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!


The Future is Ultraviolet

Researchers at Columbia University have been studying ways of using ultraviolet light to kill airborne viral influenza particles. You may be wondering - “isn’t ultraviolet light the stuff that we should be staying away from?” - it’s actually a specific type of UV light! While ultraviolet A (UVA) and B (UVB) light is harmful to the skin and eyes, Dr. David Brenner and researcher David Welch figured out that far ultraviolet C light (far UVC) doesn’t penetrate the skin and so can be used relatively closer to people than UVA or UVB light. This far UVC light is predicted to be able to kill the viral particles in the air, for example after someone sneezes. Welch was quoted as saying “With a very small dose, we were able to kill 95 percent of viruses.” The possibilities of using this light in hospitals or schools is attractive, however even though these researchers haven’t seen any biological hazards or health consequences of using this far UVC light, more research will likely be needed. Another thing holding this process back is the fact that the light would cost $1000, though they’ve said that once it is mass produced, the cost is expected to steeply decrease.


Lassa Fever in Nigeria

This year is an unsually high number of Lassa fever cases for Nigeria, according to the Nigerian WHO Representative Dr Wondimagegnehu Alemu. Currently the Nigerian Center for Disease Control (NCDC) has been working with WHO to provide medical supplies to areas iwhtin Nigeria that are experiencing the high number of Lassa fever cases. A danger that has been mentioned is that due to infection and control procedures not being strictly adhered to in health care settings, health care workers in Nigeria are at higher risk of contracting the disease. Eleven health care workers have been infected with the virus and four subsequently died. According to WHO, within the last month hundreds of individuals in Nigeria were infected with the virus, by last count 40 people have died from the disease. Public health officials have broadcast health warnings to the people of Nigeria and currently are working on ensuring that the public knows how to prevent the spread of the disease. The Lassa fever virus is a zoonotic virus that in Nigeria has been spread by rats. Officials have warned residents to avoid bush burning as the act displaces the rats and allows them to scurry into homes where they leave excrement which can infect the food, water, and utensils within the home. Residents are warned to keep water in rat-proof containers, make sure that all food they buy is properly washed and cooked, and to practice good hygiene in order to avoid further spread of the disease.


Tracking the College Flu!

Ah, college dorms - a place for learning, fun, and an intimate affair with viral infections! Recently, ScienceNews published an article about an ongoing study that is looking at the spread of respiratory viruses across a college campus. At the University of Maryland the study, aptly named “C.A.T.C.H. the virus” (Characterizing and Tracking College Health), is testing blood samples, nasal swabs, and breath samples from infected freshmen and their close contacts. But what exactly are they looking for?

The researchers are specifically asking for any participants that have symptoms of a respiratory infection and are looking at viruses such as influenza, adenovirus, coronaviruses, and respiratory syncytial virus. According to the researchers, they’ve reported that you could technically be at risk by just breathing next to someone that has the flu! With this year being one of the worst flu seasons in a decade, this study is all the more important. Is sneezing and coughing into a tissue or your elbow not enough precaution anymore? The researchers are hoping to establish a lead on how the virus mutates throughout college dorms by following each contact of an infected student. At the published time, the flu virus hadn’t swept through the University of Maryland dorms yet - but it’s just a matter of time. We’ll have to wait and see if the research time will be able to pinpoint more effective measures of making college dorms a safer place to house the many students. As their tagline says, “It’s snot your average research study.”


Darkness for the Sparrow

A recent article in ScienceNews has discussed whether light pollution can impact spread of diseases such as West Nile virus and malaria. The innocent looking house sparrow is a healthy looking home to viruses such as West Nile virus. The researchers have found that these house sparrows- which are present all across the United States are able to transport this virus to many regions. Mosquitos that bite the house sparrows can transfer the virus onto humans. Environmental researchers at the University of Nevada and South Florida have taken a keen interest in how the birds interact with human populations in the U.S. One theory that they have tested is to see whether light pollution lends itself to increase in spread of disease. House sparrows that are housed in darkness were shown to have high virus concentration in their blood for 2 days as opposed to when housed in dim lighting they had 4 days of high virus concentration. The light pollution at night only increases the amount of time it takes for the house sparrow immune system to fight off viral infection which just increases the time in which mosquitos may bite the house sparrow and pick up significant viral load to then transmit to humans. This article brings up the question of whether light pollution has impacted malaria transmission as well. If we target light pollution, could we decrease the incidence of diseases like west nile virus and malaria? As the saying goes, more research is needed.


Hepatitis B and C in homeless populations in London

As we all know, homeless populations across the globe do not have the same levels of access to health care as housed individuals. This has only become more apparent in a recent article published in the British Thoracic Society Journals investigating the high incidence of hepatitis B virus, hepatitis C virus, and latent tuberculosis infection in homeless populations. The researchers found that a substantial population were not immune and hadn’t been vaccinated against hepatitis B virus. Those of the population that consented to the study that were intravenous drug users were more likely to be vaccinated due to them being a target population for vaccination outreach in the UK. The hepatitis B vaccine is available and effective at protecting against hepatitis B infection - so why is it that the homeless population in the UK has not been targeted for vaccination outreach? This study described the population as “usually hard-to-reach” and thus used convenience sampling. They weren’t able to have intoxicated individuals participate due to consent issues, which only makes a stronger case for helping homeless individuals stave off these blood-borne viral infections. The provided data in the study could potentially be used to estimate cost-effectiveness of at least giving the hepatits B vaccine to homeless people in the UK. This published article has only reinforced the need for support for homeless populations in the UK.


Viruses Save the NZ Honeybees!

Honeybee colony devastations across the nation have spurred on researchers to try and find new ways to save the honeybees. In an article published in the New Zealand Herald, researchers may have found a way to help save the honeybees!  American Foulbrood (AFB) is a bacterial pathogen that quickly infects large colonies of honeybees in New Zealand, and due to laws banning the use of antibiotics to control the pathogen, beekeepers have had to take preventative measures to ensure continuation of honeybee colonies. Microbiologist Dr. Heather Hendrickson heads a new project to use viruses to prevent infection of honeybee hives. Dr. Hendrickson’s project involves isolating bacteriophages from the soil beneath the healthy hives and using simple viruses to infect AFB and destroy it from within. While it has not been field-tested yet, Hendrickson and her team are confident that the simple viruses will be able to destroy the pathogen and then naturally degrade over time leaving no residue on the honey. The research team is hoping to develop a product that incorporates the simple viruses and can be used by all New Zealand beekeepers.


Iceland to “Ice” HCV by 2030

Hepatitis C virus (HCV) affects nearly 71 million people worldwide and is most commonly transmitted through the blood via injection drug use, contaminated blood transfusion, or unsafe health practices. Thus, most people infected by the virus were infected when the virus was not known about. It causes acute to chronic infection and may lead to fulminant hepatic failure in a few rare cases. Furthermore, as a leading cause of death due to cirrhosis or hepatocellular carcinoma, the pathway to eradication of HCV is a worthy one but it precluded by the lack of access many people have to the drugs that can cure them of the virus. These drugs, like sofosbuvir, are incredibly expensive, but countries like Iceland are leading the world in making them available to those who need them. The TraP Hep C program in Iceland hopes to administer these curative drugs through government and private health organizations (and the penitentiary system) to hopefully eradicate the virus from the country by 2030. While ambitious, I think that the United States has much to learn from such endeavors.



The Multifunctional VP40 Ebola Protein

Researchers at Purdue have recently discovered that the introduction of mutations at certain amino acids along the stretch of VP40, an Ebola envelope protein, can vastly diminish the virus’ ability to enter and replicate in new cells. While this may come at no surprise considering envelope proteins usually allow for viral entry and exit from the cell, the dynamics of this experiment shed light on the way structure and overarching functions of VP40 in Ebola infection. More specifically, it was found that the shape of VP40 may change depending on where in the viral lifecycle it is, most likely due to pH differences in the cell. More importantly, it was shown to be in a monomer, dimer, or octamer in cells, with the octamer being a better tropogen for phosphatidylserine, a lipid on the cell membrane. Mutations to the protein make VP40 more likely to be in the less effective dimeric or monomeric forms on the viral envelope, which translates to a diminished ability for the virus to infect the cell. Moving forward, such studies show that VP40 may be a good target for therapeutics against Ebola because it seems to be so integral to viral replication throughout the cycle.