In
1966, the June issue of Indian Pediatrics published four
observational studies (clinical profile of children with lower
respiratory tract disease, clinical profile of pediatric tuberculosis,
histo-pathological profile of hepatic lesions in tuberculosis, and
significance of radiological findings in evaluation of maturity in
newborns). For this write-up, we selected the research paper on
Tuberculosis (TB) [1]. We shall be discussing the diagnostic approach
and clinical profile of pediatric TB in relation to what it was fifty
years back and how these aspects have evolved over the years.
The Past
The study contents: Authors from Thanjavur
Medical College in Tamil Nadu ( India) presented data from a
retrospective observational study of children (age 0-12 y) attending
their outpatient TB Clinic in 1964 [1]. Children with suspected TB
underwent a detailed clinical evaluation followed by a tuberculin skin
test (TST) and chest radiograph. A child was registered as a case of TB
if at least two of the following criterion were satisfied: clinical
history suggestive of TB, positive TST and/or evidence of TB on chest
X-ray. Although 450 children were registered during the 10 month
study period, data were presented for 365. Maximum number of TB cases
(46.8%) was observed in children aged between 0 to 2 years, followed by
43% in the 2 to 6 year olds and 10.2% in the 6- to 12-year-olds. Only
10% had a positive history of contact with TB. The clinical
manifestations were: not gaining weight, decreased appetite or loss of
weight (60%), irregular episodic fever (44.6%), chronic diarrhea
(37.6%), lymphadenopathy (29.8%), repeated respiratory infections
(27.6%), meningitis (11.8%), wheezing (9.8%), hepatomegaly (7%), lung
signs (3.8%), hepatosplenomegaly (1%) and splenomegaly (0.8%). The
majority (87.9%) were TST positive. Radiological features suggestive of
TB included superior mediastinal adenitis (27.1%), hilar adenitis (15%),
primary complex (8.7%), progressive primary TB (24.1%), miliary mottling
(0.2%), pleural effusion (0.2%) and pneumothorax (0.2%). The authors
stated that a triad of failure to thrive, irregular fever and chronic
diarrhea warranted tubercular workup as did more than 4 to 5 episodes of
cough and cold in a year. In the article it was emphasized that a
negative TST did not rule out TB, as this could be due to faulty
technique, poor nutritional status or steroids. The authors stated that
even radiological findings considered typical of TB were inconclusive
when taken in isolation as they were also found in non-tubercular
pulmonary infections. Authors concluded that children are extremely
susceptible to infection from infected adults, children less than 2
years are more prone to military and meningitic TB, and dormant disease
flares up with malnutrition or debilitating disease.
Historical background and past knowledge: In
1966, TB was a major health problem worldwide. In India, the overall
burden was gauged by indirect parameters like an annual mortality of
500,000 people from TB [1]. Conventional means of diagnosing TB were
well developed by this time. TST was discovered in the end of the
nineteenth century. The Ziehl-Neelsen stain for acid-fast bacilli (AFB)
was developed by the bacteriologist Franz Ziehl (1859-1926) and
pathologist Friedrich Neelsen (1854-1898). The Lowenstein Jensen media
was being used for culture. Radiographs started being used extensively
by 1925. All these methods were being used in adults, but for children
the diagnostic approach was primarily clinical. This included suspicion
(evidence of contact, suggestive history and examination findings) and
investigations limited to TST and the chest radiograph.
The National Tuberculosis Control Program (NTCP) was
the first nationwide organized effort that was launched to tackle TB in
India in 1962 that emphasized on BCG vaccination and TB treatment [2].
However, childhood TB was not given equal importance as adult TB as it
was considered non-infectious, was difficult to diagnose, was assumed to
be much less in magnitude, and it was assumed that effective control in
adults would prevent childhood TB [3]. A lot of scientific interest was
generated that was reflected by the numerous scientific papers on TB
that were published in Indian Pediatrics in the mid-sixties.
The Present
Globally, pediatric TB accounts for 1 million cases
per year, comprising 10-15% of all cases of TB, and is associated with
more than 100,000 deaths annually. The status of a reliable public
health surveillance system in India is still dismal, and till date the
exact magnitude of incidence, prevalence, morbidity and mortality
remains unknown. Hopefully now that the Government of India has declared
Tuberculosis a ‘notifiable disease’ in 2012, surveillance will gradually
improve [4].
Present scientific literature substantiates the
observations made that tubercular infection rapidly progresses to
disease in children less than 2 years of age, and children between 5-10
years are at low risk [5]. Currently the most common presentations of
pediatric TB are pulmonary parenchymal disease and intrathoracic
lymphadenopathy, accounting for 60-80 % cases. Over the last 50 years,
several modifications of conventional methods (microscopy and culture)
and many newer diagnostic tests have emerged. Despite this, accurate
diagnosis of pediatric TB still remains elusive. The major challenges
are difficulties in obtaining samples for bacteriological confirmation
(inability to expectorate sputum), frequency of conditions that closely
mimic TB, and the paucibacillary nature of childhood TB. TST is now
known to have only limited application in endemic countries where most
individuals acquire infection and become TST positive during childhood
and adolescence. Nonetheless, it is still included in diagnostic
algorithms. Radiographs are still largely supportive and need to be
correlated clinically; till date not a single pathognomonic radiological
feature for TB has been found.
In 2012, the Updated National Guidelines for
Pediatric Tuberculosis were formulated [3]. Besides other changes,
existing diagnostic algorithms were modified to include other types of
extra-pulmonary TB and the use of Cartridge-based nucleic acid
amplification tests (CBNAAT) like GeneXpert, wherever available. The
advantages of CBNAAT is that it detects TB within 2 hours, and also
determines Rifampicin sensitivity. Presently, there are more than 600
CBNAAT machines throughout India that offer prioritized testing for
pediatric samples along with patients with suspected
multidrug-resistance and HIV.
The more things change, the more they remain the
same! This stands true for the circumstances in which pediatricians
diagnosed TB 50 years ago, and nowadays. The diagnostic approach used in
pediatric TB is still a combination of epidemiological and clinical
information supported by the results of a few limited investigations.
However, structured diagnostic algorithms are being used and more
sophisticated diagnostic modalities are available. We can only hope for
a brighter TB-free future if all of us help in surveillance by
diligently notifying our cases to the requisite authorities.
References
1. Ramachandran RS, Purnayyan S. Tuberculosis in
children. Indian Pediatr. 1966;3:218-23.
2. Khatri GR. National tuberculosis control programme.
J Indian Med Assoc. 1996;94:372-5.
3. Kumar A, Gupta D, Nagaraja SB, Singh V, Sethi GR,
Prasad J. Updated National Guidelines for pediatric tuberculosis in
India, 2012. Indian Pediatr. 2013;3:301-6.
4. Ministry of Health and FamilyWelfare. TB
Notification Order: Available from:
http://tbcindia.nic.in/showfile.php. Accessed May 08, 2016.
5. John TJ, Vashishtha VM, John SM. 50 years of tuberculosis control
in India: Progress, pitfalls and the way forward. Indian Pediatr.
2013;50:93-8.