Earlier this year, principal investigators, project coordinators and technicians at the Center for Infection and Immunity (CII) at Columbia’s Mailman School of Public Health were bustling around the lab, getting ready for the exercise that was to take place that night.
Their job was to decipher what pathogens were present in unknown samples. They were not told what was in them. Their instructions were to detect, as quickly as possible, the microbes that were responsible for diseases described in the tip sheet and to collaborate with other labs performing the same tests.
Scientists at CII do this type of microbe hunting every day using various multiplex assays that they have at their disposal.
“The ultimate goal is to be prepared to identify potential biothreats,” said Meera Bhat, a coordinator at CII.
These days, those threats are plentiful: outbreaks of avian and swine flus, SARS, anthrax, measles, Ebola, antibiotic-resistant E.coli, and even bubonic plague have made headlines recently.
Given these risks to public health, a strong focus on surveillance is increasingly important.
This very point became vividly clear to CII Director Ian Lipkin (pictured right) while he was working as a resident at the University of California, San Francisco during the start of the AIDS epidemic in the 1980s.
“Nobody knew why people were ill. There were no diagnostic tests, no way to know who was infected or how to prevent disease. That experience was transformative and it became clear that there had to be a better way to monitor and manage new diseases,” Lipkin said.
At the time that HIV emerged, its origins were unclear. Now, scientists suspect that HIV jumped from chimpanzees and sooty mangabeys to humans due to consumption of bushmeat. The emergence of HIV took the scientific and medical community by surprise, and at the time that it surfaced, the idea that it could have zoonotic origins was not a leading theory.
“The bellwether for zoonotic diseases really came much later, in 1999, when we began to see West Nile Virus, Nipah, and Hendra. It was then that people really began talking about these threats. HIV didn’t do it, now in retrospect should it have? Of course,” Lipkin commented.
When West Nile first emerged in the United States, people initially thought it was St. Louis encephalitis, a disease that causes brain inflammation and, like West Nile, is transmitted by infected mosquitoes. As cases of human encephalitis mounted around New York, crows also began to die. Because clinicians and veterinarians did not readily speak with each other, the connection between these two seemingly unrelated events went unnoticed. It was only after the convergence of two independent lines of investigation led by Tracey McNamara, a pathologist at the Bronx Zoo and Wildlife Conservation Society, and Lipkin, then at the University of California, that West Nile was identified as the causative agent.
Lipkin described the emergence of West Nile, which had never been documented in the Western Hemisphere, as a zeitgeist that created a paradigm shift in the way people viewed zoonotic and vector-borne diseases. As a result, the public became more aware of the potential threats of these types of infections. However, a deep appreciation for the way that changes in habitat affect cross-species transmission of these viruses is still lacking.
Over the last decade, CII has led a series of projects that focus on monitoring wildlife viruses and changes in habitat to study viral evolution and to identify the next pandemic threat.
“We already know that regions are primed for emergence of disease when habitats are disturbed,” said Simon Anthony, a post-doctoral fellow who works on this line of research at CII.
In collaboration with USAID PREDICT and the EcoHealth Alliance, Anthony (pictured left) is currently working with a group of scientists in Mexico to monitor thick-billed parrots, an endangered species that lives in the Sierra Madre mountains in Northern Mexico. The birds’ habitat used to extend into the southwestern United States, but the destruction of their habitat, the drug trade, human contact, and mosquitos have resulted in drastic population drops. Education of local populations is crucial for successful conservation efforts and for comprehensive surveillance of potential health threats. To that end, Anthony traveled to South America this summer to teach local scientists how to collect and analyze samples, some of which will be sent back to CII to test for novel pathogens.
Other investigators at CII are also working on similar issues.
Working with colleagues Ana Negredo and Antonio Tenorio of the National Center of Microbiology in Madrid, Spain, Gustavo Palacios, a former Assistant Professor at CII, discovered an ebola-like virus in bats in a cave in Spain. Earlier this year Palacios and colleagues Michael Cranfield and Linda Lowenstine at the University of California, Davis showed that wild mountain gorillas living in natural parks in Rwanda were most likely exposed to human metapneumonic virus (HMPV) due to increased ecotourism. Two of these endangered gorillas died, highlighting the importance of educating tourists about the concept that cross-species infection is, as Palacios put it, “a two-lane highway.”
Similarly, Thomas Briese (pictured left), the Associate Director of CII, in collaboration with German colleagues Fabian Leendertz at the Robert Koch Institute, Berlin, and Christophe Boesch at the Max Planck Institute, Leipzig, found HMPV and human respiratory syncytial virus (HRSV) among chimpanzees that died during outbreaks of respiratory infections at Taï National Park in Côte d’Ivoire in the late 1990s and early 2000s. This discovery marked the first known instance of viral transmission from humans to wild apes.
The strains that Briese found among these chimpanzees, like those found by Palacios in gorillas, were closely related to strains involved in human epidemics, suggesting that people introduced the virus to great ape populations.
Altogether, researchers at CII have characterized over 400 viruses.
Assistant Professor Amit Kapoor, who discovered gorilla bocavirus, the first non-human primate bocavirus, recently identified canine hepacivirus, which is very closely related to human Hepatitis C. Visiting Professor Amadou Sall, who founded the International Course on Arboviruses and Viral Hemorrhagic Fever Diagnosis, Prevention, Control and Outbreak Management, is pursuing field outbreak investigations in Africa; postdoctoral fellow Kirsi Honkavuori studies avian diseases and has discovered novel picornaviruses and bornaviruses; and her colleague Nicole Arrigo is developing in vivo animal models for pathogen discovery and characterization.
These and other projects are rooted in the philosophy of One Health, which is an integral part of CII's mission. (The concept was pioneered by German physician Rudolf Virchow who also coined the term zoonosis.)
“We are best known for our work in pathogen discovery but our larger commitment is to integrated global surveillance, conservation of habitats and natural resources, and to building awareness of the continuity of life on earth,” Lipkin said.
— Daniela Hernandez
This article appears in the current One Health Initiative Newsletter.
Photographs courtesy of Christopher Dawes and Dr. Natalie Lamberski, DVM.