Friday, May 16, 2014

Will MERS-CoV be the next SARS? Predicting Highly Pathogenic Pandemics



image:www.neatorama.com
"At the end of April, 2014,   the WHO reported that about three-fourths of new cases of MERS-CoV were 'secondary infections' spread between people, mostly doctors and nurses at hospitals treating MERS patients. The growing evidence that the virus is being transmitted between people, and not just from sick camels to people as had previously been suspected, raised fears of a possible epidemic. Even so, experts said MERS is not spreading easily between people and would have to undergo a mutation to present a grave threat to the world." While the origins of transmission appear mainly zoonotic, the human to human transmission rate is increasing. Given that Saudi Arabia is host to the Hajj usually in October, the recent jump in human to human transmission is concerning. See:http://www.huffingtonpost.com/2014/04/30/mers-virus-spread_n_5242783.html An article entitled: "Don't Panic About MERS Yet, Health Experts Say by Joshua Hersh the following insights case some doubt on the probably of the rapid evolution of MERS.



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"Every case has had some direct contact with the Arabian Peninsula," said Dr. David Swerdlow, the head of the MERS monitoring team at the U.S. Centers for Disease Control and Prevention. "If the virus doesn't generally infect more than one person, it's not going to lead to sustained transmission," Swerdlow added. "We are watching carefully the situation in Saudi Arabia and the U.A.E., and we are watching for evidence of sustained transmission, which would be a very big cause of concern. Are we concerned? Yes, we are, but we've also been concerned for a year and a half." 

"Saudi and WHO officials have indicated that the recent spike in MERS cases may be related to seasonal and weather conditions. Saudi Arabia reported a similar spike in March and April of 2013. A mutation that would allow MERS to spread more easily among humans would not be unprecedented. In 2003, the SARS virus, which is closely related to MERS, made a major leap into humans in China when a key protein changed. That disease went on to kill about 800 people, and sickened several thousand." See: http://www.huffingtonpost.com/2014/04/30/mers-virus-spread_n_5242783.html

The Centers for Disease Control and Prevention provides the following definition of Coronaviruses (CoV): "Coronaviruses are common viruses that most people get some time in their life. Human coronaviruses usually cause mild to moderate upper-respiratory tract illnesses. Coronoviruses are named for the crown like spikes on their surface. There are three main sub-groupings of coronaviruses, known as alpha, beta and gamma, and a fourth provisionally assigned new group called delta coronoviruses. Human CoV were first identified in the mid 1960's. The five CoV that can infect humans are: alpha CoV229E and NL63 and beta CoV 0C43, and SARS-CoV, the coronavirus that causes severe acute respiratory syndrome. CoV may also infect animals. Most of these usually infect only one species or at most a small number of closely related species. However, SARS-CoV can infect humans and animals, including monkeys, Himalayan palm civets, raccoon dogs, cats, dogs and rodents." See:  http://www.cdc.gov/coronavirus/about/index.html

"A novel coronavirus called “Middle East Respiratory Syndrome Coronavirus” (MERS-CoV) was first reported in 2012 in Saudi Arabia. It has caused severe illness and death in people from several countries. On May 2, 2014, the first confirmed case was reported in a traveler to the United States. On May 11, 2014, a second U.S. imported case of MERS was confirmed in a traveler who also came to the U.S. from Saudi Arabia. The two cases are not linked and MERS as of 14 May 2014 is not considered a public health emergency." See: http://www.cdc.gov/coronavirus/about/index.html


image:www.delhidaily.news.com

While MERS-CoV is not yet considered highly pathogenic and remains primarily zoonotic (passing from camels to humans), the history of virus evolution does not bode well for the eveolution of MERS-CoV into a more highly pathogenic strain. When we look at the evolution of viruses several events come into play. "Pathogenicity is the potential capacity of certain species of microbes or viruses to cause a disease. It is characterized by complex pathogenic properties which evolve during their struggle for existence. Pathogens are characterized by specific actions. Each species is able to give rise to different infectious processes. It is often used interchangeably with the term 'virulence', although virulence is used more specifically to describe the relative degree of damage done by a pathogen, or the degree of pathogenicity caused by an organism. A pathogen is described partly through its virulence by its ability to produce toxins, enter tissue,colonize, hijack nutrients, and its ability to immunosuppress the host.  Pathogenicity is only one factor however and coronavirus are likely to evolve. Discussing Avian flu H5N1, Georgii Bazvkin of the faculty of Bioengineering and Bioinformatics of the Moscow State University in collaboration with the Central Research Institute for Information Transmission Problems of the Russian Academy of Sciences (IITP) and Professor Alexy Kondrashov published a paper on the evolution of Avian influenza: 

"A reassortment may produce a highly virulent strain because strong genetic shift makes it "unfamiliar" to the immune system of most humans. which allows the virus to spread efficiently throughout the population. This evolutionary scenario  is known as antigenic shift. Another path, knowns as antigenic drift is a process of gradual accumulation of smaller mutations. These mutations cause changes in the viral antigenic proteins, primarily the surface antigens hemagglutinin (HA) and the neuraminidase (NA). The genes coding for these proteins evolve rapidly in the course of the arms race between the virus and immune system. The seasonal flu outbreaks are primarily caused by this antigenic drift, — explains Georgii Bazykin. — Hence every year many of us catch a flu caused by a new strain of the constantly evolving virus.”Both processes are due to changes in the viral genome, but of a different degree. The differences in the seasonal flu usually result from point mutations in the influenza virus genes, while major pandemics are often connected to profound genetic shifts known as reassortments." See: http://globalbiodefense.com/2014/01/13/prediction-of-the-future-flu-virus/#sthash.rAogNrOn.dpuf When we consider antigenic shift and pandemics, MERS may be more concerning. "Drs. David Morens and Anthony Fauci warn in a new paper: 

While it has become possible to eradicate certain infectious diseases [smallpox and the veterinary disease rinderpest], and to significantly control many others [dracunculiasis, measles, and polio, among others], it seems unlikely that we will eliminate most emerging infectious diseases in the foreseeable future. Pathogenic microorganisms can undergo rapid genetic changes, leading to new phenotypic properties that take advantage of changing host and environmental opportunities. Influenza viruses serve as a good example of emerging and re-emerging infectious agents in their ability to rapidly evolve in response to changing host and environmental circumstances via multiple genetic mechanisms. New ‘founder’ influenza viruses appear periodically, cause a pandemic, raise widespread population immunity, and then, in response to human immune pressures, evolve and persist for decades using multiple genetic evolutionary mechanisms to sustain continual immune escape. The 1918 influenza pandemic virus is one example: over the past 95 years, its descendants have evolved continually by antigenic drift, intrasubtypic reassortment, and antigenic shift, the latter producing new pandemics in 1957 and 1968. Even the genetically complex 2009 pandemic H1N1 influenza virus is a descendant of the 1918 virus. Such continuous genetic hyperevolution forces us to develop new influenza vaccines containing new antigens on an annual basis." See:http://science.time.com/2013/07/10/from-aids-to-sars-to-mers-emerging-infectious-diseases-remain-a-dire-threat/ 

Catching MERS-CoV before it evolves is critical to prevention. Novavax announced it has developed a vaccine which successfully stopped MERS infections in laboratory based trials with applications for both humans and animals (camels are suspected to be the primary host). http://basicsmedia.com/novavax-inc-nasdaqnvax-taking-mers-by-the-horns-9412 Although the vaccine is considered highly experimental it will be interesting to see the evolution of MERS and Novovax research and drug development efforts to control this. When we consider pandemics, literature on MERS would seem to suggest that the risk of MERS becoming a pandemic remain rather low, however, as we encounter emerging diseases of the future, we must pay close attention to the potential of pandemic diseases. 
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