Study Finds Dangerous Pathogens Lurk in the City’s Rat Population, New Animal Model for Hepatitis C
NEW YORK (Oct. 14, 2014)—In the first study to look at would-be diseases carried by New York City rats, scientists at the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health identified bacterial pathogens, including E. coli, Salmonella, and C. difficile, that cause mild to life-threatening gastroenteritis in people; Seoul hantavirus, which causes Ebola-like hemorrhagic fever and kidney failure in humans; and the closest relative to human hepatitis C. Results appear in the journal mBio.
The researchers trapped 133 Norway rats at 5 sites in New York City, focusing on rats trapped inside residential buildings. In the lab, targeted molecular assays confirmed the presence of 15 of the 20 bacterial and protozoan pathogens they looked for and one virus: Seoul hantavirus was present in eight rats. It is the first time the virus has been documented in New York City, and genetic clues suggest that it may be a recent arrival. Human infection has been associated with multiple cases of hemorrhagic fever with renal syndrome, and chronic renal disease in Maryland and Los Angeles. The virus has also been implicated in cases of hypertension.
It is unknown how often humans become sick from rats and what viruses cross over, but according to first author Cadhla Firth, PhD, transmission could happen in any number of ways. Rats leave behind quantities of the pathogens in saliva, urine, or feces that people or their pets come in contact with.
“New Yorkers are constantly exposed to rats and the pathogens they carry, perhaps more than any other animal,” explains Dr. Firth, who conducted the study as a research scientist at Columbia’s Center for Infection and Immunity. “Despite this, we know very little about the impact they have on human health. ”
Animal Model for Hepatitis C
High throughput screening methods developed by the Center for Infection and Immunity employed to test for the presence of known and unknown microbes identified 18 novel viruses, including two rat hepaciviruses dubbed NrHV-1 and NrHV-2. Although these are not the closest relatives to human hepatitis C discovered, the identification of these viruses in a species commonly used in medical research is extremely important, the researchers say. Notably, the two viruses replicate naturally in the animal’s liver, which suggests that their lifecycle is similar to human hepatitis C virus.
“With the loss of the chimpanzee model for hepatitis C, the availability of an animal model that has fidelity to the human model is extremely important to efforts to develop drugs and vaccines,” says senior author W. Ian Lipkin, MD, John Snow Professor of Epidemiology and director of the Center for Infection and Immunity at Columbia’s Mailman School, who has discovered more than 600 viruses over the course of his career.
An estimated 3.2 million Americans and 130-150 million people worldwide have a chronic hepatitis C virus infection, which can lead to liver cancer and cirrhosis.
Rats as Sentinels for Human Disease
The study developed out of conversations between Dr. Lipkin and the late Joshua Lederberg, a molecular biologist and Nobel laureate. The two scientists wanted to study rats in New York City to have a point of comparison in case a pathogen crossed over and caused a human outbreak. “It started as a biodefense initiative,” says Dr. Lipkin. “If we are to pick up something that is a novel threat to public health, we have to know the baseline microflora.”
Dr. Lipkin continues: “Rats are sentinels for human disease. They’re all over the city; uptown, downtown, underground. Everywhere they go, they collect microbes and amplify them. And because these animals live close to people, there is ample opportunity for exchange.”
Continual monitoring of the rat population is needed along with studies in people to understand how the animals and the microbes they carry make us sick, Dr. Lipkin notes. With modern disease surveillance methods, a repeat of the rat-borne Black Death, which killed as much as 60 percent of the population of 14th Century Europe, or a similar outbreak need not happen.
Dr. Firth is currently a research scientist at CSIRO in Geelong, Australia. Co-authors include Meera Bhat, Simon H. Williams, Juliette M. Conte, James Ng, Joel Garcia, Nishit P. Bhuva, Bohyun Lee, Xiaoyu Che, and Phenix-Lan Quan at the Center for Infection and Immunity; Matthew A. Firth at Memorial Sloan-Kettering Cancer Center; Matthew J. Frye at Cornell University; and Peter Simmonds at the University of Edinburgh.
Lipkin Op-Ed in Wall Street Journal
Posted 8/4/2014 1:20:46 PM
Ebola: How Worried Should We Be?
Appeared 3 Aug 2014 in the Wall Street Journal
Few people alive today personally recall the influenza pandemic of 1918 that killed between 50 million and 100 million people. But I have vivid memories from 2003 of deserted airports and streets when the SARS virus, which infected fewer than 9,000 people and killed fewer than 800 world-wide, brought Beijing, Hong Kong, Singapore and Toronto to their knees. On several trips to Saudi Arabia in the past 18 months I’ve also seen the impact of MERS, caused by a similar virus, which has infected at least 837 people and killed at least 291.
The Ebola outbreak in West Africa has so far infected more than 1,450 people and killed close to 800. But while the outbreak is a frightening and formidable challenge, this viral disease does not pose the risks of a pandemic influenza, SARS or MERS.
In addition to its effect on public health, the emergence of a new lethal infectious agent, or the re-emergence of a known one, can slow travel and trade. This can have profound effects on the economies where the disease appears, and elsewhere given global integration. The costs of surveillance, containment and treatment can be crippling, particularly in the developing world, where most new infectious diseases emerge.
Epidemiologists ask several questions to assess the risks from an infectious agent. How easily is it transmitted? How many of those infected have serious illness? How many die? Are there vaccines or drugs to prevent or treat the disease? For example, seasonal influenza is highly transmissible and infects large numbers of people every year, though only a small proportion develops serious disease. Nonetheless, influenza kills up to 30,000 people annually in the U.S. alone. Although not 100% effective, vaccines to prevent influenza and drugs to treat it are available.
Like influenza, the viruses that cause SARS and MERS are primarily transmitted through droplets in the air and on surfaces, droplets released when an infected person coughs or sneezes. While we could vaccinate against MERS or SARS, the current risk of disease is too low to warrant wide-scale vaccine campaigns. There have been no cases of SARS since May 2004, and the virus responsible for MERS does not typically cause severe disease in otherwise healthy people.
Ebola, in contrast, has a high mortality rate (up to 90%) but is spread only through intimate contact with bodily secretions such as vomit, blood or feces. There is no risk in sitting next to an infected traveler on an airplane. In principle, therefore, transmission can be prevented by isolating people with the disease.
About 70% of emerging infectious diseases, including HIV/AIDS, West Nile, influenza, SARS, MERS and Ebola, are animal infections that have jumped to humans, frequently through a domesticated animal. Pigs are a common intermediate for respiratory viruses including influenza. Opportunities for such cross-species jumps are increased by the loss of wildlife habitat to development as well as the human consumption of bushmeat due to poverty or cultural preference. A warming climate may also increase the geographic range of insects like mosquitoes and ticks that can carry diseases such as dengue, malaria and chikungunya. By analogy to a related virus, Marburg, scientists presume that Ebola originated in bats, although there is no proof.
We may not be able to directly address the drivers of infectious disease, but we can invest in surveillance in the developing world where cross-species transmission is likely to occur. We also can improve diagnostics and pursue new strategies for rapidly developing and manufacturing drugs and vaccines.
The most common question I hear is whether Ebola can travel to the United States. It can. John F. Kennedy airport in New York City annually receives more than 21 million international passengers on more than 190,000 international flights.
An infected individual could board a flight in West Africa, become symptomatic in the air or after landing and then expose others to the virus. At worst, this might result in a few other people becoming infected and possibly dying. But sustained outbreaks would not occur in the U.S. because cultural factors in the developing world that spread Ebola—such as intimate contact while family and friends are caring for the sick and during the preparation of bodies for burial—aren’t common in the developed world. Health authorities would also rapidly identify and isolate infected individuals.
What else can be done to mitigate risk in America? Nonessential travel to areas where Ebola is active should be curtailed, and individuals returning from these areas must be monitored.
In 2003, travelers to the U.S. from areas at risk for SARS, including China, Southeast Asia and Canada, were given cards on landing that directed them to report to the local board of health if they developed symptoms of respiratory disease within 10 days (the virus incubation period). I became ill on returning to New York from Beijing in 2003 and was placed into isolation; I just had a bad case of influenza. Eight Americans contracted SARS; none died. In Canada 438 people contracted SARS and 44 died.
However, neither curtailing travel to Ebola hot zones nor monitoring individuals who return from them will address the crisis unfolding in West Africa. Nor will they reduce the future risk of pandemic disease.
There is also more we can to reduce the risk of pandemic disease. The economic downturn of the past several years has reduced funding for the World Health Organization, U.S. national health agencies such as the Centers for Disease Control and the National Institutes of Health, impairing their ability to respond to outbreaks such as Ebola. But clinical, laboratory and support staff and supplies are urgently needed in Guinea, Sierra Leone and Liberia for patient care, infection control, contact tracing and community engagement.
The U.N.’s International Health Regulations, adopted in 2005, commit all member states to respond to the spread of diseases throughout the world that pose risks to public health without unnecessarily disrupting international traffic and trade. The U.S. must honor this commitment by investing in science and public-health surveillance at home and abroad. This is the right thing to do. It is also—for more threatening infectious diseases if not for Ebola—in our own self-interest.
Dr. Lipkin is professor of epidemiology and director of the Center for Infection and Immunity at the Mailman School of Public Health and College of Physicians and Surgeons, Columbia University.
BLOOMBERG NEWS Taking Stock The Ebola Outbreak: Assessing the Global Threat (August 4, 2014)
FOX NEWS The Real Story with Gretchen Carlson: How is Ebola outbreak being contained, dealt with? (August 4, 2014)
NEWSWEEK The U.S. Is Sitting on Promising Ebola Vaccines by Zoë Schlanger and Elijah Wolfson (August 4, 2014)
FOX NEWS The Real Story with Gretchen Carlson: What would happen if Ebola hit the US? (July 31, 2014)
NEW YORK POST Airports on high alert for fliers with Ebola symptoms by Bob Fredericks (July 30, 2014)
CNN Erin Burnett Outfront: Expert: Ebola could arrive in the U.S. (July 30, 2014)
NATIONAL GEOGRAPHIC Q&A: What's Behind Worst-Ever Ebola Outbreak in West Africa? by Karen Weintraub (June 27, 2014)
BUSINESS INSIDER How Much Should People Worry About The 'Unprecedented' Ebola Outbreak In Guinea? by Lauren F. Friedman (March 31, 2014)
Wind Currents Behind Children’s Heart Disease
Posted 5/22/2014 12:16:06 PM
Kawasaki disease in Japan linked to an environmental trigger in winds from agricultural regions in northeast China
NASA Earth Observatory image by Jesse Allen
May 22, 2014—Kawasaki disease, the leading cause of acquired heart disease in children worldwide, may be caused by fungal particles or toxins carried on wind currents from dense croplands in northeastern China to Japan, according to a new study by an international team, including researchers at the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health. Results appear in the Proceedings of the National Academy of Sciences.
The causative agent of Kawasaki disease, first observed in Japan in the 1960s and that has since then been recognized in other countries in the world, is yet unknown. Noting that the timing of disease outbreaks coincided with certain wind patterns from Asia, researchers used computer models to simulate air currents and airborne particle transport on days with high Kawasaki disease incidence in Japan using records dating to 1977. The model results suggested that the disease peaked in many locations around Japan, in and out of epidemic years, only when winds originated from a densely cultivated region in northeastern China characterized by vast extensions of cereal croplands.
Further analysis pointed to a very short incubation time of less than 24 hours between exposure and fever onset. This, combined with the evidence of widespread simultaneous occurrence of the disease in many cities around Japan, led the scientists to reason that the source of the disease is unlikely to be an infectious agent requiring replication inside the human host, and suggests instead exposure to an antigenic or toxic trigger.
In an attempt to further characterize the trigger, the authors developed an air filter and performed atmospheric monitoring by aircraft over Japan on days during Kawasaki disease season when air currents originated only from the same region in northeastern China. Detailed genetic analysis of the samples by Brent L. Williams, PhD, associate research scientist, and W. Ian Lipkin, MD, director, the Center for Infection and Immunity at the Mailman School, detected Candida species as the dominant fungus aloft, demonstrating the potential for human disease in aerosols transported by wind currents. Candida are the most common cause of fungal infections worldwide. Prior studies in the laboratory had confirmed Kawasaki-like symptoms in mice exposed to Candida. This result suggests a new paradigm in which toxins such as those in the fungus or any others linked to those agricultural lands, carried by the wind, may trigger Kawasaki disease, according to the authors.
The researchers now plan to conduct more flights over Japan and northeast China during the high season for Kawasaki disease, as well as future studies in which the capacity for those microbes, antigens or toxins contained in the aerosol samples are tested to see if they elicit a similar immune response as that seen in Kawasaki disease patients.
The authors have recently launched a fund-raising initiative to gather funds to perform these aircraft monitoring campaigns this year and the next. For more information, visit www.kawasaki-disease.com.
Xavier Rodó, the lead author of the study, is an ICREA Professor at the Institut Català de Ciències del Clima, IC3, in Barcelona, Spain. Additional co-authors include senior author Josep-Anton Morgui and Roger Curcoll and Marguerite Robinson, also at IC3; Joan Ballester, at both IC3 and the California Institute of Technology; Jane C. Burns from the KD Research Center at the University of California, San Diego School of Medicine’s and the Rady Children’s Hospital San Diego, Dan Cayan from the Scripps Institution of Oceanography/UCSD and the US Geological Survey in LaJolla; W. Ian Lipkin, Brent L. Williams, and Mara Couto-Rodriguez at Center for Infection and Immunity at the Mailman School; Yoshikazu Nakamura and Ritei Uehara from the Jichi Medical Hospital, Togichi, Japan; and Hiroshi Tanimoto, from the National Institute for Environmental Studies, Tsukuba, Japan
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