Hamid is a handsome Tanzanian man with a soft voice and impeccably-pressed clothes who works as a driver for our research program in Dar es Salaam. We talked about his family and his aspirations as we drove back and forth in Dar es Salaam, between meetings and social occasions.
Hamid (not his real name) was more subdued than usual. His voice was raspy, his eyes bloodshot, and he coughed into his hand as we drove back and forth in his air-conditioned car.
I was there to welcome two of our collaborators back to Tanzania and to celebrate the opening of their new lab. We hope those labs and other efforts at our sister institution, the Muhimbili University of Health and the Allied Sciences (MUHAS), will help developing world countries like Tanzania build the capacity to research modern day plagues like tuberculosis (TB) and HIV.
With our colleagues at MUHAS we are studying how the immune system can protect from TB.
In the United States lab tests measuring immune responses to TB are commonly used to detect risk of TB. The idea is that people who have immune responses to TB must have been exposed to TB, and therefore they are more at risk of developing TB than people who have never been exposed.
Or at least that's the dogma. It's not that simple in Tanzania, and I suspect elsewhere around the world where TB still kills over a million people a year.
Over a million people a year. Numbers like that are hard to understand - it's hard for me to wrap my brain around statistics like 1.4 million deaths from TB yearly. But those statistics point to real-life catastrophe.
Like Hamid's. Soon after I left Dar es Salaam, Hamid presented to our clinic with a worsening cough, fevers, and a chest x-ray showing pneumonia. A thin man already, he had lost 15 pounds. Hamid had TB.
In Tanzania, and most developing world countries, nearly everyone has been exposed to TB. That means having detectable immune responses to TB might not be that unusual. Plus, among people with HIV, having weak immune responses to TB is probably why people get TB in the first place. So for them having no detectable responses to a very common infection like TB could be risky.
To find news ways of fighting TB, our team in Dar es Salaam, Tanzania has been studying a new TB vaccine which was shown in a huge study to protect people with HIV against TB. The team is called DarDar, which is an amalgam of Dar es Salaam and Dartmouth that mimics the Kiswahili word dada, which means sister.
The photo below depicts some of the major members of our team, including the folks who work at our Infectious Diseases Clinic in Dar es Salaam, and our fearless leader Ford von Reyn. He's the white guy in front, and while he is genteel and a total joy to work with I also think he is visionary who will save millions of lives. I'm lucky to work with him.
Using data from the DarDar study, we have been studying how immune responses protect people from TB. The hope is that this will help us figure out how to make better vaccines and to predict better who is most in need of protection.
Do immune responses to TB signal risk, or do they confer protection? In a paper published in The Journal of Infectious Diseases, we showed that it was the latter among adults with HIV in Tanzania: people who had detectable immune responses to TB proteins were less likely to get TB than those who did not. Having strong immune responses against TB was good.
Are all immune responses to TB good, or are some better than others? In our next study, we asked whether having detectable immune responses to lots of TB proteins provided better protection than immune responses against single TB proteins. Eureka! In a paper in PLoS ONE, we showed that detectable immune responses to multiple TB proteins among adults with HIV in Tanzania was associated with the best protection against TB. In this case, more is better.
Most recently, we studied whether immune responses against TB proteins contribute to control of TB even when TB disease happens. The idea was to see if the size of the immune response to TB proteins had any impact on the amount of TB in the body of adults with HIV and active TB disease. Would strong immune responses help keep TB under some degree of control, perhaps by leading to a milder form of disease?
In a new paper in The Journal of Infectious Diseases, we found that greater immune responses to TB proteins among HIV-infected adults in Tanzania were associated with a smaller burden of TB disease. The people with bigger immune responses had less TB in cultures of their sputum. That means that even when immune responses were unable to prevent TB disease entirely, at least they did help keep TB from spreading as virulently around the body.
This gives us hope that vaccines designed to boost immune responses against TB might work.
That's incredibly important, because although Hamid was unfortunate to contract TB, he was actually one of the lucky ones. Hamid had access to a good clinic and caring doctors who were able to provide him with effective treatments. Not everyone with TB has access to resources like those - in fact most don't. Soon after his diagnosis, Hamid started a six month course of four potent anti-TB drugs, and began to recover.
If we are going to protect people like Hamid from TB, we need a better TB vaccine. There is already an old vaccine, called BCG, which protects kids from the most severe manifestations of TB. But it doesn't protect most adults from TB. That means a worldwide hunt is on to find a new TB vaccine.
Unfortunately, there was bad news from South Africa recently: a promising candidate failed to provide any protection against TB in kids. The vaccine - called, memorably, MVA Ag85 - seemed to boost immune responses against a single TB protein, but kids were not protected by those responses.
Hope is not lost. There are many other new TB vaccine candidates out there, including our new vaccine DAR-901 which is being manufactured and studied in collaboration with a big Gates-funded foundation called Aeras. One theory we are testing is that our vaccine - which contains many many proteins - might provide better protection than the single protein vaccine MVA Ag85 vaccine that failed in South Africa.
Stay tuned - we hope to follow these clues about immune protection from TB straight to a new vaccine against TB. In the meantime, Hamid is back in action: having completed six months of therapy with four anti-TB drugs, he is back working with the DarDar group and helping fight TB.