Why Neglected Tropical Diseases Should Matter to Americans
Daisy Hernández was five years old when one of her favorite aunts was struck with a mysterious illness. Tía Dora had stayed behind in Colombia when Daisy's mother immigrated to Union City, New Jersey. A schoolteacher in her late 20s, she began suffering from fevers and abdominal pain, and her belly grew so big that people thought she was pregnant. Exploratory surgery revealed that her large intestine had swollen to ten times its normal size, and she was fitted with a colostomy bag. Doctors couldn't identify the underlying problem—but whatever it was, they said, it would likely kill her within a year or two.
Tía Dora's sisters in New Jersey—Hernández's mother and two other aunts—weren't about to let that happen. They pooled their savings and flew her to New York City, where a doctor at Columbia-Presbyterian Medical Center with a penchant for obscure ailments provided a diagnosis: Chagas disease. Transmitted by the bite of triatomine insects, commonly known as kissing bugs, Chagas is endemic in many parts of Latin America. It's caused by the parasite Trypanoma cruzi, which usually settles in the heart, where it feeds on muscle tissue. In some cases, however, it attacks the intestines or esophagus. Tía Dora belonged to that minority.
In 1980, U.S. immigration laws were more forgiving than they are today. Tía Dora was able to have surgery to remove a part of her colon, despite not being a citizen or having a green card. She eventually married a legal resident and began teaching Spanish at an elementary school. Over the next three decades, she earned a graduate degree, built a career, and was widowed. Meanwhile, Chagas continued its slow devastation. "Every couple of years, we were back in the hospital with her," Hernández recalls. "When I was in high school, she started feeling like she couldn't swallow anything. It was the parasite, destroying the muscles of her esophagus."
When Tía Dora died in 2010, at 59, her niece was among the family members at her bedside. By then, Hernández had become a journalist and fiction writer. Researching a short story about Chagas disease, she discovered that it affected an estimated 6 million people in South America, Central America, and Mexico—as well as 300,000 in the United States, most of whom were immigrants from those places. "I was shocked to learn it wasn't rare," she says. "That made me hungry to know more about this disease, and about the families grappling with it."
Hernández's curiosity led her to write The Kissing Bug, a lyrical hybrid of memoir and science reporting that was published in June. It also led her to another revelation: Chagas is not unique. It's among the many maladies that global health experts refer to as neglected tropical diseases—often-disabling illnesses that afflict 1.7 billion people worldwide, while getting notably less attention than the "big three" of HIV/AIDs, malaria, and tuberculosis. NTDs cause fewer deaths than those plagues, but they wreak untold suffering and economic loss.
Shortly before Hernández's book hit the shelves, the World Health Organization released its 2021-2030 roadmap for fighting NTDs. The plan sets targets for controlling, eliminating, or eradicating all the diseases on the WHO's list, through measures ranging from developing vaccines to improving healthcare infrastructure, sanitation, and access to clean water. Experts agree that for the campaign to succeed, leadership from wealthy nations—particularly the United States—is essential. But given the inward turn of many such countries in recent years (evidenced in movements ranging from America First to Brexit), and the continuing urgency of the COVID-19 crisis, public support is far from guaranteed.
As Hernández writes: "It is easier to forget a disease that cannot be seen." NTDs primarily affect residents of distant lands. They kill only 80,000 people a year, down from 204,000 in 1990. So why should Americans to bother to look?
Breaking the circle of poverty and disease
The World Health Organization counts 20 diseases as NTDs. Along with Chagas, they include dengue and chikungunya, which cause high fevers and agonizing pain; elephantiasis, which deforms victims' limbs and genitals; onchocerciasis, which causes blindness; schistosomiasis, which can damage the heart, lungs, brain, and genitourinary system; helminths such as roundworm and whipworm, which cause anemia, stunted growth, and cognitive disabilities; and a dozen more. Such ailments often co-occur in the same patient, exacerbating each other's effects and those of illnesses such as malaria.
NTDs may be spread by insects, animals, soil, or tainted water; they may be parasitic, bacterial, viral, or—in the case of snakebite envenoming—non-infectious. What they have in common is their longtime neglect by public health agencies and philanthropies. In part, this reflects their typically low mortality rates. But the biggest factor is undoubtedly their disempowered patient populations.
"These diseases occur in the setting of poverty, and they cause poverty, because of their chronic and debilitating effects," observes Peter Hotez, dean of the National School of Tropical Medicine at Baylor University and co-director of the Texas Children's Hospital for Vaccine Development. And historically, the everyday miseries of impoverished people have seldom been a priority for those who set the global health agenda.
That began to change about 20 years ago, when Hotez and others developed the conceptual framework for NTDs and early proposals for combating them. The WHO released its first roadmap in 2012, targeting 17 NTDs for control, elimination, or eradication by 2020. (Rabies, snakebite, and dengue were added later.) Since then, the number of people at risk for NTDs has fallen by 600 million, and 42 countries have eliminated at least one such disease. Cases of dracunculiasis—known as Guinea worm disease, for the parasite that creates painful blisters in a patient's skin—have dropped from the millions to just 27 in 2020.
Yet the battle is not over, and the COVID-19 pandemic has disrupted prevention and treatment programs around the globe.
A new direction — and longstanding obstacles
The WHO's new roadmap sets even more ambitious goals for 2030. Among them: reducing by 90 percent the number of people requiring treatment for NTDs; eliminating at least one NTD in another 100 countries; and fully eradicating dracunculiasis and yaws, a disfiguring skin infection.
The plan also places an increased focus on "country ownership," relying on nations with high incidence of NTDs to design their own plans based on local expertise. "I was so excited to see that," says Kristina Talbert-Slagle, director of the Yale College Global Health Studies program. "No one is a better expert on how to address these situations than the people who deal with it day by day."
Another fresh approach is what the roadmap calls "cross-cutting" targets. "One of the really cool things about the plan is how much it emphasizes coordination among different sectors of the health system," says Claire Standley, a faculty member at Georgetown University's Center for Global Health Science and Security. "For example, it explicitly takes into account the zoonotic nature of many neglected tropical diseases—the fact that we have to think about animal health as well as human health when we tackle NTDs."
Whether this grand vision can be realized, however, will depend largely on funding—and that, in turn, is a question of political will in the countries most able to provide it. On the upside, the U.S. has ended its Trump-era feud with the WHO. "One thing that's been really encouraging," says Standley, "has been the strong commitment toward global cooperation from the current administration." Even under the previous president, the U.S. remained the single largest contributor to the global health kitty, spending over $100 million annually on NTDs—six times the figure in 2006, when such financing started.
On the downside, America's outlay has remained flat for several years, and the Biden administration has so far not moved to increase it. A "back-of-the-envelope calculation," says Hotez, suggests that the current level of aid could buy medications for the most common NTDs for about 200 million people a year. But the number of people who need treatment, he notes, is at least 750 million.
Up to now, the United Kingdom—long the world's second-most generous health aid donor—has taken up a large portion of the slack. But the UK last month announced deep cuts in its portfolio, eliminating 102 previously supported countries and leaving only 34. "That really concerns me," Hotez says.
The struggle for funds, he notes, is always harder for projects involving NTDs than for those aimed at higher-profile diseases. His lab, which he co-directs with microbiologist Maria Elena Bottazzi, started developing a COVID-19 vaccine soon after the pandemic struck, for example, and is now in Phase 3 trials. The team has been working on vaccines for Chagas, hookworm, and schistosomiasis for much longer, but trials for those potential game-changers lag behind. "We struggle to get the level of resources needed to move quickly," Hotez explains.
Two million reasons to care
One way to prompt a government to open its pocketbook is for voters to clamor for action. A longtime challenge with NTDs, however, has been getting people outside the hardest-hit countries to pay attention.
The reasons to care, global health experts argue, go beyond compassion. "When we have high NTD burden," says Talbert-Slagle, "it can prevent economic growth, prevent innovation, lead to more political instability." That, in turn, can lead to wars and mass migration, affecting economic and political events far beyond an affected country's borders.
Like Hernández's aunt Dora, many people driven out of NTD-wracked regions wind up living elsewhere. And that points to another reason to care about these diseases: Some of your neighbors might have them. In the U.S., up to 14 million people suffer from neglected parasitic infections—including 70,000 with Chagas in California alone.
When Hernández was researching The Kissing Bug, she worried that such statistics would provide ammunition to racists and xenophobes who claim that immigrants "bring disease" or exploit overburdened healthcare systems. (This may help explain some of the stigma around NTDs, which led Tía Dora to hide her condition from most people outside her family.) But as the book makes clear, these infections know no borders; they flourish wherever large numbers of people lack access to resources that most residents of rich countries take for granted.
Indeed, far from gaming U.S. healthcare systems, millions of low-income immigrants can't access them—or must wait until they're sick enough to go to an emergency room. Since Congress changed the rules in 1996, green card holders have to wait five years before they can enroll in Medicaid. Undocumented immigrants can never qualify.
Closing the great divide
Hernández uses a phrase borrowed from global health crusader Paul Farmer to describe this access gap: "the great epi divide." On one side, she explains, "people will die from cancer, from diabetes, from chronic illnesses later in life. On the other side of the epidemiological divide, people are dying because they can't get to the doctor, or they can't get medication. They don't have a hospital anywhere near them. When I read Dr. Farmer's work, I realized how much that applied to neglected diseases as well."
When it comes to Chagas disease, she says, the epi divide is embodied in the lack of a federal mandate for prenatal or newborn screening. Each year, according to the Centers for Disease Control and Prevention, up to 300 babies in the U.S. are born with Chagas, which can be passed from the mother in utero. The disease can be cured with medication if treated in infancy. (It can also be cured in adults in the acute stage, but is seldom detected in time.) Yet the CDC does not require screening for Chagas—even though newborns are tested for 15 diseases that are less common. According to one study, it would be 10 times cheaper to screen and treat babies and their mothers than to cover the costs related to the illness in later years. Few states make the effort.
The gap that enables NTDs to persist, Hernández argues, is the same one that has led to COVID-19 death rates in Black and Latinx communities that are double those elsewhere in America. To close it, she suggests, caring is not enough.
"When I was working on my book," she says, "I thought about HIV in the '80s, when it had so much stigma that no one wanted to talk about it. Then activists stepped up and changed the conversation. I thought a lot about breast cancer, which was stigmatized for years, until people stepped forward and started speaking out. I thought about Lyme disease. And it wasn't only patients—it was also allies, right? The same thing needs to happen with neglected diseases around the world. Allies need to step up and make demands on policymakers. We need to make some noise."
Podcast: The Friday Five - your health research roundup
The Friday Five is a new podcast series in which Leaps.org covers five breakthroughs in research over the previous week that you may have missed. There are plenty of controversies and ethical issues in science – and we get into many of them in our online magazine – but there’s also plenty to be excited about, and this news roundup is focused on inspiring scientific work to give you some momentum headed into the weekend.
Covered in this week's Friday Five:
- Puffer fish chemical for treating chronic pain
- Sleep study on the health benefits of waking up multiples times per night
- Best exercise regimens for reducing the risk of mortality aka living longer
- AI breakthrough in mapping protein structures with DeepMind
- Ultrasound stickers to see inside your body
CandyCodes could provide sweet justice against fake pills
When we swallow a pill, we hope it will work without side effects. Few of us know to worry about a growing issue facing the pharmaceutical industry: counterfeit medications. These pills, patches, and other medical products might look just like the real thing. But they’re often stuffed with fillers that dilute the medication’s potency or they’re simply substituted for lookalikes that contain none of the prescribed medication at all.
Now, bioengineer William Grover at the University of California, Riverside, may have a solution. Inspired by the tiny, multi-colored sprinkles called nonpareils that decorate baked goods and candies, Grover created CandyCodes pill coatings to prevent counterfeits.
The idea was borne out of pandemic boredom. Confined to his home, Grover was struck by the patterns of nonpareils he saw on candies, and found himself counting the number of little balls on each one. “It’s random, how they’re applied,” he says. “I wondered if it ever repeats itself or if each of these candies is unique in the entire world.” He suspected the latter, and some quick math proved his hypothesis: Given dozens of nonpareils per candy in a handful of different colors, it’s highly unlikely that the sprinklings on any two candies would be identical.
He quickly realized his finding could have practical applications: pills or capsules could be coated with similar “sprinkles,” with the manufacturer photographing each pill or capsule before selling its products. Consumers looking to weed out fakes could potentially take a photo with their cell phones and go online to compare images of their own pills to the manufacturer’s database, with the help of an algorithm that would determine their authenticity. Or, a computer could generate another type of unique identifier, such as a text-based code, tracking to the color and location of the sprinkles. This would allow for a speedier validation than a photo-based comparison, Grover says. “It could be done very quickly, in a fraction of a second.”
Researchers and manufacturers have already developed some anti-counterfeit tools, including built-in identifiers like edible papers with scannable QR codes. But such methods, while functional, can be costly to implement, Grover says.
It wouldn’t be paranoid to take such precautions. Counterfeits are a growing problem, according to Young Kim, a biomedical engineer at Purdue University who was not involved in the CandyCodes study. “There are approximately 40,000 online pharmacies that one can access via the Internet,” he says. “Only three to four percent of them are operated legally.” Purchases from online pharmacies rose dramatically during the pandemic, and Kim expects a boom in counterfeit medical products alongside it.
The FDA warns that U.S. consumers can be exposed to counterfeits through online purchases, in particular. The problem is magnified in low- to middle-income nations, where one in 10 medical products are counterfeit, according to a World Health Organization estimate. Cost doesn’t seem to be a factor, either; antimalarials and antibiotics are most often reported as counterfeits or fakes, and generic medications are swapped as often as brand-name drugs, according to the same WHO report.
Counterfeits weren’t tracked globally until 2013; since then, there have been 1,500 reports to the WHO, with actual incidences of counterfeiting likely much higher. Fake medicines have been estimated to result in costs of $200 billion each year, and are blamed for more than 72,000 pneumonia- and 116,000 malaria-related deaths.
Researchers and manufacturers have already developed some anti-counterfeit tools, including built-in identifiers like edible papers with scannable QR codes or barcodes that are stamped onto or otherwise incorporated into pills and other medical products. But such methods, while functional, can be costly to implement, Grover says.
CandyCodes could provide unique identifiers for at least 41 million pills for every person on the planet.
William Grover
“Putting universal codes on each pill and each dosage is attractive,” he says. “The challenge is, how can we do it in a way that requires as little modification to the existing manufacturing process as possible? That's where I hope CandyCodes have an edge. It's not zero modification, but I hope it is as minor a modification of the manufacturing process as possible.”
Kim calls the concept “a clever idea to introduce entropy for high-level security” even if it may not be as close to market as other emerging technologies, including some edible watermarks he’s helped develop. He points out that CandyCodes still needs to be tested for reproducibility and readability.
The possibilities are already intriguing, though. Grover’s recent research, published in Scientific Reports, predicts that unique codes could be used for at least 41 million pills for every person on the planet.
Sadly, CandyCodes’ multicolored bits probably won’t taste like candy. They must be made of non-caloric ingredients to meet the international regulatory standards that govern food dyes and colorants. But Grover hopes CandyCodes represent a simple, accessible solution to a heart-wrenching issue. “This feels like trying to track down and go after bad guys,” he says. “Someone who would pass off a medicine intended for a child or a sick person and pass it off as something effective, I can't imagine anything much more evil than that. It's fun and, and a little fulfilling to try to develop technologies that chip away at that.”