Mx of Paediatric TB

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MANAGEMENT OF PAEDIATRIC TUBERCULOSIS13

CHAPTER

13

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.

Management of Paediatric Tuberculosis Soumya Swaminathan



120

TUBERCULOSIS CONTROL IN INDIA

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 bacterialpopulations, 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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Category I

Category II

Category III

Table 2 RNTCP treatment categories and regimens for children

Note: The drug abbreviations are as follows: E - Ethambutol, H - Isoniazid, R - Rifampicin, S - Streptom ycin and Z -Pyrazinamide. The number in frontof 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 Pulm onary TB other than primary com plex.

* * Seriously ill extrapulmonar y TB includes TB meningitis, dissem inated TB, TB pericarditis, TB peritonitis and intestinal TB, bilateral or extensivepleurisy, spinal TB with or without neurological complications, genito-urinary tract TB, bone and joint TB.

* * * Not-seriously ill extrapulmonary TB includes lym ph node TB and unilateral pleural effusion;

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;

Author, Countryand Year

Al Dossary et. al.

USA, 2002

Te Water Naude et .

al . S.Africa, 200 0

VarudkarIndia, 198 5

Biddulph

New Guinea, 1990

Kumar et. al.

India, 199 0

Ramachandran et. al.

India, 199 8

Diagnostic Criteria

Clinical andradiological

Clinical andradiological

Clinical andbacteriological

Clinical andbacteriological

Clinical andbacteriologicalClinical, radiologicaland bacteriological

No. ofchildren

175

89117

1004045

639

3739

6869

Regimen

2 w eeks daily HRZfollowed by 6 weeksHRZ

2 /4 RH

2

2RHZ2 /4RH

2

sss6RHZ

2HRE /4HE2 HZE / 4 HE 6 HRE

3

2 SHRZ / 4 HR2

2 HRZ2 /4 HR

2

2 HRZ / 4HR2

9 HR

2 HRZ3 / 4RH

2

Results

81 percent treatmentcom pletion 1 relapse

Treatment outcomeand adherenceequivalent 1 relapse

0 failures,0 relapses

12 (2 percent) died7 (1 percent)relapses

5/7 relapses in poorlyadherent patients.

2 Deaths not relatedto TB 0 relapse

3 (2 percent) died0 failures 3 relapses

Table 1 Results of six-month treatment regimens for tuberculosis

Type of patients

New sputum smear-positive PTB

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

Sputum smear-positive relapse Sputum smear-positive treatment failure Sputum smear-positive treatment after default Others

Sputum smear-negative andextrapulmonary TB, not seriously ill* * *

Intensive phase

2H3R

3Z

3E

3

2S3H

3R

3Z

3E

3+

1H3R

3Z

3E

3

2H3R

3Z

3

Continuation phase

4H3R

3

5H3R

3E

3

4H3R

3

Category oftreatment



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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 (smear-

positive) 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-negativepulmonary 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 child’s 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 four-drug 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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