Friday, March 27, 2015

Major Evolutionary Event: Retrovirus Invading Koala DNA!

Koalas throughout Australia are being infected with a circulating endogenous retrovirus. [Source: Quanta Magazine]

In the 1990s, a large number of koalas in Dreamworld, an Australian theme park, started dying of cancer. When it comes to animals, cancer clusters like these are often caused by retroviruses. These viruses insert their genetic material into the host genome, sometimes leading to oncogenesis. However, as veterinarians tested koalas for a retrovirus, they were shocked to discover that almost every koala was infected with koala retrovirus (KoRV).

KoRV is still spreading throughout Australia. Nearly all of the koalas in Queensland have been infected and there are moderate levels of KoRV between Queensland and the Southern islands, where the virus has yet to be detected. However, it may only be a matter of time.

The pervasiveness of KoRV indicates that it is likely infected the koala germ-line. As an endogenous retrovirus, it would be passed on from parent koalas to their offspring along with the rest of the koalas's genetic information.

All vertebrates have retroviral DNA embedded in their genomes. In fact, about 8% of the human genome is made up of endogenous retrovirus. However, these retroviral jumps into the germ-line genome occurred way back in our evolutionary history (and sometimes even drove evolution  -- we have endogenous retroviruses to thank for our placentas!)

Regular vs. Endogenous retroviruses, an infographic. [Source: Quanta Magazine]

This discovery is so exciting not only because endogenous retroviruses are awesome (certainly reason enough), but also because this is the first time scientists can observe a recent retroviral jump and its affects on a species.

Currently, KoRV is found circulating in the blood of koalas as well as in their sperm and eggs. It is also quite deadly. Usually endogenous retroviruses have been silenced in the host genome and do not cause disease. The infection was likely introduced tens of thousands of years ago (not so long on an evolutionary timescale), and KoRV already has two mutations that lowered its virulence, so this may be a general trend.

Researchers hope that KoRV will help explain one of the great endogenous retrovirus mysteries: "How does a deadly virus become one with the host without killing off the host population entirely?" Studying KoRV and its coevolution with koalas may also provide critical insights into our own evolutionary history.

References

  1. https://www.quantamagazine.org/20150303-koala-epidemic-is-invading-koala-dna/
  2. http://genomebiology.com/2006/7/11/241
  3. http://www.retrovirology.com/content/10/1/108


Promising New Antiviral - Coming Soon for Transplant Patients?

Brincidofovir is a prodrug of cidofovir, a very hepatotoxic nucleoside analog. [Source: virology.ws] 

Adenovirus is not usually on the list of deadly viruses that Ebola and HIV-1 inhabit. However, in transplant patients who have suppressed immune systems, adenovirus infection has a 60-80% mortality rate. There are currently no FDA-approved drugs against adenovirus. The current standard of care is cidofovir, a nucleoside analog with a high risk of kidney damage. It was approved for use in cytomegalovirus retinitis in AIDS patients. 

The pharmaceutical company Chimerix has developed an experimental antiviral that may offer a safer alternative. Brincidofovir is a prodrug of cidofovir. Chimerix uses a new lipid delivery technology that involves binding cidofovir with a lipid molecule. This conferees two major advantages: (1) it makes the drug absorbable by the gut (you can take it in a pill!) and (2) it can help target specific cells, where the cidofovir can be released, greatly enhancing the safety of the drug. 

The question is how can Chimerix  test the safety and efficacy of this new antiviral? The gold standard for clinical trials is a double blind trial in which one group receives the drug and another receives a placebo. However, when adenovirus infection has such a high mortality rate, is it ethical to give patients placebos? In response to this issue, Chimerix has received approval to conduct a late-stage clinical trial using “historic controls” instead. This type of study enables Chimerix to give brincidofovir to all patients who need it and compare their results with historic data. To keep these comparisons consistent, adenovirus patients will only be compared with other patients who received the same type of transplants and were treated at the same sites. The early data looks promising as it shows brincidofovir reduced the mortality of adenovirus infections by more than half.

Brincidofovir is also one of several experimental drugs approved for emergency use in the Ebola epidemic. Late-stage clinical trials for both adenovirus and CMV infection are moving forward, and there have been indications that it is useful in treating other viruses too, which is great news for transplant patients who often have multiple opportunistic infections. 

References

Thursday, March 26, 2015

German Measles Denier Ordered to Pay $106,000

Stefan Lanker - the man who claims the measles virus does not exist. Was anti-vaccination too mainstream for him?
[Source: "Question Everything" Youtube channel]

It all started with a challenge. Stefan Lanka, a German biologist known for promoting pseudoscientific theories such as HIV denialism and anti-vaccination, insisted that the measles virus did not exist. He claimed that measles is caused by a “psychosomatic illness” because of “traumatic separation.” And, to put his money where his theory is, he offered 100,000 euros (roughly $106,000 USD) to anyone who could prove that measles is viral in origin. 

David Bardens, a German doctor, responded by compiling evidence from multiple medical journals that measles is indeed caused by a virus. Of course, Lanka refused to actually pay, so Bardens sued. A German court recently ruled that Bardens’s proof was sufficient and that Lanka must pay. Lanka says that he plans to appeal.

When I first read about this case, I thought it was a hilarious publicity stunt. Then I realized that Lanka represents an all too common refusal to believe scientific evidence. He is a so-called scientist who took anti-vaccination one step farther and started going anti-virus. Such beliefs have led to precipitous declines in vaccination rates, especially for childhood diseases such as measles. Serious measles epidemics have swept the US and Europe. As herd immunity declines, innocent children, even those who have been vaccinated, may die of entirely preventable diseases. And that’s not funny at all.

References 
  1. http://www.latimes.com/business/hiltzik/la-fi-mh-a-vaccine-denier-20150320-column.html
  2. http://www.bbc.com/news/world-europe-31864218

Innovative New Design for Herpes Simplex Vaccine

Negatively stained transmission electron micrograph of herpes simplex virions. [Source: HHMI]

William Jacobs, an HHMI investigator at the Albert Einstein College of Medicine, may have a new way to vaccinate against herpes simplex virus (HSV) by turning the old vaccine paradigm on its head. HSV-1 and HSV-2 are responsible for the unsightly cold sores and genital lesions many individuals must live with. As of now, there has been no effective vaccine against either virus, but that may soon change.

The old HSV vaccine approach focused on eliciting neutralizing antibodies against the specific envelope glycoprotein gD. This protein was promising for two reasons: (1) it mediates viral entry and cell to cell spread, and (2) it stimulates a powerful immune response from the host. However, despite many attempts, there has yet to be an effective gD-based subunit vaccine.

Jacobs and his group tried something new. Instead of focusing on gD, what would happen if they got rid of it all together? They created a gD-deleted mutant HSV-2. To make the vaccine, they grew HSV-1 gD in a cell culture and then added the HSV-2 mutant to the mix. The mutant viruses soon picked up HSV-1 gD, which enabled them to infect target cells and replicate efficiently. However, without its own gD, the newly produced mutant viruses were unable to infect other cells.

This new HSV-2 vaccine was administered intravaginally and by skin contact to mice models that were later infected with wild type HSV-2. No virus was found in the vagina or any sensory nerves, where HSV is known to go latent. This vaccine also conferred immunity against both HSV-1 and HSV-2, likely due to morphological similarities between the viruses. There were also no negative side effects in immune compromised mice.

Further investigations reveal that this new vaccine strategy elicits antibody-dependent cell cytotoxicity (ADCC) instead of neutralizing antibodies, challenging old vaccine paradigms and introducing a powerful new way to confer immunity. In fact, this technology could be a scalable strategy. The HSV-2 vector could perhaps be reengineered as a vaccine against HIV, tuberculosis and other difficult-to-vaccinate mucosal infections.

References
  1. http://www.hhmi.org/news/radical-vaccine-design-effective-against-herpes-viruses
  2. http://elifesciences.org/content/4/e06054

Herpes Simplex Cluster in Mexico?

An indigenous child from Mexico's Bocoyna region putatively infected with HSV [Source: El Heraldo de Chihuahua]

El Heraldo de Chihuahua, a local Mexican news source, reported a possible herpes simplex virus (HSV) cluster in 20 children in the Bocoyna region in Mexico. These children are suffering from festering sores and scabs all over their faces. They live in a small, isolated village in the mountains where it is very difficult to obtain medical assistance. Although their families have tried to take them to the hospital, doctors refused to see them because they had no money. Currently, the infected children cannot eat or sleep because their bodies are covered in painful lesions. 

At this time, ProMed is unsure how El Heraldo determined that this disease cluster was caused by HSV, given that the children have yet to receive medical care. It would be interesting if this were caused by HSV though, given that HSV usually results in more limited lesions on either the mouth (HSV-1) or genital region (HSV-2). More serious or systemic HSV infections may be a sign of an opportunistic infection in cases of immunodeficiency. Herpes gladiatorum, one of the most infectious forms of HSV that is transmitted by skin to skin contact, may also be another culprit. So far, without any definitive tests, the differential diagnosis also includes impetigo (Staphylococcus aureus or group A beta-hemolytic streptococcus), cutaneous leishmaniasis (leishmania parasites) and ringworm (skin fungus). 

Here’s hoping that these children get the medical they need and that this outbreak is investigated and controlled. 

References:
  1. http://www.oem.com.mx/elheraldodechihuahua/notas/n3719298.htm
  2. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001552.htm
  3. http://www.promedmail.org/direct.php?id=3200640 

The Next Ebola Zones: Lessons and Predictions

Western doctors in spacesuits are not the answer to future epidemics.
[Source: NBC News] 

The Ebola epidemic, which has ravaged many countries in West Africa, is finally starting to be controlled. However, as the public health measures and practices have been set in place in Ebola-stricken countries, it’s time to think about where else it could strike next.

Save the Children has issued a report warning that at least 28 countries are vulnerable. Asides from cultural practices, one major reason that Ebola infections escalated from isolated outbreaks to a wide scale epidemic is a lack of established healthcare infrastructure. 

One of my favorite quotes is by David Satcher, the 16th US Surgeon General. On the back of my copy of the Control of Communicable Diseases Manual (20th edition), he says, 

“We can learn a lot from the agents of infectious diseases. They teach us the value of eternal vigilance and the price of neglect of our public health infrastucture. They highlight disparities in health and the impact of social determinants of health globally, as we continue to strive for global health equality.” 

So far, Ebola has infected almost 24,000 people and killed 10,000. The virus has been spread to not only neighboring West African countries, but also the US and Europe. 

Save the Children states that a “robust health system could have helped get Ebola under control much sooner, saving thousands of children's lives and billions of dollars.” Using the number of health care workers, government spending on health and mortality rates, Save the Children identified the world’s worst public health systems, which include Somalia, Chad, Nigeria, Afghanistan, Haiti, Ethiopia, Central Africa Republic, Guinea, Niger, and Mali. 

The group argues that building more effective public health systems would be cheaper than fighting full-blown epidemics. This would also save the lives of 17,000 children each day, who die of preventable diseases such as pneumonia and malaria. 

It’s essential to frame this epidemic as not only a horrifying tragedy, but also a tragic reality of global health inequality. To prevent this from occurring again, we must solve the root of the problem. 

References 
  1. http://www.nbcnews.com/storyline/ebola-virus-outbreak/next-ebola-zone-report-finds-28-high-risk-countries-n316436
  2. http://www.savethechildren.org/site/c.8rKLIXMGIpI4E/b.9208421/k.244F/Ebola_Response_in_West_Africa.htm


B Cell Populations Cooperate in Creating Potent HIV-Fighting Antibodies

          When  individuals are infected with HIV, they carry the virus for life.  Inside their bodies, the virus is mutating and evolving and can develop into multiple separate strains.  Because humans acquire HIV from other humans in whom this process is already taking place, the initial HIV virus sample that infects a susceptible healthy individual often already contains a variety of slightly different versions of the virus, accelerating virus diversification within the new patient.  The diversity of HIV strains within a given individual represents one of several challenges the human immune system faces when attempting to battle HIV.
          With other non-HIV infections, when the immune system learns to recognize the pathogen it can mobilize a swarm of cells with specificity for that pathogen to attack it and clear the infection.  The diversity of HIV strains within a patient disrupts this process.  Typically an HIV patient will develop an immune response that targets some but not all of the HIV strains present in the body those strains are dissimilar.  One set of key molecules responsible for the “recognition” of pathogens are called antibodies.  Many research efforts aspiring to develop an HIV vaccine or cure target the development of broadly-neutralizing antibodies (bnAbs), antibodies that recognize a wide range of HIV strains rather than only a subset of the strains present in an infected individual.
          Research work published by Gao et al. in the July 2014 issue of Cell investigated the mechanisms that contribute to bnAb development in an HIV patient who naturally makes these antibodies.  They found that two different populations of an immune cell type called a B cell participate in this process.  Each B cell has a certain pathogen specificity and one key part of the immune response to an infection is the selective activation of B cells specific for pathogens the body is actively trying to fend off, which causes these B cells to mature into plasma cells that mass-produce antibodies with the same specificity as the B cells.  Gao et al. found the B cells that produced bnAbs were activated because they were successful at recognizing a particular variant of the virus with a mutation in part of its surface called Loop D.  These Loop D mutant viruses had been enriched in the population of HIV virus strains within this patient by a separate population of B cells that Gao et al. called the “helper B cells.”  Having more of these Loop D mutants due to the activity of the helper B cells increased activation of bnAB B cells and therefore increased bnAb production.  The helper B cells enriched the population of Loop D mutant HIV viruses because the Loop D mutants were resistant to the helper B cells.  Because the helper B cells could not recognize the Loop D mutants, the Loop D HIV population survived while the helper B cells targeted other variants of HIV in the patient’s body.  The activity of the helper B cells enriched the Loop D mutant population, which then activated the B cells that would mature into bnAb-producing plasma cells.
          View the original publication here:  http://www.cell.com/abstract/S0092-8674(14)00812-5

I also made this diagram to help clarify the process of bnAb development described in this paper:


--Laurie Rumker

Sunday, March 22, 2015

Ebola Update—We can’t give up prematurely!


Peter Piot, one of the professors who co-discoverer of the virus back in 1976, says that the outbreak isn’t nearly over. In a recent statement he urged continuing investment in vaccine and antiviral development. The world hoped that Ebola was dying down, but it came back to Liberia just before it would have been officially “Ebola-free.” While the incidence is declining, people are still dying. The only way to contain Ebola will be to stop it at its source. Thousands more people could die if the virus were to establish in other parts of the world. These deaths aren’t even counting those from starvation, childbirth-related complications, or other health conditions that couldn’t be treated because the healthcare systems in the region were in such disarray.

Professor Piot things that there is an “underground” transmission network that public health authorities aren’t addressing. There have been a variety of proposed solutions, including Sierra Leonean President Ernest Bai Koroma’s suggestion of a three-day lockdown period. The last time the country tried this people rioted.

One particularly clever medical technology that I wouldn’t have thought about is a tablet into which healthcare workers can input patient information, and then dunk in chlorine so that the tablet can go in and out of the quarantine facilities. These tablets can also send the data wirelessly to other tablets, and access patients’ medical records when Internet connection is available. Previously, they would have to read the information to someone on the other side of a barrier before destroying the paper.

Ebola continues to ravage West Africa, and it’s going to take a lot of resources and ingenuity to contain it. The risks are too great for us to wait and hope it burns itself out.





--Joe

Saturday, March 21, 2015

Bill Gates Urges for Global Response to Future Epidemics

In an article published this week in the New England Journal of Medicine, Bill Gates advocated for the creation of a global response system that can respond to the demands of large scale epidemics - ones he fears will be larger than that of the current Ebola epidemic.

The problem with existing global systems (such as the WHO Global Outbreak Alert and Response Network), he argues, is that they are understaffed and undertrained. Furthermore, the existence of many different organizations that work on related causes results in a less organized and less streamlined response.

To remedy this issue, a global institution with the autonomy and resources to effectively tackle epidemics must be established.   In Gates' view, this would involve a reserve corps of public health workers and volunteers who can respond to the immediate needs of an outbreak.  Such a system would ameliorate exogenous factors such as weak healthcare systems in countries.  Gates also advocates for a global epidemic drug-approval process, by which experimental/unlicensed drugs could be evaluated for immediate use in cases of emergency.

The big question that remains with the implementation of a global response system is the funding.  Who should be expected to fund the system, and how much would such a system cost?  The answers to these questions will bring us one step closer to establishing a global response unit.

--Andrew Duong
http://www.latimes.com/science/sciencenow/la-sci-sn-gates-ebola-20150319-story.html

Ebola resurfaces in Liberia

As we discussed in class, Liberia became the latest country to approach "Ebola-free" status, with its last reported case before this week happening on March 5th.  To be declared "Ebola-free" officially, countries must wait 42 days after the last infected patient tests negative for Ebola.  Such a move would be huge for the country, which has seen it struggle to fight the epidemic since last winter.   However, a new report has determined that Ebola has actually resurfaced in the country, with one patient testing positive for Ebola in Monrovia.

Such an incident is not surprising, as the virus could have been present in the population but not apparent since its incubation period can theoretically last a little more than three weeks.  Furthermore, monitoring and surveillance for Ebola is not perfect, and the possibility that someone was infected in the interim period is possible as well.  Finally, there is also the possibility that the infected individual came from a different country, indicating that the virus came to the country exogenously, rather than endogenously.  At the time of reporting, it is unclear where the infected individual originated from.

The resurfacing of Ebola in Liberia highlights the importance of staying alert and aware of Ebola's deadly potential even in the midst of a weakening Ebola epidemic.  After all, the West African Ebola outbreak has already resulted in the deaths of over 10,000 people, and 24,000 additional infections.  

--Andrew Duong
http://www.nbcnews.com/storyline/ebola-virus-outbreak/ebola-returns-liberia-n327511

New Diagnostic Pathogen Test

The results of a new test that distinguishes between bacterial and viral pathogens was recently revealed by MeMed, a company that specializes in creating diagnostic solutions to equip doctors with the tools to make informed treatment decisions.

Called the ImmunoXpert diagnostic test, the test is an in vitro test that uses the body's immune response to determine the etiology (bacterial or viral) of infection.  This sort of test differs from previous diagnostic tests since it uses the immune response as its means of detections, rather than the pathogen itself.  The rationale behind the test is that viruses and bacteria stimulate different immunological responses, and that these differences can actually be detected.

In a study of more than 1,000 patients, the ImmunoXpert test yielded a sensitivity and specificity of greater than 90%, meaning that it was extremely accurate at detecting true positive cases, as well as true negative cases.  Such results outperformed existing biomarker and laboratory tests.

Given the ImmunoXpert test's accuracy and rapidness, it may serve as a promising new way to help reduce hospital costs and misuse of antibiotics since viruses and bacterial infections are sometimes difficult to distinguish in clinic.

--Andrew Duong
http://www.eurekalert.org/pub_releases/2015-03/bpl-nss031215.php

Friday, March 20, 2015

Details on HIV genome packaging

By now we (both H&V students and scientists in general) know quite a bit about HIV replication. We have studied specific proteins encoded within the retrovirus pol gene; we know how reverse transcriptase functions to incorporate viral RNA into the host cell's DNA genome; we know how retrovirus surface glycoproteins encoded in the env gene interact with immune cells. One facet of replication that we have not detailed this year, however, is the retrovirus packaging technique encoded by the gag gene.

An article recently published in Cell reveals how the Gag protein assembles copies of the retrovirus genome and viral proteins into new virus particles. The team of researchers used crosslinking-immunoprecipitation (CLIP) sequencing to observe how Gag recruits viral RNA. After Gag binds to a sequence of viral RNA known as psi, it will move to the cell's plasma membrane, undergo behavioral changes, and bind to different sites throughout the genome. Gag protein in the cytoplasm tends to bind to RNA sequences rich in guanine; at the plasma membrane, Gag is drawn to RNA sequences rich in adenine. This switch in RNA binding behavior seems to be induced by the crowding of Gag protein at the plasma membrane.

Another major discovery in the study was that Gag protein also binds to cellular tRNA, which may help regulate and pace the viral assembly process by acting as a shield against unnecessary RNA or membrane binding.

http://www.sciencedaily.com/releases/2015/02/150227112504.htm

- Nick

Some advice for your next cold

As the common cold season wanes once again, it is important to identify effective treatment strategies to curb infections that will likely afflict all of us in the near future. A recent meta-analysis published in the BMC Family Practice journal shows that high dose zinc acetate lozenges reduce nasal discharge, nasal congestion, scratchy throat, and cough caused by common cold viruses.

Zinc lozenges work by releasing zinc ions into the saliva of the pharyngeal region where common cold viruses tend to replicate most frequently. High dose zinc acetate lozenges shortened the duration of scratchy throat by 33%, sore throat by 18%, hoarseness by 43%, and cough by 46%. The mechanism by which zinc alleviates the common cold would presumably act most effectively on symptoms associated with the pharyngeal region like sore throat; however, this study found an equally powerful effect on other symptoms, including reduced duration of nasal discharge (34%), nasal congestion (37%), and sneezing (22%).

The authors conclude that doses of roughtly 80 mg/day of zinc acetate lozenges started within 24 hours of symptom onset may be an effective treatment for the common cold.

http://www.medicalnewstoday.com/releases/290943.php

- Nick

Anti-vaxxers set their sights on... rabies?

Ahh rabies. The terrifying bullet-shaped rhabdovirus that invariably leads to fatal symptoms...

Luckily, we have a good vaccine, and post-exposure prophylaxis available. Most people in the US don’t need to get vaccinated because rabies is rare, and it is very easy to know if you’ve been exposed. Unless your dog can talk and say “rat’s right, I got bit, ” 


"Rat's right!"


a dog owner might have no idea. Dogs that spend a lot of time frolicking about also tend to be more likely to find themselves exposed to rabies than people. They can also spread it to other unvaccinated mammals, whereas humans can only do so in cases of blood transfusion.

While it makes sense that we don’t vaccinate all people, it makes a lot of sense to vaccinate dogs… right?

In a surprisingly comprehensive article (http://indefinitelywild.gizmodo.com/everything-you-never-wanted-to-know-about-rabies-1692469803), Gizmodo talks about what rabies is, how you and your pets can get it, and how important it is to vaccinate. They also point out a website that claims that the rabies vaccine causes behavioral problems in dogs later on (http://www.dogs4dogs.com/truth4dogs.html). The site also says that since rabies is so rare, we don’t have to vaccinate dogs anymore.

Sound familiar?

Thankfully the site hasn't been updated in a while.

Let’s hope there’s not a “Rabies-land” analogy to the “Measley-land” outbreak. The best thing we can do is vaccinate our pets!


--Joe

New HIV Drug in development at Emory University

Antiretroviral therapies against cell receptors and key enzymatic functions of HIV-1 and HIV-2 have been synthesized since the early 1990's. These compounds, originally used as monotherapies, were somewhat ineffective due to the rapid mutation rate of HIV and the quick resistance towards the ART drugs used. As a response, cocktails of drugs, multi drug therapies were started, and greatly improved the prognosis of a patient once they had confirmed HIV infection.

Today we have quite a few different antiretroviral compounds, but they are incredibly specific in the viral functions that they inhibit. For instance, we have drugs that each individually target HIV protease, integrase, CCR5, and reverse transcriptase.  This monotherapeutic function of HIV drugs may be changing soon. A researcher at Emory University, Dr. Dennis Liotta, has found a compound that effectively inhibits CCR5, CXCR4, and Reverse Transcriptase activity. Liotta worked with Bristol Meyers Squib in order to produce this compound, which is apparently cheap to synthesize.

Although it is early in the process, a drug like this could be a great addition to the arsenal of compounds used to treat HIV. Given the cost effective synthesis of the compound, it could be incredibly useful in low income countries. Dr. Liotta is calling this potential finding a single drug "cocktail." We will have to keep tabs on the development of this drug in the next few years.


- Marcus Munoz

Read more at:

http://www.aaas.org/abstract/discovery-and-synthesis-first-generation-single-drug-cocktails-combat-hiv

Role of microRNA in liver function and HCV infection

A recent study published in Cell details how microRNA-122 interacts with both human liver cells and hepatitis C virus. Normally, liver cells use miRNA-122 to turn down gene expression by guiding several silencing proteins to various RNA transcripts. In this way, miRNA-122 helps control cholesterol and iron metabolism, circadian rhythms, and other normal liver cell functions. Though miRNA-122 serves several important cellular functions, it also plays a substantial role in persistent HCV infection. In order to establish persistence, HCV binds to miRNA-122 to stabilize and protect the virus during its replication cycle.

Using a technique called cross-linking and immunoprecipitation (CLIP), the researchers identified interactions between miRNA-122 and Argonaute, one of the proteins involved in gene silencing. They found much lower levels of miRNA-122 activity in infected liver cells compared to uninfected liver cells, which means genes that would normally get silenced remain active. The authors postulate that HCV "sops up" miRNA-122 to cause live dysfunction, an idea that provides a molecular link between HCV infection and its associated pathologies: low levels of miRNA-122 activity over a long period of time may contribute to liver damage and even liver cancer, both of which have been associated with chronic HCV infection.

http://www.sciencedaily.com/releases/2015/03/150312123606.htm

- Nick

Stomach Virus Outbreak: Sounds Like Mr. Noro is up to No Good

The master of acute gastroenteritis epidemics has struck yet again in Pennsbury, Pennsylvania. As the article states, a Stomach Virus has wreaked havoc over the unfortunate souls attending Pennsbury elementary school.

The school board decided after 25% of the student body reported symptoms today that they should close until the epidemic has stopped, reporting that this number is 5 times as large as the normal absentee rate. 120 students have fallen ill, and the district health officials have given the credit to the one and only Mr. Noro.

The school board is hoping that the viral infection will subside over the weekend, however the article keenly points out that after being infected someone can spread the virus for up to 2 weeks! The public health director's response: to not be complacent, make sure the children are asymptomatic before returning to school, and to wash hands thoroughly.

I tip my hat to you Mr. Noro. Your positive stranded RNA nature, hit and run style of viral infection, and icosahedral shape are one heck of a recipe for GI disaster.


- Marcus Muñoz

Breaking news: new Ebola case in Liberia

Liberia can no longer be considered Ebola-free.

The West African nation discharged its last Ebola disease patient just over two weeks ago on March 5th, and had only two more weeks of waiting before it could be considered free of Ebola virus. As of Friday, March 20th a new Ebola case has been confirmed and is being treated in an isolated unit at Monrovia's Redemption Hospital. Interestingly, this new patient does not seem to be linked to anyone on the Ebola contacts list and claims she had not travelled to an infected country recently.

Liberia had zero new cases of Ebola for 27 days prior to this event, which represents a slight setback in the country's Ebola-free campaign.

http://www.aljazeera.com/news/2015/03/ebola-case-ends-liberia-countdown-virus-free-150321003004879.html

- Nick

Book Review: Ebola, Culture, and Politics: the Anthropology of an Emerging Disease


“As in most areas of Africa, shortly after a person dies, the body is completely washed and dressed in a favorite outfit... The deceased is then placed outside the house or in a big living room, open for viewing by all for one day...The husband or wife, mother, or blood friends may sleep or lie next to the body. A common practice is to touch and kiss the body, face, or mouth.”(78)
Dreaded by all health care professionals for its potential to transmit infectious diseases, the funeral practice described above was targeted as part of the World Health Organization’s (WHO) Ebola outbreak control efforts. The practice was modified by the implementation of a ritual cleansing with chlorinated water at the victim’s home and supplying protective equipment for the burial team. Barry and Bonnie Hewlett, professors of Anthropology at Washington State University, use this case study as an example of the facilitation of Ebola transmission reduction that can be achieved through understanding and modifying local cultural practices. In their book, Ebola, Culture, and Politics: the Anthropology of an Emerging Disease, they produce an ethnography of Ebola with the ultimate goal of elucidating local perceptions of the disease to ultimately aid in outbreak control. They conduct a multi-sited study, in which they examine places in West Africa where small outbreaks have occurred. They study the 1997 outbreak in Gabon, the 2000 to 2001 outbreak in Gulu, Uganda, and the 2003 outbreak in Kikwit, Democratic Republic of Congo. They conduct their research as part of a WHO outbreak control team and travel with the safety and protection of the WHO team at all times. They indicate that their involvement constitutes the first time that anthropologists ever participated in Ebola control efforts.
 
The goal of their research is to elucidate the indigenous perceptions of Ebola and practices that affect Ebola transmission to ultimately apply this knowledge in control efforts. Their research is driven by physician and anthropologist Fred Dunn’s framework for integrating anthropological research into disease-control efforts. This framework entails the examination of factors in the community that are health enhancing, factors in the community that are health lowering, factors outside of the community that are health advancing, and factors in the community that are health lowering. They describe the concentration of their research, “Our fieldwork focused on cultural models and clinical medical anthropology, while at the same time themes of the impact of political-economic structures, inequality, and structural violence emerged from local peoples’ stories and experiences with Ebola”(30). They define clinical medical anthropology as an approach that provides culturally sensitive and appropriate care in the hospital setting. The theoretical assumptions driving their research is evolutionary bio cultural theory, which focuses on the analysis of how individuals weigh the costs and benefits of particular actions according to the impact of their reproductive fitness. In the context of an Ebola outbreak, they are curious to find out how individual “stakeholders,” an individual or group with a vested interest in Ebola control efforts, respond to people sick with Ebola. Their theoretical assumption that each individual is an active agent thus drives their methodology of conducting open ended interviews with "as many different people and as many different stakeholders as possible”(32) They administered surveys to and conducted numerous interviews with uninfected individuals, with survivors, and with local health care workers in one on one interviews or focus groups, "nonrandom samples of a small group of individuals asked to informally discuss a particular topic.”(33) They indicate that their fieldwork is limited to interviews and surveys due to the unique circumstances associated with the outbreak. They could not participate in the social activities that anthropologists often like to observe because due to the outbreak, the governments banned school and church services, prohibited dances, soccer matches, and large funerals, and told healers not to practice their trade. They also mention that in contrast to other anthropological research, theirs was particularly dangerous because they had to take special measures to ensure that they did not contract the disease.
Their study of cultural factors associated with the emergent infectious disease elucidated that while some cultural practices such as burial ceremonies amplified the transmission of Ebola by promoting contact of people with the dead bodies, other cultural practices positively impacted control of Ebola transmission. The authors found that significant stigmatization was associated with the disease. Infected people, health care workers, and any people who were associated with infected individuals were feared by others in the community, rejected when trying to purchase things at markets and avoided in the neighborhood. In some cases even family members would not approach them. The Hewletts attribute the stigmatization to the interactions of evolutionary psychology, ecology, and culture. They state, “Several elements of evolved psychology during an outbreak may contribute to stigmatization: inclusive fitness is threatened, fear is evoked, and humans have evolved abilities to distinguish sick from healthy individuals”(148). This stigmatization while negatively affecting the lives of the infected individuals, actually serves as a defense mechanism that the community engages in to reduce transmission.
The examination of local perceptions of the disease through surveys revealed that many people were unaware of the route of transmission of Ebola: some people attributed Ebola contraction with sorcery that is linked to accumulation of wealth and others thought it was airborne. More men than women were aware of how Ebola is actually transmitted. The majority of children also were aware of its route of transmission due to educational programs at their schools. Their research also pointed out the local people feared and distrusted international teams which came to conduct medical research or provide care because of lack of transparency, lack of friendliness, and lack of communication shown by the Westerners. Some interviews revealed that it was the accumulation of miscommunication over several years that led to the suspicion. For instance in a village in Gabon, the people indicated that Euro American researchers “moved up and down the river in fast boats, stopping only to take blood or fecal samples” without telling the people what they were going to do with them. (11) Another example of the suspicions affecting the actions of the local population was evidenced when people refused to go to the clinics because the isolation units were closed off with plastic tarps behind which nothing was visible. Due to the workers’ lack of trust building in the communities, people were reluctant to yield to biomedical treatment. But interviews with local nurses showed reduced skepticism. The Hewletts found that the local nurses work out of a sense of duty to the community and can be made great liaisons between the international team members and the local communities. The authors dedicate another portion to discuss the political and economic ecology issues such as lack of access to vital resources such as food, materials to prevent the transmission of the disease, and medications to treat other common deadly diseases such as malaria can add to the insecurities evoked by the Ebola outbreak. These are the main beliefs and behaviors that the authors elucidated in their book to indicate the social, spiritual, political, and economic dimensions of the disease.

This is part of a critical review I wrote for an Anthropology class. What do you guys think about the Hewletts' approach to researching cultural factors related to the Ebola outbreak? Do you agree with their argument that Anthropologists should comprise an essential part of the WHO outbreak control team?

By Mariam Kyarunts

Effectiveness of Airport Viral Pathogen Screenings?

A recent study conducted by researchers at the University of California, Los Angeles revealed an alarming statistic on the effectiveness of airport screenings designed to remove sick passengers from flights: more than 50% of passengers infected for pathogens screened for at the airport are missed.   These pathogens include SARS, Ebola, Middle East respiratory syndrome coronavirus, Marburg virus, Influenza H1N1 and Influenza H7N9.

Common measures used to detect illness such as fever screening fail to pick up diseases with a relatively long incubation period, such as Marburg and Ebola, although they are quite successful in detecting illnesses like swine flu.  Moreover, devices used to measure fever only show less than 70% success rate.  It is further speculated that passengers use fever reducers such as acetaminophen to reduce symptoms and/or conceal their fever.

In other measures, such as questionnaires surveying passengers about illness, only around 25 percent of passengers were found to actually answer honestly.

The researchers suggest that screening at airports can be improved given reliable data on the number of passengers who are turned away from the airport and actually report an illness as well as incentives for honest reporting.

--Andrew Duong
http://www.eurekalert.org/pub_releases/2015-02/uoc--asf022415.php

Oncolytic potential of Parvoviruses

As mentioned in class, parvoviruses are promising candidates for cancer therapy since they do not cause severe disease and have been shown to kill cancer cells.  The mechanism by which parvoviruses are able to attack cancer cells has thus far been unclear.  Recently however, researchers at the German Cancer Research Center were able to find a potential oncolytic mechanism by which parvoviruses act.

Using experimental mice, these researchers discovered that parvovirus binds to an enzyme called PDK1 kinase, which functions as a switch in important cell processes including cellular growth.  This binding leads to the activation of PDK1.

Interestingly enough, in healthy people, the parvovirus-PDK1 kinase activation pathway is not seen. However,  those with cancer (particularly those with glioblastoma) had permanently activated PDK1. In in vitro studies with constitutively active PDK1, parvoviruses were able to exploit the PDK1 pathway and replicate inside PDK1 cells, as they were in mice.  Such results are extremely exciting because they open the door for in vivo research studies that may show a link between parvovirus replication in PDK1 and cancer progression.

--Andrew Duong
http://www.eurekalert.org/pub_releases/2015-03/gcrc-dtc031115.php

H7N9 Flu Strain Evolution

The novel H7N9 avian influenza strain that has emerged in recent weeks has infected more than 500 people and killed a little over 200.  The severity of this strain in such a short time has led investigators to look into the evolution of the virus in a report published by Nature this past week.

What these investigators found was that the virus was initially detected in Shanghai late March of 2013.  The cause was attributed to birds, leading to the closure of poultry markets.  The quick response to the outbreak helped drastically decrease the incidence of the virus; however, months later, the virus returned, resulting in a second wave of human infections in the South of China.
Like other flu viruses, the virus was seen to have a winter seasonality.

As the virus spread South, it began to mutate - by the second wave, it had divided into three main branches that led researchers to draw conclusions about the spread of the virus in both human and avian populations.

The work of these researchers only reinforce the notion that careful surveillance of flu is necessary to containing outbreaks and preventing epidemics.  While such surveillance requires both time and money, it is important to do so, especially for strains like H7N9 that are believed to have pandemic potential.

Two New Flu Strains Identified

Building on my last post about the 2015-2016 flu season is news of two novel flu strains discovered by the Scripps Research Institute this past week and published in the latest issue of Cell Host & Microbe.

These two flu strains - H10N8 and H6N1 - are believed to have originated in China and Taiwan and have resulted in sporadic infections in the region.  Fortunately, both strains have not yet been extremely successful in terms of transmission.  Specifically, in H10N8, the viral tropogen hemagluttinin protein (H10) was found to have a weak affinity for human receptors.  This discovery was attributed to structural reasons revealed through X-ray crystallography.

However, scientists fear that these strains could acquire mutations that make humans more susceptible to infection.  Already, the virus has deviated from the original H10N8 virus in birds, although none of these acquired mutations have actually resulted in increased binding affinity for human receptors.  

When the same analyses were repeated for H6N1, a similar conclusion came about: there were distinct changes in the genome of H6N1, but these changes had not measurably affected binding affinity to bird or human receptors.

As the 2014-2015 flu season draws to a close, and the 2015-2016 one draws nearer, continuing to monitor novel flu strains will be important in helping select the strains that will be included in next season's vaccine.

-- Andrew Duong
http://www.eurekalert.org/pub_releases/2015-03/sri-sri031015.php

Flu Season 2015-2016

Researchers are already well under way trying to pinpoint the next influenza strain for the 2015-2016 flu season.  Specifically, researchers at Kansas State University have been examining swine flu viruses for potential leads into the next high-risk flu strain under a research grant from the National Institutes of Health.

Part of their research involves collecting samples from sick pigs and seeing if they pose any threat to humans.  Their past work actually led to the discovery of a novel H2N3 virus.  While it is too early for any results, such research is pivotal in identifying the key players of the upcoming flu season.

While such research is needed to ensure the timely delivery of a vaccine, it is this promptness that can also be detrimental to the development of a successful vaccine.  Since influenza is capable of mutating so rapidly, there is no guarantee that the influenza strains that are targeted for the vaccine will actually be circulating at high levels later this year.  With any luck, any novel strains can be accurately assessed for their potential infectivity and virulence, so that flu vaccine mismatches (as what happened this past flu season) can be avoided.

--Andrew Duong
http://www.sciencedaily.com/releases/2015/03/150303105557.htm

North Carolina Tries to Say Goodbye to Religious Exemptions to Vaccinations


Last Thursday a bill was filed that aimed to strengthen vaccination in North Carolina.  Senate Bill 346--sponsored by Jeff Tarte R-Mecklenburg, Tamara Barringer, and Terry Van Duyn--would require children to get the following vaccinations: Diphtheria-tetanus-pertussis, polio, measles, mumps, rubella, influenza type B, hepatitis B, and varicella. The only vaccine suggested by the CDC that wouldn’t be required is the HPV vaccine.  The current law says that parents and guardians could exempt children from vaccinations if they provide the school with credible proof of religious belief that is at odds with vaccination.  Adults can also exempt themselves from vaccinations using a similar religious arguments.  Senate Bill 347 would not allow religious exemption; it would only allow medical exemptions signed by doctors.  Van Duyn says that Buncombe County has the most religious exemptions in all of North Carolina, with about 4.5% of children entering schools unvaccinated.  In these counties, the religious exemption clause is being manipulated and misused.  Vaccinations have become so low that hospitals and clinics are beginning to see diseases, such as whooping cough,that were once thought to be eradicated popping back up.   Although the opposition is citing reasons of individual choice and violations of the First Amendment, it is clear that lapses in vaccination for some individuals can threaten the public health for all. Furthermore the large number of religious exemptions are directly interfering with preserving herd immunity, a key principle of vaccination.
It’s clear that passing this bill will be an uphill battle, but West Virginia and Mississippi has repealed religious exemptions to vaccinations within the past few years.  So it is possible.  In the face of the measles outbreak in California, it seems likely that this bill will gain majority support.    
  • Nalani Wakinekona

http://www.wral.com/senators-target-religious-exemption-for-vaccines/14525570/

To vaccinate or not to vaccinate against YFV?


A woman who was planning a trip to South America received the Yellow Fever vaccine, and developed a rare serious reaction to the vaccine.  The woman was healthy and in her 60s.  About  a week after receiving the vaccine, she entered the ER with a severe vomiting, diarrhea and shortness of breath.  The condition worsened, while she was at the hospital, presenting as heart damage and acute kidney failure.  She died after she had been in the hospital for three days.  The autopsy showed that she had noticeable levels of virus in several organs, but the autopsy also showed an undiagnosed tumor in her thymus, a special organ of the immune system responsible for the maturation of T cells.  After the autopsy, the doctors declared her diagnosis was yellow fever vaccine-associated viscerotropic disease, a serious reaction to the vaccine in which the virus replicates in the body; they also added that her thymus could have contributed to the progression of the disease.  Yellow fever vaccine-associated viscerotropic disease is an extremely rare disease affecting 4 out of every 1,000,000 vaccine administrations.  People are at a greater risk of developing a complication or a more serious outcome if they are over 60 years of age and if they have problems with their thymus.  Unfortunately this woman fit into both risk groups, and if her physicians had known about the cancer, they would not have proceeded with the vaccination.

The CDC maintains the position that travelers should research the vaccines they want to take, evaluate the chances of exposure in their desired destination, research the disease, and the quality of the health services in the travel destination.  In response to this event the MMWR wrote, “Although most persons have no or mild adverse events after yellow fever vaccination, the benefits of vaccination among travelers who have a limited exposure period need to be weighed against risk for adverse events.” As some food for thought the CDC reported that in a certain period of time, 5 people developed serious reactions to the vaccine while 4 unvaccinated people died of yellow fever.  It’s all a matter of knowing all the facts and making an informed decision.
  • Nalani Wakinekona

http://www.foxnews.com/health/2015/03/20/rare-case-woman-dies-after-yellow-fever-vaccine/