Tuberculosis in children

1. TUBERCULOSIS
F.Shirvani MD
Shahid Beheshti university of medical sciences,Tehran,IRAN

2. ■Tuberculosis has caused human
disease for more than 4,000 yr and is
one of the most important infectious
diseases worldwide.

3. ■ Mycobacterium tuberculosis complex: M.
tuberculosis, Mycobacterium bovis,
Mycobacterium africanum, Mycobacterium
microti, and Mycobacterium canetti.

4. ■The age range of 5-14 yr is often called
the “favored age”; in all human
populations, this group has the lowest
rate of tuberculosis disease

5. ■ A hallmark of all mycobacteria is acid
fastness—the capacity to form stable mycolate
complexes with arylmethane dyes (crystal
violet, carbolfuchsin, auramine, and
rhodamine).They resist decoloration with
ethanol and hydrochloric or other acids.

6. ■Mycobacteria grow slowly, with a
generation time of 12-24 hr.
■Isolation from clinical specimens on
solid synthetic media usually takes 3-6
wk, and drug susceptibility testing
requires an additional 2-4 wk.

7. exposure,
infection,
and disease

8. ■The hallmark of tuberculosis infection
is a positiveTST or IGRA result.

9. ■with untreated tuberculosis infection
has approximately a 5-10% lifetime
risk of developing disease. In contrast,
an infected child younger than 1 yr of
age has a 40% chance of developing
disease within 9 mo.

11. ■ The estimate for MDR tuberculosis is 4%
globally,
■ MDR-TB is defined as resistance to at least
isoniazid and rifampin;
■ Extensively drug-resistant tuberculosis includes
MDR-TB plus resistance to any fluoroquinolone
and at least 1 of 3 injectable drugs (kanamycin,
capreomycin, amikacin).

12. ■ Transmission of M. tuberculosis is usually
by inhalation of airborne mucus droplet
nuclei, particles 1-5 μm in diameter that
contain M. tuberculosis.

14. DIAGNOSTICTOOLS
■ Tuberculin SkinTesting
■ The development of delayed-type
hypersensitivity in most persons infected
with the tubercle bacillus makes theTST a
useful diagnostic tool.

15. DIAGNOSTICTOOLS
■ The MantouxTST is the intradermal injection of 0.1
mL purified protein derivative stabilized withTween
80.T cells sensitized by prior infection are recruited to
the skin, where they release lymphokines that induce
induration through local vasodilation, edema, fibrin
deposition, and recruitment of other inflammatory
cells to the area.The amount of induration in
response to the test should be measured by a trained
person 48-72 hr after administration.

16. DIAGNOSTICTOOLS
■ Tuberculin SkinTesting
■ Host-related factors: including very young age,
malnutrition, immunosuppression by disease or
drugs, viral infections (measles, mumps, varicella,
influenza), vaccination with live-virus vaccines, and
overwhelming tuberculosis, can depress the skin test
reaction in a child infected with M. tuberculosis.
■ Corticosteroid therapy can decrease the reaction to
tuberculin, but the effect is variable.

19. ■ Approximately 10% of immunocompetent
children with tuberculosis disease (up to
50% of those with meningitis or
disseminated disease) do not react initially
to purified protein derivative; most
become reactive after several months of
antituberculosis therapy

20. ■ False-positive reactions to tuberculin can be caused
by cross-sensitization to antigens of NTM, which
generally are more prevalent in the environment as
one approaches the equator.
■ These cross reactions are usually transient over
months to years and produce <10-12 mm of
induration.
■ Previous vaccination with bacilleCalmette-Guérin
(BCG) also can cause a reaction to aTST, especially if a
person has received 2 or more BCG vaccinations.
Approximately 50% of the infants who receive a BCG
vaccine never develop a reactiveTST,

21. ■ In children with no risk factors for tuberculosis,
skin test reactions are usually false-positive
results.
■ The American Academy of Pediatrics and the
CDC discourage routine testing of all children
and recommend targeted tuberculin testing of
children at risk identified through periodic
screening questionnaires
■ Possible exposure to an adult with or at high
risk for infectious pulmonary tuberculosis is the
most crucial risk factor for children.

23. Interferon-γ ReleaseAssays
■ Two blood tests (T-SPOT.TB and QuantiFERON-TB)
detect IFN-γ generation by the patient’sT cells in
response to specific M. tuberculosis antigens (ESAT-6,
CFP-10, andTB7.7).
■ The QuantiFERON-TB test measures whole blood
concentrations of IFN-γ, and theT-SPOT.TB test
measures the number of lymphocytes/monocytes
producing IFN- γ.
■ The test antigens are not present on M. bovis–BCG
and Mycobacterium avium complex, the major group
of environmental mycobacteria,

24. Interferon-γ ReleaseAssays
■ IGRAs should be interpreted with caution
when used for children younger than 5 yr
of age and immunocompromised patients
owing to the relative lack of data and the
increased propensity for indeterminate
results in these groups, makingTSTs
preferred in these populations.

25. Interferon-γ ReleaseAssays
■IGRAs are preferred andTSTs are
considered acceptable in the BCG-
immunized older child (≥5 yr) and in
those ≥5 yr who are unlikely to
return forTST reading.

26. MYCOBACTERIAL SAMPLING,
SUSCEPTIBILITY AND CULTURE
■ 1-- Induced sputum with a jet nebulizer, inhaled
saline and chest percussion followed by
nasopharyngeal suctioning is effective in
children as young as 1 yr of age. Sputum
induction provides samples for both culture and
acid-fast bacilli staining.

27. MYCOBACTERIAL SAMPLING,
SUSCEPTIBILITY AND CULTURE
■ 2-The traditional culture specimen in young
children is the early morning gastric acid
obtained before the child has arisen and
peristalsis has emptied the stomach of the
pooled respiratory secretions that have been
swallowed overnight. However, even under
optimal conditions, 3 consecutive morning
gastric aspirates yield the organisms in <50% of
cases.

28. MYCOBACTERIAL SAMPLING,
SUSCEPTIBILITY AND CULTURE
■3-The culture yield from
bronchoscopy is even
lower

29. MYCOBACTERIAL SAMPLING,
SUSCEPTIBILITY AND CULTURE
■The presence of a positiveTST or IGRA,
an abnormal chest radiograph
consistent with tuberculosis, and
history of exposure to an adult with
infectious tuberculosis is adequate for
the probable diagnosis of tuberculosis
disease.

30. MYCOBACTERIAL SAMPLING,
SUSCEPTIBILITY AND CULTURE
■Confirmation of extrapulmonary
tuberculosis is best achieved with a
positive culture.

31. Nucleic Acid Amplification
■The main form of nucleic acid
amplification studied in children with
tuberculosis is PCR, which uses specific
DNA sequences as markers for
microorganisms. Evaluation of PCR in
childhood tuberculosis has been
limited.

32. Nucleic Acid Amplification
■Compared with a clinical diagnosis of
pulmonary tuberculosis in children, the
sensitivity of PCR has varied from 25-
83%, and specificity has varied from
80-100%.
■ A negative PCR result never eliminates
the diagnosis of tuberculosis, and the
diagnosis is not confirmed by a positive
PCR result.

33. Different types of disease:
■pulmonary

34. Primary complex

35. Primary pulmonary tuberculosis

37. ■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

38. ■ The symptoms and physical signs of primary
pulmonary tuberculosis in children are
surprisingly meager considering the degree of
radiographic changes often present.When
active case finding is performed,

39. ■Extrapulmonary manifestations
are more common in children
than adults and develop in 25-
35% of children with
tuberculosis, compared to
approximately 10% of
immunocompetent adults.

40. PleuralTB
■Tuberculous pleural effusion
is uncommon in children
younger than 6 yr of age and
rare in children younger
than 2 yr of age

41. PleuralTB
■. Effusions are usually unilateral but
can be bilateral.They are rarely
associated with a segmental pul-
monary lesion and are uncommon in
disseminated tuberculosis. Often the
radiographic abnormality is more
extensive than would be suggested by
physical findings or symptoms

42. PleuralTB
■ Clinical onset of tuberculous pleurisy is often sudden,
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.
■ TheTST 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.

43. PleuralTB
■ The pleural fluid is usually yellow and
only occasionally tinged with blood.
The specific gravity is usually 1.012-
1.025, the protein level is usually 2-4
g/dL, and the glucose concentration
may be low, although it is usually in the
low-normal range (20-40 mg/dL).

44. PleuralTB
■ Typically there are several hundred to
several thousand white blood cells per
microliter, with an early predominance
of polymorphonuclear cells followed
by a high percentage of lymphocytes.
Acid-fast smears of the pleural fluid are
rarely positive. Cultures of the fluid are
positive in <30% of cases.

46. ■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, whereas renal lesions become
evident decades after infection.

47. DisseminateTB

48. DisseminateTB
■As the pulmonary disease
progresses, an alveolar-air
block syndrome

50. DisseminateTB
■ Choroid tubercles occur in 13-87% of
patients and are highly specific for the
diagnosis of miliary tuberculosis.
Unfortunately, theTST is nonreactive in up
to 40% of patients with disseminated
tuberculosis

52. DisseminateTB
■ Cutaneous lesions include
papulonecrotic tuberculids,
nodules, or purpura

53. HIV with papulonecrotic lesions

54. Other cutaneous tuberculosis

55. Extrapulmonary : lymph node disease
■ Infected nodes in the inguinal,
epitrochlear, or axillary regions result from
regional lymphadenitis associated with
tuberculosis of the skin or skeletal system.
The nodes usually enlarge gradually in the
early stages of lymph node disease.They
are discrete, nontender, and firm but not
hard. often unilateral

56. Extrapulmonary : lymph node disease
■multiple cervical nodes are
infected, resulting in a mass
of matted nodes. but the
chest radiograph is normal
in 70%

58. CNSTuberculosis:
meningitis
■Tuberculous meningitis complicates
approximately 0.3% of untreated
tuberculosis infections in children.
■It is most common in children between
6 mo and 4 yr of age

59. CNSTuberculosis:
meningitis
■ The brainstem is often the site of greatest
involvement, =dysfunction of cranial nerves III,
VI, andVII.
■ The exudate also interferes with the normal
flow of cerebrospinal fluid (CSF) ,basilar
cisterns, leading to a communicating
hydrocephalus

60. CNSTuberculosis:
meningitis
■ The 1st stage typically lasts 1-2 wk and is
characterized by nonspecific symptoms
such as fever, headache, irritability,
drowsiness, and malaise.

61. CNSTuberculosis:
meningitis
■ The 2nd stage usually begins more
abruptly.The most common features are
lethargy, nuchal rigidity, seizures, positive
Kernig and Brudzinski signs, hypertonia,
vomiting, cranial nerve palsies, and other
focal neurologic signs.

62. CNSTuberculosis:
meningitis
■ The accelerating clinical illness usually correlates
with the development of hydrocephalus,
increased intracranial pressure, and vasculitis.
■ Some children have no evidence of meningeal
irritation but can have signs of encephalitis, such
as disorientation, movement disorders, or speech
impairment.

63. CNSTuberculosis:
meningitis
■The 3rd stage is marked by
coma, hemi- or paraplegia,
hypertension, decerebrate
posturing, deterioration of vital
signs, and eventually death.

64. CNSTuberculosis:
meningitis
■ The in up to 50% of
cases,
.The most
important laboratory test for the
diagnosis of tuberculosis meningitis is
examination and culture of the lumbar
CSF.

65. CNSTuberculosis:
meningitis
■ The CSF leukocyte count usually ranges
from
may be
present initially, but lymphocytes
predominate in the majority of cases.
The CSF glucose is typically <40 mg/dL
but rarely <20 mg/dL..

67. CNSTuberculosis:
tuberculoma
■ Another manifestation of CNS
tuberculosis is the tuberculoma, a
tumor-like mass resulting from
aggregation of caseous tubercles that
usually manifests clinically as a brain
tumor.

68. CNSTuberculosis:
tuberculoma
■ Tuberculomas account for up to 30% of
brain tumors in some areas of the
world but are rare .
■ In adults tuberculomas are most often
but in children they are
often infratentorial, located at the base
of the brain near the cerebellum

69. CNSTuberculosis:
tuberculoma
■ Since the advent of CT, the paradoxical
development of tuberculomas in
patients with tuberculosis meningitis
who are receiving ultimately effective
chemotherapy has been recognized.

71. Bone and Joint Disease
■ is most likely to involve the vertebrae.The
classic manifestation of tuberculous spon-
dylitis is progression to Pott disease, in
which destruction of the vertebral bodies
leads to gibbus deformity and kyphosis
Multifocal bone involvement can occur.

72. Bone and Joint Disease
■ A bone biopsy is to confirm
the diagnosis. Surgical intervention is
generally not necessary for cure and

74. Abdominal and Gastrointestinal Disease
■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.

75. Abdominal and Gastrointestinal Disease
■Abdominal pain or tenderness, ascites,
anorexia, and low-grade fever are
typical manifestations.
■TheTST is usually reactive.The
diagnosis can be confirmed by
paracentesis with appropriate stains
and cultures

76. Abdominal and Gastrointestinal Disease
■Tuberculous enteritis is caused
by
or by swallowing
tubercle bacilli discharged from
the patient’s own lungs.

77. Abdominal and Gastrointestinal Disease
■The jejunum and ileum near Peyer
patches and the appendix are the
most common sites of involvement.
The typical findings are shallow
ulcers that cause pain, diarrhea or
constipation, weight loss, and low-
grade fever.

79. Genitourinary Disease
■Renal tuberculosis is rare in children,
because the incubation period is
several years or longer.Tubercle bacilli
usually reach the kidney during
lymphohematogenous dissemination.

80. Genitourinary Disease
■Dysuria, flank or abdominal pain,
and gross hematuria develop as the
disease progresses. Hydronephrosis
or ureteral strictures can complicate
the disease.

81. Genitourinary 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.TheTST is nonreactive in up to
20% of patients.A pyelogram or CT scan often
reveals mass lesions, dilation of the proximal
ureters, multiple small filling defects, and
hydronephrosis if ureteral stricture is present.
Disease is most often unilateral

83. TREATMENT
■ The standard therapy of intrathoracic tuberculosis
(pulmonary disease and/or hilar lymphadenopathy) in
children, = 6 mo regimen of isoniazid and rifampin
supplemented in the 1st 2 mo of treatment by
pyrazinamide and ethambutol.
■ OR Nine-month regimens of only isoniazid and
rifampin are also highly effective for drug-susceptible
tuberculosis
■ incidence of clinically significant adverse reactions of
<2%

84. ‫نگه‬ ‫مرحله‬
‫دارنده‬
‫حمله‬ ‫مرحله‬
‫اي‬
‫تحت‬ ‫بيماران‬
‫درمان‬
‫درماني‬ ‫گروه‬
4HR 2HRZS 1 ‫بيماران‬ ‫ي‬ ‫همه‬
‫جديد‬
( ‫اسمير‬ ‫از‬ ‫اعم‬
‫مثبت،اسمير‬
‫خارج‬ ،‫منفي‬
‫ريوي‬)
1
5HRE 2HRZES
‫سپس‬ ‫و‬
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،‫شكست‬ ‫از‬ ‫بعد‬
‫از‬ ‫بعد‬ ‫درمان‬
‫غيبت‬
2

85. TREATMENT
■ When directly observed therapy is used,
intermittent (twice or thrice weekly) administration of
drugs after an initial period as short as 2 wk of daily
therapy is as effective in children as daily therapy for
the entire course.

86. TREATMENT
■ Extrapulmonary tuberculosis is usually
caused by small numbers of mycobacteria.
In general, the treatment for most forms of
extrapulmonary tuberculosis in children,
including cervical lymphadenopathy, is the
same as for pulmonary tuberculosis.
Exceptions are bone and joint,
disseminated, and CNS tuberculosis,

87. TREATMENT
■These conditions are treated for 9-12
mo. Surgical debridement in bone and
joint disease and ventriculoperitoneal
shunting in CNS disease may be
necessary adjuncts to medical therapy.

88. Latent Mycobacterium tuberculosis Infection
■ children with LTBI have more years at risk for
development of disease than adults. Because of these
factors, and the excellent safety profile of isoniazid in
children, there is a tendency to err on the side of
overtreatment in infants, young children and
adolescents.
■ Isoniazid therapy for LTBI appears to be more
effective for children than adults, with several large
clinical trials demonstrating risk reduction of 70-90%.

89. Latent Mycobacterium tuberculosis Infection
■Isoniazid should be given to children
younger than 5 yr of age who have a
negativeTST or IGRA

90. Latent Mycobacterium tuberculosis Infection
■This practice is often referred to as
window prophylaxis. By the time
delayed hypersensitivity develops (2-3
mo), an untreated child already may
have developed severe tuberculosis.

91. Latent Mycobacterium tuberculosis Infection
■ For these children, tuberculin skin or
IGRA testing is repeated 3 mo after
contact with the source case for
tuberculosis has been broken (broken
contact is defined as physical
separation or adequate initial
treatment of the source case).

92. Latent Mycobacterium tuberculosis Infection
■ If the second test result is
positive, isoniazid therapy is
continued for 9 mo, but if the
result is negative, treatment
can be stopped.