Indian Pediatr 2010;47: 93-96
Intermittent Short Course Therapy for
Indumathi, K Kumar Prasanna, Chitra Dinakar, Anita Shet and S Lewin
From the Department of Pediatrics, St John’s Medical
College Hospital, Bangalore, India.
Correspondence to: Dr Indumathi CK, Assistant Professor,
Department of Pediatrics, St John’s Medical College Hospital, Sarjapur
Road, Bangalore 560 034, India.
Email: ckindumathi@gmail. com
Received: February 5, 2009;
Initial review: March 12, 2009;
Accepted: July 27, 2009.
Published online: 2009 October
We conducted this study to assess the efficacy of
intermittent short course therapy in all forms of pediatric tuberculosis
using a coordinated approach with Revised National Tuberculosis Control
Programme (RNTCP). Sixty-five children were treated using RNTCP
protocols with some modifications, such as dose adjustments or
prolongation of treatment in selected children. Overall response rate
was 95% (pulmonary 94% and extra pulmonary 97%). There was one case with
possible relapse. With dynamic inputs from both the treating
pediatrician and personnel from Directly Observed Treatment –
Short-course (DOTS) centers, we could successfully implement RNTCP
protocols in childhood tuberculosis.
Key words: Childhood tuberculosis, Intermittent therapy, RNTCP.
evised National Tuberculosis
Control Programme (RNTCP) recommends intermittent short course
chemotherapy (ISSC) under Directly Observed Treat-ment-Short course (DOTS)
strategy and the Indian Academy of Pediatrics endorses the same for all
forms of childhood tuberculosis(1). Though there are reports of efficacy
of ISSC in children with pulmonary tuberculosis (PTB) and other
non-serious forms(2-7), there are limited published data on its efficacy
in serious extra pulmonary tuberculosis (EPTB)(8-10). Regarding the
efficacy of ISSC in tubercular meningitis (TBM), the published evidence is
almost non-existent in children, and scarce in adults(11). This
lack of published evidence limits the utilization of RNTCP in childhood
tuberculosis(1). Concerns regarding inadequate dosages with
available pediatric patient-wise boxes in some weight bands(12), and lack
of trained personnel at DOTS centers to determine treatment endpoints in
children, especially in sputum negative PTB and EPTB, contribute to low
referral of pediatric tuberculosis patients to DOTS centers(1). This study
evaluated the efficacy of ISCC in both pulmonary and serious extra
pulmonary tuberculosis in children using a coordinated approach with DOTS
This prospective study conducted between January 2005
and July 2008 enrolled children diagnosed at the pediatric
department, St. John’s Medical College Hospital with tuberculosis of all
forms, except those co-infected with HIV. They were diagnosed, classified
and treated using RNTCP protocol(1). All children with PTB, intracranial
tuberculoma, abdominal, disseminated and lymph node tuberculosis were
started on ISCC (thrice weekly) at the outset. Children with TBM received
daily treatment for first 2 weeks followed by ISCC. All children were
referred to DOTS centers for drugs and also followed up at the study
center by a pediatrician once in 2 weeks in intensive phase, once a
month in continuation phase and once in 2 months after completion of
treatment. The pediatrician also communicated regularly with the
DOTS centers ensuring dosage appropriateness. Doses were calculated
according to bodyweight at baseline and adjusted for gain in weight.
Dosages were as follows. INH 10-15 mg/kg rifampicin 10 mg/kg
pyrazinamide 30-35 mg/kg ethambutol 30 mg/kg and streptomycin 15 mg/kg.
Loose drugs available at DOTS centers were used initially followed by
pediatric patient-wise boxes once they became available. ‘Top-up’ doses
were prescribed when available pediatric combinations were found to be
under dosed. Adherence to top up doses was ensured by using a family
member as the DOTS provider. Treatment was extended to 9 months in PTB if
there were slow clinical and radiological responses (<2/3rd
clearance at 6 months) not amounting to treatment failure. This
individualized treatment was again achieved by coordination between
pediatrician and DOTS officers. Ethical clearance for the study was
obtained by the Departmental ethical committee and parental consent was
A total of 65 children with tuberculosis (34
pulmonary and 31 extra-pulmonary) were analyzed. Mean age was 7.6 years
(range 5 months to 17 years) with a male to female ratio of 0.8:1. Acid
fast bacilli (AFB) positivity was documented in 9 (12%) cases (sputum - 6,
lymph node - 1, breast tissue-1, lung tissue-1). 68% of cases were treated
as RNTCP category 1, 6.7% as category 2, and 25.3% as category 3.
Treatment outcome is tabulated in Table I.
The overall cure rate was 95% (94% in pulmonary and 97% in
extra-pulmonary TB). There were 2 failures among PTB. Additionally, two
children required extension of treatment to 9 months. All six children
with sputum positive for AFB became negative at the end of intensive
phase. Radiological response was noted in 90% of children.
Treatment Outcome in Childhood Tuberculosis
|Type of tuberculosis
||Mean (range) duration
||of follow up (mo)
| Pleural effusion
Of the 14 cases with neurotuberculosis, seven had
meningitis (2 in stage 3 and 5 in stage 2), six had tuberculoma, and one
had spinal arachnoiditis. Twelve (86 %) children had complete cure without
sequelae, one (7%) had clinical cure with motor deficit and one (7%) had
clinical failure due to poor adherence. There was no mortality. All cases
of disseminated, abdominal and lymph node TB responded with a 100% cure
rate (Table I).
Of 65 children initiated on ISCC, 1 with PTB died; 1
with failed therapy for meningitis was lost to follow up; and, 4 were lost
to follow up after successful completion and response to ISCC. The
remaining 59 children were followed up post treatment for a mean period of
9.4 months (SD 8.5 mo), of which 40% were followed for 1 year or more. One
child with meningitis had suspected relapse after 6 months. Clinical
hepatitis was not encountered in any child. Sixty children were found to
be adherent to treatment, having received more than 95% of doses.
Eight children were given ‘top-up’ doses; 2 children in
6-10 Kg weight band, and 3 each in 11-16 Kg and 17-25 Kg weight bands. Two
children with PTB and one with EPTB required prolongation of treatment to
This study revealed an overall response of 95%, which
is comparable to 90-100% response reported with daily therapy(2,4,5). The
94% cure rate of PTB is again comparable to response reported with daily
therapy(2,4). Extension of treatment beyond 6 months was required in 3
(4.6%) children compared with 15% in another report(13). Residual
radiological lesions were found in 13% of patients on par with another
study(4). Cure rates of 86% in neurotuberculosis is encouraging, though
this could not be compared with other studies with daily therapy(14,15),
in view of very small numbers. Further studies with a larger number of
patients with neurotuberculosis are needed to validate these conclusions.
No child developed hepatitis compared to 2.2-5% reported with daily
therapy(3,13). More than 95% adherence achieved has an important
implication in preventing MDRTB. The main limitation of our study was the
absence of a control group.
Though RNTCP guidelines for diagnosis and
categorization could be implemented in the existing form, we had to modify
the dosage schedules in few children. Under-dosage was a problem in
children at the upper end of weight bands across the ranges of 6-10 Kg,
11-16 Kg and 17-25 Kg. We feel that this is an important limitation in
RNTCP that needs to be addressed. We recommend to include a revision of
the weight bands to narrower ranges and provision for increasing dosage
with weight gain during therapy, in addition to having trained personnel
at DOTS centers to determine treatment endpoints for children.
We sincerely thank personnel of DOTS centers for the
Contributors: ICK: concept, planning and conduct of
the study. ICK, PKK: drafting and data collection. CD, AS and SL: critical
revision of the manuscript.
Competing interests: None stated.
What This Study Adds
short course chemotherapy is effective in childhood tuberculosis
including serious forms of extra-pulmonary tuberculosis.
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