Tuberculosis in children

1. Pediatric TB

2. Learning outcomes
 Tuberculosis:
 Epidemiology
 Riskfactors
 Etiology
 Pathogenesis andpathology
 Clinicalmanifestation
 Diagnosis
 Management

3. Overview of Tuberculosis
 Tuberculosis (TB) is the most common cause of
infection-related death worldwide.
 In 1993, the World Health Organization (WHO)
declared TB to be a global public health
emergency.
 The acid-fast characteristic of the mycobacteria is their
unique feature.
 M tuberculosis is:
 Non–spore-forming
 Non-motile

4. Overview of Tuberculosis…
 Most persons infected with M tuberculosis do not develop
active disease.
 In healthy individuals, the lifetime risk of developing disease
is 5-10%.
 In certain instances, such as extremes of age or defects in
cell-mediated immune (CMI) response TB may develop.
• HIV infection
• malnutrition
• administration of chemotherapy,
• prolonged steroid use
 For patients with HIV infection, the risk of developing TB is
7-10% per year.

5. Characteristic presentations of TB in Children
• TB may present in children at any age
– but most commonly in less than 5 years of age.
• The age range of 5-14 yr is often called the “favored age,” because in all human
populations this group has the lowest rate of TB disease.
• Pulmonary TB is the commonest form though up to 30-40% may have EPTB.
• Infants and young children (especially those under 2 years) are at greatest risk of developing
severe disseminated disease
• The time between infection and disease can be shorter than in older children.
• Children under one year of age are more liable to develop disseminated and severe forms
of TB, such as Miliary TB or TB meningitis.
• The presentation and approach to diagnosis of pulmonary TB in older children (> 10 years)
and adolescents is similar to that for adults.
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BY: Wandimu M.

6. Latent TB Infection
• TB bacteria can live in the body without making you sick.
– This is called latent TB infection.
• People with latent TB infection:
– Have no symptoms
– Don’t feel sick
– Can’t spread TB bacteria to others
– Usually have a positive TB skin test reaction or positive TB
blood test
– May develop TB disease if they do not receive
treatment for latent TB infection
– Cannot spread TB bacteria to others
• Many people who have latent TB infection never develop TB
disease.
– remain inactive for a lifetime without causing disease.
– In those with weak immune system, the bacteria become active,
multiply, and cause TB disease. 2/5/2024
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BY: Wandimu M.

7. Etiology
 M. tuberculosis, M. Bovis, M. Africanum, M. microti and M.
canetti.
 Acid fastness (they resist decoloration with ethanol and
hydrochloric or other acids)
 These mycobacteria grow best at 37-41°C , produce niacin,
and lack pigmentation.

8. Clinical Stages
Has three clinical stage
 Stage 1: Exposure
 a child has had significant contact (shared the air)
with
 an adult or adolescent with infectious tuberculosis
but lacks proof of infection.
 The TST result is negative
 The chest radiograph is normal
 The physical examination is normal and

9. Clinical Stages…
Stage2: Tuberculosis infection (TBI)
 occurs when the child inhales droplet nuclei containing M.
tuberculosis
 survive intracellularly within the lung and associated lymphoid
tissue.
 The hallmark of TBI is a positive TST result.
 The child has no signs or symptoms
 A normal physical examination and
 The chest radiograph is either normal or reveals only granuloma
or calcifications in the lung parenchyma.

10. Clinical Stages…
Stage 3: Disease
 Occurs when signs or symptoms or
 Radiographic manifestations caused by M. tuberculosis
become apparent.
 The risk of developing disease is varies with age
 An immunocompetent adult with untreated TBI has
approximately a 5–10% lifetime risk of developing disease.
 an infected child <1 yr old has a 40% chance of developing
TB disease within 9 mo.

11. Epidemiology
 In 2015, (WHO) declared tuberculosis (TB) encounter more deaths
than any other single infectious disease.
 WHO estimate in 2014,
 In 1 million new cases of childhood TB, 136,000 resulting in deaths.
i.e
 Among 1m.tb patient at least, 14% will die.
 The WHO 2016 Global Tuberculosis Report estimates that in 2015 there
were 1 million childhood incident cases.
 170,000 TB-associated deaths among non–HIV-infected children and
 40,000 TB-associated deaths among HIV infected children.
(Nelson text book 2021).

12. Epidemiology…
 The global burden of tuberculosis is influenced by several
factors, including:
 The HIV pandemic
 The development of (MDR-TB); and
 Lack of both diagnostic tests and effective medical therapy in low-
resource settings worldwide
(Jenkins, 2016, Nelson text book 2021)

13. Epidemiology…
 In Ethiopia the death rate among children on TB treatment was
unacceptably high
 25% of children under the age of two being disproportionately
impacted.
 In Ethiopia child mortality from tuberculosis is common among
the patient with;
 HIV infection (aHR = 4.2)
 under nutrition (aHR = 4.2)
 being under 10 years old (aHR = 4.1)
 relapsed TB (aHR = 3.7)
 undernourished two months after starting TB treatment

14. Route of transmission/TB
 When a person breathes in TB bacteria, the bacteria can
settle in the lungs and begin to grow.
– From there, they can move through the blood to other
parts of the body, such as the kidney, spine, and CNS
(brain).
 TB disease in the lungs or throat can be infectious.
– This means that the bacteria can spread to other people.
– TB in other parts of the body, such as the kidney or
spine, is usually not infectious.
 People with TB disease are most likely to spread it to
people they spend time with every day.
– This includes family members, friends, and coworkers
or schoolmates.

15. Route of transmission/TB…
 The probability of transmission depends on the dynamics of
four major factors:
 The susceptibility of the host
 Degree of infectiousness of the person with TB disease
 Environmental factors and
 Level of exposure (proximity, frequency and
duration).
 Key risk factors for development of TB in children include:
 Household contact or other close contact with pulmonary
TB cases
 Child’s age younger than 5 years
 HIV infection and
 Severe malnutrition.

16. Route of transmission…
• TB is NOT spread by
• shaking someone’s hand
• sharing food or drink
• touching bed linens or toilet seats
• sharing toothbrushes
• Kissing
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17. Pathogenesis
 The time b/n initial infection & clinically apparent
disease is variable:
 Disseminated & meningeal TB are EARLY
 manifestations (2-6mo after infection)
 TB LAP & endobronchial TB(3-9mo)
 Bones & joints take several years
 Renal TB takes DECADES after infection
 PTB that occurs more than a year after primary
infection is usually due to endogenous regrowth of
bacilli persisting in partially encapsulated lesions

18. Immunity reaction
The pathologic events:
 Depend on the balance among the mycobacterial antigen load
&cell-mediated immunity
1. Small antigen load and high degree of tissue sensitivity ,
granuloma formation results
2. High antigen load and high degree of sensitivity, results
in formation of caseous material
3. Low degree of tissue sensitivity, the reaction is
diffuse andthe infection is not well contained

19. Evaluation of TB
A child with
symptoms
suggestive of

20. Neonates With Household Contacts With TB
 The AAP and CDC guidelines advocate avoidance of separation of
the mother and infant, if possible.
 Mother with a positive TST result and no evidence of current
disease
 Because the positive tuberculin skin test (TST) result may be
evidence of an unrecognized case of contagious tuberculosis
(TB) within the household
 Perform a Mantoux test when the infant is aged 4-6 weeks
and 3-4 months.
 Consider administration of isoniazid (INH) (10 mg/kg/d) to the
infant if the family cannot be promptly tested.
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21. Approaches to diagnose TB in
children:
 Careful history (including history of TB contact and symptoms consistent
with TB)
 Clinical assessment (including growth assessment)
 Diagnostic tests –
 Bacteriologic confirmatory tests: mWRDs (e.g. Xpert MTB/RIF or
Xpert Ultra assay), AFB microscopy, & culture on expectorated or
induced sputum, stool, nasopharyngeal aspirate, gastric aspirate,
lymph node aspirate.
 Chest X-ray
 HIV testing
 Histopathology, mainly for suspected EPTB
WHO consolidated guidelines on tuberculosis: Module 5:
Management of tuberculosis in children and adolescents.

22. PPD Test
 72 hrs
 0.1 ml ID, ventral surface of for arm below elbow
 < 5mm Negative
 5-10mm Indeterminate
 >10mm positive
 > 5 mm Positive in HIV

23. PPD Test
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24. PPD test…
False –ve PPD test
 Severe PEM
 Measles
 Overwhelming TB
 Wrong techniques
 HIV
 Steroids
 Cancer
False +ve PPD test
 Atypical mycobacterial
infections
 Hypersensitivity to
constituents
 BCG vaccination

25. Clinical TB Diagnosis
 Two or more of the ff
symptoms
 Cough > 2weeks
 Weight loss or poor
weight gain
 Persistent fever and/or
night sweats > 2 weeks
 Fatigue, reduced
playfulness, less active
 Two or more of the ff sign
 Positive contact history
 Respiratory signs
 CXR suggestive of PTB
(where available)
 Positive Mantoux test
(where available)

26. Diagnosis
 Features suggestive of TB:
• recent close contact with an infectious case
• a positive tuberculin skin test(TST)
• Symptom complex oftuberculosis
• CXR suggestive ofTB
• Not responding to broad spectrumantibiotics
 Chest X-ray appearance:
• Hilar/ mediastinallymphadenopathy
• Colaps-consolodation Miliarypattern
• Pleuraleffusion

27. Hilar lymphadenopathy

28. Diagnosis of DR-TB in Children
 Children with the following conditions should be
presumed to have DR-TB:
 Features in the index case suggestive of drug resistant
TB
– Index case remaining smear-positive after 3 months
of treatment
– History of previous TB treatment interruption,
treatment failure or retreatment case or recently

29. TB Preventive Therapy
 INH preventive therapy (IPT, specifically referring to TPT using isoniazid)
 Indications
– Infants <12 months of age living with HIV who do not report any of
the symptoms of poor weight gain, fever, or current cough, and who do
not have history of contact with an index PTB case are unlikely to have
active TB or LTBI and should not receive TPT.
– Children > 12 months of age living with HIV who do not report any of
the symptoms of poor weight gain, fever, or current cough, are unlikely
to have active TB and should receive TPT regardless of the contact
history.
– Adolescents (< 15 years of age) who have been exposed to an index
PTB case and who do not report any of the symptoms

30. Treatment of drug susceptible TB(DS-
TB)
Objectives of TB treatment
The aims of treatment of Tuberculosis are:
 To cure the patient from TB
 To prevent death from TB disease and its late effects
 To prevent relapse of TB
 To prevent the development of acquired drug resistance, and
 To decrease TB transmission

31. Treatment of (DS-TB)
First line TB drugs
 Rifampicin(R)
 The most bactericidal and potent sterilizing agent
 Isoniazid(H)
 Highly bactericidal especially in the first few days
 Pyrazinamide(Z)
 Bacteriostatic and only active in acidic environment and
bacilli inside macrophages.

32. Treatment of (DS-TB)
 Essential properties of Tuberculosis treatment
 In order to achieve the desired aim of treatment, an anti-TB
treatment regimen needs to be administered:
• in appropriate combination of drugs
• in the correct dosage
• regularly taken by the patient, and
• For a sufficient period of time.

33. Dosing of anti-tuberculosis drugs
Recommended pediatric Dosage
 Isoniazid 10 (7-15) (mg/kg body weight) ,Max=300mg
 Rifampicin 15 (10-20) (mg/kg body weight), Max=600mg
 Pyrazinamide 35 (30-40)
 Ethambutol 20 (15–25)
NB: Children weighing 25kg and more can be treated using
recommendation for adults.

35. LTBI treatment
 Children over 2 years of age can be treated for latent TB infection
with
– once-weekly isoniazid and rifapentine for 12 weeks ( w five to
10 minutes after meal)
 Alternative treatments for latent TB infection in children include
– 4 months of daily rifampin or 9 months of daily isoniazid.
 The regimens are equally acceptable; however, health care providers
should prescribe the more convenient shorter regimens, when
possible.
– Patients are more likely to complete shorter treatment regimens

36. Treatment of EPTB
 Treat patient with extra-pulmonary TB involving any
site for six-month with standardized first-line
regimen
 Treat CNS TB( meningitis, tuberculoma) and
Osteoarticular TB (including vertebral bones, joint
and osteomyelitis)
– require prolongation of the continuation phase for 10 months:
2RHZE/10RH.
– An initial adjuvant corticosteroid therapy with dexamethasone or
prednisolone tapered over 6-8weeks (Tuberculosis meningitis
and/or pericarditis)
 Children (<14 years) should be given prednisolone 4mg/kg/24 hrs
(or equivalent dose dexamethasone: 0.6 mg/kg/24 hrs) for 4
weeks, followed by a tapering course over 4 weeks.
 TB Care Provider (TB focal at the HF) should request sputum for
AFB

37. In Treatment of children for TB
 Ethambutol is safe in children at a dose of 20 mg/kg (range 15– 25
mg/kg) daily.
 Children receiving treatment must be weighed at least every month
 Children weighing 25 kg and more should be treated with Adult dosage
 Treatment doses should be adjusted as soon as a child changes weight
bands
 Monitor nutritional status/response during treatment using growth
chart
 Check tablet strengths regularly to avoid toxicity
 Adverse events are less common in children than in adults.
 A child who is not responding to anti-TB treatment should be referred
for further assessment and management.

38. Complications of TB Disease
 Miliary disease and tubercular (TB) meningitis are
the earliest and most deadly complications of
primary TB.
 Pleural effusions
 pneumothorax.
 Complete obstruction of a bronchus
 atelectasis of the involved lung.
 Bronchiectasis
 stenosis of the airways

39. Outcomes of TB Disease
 The prognosis of TB varies according to the clinical
manifestation.
 Poor prognosis is associated with disseminated TB,
miliary disease, and TB meningitis.
 The prognosis of TB meningitis varies according to
the stage of the disease at the time treatment is
started.
– Stage 1-2 has a good prognosis
– Stage 3 usually have sequelae such as deafness, blindness,
paraplegia, mental retardation, movement disorders, and
diabetes insipidus.

40. Monitoring treatment responses
A. Clinical Monitoring of TB patients:
 During scheduled visit, a patient receiving TB treatment
should be checked for:
 Persistence or reappearance of clinical feature of TB,
including weight monitoring*
 Treatment adherence by reviewing the “treatment
supporter card” or UNIT TB register
 Risk for developing acquired drug resistance, and need for
DST screening
 Occurrence of Adverse drug reaction, and
 Development of TB complications

41. Monitoring treatment responses …
B. Bacteriologic monitoring of bacteriologically confirmed
pulmonary TB patients:
 Besides the clinical monitoring, bacteriologically confirmed pulmonary
TB patients (i.e. those diagnosed by identification of bacilli by smear
microscopy, Xpert MTB/RIF assay, other mWRDs or culture) need their
sputum specimen to be checked using AFB microscopy.
 TB Care Provider (TB focal at the HF) should request sputum for AFB
microscopy at the end of 2nd, 5th, and 6th months of therapy
 Molecular techniques like Xpert MTB/RIF assay are not recommended
for monitoring response to TB treatment.
C. Management of adverse reaction to First line Anti-TB drugs
 Generally first line anti TB drugs have fewer side effects.
 However, the health workers should regularly monitor for
occurrence of side effects to the Anti-TB drugs administered to the
patient

42. Multidrug-Resistant TB
 Infection caused by multidrug resistant (MDR)
organisms, defined as organisms resistant to at
least isoniazid (INH) and rifampin.
 Categories of TB drug resistance
Primary resistance
– is defined as the occurrence of resistance to anti-TB treatment in an
individual who has no history of previous treatment.
Secondary resistance
– involves the emergence of resistance during the course of ineffectual
anti-TB therapy.
 The initial treatment regimen for patients with MDR TB should

43. Follow up
 Patients visit the health facility
• weekly during intensive phase and
• every two weeks during continuationphase.
 During the visit, the child should be assessed
for:
 Adherence
 Drugtoxicity
 Weightgain
 Symptomassessment
 Sputum should be taken for AFBs at
• months 2, 5 and 6 for those who were smear positive at the beginning
of treatment
• CXR is not required in follow-up if the child is respondingwell to
anti-TB treatment

44. Poor Response to Treatment
 Most children show signs of improvement within 4 – 8 weeks of anti-
TB treatment.
 Weight gain is a sensitive indicator of good response
 Potential causes of poor response to treatment include:
 Poor adherence
 HIV infection, Wrongdiagnosis
 Other concurrent chronic lungdiseases
 Under dosage of drugs Resistant form of TB Complications e.g.
neurological complications

45. Treatment failure
 Consider treatment failure if child is receiving anti-TB
treatment and:
 There is no symptom resolution or symptoms are getting
worse.
 In this case, always confirm adherence is good.
 If uncertain, a child can have health care worker DOTs at the health
facility
 There is continued weight loss
 If smear positive at baseline and remains smear positive up
to 5 months
 Refer children with suspected treatment failure

46. Treatment Interruptions
 If a child interrupts anti-TB treatment for a period less than 1
month, continue with their TB treatment when they resume.
 If the child interrupts anti-TB therapy for a period longer
than 1 month, put them on a re-treatment regimen when they
resume

47. Drug Resistant TB
 Resistance to Rifampicin and/or Isoniazid is
the most important DRTB should be suspected if:
1.Child has contact with a known case of DRTB
2.Child has contact with an adult who has
suspected DRTB as follows:
 The adult remains sputum smear positive
after 2 months of treatment,

48. Treatment of drug resistant TB

49. Drug rec. for the treatment of
RR/MDR-TB

50. TB treatment Outcome
 The final result of treatment outcome of TB patients should
be defined and recorded on treatment register.
 These outcomes are mutually exclusive and only one
outcome should be assigned per patient per treatment
course
 The treatment outcome definitions differ between DS-TB
and DR-TB cases.

51. Outcome…

52. Outcome…
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53. Outcome…
 Proposed new definitions for DS-TB/DR-TB Treatment
outcomes by WHO
 Treatment failed: A patient whose treatment regimen needed to be
terminated (permanently changed to a new regimen)
 Cured: A pulmonary TB patient with bacteriologically confirmed TB at
the beginning of treatment who completed treatment as recommended
by the national policy
 Treatment completed: A patient who completed treatment as
recommended by the national policy, whose outcome does not meet the
definition for cure or treatment failure.
 Died: A patient who died before starting treatment or during the course
of treatment.
 Lost to follow-up: A patient who did not start treatment or whose
treatment was interrupted for 2 consecutive months or more.
 Not evaluated: A patient for whom no treatment outcome was
assigned.
 Treatment success: The sum of cured and treatment completed.
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54. TB Prevention
A. Screening for Child Contacts of Known TB Cases
B. Management of TB exposed child
C. BCG vaccination
D. Tracing of TB Source
E. Follow up
F. TB Infection Control
A. Screening for Child Contacts of Known TB Cases
The risk of infection is greatest for close and prolonged contact.
IPT should be given at a dose of 10mg/kg for duration of 6 months.
For the high risk children who have no signs or symptoms ofTB
disease i.e
• All children aged under 5 years &
• All HIV infected children
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BY: Wandimu M.