“A child with TB [is] as likely as an adult with TB to have MDR-TB [multi-drug resistant TB],” notes the WHO Global Tuberculosis Report 2013. that was released last month. “It is therefore essential that the identification of MDR-TB in children be strengthened.”
WHO did not stop at that. “Efforts should be made to systematically conduct household contact investigation of all patients with MDR-TB, including children,” it underlined.
The reason for the emphasis on MDR-TB detection is not difficult to fathom. Patients with MDR-TB do not respond to, or respond extremely poorly to standard first-line anti-TB drugs. A person is said to have MDR-TB when he is resistant to at least isoniazid and rifampicin, two of the first-line anti-TB drugs.
This makes it all the more important to trace the vulnerable groups well before they become diseased with drug-resistant TB. And children younger than five years from the same household as an adult (index case) who have been recently diagnosed with MDR-TB disease are one such vulnerable population. A 2002 study published in Pediatrics journal suggested two child contacts for every adult MDR-TB source patient in a high-burden setting.
“As many as a million children could be exposed to MDR tuberculosis globally each year, many of whom, in the absence of effective preventive therapy, will go on to develop MDR-TB disease,” the 2002 paper notes.
“Preventive chemotherapy for children with second-line drugs is debated. Hence preventive chemotherapy for MDR-TB among contacts of MDR-TB patients is not a policy globally as enough scientific evidence is not available,” Dr. K.S. Sachdeva, Additional Deputy Director General at Central TB Division, Ministry of Health & Family Welfare said in an email to this Correspondent.
But there is a gradual shift in policy outside India.
Incidentally, even the implementation of the WHO-recommended, RNTCP-approved contact screening and preventive therapy using the first-line drug isoniazid for six months in children younger than five years who are asymptomatic or infected with drug-sensitive TB as a TB-diseased adult in the same household is “sub-optimal,” as a few studies have revealed.
Even the diagnosis and treatment of children with MDR-TB disease is far below par. “Very few children are diagnosed and treated for MDR-TB,” said Dr. Soumya Swaminathan, Director of the Chennai-based National Institute for Research in Tuberculosis (formerly TRC). “Awareness is itself low. Doctors think children can’t get infected with MDR-TB.” (click here for Podcast)
This is despite the fact that India and China together carry nearly 50 per cent of the global MDR-TB burden. The prevalence of MDR-TB in India is estimated to be 64,000. The estimated percentage of new MDR-TB cases diagnosed by RNTCP is 2.2 per cent. It is 15 per cent in the case of retreatment TB cases. The number of MDR-TB cases diagnosed in 2012 was about 16,500; it was about 4,200 in 2011.
According to an October 25 article in the Wall Street Journal, 6.7 per cent of TB patients tested in 2012 at 18 sites using a rapid molecular diagnostic test — Xpert MTB/RIF — turned out to be drug-resistant TB cases, more than double the figure quoted by WHO.
“India has been offering all the four WHO recommended diagnostic tests for the diagnosis of MDR-TB. There are 51 laboratories which offer the Drug Sensitivity Test [DST],” said Dr. Sachdeva. “Some labs offer more than one DST facility.” Of the 51 labs, 37 labs offer solid culture based DST, 12 labs offer liquid culture based DST also, and 41 labs offer Line Probe Assay [LPA].” In addition to the labs offering DST, “there are 38 Gene Xpert machines in 30 locations.”
Gene Xpert can only reveal resistance to rifampicin drug. A vast majority of people who are resistant to rifampicin are also resistant to isoniazid.
“If Xpert shows rifampicin resistance in a patient with risk factors for MDR, one can begin second-line therapy while waiting for culture and full-drug susceptibility profile. So, one does not need to wait to act, but all Xpert Rif resistance results must be followed up with culture and DST,” Dr. Madhukar Pai, Associate Professor, McGill University, Montreal clarified in an email to this Correspondent.
But all the four techniques — solid/liquid culture, LPA and Xpert — require sputum samples. And children aged under five years very often are unable to produce a sputum sample. Hence other techniques need to be used to get a sputum sample.
Besides the difficulty in getting sputum samples from young children, the number of TB bacilli present would be fewer even when sputum samples become available. “Diagnosing is difficult in children,” Dr. Swaminathan said. “It is difficult to confirm the diagnosis bacteriologically even by culture.”
The problem gets compounded in the case of extra-pulmonary TB. “Young children have nearly 30 per cent chances of having extra-pulmonary TB,” she said. “The younger the child, the more the chances of seeing disseminated TB.”
This explains why we see more instances of TB meningitis in young children. “But getting CSF [cerebrospinal fluid] and positive culture is so very rare. Maybe 10 to 15 per cent, not more than that,” she said. “So in a vast majority of the cases won’t get bacteriologically confirmed diagnosis for MDR-TB in extra-pulmonary cases.”
The irony is that in such situations, there is no provision in the national TB control programme to treat the children. “The drug-resistant TB programme is looking for a confirmed bacteriological report from an RNTCP-accredited lab,” she explained. “Unless they go with that report, they will not be started on MDR-TB regimen. [But] it is very rare for a young child to produce such a report.”
(The Correspondent is a recipient of the 2013 REACH Lilly MDR-TB Partnership National Media Fellowship for Reporting on TB)