Neglected Tropical Diseases Q&A With Dr. Laura-Isobel McCall

April 14, 2022

Laura-Isobel McCall, Ph.D., from the University of Oklahoma provides an overview of strategies for preventing, mitigating, treating and ultimately eliminating, Neglected Tropical Diseases.

Video Transcript

Q1- How Would You Define a Neglected Tropical Disease [NTD]?

Answer: "I think it comes in 3 parts. There's the disease part, of course—most of them are infectious. So there are 20 official NTDs: 19 are infectious, and then the last 1 is snake bite, which is not.
 
The tropical part, I think, is a bit of a misnomer. They are primarily associated with tropical, subtropical regions, but many of them you can find in in the US. There's Trypanosoma cruzi in Oklahoma, and I think no one would describe Oklahoma as tropical.

To me, neglected is the most important aspect. It's a condition that affects often the poorest, underserved people. It's being ignored by big pharma—so ignored in terms of drug development—most of the treatments are very old or lacking, most of the diagnostic methods are very old or lacking. And it's also honestly being ignored by a lot of academic research as well, which means that there's huge gaps in knowledge about these diseases."

Q2- What is Chagas Disease?

Answer: "Chagas disease is 1 of the 20 neglected tropical diseases. It's caused by Trypanosoma cruzi parasites. So these are unicellular parasites that are transmitted by kissing bug vectors to humans. And this is a very slow-progressing, long-progressing disease. A lot of people don't know that they become infected, but then the parasite persists in their body for decades. And over the following 20/30/40 years, damage accumulates, especially in the heart, the esophagus and the colon. And that will lead to progressive cardiac damage, ultimately leading to cardiac failure or to megaesophagus/megacolon symptoms.

I think Chagas disease illustrates the issues with NTDs, because there are all these gaps in the field. There's so many things we don't know about Chagas disease and there's so many needs—clinical needs—that intersect with that."

Q3- How are NTD Outbreaks Detected? What is the State of Diagnostics for NTDs? What Areas are Open for Improvement?

Answer: "Methods to diagnose NTDs, I think, are very dependent on which NTD you're talking about. So you won't diagnose a soil-transmitted helminth infection the same way you would diagnose visceral leishmaniasis or Chagas disease. And so for example, for an Ascaris infection, one of the main ways to diagnose is still microscopy on stool samples. For Chagas disease, there are some serological tests, that's the main way. And you can also use techniques like PCR to look for parasite DNA. There are issues with all those different test methods.

Microscopy, it's very time consuming, it requires a skilled operator and sensitivity is often low because you need to be looking through many of those fecal smears, fecal floats to find the parasites. If you look at sero-diagnosis, that can be a lot more specific, but at least in the context of Chagas disease, there's a lot of genetic variability with the parasites. And so those tests don't always work equally well depending on what region you're from, where you got your T. cruzi infection."

Q4- What Sort of Treatment Options Exist for NTDs? What are the Most Promising Ways to Better Cure or Prevent NTDs in the Future?

Answer: "Treatment for NTDs, I think, is again going to depend on which particular NTD you're talking about. So you would treat a snake bite very differently from schistosomiasis. Mass drug administration campaigns are a big part of NTD control strategies. So going into a location, administering treatment to either everyone, or to children under a specific age, and then you would repeat that either annually or at specific age milestones. The idea behind that is to treat all the active infections, but at the same time, that also prevents or reduces community spread, thereby preventing new infections.

With conditions like Chagas disease, the treatment would be only when people present with Chagas disease. The problem is that Chagas is better treated before severe symptoms occur. And so now you have this catch-22 situation where the treatments work best at a time point where patients are unaware of their disease.

If you're trying to find new treatments for Chagas disease, you want a good marker of cure. And right now we don't, which means that if you're running a clinical trial, you need to plan in the ability to follow patients for 5-10 years, which raises the costs of drug development, which is even more problematic for a condition that's so strongly tied to poverty."

Q5- What Factors Contribute to the Appearance and Persistence of NTDs?

Answer: "I think one part of it is financial. There's not much of a financial incentive to develop drugs or treatments for people who won't ever be able to pay for those interventions. A big part of this is healthcare infrastructure, access to care, access to treatments and hospitals, but also primary care physicians.

Community care is also a big aspect. Many of these are vector-borne, and so if you have a breakdown of infrastructure, that will also create places for those vectors to breed and spread those infections. If you don't have access to houses that are closed off, repellents, netting, then you're again at higher risk of exposure.

Poverty is definitely a big factor here because you have a self-reinforcing cycle here where poverty limits access to care. It limits the ability to pay for care, so care is then less available. But at the same time, the disease may make it harder for you to work, harder for a child to pay attention in school. And that reinforces poverty. You have this vicious, reinforcing cycle that goes on.

Climate will play a big role, and I think that's going to be increasingly evident. As climate changes—as places get warmer—I expect the range of many of these conditions to expand."

Q6- What Can Be Done About NTDs?

Answer: "It all starts to me with awareness. So being aware that something is a problem.

The concept of neglected tropical diseases really arose from the idea of needing to give an identity to those other diseases, because if you're just other, you can't build momentum, you can't build willpower around it. But we need to make sure that we're not grouping mechanisms and interventions and solutions all together. Understanding that there's differences between the conditions. Chagas disease is very different from schistosomiasis in terms of pathogenesis, in terms of transmission, in terms of geographic distribution.

I think one of the biggest barriers that people in the United States face with NTDs is that people don't know what they have. They'll go to doctor, they'll be misdiagnosed and they'll be told, "Oh, it's not possible that you have that, there's no such thing in America." And so then you have a situation where people are not getting the care they need. If people know that these conditions exist, and if people avoid stigmatizing people that have those conditions, I think that's something we can all do."
Read more about the biology of Chagas Disease this next article, "Chagas Disease in the U.S.: What We Do and Don't Know."


Author: Geoff Hunt, Ph.D.

Geoff Hunt, Ph.D.
Geoff Hunt earned his Ph.D. in molecular biology from Princeton University.