Prevalence of Mycobacterium tuberculosis infection in children in western Uttar Pradesh.
ABSTRACT This study was conducted to estimate the prevalence of tubercular infection and compute the Annual risk of tuberculosis infection (ARTI) in Bijnor district of western Uttar Pradesh through a hospital-based tuberculin survey conducted at a pediatric hospital. A total of 1085 children below 18 years (0-4 years 866, 5-17 years 219), attending the out-patient department during October 2007 through September 2008 were included. Tuberculin skin test using standard PPD RT23 with Tween 80 was performed on every 4th child attending the out-patient department and induration was measured after 48 to 72 hours. Using a cut-off of 15 mm among 0-4 y aged children, the average prevalence rate was 7.4%, and using cut-off of 10 mm in 5-17 y age group the average prevalence rate was 26.9%. ARTI was 4.11% (95% CI 3.09-5.14) and 3.50 % (2.46-4.48), respectively in the two age groups.
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ABSTRACT: The tuberculin skin test, which involves monitoring the immune reaction to an injection of Purified Protein Derivative (PPD), has been the most widely used method for detecting infection with Mycobacterium tuberculosis since its development in 1930s. Until recently, the molecular composition of PPD was unknown. This thwarted the discovery of improved skin testing reagents and drastically hindered efforts to define the mechanism of action. Proteomic evaluation of PPD combined with a detailed analysis in the guinea pig model of tuberculosis led to further definition of the molecular composition of PPD. This communication reviews the history and current status of PPD, in addition to describing candidate next-generation PPD reagents, based on the use of an individual protein or protein cocktails. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.FEMS Immunology & Medical Microbiology 07/2012; · 2.68 Impact Factor
(ARTI)(1). Tuberculosis control is defined as
cumulative prevalence of <1% infection by age 14
years (2-7). This translates to an average ARTI of
about 0.07% below 14 years of age(2-7). Currently
ARTI is about 1% per year in many regions of India
(5-9). In the absence of any baseline data from
western Uttar Pradesh, we conducted this tuberculin
uberculin surveys help us to estimate the
prevalence of tuberculosis
infection and to compute the annual
incidence (annual risk) of MTb infection
This study was conducted at a secondary-care
pediatric hospital in Bijnor, western Uttar Pradesh.
Ethical clearance was obtained from the ethics
committee of the hospital. The study population
consisted of children below 18 years, attending the
out-patient department (OPD) during October 2007
through September 2008. Every 4th child attending
the OPD was included, irrespective of the presenting
complaints, avoiding bias or possible non-random
clustering effect that might have occurred if all
children had been tested at one point of time.
Exclusion criterion was any illness that included TB
in the differential diagnosis.
The tuberculin skin test (TST) was performed
using the standard PPD RT23 with tween 80 (Span
Diagnostics, Sachin, Gujarat; dose equivalent to 5
TU old tuberculin). However, it is to be understood
that the 5 TU is equivalence value for
standardization - 2 TU PPD with Tween 80 has
potency equal to 5TU old tuberculin. Test result was
read after 48 to 72 hours by one of the authors and
recorded as the transverse diameter (in millimeters)
of palpable induration(1).
97VOLUME 47__JANUARY 17, 2010
S H O R T C O M M U N I C A T I O N
Prevalence of Mycobacterium tuberculosis Infection in
Children in Western Uttar Pradesh
VIPIN M VASHISHTHA AND T JACOB JOHN
From Mangla Hospital, Shakti Chowk, Bijnor, Uttar Pradesh, India.
This study was conducted to estimate the prevalence of tubercular infection and
compute the Annual risk of tuberculosis infection (ARTI) in Bijnor district of western
Uttar Pradesh through a hospital-based tuberculin survey conducted at a pediatric
hospital. A total of 1085 children below 18 years (0-4 years 866, 5-17 years 219),
attending the out-patient department during October 2007 through September
2008 were included. Tuberculin skin test using standard PPD RT23 with Tween 80
was performed on every 4th child attending the out-patient department and
induration was measured after 48 to 72 hours. Using a cut-off of 15 mm among 0-4
y aged children, the average prevalence rate was 7.4%, and using cut-off of 10 mm
in 5-17 y age group the average prevalence rate was 26.9%. ARTI was 4.11% (95%
CI 3.09-5.14) and 3.50 % (2.46-4.48), respectively in the two age groups.
Key words: Annual rate of tuberculosis infection, Child, India, Prevalence,
Tuberculin skin test, Tuberculosis.
Vipin M Vashishtha,
Director and Consultant pediatri-
cian, Mangla Hospital, Shakti
Chowk, Bijnor, Uttar Pradesh,
246 701, India.
Received: February 18, 2009;
Initial review: March 12, 2009;
Accepted: September 21, 2009.
98VOLUME 47__JANUARY 17, 2010
VASHISHTHA AND JOHN
M. TUBERCULOSIS PREVALENCE IN UP
The study children were grouped in two subsets,
0-4 years and 5-17 years. The prevalence rates in
both the subsets were estimated at different cut-off
The annual risk of MTb infection (ARTI) was
calculated from the prevalence of infection (P) by
using the equation: ARTI = l – (l – P) 1/A where A is
the mean age of tested children (6,9,10). Prevalence
frequencies of infection were analyzed by Chi-sqare
test to calculate P values.
A total of 1137 children were recruited; 1085
(95.4%) of them were test-read. The age of tested
children ranged from infants to 17 years (Table I).
The distribution of tuberculin indurations (Figure 1)
in the entire study children (Panel A) as well as in the
age-group of 0-4 years (Panel B) appeared to be
bimodal, with the first mode clearly at 4 mm. As the
second mode was not clearly demarcated, the
antimode could not be precisely identified. Visually
the best fit antimode appears to be at 12 or 14 mm.
The distribution of tuberculin indurations in the age
group 5-17 years (Panel C) appeared to be trimodal,
with the modes of the first 2 clusters at 7 and 9-10
mm, respectively and the 2 antimodes were at 8 and
12 mm, respectively.
The detection of the antimode for the
determination of the cut off value is an important
step in distinguishing MTb-specific response from
non-specific response(6,7,9,11). Since the antimode
was not clear, to measure the prevalence of MTb
infection, we used 15 mm as a conservative cut-off
value in the first subgroup (0-4 y), to minimize the
inclusion of responses induced by BCG or other
environmental mycobacteria and to increase the
confidence of identifying MTb infection(12).
Similarly, we used 10 mm (midway between the 2
antimodes) as cut off for children in the second
subgroup (5-17 y) to measure the prevalence of MTb
The prevalence rates of MTb infection in
different age groups was 6.1 to 6.7% (0-2 y), 12.7%
(3-4 y), 20.5 to 27.8% (5-10 y), 47.6% (11-12 y) and
50% (13-16 y). There was no significant sex-wise
Our results show alarmingly high rates of MTb
infection prevalence in children and consequently,
very high ARTI values. However, our study has some
limitations. Strictly speaking, the study subjects do
not ‘represent’ children in the community. In order to
minimize the potential for over-representation of
MTb infected children, we selected a systematic
sample of every fourth child. To maximize
specificity, even at the cost of some sensitivity, we
chose PPD reaction cut off values of 15 mm for
children under 5, even though the antimode was 12
or 14 mm. Similarly, we chose a cut off value of 10
mm for children above 4 years, even though the first
antimode was 8mm. Many other investigators have
also used such cut off values(6,9,12). The study
methodology was similar to that described for TST
surveys(1,3,7). We did not attempt to correlate
tuberculin sensitivity with a history of BCG
vaccination as many studies have shown that it does
not interfere with TST result in children at and above
5 years(6,7). As for children below 5, by using 15
mm as cutoff value we have avoided cross reactions
There is paucity of data on Mtb prevalence and
ARTI rates in various districts of Uttar Pradesh. One
community based tuberculin survey had been
conducted amongst 1-9 years old rural children in
three districts of central and eastern UP(13). The
ARTI computed from the prevalence of infection,
using the cut off value of 14 mm, was 2.3% in rural
areas of Rae Barelli, 1.9% in Hardoi and 1.5% in
Jaunpur(13). These rates are among the highest
TABLE I PREVALENCE OF TUBERCULAR INFECTION IN THE
Age 0-4 years
Median induration (IQR)
Mean induration (SD)
Prevalence (95% CI)
ARTI (95% CI)
ARTI: Annual risk of tuberculosis infection.
99VOLUME 47__JANUARY 17, 2010
VASHISHTHA AND JOHN
M. TUBERCULOSIS PREVALENCE IN UP
Frequency distribution of tuberculin reaction
sizes among study children. Panel A. All children
(0-17 yrs); Panel B. Children 0-4 yrs; Panel C.
Children 5-17 yrs.
frequency of 0.07%(3,4,7,8). Against that goal, the
frequency of 3.5-4.11% is 50 times higher. By 14
years the infection frequency had gone up to 50%,
also clearly over 50 times higher than the goal of TB
Our findings should be taken as an alert to the
National TB control programme and program
officers should conduct systematic community based
tuberculin surveys to independently measure the
prevalence and incidence of MTb infection in Bijnor
as well as in other populations in western UP.
Competing interest: None stated.
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reported anywhere in India, showing relatively high
intensity of transmission of MTb.
Our study results show even higher ARTI in
Bijnor – 4.11% below 5 yr and 3.5% between 5 and
17 yr. There were 4 age intervals when the rise in
infection frequency were relatively steep, namely
during infancy (0 to 6%), during 2 to 3 yr (6.8 to
12.8%), during 4 to 5 yr (12.8 to 20.5%) and during
9/10 to 11/12 yr (27.8 to 47.6%). Whether this
pattern is artifactual or real can only be settled by a
larger survey of PPD response in children selected
from the community.
The aim of Revised National Tuberculosis
Control Program is to bring down the infection rate
to <1% by 14 years of age, for an annual infection
WHAT THIS STUDY ADDS?
• The population studied showed an Annual rate of tuberculosis infection of >3%, which is higher than that in other
regions of UP and other States in India.
100VOLUME 47__JANUARY 17, 2010
VASHISHTHA AND JOHN
M. TUBERCULOSIS PREVALENCE IN UP
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