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MANAGEMENT OF PAEDIATRIC TUBERCULOSIS

CHAPTER

Management of Paediatric Tuberculosis



Soumya Swaminathan

Diagnosis of Paediatric TB
The difficulty in obtaining sputum, non-specific radiographic findings and the
paucibacillary nature of the disease often makes the diagnosis of tuberculosis (TB) in
children difficult. Clinicians should suspect pulmonary TB in children presenting with:

Fever and /or cough for more than three weeks, with or without;

Loss of weight/no weight gain; and

History of contact with a suspected or diagnosed case of active TB disease within the
last two years.

The evaluation of some of the many available scoring systems have shown them to have
high sensitivity but low specificity, which may lead to over-diagnosis and unnecessary
treatment of non-TB patients. Currently, the use such scoring systems for the diagnosis of
patients it is not recommended . Further research needs to be undertaken to evaluate the
utility of scoring charts in the Indian context.
Further screening of TB suspects should be done by:

Bacteriological Testing: Sputum examination should be done wherever possible. Gastric
lavage may be used when sputum is not available. Multiple samples should be tested by
both smear and culture, if facilities are available.

Tuberculin test: Mantoux test using 1 TU PPD RT 23 Tween 80 intradermal should be

performed in Paediatric TB (PTB) suspects. The test will be read as positive if there is
more then 10 mm induration at 48-72 hours. Testing with BCG is not recommended.

Radiology: Chest x-ray should be taken in upright position PA view. Radiological lesions
are not confirmatory for tuberculosis, as there are no pathognomonic radiological signs of
TB. However, x-ray findings suggestive of TB include mediastinal/hilar lymphadenitis
with or without parenchymal lesions, pleural effusion, miliary and fibrocaseous pictures.
Persistent pneumonia beyond four weeks in a symptomatic child in spite of antibiotic therapy,
suggests probable TB.

PCR: The sensitivity of PCR is variable and may be as low as 20 percent in gastric
aspirate samples; the sensitivity can be increased by using two or more probes. However,
routine use of PCR is not recommended at present.

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Serology: Due to many variable factors in the host, mycobacterium and environment,
serology is not useful in childhood TB. The sensitivity, specificity as well as predictive
value of commercially available serological tests such as ELISA for TB, do not justify
their use in our setting at present.

Children who do not fulfil the diagnostic criteria but need further evaluation should be
referred to a paediatrician. A high index of suspicion must be maintained when the child is
aged < 1 year, there is a recent history of measles/whooping cough, immunocompromised
state and steroid therapy. Significant superficial lymphadenopathy should be looked for as
it is present in > 40-50 percent of patients.
A diagnostic algorithm for Paediatric Pulmonary TB is given in Figure 1.

Figure 1

RNTCP diagnostic algorithm for paediatric pulmonary TB

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Treatment of Paediatric TB
Principles of Short-Course Chemotherapy (SCC)
The biological characteristics of the tubercle bacilli (lag phase, size and types of bacterial
populations, easy development of resistance when exposed to a single drug, presence of
natural drug-resistant mutants) determine the principles of short-course treatment for
tuberculosis.

A combination of at least three to four drugs should be used in the initial intensive phase
(two months). The drugs are Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), and either
Streptomycin (S) or Ethambutol (E). This combination ensures rapid killing of all
populations of bacilli.

Drugs can be given either daily or intermittently (twice or thrice weekly)

The minimum duration of treatment is six months when Rifampicin is used throughout
and Pyrazinamide is used in the initial intensive phase. If only two drugs are used, the
duration of treatment has to be at least nine months.

The drugs should preferably be given together and administered as a single dose.
The advantages of SCC are:

I. It has a faster and more powerful bactericidal and sterilising action so that even if the
patient defaults after the first few months of therapy, they are likely to be cured.
II. The patient is exposed to potentially toxic drugs for shorter periods of time.
III.The regimens are less expensive and more cost-effective than traditional therapy.
IV.More time and resources can be allotted to ensuring adherence.
Various studies in adults have shown that, with a combination of Rifampicin, Isoniazid
and Pyrazinamide with either Streptomycin or Ethambutol, about 90 percent of patients
become culture-negative by the end of two months (bactericidal effect of the regimen).
Continuing the treatment with Rifampicin and Isoniazid for a further four months results
in almost 100 percent of patients with drug sensitive organisms becoming culture-negative,
and bacteriological relapse occurring in only about 5 percent of patients (sterilising effect
of the regimen). If Rifampicin is not administered in the second phase, the total duration of
treatment has to be at least eight months. Table 1 shows the results of SCC studies in
children. In all these trials, the overall success rate was greater than 95 percent for complete
cure and 99 percent for significant improvement. The incidence of clinically significant
adverse reactions was less than 2 percent. Several studies included a significant number of
children with moderate to severe malnutrition, and these children generally did well. Several
of these studies again demonstrated that over half of the children continued to have
abnormalities in the chest radiograph at the end of six months of therapy, but the radiographic
picture continued to improve after the completion of therapy when medications were
discontinued after six months. At a consensus meeting of TB experts and paediatricians
held in August 2003 in Delhi, it was therefore recommended that children with tuberculosis
be treated using the regimens available in the RNTCP.

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TUBERCULOSIS CONTROL IN INDIA 

Author, Country
and Year

Diagnostic Criteria

No. of
children

Regimen

Results

Al Dossary et. al.

Clinical and
radiological

175

2 weeks daily HRZ

followed by 6 weeks
HRZ2 /4RH2

81 percent treatment
completion 1 relapse

89
117

2RHZ2/4RH2
6RHZ
sss

Treatment outcome
and adherence
equivalent 1 relapse

USA, 2002
Te Water Naude et.
al. S.Africa, 2000
Varudkar
India, 1985

Clinical and
radiological

100
40
45

2HRE /4HE
2 HZE / 4 HE 6 HRE3

0 failures,
0 relapses

Biddulph

Clinical and
bacteriological

639

2 SHRZ / 4 HR2
2 HRZ2 /4 HR2

12 (2 percent) died
7 (1 percent)relapses
5/7 relapses in poorly
adherent patients.

Kumar et. al.

India, 1990

Clinical and
bacteriological

37
39

2 HRZ / 4HR2
9 HR

2 Deaths not related

to TB 0 relapse

Ramachandran et. al.

India, 1998

Clinical and
bacteriological
Clinical, radiological
and bacteriological

68
69

2 HRZ3 / 4RH2

3 (2 percent) died
0 failures 3 relapses

New Guinea, 1990

Table 1 Results of six-month treatment regimens for tuberculosis

In addition, the consensus meeting recommended that some modifications in the type of
patients under each treatment category be made (Table 2), keeping in mind the different
diagnostic criteria used in children, namely:

In patients with TB meningitis on Category I treatment, the usual four-drug regimen

used during the intensive phase HRZE should be replaced by HRZS as Ethambutol
does not penetrate the CSF well;

Category of
treatment

Type of patients

Category I

Category II

Category III

New sputum smear-positive PTB

Seriously ill sputum smear-negative PTB*
Seriously ill extrapulmonary TB**

Intensive phase

Continuation phase

2H3R3Z3E3

4H3R3

2S3H3R3Z3E3+
Sputum smear-positive relapse
Sputum smear-positive treatment failure
1H3R3Z3E3
Sputum smear-positive treatment after default
Others

5H3R3E3

Sputum smear-negative and

extrapulmonary TB, not seriously ill***

4H3R3

2H3R3Z3

Table 2 RNTCP treatment categories and regimens for children

Note: The drug abbreviations are as follows: E - Ethambutol, H - Isoniazid, R - Rifampicin, S - Streptomycin and Z -Pyrazinamide. The number in front
of the regimen denotes the number of months and the subscript after the drugs denote the frequency of administration (number of doses per week).
*Seriously ill sputum smear-negative PTB will include all forms of Pulmonary TB other than primary complex.
**Seriously ill extrapulmonary TB includes TB meningitis, disseminated TB, TB pericarditis, TB peritonitis and intestinal TB, bilateral or extensive
pleurisy, spinal TB with or without neurological complications, genito-urinary tract TB, bone and joint TB.
***Not-seriously ill extrapulmonary TB includes lymph node TB and unilateral pleural effusion;

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The continuation phase of treatment in TB meningitis (TBM) and spinal TB with

neurological complications should be given for six to seven months, extending the total
duration of treatment to eight to nine months; and

Steroids should be used initially to reduce inflammation in hospitalised cases of TBM

and TB pericarditis, and reduced gradually over six to eight weeks.

Chemoprophylaxis
Asymptomatic children under six years of age, exposed to an adult with infectious (smearpositive) TB, will be given six months of daily Isoniazid (5 mg per kg) chemoprophylaxis.

Monitoring and Evaluation

Monitoring of response to treatment in children needs to address the difficulties associated
with obtaining sputum samples from children. A combination of the following is thus
proposed:

Wherever possible, follow-up sputum examinations are to be performed at the same

frequency as in adults;

Clinical or symptomatic improvement to be assessed at the end of the intensive phase of

treatment and at the end of treatment. Improvement should be judged by the lack of
fever or cough, a decrease in the size of lymph node(s), weight gain, etc.; and

Radiological improvement to be assessed by chest x-ray examination in all smear-negative

pulmonary TB cases at the end of treatment.

Drug-resistant Tuberculosis in Children

Drug-resistant tuberculosis exists in India, mainly due to poor treatment adherence by
the patient and poor management by physicians. Initial drug resistance to Isoniazid is
reported to be in the range of 10 to 15 percent and for Rifampicin, the range is 2-3 percent.
These rates are much higher in patients who have taken prior, irregular treatment. Patterns
of drug resistance in children tend to mirror those found in adult patients in the population.
As it is difficult to isolate M. tuberculosis from children with TB, the clue to drug resistance
usually comes from adult contact. Drug-resistant tuberculosis should be suspected in the
following circumstances:
I. The child is in contact with a known case of drug-resistant tuberculosis;
II. The childs adult contact has been on chronic irregular treatment and continues to be
sputum positive;
III.The adult contact died after taking irregular treatment; and
IV.The child shows initial improvement to anti-tuberculosis treatment but then deteriorates
(clinically and radiologically).
The only definitive way of diagnosing drug resistance is by isolating the strain of M.
tuberculosis and assessing its susceptibility pattern, which takes up to eight weeks. Therapy
for drug-resistant tuberculosis is successful when at least two bactericidal drugs to which

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the infecting strain of M. tuberculosis is susceptible are given. Exact treatment regimens
can be tailored to the specific pattern of drug resistance, if known. If not, at least three
drugs to which the patient has not been exposed earlier should be given. Resistance to
Isoniazid or Streptomycin alone can usually be managed with any of the standard fourdrug regimens with good results. However, when resistance to both Isoniazid and Rifampicin
is present (i.e. multi-drug resistant TB), the management is more complicated and requires
the use of second line drugs. The duration of therapy is usually extended to nine to 12
months if either Isoniazid or Rifampicin can be used, and to at least 18-24 months if resistance
to both drugs is present. Occasionally, surgical resection of a diseased lung or lobe is
required.

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