PEDIATRIC TUBERCULOSIS
A. EPIDEMIOLOGY:
- At least half a million children become ill with TB each year
- 70-80% have PTB; 20-30% have EPTB
- 2013: 80,000 HIV negative children died due to TB
- 2014: 6.5% cases are children <15y.o; 359,000 new and relapse cases among
children were reported (↑30%)
- ~550,000 children become ill with TB
- Additional 81,000 (69,000-93,000) TB deaths among HIV-children (27% of total
HIB-TB death)
- Largest increase were in India (~30,000) and Philippines (~10,000)
B. UNIQUE FEATURES OF TB IN CHILDREN:
- The diagnosis of childhood TB is especially difficult compared to that of an adult in
the absence of a gold standard in many cases
- Important:
o Age
o Stage of development
o vulnerability of the young
offer the way to approach management in this age group
common barriers to early recognition and the needed intervention or preventive
treatment
- A common misconception that presents a barrier is that children rarely develop
life-threatening TB
- Accurate rates of mortality and morbidity, disease prevalence and incidence are
hampered by low resources particularly in high-burden countries
- The lag time from exposure to infection and disease is difficult to assess.
- Child TB has been referred to as missing diagnosis mainly because of the
occurrence of asymptomatic infection (latent TB infection) and in early disease
- Children present with protean manifestations (fever, cough, weight loss,
weakness, etc.) difficult to distinguish from other childhood diseases; at greater
risk for dissemination, serious complications and death, than adults
- Adults present more frequently with localized disease, often with pulmonary
symptoms like cough, with less constitutional manifestations than children
- Definitive diagnosis by sputum smear and culture of Mycobacterium tuberculosis is
even more difficult because of the poor bacteriologic yield brought on by the
paucibacillary character of majority of TB in the young and the difficulty of
collecting specimen in them
- Demonstration of AFB on microscopy and/or histologic changes on biopsy can
only provide presumptive diagnosis in the absence of a positive culture
- Radiologic examination is often equivocal (requires consensus among radiologists
for a clear-cut set of criteria)
- The TST has logistic limitations on top of high false-negative finding even under
ideal settings
C. ENTRY POINTS FOR THE RECOGNITION AND CASE FINDING OF TB IN CHILDREN:
1. Symptomatology
 When there is symptomatic child consulting for signs and symptoms
suggestive of tuberculosis, one of the five criteria discussed under the 1997
PPS Consensus Statement (clinical manifestations) and under DOH/NTP
Manual of Procedure as a presumptive TB case requiring further studies to
confirm the diagnosis
 The refined systematic symptom-based approach mentioned earlier are
recommended for the initial screening of children for TB disease
2. Contact Screening
 Screening of children who belong to the household or close environment of a
registered TB case
 These entry points are incorporated in the MOP2015 algorithms reproduced
in Appendix 1, including conditions where there are no resources for TST and
chest X-ray
D. TB EXPOSURE, INFECTION, AND ACTIVE PULMONARY DISEASE
TB Exposure
 a child is in close contact with contagious adult or adolescent TB cases, without
any signs and symptoms of TB, negative TST reaction, no radiologic and laboratory
findings suggestive of TB
TB Infection or Latent TB Infection (LTBI)
 a child has no signs or symptoms presumptive of TB nor radiologic or laboratory
evidence but has a positive TST reaction
TB Disease
 A presumptive TB who after clinical and diagnostic evaluation (TST and/or
radiology) is confirmed to have TB
 Classification is based on :
Bacteriological Status
1. Bacteriologically Confirmed – Biological specimen is positive by smear
microscopy, culture or rapid diagnostic tests (such as Xpert MTB/RIF)
2. Clinically Diagnosed – Doesn’t fulfill the criteria for bacteriological
confirmation but has been diagnosed with active TB by clinical or other
medical practitioner who has decided to give the patient a full course of TB
treatment (cases diagnosed on the bases of X-ray abnormalities or suggestive
histology, and extrapulmonary cases without laboratory confirmation are
also included)
Anatomical Site
1. Pulmonary TB (PTB): involves the lung parenchyma and tracheobronchial
tree (px with both P/EPTB should be classified as a case of PTB
2. Extrapulmonary TB (EPTB): a case of tuberculosis involving organs other than
the lungs (larynx, pleura, lymph nodes, abdomen, GUT, skin, joints and
bones, meninges); Histologically-diagnosed EPTB through biopsy of
appropriate sites will be considered clinically-diagnosed TB. Laryngeal TB,
though likely sputum smear-positive, is considered an extrapulmonary case
in the absence of lung infiltrates on CXR.
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E. CLINICAL FEATURES BETWEEN PEDIATRIC AND ADULT TB G. TUBERCULIN SKIN TEST/MANTOUX TEST
- Generally, TB in children follows primary TB infection while that of adult TB - the standard and recommended method of using tuberculoprotein or tuberculin
represents reactivation of previous infected foci for TB screening

F. RECOMMENDED APPROACH TO THE DIAGNOSIS OF TB IN CHILDREN

 2008:
o DOH released Administrative Order No. 2008-001 on Guidelines for
Implementing Tuberculosis Control Program in Children
o This provided a standard policy for case finding, treatment of children
with TB, contact tracing of children at risk for developing TB for
preventive therapy
o It included all childhood cases of TB in the routine NTP recording and
reporting activities using DOTS strategy
o Contacts for screening were defined as all children from 0-4 years of
age and symptomatic children from 5-14 years who are in close contact
(living in the same household or infrequent contact) with a case of PTB
o Diagnosis is made through data obtained from the history, physical
exam and diagnostic exam results
 The following are the guidelines in approaching TB in children:
o Symptoms
 A child shall be considered a TB symptomatic if at least 3 of
these are presented:
1. Chronic cough or wheezing of 2 weeks or more
2. Unexplained fever for more than 2 weeks (malaria and
pneumonia have been ruled out)
3. Unexplained weight loss or failure to gain weight, or
loss of appetite
4. Failure to respond to 2 weeks of appropriate antibiotic

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 H. BCG VACCINATION: EFFECTIVITY IN TB PREVENTION
Role of BCG Vaccinations and its Effectiveness in the Prevention of TB Infection and Disease
RECOMMENDATIONS FOR THE POSITIVE CUT-OFF SIZE OF THE MANTOUX TEST
 Positive TST as an area of skin induration measuring a diameter of 10 mm or more regardless
of BCG status
 An induration of 5 mm or more is considered positive in the following conditions:
o Severely malnourished children (with clinical evidence of marasmus or
kwashiorkor)
o Those are who are immunocompromised (with congenital immune deficiencies,
HIV-AIDS or with a history of prolonged intake of immunosuppressants)
 Results of the TST to be interpreted in the context of the patient’s risk for M.tb infection
(exposure to TB disease or risk of progression to TB disease)
 3 cut-off points when defined according to risk factors will improve the sensitivity and
specificity of the TST as follows: An induration of ≥5 mm is considered positive for populations
with the highest risk of having TB infection and disease; they are expanded to:
o HIV-infected persons
o Those who have had close contact with an infectious TB source
o Persons with chest radiographs consistent with prior untreated TB
o Organ transplant recipients
o Other immunosuppressed patients (those taking the equivalent of >15 mg/day of
prednisone for 1 month/those taking TNG-α antagonists)
 The ≥ 10 mm cut-off point is recommended for populations with high risks of having TB
infection and disease and for persons living in areas where TB is highly prevalent and 10 mm
cut-off points is recommended for populations with high risks of having TB infection and
disease and for persons living in areas where TB is highly prevalent
 ≥ 15 mm cut-off point is for populations with no risk factors
SPECIAL CONSIDERATIONS FOR TUBERCULIN TESTING
Anergy
- The ability to react to a TST because of a weakened immune system
- Absence of a reaction to the TST doesn’t rule out the diagnosis of TB infection
- May be caused by many factors (HIV infection, severe febrile illness, measles/other viral
infections, Hodgkin’s disease, sarcoidosis, live-virus vaccination, administration of corticosteroids
or immunosuppressive drugs, underdeveloped immune system in young infants)
- The use of anergy testing in conjunction with tuberculin skin testing is not routinely
recommended
Skin Test Conversion
- Refers to a change from a negative to a positive result
- Indicative of recent infection with M. tuberculosis, regardless of age
- An increase in reaction size to ≥ 10 mm induration within a period of two years for persons with
previous negative TST reactions is classified as conversion to positive
 Bacille Calmette Guerin (BCG) is a vaccine derived from a live attenuated strain of
M.bovis and is the only known vaccine used against TB
 BCG vaccination induces artificial primary immunity to TB for prevention of subsequent
illness caused by virulent bacilli
 ~4 billion people were immunized with BCG since its discovery (most widely used
vaccine worldwide)
 Use has shown varied differences in protective efficacy results in different studies
 The variation in protective effect from different trials ranged from 0%-80%
 This has been attributed to differences in BCG strains, differences in prevalence of
infections with environmental mycobacteria, genetic and physiological differences
between the populations, different immunological mechanisms against forms of disease
with varying pathogenesis
 BCG vaccination of newborn & infants reduces the risk of TB by 50% on average
 The protective effect and confidence intervals for pulmonary and meningeal or miliary
disease
o Immunological mechanisms operate against different forms of disease, with
BCG being more effective in preventing the hematogenous spread of TB
bacteria as in meningitis and miliary forms
o In a high burden country for TB, BCG confers protection against incident TB
disease among those with household exposure in those <10y.o
 The recommendation to give BCG at birth is supported by the theory that exposure to
certain varieties of mycobacteria can give rise to a cell-mediated response which
opposes the protective effect of subsequent BCG vaccination
 Recommendation is to give BCG at birth or soon thereafter before any exposure to
environmental mycobacteria
 BCG is not recommended in countries where TB rates are low, since it would increase
tuberculin reactivity, thereby making the tuberculin test less accurate
 BCG is not recommended to be given to immunocompromised individuals
 BCG accelerated test should not be used for TB screening
 Persons who have received BCG vaccination are not recommended to be vaccinated
again, since available evidence does not support such practice
 Multiple vaccinations are not recommended for anyone
 Best strategy to eliminate TB is through a new and more effective TB vaccine:
o It should be safe even when administered to immunocompromised persons
and not hypertensive to PPD that will cross-react with TST and thereby
limiting its specificity.
o It should protect against diseases resulting from subsequent infection (pre-
exposure), as well as, endogenous reactivation of an earlier ( post-infection)
o An effective post-infection vaccine could not be the most important new
tool to help eliminate TB
o In high-incidence countries, a post-infection vaccine could be administered
even among adults in high-risk groups (e.g. health-care workers), and its
wide application could have a major global impact.
o Early detection and completion of appropriate treatment (through DOTS)
of LTBI and TB disease would remain as the best strategy to effectively
control TB
 The main vaccine targets are prevention of infection in naïve individuals, prevention of
reactivation of latent infection, and therapeutic vaccines to prevent relapse in TB
patients
 The decrease in effectiveness of BCG against PTB has been hypothesized to be a
consequence of increased immune suppression of BCG antioxidants.
 Restoration of lost BCG strain epitopes may be useful future vaccine developmental
strategy.
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I. SCREENING OF PEDIATRIC DRUG-SUSCEPTIBLE HOUSEHOLD CONTACTS OF TB
Recommended Regimens
J. ANTI-TB CHEMOTHERAPY IN CHILDREN
As of December 2015, the WHO and its partners have announced the availability of FDCs
with the following formulations:
 Intensive phase: Rifampicin 75 mg + Isoniazid 50 mg + Pyrazinamide 150 mg
 Continuation phase: Rifampicin 75 mg + Isoniazid 50 mg
 Treatment can then be administered more efficiently, with fewer pills to be used
over less weight bands
 Ethambutol (15-25 mg/kg) should be added in the intensive phase for children
with extensive disease or living in settings where the prevalence of HIV or of
Isoniazid resistance is high, as in the Philippines
 Though these FDCs will provide Isoniazid at a dose <10-15 mg/kg/day in some
weight bands, the WHO has noted that an isoniazid dosage of 7 mg/kg will provide
adequate levels in almost all children
 Isoniazid dosing range may be extended for 7-15 mg/kg, with the mid-range placed
at 10 mg/kg
 Drug therapy regimens employed in tuberculosis are designed to achieve varying
goals.
 For the patient exposed to M. tuberculosis without evidence of infection or active
disease, the objective is to prevent the onset of infection (“primary prophylaxis”).
 For the patient with latent TB infection, the drug regimen aims at preventing
progression of infection to active disease (“secondary prophylaxis”).
 Finally, for the patient classified as having disease, the goals include not only cure
for the individual patient, but also decrease in transmission to the community.
 There is a Standard Code for Anti-TB Treatment Regimens, which uses an
Abbreviation for each Anti-TB Drug:
o Isoniazid – H
o Rifampicin – R
o Pyrazinamide – Z
o Ethambutol - E
 A regimen consists of two phases:
o Initial Phase
o Continuation Phase
 The number at the front of each phase represents the duration of that phase in
month; a subscript number following a drug abbreviation is the number of doses
per week of that drug (if there is no subscript number following a drug
abbreviation, treatment with that drug is daily)
 An alternative drug (or drugs) appears as an abbreviation/s in parentheses
 Example: 2HRZE/4H
o The initial phase is 2HRZE.
o Duration of this phase is 2 months
o Drug treatment is daily (no subscript numbers after the abbreviation)
with isoniazid, rifampicin, pyrazinamide and ethambutol
o The continuation phase if 4HR
o Duration of this phase is 4 months, with isoniazid and rifampicin once
daily on empty stomach (one hour before, or two hours after a meal).
 Treatment regimens are assigned based on the anatomical site of involvement,
bacteriologic confirmation status as well as history of previous treatment
 The WHO’s most recent guideline as well as the 2nd edition of the Guidance for
National Tuberculosis Programs on the Management of Tuberculosis in Children
outlines a strategy that has become the basis of the DOH’s recommendations
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