Chances for Outbreaks of Another African Viral Infection Rising
Earlier Surveillance Needed to Prevent “the Next Epidemic”
Another family of viruses, deadly in some cases, may have already jumped from fruit bats into humans in Africa, according to a study published today in the journal Nature Communications. The study provides the first, preliminary scientific evidence that “spillover” of henipaviruses into human populations is underway.
Henipaviruses are known to cause rare infections, with some strains harmless, and others with mortality rates approaching 90 percent (similar rates to Ebola). This family of viruses has been a concern since two of its members, Nipah and Hendra, emerged in Australia and Southeast Asia less than 20 years ago.
Henipavirus infections were thought to be confined to undeveloped areas near bat habitats in Australia and Asia until a recent, surprising study found that the common fruit bat species across Africa were carrying several related viruses. The current study set out to determine whether or not these African viruses were jumping into humans as they encroach further into traditional bat habitats.
“Our study found the first evidence – written in the immune cells of people living in our African study area – that humans have been exposed to henipaviruses, and also that the risk of infection goes up with exposure to a bat’s bodily fluids,” said Benhur Lee, MD, the Ward-Coleman Chair in Microbiology at the Icahn School of Medicine at Mount Sinai and lead author of the study. “The tragedy of Ebola, which also jumped into humans from bats in Africa, argues that we must heighten our surveillance of viruses on the verge of spillover from animals into humans. HIV, SARS and West Nile virus were also unknown until they emerged.”
To measure the potential for henipavirus spillover among humans in Africa, the research examined sets of bat and human blood serum samples for evidence of past exposure. The study results, while preliminary, provide scientific evidence that henipavirus are making the bat-to-human jump in the African nation of Cameroon. This looks to be especially true in people who regularly butcher bats as game or bush meat.
“The high mortality rates seen with some strains of heniparviruses in humans and the ability of the viruses to spread efficiently among non-reservoir hosts such as pigs and horses, pose a threat to global health and economy,” said study co-author Brad Schneider, PhD, Director of Laboratory Sciences at Metabiota, the company that designed the surveillance system used to identify the spillovers in the current study. “Active surveillance is critical to developing strategies that help prevent a widespread outbreak.”
The study results support the theory that henipavirus infections are more common than once thought, Dr. Lee said, but either hidden as undiagnosed brain infections (encephalitis) in remote villages, or mistakenly blamed on malaria, yellow fever or typhoid, which cause similar fevers. This scenario is made more plausible by the case loads (often more than 10,000 people) carried by African doctors. Alternatively, the explanation could be that the strains encountered in Africa do not cause serious symptoms. Further studies will tell.
Animals to Humans
To understand how viruses become threats, researchers look closely at zoonosis, the process by which a virus is transmitted between species. Many diseases infected animals first, including HIV, SARS, and influenza, and Ebola; the animals serve as reservoirs (long-term homes) for a virus. Often a reservoir species like a bat or pig will be not be harmed by a virus which becomes deadly when it jumps into humans, whose immune systems cannot adequately control it. Once discovered, reservoirs complete the understanding of any virus’s survival strategy.
Given the presence of the henipaviruses in African bats, the current study’s authors designed a highly sensitive and specific test that signals whether or not humans may have been exposed to henipaviruses in a region with infected bats. The test involves the clever use of antibodies, a set of proteins that plays a key role in the human immune system’s recognition of viruses.
The body makes a great variety of these proteins that float around waiting to encounter foreign organisms. When an antibody comes across a viral protein of the right shape, it labels it for precise and massive attack by other immune cells. Once exposed to a given virus, a person will have antibodies primed to recognize that virus forever after, and antibody tests can be used to reveal populations exposed to a given virus, even after they have recovered. Such antibodies can also recognize closely related viruses, a principle exploited in the current study.
Fieldwork for the current study was led by Metabiota, a San Francisco-based company that specializes in deploying surveillance systems to detect outbreaks early. Metabiota has resources on the ground in viral hotspots globally, and provided the research team with almost 500 human serum samples, collected from 13 rural locations across southern Cameroon. Screening revealed antibody responses indicating they had been exposed to a henipavirus or henipa-like virus. According to the study authors, this is the first study to demonstrate the presence of anti-henipavirus antibodies in human populations from Africa.
“It is clear that viral spillovers from animals represent grave and growing threats to the world,” said Dr. Nathan Wolfe, CEO and founder of Metabiota. “We must get ahead of these threats by strengthening local infrastructure, developing innovative surveillance systems, and aggregating data on future viral threats.”
The study provides evidence that suggests henipavirus-like spillover events from their natural bat reservoirs into the human population in Cameroon. Using their newly designed, more sensitive antibody test, the research team detected antibodies indicating previous exposure to a henipavirus in 48 percent of bat samples and 3-4 percent of 227 human blood samples (out of 500 total) collected from a high risk group that reported having had contact with bats.
The research team identified at least seven henipavirus-seropositive people in this sample that may have been exposed. While the numbers are small, a close look at the data reveals that three of the seven people who tested positive for potential exposure came from the same village. With three people testing positive in a village where just 12 volunteered to be part of the study, the potential exposure (seroprevalence) rate there was 25 percent. Tellingly, the three participants with evidence of exposure were all young adults and documented bat butchers. The close association between butchering bats and henipavirus seropositivity suggests that close contact with bodily fluids is likely required for cross-species transmission.
Furthermore, using a combination of on-site reporting from field staff and the latest maps of forest cover changes, the team identified recent deforestation as a significant risk factor associated with seropositivity. As humans and their domesticated animals move into ecological niches occupied by the reservoir hosts, increased opportunities for contact occur.
If henipaviruses are so deadly, then why are there living survivors in which to find antibodies? The answer may be that the henipaviruses infecting the current study participants were not deadly like those seen in some past Asian outbreaks. “It’s also possible that what we are seeing is the tip of the iceberg in Africa, and that we are finding the survivors out of those that have lost their lives to such viruses without being diagnosed,” said Dr. Lee.
“It’s important to note that much broader surveillance efforts will be required before we can make generalizations about the risks of henipavirus spillover across Africa,” Dr. Lee said. “On the other hand, for a disease that is not supposed to exist, a 3-4 percent henipavirus infection rate in a village would be highly significant if seen in other villages. The prevalence of HIV in Cameroon is 5 percent, and it’s perceived as an African epidemic.”
About the Research Team
In addition to Dr. Lee, Mount Sinai authors of the Nature Communications study were graduate student Shannon Beaty and postdoctoral fellow Arnold Park, both in the Department of Microbiology within the Icahn School of Medicine at Mount Sinai. Authors from Metabiota and the not-for-profit Global Viral were Bradley Schneider, Matthew LeBreton, and Nathan Wolfe.
Also making important contributions were study authors Tatyana Yun and Alexander Freiberg in the Department of Pathology, University of Texas Medical Branch, Galveston; Trevor Zachariah of the Brevard Zoo Veterinary Services in Melbourne, Florida; Thomas Bowden in the Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, United Kingdom; Peta Hitchens and Jonna Mazet in the Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California at Davis; Christina Kitchen in the Department of Biostatistics, School of Public Health, UCLA; and Peter Daszak of the EcoHealth Alliance in New York. The last study author, Olivier Pernet, was Dr. Lee’s postdoc at UCLA.
This project was funded by the Pacific Southwest Regional Center of Excellence (PSWRCE) and the National Institutes of Health (AI069317). Metabiota’s contribution to this study was made possible by the generous support of the American people through the United States Agency for International Development (USAID) Emerging Pandemic Threats Program. Global Viral was supported by Google.org and the Skoll Foundation.
Metabiota, Inc. develops systems to mitigate microbial threats. The company specializes in disease and pathogen detection, evaluation and response through the integration of field and lab research with health data analytics. Metabiota has a demonstrated track record in international collaboration, scientific and public health surveillance capacity building, and research with high public health impact.
For more information, visit http://metabiota.com/.
About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community-based facilities to tertiary and quaternary care.
The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals."