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.

Lipkin Op-Ed in CNN

Posted 5/21/2014 11:59:57 AM

Editor's note: W. Ian Lipkin is John Snow professor of epidemiology and director of the Center for Infection and Immunity at Columbia University. The opinions expressed in this commentary are solely those of the author.

(CNN) -- A third case of Middle East Respiratory Syndrome in the United States has been reported. An unidentified Illinois man was infected after having "extended face-to-face contact" with an Indiana man who was diagnosed with the MERS virus. Fortunately, he is no longer ill.

The rise in the reported number of MERS cases in the United States, Asia and Europe has fueled concern that this may be the big one: the 21st century equivalent of the 1918 influenza pandemic that killed 3% to 5% of the world population.

Concern is appropriate, because the coronavirus responsible for MERS can evolve to become more potent public health threats. However, I don't yet see evidence that will happen.

W. Ian Lipkin
W. Ian Lipkin

For one thing, an increase in the number of reported cases is not equivalent to an increase in the number of actual cases. As MERS testing is expanded from people with severe disease to include those with mild disease or only a history of potential exposure, we will detect more cases of infection. The mortality rate associated with infection will decrease from the current estimate of 30%. In short, we don't yet know the extent to which an increase in the reported number of cases only reflects better case ascertainment.

MERS, like 70% of all emerging infectious diseases, including influenza, SARS, HIV/AIDS and ebola, originates in wildlife. With MERS, both bats and camels may be implicated. Studies of camels in Saudi Arabia indicate that the majority have a history of MERS coronavirus infection. Infection appears to occur in early life and then clears. Up to a third of young camels carry this infectious virus. Because camels are born in the spring, there may be an increased amount of virus circulating in camels in spring and summer months. This may contribute to a seasonal spike in the reported number of MERS cases.

Humans may become infected through contact with infected animals, meat or other animal products such as milk. However, pandemic spread cannot occur without efficient human-to-human transmission. The MERS coronavirus grows deep in the human respiratory tract, so it is less likely to be transmitted than viruses that grow in teh nose, mouth or upper airways where a sneeze or a cough is sufficient to create an infectious aerosol.

Hospitalized patients with pneumonia-like MERS receive vigorous respiratory interventions such as intubation, assisted ventilation, drugs that dilate airways and chest percussion. These interventions may bring virus into the environment in aerosols and on the surfaces of medical equipment, resulting in infection of hospital personnel and other patients. Since the MERS coronavirus has been shown to be stable for up to 48 hours, it may be difficult to determine the source of infection as people and equipment circulate in the health care environment.

To date, cases of human-to-human transmission have only been reported in hospitals and in families where there is intimate contact with an infected person. If we notice a change in this pattern such that clusters of infections begin to appear in communities with more casual contact, that would be a strong sign that the virus is evolving to become a pandemic threat.

The MERS cases in new countries are disturbing but not surprising given how globally connected we are. International travel and foot traffic make it easier to spread a virus.

The first two cases reported in the United States, in Indiana and Florida, were health care workers returning from Saudi Arabia. Although a third case has been linked to contact with the Indiana case, I am cautiously optimistic that a cluster of cases will not be triggered.

Nonetheless, vigilance is essential. Saudi Arabia has more than 7 million foreign workers and hosts more than 3 million religious pilgrims annually. If new cases arise they will almost certainly be imported.

The key to an effective pandemic response is to acknowledge that infectious disease challenges are global rather than national. Information and biological samples must be shared freely to facilitate surveillance and the development of diagnostics, drugs and vaccines.

In this spirit, the government of Saudi Arabia has recently invited teams of international experts to join forces in addressing the global challenge of MERS. Although we are focusing on MERS now, the reality is that viruses and antibiotic resistant bacteria with pandemic potential are continuously emerging and re-emerging worldwide.

The recent MERS cases should not trigger an alarm. But if a pandemic happens, it is important we are prepared to combat it.

Live Virus Implicates Camels in MERS Outbreak

Posted 4/28/2014 5:27:52 PM

Image courtesy of Bjørn Christian Tørrissen, 2011

NEW YORK (April 29, 2014)—There is new, more definitive evidence implicating camels in the ongoing outbreak of Middle East Respiratory Syndrome, or MERS. Scientists at the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health, King Saud University, and EcoHealth Alliance extracted a complete, live, infectious sample of MERS coronavirus (MERS-CoV) from two camels in Saudi Arabia. The sample matched MERS-CoV found in humans, indicating that the virus in camels is capable of infecting humans and that camels are a likely source of the outbreak.

Results appear online in the journal mBio

The researchers examined nasal samples collected during a countrywide survey of dromedary camels and selected samples from two animals with the highest viral load. They cultured and obtained complete genomic sequence from both animals as well as virus in nasal samples from several other camels.

The mathematical means of all genetic sequences (the consensus genomic sequences) were consistent with viruses found in human cases; however, samples from camels contained more than one virus genotype. Over a period of 48 hours of culture in primate cells, the genomic variation of viruses narrowed, mirroring the lower sequence diversity reported in MERS-CoV found in humans. 

“The finding of infectious virus strengthens the argument that dromedary camels are reservoirs for MERS-CoV,” says first author Thomas Briese, PhD, associate director of the Center for Infection and Immunity and associate professor of Epidemiology at the Mailman School. “The narrow range of MERS viruses in humans and a very broad range in camels may explain in part why the human disease is uncommon: because only a few genotypes are capable of cross species transmission,” adds Dr. Briese. 

“Given these new data, we are now investigating potential routes for human infection through exposure to camel milk or meat products,” says co-author Abdulaziz N. Alagaili, PhD, director of the Mammals Research Chair at King Saud University. “This report builds on work published earlier this year when our team found that three-quarters of camels in Saudi Arabia carry MERS virus.”

To date, at least 300 people have been infected with the virus that causes MERS and approximately 100 have died since the first documented case in Saudi Arabia in September 2012. Of these, more than 60—about one-fourth of the global total since MERS was identified—have been reported in the past month. Most cases have been in Saudi Arabia, with lower numbers in Jordan, Qatar, Tunisia, and the United Arab Emirates. France, Germany, Italy, and the United Kingdom, and more recently Malaysia and the Philippines, have also reported cases related to travel to the Middle East. While human-to-human transmission has occurred, the source of the disease in most cases has remained a mystery. 

“Although there is no evidence that MERS-CoV is becoming more transmissible, the recent increase in reported cases is a cause for concern,” says senior author W. Ian Lipkin, MD, director of the Center for Infection and Immunity and the John Snow Professor of Epidemiology at the Mailman School. “It is essential that investigators commit to data and sample sharing so that this potential threat to global health is addressed by the entire biomedical research community.”

Additional co-authors include Nischay Mishra and Komal Jain at the Center for Infection and Immunity; Iyad S. Zalmout and Osama B. Mohammed at KSU Mammals Research Chair; Omar J. Jabado at the Icahn Medical Institute; and William B. Karesh and Peter Daszak at EcoHealth Alliance.

W. Ian Lipkin, MD, director of the Center for Infection and Immunity (CII) and the John Snow Professor of Epidemiology at the Mailman School, is the study’s senior author. Additional co-authors include Nischay Mishra and Komal Jain at CII; Iyad S. Zalmout and Osama B. Mohammed at KSU Mammals Research Chair; Omar J. Jabado at the Icahn Medical Institute; and William B. Karesh and Peter Daszak at EcoHealth Alliance.

The KSU Mammals Research Chair is supported by the Deanship of Scientific Research, King Saud University. Work in the Center for Infection and Immunity and EcoHealth Alliance is supported by awards from the National Institutes of Health (AI057158) and the United States Agency for International Development’s Emerging Pandemic Threat Program, PREDICT project, under terms of Cooperative Agreement Number GHN-A-OO-09-00010-00.

 

Click here to read the full publication.

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