Middle East Respiratory Syndrome (MERS) is described by the Centers for Disease Control as a novel viral respiratory illness first reported in Saudi Arabia in 2012, caused by a coronavirus called MERS-CoV. Most people who have been confirmed to have MERS-CoV infection developed severe acute respiratory illness characterized by high fever, cough, and shortness of breath. About half of these people died.
So far, all cases have occurred in or been linked to four countries in or near the Arabian Peninsula. No cases have been identified in the U.S. This virus has spread from ill people to others through close contact. However, the virus has not shown to spread in a sustained way in communities. The situation is still evolving.
The CDC is working with partners to better understand the risks of this virus, including the source, how it spreads, and how infections might be prevented, has provided information for travelers, and is working with health departments, hospitals, and other partners to prepare for possible cases in the United States.
MERS shares some similarities with the SARS virus that caused a worldwide epidemic and claimed 916 lives in 2002-2003, but it is caused by a different type (“Lineage C”) of coronavirus (MERS-CoV) that was identified in September 2012, before the current outbreak began. MERS was first identified in Saudi Arabia and Jordan, and cases have been reported in Qatar, the United Arab Emirates and Tunisia, as well as a few having been imported into France, Britain and Italy.
Both coronaviruses seem to share the same two to ten day interval between exposure and the onset of symptoms; both cause fever and cough, and in some instances diarrhea; most cases of both are severe to lethal, and both have spread in hospitals to other patients in multiple chains of person-to-person transmission, and with spread between hospitals occurring when a patient is moved from one institution to another.
However, compared with SARS, with which otherwise healthy individuals became afflicted with severe, sometimes fatal cases of the disease, severe MERS cases have thus far manifested mainly in older males with underlying disease conditions, and while as with SARS there has been some spread from patients to health care workers with MERS, the latter has proved less lethal.
A Canadian Press report this week by award-winning medical reporter Helen Branswell notes that scientists in Italy say they’ve engineered a MERS virus that could be used in a vaccine, the second such announcement in recent days of progress toward developing a MERS vaccine with the news likely to generate hopeful headlines and perhaps create a popular impression that if MERS starts to spread globally, a vaccine might be quickly available to help combat the new virus.
“Don’t bet on it,” warns Ms. Branswell, who reports that a loose consensus among several experts she’s consulted is that it would take at least five to 10 years to develop and test a MERS vaccine, get it approved by drug regulatory agencies and scale up production to the point where a commercial product is available for widespread distribution, observing that at this present juncture, it’s not at all clear any pharmaceutical manufacturer would be prepared to assume the financial risk involved in accelerating a MERS vaccine project past the early scientific phases.
Ms. Branswell cites Dr. Peter Hotez, founding dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston observing that “There’s a long way to go from showing in a research laboratory that you’ve got a potential candidate vaccine to actually producing a bottle of that vaccine that is going to be used or stockpiled,” adding that “Our technical ability to make (experimental) vaccines has sort of outpaced our social and political and economic infrastructure to figure out how to do this.”
Dr. Hotez is also President of the Sabin Vaccine Institute (Sabin), a Professor of Pediatrics and Molecular Virology & Microbiology and Chief of the Section of Pediatric Tropical Medicine at BCM, Endowed Chair of Tropical Pediatrics at Texas Children’s Hospital, heads the Children’s Hospital Center for Vaccine Development, and was recently named the Fellow in Disease and Poverty at Baker Institute for Public Policy at the Rice University.
Ms. Branswell also quotes Dr. Thomas P. Monath, MD, a vaccinologist who is a founder of the One Health Initiative (OHI). and Michael T. Osterholm, PhD, MPH, a distinguished member of the OHI Team’s Honorary Advisory Board. Drs. Monath and Osterholm indicate that they support the idea for developing a vaccine for camels, which are suspected to be a zoological disease vector for MERS, explaining that they prefer steering the current vaccine work towards an animal product if feasible for various reasons.
For example, a research report letter published online last weekend by the journal Nature Medicine, entitled ““Treatment with Interferon a2b and ribavirin improves outcome in MERS-CoV–infected rhesus macaques” (corresponding co-author Heinz Feldmann, Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada – Nature Medicine 2013 doi:10.1038/nm.3362) reports that a team of researchers based at Disease Modeling and Transmission Unit, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories in Hamilton, Montana found that a combination of Interferon alfa 2b and ribavirin was effective in reducing MERS-CoV replication in vitro, and after inoculation of rhesus macaques. In contrast to untreated, infected macaques, the treated animals did not develop breathing abnormalities and showed no or very mild radiographic evidence of pneumonia. Moreover, the abstract notes that treated animals showed lower levels of systemic (serum) and local (lung) proinflammatory markers, in addition to fewer viral genome copies, distinct gene expression and less severe histopathological changes in the lungs. Taken together, the researchers say these data suggest that treatment of MERS-CoV infected rhesus macaques with Interferon alfa 2b and ribavirin reduces virus replication, moderates the host response and improves clinical outcome. As these two drugs are already used in combination in the clinic for other infections, IFN-a2b and ribavirin should be considered for the management of MERS-CoV cases.
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The One Health Initiative is dedicated to advancing health care for the 21st century and beyond by accelerating biomedical research discoveries, enhancing public health efficacy, expeditiously expanding the scientific knowledge base, and improving medical education and clinical care, with a focus on the intersection of animal and human diseases. Recognizing that human health (including mental health via the human-animal bond phenomenon), animal health, and ecosystem health are inextricably linked, One Health’s mission statement objective is to promote, improve, and defend the health and well-being of all species by enhancing cooperation and collaboration between physicians, veterinarians, other scientific health and environmental professionals and by promoting strengths in leadership and management to achieve these goals. Regarding MERS, Dr. Monath notes in the article that: “We still don’t have a human vaccine. I mean, we have an experimental human vaccine, but nothing approved.”
Ms. Branswell notes that when there’s a new global epidemic or pandemic disease threat, such as SARS in 2003 and MERS now — there’s an initial burst of activity as scientists try to figure out how to design vaccines or drugs to prevent or cure the infection, with progress in their efforts publicized in media reports and published in scientific journals, the academic institution or institute where the work was done issuing press releases, and so forth. However, she observes that just because a vaccine can be made doesn’t mean it will be, since ultimately they are commercial products, and there has to be a business case for producing them.
“Companies don’t make big investments in bringing forward new vaccines just because they think somebody might want it someday,” Ms. Branswell cites Dr. Michael Osterholm commenting. As well as being a member of the OHI board, Dr. Osterholm is director of the Center for Infectious Disease Research and Policy (CIDRAP), director of the NIH-supported Center of Excellence for Influenza Research and Surveillance within CIDRAP, a professor in the Division of Environmental Health Sciences, School of Public Health, and an adjunct professor in the Medical School, University of Minnesota. Dr. Osterholm is is also a member of the Institute of Medicine (IOM) of the National Academy of Sciences and the Council of Foreign Relations, and in June 2005 was appointed by Michael Leavitt, Secretary of the Department of Health and Human Services (HHS), to the newly established National Science Advisory Board on Biosecurity. In July 2008, Dr. Osterholm was named to the University of Minnesota Academic Health Center’s Academy of Excellence in Health Research. In October 2008, he was appointed to the World Economic Forum Working Group on Pandemics.
Dr. Monath is cited observing that the cost of developing a vaccine is “roughly $200 million to $500 million” at minimum, and that many vaccines cost $1 billion or more to develop, with the only entities with pockets that deep are governments and the larger major pharmaceutical enterprises, with the latter only willing to push through their development and marketing pipelines products that will sell. “If there’s a market, things get made,” notes Dr. Monath, who was formerly chief scientific officer for vaccine maker Acambis, a British biotechnology company that since 2008 has been a wholly-owned subsidiary of Sanofi Pasteur Holding, parent company of French vaccine maker Sanofi Pasteur, the vaccines division of Sanofi, claimed to be the largest company in the world devoted entirely to making human vaccines. At Acambis, which specializes in developing novel vaccines targeting infectious diseases, addressing significant unmet medical needs or substantially improving standards of care, Dr Monath oversaw development projects on vaccines for C. difficile, West Nile virus and smallpox, among other diseases. For example, current Acambis development-stage projects include ChimeriVax-JE, which has shown excellent safety and efficacy profile in Phase 3 clinical testing and is currently undergoing paediatric trials in India, intended to provide an “ideal’ vaccine to address the estimated 50,000 cases of this viral disease in Asia every year. Acambis’ proprietary ChimeriVax technology, developed in association with St Louis University, has also been used to develop ChimeriVax-West Nile, which is undergoing Phase 2 clinical testing, making it the most advanced investigational vaccine against the West Nile virus. Acambis also has the only vaccine in development against Clostridium difficile bacteria, a leading cause of hospital-acquired infections.
“There has to be a substantial demand,” Dr. Osterholm explains, “That’s why today we’ve not seen the commercialization and licensure for example for either of an Ebola virus or something as common as West Nile virus,” Ms. Branswell noting that for example, childhood vaccines are business favorites because new customers are born every year, but to date, MERS fits more firmly into the Ebola model, having infected only about 130 people in four countries on the Arabian Peninsula over an 18-month period, and with an unpredictable future trajectory that is another strike against the business prospects of a MERS vaccine. It’s still an imponderable whether the virus will spread out of the region where it originated as SARS did from Hong Kong, or continue the way it has so far — infecting small numbers of people in a few countries, eventually like SARS, to run its course and then fizzle out.
On the other hand, some people fear that if there’s a MERS breakout from Saudi Arabia when several million Muslims disperse back to their home countries after next month’s Hajj pilgrimage, there will be no vaccine with which to counter it. In a in a June 7 Scientific American article Ms. Branswell noted that during, during the Muslim month of fasting, Ramadan that took place in July and August, and the even larger hajj pilgrimage to Mecca, this year expected to fall between October 13-18, with as many as two million people from around the globe expected to make umrah pilgrimages to holy sites of Saudi Arabia, infectious disease control would and will be a challenge.
In a Canadian Press report last March, Ms. Branswell cited Dr. Kamran Khan, who tracks global travel patterns as a tool to predict and interpret spread of diseases, noting that about 25 percent of people who travel from Saudi Arabia, Qatar and Jordan — all of which which have reported MERS-CoV cases — go to massively populated countries of South Asia like India, Pakistan and Bangladesh. In that article, Ms. Branswell also quotes Dr. Michael Osterholm, commenting: “These RNA viruses [Coronaviruses are RNA viruses, which mutate rapidly] you just can’t predict what they’re going to do. So the longer they stay in the human population, the more likely it is they’re going to do something that’s not good.”
“Vaccines are slow-moving boats,” comments BCM’s Dr. Hotez in the Sept. 10 Canadian Press article. “You could accelerate it so it’s not going to take a decade. But it’s not going to be done in two years either.” Ms. Branswell notes that Drs. Osterholm and Monath both support the idea that developing a vaccine for camels — or steering the current vaccine work toward an animal product — would make more sense if it can be demonstrated that camels are actually involved in the spread of the virus to people, noting that so far the evidence, while persuasive, but not proof-positive. However, Dr. Hotez expresses the opinion that that option will only work while MERS is still an animal virus that occasionally jumps into people — as opposed to mutating into a variant that starts spreading person to person, at which point it will be too late to try the animal vaccination approach. Dr. Osterholm, who is a member of the World Economic Forum Working Group on Pandemics, counter-argues that the various obstacles shouldn’t stop efforts to develop human MERS vaccines, contending that work done now would help if the world needs a vaccine later.
Dr. John J. Treanor, chief of the Infectious Diseases Division at the University of Rochester Medical Center in Rochester, N.Y., which specializes in viral infections such as Human Immunodeficiency Virus (HIV), Influenza, Human Papilloma Virus (HPV), and Dengue, suggested to Ms. Branswell that a MERS vaccine might be the type of product governments might want to develop and stockpile, similarly to the way the U.S. government has accumulated stocks of smallpox, anthrax and H5N1 bird flu vaccines. However, she notes that most governments can’t afford such expensive emergency supplies. And even those that can may choose not to spend scarce funds on expensive insurance against an epidemic that may never materialize, which muddies the prospects of commercial development of a MERS vaccine.
However, the experts do seem to agree that we shouldn’t be holding out breath, so to speak, waiting for a human vaccine for MERS to become available in the unhappy circumstance of a breakout epidemic or pandemic occurring.
SARS-CoV was transmitted from person to person mainly through respiratory droplets that are produced when a person sneezes or coughs and also through direct contact with a surface contaminated with infected respiratory droplets. “Once we figured out that infection control worked to stop the transmission, people started to get serious about it,” http://www.utmb.edu/scvd/faculty/ksiazek.shtml University of Texas Medical Branch epidemiologist and virologist Dr. Thomas Ksiazek, told ABC News in May. Dr. Ksiazek, who is Director of the National Biocontainment Training Center (NBTC) and a professor in the department of pathology at the University of Texas Medical Branch in Galveston, and who served as chief of the U.S. Centers for Disease Control and Prevention Special Pathogens Branch during the 2003-’04 SARS outbreak recalls that “We were pretty lucky, but the key was infection control and mindfulness,” noting to ABC that “mindfulness” will be key once again in containing the current outbreak since a vaccine for nCoV could take years to develop and test.
Dr. Peter Hotez noted to Houston Chronicle SciGuy blogger Eric Berger earlier this year that while there’s a lot that researchers don’t know about the MERS-CoV virus, what they do know is that mortality — some 60 percent — has been pretty high, but with the caveat that milder cases of the disease may not be getting reported, so it’s difficult to get a handle on the actual mortality rate so far. Dr. Hotez also observed that while evidence indicates that MERS is transmissible from person to person, up to now the rate has been low, although that doesn’t mean the virus can’t mutate, and could become much more easily transmissible. Nevertheless, he advises that we should not worry too much about MERS-CoV — at least yet. “It’s a delicate balance, you want to raise an appropriate level of concern, but you don’t want to make people overly worried,” he told Berger. “In Texas a far bigger concern would be diseases such as West Nile Virus, which in a surprisingly strong outbreak in 2012 killed 89 people.
If MERS becomes more easily transmittable, and begins to spread globally with umrah or hajj pilgrims returning from Saudi Arabia, possibly including some superspreaders, the disease could gain traction outside the current affected zone and that would be the time to start worrying.
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