Friday, March 23, 2018

Dengue Fever Now Linked to Stroke

            Everyone’s favorite antibody-dependent enhanced Flavivirus is back in the news this month, with an article from the Canadian Journal of Health linking the arbovirus to stroke, especially in the 2 months following infection.
            Dengue infects about 100 million people annually and threatens about 4 billion worldwide. It usually causes flu-like symptoms, but occasionally it presents with a hemorrhagic fever that can lead to spontaneous bleeding, organ failure and death. It is spread primarily by mosquitos.
Researchers at China Medical University Hospital in Taichung, Taiwan found that those recently diagnosed with dengue had almost 3x the risk for a stroke in the following 2 months, a phenomenon that is being noted by medical personnel in dengue-impacted regions. The data, collected between 2000 and 2012, was from 13,787 patients (most between 31 and 60 years of age) with newly diagnosed dengue.
Hopefully this study will spur further investigation into the etiology of this increased risk, so that it can possibly be mitigated or utilized by clinical evaluations.
-J. Cole Holderman

New Study Dispels Some Oseltamivir Fears

            Oseltamivir, more popularly known by the brand name Tamiflu, is an influenza antiviral drug that has undergone controversy in the last few years. It’s a neuraminidase inhibitor that was approved by the FDA in 1999 after a number of trials, primarily funded Roche, showed a favorable efficacy profile with no major side-effects. Tamiflu seemed to be a godsend against pandemic flu, and in 2005 and 2009, flu season fears lead to Tamiflu recommendations by several regulatory organizations, including the CDC, the WHO, and the European Medicines Agency.
            However, all was not right with the new medication. In 2007 a study in Japan found that the antiviral drug was associated with a significant increase in the occurrence of unconscious mind and a 50% increase in the risk of neuropsychiatric events in children. Japan was quick to restrict the drug’s use and include a warning on the package inserts for Tamiflu. Roche reviewed its data and declared that there was no increase in neuropsychiatric risk, but data continued to come from similar adverse events in other areas of the world.
            In the meantime, case reports of abnormal behavior manifested in the United States, prompting the FDA in 2006 to require a warning insert for hallucinations, delirium, self-harm, and suicide.
            Since then, studies have mostly found only ambiguous results, with data to murky to rule out or confirm these behavioral side-effects.
            Recently a study by researchers from the University of Illinois at Chicago seems to suggest that Oseltamivir may be safe after all. Researchers used historical data to compare changes in mental state of children who received Oseltamivir for a flu diagnosis to children who had a flu diagnosis but did not receive Oseltamivir. They controlled for personal influencers of suicidal ideation by benchmarking the mental states of children to their mental states before the flu diagnosis at set intervals, establishing the metric as ‘overall change in mental health over the case of influenza infection as modified by Oseltamivir.’
            The data showed no significant difference in changes of mental state between children taking Oseltamivir and those who were no prescribed the antiviral. This seems to suggest that Oseltamivir is safe to use in children, but it will likely take more evidence to convince the medical community that this is really the case.

            -J. Cole Holderman

For Some Reason, the Majority of the U.S. Appears to be Willing to Pay to be Vaccinated for Ebola

            A recently published study, conducted during the height of the Zaire ebolavirus epidemic in Western Africa by George Mason University researchers has found that 59.6% of Americans would be willing to pay at least $1 to be vaccinated for Ebola virus, despite being at incredibly low risk for infection. One wonders if protection from this miniscule risk would even outweigh the side effects of a potential vaccine, but it seems that media sensationalism and panic play a larger role in the medical decisions of the American public than such measures.

            The study was part of a larger effort to quantify potential demand for an Ebola vaccine worldwide. Despite the (perhaps dubious) validity of the American public’s views on the matter, this number is promising for those in areas actually at risk for another Ebola outbreak. They indicate that if push comes to shove, Americans are likely willing to foot the bill to make up the development costs of a protective vaccine in these areas. That’s probably good news, regardless of the motives.   

            -J. Cole Holderman

Thursday, March 22, 2018

CTCF & Herpes Latency

Researchers at Harvard Medical School are discovering more and more about herpesviruses latency periods that give us insight into how the infection is able to be sustained in the cells, waiting and “ready to strike.” The research team, which included Microbiology and Genetics Professor David Knipe, found that the herpes simplex viruses use a “host protein called CTCF, or cellular CCCTC-binding factor” in order to control its own latency and active cycles. CTCF protein is able to bind to viral DNA and act as a key regulator. This host protein and viral interaction is an incredible advantage for the herpes simplex viruses as it allows the virus to go from silent to active meaning that the pathogen can continue on from one host to the next. During the latent period of herpesvirus infection, there are no symptoms and the virus does not replicate due to latency genes (LAT) turning off the genes that encode for viral RNA transcription. Next to the LAT gene is a gene called the ICP0 that stimulates replication and indicates active viral infection. The alteration of these two genes along with the new finding that the CTCF protein enhances this alteration is important in learning more about persistence in herpesvirus. In a knockout gene mice study, the researchers found that without the CTCF binding sites, the protein had nowhere to bind to and thus hindered the herpesvirus’ ability to switch from silent to active infection.


Isn’t it time to get rid of the last of the smallpox?

Smallpox, a disease that’s been clinically unseen as it was eradicated in 1980 and there are only 2 stocks of the disease left in the world! Those two stocks are in Moscow and at the CDC in Atlanta. Due to the time since the last instance of smallpox, the article states that the majority of the population may have suppressed immunity to smallpox. However, the pox viruses are cross reactive and can be protective against one another so people that have had the vaccinia vaccine have antibodies against the pox viruses. Smallpox, a class A bioterrorism agent, is easily transmissible and can infect a large portion of the population and incites fear in all people due to the severity of the disease. This is relevant to the world right now as we have to consider whether it is time to get rid of the smallpox stocks is now -- the recent chemical attack in Salisbury has made people nervous about any kind of stockpiling of dangerous diseases that could be weaponized to hurt a majority of the population. With an increasing population of immunosuppressed people, the protection and safety plans for a bioterrorism attack with smallpox must be re-evaluated as it doesn’t consider this data. In the event of a smallpox attack, officials say that the non-licensed vaccines for immunosuppressed populations would be granted emergency approval for use. Implications for this published research could be potentially dangerous as it estimates the infectious and lethal impacts of releasing the smallpox virus on NYC and Sydney. This article brings to the forefront the question - isn’t it time to get rid of the smallpox stocks?


Hiking through Yellowstone for Gene Therapy

Rebecca Hochstein, a recent doctorate from Montana State University’s Microbiology and Immunology department, has dedicated seven years of her life to hiking through Yellowstone on the search for the mysterious pathogens within the steaming hot springs. Hochstein and her research team recently found a new DNA virus called the “Acidianus virus” with a capsid described as “lemon-shaped” and able to transform into “long, thin cylinders” unlike normal icosahedral and helical capsids. They are investigating the way that this lemon-shaped virus assembles its capsid and how it is able to eject its DNA into a host. Much like squeezing a lemon, the virus squeezes out its DNA when transforming from the lemon shape to the long, thin cylinders. Research into this new pathogen gives the virology world a better basic understanding of this shape of virus and provides a potential for new gene therapy mechanisms. The Acidianus virus was isolated from the boiling acid hot springs at a temperature of 80℃ - a heat resistance that can be used to benefit this virus as a vector. The high heat-resistance of Acidianus virus along with its ability to operate in acidic conditions means that the capsid would be able to have an extended life within the host, thereby implying that the gene therapy can be used for longer periods of time within patients. Research teams have already provided experimental models that support the idea that this virus can be used as a viral vector in the GI tract of animals which only opens more doors for smart drug delivery. The main issue the team is facing is that the virus can’t grow in the lab which makes retrieval of the virus dangerous and difficult to study further. We may be on the right track to developing a new viral vector, but we’ve got a bit of a way to go!


Our hero: cervicovaginal mucus!

Dr. Samuel Lai and his team at the University of North Carolina’s Eshelman School of Pharmacy in Chapel Hill have been researching the properties of cervicovaginal mucus (CVM) and how it can prevent STI transmission. CVM helps protect the cervix and the vaginal walls from trauma and abrasions that can cause susceptibilites to different viruses like HIV and other STIs by providing lubrication and trapping contaminants. Live epithelial cells are less exposed than the dead epithelial cells within the cervix which makes them less susceptible to viruses. The mucus not only protects these cells from the outside but also from the innate defense molecules within it. HIV, however, can infect the mucus and even one HIV cell can lead to serious infection. Some women have different types of CVM that makes them more resistent to HIV infection. Researchers are studying how this first line of defense against HIV can be reinforced and improved to decrease the rate of infection by inducing local antibody secretion. This reinforcement of the mucus barrier has been shown to be effective in decreasing herpesvirus transmission. The research team has been developing a vaginal ring that can secrete the local antibodies in order to reinforce the mucus barrier and protect against other STIs and potentially HIV infection. The implications of this research reaches beyond just STIs as well, as the research team states that the reinforcement of the mucus barrier can be applied to airway mucosa which means that it could potentially be protective against influenza!