Thursday, September 29, 2016

When to get the flu vaccine and why bad science reporting hurts people

An infographic I made to address what effectiveness means.

Anyone who's followed my page for awhile knows how much I dislike bad science reporting. I don't know if it's been a slow news day or what, but several news outlets have run a story with a headline that is misleading and may make some question getting the flu vaccine. The article, "Getting a flu shot? It may be better to wait," poses the question if people should wait to get the flu vaccine or not. They argue that since the flu vaccine loses effectiveness as the season progresses that people should delay getting it. I should note that vaccine effectiveness only measures the prevention of infection and doesn't include the reduction in symptom severity, disease duration or the number of hospitalizations that are seen with the vaccine. The problem with this is that the argument is based on a single study from a region in Spain when the flu season was atypical. The season started later than normal and the strains circulating in that region of Spain were different than what was covered by the vaccine. The research is an important finding that helps researchers refine plans for future flu seasons. However, the authors themselves make some caveats that the reporting on this topic has overlooked.

The first is that the number of cases were so small that the confidence intervals were very large and went all the way down to 0. Because of this, the authors caution that their findings may not apply to other geographical locations. Another issue is that the number of hospitalizations were too low to estimate how well the vaccine reduced the number of hospitalizations. This was not discussed in the article when the vaccine was discussed. Even if the vaccine looses the ability to prevent infection later in the season, that protection still appears to be intact. 
Another issue is that the loss of effectiveness was only seen in those older than 65. Those younger than 65 had a rate of vaccine effectiveness that was similar to other locations. The issue of vaccination in those older than 65 is a well known problem that isn't limited to the flu vaccine. This could be solved through the use of adjuvants or possibly boosters part way through the season. But probably the biggest issue is the timing of the reporting of this article. If this had come out in July, it would be one thing. However, it got picked up by news sources in mid-September, right when people should start looking to vaccinate for the flu. Compounding problems, this article will probably get shared into December and may make some people delay vaccinating far too long. This is irresponsible journalism and bad science reporting. I'm working on a blog about this topic, but accuracy is crucial for science reporting as a bad report can cause great harm (such as causing people to delay getting a valuable vaccine when the time for delay has already passed).

This article is correct in one aspect though. There really isn't a need to get vaccinated for the flu in July or August if you are in the Northern Hemisphere. It could have better addressed this rather than make it sound like the vaccine loses effectiveness for everyone and not just the elderly (or at least has been observed in an atypical season). Late September and October are still good times to get the vaccine, unless there is no other choice. It's better to get this vaccine early than it is to delay getting it too long and risk infection before an immune response from the vaccine can develop. There are a lot of factors that go into this and it's not nearly as black and white as the reporting on this article make it seem. 

Saturday, September 24, 2016

Not another "zombie" virus (it's nothing to be scared of unless you are an amoeba)

Imaging of Mollivirus particles. (A) Scanning electron microscopy of two isolated particles showing the apex structure. (B) Transmission electron microscopy (TEM) imaging of an ultrathin section of an open particle after fusion of its internal lipid membrane with that of a phagosome. (C) Enlarged view of the viral tegument of a Mollivirus particle highlighting the layer made of a mesh of fibrils (black arrow), resembling Pandoraviruses’ intermediate layer, and the underneath internal membrane (white arrow). Three ∼25-nm interspaced rings are visible around the mature particle. (D) Light microscopy (Nomarski optics 63×) imaging of a lawn of Mollivirus particles, some of them (black arrow) exhibiting a depression at the apex. Figure via Legendre et al., 2016.

new study details the discovery of another giant DNA virus found in the Siberian permafrost. The new virus, called Mollivirus, is similar to another giant DNA virus that was also discovered in the permafrost, Pithovirus. However, although the pithovirus is oblong, the mollivirus is more round. It is also similar is structure to pandoraviruses, another set of large DNA virus. The mollivirus is smaller than some of the other large DNA viruses at 500-600 nm in diamter; however, it is still large enough to be seen with a light microscope (as seen by panel D in the picture above). Like the pithovirus, the researchers were able to infect an amoeba with the mollivirus and revive it. The genome is 651 kb long encoding for 523 proteins; 16% of the genes have their nearest orthologs to genes from pandoravirus and 10% to Acanthamoeba castellanii, most likely through horizontal gene transfer. As with these other large DNA viruses, most of the genes have no known orthologs. One of the more surprising findings is that ribosomes from the host are packaged into the virions. 

These large DNA viruses have changed the way we think about viruses. With genome sizes in these viruses ranging from 0.6 to 2.8 Mb, they are comparable in size to the smallest eukaryote parasites. Theses viruses have diverse morphologies as seen below. 

A Pithovirus. Credit: ulia Bartoli & Chantal Abergel; Information Génomique et Structurale, CNRS-AMU via Nature.

Marseillevirus at different stages of its formation in an amoeba.
Credit: Copyright Raoult / URMITE via Science Daily.

The complex interior of a Mimivirus. Electron microscopy at magnification of about 200.Credit: Didier Raoult, picture by N. Aldrovandi via Live Science.

Megavirus virion via Virology Blog.

Pandoravirus virion via Virology Blog.

Hopefully the reporting on the discovery of the mollivirus will be better than that of the pithovirus. When the pithovirus sample from Siberia was revived in amoebas, many science news sites proclaimed the scientists had resurrected a zombie virus and that unknown dangers lay in wait. The headlines from other news sources were much worse and I won't bother linking to them. Some news reports were much better and specifically mentioned that this virus posed no risk to humans. These viruses pose a risk to some organisms, but if you aren't an amoeba, then you'll be fine. These discoveries are offering vital clues into the evolution of viruses. Their discovery has also helped restart a conversation of if viruses are alive or not and what the definition of life should be. 

Tuesday, September 20, 2016

Zika: What does herpes have to do with it?

HSV-2 virus particle. (Courtesy of Linda M. Stannard, University of Cape Town) via Virology Online

New research has discovered an important risk factor for Zika virus crossing the placental barrier: co-infection with Herpes simplex virus-2 (HSV-2). In the study, the researchers used a first trimester trophoblast cell line that has been well characterized and infected it with two different strains of Zika virus and one of Yellow fever virus. The cells infected with Yellow fever virus survived despite the virus actively replicating whereas both strains of Zika induced apoptosis in infected cells. The researchers also discovered that infection with Zika inhibited the type I-β interferon pathway (a signaling protein that triggers an immune response against viral infection). Zika infection also interfered with trophoblast differentiation into spheroids (something that this cell line does under the right conditions). 

These are very important findings that help us understand the biology of Zika. It's when researchers tested Zika virus infection in cells already infected with HSV-2 that they found something very interesting. When the cells were infected with HSV-2, the expression of three receptors, required for flavivirus entry into cells, were increased. To test to see if this helps Zika virus cross the placental barrier, mice were infected with Zika virus in either a single infection or after prior HSV-2 infection. Zika viral RNA levels were low in the mice only infected with Zika; however, in  the mice previously infected with HSV-2, the Zika virus RNA titer was incredibly high. These results suggest that prior HSV-2 infection could aid Zika virus in crossing the placental barrier. 

The researchers tested HSV-2 infection because HSV-2 is prevalent in NE Brazil where microcephaly cases seem to be higher than in other places. The researchers hypothesize that the prevalence of HSV-2 in NE Brazil could help account for the increase in Zika-associated microcephaly cases there. Prior HSV-2 infection could be a risk factor that may make Zika infection worse in pregnant mothers, so these are very important findings. Hopefully researchers will investigate further with retrospective studies to see if there is an association here.  

Saturday, September 17, 2016

Zika update 9-17-16: TORCHZ, Culex and more

Aedes aegypti feeding. Via Arizona State University Biodesign Institute

It's been an interesting couple of weeks for Zika research and news. As always, there's been good and bad news. There has also been a huge development that I'm saving for last.

In Florida, the zone of local infection in Miami Beach has been increased by three times. The number of local transmission cases are up to 93 (or were at the time of the article). The area of local infection is likely to increase further. In Puerto Rico, the outbreak is continuing to grow and the number of confirmed cases have increased to almost 20,000. Because most cases are asymptomatic, the total number of cases is likely much higher and some are predicting that as many as 1 in 4 could be infected before the outbreak stops. It's disappointing that much of the news focus has been on Florida when Zika is causing outbreaks in US territories to a much larger extent.

Also reported is that Zika can be transmitted through bodily fluids. The CDC has released an initial report on a case from Utah where an elderly patient died from Zika infection. A relative of this patient contracted the virus without the normal transmission routes. It turns out that the titer of Zika in his blood was 100,000 times above normal, and likely passed the virus to his relative through normal exposure from personal care. The CDC has also officially announced that Zika can be transmitted by sexual contact with an infected male or female. They have also released a preliminary guideline for dealing with sexual transmission. Basically, use protection or abstain from sex. 

Now for some good news. Culex pipens and Aedes triseriatus are not vectors for Zika virus. This is great news because C. pipens is a widespread mosquito and is a vector for West Nile virus. If C. pipens were a vector, then Zika could spread throughout much of the world. However, there is still some bad news. Zika virus was recently found to not only replicate in C. quinquefasciatus, but it was also found in the salivary glands where it also replicated. To be vectored by an arthropod, a virus would need to pass through the gut barrier and then migrate to the salivary glands. Replication in the salivary glands is a good indicator that the arthropod might be a vector. This is a good review on arthropod transmission of plant viruses (the principles are the same for other arboviruses). If C. quinquefasciatus is a vector for Zika, then it could spread further than we are anticipating now. Vector transmission assays still need to be conducted to determine if it is a vector or not. 

The most interesting new study on Zika is the case controlled study that confirms that Zika causes birth defects. The results showed a strong correlation between detection of Zika virus in the mother and microcephaly in the baby. Further work is required to determine the exact risk associated with Zika infection during pregnancy, but at this point the role of Zika in causing birth defects is definitive. The authors did recommend that the TORCH acronym be changed to TORCHZ. I made an infographic awhile ago on whether Zika should be added to the list or not. I'll have to update it now.

My infographic on adding Zika to the list of TORCH pathogens. 

Friday, September 16, 2016

Hepatitis A virus: A new model system allows for basic research on the pathogenesis

Transmission electron micrograph of Hepatitis A virus. Credit: CDC/Betty Partin

New research helps to shed light on how Hepatitis A virus damages the liver cells. Using a mouse model system (which is a feat in of itself as this virus was previously found to only infect primates), the researchers were able to identify the mechanism that causes the damage. The virus induces the apoptosis pathway in the liver cells (this is often referred to as programmed cell death) as a result on an innate immune system response to infection. Apoptosis is a complex signaling pathway that is a safety system to limit the spread of infections and prevent unregulated cell growth (cancer). Wikipedia has a detailed article on apoptosis. 

An overview of signal transduction pathways for apoptosis. Credit: Wikipedia

Using the newly developed mouse model, researchers have already begun to unlock of of the mysteries of Hepatitis A virus with many more to come. But more importantly, the researchers were able to identify why mice are not a normal host for the virus (their interferon response overcomes the ability of the virus to infect them). Hopefully, this work will lead to new therapies to combat this important human pathogen.

Thursday, September 8, 2016

A gene from an edible fern is highly effective as an insecticide against whiteflies

Bemisia tabaci (also known as the silverleaf whitefly) feeding on a leaf. Via Wikipedia.

When I got home from work last night, I spent a few minutes on Facebook while waiting for dinner to cook and I stumbled on something that floored me on the page We Love GMOs and Vaccines. Researchers in India have developed the first GE crop to produce compounds to kill whiteflies. They began this project in 2007 and developed the first GE cotton plant by 2012; the paper was just accepted a couple of days ago. In their work, the researchers purified a compound, called Tma12, from an edible fern, Tectaria macrodonta, and then fed it to whiteflies. The researchers observed that a very small amount of the purified compound (1.49 μg/ml) was lethal to the whiteflies. From there, the gene for this compound was identified, cloned and later transformed into cotton.

Tectaria macrodonta via Flickr

From there, the researchers tested the GE-Tma12 cotton in field trials and found that plants expressing ~0.01% Tma12 in leaf material were resistant to whitefly feeding. Furthermore, the whiteflies didn't transmit virus to the plants before they died (more on that in a second). To test the safety of this GE plant, the researchers fed leaf material to rats and no histological or biochemical differences were observed between those fed the GE plant and those fed the control. Since Tma12 lacked any known allergen motifs and did not harm the rats, the researchers concluded that this GE trait would pose little risk to the public. 

It's quite a breakthrough for a group to develop a GE trait specific to whiteflies; however, that isn't what stunned me. It's the implication that this trait might have for my own work. Whiteflies are one of many arthropods that vector plant viruses. However, they transmit many plant viruses that are of great economic importance and can cause famines as they infect many staple crops that people grow in developing nations. Cassava gets cassava mosaic caused by several begomoviruses transmitted by whiteflies. Sweet potato gets viruses from three different genera (Begomovirus, Crinivirus and Ipomovirus). Cotton has a number of begomoviruses that infect it as does tomato, which also gets criniviruses. These are just a few examples of the many crops infected by whitefly-transmitted viruses. In fact, there are over a hundred different viral species transmitted by whiteflies. Some viruses, like ipomoviruses, are transmitted shortly after feeding whereas others, like the begomoviruses, are only transmitted after the whitefly has feed for a long time. The Tma12 trait would be most effective at preventing transmission of the viruses that take longer periods of feeding before transmission takes place. For the viruses that take only a few seconds of feeding, this would not control them.

The thing that struck me most is the way that whiteflies feed. They feed by piercing the leaf and sucking sap from the phloem tissue (think of this as the artery of the plant). There are many other insects that feed this way (many in the order Hemiptera), including many plant disease vectors from aphids to mealybugs to plant/leaf-hoppers to psyllids (a psyllid is responsible for transmitting the bacteria that causes citrus greening). It would be interesting to see if Tma12 is effective against other insects, especially these very important plant disease vectors.

But what does this all mean? As is, this new trait will help make cotton production more sustainable. If this trait were deployed in other crops, the impact of whitefly-transmitted plant viruses in food production could be greatly reduced. If it's effective against other vectors, then this could truly revolutionize agriculture and pest management. 

Wednesday, September 7, 2016

How effective is the chickenpox vaccine? In a word, very

A transmission electron microscopy image of Human herpes virus 3 (also known as the Varicella zoster virus), the virus that causes chickenpox and shingles. Via wikipedia

I've posted many times about the chickenpox and shingles on my page. It's a viral disease that many people catch as children, but the older you get, the worse the symptoms are with an increased risk of death. It also has the nasty habit of hiding out in people's nerves and reemerging later in life as a very painful condition called shingles. I've made three infographics on this virus and the vaccine that can prevent it, but there is new data on how effective the vaccine really is.

First the infographics:

An infographic on the chickenpox.

An infographic on shingles.

An infographic on the impacts of the chickenpox vaccine.

The CDC has released new calculations on how effective this vaccine is with the two-dose series. The initial one-dose series reduced incidence of chickenpox by 90%. However, there were still outbreaks of the disease so researchers and healthcare professionals recommended a second dose. This second dose has been highly effective, reducing incidence a further 84.6% with the greatest impact on those 5 to 9 years old (89.3% reduction). Overall, the vaccine has reduced incidence by 97%. In some states, it was difficult to determine the incidence as the disease had been significantly reduced. 

There are some countries that don't use this vaccine (the UK being one); however, based on how effective this vaccine is, they have begun clinical trials of the vaccine. Hopefully, they adopt this vaccine; as it protects against both the chickenpox and later on shingles (if you are immune to the chickenpox without being infected by the virus, you don't get shingles). 

Tuesday, September 6, 2016

How viruses made us what we are- Muscle cells

Cross section of mouse muscle (in blue: labeling of nuclei; in green: labeling of muscle fiber membranes). Normal male mice display larger muscle fibers than those seen in mutant, syncytin knock-out mice.
Credit: François Redelsperger via ScienceDaily

I've previously talked on my page about how an ancient retrovirus that integrated into early mammals helped to drive our evolution in a number of ways, including being responsible for placenta formation. A retroviral envelope gene called syncytin helps the placenta form as it mediates cell-cell fusion. Previously researchers had observed an increased expression of this gene at the interface between the fetus and the mother which later gives rise to the placenta. 

New research expands what we know on the topic and suggests that these integrated syncythins are responsible for the increased muscle mass that males have. When this gene was knocked out in mice, the muscle cells were smaller (see the picture above) and the mice had a 20% reduction of muscle mass. However, this reduction in muscle mass was only observed in males. The researchers then confirmed that knocking out this gene resulted in smaller muscle cells by knocking syncytin out in sheep, dog and human primary myoblasts. The cell sizes were reduced 20-40% when synctin was silenced. These results not only demonstrate that syncytin is involved in muscle cell fusion, but that it is required for the increased muscle mass seen in male mammals. This could help explain some of the sexual dimorphism seen between male and female mammals.

This work adds to what we know about ourselves and how viruses have played a role in making us what we are. 

Monday, September 5, 2016

Vaccines aren't just for humans Pt.1- A new vaccine for a serious pig disease

A cute baby pig. Credit: Brittney
Porcine epidemic diarrhea virus is a debilitating viral disease of pigs that can cause the death of infected piglets. It can spread rapidly within a population and as the name suggests, it causes severe diarrhea. Many fear that this disease will increase the cost of pork products more than it already has. In the 1990's, an inactivated vaccine was developed in China that limited the spread of this disease. However, in 2010, outbreaks began occurring again making some believe that the vaccine was no longer working. Then the virus spread to the US in 2013 and Canada in 2014. Further work found that the vaccine strains were divergent from the currently circulating strains and may not offer full protection with the possibility of shedding wild-type virus after challenge. Because of this, many researchers started working on this debilitating disease that cost farmers over $400 million in the US alone and cost the lives of many infected pigs. 

However, there is good news now. Researchers at the University of Saskatchewan have developed a new vaccine that is based on currently circulating PEDV strains and field trials have begun. Hopefully, this new vaccine is successful and the devastating loss and suffering of infected pigs can be stopped.

Sunday, September 4, 2016

Persistence of the Ebola virus in a patient for more than 500 days

Electron micrograph of Ebola Zaire virus. This is the first photo ever taken,on 10/13/76 by Dr. F.A. Murphy, now at UC Davis, then at CDC. Via
A new case study has shown that Ebola virus can survive in human testes for far longer than anticipated and is capable of causing an outbreak more than a year after recovery from symptoms. To be more precise, the Ebola virus was detected in his semen 531 days after he recovered from Ebola and 470 days after he recovered, the virus was sexually transmitted and a new outbreak of the disease happened in Guinea and Liberia until it was contained. To date, this is the longest record of a period of a filvovirus being found still in a patient.

This study presents new findings that could impact the control strategies for future Ebola outbreaks. Right now we don't know how many people can harbor the Ebola virus after survival and if this individual is unique in this regard. However, this study shows the benefit that surveillance after an Ebola outbreak can have. If surveillance stops too early, a resurgent outbreak could be missed until it's widespread. Luckily in this case, health care authorities were able to contain the outbreak before it spread too far.

Saturday, September 3, 2016

Zika update 9-3-16

Electron microscope image of Zika virus. Credit:
Purdue University/Kuhn and Rossmann research groups via The Verge

This has been a pretty bad week for news on Zika virus overall, but there has been some good news.

Among the bad news, the announcement that the limited funding to fight Zika virus in the US is almost gone was the most disheartening. Earlier this year, the CDC was allocated $222 million to fight Zika as a temporary measure until a larger funding bill was passed by Congress. However, that bill has been tied up in Congress as there is a fight over an attempt to prevent any funding from going to Planned Parenthood. Given that Zika can cause severe birth defects if a pregnant woman catches it, it only makes sense to have all options on the table for dealing with this virus. Right now, the CDC has spent $194 million of what they have. President Obama has shifted more funds to vaccine development, but this is only a temporary measure as well. Congress is set to vote on the funding bill again once they return from their recess, so hopefully they can come to a compromise and this vital funding can be dispensed.

Meanwhile, the outbreak in Florida has continued and health officials there have reported more cases of local Zika transmission and also detected Zika in the local mosquito population. Taken alone, this isn't terrible news. However, due to not only the recent findings that Zika can be passed from an infected female mosquito to her eggs, the recent hurricane that dumped a lot of water on Florida, and the continued fight against deploying the genetically engineered Aedes aegypti mosquitoes that pass on a lethal gene to their offspring, this has significant implications for the epidemiology of Zika in the US. Worldwide, the vertical transmission can help explain the spread of this virus and inform the decisions of researchers and healthcare officials in combating this virus. Because the virus can survive in its vector, reducing the vector population is one of the best ways to combat it. The GE mosquitoes are very effective at reducing the vector population without needing pesticide applications that can sometimes have unintended effects, such as the accidental killing of bees in South Carolina recently.

Worldwide, there is more bad news for Zika. A large outbreak has begun in Singapore with over 150 testing positive for the virus and likely many more are infected. There has also been a case of travel related Zika that made it to Malaysia from Singapore. Officials are taking steps to try and limit the chance of local transmission of Zika, but since the vector is endemic, it may just be a matter of time before it spreads, much like what happened in Florida.

The WHO has also recently expanded the recognized range of conditions caused by Zika to include other birth defects. The WHO recently held a press conference on it that they shared to Facebook. Making matters worse, new research has linked Zika virus to a worldwide increase in 

But the news on Zika this week hasn't been all bad news. I recently mentioned a new study that described an improved method for screening existing compounds for activity against Zika. This is a promising approach to not only quickly screen drugs we already have, but also newly developed drugs to combat this virus.

Also on the good news side, Cuba is reporting great success in controlling Aedes aegypti and by extension Zika. As soon as Zika started spreading to the Caribbean in February, the Cuban government immediately took steps to combat the vector. They began spraying inside peoples homes and taking steps to eliminate standing water where the mosquito can breed. Their approach may not work in other countries as the government is led by a single party and has great control over the population. This can be seen with what has happened with attempts to control the vector in the USA; deployment of an effective and safe control measure being blocked by protesters.

Perhaps if the US had started trying to control the vector back in February, we could have avoided the outbreak that we have now, but we waited until the virus had local transmission before much of the general population agreed it was a problem. Hopefully, we can take decisive action now and stop further spread of Zika and complete work on a vaccine. But we need funding to do so.