In cases where there is a serious disease like TB meningitis, the index of suspicion for MDR-TB should be very high

The Sentinel Project on Pediatric Drug-Resistant Tuberculosis is a collective power of a global partnership by experts and others who share the same vision of ensuring that no child dies of drug-resistant TB that is curable. “We are collaborating to raise the visibility of this vulnerable population of children, and to share evidence and resources that can increase children’s access to prompt and effective treatment,” Mercedes C. Becerra, Associate Professor in the Department of Global Health and Social Medicine at Harvard Medical School said in an email to this Correspondent.

It all started in April 2011 when Dr. Soumya Swaminathan, Director of the Chennai-based National Institute for Research in Tuberculosis and Prof. Becerra met in New Delhi at a workshop to examine the barriers to scaling up drug-resistant TB (DR-TB) treatment in India.

“[After our respective presentations] we realised that globally, despite much work being done on DR-TB, children with DR-TB were in essence invisible. This was itself a major barrier to advocacy for better science and improved treatment access for children,” Prof. Becerra said. “Dr. Soumya and I thought that we should try somehow to raise the visibility of this vulnerable population, and that it should also be a way to link individuals who saw themselves as stakeholders.”

The two of them came up with an idea of linking in a virtual network like-minded people who shared the vision that no child should die of DR-TB — a curable and preventable disease. The two individuals in their respective ways reached out to people in the same field across the world. “All of them supported the idea and expressed eagerness to join such a new virtual community,” she noted. The project gained traction after an October 2011 international conference where the two made a public announcement of starting this virtual network and invited all interested colleagues to join.

Within a few weeks, over 200 scientists from over 20 countries responded to the call. Today, the Sentinel Project network includes over 300 people from over 50 countries.

“We have come up with a set of guidelines [a field guide] that will help in managing MDR-TB in children when there is no bacteriological report based on culture,” Dr. Swaminathan explained (Click here for Podcast). “The guidelines highlight the situations when you can actually suspect and call it [a case] as probable MDR-TB even when there is no [bacteriological] report [confirming the disease].”

According to Prof. Becerra, the field guide, along with a paper published in the American Journal of Respiratory and Critical Care Medicine, provides extensive and detailed practical recommendations to doctors about managing children with MDR-TB. The field guide, which is consistent with WHO and other guidelines, is one of the documents prepared by the Project.

Close contacts

One of the most important contributions of the Sentinel Project’s field guide is its algorithm for managing a child who is in contact with an infectious adult with MDR-TB disease. Though WHO has not come out with guidelines on chemoprophylaxis for children, especially those younger than five years, who are close contacts of MDR-TB patients, several other agencies have come out with theirs. “The question about chemoprophylaxis is not addressed in the same way among several global guidelines,” Prof. Becerra noted. “But the aim of the Sentinel Project has been to provide guidance on this and other challenges based on the collective expert opinion and observations of colleagues across the globe.”

There are two instances when children aged younger than five years who are asymptomatic, growing well and have no clinical signs of TB but have been in contact with an adult (index case) would be eligible for preventive therapy. The first is when the index case is resistant to rifampicin drug alone. In such a case, the child needs to be treated with 15-20 mg/kg of isoniazid drug for six months. The second instance is when the index case has confirmed MDR-TB but is susceptible to ofloxacin. In such cases, the child may be treated as per the national TB programme, or by one of the five regimens listed in the Sentinel Project.

India focus

Dr. Swaminathan has conducted two training programmes — one in Chennai (June this year) and another in Dhaka (July 2013) — for paediatricians. There were over 45 paediatricians for the Chennai training programme; RNTCP officials were also present. “I sent the recommendations to RNTCP and asked them to expand the guidelines to consider children for MDR-TB treatment under the following three conditions.”

The three conditions are — if the child is a close contact of a person with known MDR-TB patient; or if children were close contacts of a person who is highly irregular on drug intake or has failed TB treatment or has died from TB; and finally in situations where a child is not improving or is actually deteriorating on [first-line TB] treatment.

“Especially in cases where there is a serious disease like TB meningitis, the index of suspicion for MDR-TB should be very high,” Dr. Swaminathan explained. “We cannot wait endlessly till the child with meningitis goes on deteriorating, especially if the drug compliance is good… because it affects the brain permanently. These things need to be brought into the guidelines and people must be made aware of them.”

Another important goal of the Sentinel Project is to come as close as possible in knowing the true burden of TB disease in children. Since bacteriological confirmation is difficult in children younger than five years, there is a need to have more data on the number of children suffering from drug-sensitive TB and drug-resistant TB. “Through the network, we hope to implement multi-site initiatives to improve our understanding of how many children at each location have TB disease in its different forms,” Prof. Becerra said.

“I think Sentinel project has had an impact at the global level,” Dr. Swaminathan noted. “Many of the members of the Project are also involved in WHO policy making. A lot of advocacy has been done and the WHO is now taking seriously the problem of estimating TB burden in children.”

The fact that the 2013 WHO Global Tuberculosis report has made mention of drug resistant TB indicates that the Project is beginning to have an impact.

(The Correspondent is a recipient of the 2013 REACH Lilly MDR-TB Partnership National Media Fellowship for Reporting on TB.)