How could the world dramatically lower the incidence of tuberculosis and save millions of lives?
An effective TB vaccine would revolutionize the response to TB, which kills about 5000 people each day, and eliminate the need for lengthy and often difficult drug treatment.
An effective vaccine would be of tremendous benefit all over the world, including in the United States, where there were 13,299 cases of active TB reported in 2007 and about 11 million people with latent TB.
Of course, there’s no question that much more can be done to prevent TB using existing methods, notably the Three I’s. But, imagine what an effective vaccine could do. Vaccination of newborns with a successful TB vaccine could decrease global TB incidence by 39 percent to 52 percent by 2050, and mass vaccination could result in a nearly 80 percent decrease of TB by 2050, according to a recent estimate.
What’s exciting is that the effort to develop such a vaccine is proceeding rapidly and could produce results in just a few years — that is, if the United States government and other donors provide the funding necessary for large-scale clinical trials.
Right now, that’s a very big “if.”
South Africa is a leader in TB vaccine research, and I recently had the opportunity to visit a tuberculosis vaccine facility in Worcester, 120 km northwest of Cape Town, and to take some photos. The facility has the strong support of the US-based Aeras Global TB Vaccine Foundation, and it is a terrific example of capacity building and international cooperation.
In fact, Aeras is supporting this kind of capacity building and healthcare infrastructure strengthening (including laboratories and disease detection) not only in South Africa but at partner sites in Kenya, Mozambique, Uganda, Cambodia and India as well.
The area called the Boland, where facility is located, is one of the most beautiful places I have ever visited. It is the source of world-class wine as well as those delicious Ceres fruit juices you can find in supermarkets in the US and other countries.
Unfortunately, this rural area also has one of the highest rates of TB in the world.
TB incidence in the research area is about 100 times that which we have in the United States. The level of TB incidence in this area is at 1400 cases per 100,000 people, even higher than the overall South Africa rate of 900 per 100,000.
The situation in South Africa is aggravated by unemployment, poor housing conditions (cramped and with inadequate air circulation), extreme inequity in access to medical care, and HIV/AIDS.
As we explored in Deadly Synergy, TB is having an enormous and deadly impact on people who are living with HIV/AIDS. Since 2007, HIV and TB co-infection has been the most significant cause of premature death in the province of Western Cape.
However, it is also worth noting that, globally, most people with TB disease are not HIV positive.
In fact, in the Western Cape, HIV prevalence is less than the overall rate in South Africa as a whole. Hassan Mahomed, the SATVI Clinical Director, told us that there are other factors in addition to HIV which are driving the TB problem in the area, which predates the escalation of HIV.
He told us that the long, cold and rainy winters in the area lead people to staying indoors where they can become infected by TB. He said poverty and alcoholism were also major factors, with many of the people receiving low wages for seasonal work on the many farms in the area.
Children can suffer terrible forms of TB disease, such as TB meningitis, which can lead to severe brain damage and paralysis.
While children in South Africa receive some protection from the BCG vaccine, developed about 90 years ago, this does not protect them against pulmonary TB and the protection does not last into adulthood.
But research is advancing rapidly. There are now 10 new TB vaccine candidates in clinical trials worldwide, and four of them are being tested in Worcester, at the field site of the South African Tuberculosis Vaccine Initiative (SATVI).
We happened to arrive at the site on a day when mothers were bringing in their babies to receive an already-proven vaccine against pneumococcal disease. Children in the TB vaccine study area are provided with other vaccinations free of charge, whether or not their parents choose to enroll them in the study.
I asked one of the mothers if the 150 Rand (about $19 USD) payment she receives for each clinic visit was a help to her, and she said yes but the even more important benefit was that as a study participant her baby also receives regular medical check-ups.
On our visit to the site, I got a chance to meet four month old Janenique Pienaar of Worcester. Her mother was beaming, clearly delighted that her daughter is making history as the first baby in 80 years to be vaccinated in a proof-of-concept efficacy trial (Phase IIb) of a candidate TB vaccine.
This vaccine candidate, called MVA85A/AERAS-485, would be a booster to the BCG vaccine, and it has already been shown to be safe in a number of Phase I and Phase II clinical trials.
To study this vaccine candidate, SATVI is enrolling 2783 healthy, already BCG vaccinated, babies, at about 4 months of age to participate in the trial. Half the babies will be given the new vaccine, and the other half a placebo.
The children will then be monitored for two years to compare the incidence of TB in the two groups. If successful, the vaccine would proceed to a much larger, and more costly, Phase III clinical trial in 2011.
This vaccine could be ready for wide-scale use by 2016, if the trials are successful. Unfortunately, funding for later stage clinical trials for TB vaccines is at present very much in doubt, and the funding shortfall could significantly delay progress.
While the NIH and CDC have funded some early stage TB vaccine research and epidemiology studies, funding for the kind of late-stage trials conducted in South Africa is authorized under the PEPFAR law (Lantos-Hyde) to come through USAID.
USAID is already investing significantly in AIDS and malaria vaccine research, but unfortunately it has not provided funding for TB vaccine research, whether through Aeras or another program.
The Obama Administration supported a tiny increase of only $10 million for USAID’s TB program in 2010. Congress is now on course to provide a larger increase for 2010, but it will be roughly a $150 million increase at best — far less than the increase of about $500 million we and other advocates had sought for implementation of TB programs and research.
The Aeras Global TB Vaccine Foundation needs over $30 million per year in additional funding to support a late stage clinical trial of a TB vaccine candidate.
We hope that the Administration proposes a substantial increase for TB in its 2011 budget proposal, yet the signs so far are not good.
TB is not just any disease. It’s the third leading cause of morbidity and mortality combined in women of reproductive age in developing countries. India’s national TB program estimates that some 100,000 women in India alone are rejected by their families every year because of TB.
Yet, the Administration’s draft, 6-year strategy on TB omits any reference to the TB funding levels “authorized” last year in the Lantos-Hyde bill, now US law.
That bill specified $4 billion over 5 years for TB, or $800 million per year, including for vaccine development. But, to become a reality, this funding level needs annual support from Administration and from the Budget Chairmen and Appropriators in Congress.
What we have heard from government insiders is that the Administration feels the amount of TB funding now provided through PEPFAR, which directs some of its funding to addressing TB-HIV coinfection, in effect addresses the TB funding need. Would that were the case!
President Obama just awarded the Presidential Medal of Freedom to Archbishop Emeritus Desmond Tutu. He, like Nelson Mandela, is a TB survivor, and both have called for bold action to confront TB. Tutu has appealed for funding for TB and HIV programs, even in these difficult times.
We must heed their call to action. TB is estimated to deplete the incomes of the world’s poorest communities by $12 billion per year. South Africa has made progress in the fight against TB, but there is still much to do. As Tutu has stated, “As we have overcome apartheid, so we shall defeat TB and HIV/AIDS, these ungodly twin killers.”
— David Bryden, Senior Program Policy Officer, Center for Global Health Policy