2. Tuberculosis is an infectious disease
caused by Mycobacterium tuberculosis.
3. TB infection is when a person carries the
Mycobacterium tuberculosis bacteria inside the body.
Many people have TB infection and are well. A
positive TST indicates infection - but a negative TST
does not exclude the possibility of infection.
TB disease occurs in someone with TB infection
when the bacteria inside the body start to multiply
and become numerous enough to damage one or
more organs of the body. This damage causes clinical
symptoms and signs and is referred to as
“tuberculosis” or active disease.
4. Index Case: Usually an adult with smear
positive pulmonary TB.
Close contact is defined as living in the same
household as, or in frequent contact with
(e.g. child minder, school staff), an index case
with PTB.
5. Pulmonary TB sputum positive - A child is defined as smear
positive if any of the following is true:
◦ AFB are detected via microscopy on either a sputum or gastric
lavage sample.
◦ MTB is isolated by culture on either a sputum or gastric lavage
sample.
◦ MTB is detected by MTB/RIF Gene Xpert on either a sputum or
gastric lavage sample.
Pulmonary TB sputum negative - A child that has the signs
and symptoms for pulmonary TB, but does not meet the
above criteria for pulmonary TB sputum positive is classified
as smear negative TB. This also includes children in whom
sputum smear not done or not available.
6. Extra pulmonary TB - Any TB occurring outside the lungs is
classified as EPTB. 3
Drug Resistant TB - This is a laboratory diagnosis. Drug
resistant TB should be suspected if:
◦ Child has contact with a known case of DRTB
◦ Child has contact with an adult who has suspected DRTB as
follows:
The adult remains sputum smear positive after 2 months of
treatment,
An adult who has a history of previously treated TB,
An adult with a history of treatment interruption.
◦ Child is not responding to the anti- TB treatment
regimen
◦ Child has a recurrence of TB after successful TB treatment
7. 9M new annual cases
11% under 14 yrs world average (Range3-
25%)
2M annual deaths (25% HIV +ve)
40% children
22 countries= 80% of the cases- SSA 25%
SEA
In SSA Kenya 5/8 (15/22 globally)
41% of all reported TB in Kenya are HIV +ve
WHO, 2006; WHO report on TB of 2011
8. In 2010, In Kenya Total new 95 604 of which 5
721 < 15 years.
Global burden of Tb increasing due to:
HIV co-infection
Popn. migration patterns
In 2005 over 35% of all notified TB cases in Kenya were from
five largest urban areas of Nairobi , Mombasa , Kisumu,
Nakuru and Eldoret,
Increasing poverty
Crowded living condition
Inadequate health coverage/poor access
Inefficient TB control program
The WHO estimates that the Case Detection Rate (CDR) for
2004 was around 47% while the treatment success rate has
been a steadily increase with 85.43 % in the year 2009
(Kenyan).
WHO report on TB of 2011, DLTLD, Ministry of Public Health
9. Age: More likely between 1-4yrs, favoured
age 5-14yrs
Sex: No significant difference in gender in
children, Adults 2/3 male
Untreated infants with LTBI have upto 40% of
developing TB.
Risk of progression to disease decreases
gradually to lifetime risk of 5-10%
10. Transmission:
Person to person,
Airborne mucus droplet nuclei <5 microM
Chance higher in:
Sputum +ve
Extensive lobe infiltrate or cavity
Copious production
Severe forceful cough
Enhanced by: Poor air circulation, poor lighting &
overcrowding
11. Risk factors for TB infxn:
Children exposed to high risk adults
Poverty
Homeless persons
Risk factors for Dse progression:
Age <5yrs
Co-infection with HIV
Other forms of Immuno-suppression:
Malnutrition
Malignancy
DM
CRF
Steroid use
Organ Transplantation
12. 130+ Mycobacterium species
TB and non-TB mycobacteria (NTM)
Grouped in complexes of mycobacteria that
are similar to each other
M TB complex (M tuberculosis, M bovis, M
africanus, M microti, M. canetti)
The tubercle bacilli is non-spore forming,
nonmotile, weekly GP curved 2-4microM
long.
Hallmark of all mycobacterium is acid
fastness.
13. Inhalation and deposition in the lungs of the
tubercle bacillus leads to:
Immediate clearance of the organism
Chronic or latent infection
Rapidly progressive disease (or primary disease)
Active disease many years after the infection
(reactivation disease)
14. Schematic illustration of potential disease progression following primary
pulmonary infection with M. tuberculosis.
15. Risk of progression to TB disease
Age at
primary
infection
(yr)
No disease Pulmonary disease Disseminated
disease or TB
meningitis
<1 50% 30-40% 10-20%
1-2 75-80% 10-20% 2-5%
2-5 95% ~5% ~0.5%
5-10 98% ~2% <0.5%
>10 80-90% 10-20% <0.5%
16. Majority of inhaled bacilli are trapped in the
upper airways and expelled by ciliated
mucosal cells, <10% reach the alveoli.
Nonspecifically activated alveolar
macrophages then ingest the bacilli after
association of C2a with the bacterial cell wall
followed by C3b opsonization and
recognition by the macrophages.
17. The host's macrophages contain bacillary
multiplication or
Rapid multiplication of bacilli results in lysis
of the macrophages with release of the
bacilli.
These are ingested by nonactivated
monocytes attracted from the bloodstream to
the site by various chemotactic factors.
The patient remains asymptomatic at this
stage.
18. 2 - 4 wks after infection, a tissue-damaging
and a macrophage-activating host response
occurs.
A delayed-type hypersensitivity (DTH) rxn to
the bacillary antigens then destroys
nonactivated macrophages that contain
multiplying bacilli.
The macrophage-activating response is cell-
mediated & results in the activation of
macrophages capable of killing and digesting
tubercle bacilli.
19. Devt of specific immunity results in
accumulation of activated macrophages and
lymphocytes.
Early solid necrosis occurs in the center of the
tubercle and M. tuberculosis’ growth is
inhibited in the necrotic envt.
Healing with fibrosis and calcification occurs.
20. In a few cases, there is intensified DTH
reactions, which lead to tissue destruction.
The lesion enlarges further, caseous material
liquefies at the centre and cavities are formed.
Within the cavity, tubercle bacilli multiply and
spread into the airways and the envt.
21. In young children with poor natural immunity,
haematogenous spread may result in fatal
TBM or miliary tuberculosis.
CMI confers partial protection against M.
tuberculosis, while humoral immunity has no
defined role in protection.
22. Bacterial replication is more likely to occur in
lung apices, brain, kidneys, and bones.
Disseminated tuberculosis occurs if the
number of circulating bacilli is large and the
host cellular immune response is inadequate
23. The time btn initial infection & disease is
variable.
Disseminated and meningeal TB are early
manifestations, occur within 2–6 mo of the
infxn.
Lymph node or endobronchial TB appears
within 3–9 mo.
Lesions of the bones and joints take several
years
Renal lesions take decades to appear.
25. Alveolar macrophages secrete a number of
cytokines:
Interleukin (IL) 1 contributes to fever;
IL-6 contributes to hyperglobulinemia;
TNF-α contributes to the killing of mycobacteria,
the formation of granulomas, and a number of
systemic effects, such as fever and weight loss.
Macrophages are also critical in Ag
presentation to T lymphocytes resulting in
proliferation of CD4+ lymphocytes.
26. Reactive CD4+ lymphocytes produce
cytokines of the TH1 pattern and participate
in MHC class II–restricted killing of infected
cells.
TH1 CD4+ cells produce IFN-γ and IL-2 ,
promoting CMi.
TH2 cells produce IL-4, IL-5, and IL-10 and
promote humoral immunity.
This interplay determines the host's
response.
27. >50% infants & children have no physical
signs
Nonproductive cough and mild dyspnea.
Systemic complaints e.g. fever, night sweats,
anorexia, FTT and decreased activity occur
less often.
Bronchial obstruction may cause localized
wheezing or decreased breath sounds +/-
respiratory distress.
28. Originates from the discharge of bacilli into
the pleural space from a subpleural
pulmonary focus or caseated lymph node.
Infrequent in pts <6 yr, rare in <2 yr of age.
Usually unilateral but can be bilateral.
Often the XR abnormality is more extensive
than would be suggested by physical findings
or symptoms.
29. Clinical onset is sudden.
Characterized by fever, shortness of breath,
chest pain on deep inspiration, & diminished
breath sounds.
The prognosis is excellent.
Scoliosis is a rare complication.
32. Miliary TB can be a complication of primary
TB in young children.
A rapid onset of fever, +/- signs of
respiratory distress
Hematogenous spread may result in disease
in the brain and liver.
Infants are particularly prone
34. 30 - 50 % of children with miliary TB have
meningitis at the time of diagnosis.
Occurs in 5-10 % cases of TB in children
<2yr. Thereafter, the frequency drops to < 1
%.
The signs and symptoms include;
◦ low-grade persistent fever,
◦ malaise, anorexia, weight loss, fatigue,
35. – hepatomegaly, splenomegaly
– gen. lymphadenopathy,
– alteration in consciousness and sensorium, stupor
– the emergence of focal neurological signs.
• CSF:
– a moderate lymphocytic pleocytosis,
– low glucose level and
– an elevated protein concentration.
• Head CT scan with contrast.
36. • Occurs in 1-6% of untreated primary TB
• Often involves large weight-bearing bones or
joints
• vertebrae (50 %),
• hips(15 %), and knees (15 %).
• Less commonly the femur, tibia, and fibula.
• “gibbus deformity” +/- severe kyphosis with
destruction of the vertebral bodies.
• Atlantoaxial subluxation may lead to
paraplegia or quadriplegia.
37. Rare , caused by lymphohematogenous
spread during pregnancy from an infected
placenta or aspiration of contaminated
amniotic fluid.
Congenital TB diagnosis is based on presence
of at least one of the following proven TB
lesions;
◦ skin lesions during the 1st wk of life, including
papular lesions or petechiae,
38. ◦ necrotic or purpuric lesions
◦ choroidal tubercles in the retina
◦ documentation of TB infection of the placenta or
the maternal genital tract
◦ presence of a primary hepatic complex (liver and
regional lymph-node involvement)
◦ exclusion of the possibility of postnatal
transmission
39. Diagnosis in children is challenging
Thorough history
◦ TB contact, cough, fever, FTT.
Thorough clinical examination
◦ Gibbus, LN, Swollen joint, P.Effusions, TBM
40. The "gold standard" for the diagnosis of TB is
culture-isolation of the organism
Sputum culture yields are generally low:30–
40%
Sputum smear microscopy is positive in 10–
15% of children with TB,
Ziehl-Neelsen method, auramine-rhodamine or
auramine O fluorescence staining.
Scoring charts; their value especially with HIV
co-infection has not been established
41. sensitivity of 73%; if, one point for marasmus was added
the sensitivity became 93%
42.
43. The "gold standard" for the diagnosis of
tuberculosis is culture-isolation of the organism
Sputum examination, the AFB smear —
High-quality, spontaneously expectorated sputum is
stained by Ziehl-Neelsen method, auramine-rhodamine or
auramine O fluorescence staining.
Whenever possible, it is particularly important to
make a bacteriologic diagnosis in the following
situations:
◦ Suspected drug resistant TB
◦ Severe and complicated disease
◦ HIV infected
◦ Diagnostic uncertainties
44.
45. Histopathology
◦ reveals characteristic granulomatous lesions with
epithelioid macrophages, Langhan's giant cells, and
lymphocytes predominating with central caseation.
Molecular methodologies
◦ nucleic acid amplification tests (NAAT)
◦ provide rapid diagnosis within 24 to 72 hours.
46.
47. The Xpert MTB/RIF is a cartridge-based, automated
diagnostic test that can identify MTB and resistance
to RIF.
It was co-developed by Cepheid, Inc and NIH.
In Dec 2010, WHO endorsed its use in TB endemic
countries and declared it a major milestone for global
TB diagnosis.
The Xpert is a highly sensitive, rapid and simple-to-
use nucleic acid amplification test (NAAT).
It purifies, concentrates, amplifies (by real-time PCR)
and identifies targeted nucleic acid sequences in the
TB genome, and provides results from unprocessed
sputum samples in 90 minutes, with minimal
biohazard and very little technical training required to
operate.
48. • CXR:
– hilar and para-tracheal lymphadenopathy is the
hallmark of primary TB in children.
– Other features : linear, interstitial and nodular
densities, cavities with consolidation, empyema,
bronchiectasis or focal masses.
• CT scanning:
– Hilar lymphadenopathy, endobronchial TB,
pericardial invasion, and early cavitations or
bronchiectasis
– In TBM shows basal cistern inflammation,
hydrocephalus, tuberculomas and infarction.
49. Imaging in skeletal TB:
◦ irregular areas of destruction,
◦ sclerosis, osteopenia, minimal periosteal reaction and
slow enlargement of the focus.
◦ In children, TB typically affects the metaphysis and can
intrude into the growth plate.
-TST-Tuberculin skin test(mantoux/PPD)used to
determine if someone has developed an immune response
to m.tb. can occur in
◦ active TB,
◦ Past infection,
◦ BCG vaccine
50. Presence of 2 or more of the following symptoms
Cough > 2weeks Weight loss or poor weight gain
Persistent fever and/or night sweats > 2 weeks
Fatigue, reduced playfulness, less active PLUS
Presence of 2 or more of the following: Positive
contact history Respiratory signs CXR suggestive of
PTB (where available) Positive Mantoux test (where
available)
Then PTB is likely, and treatment is
justified
51.
52.
53.
54. Aims of TB treatment are:
Cure the child of TB
◦ Prevent death from TB
◦ Prevent the complications arising from TB disease
◦ Prevent TB relapse by eliminating the dormant
bacilli
◦ Prevent the development of drug resistance by
using a combination of drugs
◦ Decrease TB transmission to others
55. Some of the important points to note about TB
treatment in children are:
◦ Children usually have paucibacillary disease, as cavitating
disease is relatively rare (about 6% or less) in children under
13 years of age and the majority of the organisms in adult-
type disease are found in cavities.
◦ Children develop extra-pulmonary TB (EPTB) more often
than do adults.
◦ Severe and disseminated TB (e.g., TB meningitis and miliary
TB) occur especially in young children (less than 3 years
old).
◦ Treatment outcomes in children are generally good even in
the HIV infected provided treatment is started promptly.
◦ Children generally tolerate the anti- TB drugs better than
adults.
56. 1st line agents: INH,RIF,PZA,ETH,
well absorbed after oral administration with
peak serum levels at 2-4h and nearly
completely eliminated within 24 h.
2nd line agents:streptomycin,quinolones
,aminoglycosides
57. Are well absorbed after oral administration
with peak serum levels at 2-4h and nearly
completely eliminated within 24 h.
They are bactericidal, have sterilizing activity,
and have low rate of induction of drug
resistance.
Streptomycin is used in drug-resistant dx ,
severe dx & retreatment.
Supportive care-nutrition.
58.
59. Drug Old dose
range
New dose
range
Average
dose
Maximum
dose
Isoniazid 5-10 10- 15 10 300mg
Rifampicin 8-12 10-20 15 600mg
Pyrazinamid
e
20-30 30-40 35 1500mg
Ethambutol 15-25 15-25 20
Streptomycin 12-18 12-18 15
60. 1. Non Severe TB
◦ Pulmonary TB without extensive parenchymal lung disease
◦ TB lymphadenitis
◦ TB pleural effusion
2. Severe TB
◦ PTB with extensive parenchymal lung disease
◦ Miliary TB
◦ TB bone or joint TB meningitis Pericardial TB Abdominal TB
◦ All other forms of extra-pulmonary TB
3. Retreatment
4. Multi-drug resistant TB
61.
62. Other important observations to note include:
◦ Treatment regimens are the same for HIV-
infected and HIV-uninfected children
◦ Response to treatment in HIV infected may be
slower.
◦ Report all children receiving anti-TB treatment to
the National TB Program
◦ TB drugs are very well tolerated in children
◦ Side-effects may occur but are not common. The
most important is hepatotoxicity
◦ Ethambutol can be safely used in all children of
all ages at recommended dosages of 20 mg/kg.
63. Where scar formation may lead to serious
consequences.
These include:
◦ TBM, lymphobronchial TB, genitourinary TB,PTB
with respiratory distress, PTB with airway
obstruction by hilar lymph nodes, Severe Miliary TB,
pericardial effusion
Give prednisone at 2mg/kg once daily for 4
weeks, and then taper down over 2 weeks
(1mg/kg for 7 days, then 0.5mg/kg for 7
days)2mg/kg/day
64. Give pyridoxine 5 – 10 mg once daily to:
◦ All malnourished children throughout the anti-TB
therapy.
◦ HIV infected children
◦ Breast feeding infants.
◦ Pregnant Adolescents
65. Severe forms of PTB and EPTB (e.g. Spinal TB) for
further investigation and initial management.
TB meningitis
Severe malnutrition for nutritional rehabilitation
Signs of severe pneumonia (i.e. chest in-drawing)
Other co-morbidities e.g. severe anaemia
Social or logistic reasons to ensure adherence
Severe adverse reactions such as hepatotoxicity
66. Types:
Primary resistance; infection with M. tb that is
already resistant to a particular drug.
Secondary resistance; drug-resistant
organisms emerge as the dominant
population during treatment.
67. Multidrug-resistant tuberculosis (MDR-TB) :
◦ Resistance to at least INH and RIF, and possibly
additional chemotherapeutic agents.
Extensively drug-resistant Tb (XDR-TB) :
◦ Resistance to at least INH,RIF and also
fluoroquinolones and either aminoglycosides
(amikacin, kanamycin) or capreomycin, or both.
Diagnosis:
◦ Culture and sensitivity
◦ Rapid test (MTBDRplus):
a molecular probe that detects resistant mutations in 3
TB genes: rpoB (rifampin), and katG and inhA (INH)
68. INH monoresistance:
◦ RIF, PZA, ETH for 6-9mo; +/- quinolone
◦ 95-98% success rate (Hong Kong Chest Service/British
Medical Research Council)
RIF monoresistance:
◦ Assoc with HIV infection with advanced ISS on
highly intermittent Tb Rx.
◦ INH, PZA and streptomycin for 9-12 mo
◦ INH, PZA and ETH for 12-18mo +/- quinolone or
streptomycin for 2-3mo
◦ >95% success rate
Pyrazinamide monoresistance:
◦ 9mo of INH & RIF
69. Empiric Rx for MDR:
◦ at least 4 drugs effective against the most prevalent
drug-resistant strains.
Documented MDR
◦ discontinue the drugs to which the isolate is
resistant and to add at least two new drugs to
which the isolate is susceptible.
◦ IV/IM aminoglycoside and a quinolone for 6mo.
◦ At least 4 effective drugs for 18- 24mo
70.
71. Do not add a drug to a failing regimen.
Treat the child according to the drug susceptibility pattern and use the
treatment history of the source case’s M. tuberculosis strain if an isolate
from the child is not available.
Use at least four drugs certain to be effective.
Use daily treatment only; directly observed therapy is essential.
Counsel the child’s caregiver at every visit, to provide support, advice about
adverse events and the importance of compliance and completion of
treatment.
Follow-up is essential: clinical, radiological and bacteriological
(mycobacterial culture for any child who had bacteriologically confirmed
disease at diagnosis).
Treatment duration depends on the extent of the disease, but in most cases
will be 20 months or more (or at least 12 months after the last positive
culture).
With correct dosing, few long-term adverse events are seen even with the
more toxic second line drugs in children, including Ethionamide and the
Fluoroquinolone.
72. Reappearance of positive cultures after the
cultures convert to negative while the patient
is receiving treatment
When cultures do not become negative during
the course of treatment
At least 4 drugs likely to be effective, one of
them a parenteral agent
2SRHZ(E)/1RHZ(E)/5RH(E)
73. Rule out active disease before IPT.
INH 10mg/kg/d is used unless there is
resistance, in which RIF is given.
Congenital infection: treat with INH upto 6mo
then rpt TST if positive treat for 9mo.
(TST-tuberculin skin test)
COMPLICATIONS:Hemoptysis,pneumothorax,
bronchiectasis,extensive pulm
disease,maligancy.
74.
The BCG vaccine has existed for 80 yrs and is
one of the most widely used of all current
vaccines.(99% coverage 2010)
Given intradermally at birth or first contact
Dosing;0.05ml(<1yr) /0.1ml(>1yr)
Vaccine prevents childhood TBM and
disseminated TB.
It does not prevent primary infection.
does not prevent reactivation of latent
pulmonary infection.
76. Nelson textbk of pediatrics 19th edition
Kenya TB guidelines 2013.
Up to date 19.3.
WHO revised guidelines
Stegen G, Jones K, Kaplan P (1969). Criteria
for guidance in the diagnosis of TB.
Pediatrics, 43:260-263.
Mathur HC, Saxena S, Bhardwaj RM (1974).
Evaluation of Kenneth Jones criteria for
diagnosis of childhood TB.Indian Journal of
Pediatrics, 41:349-355.
A research agenda for childhood TB - WHO
1. All children with TB should be tested for HIV
2. Mantoux test should be regarded as positive if:
>5mm diameter of induration in high risk children (includes HIV-infected, immune-suppressed and severely malnourished children)
>10 mm diameter of induration in other children ( whether they have received vaccination or not)
3. Please note that a mantoux may be negative despite the child having TB especially in severe disseminated TB, malnutrition and HIV disease.
4. Smear Positive result can be obtained from microscopy for ZN, TB culture, GeneXpert
5. A child in close contact with smear positive household member should be considered TB infected and TST may not be necessary.