According to the World Health Organization, Tuberculosis (TB) is the world’s leading infectious cause of death. Despite significant advances in reducing mortality in recent decades through improved diagnosis and drug treatment regimens, TB still causes enormous human suffering. It’s a major economic burden, and it’s one of the major drivers of global inequity1.
The Bacille Calmette Guérin (BCG) vaccine can provide decades of protection against TB, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. Today, there is a broad portfolio of platform technologies and insights that can be leveraged to expedite TB vaccine development. However, the global TB vaccine pipeline has slowed its progress over the last few years. New tools and insights from technologies and discovery research are needed to feed into a rich and diverse pipeline in the future2.
While TB is not as prevalent in the United States or Europe, it is extremely prevalent in sub-Saharan Africa. Unfortunately, little information is shared there about the seriousness of TB. In light of Tuberculosis Awareness Day, we gathered together PRA experts from the Center for Vaccine Research and physicians from the University of Siena’s Master’s in Virology Program, to hear their insights on this infectious disease. Lynlee Burton, Sr. Director Therapeutic Expertise, Darin Seehafer, Director of Therapeutic Expertise, and interns Keiko Pempho Msusa and Nginache Victoria Nampota Gino, spoke with us about the big questions surrounding TB.
What impact has tuberculosis had around the world?
The truth of the matter is, the vaccine is not good. TB is not a disease that’s prevalent here in the United States or even somewhat in Europe. What's interesting though, if you think back to when you're at the doctor, or you may be getting a vaccine of some other type, people will say, “Have you been tested for TB?” and the TB test is that little skin prick kind of test.
So, we hear about it. We know about it. But it's a lot bigger deal than we think.
Malawi has a National Tuberculosis and Leprosy Control Strategic Plan. Recently, they've been trying to utilize social media and cell phones to communicate the message about TB. However, with this being a low-resource setting, I don't think that’s worked out very well. They have also utilized community health workers and even adolescents to spread the word. They just give them what the symptoms are and if they have come in contact with anybody with TB, they should report to the hospital. If they’re immunosuppressed and they're coughing, they should go to hospital. If they've had a cough for more than two weeks, they should report the hospital.
Spreading messages like that is crucial. They're trying to utilize the community, but I don't think the social media strategy would work very well. Most of the rural settings where there is high burden of TB do not have the network or access to technology like we do in the urban settings.
From my facts on our national program, the last known incidents were 131 per 100,000, and about 50% of these will be HIV positive. Although preventative methods already exist due to the increase in HIV associated TB, especially in sub-Saharan Africa and the emergent multi-drug-resistant TB, the incident is slowly going up. If you live in an area with easy access to healthcare and disease prevention, it can be easy to take for granted your freedom from worry for most infectious diseases
“It’s important to consider the financial and emotional burden this disease can have on families as well. I personally know two people who got TB. Both of them were my classmates. There was one gentleman in a hospital who developed TB and had to drop out of school for the year, so he ended up finishing a whole year after me.
Then, during my internship, another friend of mine had neck pain and no one could explain why. Eventually they found out that she also had TB in her bones. For people like us who work in the hospitals, we are at risk just by simply participating in patient care. It’s definitely a huge issue for us in Malawi.
The vaccine that's used is called Bacillus Calmette–Guérin (BCG). It’s not widely used in the US, but it is used around the world. I would say that it is given to children more often, but it doesn't always do a good job of protecting people. It’s about 70 to 80% effective against most severe forms of TB in children. But it's less effective in adults, especially in adults with respiratory disease.
Why isn't the vaccine more prominent in other countries? Why are some countries more at risk than others?
Regarding a case study of Malawi, vaccine coverage is actually around 90%, and it's been in the 90s for the last couple of years, sometimes going as high as 99%. It's not that people are not getting their vaccine, it's just that it's not working. From all the diseases we had, for example in 2018, 17% came from children despite the fact that they had just received the vaccine.
Populations in sub-Saharan Africa are particularly at risk, mostly HIV-positive people. In such people, we also give them preventative treatment and viral therapy. They take it daily to prevent TB. At every visit with the hospital, we're supposed to screen patients for TB. If we think they might have symptoms of TB, we need to find their families and make sure the little ones, including children younger than five, so we can take extra efforts because we have at-risk populations.
The risk people have in Malawi is mostly because of HIV. The immune systems of those populations who have HIV are generally not as strong as healthy populations, so they tend to be more at risk. Living conditions in Malawi also increases the risk—the houses are so close together and have so many people. Living conditions, resources, and HIV are all the reasons why it’s so prevalent here.
We can’t ignore malnutrition as a contributor. You see this in in areas that are overcrowded and in underserved population. Malnutrition becomes an issue, as well as access to healthcare. These all go hand-in-hand and create the perfect environment for this to spread.
Looking at some places like the United States, it's not like we don't have our poor areas and it's not like we don't have overcrowding. But I think one thing that we do have is a little bit better access to healthcare. That’s why we don't utilize the vaccine as much. Our living conditions aren’t as big of an issue. You can't underscore the importance of the number of HIV-positive people—it spreads like wildfire through that population because they don't have the natural defenses to protect themselves from it.
What are the main ways that you're all working to educate the public on TB and how can we help end any stigma surrounding it?
There’s a lot of resources out there. I think one of the areas that PRA’s Center for Vaccine Research is focusing on right now is the attention to public health.
The Centers for Disease and Control Prevention (CDC) has resources, the World Health Organization (WHO) has resources, and the United Nations has resources that we can tack onto. It’s one thing to have the tools in your toolbox. But it might not resonate with people, or you might not have the ability to effectively deliver that message to communities where it's most needed. In that case, pretty little messages on paper or on a screen won’t do a lot of good.
I think that's something that needs to be looked into more closely—more effective ways to communicate this message in a way that's receptive to at-risk people.
It’s important to consider how dense society is in some of these other countries, like in sub-Saharan Africa. In the US, I can go to the grocery store, get my stuff, and hardly have to come within 10 feet of somebody. I can self-checkout. That’s radically different than the density of population in Asian and Africa. It just makes it so much more difficult to control.
What are some ways that the world can help to stop the progression of TB?
There are immunization programs and there's testing. But there's actually a much more accurate blood test.
Just using proper precautions when you're coughing and sneezing—that’s important. This is a droplet illness, so you want to be careful. It’s one of those diseases that can be latent in your body for a long time, and then all the sudden it starts to manifest. That's when you become contagious. You might not even be aware, and that's the hallmark of the disease—it can be very quiet initially.
When it comes to preventing TB from becoming more and more of an issue, how might you address concerns people might have about getting the vaccine? How would we encourage them to get it if they aren't necessarily aware that they should be getting it?
Nothing motivates people to get a vaccine faster than having a circulating disease, and nothing will stop a society from getting a vaccine faster than when diseases aren’t prevalent.
That's exactly why you see more widespread vaccine use in other countries where TB is more prevalent. Remember, this is not a great vaccine, and there are studies going on right now to try to improve that vaccine. But something is better than nothing, and the more you see the disease, the more at risk you are—it’s more likely you’ll sign up and get vaccinated.
Resistance to getting a vaccine is kind of a first world problem, simply because the disease isn’t readily apparent to us, so we're not going to take that vaccine. That’s not something you see in other countries for other diseases where they’re circulating.
Think about what we saw a few years ago, where the US was trying to get the uptake of HPV vaccine. Now HPV is typically seen as vaccine for a sexually transmitted disease, but the truth is, it wasn't obvious to society that there was a need.
It’s a preventative for cancer later in life. However, not many of us think that it's necessary to get a vaccine for something that you may or may not get. You're not really sure how you get it, and don't know that much.
Education is the primary mechanism. We've done a lot to educate society about HPV. Currently there is a push to get trials for a meningitis vaccine for infants. We've ran our medical informatics against it and there's just not much circulating meningitis in infants. But if you get it, there's a high mortality rate. Nobody talks about it. Nobody knows about it. So, it's very difficult to run a clinical trial for a study where nobody knows about it.
If you're a teenager or a parent of a teenager going to college, you definitely hear about it because it’s a disease that you get when you're in close contact with others. We definitely vaccinate our teenagers, but do we really want to add one more vaccination to an infant? No matter the vaccine, it’s really about education and making sure people understand why and what the risks are for getting the disease.
Regarding recent innovations in our industry around clinical research, what have been the big dates or big markers that have occurred with this vaccine?
There's always the advent of the vaccine. There's been the advent of social messaging, and also just flat-out public health messaging around TB. Anytime there is a disease identified that is a contagious disease, one that puts populations at risk, your first line is obviously to try to look for a vaccine while you're working on ways to treat the disease.
But then there's also public health measures that would have gotten put in place. The BCG vaccine took over 13 years to develop, from 1908 to 1921. That was the last time we've seen an improvement in the vaccine.
Just like in any other vaccine, over time there's going to be new development and therefore you're going to try to improve upon those vaccines. The TB vaccine is just one of those vaccines that’s complicated to address. There's really no significant development to improve it. But right now, there are clinical trials that are looking to improve the overall efficacy of the vaccine and also probably make it more effective against respiratory illness.
- “Tuberculosis Vaccine Development.” World Health Organization, World Health Organization, 16 Jan. 2020, www.who.int/immunization/research/development/tuberculosis/en/.
- Voss, Gerald et al. “Progress and challenges in TB vaccine development.” F1000Research vol. 7 199. 16 Feb. 2018, doi:10.12688/f1000research.13588.1
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