Q&A: What malaria and TB can teach us about HIV

Tuberculosis and malaria are diseases that have existed in the human population for thousands of years. Although effective treatments for both conditions are now available, new cases of these diseases continue to be seen each year.

TB is a treatable and curable disease, and the four primary treatments for this disease have been in existence since the mid-20th century. Yet in 1993, WHO declared TB to be a global emergency, and in 2015, TB surpassed HIV as the leading cause of infectious disease deaths globally.

Alana Sharp
Alana R. Sharp

Similarly, an effective treatment currently exists for malaria. This treatment lasts for 3 days and yields total clearance of the parasite. Nevertheless, more than 200 million cases of malaria and almost 430,000 deaths occurred in 2015.

Given the recalcitrant presence of these diseases in the face of effective treatment, a report by amfAR, the Foundation for AIDS Research, cautions against prematurely forecasting “the end of AIDS” in a similar fashion. In the report, “How Cures Can Fail,” amfAR advises learning from the disease trajectories of TB and malaria, and applying those lessons to the ongoing battle against HIV and AIDS. Although the report does not seek to hinder ambitious goals for curing HIV, it emphasizes that effective treatments and cures are only one step in controlling a disease.

Infectious Disease News spoke with Alana R. Sharp, policy associate at amfAR, about the lessons learned from TB and malaria, and how this knowledge can be used to improve treatment of HIV/AIDS. – by Jennifer Byrne

What lessons can be learned through the histories of TB and malaria?

I think the history of TB and malaria are very interesting because these diseases have been around for a very long time. We think they’ve been infecting and killing people for thousands of years. In the 20th century, we saw a lot of successes. We started to develop treatments. We found antimicrobials that completely cured TB. We developed chloroquine, which cures malaria, and related to malaria, we developed DDT to control mosquitoes.  I think it was a big shift where suddenly, these diseases were treatable and actually curable.

We discuss in our report how there was actually so much excitement and optimism around malaria that in the 1950s, WHO rolled out its Global Malaria Eradication Program, with the idea being that we could actually eradicate malaria by spraying with DDT and treating everyone. Yet here we are today, and it’s something like 2 million people each year dying from TB or malaria. The eradication program was eventually dropped, and in some of the countries where it was focused, the incidence rates were actually higher when they abandoned the program than when they started it.

Why is it that these treatments and cures have not stopped the incidence of new cases and deaths from these diseases?

I think there are a lot of issues that contribute to ongoing cases and deaths. The three we are talking about are not identifying people who have the diseases, the growing problem of drug resistance that makes the therapies we have ineffective, and failure to maintain our commitment to research and development for new diagnostic technologies, new drugs and new implementation strategies to deliver these treatments to people.

What role does the failure to identify or diagnose these conditions play in their ongoing presence?

It’s a huge problem. The stats we have are that something like 63% of people who have TB are ever diagnosed, and according to one estimate, it’s about 10% of malaria cases that are actually identified. So, we can have the best treatments in the world, but if we don’t find the people who have the disease, you’re not going to be able to treat them.

There are a few reasons for this failure to identify TB and malaria patients. One of them is what we call presumptive diagnosis or syndromic management. This is where you treat patients without actually going through the appropriate formal diagnostic procedures. So, with malaria, if a kid comes in with a fever, you might assume that this person has malaria, or if someone comes in with a cough that isn’t going away, you might assume they have TB.

Why is presumptive diagnosis used?

The tests are all so difficult — they take a long time. Some of them are inaccurate. I think with a case of malaria, you really need to have good staff training and high-quality equipment for the diagnostic tests that we have to actually be effective. So, if we’re not finding the people, we can’t treat them, and then they go back into their communities and continue to transmit to people around them. This actually relates to the issue of drug resistance — when you don’t identify what is causing a person’s symptoms, then you’re possibly give them the wrong treatment. It can work, or it can contribute to increasing drug resistance.

The lack of identification has been a big problem, and I think we’re seeing that in the case of HIV, absolutely. Right now, about half of the people in the world living with HIV today don’t know they’re infected. Here in Africa, it’s less than half. That’s a huge issue. It’s a little bit different from TB and malaria; with HIV, it’s not as though people are going to be given the wrong medications if they’re not diagnosed appropriately. It just means they’re not in care.  Based on some of the information we’ve discovered recently, we know that if a patient is on treatment, they reduce the risk of transmission by 96%, so we’re also missing this opportunity to prevent new infections.

How much of a problem is drug resistance in controlling these diseases?

I think multidrug resistant TB, and just drug resistance overall, is becoming a big deal. It’s not something we’ve thought about so much in the context of HIV. We’ve had some drug resistance in the United States and high-income countries, but as we start to develop treatment programs, we’re starting to see it in middle and low-income countries, and we have to learn from our experiences with TB, because it becomes very expensive. It becomes very difficult to treat patients, and we start to get much higher mortality, if our drugs stop working.

We’ve also seen it with malaria. Chloroquine is one of the major drugs, and drug resistance to it is everywhere. There have been some outbreaks of multidrug-resistant malaria in some Southeast Asian countries.
I don’t think we are at the point with malaria where we’re losing the ability to treat patients, but it’s always an issue with infectious disease.

What measures can be taken to combat drug resistance?

We need to identify drug resistance at the time of diagnosis; we need to monitor patients’ responses to drugs and be proactive in ensuring that patients are adhering to treatment. We’ve actually seen some things just recently about some countries in Africa where viral load suppression among young people was less than 50%, so we need to make sure we are reaching all the populations and making sure they stay on treatment, because if they go off treatment, that’s when you start to see drug resistance.

The report also mentions late diagnosis and treatment as contributing to a greater likelihood of mortality. What are the reasons for late diagnosis?

We have really good data that show that people who get on treatment later have much worse prognoses. Patients who are identified at late stages are more than 10 times more likely to die in a year, so we have to address that and bring people into testing. That’s going to be dealing with issues like stigma or fear of diagnosis, or cost to the patient; things like that.

I think there’s a lot of fear of diagnosis, and it’s a big barrier to people getting tested, because they don’t want to know. They’re worried about having a lifetime of taking medication, so it can still be a death sentence for people who are not diagnosed appropriately, who are not on treatment, or are not staying on treatment.

HIV is less deadly today than it was when it was first identified, yet new cases continue to emerge. How might this disease trajectory be similar to those observed with TB and malaria?

The development of treatment has been huge in making both of those diseases less deadly over time, so I think that is a big deal. Recently, though, with TB we’re basically using the same treatments we have since the 1960s. Bedaquiline is a drug that has come out fairly recently, but other than that, we really haven’t made much  progress in developing new drugs. With TB, that’s a bit of a problem, because we have difficult side effects from the treatments we’re using right now. This makes it more difficult for patients to continue taking their drugs.

How might geography or socioeconomic status affect the ability to control any of these diseases?

I think HIV is a disease where we talk a lot about key populations, with those being groups that have a higher risk of becoming infected with HIV. I don’t see that happening quite as much with TB, and certainly not with malaria. We do see socioeconomic disparities as a barrier to accessing care if it’s not affordable to the patient.

On this topic, there is the issue of the way we treat TB. Oftentimes, because we’re very concerned about drug resistance, we require patients to take their medications while a clinician or health care worker is watching to ensure that the patient actually takes the medicine. What that can mean is that some people have to go to the health clinic every day or several times a week. As you might imagine, those costs add up. The patient has to take a day off work, find child care, pay for transportation. These kinds of costs build up and can contribute to people dropping out of care.

In terms of geography, one of the risk factors for TB infection is living in crowded environments, so things like living in an urban slum would predict infection. As far as access to care, if you’re living in a rural area, it’s a lot harder to get anywhere. You’re not going to have clinics nearby to provide appropriate treatment.

What steps does the recent report advise in terms of applying the lessons of TB and malaria to HIV, and also to improved control of those diseases?

Looking at it from the perspective of that brief, we imagined a hypothetical world where suddenly we have a cure for HIV, and we thought about what that would mean, what it would take to get there, and what we could learn from TB and malaria to achieve that.

What we came up with is that we would have to quickly and effectively find every single person with HIV to bring them back for treatment. We have to be really proactive about quickly and immediately diagnosing whether new infections are drug resistant, and implementing things like viral load monitoring to determine immediately when HIV treatments are failing due to drug resistance.

We would also have to do things like provide a supportive environment for patients with HIV, to help them stay on their treatment and stay healthy. Another big thing will be funding ongoing research so that we have new diagnostic tools and new cures, because we know from TB and malaria that having one cure or one treatment is not the end of the story.

The need for ongoing funding is mentioned in the report. Can you address the importance of this?

Just in terms of where we are right now, I think we’re also in a bit of a crossroads with funding generally. Just recently, we’ve been hearing about how the new administration is talking about cutting the budgets of PEPFAR and USAID by maybe 37%, so I think it’s very important for us that we make clear that, although our HIV response is a small part of the budget, we need to continue to maintain our focus, because otherwise, we could lose that funding.

Where does research stand right now on HIV, malaria and TB?

I know TB right now has some very exciting things coming out in terms of diagnostics, and the idea is that we are going for a diagnostic technology that can tell you the full drug resistance profile of the TB you are infected with.
Then there are some drugs coming out; they’re going through the pipelines, and we’ll see how that goes. There’s a lot of work in malaria about diagnostic tests, also.

In HIV, we have some really exciting research on long-acting formulations, medications you can take in an injectable form and not have to go back and take pills every day. That’s an exciting development.

References:

amfAR. How Cures Can Fail. http://www.amfar.org/uploadedFiles/_amfarorg/Articles/On_The_Hill/2017/DC-2016-How-Cures-Fail-011117-Web.pdf. Accessed March 8, 2017.

Grange JM, Zumla A. J R Soc Promot Health. 2002;122:78-81.

WHO. Global tuberculosis report 2016. http://apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf. Access March 8, 2017.

WHO. Malaria. http://www.who.int/mediacentre/factsheets/fs094/en. Accessed March 8, 2017.

For more information:

Alana R. Sharp can be reached at amfAR, 1100 Vermont Avenue, NW, Suite 600, Washington, D.C. 20005; email: alana.sharp@amfar.org.

Disclosure: Sharp reports no relevant disclosures.

Tuberculosis and malaria are diseases that have existed in the human population for thousands of years. Although effective treatments for both conditions are now available, new cases of these diseases continue to be seen each year.

TB is a treatable and curable disease, and the four primary treatments for this disease have been in existence since the mid-20th century. Yet in 1993, WHO declared TB to be a global emergency, and in 2015, TB surpassed HIV as the leading cause of infectious disease deaths globally.

Alana Sharp
Alana R. Sharp

Similarly, an effective treatment currently exists for malaria. This treatment lasts for 3 days and yields total clearance of the parasite. Nevertheless, more than 200 million cases of malaria and almost 430,000 deaths occurred in 2015.

Given the recalcitrant presence of these diseases in the face of effective treatment, a report by amfAR, the Foundation for AIDS Research, cautions against prematurely forecasting “the end of AIDS” in a similar fashion. In the report, “How Cures Can Fail,” amfAR advises learning from the disease trajectories of TB and malaria, and applying those lessons to the ongoing battle against HIV and AIDS. Although the report does not seek to hinder ambitious goals for curing HIV, it emphasizes that effective treatments and cures are only one step in controlling a disease.

Infectious Disease News spoke with Alana R. Sharp, policy associate at amfAR, about the lessons learned from TB and malaria, and how this knowledge can be used to improve treatment of HIV/AIDS. – by Jennifer Byrne

What lessons can be learned through the histories of TB and malaria?

I think the history of TB and malaria are very interesting because these diseases have been around for a very long time. We think they’ve been infecting and killing people for thousands of years. In the 20th century, we saw a lot of successes. We started to develop treatments. We found antimicrobials that completely cured TB. We developed chloroquine, which cures malaria, and related to malaria, we developed DDT to control mosquitoes.  I think it was a big shift where suddenly, these diseases were treatable and actually curable.

We discuss in our report how there was actually so much excitement and optimism around malaria that in the 1950s, WHO rolled out its Global Malaria Eradication Program, with the idea being that we could actually eradicate malaria by spraying with DDT and treating everyone. Yet here we are today, and it’s something like 2 million people each year dying from TB or malaria. The eradication program was eventually dropped, and in some of the countries where it was focused, the incidence rates were actually higher when they abandoned the program than when they started it.

Why is it that these treatments and cures have not stopped the incidence of new cases and deaths from these diseases?

I think there are a lot of issues that contribute to ongoing cases and deaths. The three we are talking about are not identifying people who have the diseases, the growing problem of drug resistance that makes the therapies we have ineffective, and failure to maintain our commitment to research and development for new diagnostic technologies, new drugs and new implementation strategies to deliver these treatments to people.

PAGE BREAK

What role does the failure to identify or diagnose these conditions play in their ongoing presence?

It’s a huge problem. The stats we have are that something like 63% of people who have TB are ever diagnosed, and according to one estimate, it’s about 10% of malaria cases that are actually identified. So, we can have the best treatments in the world, but if we don’t find the people who have the disease, you’re not going to be able to treat them.

There are a few reasons for this failure to identify TB and malaria patients. One of them is what we call presumptive diagnosis or syndromic management. This is where you treat patients without actually going through the appropriate formal diagnostic procedures. So, with malaria, if a kid comes in with a fever, you might assume that this person has malaria, or if someone comes in with a cough that isn’t going away, you might assume they have TB.

Why is presumptive diagnosis used?

The tests are all so difficult — they take a long time. Some of them are inaccurate. I think with a case of malaria, you really need to have good staff training and high-quality equipment for the diagnostic tests that we have to actually be effective. So, if we’re not finding the people, we can’t treat them, and then they go back into their communities and continue to transmit to people around them. This actually relates to the issue of drug resistance — when you don’t identify what is causing a person’s symptoms, then you’re possibly give them the wrong treatment. It can work, or it can contribute to increasing drug resistance.

The lack of identification has been a big problem, and I think we’re seeing that in the case of HIV, absolutely. Right now, about half of the people in the world living with HIV today don’t know they’re infected. Here in Africa, it’s less than half. That’s a huge issue. It’s a little bit different from TB and malaria; with HIV, it’s not as though people are going to be given the wrong medications if they’re not diagnosed appropriately. It just means they’re not in care.  Based on some of the information we’ve discovered recently, we know that if a patient is on treatment, they reduce the risk of transmission by 96%, so we’re also missing this opportunity to prevent new infections.

How much of a problem is drug resistance in controlling these diseases?

I think multidrug resistant TB, and just drug resistance overall, is becoming a big deal. It’s not something we’ve thought about so much in the context of HIV. We’ve had some drug resistance in the United States and high-income countries, but as we start to develop treatment programs, we’re starting to see it in middle and low-income countries, and we have to learn from our experiences with TB, because it becomes very expensive. It becomes very difficult to treat patients, and we start to get much higher mortality, if our drugs stop working.

We’ve also seen it with malaria. Chloroquine is one of the major drugs, and drug resistance to it is everywhere. There have been some outbreaks of multidrug-resistant malaria in some Southeast Asian countries.
I don’t think we are at the point with malaria where we’re losing the ability to treat patients, but it’s always an issue with infectious disease.

PAGE BREAK

What measures can be taken to combat drug resistance?

We need to identify drug resistance at the time of diagnosis; we need to monitor patients’ responses to drugs and be proactive in ensuring that patients are adhering to treatment. We’ve actually seen some things just recently about some countries in Africa where viral load suppression among young people was less than 50%, so we need to make sure we are reaching all the populations and making sure they stay on treatment, because if they go off treatment, that’s when you start to see drug resistance.

The report also mentions late diagnosis and treatment as contributing to a greater likelihood of mortality. What are the reasons for late diagnosis?

We have really good data that show that people who get on treatment later have much worse prognoses. Patients who are identified at late stages are more than 10 times more likely to die in a year, so we have to address that and bring people into testing. That’s going to be dealing with issues like stigma or fear of diagnosis, or cost to the patient; things like that.

I think there’s a lot of fear of diagnosis, and it’s a big barrier to people getting tested, because they don’t want to know. They’re worried about having a lifetime of taking medication, so it can still be a death sentence for people who are not diagnosed appropriately, who are not on treatment, or are not staying on treatment.

HIV is less deadly today than it was when it was first identified, yet new cases continue to emerge. How might this disease trajectory be similar to those observed with TB and malaria?

The development of treatment has been huge in making both of those diseases less deadly over time, so I think that is a big deal. Recently, though, with TB we’re basically using the same treatments we have since the 1960s. Bedaquiline is a drug that has come out fairly recently, but other than that, we really haven’t made much  progress in developing new drugs. With TB, that’s a bit of a problem, because we have difficult side effects from the treatments we’re using right now. This makes it more difficult for patients to continue taking their drugs.

How might geography or socioeconomic status affect the ability to control any of these diseases?

I think HIV is a disease where we talk a lot about key populations, with those being groups that have a higher risk of becoming infected with HIV. I don’t see that happening quite as much with TB, and certainly not with malaria. We do see socioeconomic disparities as a barrier to accessing care if it’s not affordable to the patient.

On this topic, there is the issue of the way we treat TB. Oftentimes, because we’re very concerned about drug resistance, we require patients to take their medications while a clinician or health care worker is watching to ensure that the patient actually takes the medicine. What that can mean is that some people have to go to the health clinic every day or several times a week. As you might imagine, those costs add up. The patient has to take a day off work, find child care, pay for transportation. These kinds of costs build up and can contribute to people dropping out of care.

In terms of geography, one of the risk factors for TB infection is living in crowded environments, so things like living in an urban slum would predict infection. As far as access to care, if you’re living in a rural area, it’s a lot harder to get anywhere. You’re not going to have clinics nearby to provide appropriate treatment.

PAGE BREAK

What steps does the recent report advise in terms of applying the lessons of TB and malaria to HIV, and also to improved control of those diseases?

Looking at it from the perspective of that brief, we imagined a hypothetical world where suddenly we have a cure for HIV, and we thought about what that would mean, what it would take to get there, and what we could learn from TB and malaria to achieve that.

What we came up with is that we would have to quickly and effectively find every single person with HIV to bring them back for treatment. We have to be really proactive about quickly and immediately diagnosing whether new infections are drug resistant, and implementing things like viral load monitoring to determine immediately when HIV treatments are failing due to drug resistance.

We would also have to do things like provide a supportive environment for patients with HIV, to help them stay on their treatment and stay healthy. Another big thing will be funding ongoing research so that we have new diagnostic tools and new cures, because we know from TB and malaria that having one cure or one treatment is not the end of the story.

The need for ongoing funding is mentioned in the report. Can you address the importance of this?

Just in terms of where we are right now, I think we’re also in a bit of a crossroads with funding generally. Just recently, we’ve been hearing about how the new administration is talking about cutting the budgets of PEPFAR and USAID by maybe 37%, so I think it’s very important for us that we make clear that, although our HIV response is a small part of the budget, we need to continue to maintain our focus, because otherwise, we could lose that funding.

Where does research stand right now on HIV, malaria and TB?

I know TB right now has some very exciting things coming out in terms of diagnostics, and the idea is that we are going for a diagnostic technology that can tell you the full drug resistance profile of the TB you are infected with.
Then there are some drugs coming out; they’re going through the pipelines, and we’ll see how that goes. There’s a lot of work in malaria about diagnostic tests, also.

In HIV, we have some really exciting research on long-acting formulations, medications you can take in an injectable form and not have to go back and take pills every day. That’s an exciting development.

References:

amfAR. How Cures Can Fail. http://www.amfar.org/uploadedFiles/_amfarorg/Articles/On_The_Hill/2017/DC-2016-How-Cures-Fail-011117-Web.pdf. Accessed March 8, 2017.

Grange JM, Zumla A. J R Soc Promot Health. 2002;122:78-81.

WHO. Global tuberculosis report 2016. http://apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf. Access March 8, 2017.

WHO. Malaria. http://www.who.int/mediacentre/factsheets/fs094/en. Accessed March 8, 2017.

For more information:

Alana R. Sharp can be reached at amfAR, 1100 Vermont Avenue, NW, Suite 600, Washington, D.C. 20005; email: alana.sharp@amfar.org.

Disclosure: Sharp reports no relevant disclosures.