X-ray suggestive of TB.
• Recommended approach to diagnose TB in
children
• 1. Careful history (including history of TB
contact and symptoms consistent with TB)
• a. Contact
• Close contact is defined as living in the same
household as or frequent contact with a
source case (e.g. the child’s caregiver) with
sputum smear-positive pulmonary TB.
The following points concerning contact are of importance for
diagnosing TB in children

• All children who are symptomatic, who have been in close

contact with a smear-positive TB case, must be screened for
TB
• When any child (aged less than 15 years) is diagnosed with TB,
an effort should be made to detect the source case (usually an
adult with sputum smear-positive pulmonary TB) and any
other undiagnosed cases in the household.
• If a child presents with infectious TB, child contacts must be
sought and screened, as for any smear-positive source case.
• Children should be regarded as infectious if they have sputum
smear-positive pulmonary TB or cavitary TB on CXR.
 Symptoms

2. Chronic cough
▫ An unremitting cough that is not improving and has been
present for more than 2-3 wks.
3. Fever
▫ Body temperature of >38 °C for 14 days, after common
causes such as malaria or pneumonia have been excluded.
4. Weight loss or failure to thrive .
• In addition to asking about weight loss or failure to
thrive, it is necessary to look at the child's growth
chart.
• Clinical examination (including growth assessment)
• There are no specific features on clinical
examination that can confirm that the presenting
illness is due to pulmonary TB.
• a. physical signs highly suggestive of
extrapulmonary TB:
▫ gibbus, especially of recent onset (resulting from
vertebral TB)
▫ non-painful enlarged cervical lymphadenopathy with
fistula formation
• b. physical signs requiring investigation to exclude
extrapulmonary TB:
▫ meningitis not responding to antibiotic treatment, with
a subacute onset or raised intracranial pressure
▫ pleural effusion
▫ pericardial effusion
▫ distended abdomen with ascites
▫ non-painful enlarged lymph nodes without fistula
formation
▫ non-painful enlarged joint
 Bacteriological confermation
• Bacteriological confirmation is especially
important for children who have:
– suspected drug-resistant TB
– HIV infection
– complicated or severe cases of disease
– an uncertain diagnosis.
 Expectoration

• Sputum should always be obtained in adults

and older children (10 years of age or older)
who are pulmonary TB suspects.
• Among younger children, especially children
under 5 years of age,sputum is difficult to
obtain and most children are sputum smear-
negative.
 Gastric aspiration
• Gastric aspiration using a nasogastric feeding
tube can be performed in young children who
are unable or unwilling to expectorate
sputum.
• Gastric aspirates should be sent for smear
microscopy and mycobacterial culture, gene
xpert
• A gastric aspirate should be obtained on each
of three consecutive mornings.
 Pulmonary TB, sputum smear-positive

• The criteria are:

▫ two or more initial sputum smear examinations positive
for acid-fast bacilli; or
▫ one sputum smear examination positive for acid-fast
bacilli plus CXR abnormalities consistent with active
pulmonary TB; or
▫ one sputum smear examination positive for acid-fast
bacilli plus sputum culture positive for M.tuberculosis.
▫ Children with smear-positive disease are more likely to
be adolescent or of any age with severe intrathoracic
disease.
 Pulmonary TB, sputum smear-negative

• 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
anti-TB chemotherapy.
 Extrapulmonary TB

• Children with only extrapulmonary TB should

be classified under this case definition.
Children who have both pulmonary and
extrapulmonary TB should be classified under
the case definition of pulmonary TB.
 Anti-TB treatment in children

• The main objectives of anti-TB treatment are to:

1. cure the patient of TB (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.
 Case definition
New case (N):
• A patient who never had treatment for TB, or has been on previous anti-TB treatment for less than four
weeks.
Relapse (R):
• A patient declared cured or treatment completed of any form of TB in the past, but who reports back to the
health service and is now found to be AFB smear-positive or culture positive
Treatment Failure (F):
• A patient who, while on treatment, is smear-positive at the end of the fifth month or later, after commencing.
Treatment failure also includes a patient who was initially sputum smear-negative but who becomes smear-
positive during treatment.
Return after default (D):
• A patient previously recorded as defaulted from treatment and returns to the health facility with smear-
positive sputum.
Transfer out (T):
• A patient who started treatment in one treatment unit and is transferred to another treatment unit to
continue treatment.
Chronic (C):
• A TB patient who remains smear-positive after completing a re-treatment regimen.
Other (O): A patient who does not fit in any of the above mentioned categories (e.g., a PTB smear negative who
returns after treatment interruption).
 Treatment categories
TB TB cases Regimena
diagnostic
category Intensive Continuation
phase phase

I New smear-positive pulmonary TB 2HRZE 4RH

New smear-negative pulmonary TB with
extensive parenchymal involvement
Severe forms of extrapulmonary TB (other than
TB meningitis)
Severe concomitant HIV disease
I TB meningitis 2HRZS 4HR
II Previously treated smear-positive pulmonary TB: 2HRZES/ 5HRE
Relapse 1HRZE
Treatment after interruption
Treatment failure
III New smear-negative pulmonary TB (other than in 2HRZ 4RH
category I)
Less severe forms of extrapulmonary TB
IV Chronic and MDR-TB Specially designed standardized
THANK YOU!!