Flow and the Time of Cholera

“A time and a place for everything.” As true for human experiences as it is for cellular survival, this maxim speaks to the most hopeful and cynical of our beliefs. Without exception, every occasion to suffer or opportunity to thrive is guaranteed, however quietly, to end. But the illusion of forever is a strong one, especially when a crisis lasts long enough to feel permanent.

Pandemics can be like that.

The first cholera pandemic began in South Asia in the early nineteenth century. A British imperial expedition to survey remote swampland in the Ganges Delta encountered water carrying the bacteria now known as Vibrio cholerae. Workers fell ill and died in as little as hours. The disease, spreading rapidly, flourished around the world.

A century later, engineering intervened, playing a starring role in the development of modern infrastructure to store and deliver clean water across astonishing distances. Using mathematics to shape and contain the natural world, engineers relied on fluid mechanics, the physics of flow, to sustain life through pipes.

Cholera — along with other water-borne diseases, such as typhoid and dysentery — saw a steep drop in outbreaks.

But it did not disappear. There have been six additional cholera pandemics since its initial contact with humans, killing tens of millions. Starting in the early 1900s, most of these deaths have occurred in marginalized countries and communities. The current pandemic has been ongoing since the 1960s.

In the early twentieth century, massive infrastructural expansion required science to reshape nature into a utility service, plumbing treated water into homes. Today, researchers at the University of Pennsylvania School of Engineering and Applied Science are working closely with nature on its own terms to understand and predict the movement of microscopic bacteria through flowing water and how this physics is linked to human infection.

Engineers are again turning to fluid mechanics to keep humans safe from cholera, working not at the epic scale of infrastructure but the subtle level of microscopic cells.

Paulo Arratia, Professor in Mechanical Engineering and Applied Mechanics (MEAM) and Boyang Qin, Ph.D. graduate in MEAM and current postdoctoral fellow at Princeton University, have found that keeping communities safe from cholera is a matter of time, debuting groundbreaking research that lays the foundation for water security interventions to disrupt the motility and reproduction of pathogens.

Their work, published in Science Advances, is the first to characterize the relationship between microswimmers — miniscule self-propelling organisms, such as bacteria — and the dynamic flows of their environment. Their computational simulations and experiments with Vibrio cholerae create a path for technologies that both contain and disburse masses of bacteria before they can pose a threat to humans.

“We already knew a lot about the way the swimmers move,” says Arratia. “Vibrio cholerae are so-called smooth swimmers, meaning they don’t change direction when they move. They swim like a fish, not in a perfectly straight line but using a small amount of back-and-forth motion. Our work factors in the key variable of flow. When fish or a cell swim through a river, they both are affected by flow in that environment and they affect it. They modify the way the river moves, and vice versa.”

Central to their findings is that flow is not only a matter of force but also frequency.

“It’s the interplay between cell motility and the time of flow that matter most here,” says Qin. “This relationship determines how and when masses of bacteria are dispersed or confined in an aquatic environment and how this dispersion or confinement can be the deciding factor in human safety or infection.”

Arratia and Qin found that Vibrio cholerae form a prime demonstration of this principle, given that this pathogen tends to congregate in aquatic biofilms, persistent bacterial communities that are the cause of most pandemic cholera outbreaks in recent decades.

“Rivers with seasonal flows and daily variations are occasions for these time-periodic, dynamic environments where transmission is high,” says Qin. “Public health and medical approaches struggle to contain the illness during these flare-ups especially. Fluid mechanics allowed us to reveal that infection is not simply caused by the presence or movement of bacteria but is heavily dependent on the way a body of water moves through time. As engineers, we can contribute tools to prevent suffering before it begins. Our methodology reveals exactly where and when to intervene to protect people from infection.”

Ingested via contaminated water, the bacteria responsible for cholera remain intact and mobile in the stomach. When Vibrio arrive in the intestine seeking nutrients, their self-protective toxins activate a physical defensive response. The body goes into survival mode, diverting water to the gut to flush the toxin. This evacuation contributes to the bacteria’s spread, endangering others.

Rather than any direct effect of the pathogen, it’s the body’s resistance that proves fatal. When people die of cholera, they die of dehydration.

Treatment and prevention are therefore uniquely straightforward: sanitary water sources, IV liquids and rehydration salts. Antibiotics help. There’s even a cheap and effective vaccine.

Yet none of these solutions have proven robust enough to contain the illness.

Environmental strain, political violence and economic stress at local and global scales all trigger cholera outbreaks. Warming temperatures encourage bacterial reproduction. Refugee camps have become hotspots for the disease as displaced people are forced far from water-protective infrastructure and medical care. Vaccine shortages due to manufacturing deficits have forced providers to cut the two-dose regimen in half to stretch supply, which may soon peter out altogether.

Persisting beyond discovery of its cause and cure, cholera is a fluid story in search of an ending.

“We are establishing the fundamentals,” says Arratia. “Our next steps will be to translate this methodology into tools and work with communities. The mathematics are in place, now we would like to partner with ecologists, public health workers, biologists, and above all, people who live in relationship to bodies of water to help bring the cholera pandemic to a close.”

After all, it’s time.

 

This work was supported by NSF-DMR-1709763.