Pediatric tuberculosis

Objectives
 Define tuberculosis
 Mention etiologic factors of TB in children
 Describe Pathogenesis of TB infection
 Explain methods of TB spreading
 Classify TB infection
 Describe clinical manifestations of TB
 Explain diagnosis method of TB
 Discuss management of TB infection
 What is tuberculosis?
 Tuberculosis is an ongoing (chronic) highly
infectious granulomatous disease caused by
Mycobacterium tuberculosis.
 Tuberculosis generally affects the lungs but can
also affect other parts of the body.
 Is historically called “consumption” the marked
weight loss.

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 Epidemiology
 As WHO (2018) estimated that one third of
the world’s population is infected with
Mycobacterium.
 Each year, about 9 million people develop TB,
of whom about 2 million die.
 Of the 9 million annual TB cases, about 15%
occur in children (under 15 years of age).

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 Cont….
 TB in children is often missed or overlooked
due to non-specific symptoms and difficulties
in diagnosis.
 This has made it difficult to assess the actual
magnitude of the childhood TB epidemic.
 Untreated infants with LTBI have up to a 40%
likelihood of developing tuberculosis,

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 Cont…
 70-80% of children with TB have the disease in
their lungs (pulmonary TB).
 The rest 20-30% are affected by TB disease in
other parts of their body (extra pulmonary TB).
 In high burden TB settings it has been noted
that 15-20% of all TB cases are among
children,
 whereas in low burden TB settings it is
estimated that 2-7% of all TB cases are among
children.

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 Cont…
 The global burden of TB remains enormous in:
HIV epidemics and other immunosuppressed
patients
Children
Poverty
Over crowding
Inefficient TB control programs
Inadequate health coverage & poor access to
health services.
 Etiology
 Mycobacterium Tuberculous complex:
 [Link] = Mainly
 [Link] = sometimes
 [Link]
 [Link]
 [Link]
 All belong to the order Actinomycetales and
family Mycobacteriaceae.
 Cont…
 M. tuberculosis is the most important
cause of tuberculosis disease in humans.
 The tubercle bacilli are:
 Non–spore-forming
 Non-motile
 Pleomorphic
 Weakly gram-positive
 Curved rods
 2–4µm long
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 Risk factors
Risk of infection depends on 2 factors:
 Extent of exposure to infectious droplet nuclei
and
 Susceptibility to infection.
 Close contacts of person with TB
 Low socio-economic status
 Infants & children below 5yrs of age (esp.<2yrs)
 Co-infected with HIV
 Immuno-compromization (malignancy, drugs,
DM, malnutrition)
 Others
 Pathophysiology
Understanding the natural history of TB is
fundamental to appreciate the variable vulnerability
and the diverse spectrum of disease observed in
children.
 A few bacilli reach a terminal airway.
 Then, localized inflammatory process occurs
with in the lung, referred to as the primary
(Ghon) focus.

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 Cont..

 From where bacilli the systemic

circulation via regional lymph nodes and
to other body parts.
 Bacilli may survive and attack target
organs for prolonged period depending on
pathogen-host interaction at the site of
deposition.

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Pathogenesis
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 Transmission
 Usually by airborne mucus droplet nuclei when
coughing, sneezes, speaks, sings or loughs.
 Rarely occurs by direct contact with an infected
discharge.
 Vertical transmission (before, after and during
birth).
The chance of transmission increases:
 When the patient has an acid-fast smear positive
 An extensive upper lobe infiltrate or cavity
 Copious production of thin sputum
 Severe and forceful cough.
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Cont…

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?
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 Cont…
Transmission of TB via airborne droplet nuclei with
Aerosol-producing investigations; 10-200 droplets
can cause TB infection.
 Cough – 3000 droplet nuclei
 Sneeze – up to 1 million droplet nuclei
 Cont…
 Droplet nuclei can stay airborne for up to 72
hours (like dark, damp rooms), but sunlight kills
them.
 The most infectious person has PTB and lung
cavities – usually older than 12-years-old.
 EPTB is generally not infectious unless they also
have PTB.
 Latent TB is not infectious because TB is not
replicating or causing them to cough.
 Classification of Tuberculosis
 Pulmonary TB = Affects the lungs
 Extra Pulmonary TB =Not primarily located in the
lungs
 Lymph node TB, TB meningitis, Milliary TB,
TB spondylitis, cutaneous TB, GU TB, GIT TB
of bones and joints & others
 Drug resistance TB
 Mono-resistance TB, Poly-resistance TB
 MDR-TB, XDR-TB and TDR-TB

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Cont…

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 The stages of TB

Exposure: Contact of child with person who has TB

,but negative skin test, normal chest x-ray and no
S/S.
Tuberculosis infection (latent stage TB):
 The tuberculin skin test (TST)/PPD/
mantoux test is positive, but absence of
clinical manifestation and normal Chest
radiograph is radiographic.

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 Cont..
Tuberculosis disease (Active TB stage):
“The word tuberculosis refers to disease.”
 Clinical signs and symptoms of TBC
Chronic cough (> 2 weeks)
Night sweat, loss of appetite
Unexplained weight loss
Unexplained fever for > 2 weeks
Failure to respond to broad spectrum antibiotics
 Chest findings
 Signs of consolidation/cavitation/Collapse
 Signs of fluid especially on the left side
 Localized wheezing
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 Diagnosis of Tuberculosis
 Using clinical features
 On examination
 Assessing contact history ???
 Perform mantoux test/TST/PPD skin test.
 AFB detection via microscopy
 MTB isolation by culture
 MTB/RIF detection by Gene Xpert
 Obtain a chest X-ray.

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 Diagnosis of Tuberculosis
 Using clinical features
 On examination
 Assessing contact history ???
 Perform mantoux test/TST/PPD skin
test.
 Interferon Gamma Release Assays
(IGRA) blood tests
 AFB detection via microscopy
 MTB isolation by culture
 MTB/RIF detection by Gene Xpert
 Obtain a chest X-ray.

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 Interpreting Mantoux test

Mantoux is positive if induration is:

≥10mm in a well nourished, HIV negative child
≥5mm in a malnourished, or HIV infected child
A negative Mantoux does not rule out TB disease or infection (especially in the
HIV positive or malnourished child)
 Criteria for the diagnosis of TB in
children
Suspected tuberculosis:
 An ill child with a history of contact with a
confirmed case of pulmonary tuberculosis.
 With loss of weight, cough and wheeze not
responding to antibiotic therapy for respiratory
disease

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 Cont…

Probable tuberculosis:
A probable TB suggested when;
 Positive (10 mm in diameter) induration on
tuberculin.
 Suggestive appearance on chest radiograph
 Suggestive histological appearance of biopsy
material.

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 Cont….

Confirmed tuberculosis:
 Detection by microscopy or culture of
tubercle bacilli from secretions or tissues.
 Identification of tubercle bacilli as
Mycobacterium, tuberculosis by culture.

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 Differential Dx of PTB
 Pneumonia
 Generalized bacterial and viral infections
 Malnutrition
 HIV

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 Extra pulmonary TB

Lymphohematogenous (disseminated) disease :

 Tuberculosis of the superficial lymph nodes is
the most common form of extra pulmonary
tuberculosis in children.
 Most cases occur within 6–9 months of initial
infection by M. tuberculosis.

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Cont…

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 Cont..

Consider TB lymphadenitis in a child who

has;
 Painless enlargement of cervical nodes.
 No lesion on the head that could cause the lymph
gland enlargement.
 No response to antibiotics
 Nodes are firm, non tender. but not hard.
 Disease is most often unilateral/cervical.
 As infection progresses, multiple nodes are
infected, resulting in a mass of matted nodes.
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 Diagnosis
Clinical presentation:
 Contact with a person who has infectious TB.
 Lack of interest in playing or change in behavior.
 Headache, especially if accompanied by early
morning vomiting.
 Irritability, drowsiness, convulsions, weight loss.
Definitive diagnosis:
 Histologic or bacteriologic confirmation with
FNA.

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 DDX

 Nontuberculous mycobacteria (NTM)

 Pyogenic infection
 Cat scratch disease (Bartonella henselae),
 Brucellosis
 Toxoplasmosis
 Tumor
 Branchial cleft cyst
 Cystic hygroma, and Tularemia

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 Miliary tuberculosis
 This is clinically significant form of
disseminated tuberculosis.
 which occurs when massive numbers of
tubercle bacilli are released into the
bloodstream, causing disease in two or more
organs.
 Miliary tuberculosis usually complicates the
primary infection, occurring within 2–6 months
of the initial infection.

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 S/S

 Lymphadenopathy
 Hepato-splenomegaly
 Fever,
 Tachypnea
 Cyanosis
 Respiratory distress.
 Other signs - Papular, lesions on the skin or
choroidal tubercles in the retina

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 Diagnosis
 Often the patient presents with fever of unknown
origin.
 Early sputum or gastric aspirate cultures have a
low sensitivity.
 Biopsy of the liver or bone marrow
 Occasionally, corticosteroids hasten symptomatic
relief, especially when air block, peritonitis, or
meningitis is present.
 The prognosis is excellent if the diagnosis is made
early and adequate chemotherapy is given.

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 Tuberculosis Meningitis
 Tuberculosis of the central nervous system is the
most serious complication in children and is fatal
without effective treatment.
 TB Meningitis is associated with a high
morbidity and mortality if there is a delay in
diagnosis.
 Tuberculosis meningitis complicates about 0.3%
of untreated tuberculosis infections in children.
 It is most common in children between 6 months
and 4 years of age.
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Cont…

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 Sign and symptoms
More commonly, the signs and symptoms progress
slowly over several weeks and can be divided into
three stages.
 The first stage, which typically lasts 1–2 weeks,
is characterized by nonspecific symptoms, such as
fever, headache, irritability, drowsiness, and
malaise.
 Focal neurologic signs are absent, but infants may
experience a stagnation or loss of developmental
milestones.

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 Cont…
 The second stage usually begins more abruptly.
 The most common features are lethargy, nuchal
rigidity, seizures, positive Kernig or 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.

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 Cont…
 The third 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 of
illness at the time treatment is initiated.

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 Diagnosis
 The most important laboratory test for the diagnosis
of TB meningitis is examination and culture of the
lumbar CSF.
The CSF leukocyte count usually ranges from 10
to 500 cells/mm3.
The CSF glucose is typically <40 mg/dL.
 The protein level is elevated and may be
markedly high (400–5,000 mg/dL) secondary to
hydrocephalus and spinal block.
 Radiographic studies.

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 Drug resistance TB
 Mono- drug resistance (MR) TB- Resistance to one
first line anti TB drug only.
 Poly-drug resistance ( PR) TB- Resistance to more
than one first line anti TB drug (other than
combination containing both isoniazid and
rifampicin).
 Multidrug-resistant tuberculosis (MDR-TB)-
Resistance for at least, isoniazid and rifampicin, the
two most powerful, first-line (or standard) anti-TB
drugs.

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 Cont..
 Extensively drug-resistant TB (XDR-TB)-
MDR plus resistance to most effective second-
line injectable anti-TB drugs.
 Total drug-resistant TB (TDR-TB), TB caused
by bacteria that do not respond to all drugs of
TB treatment.

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MR

TDR

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 Features of a child suspected of having drug-resistant TB:

 Contact with a known case of drug-resistance TB.

 Not responding to the anti-TB regimen.
 Recurrence of TB after adherence to treatment
 Remains sputum smear-positive after 3 months of
treatment
 History of previously treated TB.
 History of treatment interruption.

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 TB management
 Any TB treatment has two phases:
Intensive phases
Continues phases
 DOT/VDOT ??? should be used for all children
with TB for initiation phase.
 For latent TB ( children > 2 years) Rx with once-
weekly isoniazid-rifapentine 12 weeks or
 4 months of daily rifampin or 9 months of daily
isoniazid.

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 Cont…
For active TB, to reduce the risk for drug induced
hepatotoxity in children, follow the recommended
dosages.
 Isoniazid (H): 10mg/kg(10-15 mg/kg)
maximum dose:300mg/day
 Rifampicin (R): 15mg/kg(10-20mg/kg)
maximum dose:600mg/kg/day
 Pyrazinamide (Z): 35mg/kg (range, 30-40 mg/kg)
 Ethambutol (E): 20 mg/kg (range, 15-25 mg/kg)
 Pyridoxine HCL (Vitamin B6) 25mg
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 Cont…
WHO guidelines;
 4 drug regimen: 2HRZE: 4HR
 For all children with suspected or confirmed
pulmonary TB or
 peripheral lymphadenitis living in an area of high
HIV prevalence or
 Resistance to H is high or
 Children with extensive pulmonary disease living
in areas of low HIV prevalence or low H
resistance.

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 Cont….
3 drug regimen: 2HRZ:4HR
 For children with suspected or confirmed TB or
 TB lymphadenitis living in areas of low HIV
prevalence or low H resistance.
2HRZE:10HR
 For Suspected or confirmed TB,
 Spinal TB with neurological signs or
 Osteo-articular TB.

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 The use of Streptomycin in children is mainly
reserved for the first 2 months of treatment of TB
meningitis.
 9 to 12 months of treatment is required in the
following conditions:
 Bone and joint tuberculosis
 Tuberculous meningitis
 Miliary tuberculosis

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 Management of TB meningitis
 TB meningitis and miliary TB are more common in
young children.
 Are associated with high rates of death and disability,
particularly if the diagnosis is delayed.
 Children with TB meningitis or miliary TB should be
hospitalized, for at least the first 2 months.

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 Rx regimens of TB meningitis in children

2HRZS/4HR
2HRZ(S or Eth)/7–10HR
 Corticosteroids (usually prednisone) are
recommended for all children with TB
meningitis in a dosage of 2 mg/kg daily for 4
weeks.
 The dose should then be gradually reduced
(tapered) over 1–2 weeks before stopping so
as to prevent damage of bones.

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 Prognosis of childhood TB
 Early detection and good treatment adherence
end up with positive outcome.
 Peresence of co infection may delay recovery.
 Reoccurrence of cases leads to resistance,
high morbidity and mortality.

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 TB Rx outcome
Cured Rx completion and Smear negative.
Completed Rx completion without evidence of failure
or cured.
Failure Smear positive by the end of intensive
phase.
Relapse Re - occurrence after being cured.
Lost to follow A patient whose Rx was interrupted for
up two consecutive months more.
Died A patient who dies any reason during the
course of treatment.

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Common S/E of anti-TB medications
Rifampin Orange body fluids, drug interactions,
hepatotoxicity; thrombocytopenia
Isoniazid Neuropathy, hepatotoxicity, GI
intolerance
Pyrazinamide Hepatotoxicity, joint pains, GI
intolerance; hyperuricemia
Ethambutol Ocular toxicity (dose related), GI
intolerance
Streptomycin Auditory and vestibular toxic,
Nephrotoxic effects; Rash
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 Prevention
 BCG vaccination
 Avoid/reduce close contact
with infected individual.
 Advise for proper discharge
disposal
 Advise for using of face mask
 Space/room/ward ventilation
 preventing cause of illness
( HIV, measles…)
 Prevention of malnutrition
 Boiling milk before using

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