Saturday, February 28, 2015

New technique in the fight against filoviruses

A team of researchers at the Scripps Research Institute (TSRI) has uncovered a cross-reactive antibody that binds to Marburg virus, an equally lethal cousin of Ebola virus. By growing crystals on the antibody (attached to its viral target) and using x-ray diffraction, the team produced three-dimensional images of the antibody-virus interaction (cool image below). Though the antibody specifically targets Marburg virus, the team believes the antibody to be cross-reactive with related viruses (including Ebola viruses).

This study represents the first time that Marburg's glycoprotein has been seen in its infectious state, and may help unlock novel techniques in the development of therapeutics against Marburg virus and other filoviruses. With the proper engineering, one could hypothetically use the antibody to target and bind Ebola virus and other filoviruses to prevent host cell entry and infection.

Marburg virus (purple) and Ebola virus (blue) interactions with antibodies

-Nick Simon

ZMapp: Coming To A Town Near You

Until recently, ZMapp has only been used as a drug to treat Ebola virus infections in emergency cases, but that may be about to change. The drug is now being tested in patients with Ebola, in a joint effort by the United States and Liberian governments.

In order to qualify for the study, patients must be either (1) adults or children with EBOV infections admitted to Liberian health centers (2) healthcare professionals returning to the United States for treatment against EBOV infection or (3) adults or children infected with EBOV in the U.S. after exposure to an infected individual.

As treatment, patients in the study will receive three doses of ZMapp per day for 3 days. ZMapp is a collection of antibodies that function by targeting surface proteins of the Ebola Virus virion. In order to manufacture the drug, tobacco plants are genetically altered to synthesize the antiviral proteins.

Additionally, patients will receive supportive treatment, such as IV fluids. The control group in study will receive only supportive treatment, which also includes treating additional infections, maintaining blood pressure, and ensuring sufficient oxygen consumption.

Thus far, ZMapp has been administered as emergency treatment to only nine patients, but the study hopes to enroll 100 participants. Consequently, the joint effort by Liberian and American researchers is intended to assess how well ZMapp performs as an antiviral against Ebola.

Although control trials like the one just described appear to be common in assessing novel drug therapies, I question the ethical implications of administering potentially life-saving treatment to only a cohort of candidates. The efficacy of new drugs should be ascertained, but if we are to conduct clinical research with an explicit intent to do no harm, maybe it’s time to remodel clinical drug tests.

How do you withhold potentially life-saving treatment? How do you ensure that the treatment group is safe? I'm not entirely convinced that we're qualified to answer these questions.


Thursday, February 26, 2015

Public Health Challenges in Medical Volunteerism - You Can Haz Ebola?

A physician that traveled to West Africa to help treat patients with Ebola recently commented on media scrutiny since his return to the United States. After arriving in New York in October, Dr. Craig Spencer was diagnosed with an Ebola virus infection. He was treated and eventually recovered, but in the interim, public health officials criticized and questioned the risk he posed to the general public.

According to Spencer, he was named a public health menace by some and a hero by others, to which he responded, “...I am none of those things.”

Spencer went abroad to serve with Doctors Without Borders. He mentioned the challenges of providing medical services abroad, especially in treating such a dangerous virus, but Spencer also expressed the sense of satisfaction he felt from helping infected patients. “No matter how hour of profuse sweating in the suit and the satisfaction I got from treating ill patients washed away my fear and made me feel new again.”

Spencer’s comments raise interesting questions about the role of physician voices in public health campaigns. As Ebola. measles, and other infectious agents continue to pose substantial risks to communities domestically and abroad, it is important for the general public to hear from professionals working most proximally with these diseases.
Subjecting medical practitioners to rebuke from the media and public outcry may make it less likely for them to participate in efforts against infectious disease in developing areas, so it is critical that doctors with past or present experiences contribute to national dialogue about safe and ethical medical volunteerism.


Saturday, February 21, 2015

Dont Wash out that Dirty Mouth

Your mouth is a dirty place.

Your gums are teeming with bacteria—and don’t even get me started on the colonies living between your teeth. Some of these colonies are harmless, but some cause serious disease if they manage to get under the outer tissue layer.

One such bacterium is enterococcus faecalis. Normally it lives in the gastronintesintanl tract, but can occur in the mouth. However, if it gets into your blood stream,  the result can be endocarditis (infection of the heart) or bacteremia (bacteria in the blood stream).
Often, this bacterium causes problems for dentists and their patients—especially during root canals. And infection can be hard to dispose of, especially since the bacteria secretes a sticky protective layer called a biofilm.

A recent study in the journal of Applied and Environmental Microbiology has discovered a helpful phage—or bacteria-targeting virus—that seems to work even better than antibiotics. The phage, called EFDG1, was highly effective in all the situations the researchers tested. It almost completely eliminated the bacteria is both normal culture and ones rife with biofilm.

The coolest part of this? The phage was originally isolated from sewage. It is now being explored as a possible therapy to drastically reduce the rate of E. faecalis infection after dental surgery.      



Floridians Oppose Release of Mutant Mosquitos for Viral Vector Control

A proposal to release genetically-engineered mosquitos into Key Haven, Florida in an effort to reduce mosquito populations and limit the spread of emerging viruses like Chickungunya and Dengue has met with considerable resistance from the public.  The mosquitos are a product of for-profit biotechnology company Oxitec, which has already released 70 million of these modified mosquitos into other communities arround the globe for the same purpose.  The Oxitec mosquitoes contain a gene called OX513A that makes their offspring inviable.  When these Oxitec mosquitos are released into the normal mosquito population, they compete with normal mosquitos to breed with females, “occupying” the female population with offspring that will not survive and thereby reducing the total amount of productive mosquito breeding and limiting the growth of the mosquito population. 
Many residents of Key Haven, a peninsula town of 444 homes, are wary of these genetically-modified insects and the Mosquito Control District has received over 1,600 emails from residents voicing their opposition, in addition to a petition against the mosquito release with over 149,000 signatures.  Although the moquitos are engineered to be a self-limiting population, these residents still feel the choice to release these insects would be dangerously irrevocable and unnecessary.  Currently, the community uses alternative mosquito control strategies such as the distribution of inseciticdes by planes flying overhead.  By contrast, the mutant mosquitos offer a more targeted approach with fewer negative consequences—as well as many benefits—to the human population of Key Haven. 

However, the self-limiting nature of these bugs means they do not represent a permanent vector control solution.  When the mutant mosquitos die off, the normal mosquito population could quickly recover its former population size, leaving the Key Haven community in the same place it began.  In order to maintain a reduced moquito population continued release of the Oxitec mosquitoes would be necessary.  The Oxitec company therefore stands to make a considerable profit if the Florida Keys Mosquito Control District moves forward with this strategy.
Read the full article here:

Chikungunya Or Arthritis?

Chikungunya is an ARBO virus that is known to cause fever, rash, and joint pain and swelling. Consequently, a growing number of physicians have encountered difficulties distinguishing between the virus and rheumatoid arthritis.

Interestingly, research published in Arthritis and Rheumatology recently indicated that blood tests from chikungunya-infected patients and patients suffering from rheumatoid arthritis yield similar results. The study also argued that chikungunya-associated joint pain lasts 12 - 15 months for the majority of patients, but that the pain can persist in patients for up to 3 years. Convoluted blood tests make it additionally difficult for clinicians to discern between the two conditions.

This study was limited in terms of sample size, however, for only ten individuals were included in the study, Nevertheless, 8/10 of patients with viral infection also met the American College of Rheumatology’s criteria for arthritis, providing some evidence that further investigation may be warranted.

Originally discovered in Africa about 60 years ago, chikungunya has been increasing in prevalence around the globe ever since. The virus has spread to the Caribbean and Central and South America. Moreover, the CDC estimated that approximately 2,000 Americans were infected with the virus after traveling to other countries in 2014, and the state of Florida saw an interesting increase in cases of chikungunya, suggesting that mosquitoes in the area may be transmitting the virus.

Ultimately, this research is most salient for practicing physicians, who should take careful medical histories when meeting patients. Taking a detailed history may uncover risk factors for chikungunya that could help distinguish the disease.


Friday, February 20, 2015

Okay, is Ebola Airborne or Not?

Scientists and public health officials alike have argued over the routes of transmission of Ebola virus for a while, especially since the start of the recent outbreak in West Africa. While officially Ebola is considered to be spread only via bodily fluids, there remains some debate. Many are convinced that it can in fact be spread through respiratory droplets as well. 

While this possibility is a scary one, it’s one that is “very likely”, according to a team of researchers led by Michael Osterholm, an epidemiologist at the University of Minnesota. Blood, feces, and vomit are undeniably the primary routes of virus transmission; however, Dr. Osterholm maintains that tiny droplets of virus containing fluid hang in the air and are occasionally breathed in by others. This, he argues, provides an unrecognized method of transmission of the Ebola virus. Evidence the team uses to draw this conclusion includes Ebola virus found on the outside of face masks worn by health workers caring for Ebola victims. In addition, as described in Richard Preston’s The Hot Zone, Ebola virus has been passed between monkeys through a respiratory route. 

While this evidence in no way proves that the Ebola virus strain responsible for this massive outbreak can pass between humans by a respiratory route, it should serve to keep the door of the public and more importantly of the scientific community open to this possibility. Hopefully more rigorous research will continue to be done over the course of this outbreak, so we can better understand the nature of this disease and more effectively manage it in the future.

-        Eddie

Thursday, February 19, 2015

Chickenpox giving more than just a little Shingles

Most people know that when you get chickenpox as a child (caused by the varicella zoster virus or VZV) you get covered in annoying red spots. Most people also know that these same infected people may also experience shingles later in life: the sometimes life threatening eruption of incredibly painful rashes over the skin. That’s about it

Shingles is generally a disease of the elderly, and not a particularly pleasant disease at that. However, a recent study my Dr. Don Gilden of the Colorado School of Medicine suggests that shingles may not be the only disease that VZV is causing. While the paper does not prove a connection, it suggests that VZV may be a major co-factor.

This disease, a vessel condition known as giant cell arteritis, effects about 1 in 2000 people over the age of 80. With a normal onset in people older that 60, it causes sudden vessel inflammation in the head, neck and arms causing headaches and significant pain. Bad cases lead to stroke, blindness and death.

Usually giant cell arteritis is imperfectly treated with steroids, but the new research suggest that this correlation with VZV might make a synergistic course of anti-virals beneficial to those suffering from this disease. Perhaps, even administering the shingles vaccine could be helpful.




Are We About To Win The Battle Against HIV?

A recent study published by Nature and conducted by The Scripps Research Institute claims to have identified a new, potent compound against HIV. This drug candidate is reported to be effective and powerful against all HIV strains.

The compound appears to be effective against HIV-1, HIV-2, and SIV. In the study, the drug candidate showed high efficacy against doses of virus higher than those that usually occur in human infections. This compound is not an antibody, but it retains high neutralizing ability against the virus. Consequently, it could be developed into a vaccine alternative.

According to the report, the anti-viral protein binds to two regions of the HIV virion simultaneously, preventing viral entry. The high binding affinity is a consequence of the protein’s structure, which mimics CCR5 (the CD4 receptor targeted by HIV).

Using comparative data, researchers found that this protein neutralizes HIV better than the best antibodies currently available against the virus.

This project reflects a culmination of scientific advances. In order to administer the drug candidate, the researchers used AAV, an orphan parvovirus with no disease associations. AAV integrates into cell genomes, allowing these cells to synthesize the anti-viral protein at protective levels.

Maybe we're closer to diminishing -- or eliminating -- the HIV/AIDS epidemic than we thought. 


Tuesday, February 17, 2015

Aggressive HIV Strain In Cuba

Recent media coverage has payed close attention to the emergence of an HIV strain capable of causing AIDs in only 3 years if left untreated. (Average conversion time tends to be approximately 10 years.) Although significant progress has been made in efforts against HIV, especially in terms of antiretroviral therapy and health education, the fast conversion time of this HIV strain presents new challenges.

The strain of HIV causing concern is called CRF19. Thus far, CRF19 has been identified in some parts of Africa, but it appears to be widespread among HIV-infected patients in Cuba. Attention to the aggressive strain of HIV developed as physicians began noticing an increase in patients presenting with advanced disease.

From a public health perspective, the more aggressive strain of HIV poses significant risks, especially among patients unaware of their infection, who may go on to transmit the virus. Additionally, HIV tests may produce negative results if performed too early after infection, giving patients a false sense of security.

Researchers suggest that the CRF19’s ability to trigger AIDs conversion may be due to an enhanced ability to maintain a high viral load, driving the immune response, and hastening AIDs progression. Nevertheless, active monitoring and administration of timely antiretroviral therapy may protect infected persons from rapid AIDs development--emphasizing the importance of screening and drug access.


Thursday, February 12, 2015

Keeping Enterovirus in its Pocket

Recent research out of Purdue University helps shine light on a particular viral mechanism that has the ability to serve as the basis for future anti-viral therapy. The research, conducted by the Rossmann lab, identified the structure of a “pocket compound” in Enterovirus D68.

This “pocket compound” is a small molecule on the surface of the outer viron capsid, or shell, which acts a sort of lock. When EV-D68 attached to a human cell, this little molecule is released or pushed away which allows the virus to ditch it’s coating and be taken up by the cell for further replication.

Researchers also identified a drug called Pleconaril which was also able to bind to this same pocket. It competed with the natural “pocket factor” for the spot on the virus and, when bound, inhibited the viral un-coating, and thus infection.

The main idea is to use this new drug as a possible anti-viral agent against the recently seen uptick in pediatric EV-D68 infection. However, the drug, as it currently stands does not react with the pocket structures of the currently circulating strains—although it does react with the originally tested lab version. Scientists hope to tweak the chemical structure to make it applicable to the current clinical need.



Wednesday, February 11, 2015

Wasps as Perpetrators of Viral Bioterror Against Ladybugs

Yesterday under the Weird&Wild heading of National Geographic News an article was published about viral bioterror and mind control among insect species.  New research suggests that a wasp called Dinocampus coccinellae uses a virus designated D. coccinellae paralysis virus (DcPV) to alter the behavior of another species of insect, the spotted lady beetle Coleomegilla maculate.  

The story is a bit gory:  the wasp appears to deliberately inject the virus into the ladybug along with its own offspring.  Remarkably, the ladybug tolerates the wasp grub, which grows as it nourishes itself on ladybug's bodily fluids.  The virus initially replicates inside the wasp egg but when the wasp is ready to emerge from the ladybug it releases the virus inside the ladybug.  The virus attacks the nervous system of the ladybug, making it act like a zombie bodyguard.  The ladybug stands guard over the attached but now external cocoon of the still-developing wasp grub, involuntarily lending its many potent toxins to the cause of protecting the wasp.  The reminiscence of this behavior to that of a zombie is enhanced by the occasional spasming of the ladybug as a side effect of the viral infection in its nervous system.  Fascinatingly, there is ongoing debate about how to classify this polydnavirus--and whether it even counts as a virus--because it has ben co-evolving with the wasp for so long and its DNA is integrated into the wasp genome itself.  As if this story couldn't get any more amazingly strange, it turns out about one third of the time the ladybug actually survives and fully recovers from being eaten alive from the inside and subsequently zombified.

Read the whole story here:

A zombified ladybug stands guard.

Monday, February 9, 2015

E-cigarettes: not so innocuous after all

After a lot of talk that e-cigarettes are a much safer alternative to smoking, it turns out that they can also be very harmful, particularly increasing susceptibility to respiratory disease similar to the patterns. For those of you who may not know, e-cigarettes are simply a battery, atomizer, and a cartridge that produce a vapor that can be inhaled by a user, mimicking the effects of a cigarette. 
 After strong public health campaigns to reduce the number of people smoking due to the detrimental health effects, the number of people who smoke has gone down over the years, though it has been notoriously difficult to quit. Smoking in particular is addictive because of it nicotine content, which is actually equal to the nicotine content of e-cigarettes. Notably, e-cigarettes produce a much lower load of free radicals compared to cigarette smoke, but this amount may still pose a public health threat.

A group of researchers from the Johns Hopkins Bloomberg School of Public Health conducted a study with mice to look at these effects on the progression of respiratory disease. The mice were effectively "smoking" e-cigarettes by inhaling vapor from e-cigarettes in the experimental group or just normal air in the control group. These mice were exposed via nasal drops to bacteria causing pneumonia and sinusitis, a strain of the Influenza A virus, or nothing at all. 

Bacterial and viral infections were shown to increase the harmful effects of e-cigarette vapor. The virus was shown to compromise the immune system further and led to increased weight loss and death. This study suggests that e-cigarettes may not be as "safe" as touted by its marketers, particularly when implicated with other infectious agents like viruses. It would be interesting to see the effects of other respiratory viruses on the outcomes of the study in conjunction with e-cigarettes.

- Nicole


Thursday, February 5, 2015

The Plague of Anti-Vaxxers

The "measlesland" (rashiest place on earth?) fiasco has left a lot of concerned Americans wondering how we can fix all of this anti-vaccine nonsense. Hopefully there’s a better solution than waiting for all of them to die from measles, cervical cancer (HPV), whooping cough, and the like. It’s bad enough when misguided celebrities stoke the fires of fear and misinformation, but when politicians start offering more and more vaccine loopholes as part of their promises you know that something is seriously wrong. Maybe it's best of the pro-science congresspeople (they exist, right?) close these loopholes (because as we've talked about there are medical reasons for certain people not to get one or vaccines) before it's too late.
            But what are we to do? Andrew Wakefield became a martyr after The Lancet retracted his paper in 2011, and the more we criticize these people, the more dogged they get. It’s easy to forget that measles alone killed 145,000 children around the world in 2014. As we’ve talked about in class, even if measles doesn’t kill you, it can leave you with permanent neurological damage. Vaccine-related deaths are extremely rare in comparison. The CDC believes that most (if not all) of the deaths associated with certain vaccines don’t follow a consistent enough story for them to implicate the vaccines.
            People who fight to combat anti-vaccine sentiment have observed that it’s easier to scare people than it is to un-scare them. Studies and fact-checking don’t seem to convince these people. Even when a new study comes out that suggests that “no we really can’t find a link between vaccines and autism” or “your baby isn’t getting too many vaccines at once,” people find something else. Maybe something that looks like a scary toxin (which some pseudoscientific organization like “National Vaccine Information Center” probably made up). What does?
Well giving them more data from studies probably feels like you’re just shoving more information and calling them stupid. It may actually backfire according to one Stanford study (
One of the best things that a pediatrician can do is to talk to parents like they’re responsible adults, especially if they’re “on the fence” or “heard something about vaccines and autism” (like the father from the Penn and Teller video we saw). In the US at least, this seems to be as much of a frontier as developing new vaccines. Right now, anti-vaxxers aren’t causing a lot of death in comparison to causes like homicide and car accidents, but we have to do something before that changes.

--Joe Getsy