������ý

The Rise and Fall of Infectious Diseases

To figure out where new diseases come from—and how old diseases return—it’s tempting to first investigate the pathogens. Viruses, after all, can quickly evolve into new versions of themselves, and human antibodies that prevent an infection one year may be ineffective the next. Immunity to past variants of a virus may not guarantee protection against future ones. Similarly, pathogenic bacteria, parasites and fungi can develop resistance to existing treatments, blunting their efficacy.

Mutations and other biological factors play a role in disease emergence and reemergence, but they’re not the only culprits behind the waxing of infectious agents. They may not even be the principal drivers. “People assume that the emergence of infectious diseases is a natural phenomenon, but it’s not,” said Wubshet Mamo, Ph.D., a public health expert and clinical professor at the University of Washington in Seattle and the International Training and Education Center on Health in Ethiopia. He pointed out that viruses tend to remain stable when they’re left undisturbed in nature, and it’s only when under threat or otherwise disturbed that they develop new mutations. “The emergence of infectious disease is not merely associated with viral or bacterial evolution,” he said.

How Human Activity Drives the Spread of Disease

Mamo is among a growing chorus of researchers and public health experts who believe that factors related to human activity and behaviors are more powerful forces driving the persistence and emergence of disease. These factors include climate change, which can worsen extreme weather events like droughts and floods linked to higher risks of disease. Recent floods in Pakistan, for example, have displaced large numbers of people and increased case counts of diseases like dengue, malaria, measles and COVID-19. Human activity also includes disruptive events, like wars and political struggles, that can destabilize large populations of people; increased interactions with animals that can boost the transmission of zoonotic pathogens; and the shipping of foods and animals from country to country, running the risk of expanding the reach of parasites.

“My concern is that our increasingly unbalanced interactions with nature, such as deforestation, increased urbanization, drought and wars, could further increase the risk factors and provoke new disease emergences or re-emergence of the old infections,” Mamo said. “A large human population size favors the spread and perpetuation of diseases.”

These risk factors have been exacerbated by the global response to the ongoing COVID-19 pandemic, which has critically reshaped incidence and mortality rates for infectious diseases in locations around the world, especially in under-resourced countries. In those places, limited public health resources and infrastructure—which themselves are immediate consequences of the larger issue of global health inequities—can make the problem worse.

Tuberculosis, a disease that kills more people than any other infectious disease except COVID-19, offers a compelling case study of how infectious diseases thrive in the shadow of the pandemic.

Tuberculosis Looms Under the Shadow of COVID-19

Mycobacterium tuberculosis.
Source: Flickr. Tuberculosis, or TB, is a stubborn adversary. It spreads quickly in crowded and unventilated living situations, and it disproportionately affects individuals who are malnourished and live at or below the international poverty line. TB has always been a menace: , show that Mycobacterium tuberculosis, the pathogenic bacterium that causes most cases of the disease, was causing trouble even then. Now, M. tuberculosis is believed to infect 2 billion people—a quarter of the world’s population—and kill about 10 million yearly. TB remains the , according to the World Health Organization (WHO), and in 2014, the organization set a goal of eradicating the disease by 2035.

For microbiologists, infectious disease researchers, epidemiologists and other experts, this persistence is particularly vexing because TB is both preventable, by vaccine, and curable (in its active form), by a 6-month course of antibiotics.

Between 2015 and 2020, WHO reported that global incidence of the disease fell by about 2% per year. This was encouraging, if not quite on track with the 2035 goal. However, the COVID-19 pandemic threw a wrench into that trajectory in many parts of the world. “There were an additional 500 million deaths in 2020, which meant we were set back by almost 10 years,” said Jamie Tonsing, M.B.B.S., D.F.M., M.Sc., senior advisor for TB at the Global Fund, which financially supports global efforts to prevent and treat TB, HIV/AIDS and malaria.

. In biosafety labs in some resource-limited countries—and the 30 countries with the highest burdens of TB are all resource-limited—reagents used for TB diagnostic tests were repurposed for COVID-19. Skilled health care workers prioritized COVID-19 care, and “people focused more on testing for COVID-19 than for TB,” said microbiologist Shirematee Baboolal, Ph.D., who is based in Trinidad and Tobago and works with low- and middle-income countries to develop microbiology-based strategies for tackling TB. Surveillance, which is the cornerstone of public health strategies to respond to emerging and re-emerging diseases, took a backseat to the growing pandemic crisis.

Shifts in Tuberculosis Surveillance and Treatment in Sierra Leone

Sierra Leone, an under-resourced country in West Africa, was hit particularly hard by the convergence of COVID-19 and TB. Over the last 2 decades, TB incidence in the country peaked in 2009 but then began to fall, largely in response to global efforts to improve diagnoses and treatment in the country.

As the COVID-19 pandemic took hold, the country responded quickly with lockdowns and emergency orders. “It’s understandable, that was the fire in the house,” said Tonsing. TB resources were repurposed for the new pathogen. TB diagnostic tests that often use GeneXpert assays, for example, were now being used for COVID-19 testing instead of TB. 

Perhaps because of those early measures, or than in other parts of the world. At the same time, TB incidence in Sierra Leone rose and the treatment success rate fell. From 2019 to 2020—just a 1-year change—the case-detection rate .

. “A surveillance system is so important in a country for TB, for COVID-19, for all infectious diseases,” said Baboolal. “If you don’t have an active surveillance system working in your country, then what happens? You will not pick up the first case, so you will end up picking up many cases.”

Baboolal noted that it's simplistic to blame the pandemic alone. India accounts for an estimated one-quarter of all TB deaths worldwide, and early in the pandemic it experienced a similar drop in confirmed cases. The country’s public health agency had implemented a testing program that combined TB and COVID-19 screening and obtained hundreds more diagnostic machines. As a result, case-detection rates in India have nearly returned to pre-pandemic levels.

Going into the pandemic, Sierra Leone already had an understaffed and underfunded public health system. Another factor was poor living conditions. “Many people still live in very poorly ventilated homes,” said Baboolal. M. tuberculosis spreads in the air and can rapidly infect an entire family, especially if they live in close quarters. People who lack access to nutritious food and basic health resources face additional risks, as the 24-week treatment and its side effects can be grueling. As a result, many people abandon treatment, promoting the spread of drug-resistant TB, which is even more difficult to treat.

Measles, Malaria and More

Other diseases also surged during the pandemic. In the first 2 months of 2022, the number of measles cases reported worldwide by nearly 80% compared to the same time period in 2021. A major drop in vaccinations is likely to blame: . Most of those children live in areas that lack reliable access to routine health care or in places affected by conflict.

A 3D graphic representation of a spherical-shaped measles virus.
Source: Rawpixel. Because measles is so contagious, WHO researchers worry that the early 2022 data portend a disastrous comeback for the disease. Experts similarly worry about polio, which is caused by a virus and preventable by a vaccine. Nearly 30 countries polio vaccination campaigns in the early months of the pandemic in 2020, and despite attempts to maintain surveillance, many cases have likely gone uncounted.

Malaria, too, has been affected by COVID-19. Scott Filler, M.D., is based in Geneva, Switzerland, and leads the Global Fund’s efforts against malaria, which is caused by a plasmodium parasite transmitted by infected mosquitoes. Early in the pandemic, he and his group could see the potential for a dangerous re-emergence of malaria—again, not because of the parasite, but because of a weakened response.

“We were worried that more people would actually suffer from and potentially die from malaria than COVID-19 itself due to the concerns about health seeking related to COVID-19,” he said. “Malaria has this incredible rebound capability if you take your foot off the gas.”

A human red blood cell and malaria parasite connect.
Source: Wikipedia Commons. According to the World Malaria Report from WHO, . There were about 14 million more cases of malaria in 2020 than in 2019, and roughly 69,000 additional deaths. For comparison, the total number in 2020 was 241 million cases and 627,000 deaths, and WHO linked most of those additional deaths to disrupted systems for preventing, diagnosing and treating the disease.

But Filler said that wasn’t the worst-case scenario. “Of course, we saw perturbations due to COVID-19, but the early organization of the community—at all levels—made sure a more disastrous spread didn’t happen.”

Parasitic Infections and Outbreaks

Malaria didn’t follow the same pattern around the world, though. “No one got malaria in the U.S. because no one was traveling,” said Bobbi Pritt, M.D., who runs the Clinical Parasitology Laboratory at the Mayo Clinic in Rochester, Minn. But they did get infectious diseases connected to parasites: People who spent more time outdoors, Pritt said, were more likely to acquire a tick-borne illness like Lyme disease, which is caused by a bacterium carried by the black-legged (deer) tick.

She sees the emergence of parasitic infections as having “multifactorial” causes, but says human behaviors are likely behind most of them. For example, “there have been outbreaks of parasitic infections related to eating things,” like raw fish, she said.

Pritt suspects the rise of tickborne diseases is connected to another human activity: an increasing encroachment on natural habitats. Researchers who study zoonotic diseases, which can jump from animals to humans, worry about future outbreaks due to increasingly frequent interactions between people and animals, as on big farms or places where new construction erases wildlife habitat.

“Vigilance should be a guiding principle in watching for the emergence of zoonotic diseases,” said Tara Smith, Ph.D., an epidemiologist at Kent State University in Ohio. An estimated three-quarters of infectious diseases that infect people originated in animals, including SARS, MERS, dengue, Ebola, Zika, influenza and COVID-19. Many viruses likely lie in wait. In 2013, researchers hypothesized that animals harbor hundreds of thousands of unknown viruses. viruses that live in the world’s oceans.

Looking to the Future

Smith does, however, see signs of progress—if not in public opinion, then in science. She credits the rapid global response to COVID-19 to decades of research—going back at least to the SARS outbreak of 2003—for enabling the rapid development of a vaccine for SARS-CoV-2. “We already had so much information about what species could be infectious,” she said. Years of work on surveillance, she added, enabled researchers to quickly pivot their work and focus on SARS-CoV-2. And COVID-19, in turn, has highlighted the crucial need to better anticipate the next crisis. “We have learned so much about zoonotic coronaviruses because of it,” she said.

She and other experts can point out ways to prepare for the future. Managing multiple, human-driven factors to tamp down infectious diseases will be a Herculean undertaking, especially if another catastrophe comes along. “There are so many things to deal with, whatever is the priority,” said Tonsing. “We start working on something like that, like COVID-19, then forget that we still have TB. Or malaria. Or something else.”

Mamo, in Seattle, said next steps must include focused strategic plans—at the national and international levels—that support better surveillance systems. “The goals need to focus on intensified science; sustainable investments in research, development and innovation; strengthening laboratory capacity and surveillance; improvement in health care delivery; and equity, access and public policy issues," he said. “There is a collective responsibility associated with emerging diseases, and we need coordinated responses, especially in [under-resourced] countries.”

---