From total neglect till a few years ago, childhood TB is now taking centrestage. A couple of days back, the WHO released an updated guidance for national TB programmes (NTPs) on the management of tuberculosis in children.
The updated guidance takes into account many important developments and published evidence on childhood TB since the first guidance was published in 2006. It is targeted at the TB control programmes of the low- and middle-income countries.
Initial diagnostic test
The first new recommendation is the use of Xpert MTB/RIF, a rapid molecular assay, as the initial diagnostic test for children suspected of having multidrug-resistant TB (MDR-TB) or HIV-associated TB. In effect, Xpert displaces smear microscopy and culture as the initial diagnostic test for these two categories. The “strong recommendation” is based on the WHO policy update on Xpert released last year.
“Xpert performs clearly superiorly to smear microscopy but is not good in children who are culture negative,” Dr. Anne Detjen, Coordinator, TREAT TB Diagnostic Tools Initiative, International Union Against Tuberculosis and Lung Disease (The Union), New York, had noted in an email to this Correspondent last year (“Paediatric TB: should Xpert molecular test replace smear microscopy?” The Hindu, October 31).
Incidentally, India is only now slowly expanding the availability of Xpert test to diagnose MDR-TB in adults. Only 38 Xpert machines were available in 30 locations as of November last year.
A few days ago, for the first time in the country, the Revised National TB Control Programme, along with other agencies, took a right step in addressing the needs of children with MDR-TB. A pilot project for three months was launched to diagnose using Xpert the missed cases and children with MDR-TB in Hyderabad, Chennai, Kolkata and New Delhi.
Unlike in the case of MDR-TB, the recommendation for Xpert as a diagnostic test is only “conditional” in the case of drug-sensitive TB and extra-pulmonary TB. “Given that Xpert is so much better than microscopy, WHO recommended Xpert as a possible alternative for child TB diagnosis,” Prof. Stephen Graham from the University of Melbourne and Murdoch Children’s Research Institute, Australia, and also The Union, France said in an email. He led the team that compiled, synthesised and evaluated the evidence underlying the recent recommendations that were considered for possible revision.
But, in the case of children with TB meningitis, WHO “strongly recommends” Xpert as the first diagnostic test, considering the urgency of rapid diagnosis.
The latest guidance has seven new recommendations for contact screening of children who have come in contact with adults with TB disease and are not on treatment. Adults with sputum smear-positive pulmonary TB are most likely to transmit the bacilli to others. Hence, children below five years of age and HIV-positive children living in the same household as the diseased adult, MDR-TB included, run the greatest risk of getting infected with TB, particularly when there has been close contact for prolonged duration (Contact screening: the risk of wrong TB diagnosis, The Hindu, October 24, 2013).
It is important to note that children aged below five years run a great risk of developing TB disease within one year of infection; it is about a few weeks in the case of infants.
Therefore, there is a “strong recommendation” to undertake contact screening when an adult meets one of the following criteria: sputum smear-positive pulmonary TB; has MDR-TB; is HIV positive or if the contact is less than five years of age.
The guidance makes a marked departure from the established method of screening children who are in close contact with adults who have smear positive pulmonary TB. While the usual practice is to use tuberculin skin test (TST) for confirming infection, and chest X-ray (CXR) for confirming disease, the guidance states: “routine assessment of exposed contacts does not require CXR or TST. These tests have limitations and are often not readily available.” Hence, in the absence of TST or CXR, “clinical assessment alone is sufficient” to know if the child contact is disease-free.
Explaining the rationale behind WHO’s recommendation, Prof. Graham noted: “It is a question of balance and trying to be pragmatic and most effective and cost-effective using what is available. If [TST and CXR are] required for contact screening but are not readily available, then this becomes a barrier to contact screening and preventive therapy.”
According to WHO, the symptom-based screening has been found to be “safe and more feasible than diagnostic test-based screening in resource-limited settings.” Only children with TB symptoms need to be referred to secondary level for further assessment, it states.
The radical shift from test-based approach to symptom-based approach would mean that “screening can [now] be done by health workers at a peripheral level.” “Health workers are generally capable of differentiating whether a child has symptoms or not (i.e.) is well or sick. This symptom-based screening approach is increasingly being evaluated,” said Prof. Graham. “A prospective study in Indonesia with follow-up has shown excellent results. Vietnam has been rolling out this approach nationally since the end of 2012; early unpublished data look very promising.”
The WHO “strongly recommends” preventive therapy using a single dose of isoniazid daily for six months when the contact does not have TB disease. This recommendation is based on the “high quality of evidence.” But WHO does not recommend preventive therapy for contacts of MDR-TB index cases.
Contact screening has twin benefits: it helps in testing contacts early and starting treatment without much delay, while the isoniazid preventive therapy (IPT) “greatly reduces the likelihood” of children developing disease during childhood.
The WHO had recommended IPT a few years ago and RNTCP has also approved it, but the implementation is at best “sub-optimal” in India. Even basic systems to enable IPT are not in place, studies show. The guidance makes it explicitly clear that follow-up should be carried out “every two months until treatment is complete.”