The results of a study published in PLoS ONE journal are one more reminder of the real challenge in diagnosing TB in young children
India’s Revised National TB Control Programme (RNTCP) estimates that children comprise about 12 per cent of the total TB caseload in the country. But in all probability, 12 per cent may be an underestimation of the actual contribution.
A July 2011 study undertaken in Krishna district of Andhra Pradesh on 116 children below six years from 172 households with an adult who was recently diagnosed with sputum smear-positive pulmonary TB did not find even one child with TB disease!
The results of the study published in PLoS ONE journal is one more reminder of the real challenge in diagnosing TB disease in young children.
“The real reason for not being able to diagnose diseased children could be the non-availability of diagnostic tools like tuberculin for tuberculin skin test (TST) and X-ray facilities in peripheral health facilities or simply that such tests were never ever conducted. Or, health-care workers did not possess sufficient skills/knowledge to diagnose TB in children,” a TB expert commented.
Missing out timely detection can have grave consequences. Children under five years have a greater risk compared to older children. According to WHO, infants have a “much greater” risk of developing the disease. And if those under five can progress to the diseased state “within two years of infection,” it is just 6-8 weeks in the case of infants. Unlike older children and adults, children in this age group have greater chances of developing severe forms of the disease — disseminated TB and meningitis.
While those with active TB can be treated with multi-drug regimen, the asymptomatic children who have been infected but have not yet developed the disease can be given prophylactic treatment with isoniazid drug once daily for six months. This will prevent them from progressing from the infected stage to the diseased state.
But it’s a fact that diagnosing TB in children under five years is a challenging task. As WHO’s “Roadmap for childhood Tuberculosis,” has pointed out, there are no “effective diagnostic tests.” Unexplained loss of more than five per cent of the highest weight recorded in the past three months, or fever and/or cough for more than two weeks make TB more likely, especially when the child has been in contact with an infectious pulmonary TB patient in the same household. Yet, diagnosis cannot be made on the basis of clinical symptoms alone.
The first layer of complexity comes in the form of young children not being able to produce sputum. This is largely because their cough reflex is not fully developed; they tend to swallow the sputum. Sputum is the most basic and important sample for diagnosing pulmonary TB disease.
The next layer of complexity is that even when a sputum sample does become available, it may contain only a few TB bacteria. “Children tend to have TB with a smaller bacterial load. So, it is hard to see a few bacteria under microscopy,” Dr. Madhukar Pai, Associate Professor, McGill University, Montreal noted in an email to this Correspondent. “So, paediatric TB is called ‘pauci-bacillary disease’ (fewer bacilli).”
“TB diagnostics have the following lower limits of detection — 10-100 colony forming units (CFU)/ml for culture and much higher for smear microscopy,” Dr. Anne Detjen, Coordinator, TREAT TB Diagnostic Tools Initiative at the International Union Against Tuberculosis and Lung Disease said in her email to this Correspondent.
The sensitivity of diagnosis — by smear microscopy and culture — depends on the amount of bacteria present in the sample. “The sensitivity the of culture, depending on the age, disease severity and bacterial burden is 20-60 per cent, depending on what data you look for. For smear microscopy, it is 15-20 per cent,” Dr. Detjen noted.
But even in the absence of sputum sample for micro-bacterial confirmation, much information can be gained from tuberculin skin test (TST) and X-ray results.
But considering that nearly 40 per cent of Indians are infected with TB, and TST can only confirm infection, how useful is it for those under five years? “It is definitely helpful. A positive TST always means evidence of TB infection, regardless of age. The significance is more in young kids because they have no reason for being infected and suggests that some adult in their family has active TB,” Dr. Pai underlined.
A positive TST gains importance considering that the targeted group is children under five years from households where an adult has been recently diagnosed with sputum smear-positive pulmonary TB.
Though all infected individuals would test positive for tuberculin skin test (TST), the sensitivity may get compromised in malnourished children. Though infected, TST can be negative in infants because their immune system is not mature. This is where chest X-rays come in handy.
“Positive chest X-rays (e.g. enlarged lymph nodes inside the chest) are also indicative of TB. But X-rays can be abnormal due to many diseases (e.g. bacterial or viral pneumonia, asthma),” Dr. Pai explained.
“If X-rays are abnormal, that pushes the diagnosis towards active TB, not latent TB. But X-ray results need to be used along with other tests. A positive TST and suggestive X-ray, plus history of close contact with a TB case in the house, and symptoms (e.g. not gaining weight, fever) are most likely to point to TB diagnosis.”
The recently updated national guidelines on paediatric tuberculosis lay great emphasis on bacteriological confirmation using sputum samples even when chest X-ray is suggestive and TST is positive, and the child has received a complete course of antibiotic treatment.
“In cases where sputum is not available for examination or sputum microscopy fails to demonstrate AFB, alternative specimens (gastric lavage, induced sputum, broncho-alveolar lavage) should be collected, depending upon the feasibility, under the supervision of a paediatrician,” notes the updated national guidelines for paediatric tuberculosis in India, 2012, published in the Indian Pediatrics journal on March 16, 2013.
Facilities to collect sputum using the two different lavage methods from those under five years are available only in the tertiary centres in the urban areas. So what percentage of children from the rural areas would end up getting correctly diagnosed and treated? Incidentally, RNTCP aims to achieve “universal access” to quality assured TB diagnosis and treatment during 2012-2017.
That’s a very tall order considering that even tuberculin is often not available in peripheral health facilities! “Non-availability of a standardised tuberculin in the country was identified as a cause of great concern,” notes the National Consultation on diagnosis and treatment of paediatric tuberculosis conducted early last year.
So how many children are being wrongly diagnosed as disease-free as seen in the June 2011 PLoS ONE study?
(The Correspondent is a recipient of the 2013 REACH Lilly MDR-TB Partnership National Media Fellowship for Reporting on TB.)