The document provides a comprehensive overview of tuberculosis (TB), including its global prevalence, classification, diagnosis, transmission routes, and treatment. It highlights the significant burden of TB, particularly in high-burden countries like India and Ethiopia, and outlines clinical features and complications associated with pulmonary and extrapulmonary TB. Additionally, it discusses diagnostic methods, including culture and molecular tests, and emphasizes the importance of preventive measures and nutritional support in managing TB, especially in pediatric populations.

1. Tuberculosis
Zenawit.A( Assistant professor in
pediatics and child health)

2. Outline
• Key epidemiological data: Global, Ethiopia
• What do we mean by contact?
• Is cough important for TB transmission?
• Extent of transmission?
• Who is at risk?
• Diagnostic modalities
• TB-Prevention
• Treatment

3. Tuberculosis
• TB has been there for >4,000 yrs (studies of human
skeleton)
• First recognized as a clinical entity by Schönlein, who
used the term tuberculosis in 1830,tubercle means
lesion of consumption
• March 22, 1882, Dr.Robert Koch discovered
Mycobacterium Tuberculosis (World TB day)
• 1.7 billion of world population infected; 5-10% of
adults and up to 40% of children will develop the
disease.

4. Key facts
• 1.4 million died from Tb in 2019, including
• 208,000 HIV+ people
• 10 million people fell ill with TB
– 5.6 million men
– 3.2 million women
– 1.2 million children
• TB is one of the 10 top causes of deaths

5. Countries with high burden of TB
• Eight countries accounted for 2/3 of the global
burden: India (27%), China (9%) Indonesia (8%),
Philippines (6%), Pakistan (6%), Nigeria (4%),
Bangladesh (4%) and South Africa (3%).
• A total of 30 countries accounted for 87% of the
world’s cases.
• Ethiopia is among the first 20 high burden
countries

6. TB Classification

7. Classification based on anatomical site
• Pulmonary TB (PTB): TB involving the lung
parenchyma or the tracheobronchial tree.
• Miliary TB is classified as PTB.
• TB intrathoracic lymphadenopathy (mediastinal
and/or hilar) or pleural effusion, without CXR
abnormalities in the lungs, is a case of
extrapulmonary TB.
• A patient with both pulmonary and
extrapulmonaryTB should be classified as a case
of PTB.

8. • Extrapulmonary TB (EPTB): involving organs
other than the lungs, e.g. pleura, lymph
nodes, abdomen, GUT, skin, joints and bones,
meninges.

9. Classification based on Hx of previous
TB Tx
• New patients have never been treated for TB or
have taken anti-TB drugs for < 1 month.
• Previously treated patients: received anti TB ≥ 1
month further classified by the outcome as
follows:
– Relapse/re-infection patient diagnosed
with an episode of TB after declared cured
or Tx completed

10. _Treatment failure are those who have
previously been treated for TB and whose
Tx failed at the end of most recent Tx
_Treatment after loss to follow-up (LTFU)
patients: previously treated for TB and
were lost (previously known as Tx default )
– Other previously treated patients : treated
for TB but whose outcome after their
most recent Tx is unknown or
undocumented

11. Classification based on drug resistance
• Monoresistance: resistance to one first-line anti-
TB drug only .
• Multidrug resistance (MDR TB) : resistance to at
least both isoniazid and rifampicin.
• Polydrug resistance: resistance to >1 first-line
antiTB drug (other than both INH and rifampicin).
• Extensive drug resistance(XDR TB) : resistance to
any fluoroquinolone and to at least one of three
second-line inject able drugs (capreomycin,
kanamycin and amikacin), in addition to MDR.

12. … based on resistance
• Rifampicin resistance (RR TB) : resistance to
rifampicin with or without resistance to other
anti-TB drugs.(Mono-RR, MDR, PolyDR, XDR) .
• Patients found to have an RR-TB or MDR-TB :
should be started on second-line drug regimen

15. Lab Diagnosis
• Acid fast stains AFS : Detected > 100 yrs ago
* Ziehl–Neelsen stain
* Kinyoun stain does not need heating
* Auramine –rhodamine staining in the US
* 10,000 organisms/ml are required for
smear positivity
* Sensitivity of sputum AFS is 60% compared
with culture

16. Why collection of 3 sputum sample ?
• Detection of a single bacilli is highly suggestive
• Detection of 10 bacilli per slide is optimal
• Sensitivity increases:
* By 10% with the collection of the 2nd
sample
* By 2% with the 3rd sample

17. What fluids can be collected ?
• Any biologic fluid or material can be examined:
• Pleural fluid,
• Peritoneal fluid
• CSF
• Urine
• Gastric aspirate
• Sputum
• Pus aspirate etc
• thin fluids are best examined after sedimentation
by centrifugation.

18. Tb-Culture
• Gold standard
• Mycobacterium grow very slowly: rate 1/20
compared with the growth of conventional
bacteria
• Bacteria generation time 12-24 hrs
• Cultured on Löwenstein-Jensen culture media
• growth will take 3-6 wks( up to 12 wks)

19. Fluid samples vs Biopsies yield for Tb
culture
• Pleural fluid
• <30% are culture
• positive
• Pleural Biopsies
• 40-80% are culture
• positive
• Peritoneal fluid
• <20% are culture
• positive
• Peritoneal Biopsies
• >60% % are culture
• positive

20. Molecular tests
1. Rapid molecular test: Xpert MTB/RIF assay
* Provide result in 2 hrs
* Better accuracy than microscopy
* Positive when > 10 bacteria/ml
* Costly and needs trained Lab staffs
2. First line Probe assay(LPAs)(2008): tests
forRIF and INH
3. Second line probe assay(2016): tests for
flouroquinolones and injectable anti-Tbs

21. Transmission
Routes:
– Inhalation of airborne droplet nuclei
– Rarely by direct contact with infected discharge
or contaminated fomite
– Ingestion : M.bovis
– Trans placental route
Droplet nuclei.: particles 1–10 mcm in diameter,
the dried residue formed by evaporation of
droplets coughed or sneezed into the atmosphere
are also infective.

22. Transmission increases…
• A single bacilli is enough to infect !
• When source case has/is older child / adult
with:
* Smear positive sputum
* Copious thin sputum
* Extensive upper lobe /cavity
* Forceful cough
* Patients who are not yet Txed or Tx for <
2wks
• Most children rarely infect others: bacilli are
sparse and do not have forceful coughing

23. Is cough a prerequisite ?
• Coughing, sneezing, singing, simply talking
• The site and the mechanism of aerosolization
is important

24. Transmission rate
• With prolonged exposure to smear +ve patient
• 10-50% of contacts are infected
* 30% develop primary TB
* 70% Latent TB
* 5-10% develop secondary TB
Pulmonary >80%
70% are smear positive
Extra-pulmonary <20%

25. Who is at risk ?
• M:F= 2:1
• Children < 5years of age
• HIV +
• Malnutrition
• Immune deficiency conditions:
Cancer patients
Immune suppressive therapies
DM
• High risk behaviors:
• Household contact to smear positive/cavitary
TB patient

26. Pathogenesis

27. Clinical course of TB Disease
• Time varies between initial infection and
apparent disease:
Pulmonary TB in 70-75% of cases: with in weeks
Disseminated and meningeal TB : within 2-6
mo.
Lymph node or endobronchial TB: within 3-9
mo.
Bones and joints: several years

28. Renal TB : decades after infection.
Extrapulmonary manifestations are more
common in children, develop in 25-35% of
children with TB, compared to 10% of
immunocompetent adults.
Reactivation TB: rare in children, common
among adolescents and young adults.

29. C/F: Primary pulmonary disease
• Commonly : Nonproductive cough and mild dyspnea
• fever , night sweats, anorexia and decreased activity
• Failure-to-thrive; not improving with nutrition alone
• Pts with bronchial obstruction have localized wheezing
or decreased breath sounds, accompanied by
tachypnea or, rarely, respiratory distress.
• These Sxs & Sns are occasionally alleviated by
antibiotics, suggesting bacterial super infection.
• 50% of children with CXR finding do not have P/E
finding

30. Figure: Left Pleural effusion: Obliterated costo-phrenic and
cardio-phrenic
angles, opaque left lung

33. C/F: Progressive Primary Pulmonary
Disease:
• High fever, severe cough with sputum , weight
loss, and night sweats are common.
• P/E diminished breath sounds, rales, and
dullness or egophony over the cavity.

34. C/F: Reactivation Tuberculosis:
• Common in children who acquire the initial
infection when they are older than 7 yr of age.
• most common sites are the apical seedings
(Simon foci)
• More Sxic than children with primary
pulmonary Tb.
• Sxs : fever , anorexia, malaise, weight loss, night
sweats, productive cough, hemoptysis, and
chest pain

35. CXR :
• Extensive infiltrates or thick walled cavities in
the upper Lobes
• Pleural Effusion : from a sub-pleural
pulmonary focus or caseated lymph node.

36. Summary of Ghon complex

37. C/F:Miliary disease
•Lympho-haematogenous dissemination to spleen,
liver, lung, lymph nodes, skin, bones,
joints,kidneys,peritoneum, pericardium and
meninges
• Common in immune compromised/malnourished
• Sxs : pt gravely ill with Sx complex of TB,
• Sns : TST non reactive in 40% of pts,
hepatosplenomegaley , emaciation, Sns of
meningitis, peritonitis etc
• Resolution is slow with Tx , steroids for Sxic relief
• Excellent prognosis with early Tx

39. C/F: Cardiac TB
• Rare, only in 0.5-4% of TB cases in children:
• The most common form of cardiac TB is
pericarditis.
• Either from direct invasion or from subcarinal
lymph nodes.
• Sxs : low-grade fever, malaise, Wt loss ; chest
pain is unusual.
• Sns : pericardial friction rub or distant heart
sounds with pulsus paradoxus.

40. • Pericardial fluid: serofibrinous or hemorrhagic,
AFS -smear rarely +ve , but cultures are
positive in 30-70% of cases.
• Pericardial biopsy: culture + histology
(granulomas).
• Partial or complete pericardiectomy may be
required when constrictive pericarditis
develops.

41. C/F: Upper airway TB
• Larynx: croup like, sore throat , dysphagia
• Middle ear : painless unilateral otorrhea ,
Dxdifficult since AF stain and culture from ear
discharge are usually –ve

42. Lymph node Tb
• occurs with in 6-9 months of
infection ,
• Tonsillar , anterior cervical,
submandibular , and supraclavicular
nodes become involved secondary
to extension of upper lung fields or
abdomen.

43. • Inguinal, epitrochlear , or axillary
regions : from tuberculosis of the
skin or skeletal system.
• CXR normal in 70%
• Culture from lesion positive in 50% of
cases
• May heal by itself or ceseat and heal
by Fibrosis
• Dx FNAC /Biopsy

44. CNS TB
• CNS Tb : Follow lympho-hematogenous
dissemination of primary TB, Complicates 0.3%
of children, common between age 6mo to 4 yrs
– The brainstem is often the site of greatest
involvement, with dysfunction of cranial
nerves III, VI, and VII.
– The exudate interferes with the flow of
CSF > > communicating hydrocephalus

45. – The vasculitis, infarction, cerebral severe
edema, and hydrocephalus results in the
CNS damage gradually or rapidly .
– Profound abnormalities in electrolyte
metabolism from salt wasting or the
SIADH

46. TB meningitis:
• Stage 1 : lasts 1-2 wk ; nonspecific Sxs: fever,
headache, irritability, drowsiness, and malaise.
• Stage-2 : lethargy, nuchal rigidity, seizures, +ve
meningeal Sns, hypertonia, vomiting, cr.nerve
palsies, and other focal neurologic signs
• Stage 3 : is marked by coma, hemi- or
paraplegia, hypertension, decerebrate
posturing, deterioration of vital signs, and
eventually death

47. • Dx :
high index of clinical suspicion!
CSF WBC 10-500 with initial neutrophil
predominance, Glucose low, Protein high,
CSF AFS +ve in 30%, Culture +ve in 50-70%
TST –ve in 50%, CXR normal in 20-50%

50. Tuberculoma
• Tumor-like mass resulting from aggregation of
caseous tubercles, manifest as brain tumor .
• Accounts for 30% of brain tumors
• In adults : supertentorial ; In children;infratentorial
• Mostly singular , but may be multiple
• Sxs : head ache , fever , focal deficit , convulsion
• TST is usu reactive , CXR is normal
• CT: discrete lesions with surrounding oedema
• CT with contrast: ring enhancing lesions
• Tx: antiTB + steroids resolve most lesions +/-surgical
excision

51. • Paradoxical development of tuberculomas in
patients with TB meningitis receiving anti Tb
with out failure has been recognized. This
phenomenon should be considered whenever
a child with tuberculous meningitis
deteriorates or develops focal neurologic
findings while on treatment. Corticosteroids
can alleviate severe clinical Sns & Sxs . These
lesions can persist for months or years.

52. MRI of 3 years old child with multiple ring
enhancing lesions: pontine Tuberculoma

53. Bone and joint TB disease
• Skeletal TB account for 10% of all TB
cases and spinal TB account for 50% of
these
• Onset varies from 2 weeks to several
years
• Cold abscesses of paraspinal tissues or
psoas muscle may protrude under the
inguinal ligament and may erode into
the perineum or gluteal area (Scarpa’s
triangle).→

54. Pott’s disease
• The lower thoracic vertebrae in 40-
50%,
• Lumbar spine in 35-45%.
• Cervical spine in 10%
• Neurologic abnormalities occur in
50%
• Almost all patients have some
degree of spine deformity (kyphosis).
• Only 10-38% of cases of Pott disease
are associated with extraskeletal
tuberculosis

55. Typical TB spondylitis signs

56. GIT TB
• Most common is painless ulcer on the mucosa,
palate or tonsils
• TB of oral cavity, pharynx and parotid unusual
• Esophageal TB: secondary to tracheoesophageal
Fistula
• TB peritonitis with involvement of mesenteric
lymph nodes (doughy irregular non tender
abdomen)
• TB enteritis: secondary to haematogneous diss.
or swallowing of sputum Sxs : shallow ulcers
causing pain, diarrhea, constipation & wt loss

57. GUS TB
Renal Tb :
• Rare in children has long incubation period
• Small caseous foci develop in the renal
parenchyma and release M. tuberculosis into
the tubules.
• A large mass develops near the renal cortex that
discharges bacteria through a fistula into the
renal pelvis. Infection then spreads locally to
the ureters, prostate, or epididymis

58. • Early stages: often clinically silent in its, marked
only by sterile pyuria and microscopic
hematuria.
• Hydronephrosis or ureteral strictures are
complications
• Urine cultures for M. TB are +ve in 80-90% of
cases, and AFS of large volumes of urine
sediment are +ve in 50-70%
• TB salpingitis, endometritis, oophoritis, and
cervisitis can occur in pubertal girls
• Epididymitis and orchitis in boys

59. Patients who need hospital admission

60. Pregnancy and new born
Congenital TB:
• Is rare because the most common result of female
GUT-TB is infertility .
• Secondary to haematogenous or aspiration of
amniotic fluid
• Especially when the mother has primary infection
• Increased risk for prematurity, IUGR, LBW, and
perinatal mortality.
• Manifest by 2-3 wks of age.
• Sxs: resp distress, hepatosplenomegaley
• DDX sepsis, other TORCH infections

61. TB Treatment
1.Chemotherapy
2. Nutritional rehabilitation
3. Adjutant
4.Preventive therapy

62. Anti TB regimens

63. Pediatrics Drug formulations

65. Additional TX for TB
Corticosteroids for :
TB meningitis,
Airway obstruction by enlarged lymph nodes
and
Pericardial TB.
• Prednisone: 2 mg/kg daily, (4 mg/kg daily for
seriously ill children) with a max. dosage of 60
mg/day for 4 weeks, then taper over 1–2
weeks.

66. Pyridoxine supplementation
• INH may cause Peripheral neuropathy because
of pyridoxine deficiency, particularly in
children with SAM and HIV +ve on ART.
• Pyridoxine 5–10 mg/day
Surgical intervention when necessary

67. Nutritional support
• Do proper nutritional assessment and treat
Accordingly
• BF should continue for 24 months of age.

68. Follow up
• End of 2nd month Anti TB assess if :
- has no symptom resolution/worsening
symptoms;
- shows continued weight loss;
- Sputum smear/gastric aspirate is
positive

69. • Poor adherence is a common cause of “ Tx
failure”.
• Tx failure suggests MDR-TB
• Tx failure more common in children living
with HIV .
• If the child is doing good on 2nd month, he
will have investigative evaluations on 5th
month

70. TB Prevention

71. Latent tuberculosis infection (LTBI)
• LTBI: A state of persistent immune response to
stimulation by M. Tb Ags with no evidence of
clinically active TB.
• No gold standard test to identify M.TB
infection in humans.
• LTBI Tx is offered to individuals who are
considered to be at risk for TB disease

72. • Who are at risk ?
Those living in high TB burden countries with
immune risk factors and
Children <5 years who have contact with
patient with Open/cavitary TB

73. High/Low Tb country
• Low-TB-incidence country: Country with a
WHO-estimated TB incidence rate of <
100/ 100,000 population
• High-TB-incidence country: A country with a
WHO-estimated TB incidence rate of ≥
100/100,000 Ethiopia is
here

79. Any Ixs for LTBI?
• Tuberculin Skin Test (TST)
• TST is false negative in malnouritioned,
immune compromised children, children
with measels, mumps, varicella, influenza ;
and sever forms of TB
• TST false positive after other mycobacterial
infections(MAC etc)
• Interferon Gamma Release Assay (IGRA)
• Their absence should not limit IPT

81. Interferon-Gamma Release Assays
(IGRAs)
• IGRAs: whole-blood tests that can aid in
diagnosing M.tuberculosis infection.
• IGRA do not help differentiate LTBI from
Active TB.
• What IGRA is: WBCs from most persons
infected with M. TB will release interferon-
gamma (IFN-g) when mixed with antigens
derived from M. tuberculosis

82. What are the advantages of IGRAs?
• Requires a single patient visit to conduct the
test.
• Results can be available within 24 hours.
• Does not boost responses measured by
subsequent tests.
• Prior BCG vaccination does not cause a false
positive IGRA test result.

83. What are the limitations of IGRAs?
• Blood samples must be processed within 8-30
hours after collection while WBCs are still
viable.
• Errors in collecting or transporting blood
specimens or in running and interpreting the
assay can decrease the accuracy of IGRAs.
• Limited data on the use of IGRAs to predict
who will progress to TB disease in the future.

84. • Limited data on the use of IGRAs for:
– Children younger than 5 years of age;
– Persons recently exposed to MTb
– Immuno-compromised persons; and
– Serial testing.
• Tests may be expensive.

85. What to give
• INH for 6 months
• INH+RIF for 3-4 months for low TB burden
• countries ( caution!!! in HIV positives)

86. BCG Vaccine
• Bacille Calmette-Guerin (BCG) is a live
attenuated vaccine derived from M.bovis.
• Protection rate varies among settings
• In children who are known to be HIV-infected,
BCG vaccine should not be given for fear of
disseminated BCGitis
• HIV exposed infants whose HIV status is
unknown and who lack symptoms suggestive
of HIV, BCG vaccine should be given

87. BCG and TST
• 50% of children who are BCG vaccinated will
not have reaction to TST
• Of those who react, they start to wean with in
2-3 years, most loose it 5-10 years
• If it persists it is usually < 10 mm of
indurations

88. THANK YOU !!!