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."
Two years, six million deaths and still counting, scientists are searching for answers to prevent another COVID-19-like tragedy from ever occurring again. And it’s a gargantuan task.
Our disturbed ecosystems are creating more favorable conditions for the spread of infectious disease. Global warming, deforestation, rising sea levels and flooding have contributed to a rise in mosquito-borne infections and longer tick seasons. Disease-carrying animals are in closer range to other species and humans as they migrate to escape the heat. Bats are thought to have carried the SARS-CoV-2 virus to Wuhan, either directly or through another host animal, but thousands of novel viruses are lurking within other wild creatures.
Understanding how climate change contributes to the spread of disease is critical in predicting and thwarting future calamities. But the problem is that predictive models aren’t yet where they need to be for forecasting with certainty beyond the next year, as we could for weather, for instance.
The association between climate and infectious disease is poorly understood, says Irina Tezaur, a computational scientist at Sandia National Laboratories. “Correlations have been observed but it’s not known if these correlations translate to causal relationships.”
To make accurate longer-term predictions, scientists need more empirical data, multiple datasets specific to locations and diseases, and the ability to calculate risks that depend on unpredictable nature and human behavior. Another obstacle is that climate scientists and epidemiologists are not collaborating effectively, so some researchers are calling for a multidisciplinary approach, a new field called Outbreak Science.
Climate scientists are far ahead of epidemiologists in gathering essential data.
Earth System Models—combining the interactions of atmosphere, ocean, land, ice and biosphere—have been in place for two decades to monitor the effects of global climate change. These models must be combined with epidemiological and human model research, areas that are easily skewed by unpredictable elements, from extreme weather events to public environmental policy shifts.
“There is never just one driver in tracking the impact of climate on infectious disease,” says Joacim Rocklöv, a professor at the Heidelberg Institute of Global Health & Heidelberg Interdisciplinary Centre for Scientific Computing in Germany. Rocklöv has studied how climate affects vector-borne diseases—those transmitted to humans by mosquitoes, ticks or fleas. “You need to disentangle the variables to find out how much difference climate makes to the outcome and how much is other factors.” Determinants from deforestation to population density to lack of healthcare access influence the spread of disease.
Even though climate change is not the primary driver of infectious disease today, it poses a major threat to public health in the future, says Rocklöv.
The promise of predictive modeling
“Models are simplifications of a system we’re trying to understand,” says Jeremy Hess, who directs the Center for Health and the Global Environment at University of Washington in Seattle. “They’re tools for learning that improve over time with new observations.”
Accurate predictions depend on high-quality, long-term observational data but models must start with assumptions. “It’s not possible to apply an evidence-based approach for the next 40 years,” says Rocklöv. “Using models to experiment and learn is the only way to figure out what climate means for infectious disease. We collect data and analyze what already happened. What we do today will not make a difference for several decades.”
To improve accuracy, scientists develop and draw on thousands of models to cover as many scenarios as possible. One model may capture the dynamics of disease transmission while another focuses on immunity data or ocean influences or seasonal components of a virus. Further, each model needs to be disease-specific and often location-specific to be useful.
“All models have biases so it’s important to use a suite of models,” Tezaur stresses.
The modeling scientist chooses the drivers of change and parameters based on the question explored. The drivers could be increased precipitation, poverty or mosquito prevalence, for instance. Later, the scientist may need to isolate the effect of one driver so that will require another model.
There have been some related successes, such as the latest models for mosquito-borne diseases like Dengue, Zika and malaria as well as those for flu and tick-borne diseases, says Hess.
Rocklöv was part of a research team that used test data from 2018 and 2019 to identify regions at risk for West Nile virus outbreaks. Using AI, scientists were able to forecast outbreaks of the virus for the entire transmission season in Europe. “In the end, we want data-driven models; that’s what AI can accomplish,” says Rocklöv. Other researchers are making an important headway in creating a framework to predict novel host–parasite interactions.
Modeling studies can run months, years or decades. “The scientist is working with layers of data. The challenge is how to transform and couple different models together on a planetary scale,” says Jeanne Fair, a scientist at Los Alamos National Laboratory, Biosecurity and Public Health, in New Mexico.
Disease forecasting will require a significant investment into the infrastructure needed to collect data about the environment, vectors, and hosts a tall spatial and temporal resolutions.
And it’s a constantly changing picture. A modeling study in an April 2022 issue of Nature predicted that thousands of animals will migrate to cooler locales as temperatures rise. This means that various species will come into closer contact with people and other mammals for the first time. This is likely to increase the risk of emerging infectious disease transmitted from animals to humans, especially in Africa and Asia.
Other things can happen too. Global warming could precipitate viral mutations or new infectious diseases that don’t respond to antimicrobial treatments. Insecticide-resistant mosquitoes could evolve. Weather-related food insecurity could increase malnutrition and weaken people’s immune systems. And the impact of an epidemic will be worse if it co-occurs during a heatwave, flood, or drought, says Hess.
The devil is in the climate variables
Solid predictions about the future of climate and disease are not possible with so many uncertainties. Difficult-to-measure drivers must be added to the empirical model mix, such as land and water use, ecosystem changes or the public’s willingness to accept a vaccine or practice social distancing. Nor is there any precedent for calculating the effect of climate changes that are accelerating at a faster speed than ever before.
The most critical climate variables thought to influence disease spread are temperature, precipitation, humidity, sunshine and wind, according to Tezaur’s research. And then there are variables within variables. Influenza scientists, for example, found that warm winters were predictors of the most severe flu seasons in the following year.
The human factor may be the most challenging determinant. To what degree will people curtail greenhouse gas emissions, if at all? The swift development of effective COVID-19 vaccines was a game-changer, but will scientists be able to repeat it during the next pandemic? Plus, no model could predict the amount of internet-fueled COVID-19 misinformation, Fair noted. To tackle this issue, infectious disease teams are looking to include more sociologists and political scientists in their modeling.
Addressing the gaps
Currently, researchers are focusing on the near future, predicting for next year, says Fair. “When it comes to long-term, that’s where we have the most work to do.” While scientists cannot foresee how political influences and misinformation spread will affect models, they are positioned to make headway in collecting and assessing new data streams that have never been merged.
Disease forecasting will require a significant investment into the infrastructure needed to collect data about the environment, vectors, and hosts at all spatial and temporal resolutions, Fair and her co-authors stated in their recent study. For example real-time data on mosquito prevalence and diversity in various settings and times is limited or non-existent. Fair also would like to see standards set in mosquito data collection in every country. “Standardizing across the US would be a huge accomplishment,” she says.
Understanding how climate change contributes to the spread of disease is critical for thwarting future calamities.
Jeanne Fair
Hess points to a dearth of data in local and regional datasets about how extreme weather events play out in different geographic locations. His research indicates that Africa and the Middle East experienced substantial climate shifts, for example, but are unrepresented in the evidentiary database, which limits conclusions. “A model for dengue may be good in Singapore but not necessarily in Port-au-Prince,” Hess explains. And, he adds, scientists need a way of evaluating models for how effective they are.
The hope, Rocklöv says, is that in the future we will have data-driven models rather than theoretical ones. In turn, sharper statistical analyses can inform resource allocation and intervention strategies to prevent outbreaks.
Most of all, experts emphasize that epidemiologists and climate scientists must stop working in silos. If scientists can successfully merge epidemiological data with climatic, biological, environmental, ecological and demographic data, they will make better predictions about complex disease patterns. Modeling “cross talk” and among disciplines and, in some cases, refusal to release data between countries is hindering discovery and advances.
It’s time for bold transdisciplinary action, says Hess. He points to initiatives that need funding in disease surveillance and control; developing and testing interventions; community education and social mobilization; decision-support analytics to predict when and where infections will emerge; advanced methodologies to improve modeling; training scientists in data management and integrated surveillance.
Establishing a new field of Outbreak Science to coordinate collaboration would accelerate progress. Investment in decision-support modeling tools for public health teams, policy makers, and other long-term planning stakeholders is imperative, too. We need to invest in programs that encourage people from climate modeling and epidemiology to work together in a cohesive fashion, says Tezaur. Joining forces is the only way to solve the formidable challenges ahead.
This article originally appeared in One Health/One Planet, a single-issue magazine that explores how climate change and other environmental shifts are increasing vulnerabilities to infectious diseases by land and by sea. The magazine probes how scientists are making progress with leaders in other fields toward solutions that embrace diverse perspectives and the interconnectedness of all lifeforms and the planet.
Scientists use AI to predict how hospital stays will go
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five:
- The problem with bedtime munching
- Scientists use AI to predict how stays in hospitals will go
- How to armor the shields of our livers against cancer
- One big step to save the world: turn one kind of plastic into another
- The perfect recipe for tiny brains
And an honorable mention this week: Bigger is better when it comes to super neurons in super agers