Childhood tuberculosis

Dr. Magdy Fawzy

NTP, Egypt
PAL coordinator
 Introduction:
• One third of the world’s population is infected with
Mycobacterium tuberculosis.

• Each year, about 9 million people develop TB, of whom 2

millions die

• Of the 9 million annual TB cases, about 1 million (11%)

occur in children (under 15 years of age).

• Of these childhood cases, 75% occur annually in 22

high-burden countries that together account for 80% of
the world’s estimated incident cases.

• In countries worldwide, the reported percentage of all TB

cases occurring in children varies from 3% to more than
25%.
 Estimated new TB cases ('000s)

10
100
1000
10000

India

China

Indonesia

Bangladesh

Nigeria

Pakistan

Philippines

South Africa

Russian Federation

Ethiopia

DR Congo

Viet Nam

Kenya

UR Tanzania

Brazil

Thailand

Myanmar

Zimbabwe
22 high-burden countries: 80% of all new cases

Uganda

Cambodia

Afghanistan

Mozambique
 Which factors influence children to become infected?
Mostly “Environmental”
• Exposure
- Never exposed = never infected
- Duration of exposure
• Bacterial load in source case
• Closeness of contact
 Only Adults Transmit TB

Number of bacilli in sputum

Adult Child
108 104

Need about 105 organisms/ml for positive smear

 Transitions in Childhood Tuberculosis

Contact with smear positive index case

Not infected (50-70%) Infected (30-50%)

Diseased (10-30%)

Within 2 years (50%) Lifelong (50%)

 Exposure, infection and evolution:
• The source of infection of most children is an
infectious adult in their close environment
(usually the household).

• This exposure leads to the development of a

primary parenchymal lesion (Ghon focus) in the
lung with spread to the regional lymph node(s).

• The immune response (delayed hypersensitivity

and cellular immunity) develops about 4–6
weeks after the primary infection.
Exposure, infection and evolution, cont.:
• In most cases, the immune response stops the
multiplication of M. tuberculosis bacilli at this
stage.

• However, a few dormant bacilli may persist.

• A positive tuberculin skin test (TST) would be

the only evidence of infection.

• In some cases, the immune response is not

strong enough to contain the infection and
disease occurs within a few months.
Exposure, infection and evolution, cont.:

• Risk of progression to disease is increased when

primary infection occurs particularly in the very young
(0–4 years).

• Children who develop disease usually do so within 2

years following exposure and infection, i.e. they
develop primary TB.

• A small proportion of children (generally older children)

develop post-primary TB either due to:
– Reactivation, after a latent period, of dormant bacilli acquired
from a primary infection or
– By reinfection.
Age at primary infection Risk of disease following primary infection.

< 1year No disease 50%

Pulmonary disease (segmental) 20-40%
TBM or miliary 10-20%
1-2 years No disease 70%
Pulmonary disease (segmental) 10-20%
TBM or miliary 5-10%

2-5 years No disease 95%

Pulmonary disease (segmental) 5%
TBM or miliary 0. 5%

5-10 years No disease 98%

Pulmonary disease (segmental, effusion or adult type) 2%
TBM or miliary <0. 5%
> 10 years No disease 80%
Pulmonary disease (adult type) 10-20%
TBM or miliary <0. 5%
The key risk factors for TB are:
• Household contact with a newly diagnosed
smear-positive case.

• Age less than 5 years.

• HIV infection.

• Severe malnutrition.
Diagnosis of TB in children
Key features suggestive of TB
The presence of three or more of the following
should strongly suggest a diagnosis of TB:
– Chronic symptoms suggestive of TB
– Physical signs highly of suggestive of
TB
– A positive tuberculin skin test
– Chest X-ray suggestive of TB.
Recommended approach to diagnose
TB in children
1. Careful history
including history of TB contact and
symptoms consistent with TB.
a. history of Contact

• Close contact is defined as living in the

same household as or in frequent
contact with a source case (e.g. the
child’s caregiver) with sputum smear-
positive pulmonary TB.

• Smear-negative but culture-positive

cases are also infectious, but to a much
lesser degree.
Important points

• All symptomatic children who have been in close

contact with a smear-positive TB case, must be
screened for TB.

• When any child is diagnosed with TB, an effort

should be made to detect the source case and any
other undiagnosed cases in the household.

• Children should be regarded as infectious if they

have sputum smear-positive pulmonary TB or
cavitary TB on CXR and child contacts must be
sought and screened.
b. Symptoms
The commonest are:
• Prolonged cough
An unremitting cough that is not improving and
has been present for more than 21 days.
• Fever
Body temperature of >38 °C for 14 days, after
common causes such as malaria or
pneumonia...etc have been excluded.
• Weight loss or failure to thrive
2. Clinical examination (including
growth assessment).

 There are no specific features on clinical

examination that confirm pulmonary TB.
 Some signs are highly suggestive and
requiring investigation to exclude extra-
pulmonary TB:
• gibbus, especially of recent onset (resulting from
vertebral TB)
• non-painful enlarged cervical lymphadenopathy with
sinus formation;
• Meningitis not responding to antibiotic treatment, with
a sub-acute onset or raised intracranial pressure with
early affection of the cranial nerves.
• Pleural effusion
• Pericardial effusion
• Distended abdomen with ascites
• Non-painful enlarged joint
• Signs of tuberculin hypersensitivity (e.g. phlyctenular
conjunctivitis, erythema nodosum).
• Documented weight loss or failure to gain
weight, especially after being treated in a
nutritional rehabilitation program, is a good
indicator of chronic disease in children, of
which TB may be the cause.
3. Tuberculin skin test
• A TST is the intradermal injection of a combination of
mycobacterial antigens which elicit an immune response
(delayed-type hypersensitivity), represented by
induration, which can be measured in millimeters.

• TST using the Mantoux method is the standard method

of identifying people infected with M. tuberculosis.

• Multiple puncture tests should not be used to determine

whether a person is infected, as these tests are
unreliable (because the amount of tuberculin injected
intradermally cannot be precisely controlled).
• A positive TST occurs when a person is infected with M.
tuberculosis, but does not necessarily indicate disease.

• TST can be used as an adjunct in diagnosing TB in

children with signs and symptoms of TB and in
conjunction with other diagnostic tests.

• Use 5 tuberculin units (TU) / 0.1 ml of tuberculin PPD-S

or 2 TU / 0.1 of tuberculin PPD RT23.

• The results should be read between 48 and 72 hours

after administration. A patient who does not return within
72 hours will probably need to be rescheduled for
another TST.
Interpretation of the test
Diameter of induration of ≥5 mm is
considered positive in:
– HIV-infected children
– Severely malnourished children (with clinical
evidence of marasmus or kwashiorkor).
Diameter of induration of ≥10 mm is
considered positive in:
– Children more than 5 years or not vaccinated
with BCG.
4. Bacteriological confirmation
whenever possible
• Among younger children, especially under 5 years,
sputum is difficult to obtain.

• Most children are sputum smear-negative.

• Children who are able to produce a specimen, it is

worth sending it for smear microscopy and
mycobacterial culture if available.

• Bacterial yields are higher in older children (more

than 5 years of age) and adolescents, and in
children of all ages with severe disease.
• Appropriate clinical samples include:
– Sputum,
– Gastric aspirates
– Laryngeal swaps
– Certain other material e.g. lymph node biopsy
or other biopsies.
• Fine-needle aspiration of enlarged lymph
glands – for both staining of acid-fast
bacilli and histology – has been shown to
be a useful investigation, with a high
bacteriological yield.
Role of culture
– Increase the yield of confirmed TB
cases,
– Differentiate M. tuberculosis from other
non-tuberculous mycobacteria.
– determine the resistance pattern.
Common ways of obtaining samples
for smear microscopy and culture
a. Expectoration

• Older children (10 years of age or older).

• As with adult TB suspects, three sputum

specimens should be obtained: an on-
the-spot specimen, an early morning
specimen and a second on-the-spot
specimen.
b. Gastric aspirate
• Gastric aspiration using a naso-gastric
feeding tube can be performed in young
children who are unable expectorate sputum.

• A gastric aspirate should be obtained on

each of three consecutive mornings.

• The diagnostic yield (positive culture) of a

set of three gastric aspirates is only about
25–50% of children with active TB.
Gastric aspirate, cont.

Precautions
• Fasting for at least 4 hours (3 hours for
infants) prior to the procedure.

• Children with a low platelet count or

bleeding tendency should not undergo the
procedure.
Gastric aspirate, cont.
Procedure
• Inpatient first thing in the morning when the child wakes
up,
• Position the child on his or her back or side.
• Measure the distance between the nose and stomach, to
estimate distance that will be required to insert the tube
into the stomach.
• Attach a syringe to the nasogastric tube.
• Gently insert the nasogastric tube through the nose and
advance it into the stomach.
• Withdraw (aspirate) gastric contents (2–5 ml) using the
syringe attached to the nasogastric tube.
Gastric aspirate, cont.
• To check the position of the tube is correct, test
the gastric contents with litmus paper:

• This can also be checked by pushing some air

(e.g. 3–5 ml) from the syringe into the stomach
and listening with a stethoscope over the
stomach.

• If no fluid is aspirated, insert 5–10 ml sterile

normal saline and attempt to aspirate again.
Gastric aspirate, cont.
• If still unsuccessful, attempt this again (even if the
nasogastric tube is in an incorrect position and water or
normal saline is inserted into the airways, the risk of
adverse events is still very small).

• Do not repeat more than three times.

• Withdraw the gastric contents (ideally at least 5–10 ml).

• Transfer gastric fluid from the syringe into a sterile
container (sputum collection cup).

• Add an equal volume of sodium bicarbonate solution to

the specimen to neutralize the acidic gastric contents.
c. Sputum induction
• safe and effective in children of all ages.

• the bacterial yields are as good as or

better than for gastric aspirates.

• should be performed in an isolation room

with adequate infection control
precautions.
Sputum induction, cont.

Very few adverse events have been

reported:
–Coughing spells,
–Mild wheezing
–Nosebleeds.
Sputum induction, cont.
General approach
• Examine child before the procedure to ensure he is
well enough to undergo the procedure.

• Children with the following characteristics should not

undergo sputum induction.

– Inadequate fasting: for at least 3 hours,

– Respiratory distress (including rapid breathing,
wheezing, hypoxia).
– Intubated.
– low platelet count, bleeding tendency, severe
nosebleeds.
– Reduced level of consciousness.
– History of significant asthma
Procedure
• Administer a bronchodilator (e.g. salbutamol) to reduce
the risk of wheezing.

• Administer nebulized hypertonic saline (3% NaCl) for 15

minutes or until 5 cm3 of solution have been fully
administered.

• Chest physiotherapy is necessary; this is useful to

mobilize secretions.

• Older children now able to expectorate

• young children, do suction of the nasopharynx to collect a

suitable specimen.
5. Chest radiography

• The commonest picture is that of

persistent opacification in the lung
together with enlarged hilar or subcarinal
lymph glands.

• Adolescent patients with TB have CXR

changes similar to adult patients..
Extra-pulmonary TB
Other tests
• PCR
Not currently recommended for routine
diagnosis of childhood TB, as they have
been inadequately studied in children
and have performed poorly in the few
studies which have been done.
Scoring system
 SCORE SYSTEM FOR THE
DIAGNOSIS OF TB IN CHILDREN
• Has been rarely evaluated or validated

• The basis of a score system is the careful and

systematic collection of diagnostic
information.

• A score of 7 or more indicates a high

likelihood of TB.
 feature 0 1 2 3 4 score

General
Duration >2w 2-4w <4w
of illness

Weight for <80% 60-80% >60%

age
Family -VE Reported Proved
history +VE

Tuberculin positive
test

Malnutrition Not
improving
After 4 w

Unexplained No response to
fever and night nonspecific
sweats treatment
Local
Lymph
nodes
Joint or
bone
swelling
Abd.
mass or
ascites
CNS
findings
Angle
deformity of
the spine

Total score
TB treatment
 TB chemotherapy should be based on two
important microbiological considerations:

• The combination of drugs to avoid the

development of resistance.

• The need for prolonged chemotherapy to

prevent disease relapse.
• All mono-therapeutic regimens (real or
masked by combination with drugs to
which bacilli are resistant) lead to
treatment failure and to the development
of resistance.

• When three or more drugs are

administered, the risk of resistance is
practically zero.
 Phases of treatment:
The intensive phase
• usually covers the first 2 months of treatment.
• During this phase, most of the bacilli will be killed.
• The sputum converts from positive to negative in more than 80
% of the new patients within the first 2 months of treatment.
The continuation phase
• usually lasts 4-6 months, depending on the treatment regimen.
• This phase is intended to eliminate the remaining dormant
bacilli.
• These dormant bacilli decrease constantly as treatment intake
progresses.
• Since it is not possible to identify which patients still have
dormant bacilli, all patients should continue their treatment until
the end of the prescribed period, to limit the number of relapses.
 First-line anti-tuberculosis
drugs, action and side effects
 DRUG RECOMMENDED DAILY DOSAGE
(DOSE RANGE),mg/kg

Isoniazide (H) 5 (4–6)

Rifampicin (R) 10 (8–12)
Pirazinamide (Z) 25 (20–30)
Streptomycin (S) 15 (12–18)
Ethambutol (E) 15 (15–20)
 Treatment regimens
Treatment
Patient Category Initial Continuation
category

I New smear +ve PTB. 2/SHRZ 4/HR

New smear –ve OR
New forms of extra- 2/EHRZ
Pulmonary TB.
 Treatment regimens, cont

Treatment
Patient Category Initial Continuation
category
II Sputum smear +ve 2/SHRZE 5/HRE
Relapse. then
Treatment after failure. 1/HRZE
Treatment after interruption.
Treatment regimens for DR-TB in Egypt
Drug-resistant TB
• Drug-resistant TB is a laboratory
diagnosis.
• However, drug-resistant TB should be
suspected if any of the features below are
present.
• Features in the source case suggestive
of drug-resistant TB:
– contact with a known case of drug-resistant
TB
– remains sputum smear-positive after 3
months of treatment
– history of previously treated TB
– History of treatment interruption.
• Features of a child suspected of having
drug-resistant TB:
– Contact with a known case of drug-resistant
TB
– Not responding to the anti-TB treatment
regimen
– Recurrence of TB after adherence to
treatment.
Patient Treatment regimen
resistant
to
RHSE Regimen I
3 months: canamycin daily + Ofloxacin + Cycloserine +
Ethionamide + PAS then:
6 months canamycin 5 times a week + previous drugs then:
12 months Ofloxacin + Cycloserine + Ethionamide + PAS

RHS Regimen II
3 months: canamycin + Ofloxacin + Ethambutol +
Ethionamide + Cycloserine then:
6 months: canamycin 5 times a week + previous drugs then:
12 months: Ofloxacin + Ethambutol + Ethionamide +
Cycloserine
RH Regimen III
3 months streptomycin daily + Ethambutol + Pyrazinamide
+ Ofloxacin + PAS then:
6 months streptomycin 5 times a week + previous drugs
then:
12 months: Ethambutol + Pyrazinamide + Ofloxacin + PAS
THANK YOU