Mobilizing against TB

Every year, more than one million people around the world die from tuberculosis, a disease that has been treatable and preventable for decades.

"Although new tools are needed, we could achieve zero deaths from TB with treatments and technologies that we've had since the 1980s, but to reach that goal we need to fundamentally change the way we look at the disease," said Salmaan Keshavjee, director of the Harvard Medical School Program in Infectious Disease and Social Change and associate professor of medicine and of global health and social medicine at HMS.

"We need a road map to ensure that the medicines and methods that have already been proven to save lives make it the last mile down the road to the communities where they are needed most," he said.

To that end, on Sept. 12 Paul Farmer, Kolokotrones University Professor at Harvard and chair of the HMS Department of Global Health and Social Medicine, and Paul Stoffels, chief scientific officer and worldwide chairman of Janssen Pharmaceuticals of Johnson & Johnson, hosted a symposium on "Rethinking the Global Response to Tuberculosis" that brought together innovative researchers and care givers to address the challenges of treating and preventing TB in new ways.

The symposium also launched a new program funded by a pledge from Janssen Pharmaceuticals to HMS that will help plot a course for improved access to TB diagnosis and treatment in some of the world's most vulnerable communities.

While the disease has virtually vanished in the United States and Western Europe, TB is hiding in plain sight in India, China, the Russian Federation and South Africa, where nearly 60 percent of the world's multi-drug resistant-TB cases are found. Eastern European and Central Asian countries are hot spots for the disease, accounting for nearly one-third of new infections and two-thirds of previously treated TB infections. TB is the biggest killer of people co-infected with HIV in sub-Saharan Africa and elsewhere.

"Harvard Medical School is proud to forge a new partnership with Janssen to begin to address many of the gaps in the current approach to combatting TB—developing a new roadmap for TB treatment and prevention, working in alliance with researchers and advocacy groups here and around the world to shift outcomes, hopefully in a dramatic fashion," HMS Dean Jeffrey S. Flier said in his welcoming remarks.

Stoffels spoke about the importance of transforming the global response to tuberculosis through collaboration, stressing the importance of speeding the transition from the discovery of new science to the delivery of solutions for patients. "That requires massive partnerships," Stoffels said.

Janssen Pharmaceuticals, a company of Johnson & Johnson, developed bedaquiline, the first new medicine for TB in forty years.

Instead of funding pharmacological research or a pilot program for a new clinical model, the Janssen project will support a broad effort to promote and empower innovation and integration of effective existing TB treatments in local health systems, changes in global TB policy and the development of new community health systems needed to fight TB, with a particular focus on drug-resistant TB and TB in children.

"Stopping the spread of TB—whether in a single community or around the globe—requires strong partnerships and bold action," said Farmer. "Many in the global health community have begun to mobilize around the goal of zero tuberculosis deaths; achieving such a vision will require a major acceleration of efforts to link service delivery, research and the training of health workers. This project is a critical next step on that path."

Other symposium speakers outlined the importance of using a multi-disciplinary approach—understanding the disease in historical and cultural context and looking for solutions using the methodologies of microbiology, epidemiology, genetics and engineering, and about various potential methods to improve treatment and save lives.

Finding missing children

In the 1970s, global health policies were put in place that prioritized treating the most infectious cases of TB with the hope that strategic application of limited resources would stop TB in its tracks. This left many cases of TB untreated, or treated ineffectively, which helped fuel the rising pandemic of drug-resistant TB.

In addition, since TB in children rarely takes the most infectious forms of the disease, pediatric TB became an unseen epidemic.

"We have a perfect recipe for making TB in kids invisible," said Mercedes Becerra, associate professor of global health and social medicine at HMS and author of a recent study that doubled the estimate of the global burden of TB in children.

Childhood TB looks different than TB in adults—kids often have extra-pulmonary TB that affects their bones or other body parts instead of their lungs. And the most widely used test for the disease catches fewer than one in five children sick with TB.

"We found that a million kids are falling sick with TB every single year," Becerra said. "But TB can be prevented, and each one of those children represents a missed opportunity to stop the spread of the disease."

Fighting drug resistance

The selective treatment policies put in place also increased the risk of developing drug resistance in the bug. Drug-resistant forms of TB also often go undetected in resource-poor settings, because lab tests for resistance are difficult to administer with limited infrastructure.

Even when drug-resistant TB can be detected, the months-long therapy necessary to effectively treat the illness requires a careful integration between hospitals, clinics and community health workers.

To overcome these challenges, Keshavjee says, the support from Janssen Pharmaceuticals will help researchers, physicians and policy makers rethink how the disease should be approached worldwide.

"This is a great opportunity to rethink our whole global strategy for TB," said Keshavjee, who will serve as the leader of the new program.

The program will enable HMS to help set treatment targets based on sound science and accurate estimates of disease prevalence, partner with grassroots organizations in affected communities, assist low- and middle-income nations in developing their own initiatives to address this and other diseases within their borders, and monitor progress as we move toward achieving zero TB deaths, he said.

"Just as we need to translate research findings from the basic science lab bench to the hospital bedside, we also have to get better diagnostics and medicines into the communities and homes where patients live, currently beyond the reach of over-burdened health care systems," said Keshavjee.

"Getting to zero deaths from TB may be an aspirational goal, but we should also see it as a practical task," said Becerra. "We need to find the best way to get there before more people die unnecessarily."

Provided by Harvard Medical School