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CHILDHOODTUBERCULOSIS
Getnet Aschale
Ass.Professor
of Pediatrics and
5/7/2024
1
OUT LINE
 Introduction
 Etiology
 Epidemiology
 Clinical manifestation
 Types of tuberculosis
 Diagnosis
 Treatment
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2
INTRODUCTION
 During the last decade of the 20th century the number of new
cases of tuberculosis increased worldwide.
 Currently, 95% of tuberculosis cases occur in developing
countries because of the following
 HIV/AIDS epidemics (have had the greatest impact )
 Lack of resource for proper identification and treatment of these
diseases
 Poor social economic condition
 Over crowding living condition
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CONT’D…
 Almost 1.3 million cases and 450,000 deaths occur in children
each year.
 More than 1/3rd of the world's population is infected with
Mycobacterium tuberculosis
 According to the latest WHO Global TB Report 2011, there
were an estimated 8.8 million incident cases of TB globally
 In 2010, of which 1.1 million were among people living with
HIV
 MDR-TB is estimated to be 1.6% among all new TB cases and
12% among all previously treated TB cases
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ETIOLOGY
 53 different species of mycobacterium
 3 species cause TB in humans
 M.tuberculosis
 M.bovis
 M. africanum
 M.microti
 M. canetti
 M. tuberculosis is the most important cause of tuberculosis
disease in humans.
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Mycobacterium tuberculosis
●an aerobic
●Slow growing ,curved rod with a generation time of 12-24 hr.
A hallmark of all mycobacteria is acid fastness—the capacity to
form stable mycolate complexes with arylmethane dyes such as
crystal violet, carbolfuchsin, auramine, and rhodamine
 Once stained, they resist decoloration with ethanol and
hydrochloric or other acids
 Isolation from clinical specimens on solid synthetic media
usually takes 3-6 wk, and drug susceptibility testing requires an
additional 4 wk.
Cont’d…
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6
AFB SLIDE
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TRANSMISSION
 Inhalation
 Ingestion of milk
 Transplacental
 Increased risk with when the patient has:
 positive acid-fast smear of sputum
 an extensive upper lobe infiltrate or cavity
 copious production of thin sputum
 severe and forceful cough and sneezing (single cough can produce
3,000 bacilli.
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CONT’D…
 Latent tuberculosis infection (LTBI)
 A reactive tuberculin skin test (TST) and the absence of clinical and
radiographic manifestations are the hallmark of LTBI
 Untreated infants with LTBI have up to a 40% likelihood of
developing tuberculosis, with the risk for progression decreasing
gradually through childhood to adult lifetime rates of 5-10%.
 The greatest risk for progression occurs in the first 2 yr after
infection
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RISK FACTORS FOR PROGRESSION OF LATENT TUBERCULOSIS
INFECTION TO TB DISEASE.
 Immunity status
 Nutritional status
 Intercurrent illness
 Length of time of exposure
 # of bacteria inhaled
 Age at infection
Infants and children ≤4 yr of age, especially those <2 yr
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PATHOGENESIS
 The lung is the portal of entry in >98% of cases
 The tubercle bacilli multiply initially within alveoli and alveolar
ducts
 Most of the bacilli are killed, but some survive within non
activated macrophages, which carry them through lymphatic
vessels to the regional lymph nodes
 Primary complex (Ghon complex), which is the combination of
a parenchymal pulmonary lesion and a corresponding lymph node
site,
 Tubercle bacilli are often carried to most tissues of the body
through the blood and lymphatic vessels.
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CONT’D…
 The parenchymal portion of the primary complex often heals
completely by fibrosis or calcification after undergoing caseous
necrosis and encapsulation
 If caseation is intense, the center of the lesion liquefies and empties
into the associated bronchus, leaving a residual cavity
 Disseminated tuberculosis occurs if the number of circulating
bacilli is large and the host's cellular immune response is inadequate
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NATURAL HISTORY OF TB
 In the great majority (90-95%) of infected persons the
immunological defence either kills the inhaled or ingested bacilli or
keeps them suppressed (silent focus) causing ‘latent Tuberculosis
infection’
 Only 5-10% of such infected persons (primary infection) develop
active disease
 Following primary infection, rapid progression to disease is more
common in children less than 5 years of age.
 Patients with weakened immune systems, such as those with HIV
infection, are at greater risk of developing TB disease.
 HIV positive people with latent TB infection have a 10% annual and
50% life time risk of developing active TB disease
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 Active TB disease arises from progression of the primary lesion as a
continuous process within a year or so after infection, or from
endogenous reactivation of latent foci, which remained dormant
since the initial infection or exogenous re-infection.
 If untreated, TB leads to death within 5 years in at least 50 % of the
patients.
 Without treatment, about 20 to 25% could have natural healing and
25 to 30% could remain chronically ill, thus continuing to spread
the disease in the community.
Cont’d…
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CONT’D…
 The time between initial infection and clinically apparent disease is
variable.
 Disseminated and meningeal tuberculosis are early manifestations, often
occurring within 2-6 mo of acquisition.
 Significant lymph node or endobronchial tuberculosis usually appears
within 3-9 mo.
 Lesions of the bones and joints take several years to develop,
 Renal lesions become evident decades after infection
 Extra pulmonary manifestations develop in 25-35% of children with
tuberculosis, compared with about 10% of immuno competent adults with
tuberculosis
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IMMUNITY AND TUBERCULOSIS INFECTION
 Conditions that adversely affect cell-mediated immunity predispose to
progression from tuberculosis infection to disease.
 Cell-mediated immunity develops 2-12 wk after infection, along with
tissue hypersensitivity .
 Tuberculosis infection is associated with a humoral antibody response,
which appears to play little role in host defense.
 In immunocompetent persons the response to the initial infection with
M. tuberculosis usually provides protection against reinfection when a
new exposure occurs.
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CLINICAL MANIFESTATION
 Primary Pulmonary Disease
 Progressive Primary Pulmonary Disease
 Reactivation Tuberculosis
 Extrapulmonary tuberculosis
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PRIMARY PULMONARY DISEASE
 common type of TB in children
 The primary complex Parenchymal pulmonary focus + the
regional LN is the hall mark.
 Partial obstruction of the bronchus caused by external compression
can cause hyperinflation in the distal lung segment and complete
obstruction results in atelectasis.
 Inflamed caseous nodes can attach to the bronchial wall and erode
through it, causing endobronchial tuberculosis or a fistula tract
 The caseum causes complete obstruction of the bronchus. The
resulting lesion is a combination of pneumonitis and atelectasis and
has been called a collapse-consolidation or segmental lesion
 Erosion of a parenchymal focus of tuberculosis into a blood or
lymphatic vessel can result in dissemination of the bacilli and a
miliary pattern.
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PROGRESSIVE PRIMARY PULMONARY DISEASE
 Rare
 Serious complications
 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.
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REACTIVATION TUBERCULOSIS(20 TB)
 Reactivation TB results when the persistent bacteria in a host
suddenly proliferate
 This form of tuberculosis is rare in childhood but can occur in
adolescence
 Only 5 to 10 % of patients with no underlying medical
problems who become infected develop active disease in their
lifetime.
 The most common form is an infiltrate or cavity in the apex of
the upper lobes, where oxygen tension and blood flow are
great.
 The most common pulmonary sites are the original
parenchymal focus, lymph nodes, or the apical seeding (Simon
foci) established during the hematogenous phase of the early
infection
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IMMUNOSUPPRESSIVE CONDITIONS ASSOCIATED
WITH REACTIVATION TB
 HIV infection and AIDS
 End-stage renal disease
 Diabetes mellitus
 Malignant lymphoma
 Corticosteroid use
 Diminution in Cell Mediated Immunity associated with old
age ,measles
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CONT’D…
 In contrast to primary disease, the disease process in reactivation
TB tends to be localized, because the established immune
response prevents further extra pulmonary spread.
 there is little regional lymph node involvement and less
caseation
 The lesion typically occurs at the lung apices, and disseminated
disease is unusual, unless the host is severe immunosuppressed
 Children with a healed tuberculosis infection acquired at <2 yr of
age rarely develop chronic reactivation pulmonary disease.
 More common in those who acquire the initial infection at >7 yr
of age
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CONT’D…
 Older children and adolescents with reactivation tuberculosis are
more likely to experience fever, anorexia, malaise, weight loss, night
sweats, productive cough, hemoptysis, and chest pain than children
with primary pulmonary tuberculosis
 Most signs and symptoms improve within several weeks of starting
effective treatment, although the cough can last for several months
 The most common radiographic presentations of this type of
tuberculosis are extensive infiltrates or thick-walled cavities in the
upper lobes.
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THE MOST COMMON RADIOGRAPHIC PRESENTATIONS OF THIS TYPE
OF TUBERCULOSIS ARE EXTENSIVE INFILTRATES OR THICK-WALLED
CAVITIES IN THE UPPER LOBES
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Extra Pulmonary
Tuberculosis
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PLEURAL EFFUSION
 Larger and clinically significant effusions occur months to years
after the primary infection.
 Tuberculous pleural effusion is uncommon in children <6 yr of age
and rare in children <2 yr of age.
 Effusions are usually unilateral but can be bilateral.
 They are rarely associated with a segmental pulmonary lesion and
are uncommon in disseminated tuberculosis.
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CONT’D…
 characterized by low to high fever
 shortness of breath, chest pain on deep
inspiration, and diminished breath sounds.
 The fever and other symptoms can last for
several weeks after the start of
antituberculosis chemotherapy.
 The TST is positive in only 70-80% of
cases.
 The prognosis is excellent, but
radiographic resolution often takes months.
 Scoliosis is a rare complication from a
long-standing effusion
CXR
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DX
Pleural fluid analysis
 Color =yelow or straw color/rarely hemorrhagic.
 Cell =lymphocytic predominance
 Rarely TB empyema
 Culture <30% positive
 AFB microscopy is rarely +ve
 Pleural Biopsy demonstrate AFB /granulomatous change
 Protein level is usually 2-4 g/dL, and the glucose concentration
may be low (20-40 mg/ dL)
 The specific gravity is usually 1.012-1.025,
 Biopsy of the pleural membrane is more likely to yield a
positive acid-fast stain or culture, and granuloma formation
usually can be demonstrated.
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PERICARDIAL DISEASE
 The most common form of cardiac tuberculosis is Pericarditis.
 rare, occurring in 0.5-4% of tuberculosis cases in children.
 usually arises from direct invasion or lymphatic drainage from
subcarinal lymph nodes
 Symptoms are nonspecific, including low-grade fever, malaise, and
weight loss.
 A pericardial friction rub or distant heart sounds with pulsus
paradoxus may be present
 The pericardial fluid is typically serofibrinous or hemorrhagic.
 Acid-fast smear of the fluid rarely reveals the organism, but
cultures are positive in 30-70% of cases.
 The culture yield from pericardial biopsy may be higher, and the
presence of granulomas often suggests the diagnosis.
 Partial or complete pericardiectomy may be required when
constrictive pericarditis develops.
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LYMPHOHEMATOGENOUS (DISSEMINATED)
DISEASE
 The most clinically significant form of disseminated tuberculosis
is Miliary disease, which occurs when massive numbers of
tubercle bacilli are released into the bloodstream, causing disease
in 2 or more organs.
 The clinical picture may be acute, more often it is indolent and
prolonged, with spiking fever accompanying the release of
organisms into the bloodstream.
 Early pulmonary involvement is surprisingly mild, but diffuse
involvement becomes apparent with prolonged infection
 Bones and joints or kidneys also can become involved.
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CONT’D…
 Generalized lymphadenopathy and hepatosplenomegaly develop
within several weeks in about 50% of cases.
 Meningitis or peritonitis are found in 20-40% of patients with
advanced disease
 Cutaneous lesions include papulonecrotic tuberculids, nodules, or
purpura
 Choroid tubercles occur in 13-87% of patients and are highly
specific for the diagnosis of miliary tuberculosis
 Unfortunately, the TST is nonreactive in up to 40% of patients
with disseminated tuberculosis.
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UPPER RESPIRATORY TRACT DISEASE
 laryngeal tuberculosis have a croup-like cough, sore throat,
hoarseness, and dysphagia.
 Most children with laryngeal tuberculosis have extensive upper
lobe pulmonary disease
 Tuberculosis of the middle ear results from aspiration of infected
pulmonary secretions into the middle ear or from hematogenous
dissemination in older children.
 The most common signs and symptoms are painless unilateral
otorrhea, tinnitus, decreased hearing, facial paralysis, and a
perforated tympanic membrane.
 Diagnosis is difficult, because stains and cultures of ear fluid are
often negative.
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LYMPH NODE DISEASE
 TB of superficial lymph nodes (scrofula) is the most common
form of extra pulmonary tuberculosis in children .
 The nodes usually enlarge gradually in the early stages of lymph
node disease.
 They are discrete, nontender, and firm but not hard.
 The nodes often feel fixed to underlying or overlying tissue.
 Disease is most often unilateral, but bilateral involvement can
occur because of the crossover drainage patterns of lymphatic
vessels in the chest and lower neck.
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CONT’D…
 As infection progresses, multiple nodes are infected, resulting in a
mass of matted nodes.
 Systemic signs and symptoms other than a low-grade fever are
usually absent.
 The TST is usually reactive, but the chest radiograph is normal in
70% of cases.
 The onset of illness is occasionally more acute, with rapid
enlargement, tenderness, and fluctuance of lymph nodes and with
high fever.
 The initial presentation is rarely a fluctuant mass with overlying
cellulitis or skin discoloration
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CONT’D…
 Lymph node tuberculosis can resolve if left untreated but more
often progresses to caseation and necrosis.
 The capsule of the node breaks down, resulting in the spread of
infection to adjacent nodes.
 Rupture of the node usually results in a draining sinus tract that can
require surgical removal.
 Dx - FNAC, Biopsy ,AFB ,Tissue culture(50%+ve)
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CENTRAL NERVOUS SYSTEM DISEASE (CNS TB)
 Most serious complication in children and is fatal without prompt
and appropriate treatment.
 The brain stem is often the site of greatest involvement, which
accounts for the commonly associated dysfunction of cranial nerves
III, VI, and VII.
 It is most common in children between 6 mo and 4 yr of age.
 The clinical progression of tuberculous meningitis may be rapid or
gradual.
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CONT’D…
More commonly, the signs and symptoms progress slowly over
several weeks and can be divided into 3 stages
Stage 1
 lasts 1-2 wk
 characterized by nonspecific symptoms such as fever, headache,
irritability, drowsiness, and malaise.
 Focal neurologic signs are absent, but infants can experience a
stagnation or loss of developmental milestones.
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CONT’D…
Stage 2
 Usually begins more abruptly
 Common features are lethargy, nuchal rigidity, seizures
 positive Kernig and Brudzinski signs, hypertonia, vomiting,
cranial nerve palsies, and other focal neurologic signs.
 The accelerating clinical illness usually correlates with the
development of hydrocephalus, increased intracranial pressure,
and vasculitis.
Stage 3
 is marked by coma, hemiplegia or paraplegia
 hypertension, decerebrate posturing, deterioration of vital signs,
and eventually death
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CNS –TB FORMS
 BRAIN
1) Tb meningitis
2) encephalopathy
3) vasculopathy
4) tuberculoma
5) brain abscess
Spinal cord
1) arachidonitis
2) Para spinal abscess
3) pot’s disease
4) Radiculopathy
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CONT’D…
DX
 The TST is nonreactive in up to 50% of cases, and
 20-50% of children have a normal chest radiograph
 The CSF leukocyte count usually ranges from 10 to 500 cells/mm3.
 PNC leukocytes may be present initially, but lymphocytes
predominate in the majority of cases.
 The CSF glucose is typically <40mg/dL but rarely <20mg/dL.
 The protein level is elevated and may be markedly high (400-
5,000mg/dL) secondary to hydrocephalus and spinal block.
 MRI and CT scan , demonstrate basal enhancement with
communicating hydrocephalus.
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TUBERCULOMA
 a tumor-like mass resulting from aggregation of caseous tubercles that
usually manifests clinically as a brain tumor
 In adults tuberculomas are most often supratentorial, but in children
they are often infratentorial, located at the base of the brain near the
cerebellum
 Tuberculomas account for up to 40% of brain tumors in some areas of
the world.
 Lesions are most often singular but may be multiple.
 The most common symptoms are headache, fever, and convulsions
 On CT or MRI of the brain, tuberculomas usually appear as discrete
lesions with a significant amount of surrounding edema.
 Contrast medium enhancement is often impressive and can result in a
ring like lesion
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BONE AND JOINT DISEASE
 TB usually affects weight bearing bones or joints, and most common sites
are vertebrae, hip, knee and ankle
 The classic manifestation of tuberculous spondylitis is progression to Pott
disease, in which destruction of the vertebral bodies leads to gibbus
deformity and kyphosis .
 Tuberculous bone lesions can resemble pyogenic and fungal infections or
bone tumors
 A catastrophic complication of Pott's disease is paraplegia, which is
usually due to an abscess or a lesion compressing the spinal cord
 Multifocal bone involvement can occur
 A bone biopsy is essential to confirm the diagnosis
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]
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ABDOMINAL AND GASTROINTESTINAL DISEASE
 Any part of the GIT can be involved
TB enteritis
The pathogenesis of tuberculous enteritis has been attributed to four
mechanisms
 Swallowing infected sputum
 Hematogenous spread from active pulmonary or miliary TB
 Ingestion of contaminated milk or food
 Contiguous spread from adjacent organs
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CONT’D…
The macroscopic appearance of the intestinal lesions can be
categorized as follows
 Ulcerative type
 Hyper plastic type
 Skip lesion of the intestine
 Pan colitis form
 Hyperplasic type presented as intestinal obstruction
 Ulcerative forms usually have chronic dysentery with other
symptoms
 The jejunum and ileum near Payers patches and the appendix
are the most common sites of involvement.
 Biopsy, acid-fast stain, and culture of the lesions are usually
necessary to confirm the diagnosis.
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TUBERCULOUS PERITONITIS
 Occurs most often in young men and is uncommon in adolescents
and rare in children.
 Generalized peritonitis can arise from subclinical or miliary
hematogenous dissemination.
 Localized peritonitis is caused by direct extension from an
abdominal lymph node, intestinal focus, or genitourinary
tuberculosis.
 Rarely, the lymph nodes, omentum, and peritoneum become matted
and can be palpated as a doughy irregular non tender mass.
 Abdominal pain or tenderness, ascites, anorexia, and low-grade
fever are typical manifestations.
 The TST is usually reactive.
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 Types of TB peritonitis
1)Dry peritonitis type
2)Hyper plastic type (mass)
3) ascetic form(fluid collection)
4)Acute abdomen
 Dx
 clinical suspicions
 CXR
 Abd us
 Ascitic fluid analysis
 Biopsy
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GENITOURINARY DISEASE(RENAL TB)
 Renal tuberculosis is rare in children, because the incubation period
is several years or longer
 Usually during lymphohematogenous spread(miliary).
 In true renal tuberculosis, small caseous foci develop in the renal
parenchyma and release M. tuberculosis into the tubules.
 Infection then spreads locally to the ureters, prostate, or epididymis.
 Often clinically silent in its early stages, (marked only by sterile
pyuria and microscopic hematuria
 Dysuria, flank pain,gross hematuria (late stage)
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CONT’D…
 Hydronephrosis or ureteral strictures can complicate the disease.
 Urine cultures for M. tuberculosis are positive in 80-90% of
cases, and acid-fast stains of large volumes of urine sediment are
positive in 50-70% of cases.
 An intravenous pyelogram or CT scan often reveals mass lesions,
dilatation of the proximal ureters, multiple small filling defects,
and hydronephrosis if ureteral stricture is present.
 Disease is most often unilateral
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GENITAL TB
 In females of genital tract the fallopian tubes are most often
involved (90-100% of cases), followed by the endometrium
(50%), ovaries (25%), and cervix (5%).
 Genital tuberculosis in adolescent boys causes epididymitis or
orchitis.
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DISEASE IN HIV-INFECTED CHILDREN
 Establishing the diagnosis of tuberculosis in an HIV-infected child may be
difficult, because
 Skin test reactivity can be absent and culture confirmation is difficult
 Similar C/F to many other HIV-related infections and conditions
 Tuberculosis in HIV-infected children is often more severe, progressive,
and likely to occur in extra pulmonary sites.
 Radiographic findings are similar to those in children with normal
immune systems, but lobar disease and lung cavitations are more common.
 Nonspecific respiratory symptoms, fever, and weight loss are the most
common complaints.
 Rates of drug-resistant tuberculosis tend to be higher in HIV-infected
adults and probably are also higher in HIV-infected children.
 All children with tuberculosis disease should be tested for HIV co-
infection
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PERINATAL DISEASE
 Associated with risk for prematurity, fetal growth retardation,
low birthweight, and perinatal mortality.
 Congenital tuberculosis is rare because the most common result
of female genital tract tuberculosis is infertility.
 Primary infection in the mother just before or during pregnancy
is more likely to cause congenital infection than is reactivation
of a previous infection.
 The tubercle bacilli first reach the fetal liver, where a primary
focus with periportal lymph node involvement can occur.
 The bacilli in the lung usually remain dormant until after birth,
when oxygenation and pulmonary circulation increase
significantly.
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 Congenital tuberculosis can be caused through placenta ,aspiration
or ingestion of infected amniotic fluid.
 However, the most common route of infection for the neonate is
postnatal airborne transmission from an adult with infectious
pulmonary tuberculosis .
 Symptoms of congenital tuberculosis may be present at birth but
more commonly begin by the 2nd or 3rd wk of life.
 The most common signs and symptoms are
 Respiratory distress, fever, hepatic or spleen enlargement,
 Poor feeding, lethargy or irritability, lymphadenopathy,
 Abdominal distention, failure to thrive, ear drainage, and skin
lesions.
 Many infants have an abnormal chest radiograph, most often with
a miliary pattern.
Cont’d…
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CONT’D…
 Hilar and mediastinal lymphadenopathy and lung infiltrates are
common.
 Generalized lymphadenopathy and meningitis occur in 30-50% of
patients.
 Dx is often challenging can mimic sepsis or TORCHS
 The most important clue for rapid diagnosis of congenital
tuberculosis is a maternal or family history of tuberculosis
 The infant's TST is negative initially but can become positive in 1-
3 mo
 The mortality rate of congenital tuberculosis remains very high if
not diagnosed and treated early
 CSF should be examined and cultured, although the yield for
isolating M. tuberculosis is low
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CONT’D…
Prevention of perinatal TB
 Appropriate testing and treatment of the mother and other family
members for TB
 High-risk pregnant women should be tested with a TST or IGRA,
and those with a positive test result should receive a chest
radiograph.
 If the mother’s chest radiograph or acid-fast sputum smear
shows evidence of current tuberculosis disease,INH therapy is
recommended for the newborn after ruling out active TB.
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DIAGNOSTIC METHODS OF TB
 X-rays
 Tuberculin skin test(TST)
 Culture
 Biopsy
 Molecular test - PCR
GeneXpert MTB/RIF
Line probe Assay
 AFB Stains
 Ziel Nielson
 Flourochrome
 T-cell based interferon-gamma assays
 QuantiFERON-TB gold
 T-SPOT.TB
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TUBERCULIN SKIN TESTING
 The Mantoux TST is the intradermal injection of 0.1 mL purified
protein derivative (PPD).
Recruitment of sensitized T cells to the skin
↓
lymphokines
↓
Indurations( measure after 48-72hrs)
 Tuberculin sensitivity develops 3 wk to 3 mo (most often in 4-8 wk)
after inhalation of organisms
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CONT’D…
 A TST should be regarded as positive:
 >5 mm diameter of induration:
in children who are immunosuppressed including
HIV-positive children and
severely malnourished children, i.e. those with clinical
evidence of marasmus or kwashiorkor
 >10mm diameter of induration:
in all other children (whether they have received a
BCG vaccination or not)
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FALSE NEGATIVE PPD TEST
 Severe PEM
 Measles
 Overwhelming TB
 Wrong techniques
 HIV
 Steroids
 Cancer
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FALSE POSITIVE PPD TEST
 Atypical mycobacterial infections
 Hypersensitivity to constituents
 BCG vaccination
5/7/2024
67
AFB MICROSCOPY
 Sputum(spot/morning /spot ) ;Induced sputum AFB/Cultutre
 Gastric aspirate (three early morning sample)
 Early morning gastric aspirate(3x=50% positive culture)
 Any body fluid
 Urine…… etc(with centrifugation)
5/7/2024
68
GENEXPERT MTB/RIF
• For the diagnosis of pulmonary TB and rifampicin resistance
• Is new rapid test for TB
• Fully automated
• Provides accurate results in 100 minutes
 Indicated ( national guideline ) in:
 MDRTB
 TB/HIV
 Children
 Extra pulmonary TB
5/7/2024
69
LINE PROBE ASSAY
 new test that use molecular technology
 identify presence or absence of specific mutation on genes of
TB bacilli which are responsible for Isoniazid and Rifampcin
resistance
 Rapid and accurate test
 MDR-TB can be proved on the same day
5/7/2024
70
5/7/2024
71
# It can be difficult to clearly define what is “suggestive of PTB” on clinical or radiological
findings in HIVinfected children because of clinical overlap between PTB and other forms of
HIV-related lung disease.
# CXR abnormalities of PTB in HIV-infected child are similar to those in HIV-uninfected
child.
5/7/2024
72
ANY ONE OF THE FOLLOWING IS SUGGESTIVE OF TB:
i. Radiological picture of miliary pattern
ii. Pathologic findings compatible with TB (Pathology)
iii. Culture positive
iv. Isolation of the organism by acid fast staining
5/7/2024
73
TREATMENT
Principles of TB Treatment
1.Chemotherapy
2.Adjuvant therapy
3.Nutritional therapy
4.Family screening
5.Follow up
5/7/2024
74
1.CHEMOTHERAPY
 2 treatment phases
A. Intensive phase
4 drugs for 2 month ( New cases) and 3months (Retreatment)
 It renders the patient non-infectious by rapidly reducing the load
of bacilli in the sputum ,usually within 2-3 weeks
B. Continuation phase
 2drugs for 4mths ( new case)
 3 drugs for 5 months (retreatment)
 It ensure cure, and prevents relapse after completion of
treatment
 EXCEPTIONS In Children with TB meningitis and osteo-
articular TB , the continuation phase should be 10 months
5/7/2024
75
COMMONLY USED DRUGS FOR THE TREATMENT OF
TUBERCULOSIS IN INFANTS, CHILDREN, AND ADOLESCENTS
DRUG DAILY DOSAGE,
mg/kg
MAXIMUM
DOSE
ADVERSE REACTIONS
Ethambutol 20 1600mg Optic neuritis (usually reversible),
decreased red-green color
discrimination, gastrointestinal tract
disturbances, hypersensitivity
Isoniazid 10-15 300mg Mild hepatic enzyme elevation,
hepatitis, peripheral neuritis,
hypersensitivity
Pyrazinamide 20-40 2gm Hepatotoxic effects, hyperuricemia,
arthralgias, gastrointestinal tract
upset
Rifampicin 10-20 600 Orange discoloration of secretions
or urine, vomiting, hepatitis,
influenza-like reaction,
thrombocytopenia, pruritus
5/7/2024
76
A. FDC DOSING REGIMEN FOR NEW CASES
5/7/2024
77
B.FDC DOSING REGIMENS FOR RETREATMENT CASES
5/7/2024
78
2.ADJUVANT THERAPY
Indication for steroid
 CNS
 Pericarditis
 Miliary TB with acute air blocking syndrome
 Tb adrenalitis
 The most commonly prescribed regimen is prednisone, 1-
2 mg/kg/day in 1-2 divided doses orally for 4-6 wk,
followed by gradual tapering.
Indication for pyridoxine
 RVI pts
 Malnutrition
 Chronic diarrhea
 Breast feeding
5/7/2024
79
3.FAMILY SCREENING
 Those under five children
 Pregnant ladies
 Elders,age >65 yrs
 All HIV /AIDS pts at home
5/7/2024
80
4.FOLLOW UP
 Children, parents, and other close family members
should be educated about TB
 Directly observed therapy(DOT) should be used for all
children
 Asses two weeks after treatment initiation, after intensive
phase and every 2 month until treatment completion
 assess treatment adherence, adverse events, weight
 A follow up sputum for AFB at 2months should be done
for any child who was smear positive at diagnosis.
 A child who is not responding, should be assessed for
drug resistant TB
5/7/2024
81
AVAILABLE APPROACHES TO PREVENT TB IN CHILDREN
5/7/2024
82
TREATMENT OF LATENT TUBERCULOSIS INFECTION
Indication
 All under 5 yrs that have household contacts of a case with
sputum smear positive TB with no evidence of TB disease
 HIV infected children at all age
 Recommended dosage INH 10 mg/kg daily for 6 months
5/7/2024
83
DRUG-RESISTANT TUBERCULOSIS
 The incidence of drug-resistant tuberculosis is increasing in many
areas of the world
 There are two major types of drug resistance
 Primary resistance occurs when a person is infected with M.
tuberculosis that is already resistant to a particular drug.
 Secondary resistance occurs when drug-resistant organisms
emerge as the dominant population during treatment
 Most drug resistance in children is primary
 Secondary resistance is rare in children because of the small size of
their mycobacterial population
5/7/2024
84
CASE DEFINITION OF DRUG RESISTANCE TB
 Mono resistance: Resistance to only one first line drugs
 Poly-resistance: Resistance to more than one first line drugs, but
not to both isoniazid and rifampicin
 Multidrug resistance (MDR): Resistance to at least isoniazid
and rifampicin
 Extensive drug resistance(XDR): MDR as well as any
fluoroquinolone, and any of the second line injectable anti TB
drugs( capreomycin, kanamycin,and amikacin
5/7/2024
85
RISK FACTORS FOR DRUG-RESISTANT TUBERCULOSIS
 Personal or contact history of treatment for tuberculosis
 Contacts of patients with drug-resistant tuberculosis
 Birth or residence in a country with a high rate of drug resistance
 Poor response to standard therapy
 Positive sputum smears (acid-fast bacilli) or culture ≥2 month after
initiating appropriate therapy
5/7/2024
86
LESS COMMONLY USED DRUGS FOR TREATING DRUG-RESISTANT
TUBERCULOSIS IN INFANTS, CHILDREN, AND ADOLESCENTS
 Amikacin Am
 Capreomycin Cm
 Cycloserine Cs
 Ethionamide Eto
 Kanamycin Km
 Levofloxacin Lfx
 para-Aminosalicylic acid (PAS)
 Streptomycin S
5/7/2024
87
MDR –TB TREATMENT IN ETHIOPIA
 Patients with MDR-TB confirmation, but no full DST result available yet
Regimen E-Z-KM(Am)-Lfx- Eto-Cs
 MDR TB susceptible to kanamycin but not to quinolones
Regimen E-Z-KM(Am)-Mfx- Eto-Cs-PAS
 MDR TB susceptible to quinolone but not to Kanamycin
Regimen E-Z-Cm-Lfx –Eto-Cs
 XDR-TB (MDR-TB and resistace to quinolones and kanamycin
Regimen E-Z-Cm-Mfx –Eto-Cs-PAS
Duration of treatment
Intensive phase- the injectable agents is used for a minimum of 8 months and at
least 4 months after culture conversion
Continuation phase- The total treatment is for a minimum of 18 months beyond
culture conversion
5/7/2024
88
SCREEN EVERY PATIENT
FOR
HIV SUSPECTED TO HAVE
TB
5/7/2024
89

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Childhood Tuberculosis (Dr. Getnet).pptx

  • 2. OUT LINE  Introduction  Etiology  Epidemiology  Clinical manifestation  Types of tuberculosis  Diagnosis  Treatment 5/7/2024 2
  • 3. INTRODUCTION  During the last decade of the 20th century the number of new cases of tuberculosis increased worldwide.  Currently, 95% of tuberculosis cases occur in developing countries because of the following  HIV/AIDS epidemics (have had the greatest impact )  Lack of resource for proper identification and treatment of these diseases  Poor social economic condition  Over crowding living condition 5/7/2024 3
  • 4. CONT’D…  Almost 1.3 million cases and 450,000 deaths occur in children each year.  More than 1/3rd of the world's population is infected with Mycobacterium tuberculosis  According to the latest WHO Global TB Report 2011, there were an estimated 8.8 million incident cases of TB globally  In 2010, of which 1.1 million were among people living with HIV  MDR-TB is estimated to be 1.6% among all new TB cases and 12% among all previously treated TB cases 5/7/2024 4
  • 5. ETIOLOGY  53 different species of mycobacterium  3 species cause TB in humans  M.tuberculosis  M.bovis  M. africanum  M.microti  M. canetti  M. tuberculosis is the most important cause of tuberculosis disease in humans. 5/7/2024 5
  • 6. Mycobacterium tuberculosis ●an aerobic ●Slow growing ,curved rod with a generation time of 12-24 hr. A hallmark of all mycobacteria is acid fastness—the capacity to form stable mycolate complexes with arylmethane dyes such as crystal violet, carbolfuchsin, auramine, and rhodamine  Once stained, they resist decoloration with ethanol and hydrochloric or other acids  Isolation from clinical specimens on solid synthetic media usually takes 3-6 wk, and drug susceptibility testing requires an additional 4 wk. Cont’d… 5/7/2024 6
  • 8. TRANSMISSION  Inhalation  Ingestion of milk  Transplacental  Increased risk with when the patient has:  positive acid-fast smear of sputum  an extensive upper lobe infiltrate or cavity  copious production of thin sputum  severe and forceful cough and sneezing (single cough can produce 3,000 bacilli. 5/7/2024 8
  • 9. CONT’D…  Latent tuberculosis infection (LTBI)  A reactive tuberculin skin test (TST) and the absence of clinical and radiographic manifestations are the hallmark of LTBI  Untreated infants with LTBI have up to a 40% likelihood of developing tuberculosis, with the risk for progression decreasing gradually through childhood to adult lifetime rates of 5-10%.  The greatest risk for progression occurs in the first 2 yr after infection 5/7/2024 9
  • 10. RISK FACTORS FOR PROGRESSION OF LATENT TUBERCULOSIS INFECTION TO TB DISEASE.  Immunity status  Nutritional status  Intercurrent illness  Length of time of exposure  # of bacteria inhaled  Age at infection Infants and children ≤4 yr of age, especially those <2 yr 5/7/2024 10
  • 12. PATHOGENESIS  The lung is the portal of entry in >98% of cases  The tubercle bacilli multiply initially within alveoli and alveolar ducts  Most of the bacilli are killed, but some survive within non activated macrophages, which carry them through lymphatic vessels to the regional lymph nodes  Primary complex (Ghon complex), which is the combination of a parenchymal pulmonary lesion and a corresponding lymph node site,  Tubercle bacilli are often carried to most tissues of the body through the blood and lymphatic vessels. 5/7/2024 12
  • 13. CONT’D…  The parenchymal portion of the primary complex often heals completely by fibrosis or calcification after undergoing caseous necrosis and encapsulation  If caseation is intense, the center of the lesion liquefies and empties into the associated bronchus, leaving a residual cavity  Disseminated tuberculosis occurs if the number of circulating bacilli is large and the host's cellular immune response is inadequate 5/7/2024 13
  • 14. NATURAL HISTORY OF TB  In the great majority (90-95%) of infected persons the immunological defence either kills the inhaled or ingested bacilli or keeps them suppressed (silent focus) causing ‘latent Tuberculosis infection’  Only 5-10% of such infected persons (primary infection) develop active disease  Following primary infection, rapid progression to disease is more common in children less than 5 years of age.  Patients with weakened immune systems, such as those with HIV infection, are at greater risk of developing TB disease.  HIV positive people with latent TB infection have a 10% annual and 50% life time risk of developing active TB disease 5/7/2024 14
  • 15.  Active TB disease arises from progression of the primary lesion as a continuous process within a year or so after infection, or from endogenous reactivation of latent foci, which remained dormant since the initial infection or exogenous re-infection.  If untreated, TB leads to death within 5 years in at least 50 % of the patients.  Without treatment, about 20 to 25% could have natural healing and 25 to 30% could remain chronically ill, thus continuing to spread the disease in the community. Cont’d… 5/7/2024 15
  • 16. CONT’D…  The time between initial infection and clinically apparent disease is variable.  Disseminated and meningeal tuberculosis are early manifestations, often occurring within 2-6 mo of acquisition.  Significant lymph node or endobronchial tuberculosis usually appears within 3-9 mo.  Lesions of the bones and joints take several years to develop,  Renal lesions become evident decades after infection  Extra pulmonary manifestations develop in 25-35% of children with tuberculosis, compared with about 10% of immuno competent adults with tuberculosis 5/7/2024 16
  • 18. IMMUNITY AND TUBERCULOSIS INFECTION  Conditions that adversely affect cell-mediated immunity predispose to progression from tuberculosis infection to disease.  Cell-mediated immunity develops 2-12 wk after infection, along with tissue hypersensitivity .  Tuberculosis infection is associated with a humoral antibody response, which appears to play little role in host defense.  In immunocompetent persons the response to the initial infection with M. tuberculosis usually provides protection against reinfection when a new exposure occurs. 5/7/2024 18
  • 19. CLINICAL MANIFESTATION  Primary Pulmonary Disease  Progressive Primary Pulmonary Disease  Reactivation Tuberculosis  Extrapulmonary tuberculosis 5/7/2024 19
  • 20. PRIMARY PULMONARY DISEASE  common type of TB in children  The primary complex Parenchymal pulmonary focus + the regional LN is the hall mark.  Partial obstruction of the bronchus caused by external compression can cause hyperinflation in the distal lung segment and complete obstruction results in atelectasis.  Inflamed caseous nodes can attach to the bronchial wall and erode through it, causing endobronchial tuberculosis or a fistula tract  The caseum causes complete obstruction of the bronchus. The resulting lesion is a combination of pneumonitis and atelectasis and has been called a collapse-consolidation or segmental lesion  Erosion of a parenchymal focus of tuberculosis into a blood or lymphatic vessel can result in dissemination of the bacilli and a miliary pattern. 5/7/2024 20
  • 22. PROGRESSIVE PRIMARY PULMONARY DISEASE  Rare  Serious complications  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. 5/7/2024 22
  • 23. REACTIVATION TUBERCULOSIS(20 TB)  Reactivation TB results when the persistent bacteria in a host suddenly proliferate  This form of tuberculosis is rare in childhood but can occur in adolescence  Only 5 to 10 % of patients with no underlying medical problems who become infected develop active disease in their lifetime.  The most common form is an infiltrate or cavity in the apex of the upper lobes, where oxygen tension and blood flow are great.  The most common pulmonary sites are the original parenchymal focus, lymph nodes, or the apical seeding (Simon foci) established during the hematogenous phase of the early infection 5/7/2024 23
  • 24. IMMUNOSUPPRESSIVE CONDITIONS ASSOCIATED WITH REACTIVATION TB  HIV infection and AIDS  End-stage renal disease  Diabetes mellitus  Malignant lymphoma  Corticosteroid use  Diminution in Cell Mediated Immunity associated with old age ,measles 5/7/2024 24
  • 25. CONT’D…  In contrast to primary disease, the disease process in reactivation TB tends to be localized, because the established immune response prevents further extra pulmonary spread.  there is little regional lymph node involvement and less caseation  The lesion typically occurs at the lung apices, and disseminated disease is unusual, unless the host is severe immunosuppressed  Children with a healed tuberculosis infection acquired at <2 yr of age rarely develop chronic reactivation pulmonary disease.  More common in those who acquire the initial infection at >7 yr of age 5/7/2024 25
  • 26. CONT’D…  Older children and adolescents with reactivation tuberculosis are more likely to experience fever, anorexia, malaise, weight loss, night sweats, productive cough, hemoptysis, and chest pain than children with primary pulmonary tuberculosis  Most signs and symptoms improve within several weeks of starting effective treatment, although the cough can last for several months  The most common radiographic presentations of this type of tuberculosis are extensive infiltrates or thick-walled cavities in the upper lobes. 5/7/2024 26
  • 27. THE MOST COMMON RADIOGRAPHIC PRESENTATIONS OF THIS TYPE OF TUBERCULOSIS ARE EXTENSIVE INFILTRATES OR THICK-WALLED CAVITIES IN THE UPPER LOBES 5/7/2024 27
  • 30. PLEURAL EFFUSION  Larger and clinically significant effusions occur months to years after the primary infection.  Tuberculous pleural effusion is uncommon in children <6 yr of age and rare in children <2 yr of age.  Effusions are usually unilateral but can be bilateral.  They are rarely associated with a segmental pulmonary lesion and are uncommon in disseminated tuberculosis. 5/7/2024 30
  • 31. CONT’D…  characterized by low to high fever  shortness of breath, chest pain on deep inspiration, and diminished breath sounds.  The fever and other symptoms can last for several weeks after the start of antituberculosis chemotherapy.  The TST is positive in only 70-80% of cases.  The prognosis is excellent, but radiographic resolution often takes months.  Scoliosis is a rare complication from a long-standing effusion CXR 5/7/2024 31
  • 32. DX Pleural fluid analysis  Color =yelow or straw color/rarely hemorrhagic.  Cell =lymphocytic predominance  Rarely TB empyema  Culture <30% positive  AFB microscopy is rarely +ve  Pleural Biopsy demonstrate AFB /granulomatous change  Protein level is usually 2-4 g/dL, and the glucose concentration may be low (20-40 mg/ dL)  The specific gravity is usually 1.012-1.025,  Biopsy of the pleural membrane is more likely to yield a positive acid-fast stain or culture, and granuloma formation usually can be demonstrated. 5/7/2024 32
  • 33. PERICARDIAL DISEASE  The most common form of cardiac tuberculosis is Pericarditis.  rare, occurring in 0.5-4% of tuberculosis cases in children.  usually arises from direct invasion or lymphatic drainage from subcarinal lymph nodes  Symptoms are nonspecific, including low-grade fever, malaise, and weight loss.  A pericardial friction rub or distant heart sounds with pulsus paradoxus may be present  The pericardial fluid is typically serofibrinous or hemorrhagic.  Acid-fast smear of the fluid rarely reveals the organism, but cultures are positive in 30-70% of cases.  The culture yield from pericardial biopsy may be higher, and the presence of granulomas often suggests the diagnosis.  Partial or complete pericardiectomy may be required when constrictive pericarditis develops. 5/7/2024 33
  • 34. LYMPHOHEMATOGENOUS (DISSEMINATED) DISEASE  The most clinically significant form of disseminated tuberculosis is Miliary disease, which occurs when massive numbers of tubercle bacilli are released into the bloodstream, causing disease in 2 or more organs.  The clinical picture may be acute, more often it is indolent and prolonged, with spiking fever accompanying the release of organisms into the bloodstream.  Early pulmonary involvement is surprisingly mild, but diffuse involvement becomes apparent with prolonged infection  Bones and joints or kidneys also can become involved. 5/7/2024 34
  • 35. CONT’D…  Generalized lymphadenopathy and hepatosplenomegaly develop within several weeks in about 50% of cases.  Meningitis or peritonitis are found in 20-40% of patients with advanced disease  Cutaneous lesions include papulonecrotic tuberculids, nodules, or purpura  Choroid tubercles occur in 13-87% of patients and are highly specific for the diagnosis of miliary tuberculosis  Unfortunately, the TST is nonreactive in up to 40% of patients with disseminated tuberculosis. 5/7/2024 35
  • 37. UPPER RESPIRATORY TRACT DISEASE  laryngeal tuberculosis have a croup-like cough, sore throat, hoarseness, and dysphagia.  Most children with laryngeal tuberculosis have extensive upper lobe pulmonary disease  Tuberculosis of the middle ear results from aspiration of infected pulmonary secretions into the middle ear or from hematogenous dissemination in older children.  The most common signs and symptoms are painless unilateral otorrhea, tinnitus, decreased hearing, facial paralysis, and a perforated tympanic membrane.  Diagnosis is difficult, because stains and cultures of ear fluid are often negative. 5/7/2024 37
  • 38. LYMPH NODE DISEASE  TB of superficial lymph nodes (scrofula) is the most common form of extra pulmonary tuberculosis in children .  The nodes usually enlarge gradually in the early stages of lymph node disease.  They are discrete, nontender, and firm but not hard.  The nodes often feel fixed to underlying or overlying tissue.  Disease is most often unilateral, but bilateral involvement can occur because of the crossover drainage patterns of lymphatic vessels in the chest and lower neck. 5/7/2024 38
  • 39. CONT’D…  As infection progresses, multiple nodes are infected, resulting in a mass of matted nodes.  Systemic signs and symptoms other than a low-grade fever are usually absent.  The TST is usually reactive, but the chest radiograph is normal in 70% of cases.  The onset of illness is occasionally more acute, with rapid enlargement, tenderness, and fluctuance of lymph nodes and with high fever.  The initial presentation is rarely a fluctuant mass with overlying cellulitis or skin discoloration 5/7/2024 39
  • 40. CONT’D…  Lymph node tuberculosis can resolve if left untreated but more often progresses to caseation and necrosis.  The capsule of the node breaks down, resulting in the spread of infection to adjacent nodes.  Rupture of the node usually results in a draining sinus tract that can require surgical removal.  Dx - FNAC, Biopsy ,AFB ,Tissue culture(50%+ve) 5/7/2024 40
  • 42. CENTRAL NERVOUS SYSTEM DISEASE (CNS TB)  Most serious complication in children and is fatal without prompt and appropriate treatment.  The brain stem is often the site of greatest involvement, which accounts for the commonly associated dysfunction of cranial nerves III, VI, and VII.  It is most common in children between 6 mo and 4 yr of age.  The clinical progression of tuberculous meningitis may be rapid or gradual. 5/7/2024 42
  • 43. CONT’D… More commonly, the signs and symptoms progress slowly over several weeks and can be divided into 3 stages Stage 1  lasts 1-2 wk  characterized by nonspecific symptoms such as fever, headache, irritability, drowsiness, and malaise.  Focal neurologic signs are absent, but infants can experience a stagnation or loss of developmental milestones. 5/7/2024 43
  • 44. CONT’D… Stage 2  Usually begins more abruptly  Common features are lethargy, nuchal rigidity, seizures  positive Kernig and Brudzinski signs, hypertonia, vomiting, cranial nerve palsies, and other focal neurologic signs.  The accelerating clinical illness usually correlates with the development of hydrocephalus, increased intracranial pressure, and vasculitis. Stage 3  is marked by coma, hemiplegia or paraplegia  hypertension, decerebrate posturing, deterioration of vital signs, and eventually death 5/7/2024 44
  • 45. CNS –TB FORMS  BRAIN 1) Tb meningitis 2) encephalopathy 3) vasculopathy 4) tuberculoma 5) brain abscess Spinal cord 1) arachidonitis 2) Para spinal abscess 3) pot’s disease 4) Radiculopathy 5/7/2024 45
  • 46. CONT’D… DX  The TST is nonreactive in up to 50% of cases, and  20-50% of children have a normal chest radiograph  The CSF leukocyte count usually ranges from 10 to 500 cells/mm3.  PNC leukocytes may be present initially, but lymphocytes predominate in the majority of cases.  The CSF glucose is typically <40mg/dL but rarely <20mg/dL.  The protein level is elevated and may be markedly high (400- 5,000mg/dL) secondary to hydrocephalus and spinal block.  MRI and CT scan , demonstrate basal enhancement with communicating hydrocephalus. 5/7/2024 46
  • 47. TUBERCULOMA  a tumor-like mass resulting from aggregation of caseous tubercles that usually manifests clinically as a brain tumor  In adults tuberculomas are most often supratentorial, but in children they are often infratentorial, located at the base of the brain near the cerebellum  Tuberculomas account for up to 40% of brain tumors in some areas of the world.  Lesions are most often singular but may be multiple.  The most common symptoms are headache, fever, and convulsions  On CT or MRI of the brain, tuberculomas usually appear as discrete lesions with a significant amount of surrounding edema.  Contrast medium enhancement is often impressive and can result in a ring like lesion 5/7/2024 47
  • 48. BONE AND JOINT DISEASE  TB usually affects weight bearing bones or joints, and most common sites are vertebrae, hip, knee and ankle  The classic manifestation of tuberculous spondylitis is progression to Pott disease, in which destruction of the vertebral bodies leads to gibbus deformity and kyphosis .  Tuberculous bone lesions can resemble pyogenic and fungal infections or bone tumors  A catastrophic complication of Pott's disease is paraplegia, which is usually due to an abscess or a lesion compressing the spinal cord  Multifocal bone involvement can occur  A bone biopsy is essential to confirm the diagnosis 5/7/2024 48
  • 50. ABDOMINAL AND GASTROINTESTINAL DISEASE  Any part of the GIT can be involved TB enteritis The pathogenesis of tuberculous enteritis has been attributed to four mechanisms  Swallowing infected sputum  Hematogenous spread from active pulmonary or miliary TB  Ingestion of contaminated milk or food  Contiguous spread from adjacent organs 5/7/2024 50
  • 51. CONT’D… The macroscopic appearance of the intestinal lesions can be categorized as follows  Ulcerative type  Hyper plastic type  Skip lesion of the intestine  Pan colitis form  Hyperplasic type presented as intestinal obstruction  Ulcerative forms usually have chronic dysentery with other symptoms  The jejunum and ileum near Payers patches and the appendix are the most common sites of involvement.  Biopsy, acid-fast stain, and culture of the lesions are usually necessary to confirm the diagnosis. 5/7/2024 51
  • 52. TUBERCULOUS PERITONITIS  Occurs most often in young men and is uncommon in adolescents and rare in children.  Generalized peritonitis can arise from subclinical or miliary hematogenous dissemination.  Localized peritonitis is caused by direct extension from an abdominal lymph node, intestinal focus, or genitourinary tuberculosis.  Rarely, the lymph nodes, omentum, and peritoneum become matted and can be palpated as a doughy irregular non tender mass.  Abdominal pain or tenderness, ascites, anorexia, and low-grade fever are typical manifestations.  The TST is usually reactive. 5/7/2024 52
  • 53.  Types of TB peritonitis 1)Dry peritonitis type 2)Hyper plastic type (mass) 3) ascetic form(fluid collection) 4)Acute abdomen  Dx  clinical suspicions  CXR  Abd us  Ascitic fluid analysis  Biopsy 5/7/2024 53
  • 54. GENITOURINARY DISEASE(RENAL TB)  Renal tuberculosis is rare in children, because the incubation period is several years or longer  Usually during lymphohematogenous spread(miliary).  In true renal tuberculosis, small caseous foci develop in the renal parenchyma and release M. tuberculosis into the tubules.  Infection then spreads locally to the ureters, prostate, or epididymis.  Often clinically silent in its early stages, (marked only by sterile pyuria and microscopic hematuria  Dysuria, flank pain,gross hematuria (late stage) 5/7/2024 54
  • 55. CONT’D…  Hydronephrosis or ureteral strictures can complicate the disease.  Urine cultures for M. tuberculosis are positive in 80-90% of cases, and acid-fast stains of large volumes of urine sediment are positive in 50-70% of cases.  An intravenous pyelogram or CT scan often reveals mass lesions, dilatation of the proximal ureters, multiple small filling defects, and hydronephrosis if ureteral stricture is present.  Disease is most often unilateral 5/7/2024 55
  • 56. GENITAL TB  In females of genital tract the fallopian tubes are most often involved (90-100% of cases), followed by the endometrium (50%), ovaries (25%), and cervix (5%).  Genital tuberculosis in adolescent boys causes epididymitis or orchitis. 5/7/2024 56
  • 57. DISEASE IN HIV-INFECTED CHILDREN  Establishing the diagnosis of tuberculosis in an HIV-infected child may be difficult, because  Skin test reactivity can be absent and culture confirmation is difficult  Similar C/F to many other HIV-related infections and conditions  Tuberculosis in HIV-infected children is often more severe, progressive, and likely to occur in extra pulmonary sites.  Radiographic findings are similar to those in children with normal immune systems, but lobar disease and lung cavitations are more common.  Nonspecific respiratory symptoms, fever, and weight loss are the most common complaints.  Rates of drug-resistant tuberculosis tend to be higher in HIV-infected adults and probably are also higher in HIV-infected children.  All children with tuberculosis disease should be tested for HIV co- infection 5/7/2024 57
  • 58. PERINATAL DISEASE  Associated with risk for prematurity, fetal growth retardation, low birthweight, and perinatal mortality.  Congenital tuberculosis is rare because the most common result of female genital tract tuberculosis is infertility.  Primary infection in the mother just before or during pregnancy is more likely to cause congenital infection than is reactivation of a previous infection.  The tubercle bacilli first reach the fetal liver, where a primary focus with periportal lymph node involvement can occur.  The bacilli in the lung usually remain dormant until after birth, when oxygenation and pulmonary circulation increase significantly. 5/7/2024 58
  • 59.  Congenital tuberculosis can be caused through placenta ,aspiration or ingestion of infected amniotic fluid.  However, the most common route of infection for the neonate is postnatal airborne transmission from an adult with infectious pulmonary tuberculosis .  Symptoms of congenital tuberculosis may be present at birth but more commonly begin by the 2nd or 3rd wk of life.  The most common signs and symptoms are  Respiratory distress, fever, hepatic or spleen enlargement,  Poor feeding, lethargy or irritability, lymphadenopathy,  Abdominal distention, failure to thrive, ear drainage, and skin lesions.  Many infants have an abnormal chest radiograph, most often with a miliary pattern. Cont’d… 5/7/2024 59
  • 60. CONT’D…  Hilar and mediastinal lymphadenopathy and lung infiltrates are common.  Generalized lymphadenopathy and meningitis occur in 30-50% of patients.  Dx is often challenging can mimic sepsis or TORCHS  The most important clue for rapid diagnosis of congenital tuberculosis is a maternal or family history of tuberculosis  The infant's TST is negative initially but can become positive in 1- 3 mo  The mortality rate of congenital tuberculosis remains very high if not diagnosed and treated early  CSF should be examined and cultured, although the yield for isolating M. tuberculosis is low 5/7/2024 60
  • 61. CONT’D… Prevention of perinatal TB  Appropriate testing and treatment of the mother and other family members for TB  High-risk pregnant women should be tested with a TST or IGRA, and those with a positive test result should receive a chest radiograph.  If the mother’s chest radiograph or acid-fast sputum smear shows evidence of current tuberculosis disease,INH therapy is recommended for the newborn after ruling out active TB. 5/7/2024 61
  • 62. DIAGNOSTIC METHODS OF TB  X-rays  Tuberculin skin test(TST)  Culture  Biopsy  Molecular test - PCR GeneXpert MTB/RIF Line probe Assay  AFB Stains  Ziel Nielson  Flourochrome  T-cell based interferon-gamma assays  QuantiFERON-TB gold  T-SPOT.TB 5/7/2024 62
  • 63. TUBERCULIN SKIN TESTING  The Mantoux TST is the intradermal injection of 0.1 mL purified protein derivative (PPD). Recruitment of sensitized T cells to the skin ↓ lymphokines ↓ Indurations( measure after 48-72hrs)  Tuberculin sensitivity develops 3 wk to 3 mo (most often in 4-8 wk) after inhalation of organisms 5/7/2024 63
  • 65. CONT’D…  A TST should be regarded as positive:  >5 mm diameter of induration: in children who are immunosuppressed including HIV-positive children and severely malnourished children, i.e. those with clinical evidence of marasmus or kwashiorkor  >10mm diameter of induration: in all other children (whether they have received a BCG vaccination or not) 5/7/2024 65
  • 66. FALSE NEGATIVE PPD TEST  Severe PEM  Measles  Overwhelming TB  Wrong techniques  HIV  Steroids  Cancer 5/7/2024 66
  • 67. FALSE POSITIVE PPD TEST  Atypical mycobacterial infections  Hypersensitivity to constituents  BCG vaccination 5/7/2024 67
  • 68. AFB MICROSCOPY  Sputum(spot/morning /spot ) ;Induced sputum AFB/Cultutre  Gastric aspirate (three early morning sample)  Early morning gastric aspirate(3x=50% positive culture)  Any body fluid  Urine…… etc(with centrifugation) 5/7/2024 68
  • 69. GENEXPERT MTB/RIF • For the diagnosis of pulmonary TB and rifampicin resistance • Is new rapid test for TB • Fully automated • Provides accurate results in 100 minutes  Indicated ( national guideline ) in:  MDRTB  TB/HIV  Children  Extra pulmonary TB 5/7/2024 69
  • 70. LINE PROBE ASSAY  new test that use molecular technology  identify presence or absence of specific mutation on genes of TB bacilli which are responsible for Isoniazid and Rifampcin resistance  Rapid and accurate test  MDR-TB can be proved on the same day 5/7/2024 70
  • 72. # It can be difficult to clearly define what is “suggestive of PTB” on clinical or radiological findings in HIVinfected children because of clinical overlap between PTB and other forms of HIV-related lung disease. # CXR abnormalities of PTB in HIV-infected child are similar to those in HIV-uninfected child. 5/7/2024 72
  • 73. ANY ONE OF THE FOLLOWING IS SUGGESTIVE OF TB: i. Radiological picture of miliary pattern ii. Pathologic findings compatible with TB (Pathology) iii. Culture positive iv. Isolation of the organism by acid fast staining 5/7/2024 73
  • 74. TREATMENT Principles of TB Treatment 1.Chemotherapy 2.Adjuvant therapy 3.Nutritional therapy 4.Family screening 5.Follow up 5/7/2024 74
  • 75. 1.CHEMOTHERAPY  2 treatment phases A. Intensive phase 4 drugs for 2 month ( New cases) and 3months (Retreatment)  It renders the patient non-infectious by rapidly reducing the load of bacilli in the sputum ,usually within 2-3 weeks B. Continuation phase  2drugs for 4mths ( new case)  3 drugs for 5 months (retreatment)  It ensure cure, and prevents relapse after completion of treatment  EXCEPTIONS In Children with TB meningitis and osteo- articular TB , the continuation phase should be 10 months 5/7/2024 75
  • 76. COMMONLY USED DRUGS FOR THE TREATMENT OF TUBERCULOSIS IN INFANTS, CHILDREN, AND ADOLESCENTS DRUG DAILY DOSAGE, mg/kg MAXIMUM DOSE ADVERSE REACTIONS Ethambutol 20 1600mg Optic neuritis (usually reversible), decreased red-green color discrimination, gastrointestinal tract disturbances, hypersensitivity Isoniazid 10-15 300mg Mild hepatic enzyme elevation, hepatitis, peripheral neuritis, hypersensitivity Pyrazinamide 20-40 2gm Hepatotoxic effects, hyperuricemia, arthralgias, gastrointestinal tract upset Rifampicin 10-20 600 Orange discoloration of secretions or urine, vomiting, hepatitis, influenza-like reaction, thrombocytopenia, pruritus 5/7/2024 76
  • 77. A. FDC DOSING REGIMEN FOR NEW CASES 5/7/2024 77
  • 78. B.FDC DOSING REGIMENS FOR RETREATMENT CASES 5/7/2024 78
  • 79. 2.ADJUVANT THERAPY Indication for steroid  CNS  Pericarditis  Miliary TB with acute air blocking syndrome  Tb adrenalitis  The most commonly prescribed regimen is prednisone, 1- 2 mg/kg/day in 1-2 divided doses orally for 4-6 wk, followed by gradual tapering. Indication for pyridoxine  RVI pts  Malnutrition  Chronic diarrhea  Breast feeding 5/7/2024 79
  • 80. 3.FAMILY SCREENING  Those under five children  Pregnant ladies  Elders,age >65 yrs  All HIV /AIDS pts at home 5/7/2024 80
  • 81. 4.FOLLOW UP  Children, parents, and other close family members should be educated about TB  Directly observed therapy(DOT) should be used for all children  Asses two weeks after treatment initiation, after intensive phase and every 2 month until treatment completion  assess treatment adherence, adverse events, weight  A follow up sputum for AFB at 2months should be done for any child who was smear positive at diagnosis.  A child who is not responding, should be assessed for drug resistant TB 5/7/2024 81
  • 82. AVAILABLE APPROACHES TO PREVENT TB IN CHILDREN 5/7/2024 82
  • 83. TREATMENT OF LATENT TUBERCULOSIS INFECTION Indication  All under 5 yrs that have household contacts of a case with sputum smear positive TB with no evidence of TB disease  HIV infected children at all age  Recommended dosage INH 10 mg/kg daily for 6 months 5/7/2024 83
  • 84. DRUG-RESISTANT TUBERCULOSIS  The incidence of drug-resistant tuberculosis is increasing in many areas of the world  There are two major types of drug resistance  Primary resistance occurs when a person is infected with M. tuberculosis that is already resistant to a particular drug.  Secondary resistance occurs when drug-resistant organisms emerge as the dominant population during treatment  Most drug resistance in children is primary  Secondary resistance is rare in children because of the small size of their mycobacterial population 5/7/2024 84
  • 85. CASE DEFINITION OF DRUG RESISTANCE TB  Mono resistance: Resistance to only one first line drugs  Poly-resistance: Resistance to more than one first line drugs, but not to both isoniazid and rifampicin  Multidrug resistance (MDR): Resistance to at least isoniazid and rifampicin  Extensive drug resistance(XDR): MDR as well as any fluoroquinolone, and any of the second line injectable anti TB drugs( capreomycin, kanamycin,and amikacin 5/7/2024 85
  • 86. RISK FACTORS FOR DRUG-RESISTANT TUBERCULOSIS  Personal or contact history of treatment for tuberculosis  Contacts of patients with drug-resistant tuberculosis  Birth or residence in a country with a high rate of drug resistance  Poor response to standard therapy  Positive sputum smears (acid-fast bacilli) or culture ≥2 month after initiating appropriate therapy 5/7/2024 86
  • 87. LESS COMMONLY USED DRUGS FOR TREATING DRUG-RESISTANT TUBERCULOSIS IN INFANTS, CHILDREN, AND ADOLESCENTS  Amikacin Am  Capreomycin Cm  Cycloserine Cs  Ethionamide Eto  Kanamycin Km  Levofloxacin Lfx  para-Aminosalicylic acid (PAS)  Streptomycin S 5/7/2024 87
  • 88. MDR –TB TREATMENT IN ETHIOPIA  Patients with MDR-TB confirmation, but no full DST result available yet Regimen E-Z-KM(Am)-Lfx- Eto-Cs  MDR TB susceptible to kanamycin but not to quinolones Regimen E-Z-KM(Am)-Mfx- Eto-Cs-PAS  MDR TB susceptible to quinolone but not to Kanamycin Regimen E-Z-Cm-Lfx –Eto-Cs  XDR-TB (MDR-TB and resistace to quinolones and kanamycin Regimen E-Z-Cm-Mfx –Eto-Cs-PAS Duration of treatment Intensive phase- the injectable agents is used for a minimum of 8 months and at least 4 months after culture conversion Continuation phase- The total treatment is for a minimum of 18 months beyond culture conversion 5/7/2024 88
  • 89. SCREEN EVERY PATIENT FOR HIV SUSPECTED TO HAVE TB 5/7/2024 89

Editor's Notes

  1.       Persons with skin test conversion in the past 1-2 yr    Persons who are immunocompromised, especially in cases of malignancy and solid organ transplantation, immunosuppressive medical treatments including anti–tumor necrosis factor therapies, Diabetes mellitus, chronic renal failure, silicosis, and malnutrition
  2. ADA(40IU/dl) test is very important
  3. Pulsus paradoxus (PP), also paradoxic pulse or paradoxical pulse, is an abnormally large decrease in systolic blood pressure and pulse wave amplitude during inspiration. When the drop is more than 10 mm Hg, it is referred to as pulsus paradoxus.
  4. Choroid tubercles-Ophthal-moscopically, they appear as round pale yellow spots usually near optic disc.
  5. INTERFERON-γ RELEASE ASSAY (IGRA)
  6. Tween 80