Childhood Tuberculosis

Yoseph
Bsc in public health
 Introduction
• 95% of tuberculosis cases occur in developing
countries
• WHO estimates >8 million new cases and 2
million people die worldwide each year.
• More than 30% of the world's population is
infected with tuberculosis.
• Lung is the portal of entry in >98% of cases
• There are 5 closely related mycobacteria :
• M. tuberculosis, M. bovis, M. africanum, M.
microti, and M. canetti
• Tubercle bacilli are non–spore-forming,
nonmotile, pleomorphic, weakly gram-positive
curved rods and obligate aerobe
• A hallmark of all mycobacteria is acid fastness
• Mycobacteria grow slowly, Isolation takes 3-
6 wk.
 Transmission
• Person to person by airborne mucus droplet
• Rarely by direct contact with infected
discharge
• Increases when the patient has:-
• Positive acid-fast smear of sputum
• Extensive upper lobe infiltrate or cavity,
copious production of thin sputum, and
• Severe and forceful cough.
 transmision
• Ingestion of milk
• Skin prolonged close contacts
• Trans-placental
 Risk factors
• Presence of Contact history
• Age less than 5 years
• HIV infection
• Severe malnutrition
• Measles, pertussis, NS
• Patient on chronic steroids
• Malignancy
 Pathogenesis
• Primary infection occurs in persons without previous
exposure to tubercle bacilli.
• A localized granulomatous inflammatory process
occurs within the lung and this is called the primary
(Ghon) focus.
• From the Ghon focus, bacilli drain via lymphatics to
the regional lymph nodes.
• The Ghon focus with associated tuberculous
lymphangitis and involvement of the regional lymph
nodes is called the primary (Ghon) complex.
 Pathogenesis
• The parenchymal portion of the primary
complex:-
• Often heals completely by fibrosis or
calcification after undergoing caseous necrosis
and encapsulation
• Occasionally, this portion continues to enlarge,
resulting in focal pneumonitis and pleuritis.
• If caseation is intense, the center of the lesion
liquefies and empties into the associated
bronchus, leaving a residual cavity.
• After dissemination, bacilli may survive in
target organs for prolonged periods.
• The time between initial infection and clinically
apparent disease is variable.
• Disseminated and meningeal TB manifest
within2-6 mo
• Lymph node/ endobronchial TB within 3-9 mo.
• Bones and joints take several years
• Renal lesions become evident decades after
infection.
• Extrapulmonary manifestations develop in 25-
30% of children , compared with about 10% of
immunocompetent adults with tuberculosis.
• Pregnancy and the Newborn
• Pulmonary and extrapulmonary tuberculosis
is associated with increased risk for
• Prematurity,
• Fetal growth retardation,
• Low birthweight, and
• Perinatal mortality.
 Clinical manifestation
• Fever

• Weight loss

• Poor growth

• Cough

• Swollen glands

• Chills
 Physical finding
• DECREASED BREATH SOUND
• Rales
• Dullness or egophony
• Typical cavity on CXr
 Extrapulmonary TB
• 25-30% of children with tuberculosis have an
extrapulmonary presentation.
• Tuberculous Lymphadenitis and tuberculosis
of the Spine/Joints are the first and second
commonest form of childhood EPTB.
 Lymph Node Disease
• Tuberculosis of the
superficial lymph nodes
referred to as scrofula, is
the most common form
of extrapulmonary
tuberculosis in children
• Most cases occur within
6-9 mo of initial infection
• Disease is most often
unilateral
• Lymph node tuberculosis can resolve if left
untreated but more often progresses to
caseation and necrosis.
• Diagnosed by fine-needle aspiration of the
node and responds well to antituberculosis
therapy
• Culture of lymph node tissue yields the
organism in only about 50% of cases.
 Bone and Joint Disease
• The classic manifestation of
tuberculous spondylitis is
progression to Pott disease, in
which destruction of the
vertebral bodies leads to gibbus
deformity and kyphosis
• Multifocal bone involvement can
occur
• Bone biopsy to confirm the
diagnosis
Pott disease
 Pleural Effusion

• Discharge of bacilli into the pleural

space from a subpleural focus
/lymph node.
• clinically significant effusions occur
months to years after the primary
infection.
• uncommon in children <6 yr of age
• Effusions are usually unilateral but
can be bilateral
 Pericardial Disease
• The most common form of cardiac
tuberculosis is pericarditis.
• It is rare in children
• AFB of the fluid rarely positive
• But cultures are positive in 30-70% of cases.
 Tb Pericarditis
• Rare ( 0.5-4%) of TB cases
• From hematogenous spread or
Direct invasion or lymphatic
drainage from subcarinal LNS
( rupture of a mediastinal LN into
the pericardium space).
• Dry pericarditis: with acute pain
behind the sternum, friction rub
of the pericardium. EKG: Wide T-
wave.
• Pericardial effusion : Breathlessness, fever,
distant heart sound, pulsus paradoxus, raised
JVP, hepatomegaly and ascites.
• Constrictive pericarditis: The pericardium is
thickened, sometimes with calcifications
preventing cardiac dilatation. X-ray: small
heart shadow with or without calcifications.
• Pericardiocentesis & Culture of the pericardial
fluid is 60% positive.
• Echocardiography: fluid and strands crossing
between the two layers of the serosa.
Pericardial effusion Constrictive pericarditis
 Disseminated tuberclosis
• Tubercle bacilli are
disseminated to distant sites,
including liver, spleen, skin,
and lung apices, in all cases of
tuberculosis infection.
• The most clinically significant
form of disseminated
tuberculosis is miliary disease
causing disease in 2 or more
organs
 Upper Respiratory Tract Disease
• Children with laryngeal tuberculosis have a
croup-like cough, sore throat, hoarseness, and
dysphagia
• Tuberculosis of the middle ear results from
aspiration of infected pulmonary secretions
into the middle ear or from hematogenous
dissemination in older children
• Diagnosis is difficult
 Central Nervous System Disease
• CNS of Tuberculosis is the
most serious complication in
children and is fatal without
prompt and appropriate
treatment.
• Gelatinous exudate infiltrates
the corticomeningeal blood
vessels, producing
inflammation, obstruction, and
infarction of cerebral cortex.
• Brain stem is often involve.
• Combination of vasculitis, infarction, cerebral
edema, and hydrocephalus can occur
gradually or rapidly
• Tuberculous meningitis
• Signs and symptoms progress slowly and
divided into 3 stages
• 1st stage lasts 1-2 wk and is characterized by
nonspecific symptoms such as fever,
headache, irritability, drowsiness.
• Focal neurologic signs are absent
• 2nd stage usually begins more abruptly
• lethargy, nuchal rigidity, seizures, positive
Kernig and Brudzinski signs, hypertonia,
vomiting, cranial nerve palsies, and other focal
neurologic signs.
• 3rd stage is marked by coma, hemiplegia or
paraplegia, hypertension, decerebrate
posturing, deterioration of vital signs, and
eventually death.
• The prognosis of tuberculous meningitis
correlates most closely with the clinical stage.
• 1st stage have an excellent outcome
• 3rd stage who survive have permanent
disabilities
• The diagnosis of tuberculous meningitis
requiring a high index of suspicion.
• 20-50% of children have a normal chest
radiograph.
• Diagnosis - examination and culture of CSF.
 Tuberculoma
• A tumor-like mass resulting from
aggregation of caseous tubercles.
• Account for up to 40% of brain
tumors in some areas
• In children they are often
infratentorial
• Lesions are most often singular
but may be multiple.
• Chest radiograph is usually
normal.
 Tuberculous peritonitis
• Rare in children.
• Generalized peritonitis can arise from subclinical
or miliary hematogenous dissemination.
• Localized peritonitis is caused by direct extension
• Jejunum and ileum near Peyer patches and the
appendix are the most common sites of
involvement.
• Biopsy, AFB, and culture of the lesions necessary
to confirm the diagnosis.
 Genitourinary disease
• Rare in children
• Reach the kidney by lymphohematogenous
dissemination.
• Renal tuberculosis is often clinically silent , marked
only by sterile pyuria and microscopic hematuria.
• Hydronephrosis or ureteral strictures can
complicate the disease.
• Urine cultures positive in 80-90% of cases, and
AFB positive in 50-70% of cases.
Tuberculosis of the female genital
• uncommon in children.
• The fallopian tubes are often involved (90-
100% ), endometrium (50%), ovaries (25%),
and cervix (5%).
• Genital abnormalities and a positive TST in an
adolescent boy or girl suggests genital tract
tuberculosis.
 TB in HIV-Infected Children
• Most seen in developing countries
• The rate of tuberculosis in HIV-infected
children is 30 times higher
• Tuberculosis in HIV-infected children is often
more severe, progressive, and likely to occur
in extrapulmonary sites
• The mortality rate of HIV-infected children
with tuberculosis is high
 Diagnostic methods
• X-rays
• Tuberculin skin test*
• Culture
• Biopsy
• PCRDNA finger printing
 Mantoux tuberculin skin testing
• 0.1 ml containing 5 tuberculin units of PPD
injected Id to ante-cubital area of forearm
• Recruitment of sensitized T cells to the skin
↓
lymphokines
↓
induration (measure after 48-72hrs)
• < 5mm Negative
• 5-10mm
Indeterminate
• >10mm positive
• > 5 mm Positive in HIV
 False negative PPD test
• Severe PEM
• Measles
• Overwhelming TB
• Wrong techniques
• HIV
• Steroids
• Cancer
• False positive PPD test
• Atypical mycobacterial infections
• Hypersensitivity to constituents
• Technical error
 Criteria for TB Dx in children
• Contact history
• Symptom complex
• Positive PPD
• Compatible radiology
• AFB
• Miliary pattern on CXR
• Culture
• Biopsy
• Positive PPD in unvaccinated < 5 years of age
 General definitions
• Tuberculosis suspect:
• A person with symptoms and signs suggestive of
tuberculosis, in particular cough for two weeks or more.
• Case of tuberculosis:
• Tuberculosis has been bacteriologically confirmed, or
has been diagnosed by an experienced medical officer
• A proven case of tuberculosis:
• A patient with two sputum smears or culture positive for
Mycobacterium tuberculosis
Classification of tuberculosis cases
a. Smear-positive pulmonary TB (PTB+)
A patient with at least two initial sputum smear
examinations positive for AFB by direct microscopy,
Or
A patient with one initial smear examination positive for
AFB by direct microscopy and culture positive,
Or
A patient with one initial smear examination positive for
AFB by direct microscope and radiographic abnormalities
consistent with active TB as determined by a clinician.
b. Smear-negative pulmonary TB (PTB-)
A patient having symptoms suggestive of TB with at least 3 initial
smear examinations negative for AFB by direct microscopy, and
No response to a course of broad-spectrum antibiotics, and
Again three negative smear examinations by direct microscopy,
and
Radiological abnormalities consistent with pulmonary
tuberculosis, and
Decision by a clinician to treat with a full course of anti-
tuberculosis
Or
A patient whose diagnosis is based on culture positive for M.
tuberculosis but three initial smear examinations negative by
direct microscopy
c. Extra-pulmonary TB (EPTB)
TB in organs other than the lungs, proven by one
culture-positive specimen from an extra-
pulmonary site or histo-pathological evidence
from a biopsy,

Any patient with both sputum smear positive

pulmonary TB (PTB+) and Extra-pulmonary TB
(EPTB), should be classified as PTB+.
 Definition of type of cases
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.
 Management OF TB
• Indication for Admission
• TB meningitis or miliary TB, preferably for the
first 2 months of anti-TB treatment;
• Any child with respiratory distress;
• Spinal TB;
• Severe adverse events, such as hepatotoxicity
 Principles of treatment
 Principle of management includes
-Chemotherapy
-Prophylaxis
-Nutritional rehabilitation
-Family screening
-Follow up
 Chemotherapy
 There are 3 types of population of bacteria
1. Population in cavities
-Contain mutants
-Multiply rapidly
Needs at least 2 drugs
2. Inside macrophages
-Multiply & grow slowly
-Needs prolonged treatment
3. Closed lesion
-Dormant
-Never completely killed
 intensive phase
• uses three or more drugs for 1st 8wks
• Clears bacteria rapidly
• Make patient non-infectious
• Reduce drug resistance
 Continuation phase
• Uses at least 2 drugs for the next 6moths
• Insures that patient is permanently cured & no
relapse after completion of Rx.
 Regimen
Category I (In settings where HIV is high in
patients with suspected /confirmed PTB or LAP,
<5Child, disiminated disease, critically ill)
 2(ERZH), 4RH or 6HE (CNS Tb cotinuation
phase to 10months)
Category II (re-treatment regimen to smear +ve
relapse, Tx failure, return after default smear
negative PTb. Who become smear positive after
2 months of treatment)
 2HRZES/1HRZE, 5HRE
Category III ( for smear negative PTb., EPTb., Tb
in children age 7-14yrs who are not seriously ill)
 2RHZ , 4RH or 6HE
NB: It is important that you always check the
National protocol for
TB treatment
 Dosage of drugs-
drug daily dose max. forms
S – 20-40mg/kg 1gm 1gm vial
H – 10 mg/kg 300mg 100, 300mg tab
R – 10-20mg/kg 600mg 150, 300mg caps
E – 15-25mg/kg 2.5gm 400mg tab
Z – 25-35mg/kg 2gm 500mg tab
 Indications for steroids in TB
• Meningitis
• Pericarditis
• Pleural effusions
• Hypoadrenalism
• Laryngitis
• Severe hypersensitivity
• Renal tract Tb
• Massive LN enlargement
• Pyridoxine is recommended for infants,
children, and adolescents who are being
treated with INH and who have nutritional
deficiencies, symptomatic HIV infection, or
who are breastfeeding.
• dose10 mg/day
 Chemoprophylaxis with INH
 Breast feeding infant (No need of Isolation)
• INH for 6mon then BCG or
• INH for 3mon then PPD
• If negative, give BCG
• If positive, INH for 3mon then BCG
 under 5 child
• If symptomatic, chemotherapy
• If not, INH for 6month
 all other children if symptomatic, chemotherapy
 Adequate nutrition
 SIDE EFFECT OF ANTI TB DRUG

Drugs Adverse reaction

Ethambutol (R2) Optic neuritis, decreased red-green color

discrimination, gastrointestinal tract
disturbances, hypersensitivity

Isoniazid (H2) Mild hepatic enzyme elevation, hepatitis,

peripheral neuritis, hypersensitivity

Pyrazinamide (H1) Hepatotoxic effects, hyperuricemia,

arthralgias, gastrointestinal tract upset
 SIDE EFFECT OF ANTI TB DRUG

Drugs Adverse reaction

Rifampin (H3) Orange discoloration of secretions or
urine, staining of contact lenses, vomiting,
hepatitis, influenza-like reaction,
thrombocytopenia, pruritus; oral
contraceptives may be ineffective

Streptomycin (R1) Renal and ototoxicity

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