“First he stopped eating, then later he got a fever… the doctor said it was just a virus going around, but then his soft spot got swollen and I remembered the same thing happened to my daughter when she was diagnosed with meningitis at six months,” Myra said, speaking to a group of childhood TB activists about her young son London at a meeting Thursday hosted by the Treatment Action Group and co-sponsored by the Center for Global Health Policy.
When the doctor was finally convinced London was not getting better, they took him to the emergency room and performed a spinal tap, confirming he had TB meningitis. London was only six months old.
“They put him in isolation for a month and a half, and in the ICU for a week after that,” Myra said, with tears welling in her eyes. London was so scared in the hospital, she said, he needed her to be in physical contact with him at all times. Making matters worse, the drugs London had been taking for a month were not working – the TB was resistant. London and Myra were shuffled off to another hospital and put once again in isolation. “They had to put a catheter in because London was throwing up all the medicine,” Myra said, adding that he has had several surgeries and is now on his third catheter, since he keeps pulling them out. Shortly thereafter they were then sent to Houston where they were kept in isolation for another month.
“He’s doing unbelievably well nine months into therapy,” Myra said, but he still has 15 months of directly observed treatment to go. One of his medications caused hearing loss in one ear, so London now wears a hearing aid.
Contact tracing showed London got the disease from his father, who was put in isolation for four months in San Antonio. Both Myra and her young daughter have tested positive for latent TB.
Myra said she wished more could be done to get kids tested before they got sick, and more could be done to prevent TB in the first place. Studies have shown that the average child with TB meningitis has about four medical encounters before diagnosis, said Jeffrey Starke, MD, a professor of pediatrics at Baylor College of Medicine who also works at Texas Children’s Hospital and has helped manage London’s case.
Myra’s story resonated with those in the audience – TB in children has long been neglected. In many low-resource countries, London’s TB would never have been detected and he would not be alive today.
Dr. Sharon Nachman, a professor of pediatrics at the State University of New York School of Medicine, said drug companies that are investigating tuberculosis medications in adults do not want to look at them in children.
“It is infuriating to me to have a company say to me – oh, we are going to wait [to test this on children]. What are you waiting for?” Nachman said. Some companies and government agencies argue that they need to wait until Phase III clinical trial results are available for drugs under investigation before they are tested in children, which is not less than a five year process, according to Nachman. “If you don’t have a pediatric formulation or you don’t start thinking about a pediatric formulation, you will not get a pediatric formulation.”
Shorter duration treatments and preventive therapy are some of the items on the therapeutic agenda for drug susceptible TB, Nachman said. And one area making headway, issues relevant to children who have both TB and HIV.
Nachman works with a group called IMPAACT – the International Maternal Pediatric Adolescent AIDS Clinical Trials Group – whose mission is to decrease significantly the mortality and morbidity associated with HIV disease in children, adolescents and pregnant women. Common HIV co-infections, like TB and human papillomavirus, are researched by IMPAACT as well. The group has completed trials looking at primary Isoniazid Preventive Therapy (IPT) for TB in HIV-infected and exposed infants (IMPAACT P1041), as well as the safety of IPT strategies in HIV-infected pregnant women (IMPAACT P1078). (Pregnant women are another group commonly excluded from clinical trials).
There are also several studies in development by IMPAACT and other groups looking at several new TB drugs and formulations for treatment of HIV-infected patients – such as quinolones and rifapentine (see chart at right) – that will include pediatric evaluation, but none of these include pregnant women.
IMPAACT is also working to co-endorse a study looking at short-course rifapantine/isoniazid for treatment of latent TB in HIV-infected individuals. Drug resistant TB, like London has, is a whole other issue, Nachman said, but IMPAACT also is working to develop a pediatric safety study for MDR-TB investigating the drug bedaquiline.
It’s time to aim for zero child deaths from drug resistant TB, said Mercedes Becerra, an associate professor at Harvard Medical School and senior TB specialist at Partners in Health. “At least 5 million people have become sick with drug resistant TB, and at least 1.5 million have died, over the past ten years… Even if the numbers for children are only ten to 30 percent of these, that’s hundreds of thousands of children dying untreated, invisible,” Becerra said.
Only 0.5 percent of people with drug resistant TB are treated with WHO-approved programs with quality-assured drugs, according to Becerra, and 3.5 million patients receive treatment formulations with unknown drug quality.
Becerra showed the audience pictures of four children in Lesotho, Ethiopia, Peru and India who had died from late or poorly diagnosed and treated MDR-TB. She calls these children the “canaries in the mine” reminding us that in all of these communities where children died, they require better health systems and better medicines to treat TB.
Becerra now works with The Sentinel Project on Pediatric Drug-Resistant TB, an initiative of Harvard Medical School and the National Institute for Research in TB in Chennai, India. This global research and learning network, as she called it, aims to develop and deploy evidence-based strategies to prevent child deaths from DR TB. They even have a special sub-group to advocate for more research for childhood TB drugs and diagnostics.
“We have no funding right now,” Becerra said, except for seed funds from the host institutions to get the network started. But she has high hopes for the future.