Expect the unexpected. This adage flawlessly embodies infectious diseases and pathogens. The causative agents of infectious diseases—think viruses, bacteria, and other microbes—master the art of exploiting any shortcoming, any breach, any loophole in our defensive arsenal—sometimes in the most unanticipated of manner. They can resist our most dedicated control and eradication plans. They can defeat our most advanced antimicrobials, evade our best-trained immune system, and sabotage our most daring vaccine development efforts. Others can switch hosts and successfully use human beings to perpetuate themselves, even for just that one-time jump or zoonotic infection—those diseases transmitted between animals and humans.
And of course, they can trigger worldwide pandemics . . . or not . . . or not yet. The causative agents of infectious diseases master the art of defying our finest understanding of disease emergence and our most trusted predictions.
We have been scientifically aware of the existence of the microbial agents of infectious diseases for about 140 years or six generations. In over a century, astounding progress has been achieved to decipher their (molecular) biology, their disease-causing pathogenesis, their epidemiology, their ecology, and their evolution. Revolutionary biotechnologies have allowed researchers to mine ever deeper the mysteries of their realm. But equally dumbfounding knowledge gaps remain.
In 2006, I attended a three-week Princeton University course on tropical ecology in Kenya. A medicine man (a shaman) welcomed my class near a gigantic cave. A barely visible track, smoothed by millennia of human footsteps, ran against the craggy rocks, inviting us to penetrate the depths of the Earth. An alarm bell rang inside my head. I knew caves were home to bats and other creatures that hosted pathogens that I had never encountered, never mounted immunity against. The invisible threats may have been smeared with the animals’ droppings and secretions over the rocky walls or may have been aerosolized in the confined atmosphere. An unlucky cut or a loaded breath could turn the visit to tragedy. I explained my worries to the group and our professor. I advised them against entering the cave. One of my fellow classmates and I remained by the rim. Luckily, none of the “darers” scraped a finger.
A year later, in 2007, my premonition came true. A Dutch woman had traveled to Kenya for a holiday in Tsavo West National Park and returned with rabies. The lab where I worked during my PhD was involved in establishing the diagnosis. A bat had flown at her face and scratched the skin on her nose, which started pearling blood. The wound was washed, but she was not offered postexposure prophylaxis against rabies because the disease was thought to be only transmitted by dogs or other domestic animals in Kenya. At the time, the rather mysterious lyssaviruses circulating in African bats (Lagos bat, Mokala, and Duvenhage lyssaviruses) were known to be present in a few countries of Central, West, and southern Africa and in Ethiopia but not Kenya. Two weeks after her return to the Netherlands, the Dutch woman developed the tell-tale neurological symptoms of rabies, caused by Duvenhage virus. She was administered anti-rabies antibodies and placed under an experimental treatment protocol. But she died, 45 days after the incident with the bat.
In 2008, Marburg virus flew out of Africa with two outdoor enthusiasts who had visited Python Cave in Uganda. One of them was a Dutch woman. The lab where I worked was also involved in confirming the presence of the dreaded filovirus RNA in her samples. The route of transmission of the filovirus was never unveiled: a scratch, a loaded breath? But the depths of Python Cave had been the scene of the jump.
The Dutch woman died of the consequences of cerebral edema four days after she had broken out with the hemorrhagic fever. The tragedy was relayed in international news outlets and reached a woman residing in Colorado. She also had visited Python Cave during a two-week safari trip in January that year and had developed a severe febrile illness upon her return that needed hospitalization. She had been tested for the presence of filoviruses but had come back negative.
Shocked by the demise of the Dutch woman, she requested new tests, which revealed the presence of antibodies against Marburg virus in her blood; a retrospective analysis of one of the samples collected in January confirmed the presence of Marburg virus RNA. Why it hadn’t been detected earlier is unclear. If not for her insistence, the severe illness would have been left undiagnosed. It turned out to be the first imported case of a filovirus infection in the United States.
Today, most places on Earth are accessible by plane, train, boat, or car, within days or even hours from any departure location. The network of global air traffic is reshaping the continents into a unique, unrecognizable mesh. Time and space are shrinking. So is the distance separating us from “exotic” or “neglected” parasites and pathogens. Our astonishing technological progress left us vulnerable to invading parasites and pathogens at a scale our ancestors never experienced.
Jump-prone pathogens face a series of hurdles on their journeys to new host species. These hurdles make up what disease ecologists call the “species barrier.” First, the candidate host must make relevant contact with the pathogen or its reservoir or vector (or intermediate host) for a jump to take place. Once contact is established, the jumping pathogen must productively infect the exposed individual. The world does not lack for zoonoses. The WHO lists over 200. But a successful jump entails the breach of each successive barrier within a short window in space and time. Considering the wealth of opportunities (we are continually exposed to microbes), zoonotic jumps remain rare events. And for most, the human is a dead end.
Luckily, jump-prone pathogens are not very skilled at efficiently spreading from one individual of a new host species to the next. Transmission hurdles are many. They are, for jump-prone pathogens, the most challenging to breach. A zoonotic pathogen that readily sparks chains of human-to-human transmission is more the exception than the rule. But, as rare as they can be, the exceptions can be the causes of ravaging epidemics and global pandemics.
In the past two decades, humanity witnessed such sparks and their global consequences every four to six years: SARS in 2003, the flu pandemic in 2009, the pantropical spread of Zika and Chikun- gunya in 2013, and the COVID-19 pandemic at the end of 2019. The monkeypox epidemic that emerged in spring 2022 is the latest one unravelling. Humanity experienced some of the largest epidemics of Ebola in 2013-2016 and 2018-2020, MERS in 2015, yellow fever in 2015 and 2017, cholera in 2016, pneumonic plague in 2017, and Lassa and West Nile The largest number of dengue cases ever reported glob- ally was recorded in 2019. The race we are running against emerging pathogens is intensifying.
Excerpted from Fatal Jump: Tracking the Origins of Pandemics by Leslie Reperant. Copyright 2023. Published with permission of Johns Hopkins University Press.
