A virologist's take on the black death genome #microtwjc 2

The second paper in the Microbiology Twitter Journal Club (Tuesday the 22nd May 2012) is the paper out last year documenting the sequencing and assembly of the complete genome of a strain of Yersinia Pestis (plague) from a 14th Century burial site. It's open access so check it out here.


Here's a PBS news story (w/ interview with lead author as well):

Watch Reconstructing Black Death: Why Was Plague Microbe so Deadly? on PBS. See more from PBS NewsHour.

There's also an accompanying feature covering the history and background to Black Death research by Nature, here. Also includes some nice criticisms of this work too. There's also a Nature Blog article here. And here's New York Times article. There's a range of articles by Michelle Ziegler over at Contagions blog to have a look at. And finally before I forget, Vincent Racaniello's 'This Week in Microbiology' podcast covered it last year here.


Here's the video abstract from Nature:

A third dose of MMR is safe but do we need it?

It was recently reported - at the National Foundation for Infectious Diseases 15th Annual Conference on Vaccine Research - that the rate of adverse effects from a third dose of the measles, mumps and rubella (MMR) vaccine is the same as those of the second dose. This was conducted as part of a Centres for Disease Control study and led by Glen Abedi, an epidemiologist at the CDC and Masters student. I'm basing this on a media report of the conference as the paper has not yet been published. You can find more results here.


This is the first study to look at the safety of receiving a third dose of the vaccine in school children during an outbreak. The study has some obvious caveats but what it brings up is the question of whether we should extend 3-dose coverage to the population as a whole?


A mumps outbreak from 2009 to 2010 in and around New York City offered the CDC the chance to specifically look and see just how safe the administration of the third dose would be. In this outbreak - and in others - a very large percentage of those with clinical mumps had received two doses of MMR. We don't really know why, maybe it's a question of them getting a large dose of mumps, or maybe it's the vaccine not being perfect and inducing waning immunity.


They used this as a booster shot against the mumps virus in order to prevent further infection and spread from the community and to do so, they set up vaccination clinics in a number of school in the Orange County area of NYC. Those immunised were between 11 and 17 years old. These booster clinics have been set up before for mumps. These clinics are very money intensive and have reported to cost around $500/person. 


As a means to stem the tide of the outbreak, this three dose schedule worked and the rates of mumps infection dropped from 4.93/1000 to 0.13/1000. Although there was no reporting of antibody levels before and after the 3 doses. And we can't be sure whether the outbreak would have abruptly ended like this without vaccine intervention. One caveat with these kinds of studies is that they usually administer the dose late into the outbreak. If done earlier they may have completely controlled it's spread.


But to determine whether this was safe they had to send out questionnaires to the families of the kids, they consulted local clinics and they looked up the Vaccine Adverse Events Reporting System (VAERS). Over 90% of those immunised responded and only 115 reported adverse effects 2 weeks after vaccination. Those effects were only local pain/swelling at the injection site, muscle pain and dizziness/light-headedness. All the kinds of things that suggest that your immune system recognised the vaccine. Note that no cases of meningitis, glandular swelling  or orchitis were recognised, somewhat more serious effects of mumps vaccination in some cases.


This research highlights that in certain situations (a relatively small localised outbreak, with very targeted vaccination of schoolchildren) a third dose of MMR is safe. Of course if they wanted to definitively test this I think they would need a bigger sample size/diversity than the 1755 religious school kids. Remember also that they didn't report looking into levels of mumps immunity so time will tell whether these children were really protected and whether they may still get mumps in the next couple of years.


But the question now remains is whether or not we should extend three doses to the general population or even in cases of a localised outbreak. Mumps is a very infectious virus and hence you need very high levels of population protection to achieve herd immunity (estimated as high as 92%). In the U.S, those between 13 and 17 have an estimated 2-dose MMR coverage of 90.5% and the MMR vaccine uptake percentage in colleges etc is just shy of 90%. So maybe what this data says is that in general we should really focus on achieving very high levels of 2-dose MMR but in the cases of a mumps outbreak we could use a targeted third dose. If we didn't mind the cost. Maybe in the future to lower the costs, all schools/campuses will introduce a MMR catch-up when the new students start.


Another issue apparent is whether we need a new mumps vaccine. Clearly our current mumps vaccine has been amazingly effective to date but maybe it is not enough to completely eradicate the virus. This is something we will have to consider now that people are developing newer vaccines against the virus.



Centers for Disease Control and Prevention (CDC) (2010). Update: mumps outbreak - New York and New Jersey, June 2009-January 2010. MMWR. Morbidity and mortality weekly report, 59 (5), 125-9 PMID: 20150887

Viruses This Week in Bats

OK they're cute, but are they deadly?

I was lucky enough to appear alongside the guys over at This Week in Virology (thanks Vincent, Alan, Rich and Dickson) to discuss the recent publication of a paper (here in open access) which identified bats and rodents as potential animal reservoirs for a whole load of newly discovered RNA viruses, among other things. Check out the link above and enjoy what was an extremely fun and interesting hour and a half long experience. 

The paper, from a large group of authors right across the world (actually when you look at where they looked, it wasn't all that much of the globe but I guess it is a sample after all), looked specifically for paramyxoviruses in bats and in rodents. 

They picked paramyxoviruses because these viruses have been known to jump species from mammals into humans and other animals, they cause significant diseases (measles, mumps, respiratory infection and encephalitis and finally because I guess they had to focus somewhere. They actually tried unbiased 'deep sequencing' and quickly found it was heavily biased toward not finding paramyxoviruses. Possibly explaining the lack of paramyxovirus discovery in previous non-targeted efforts.

Their thinking was that these bats and rodents would have the potential to host a large number of viruses due to their high population sizes/densities, close contact with each other and potential to travel large distances (in the case of bats). Of course based on these criteria they could have looked in fish or birds but bats and rodents being mammals, there's a higher likelihood that their viruses could do really well in humans (although look at influenza and human metapneuomovirus). Although I bet you would find hundreds more if you explored the seas and the skies as opposed to the jungles.

They looked in over 10,000 individual animals from 15 places around the world, mostly in the tropics and were able identify 66 previously unknown 'species', more than doubling the potential number of potential paramyxoviruses previously known. They even identified the possibly first cousins of many of our deadly viruses, like mumps, nipah and respiratory syncytial virus. 

They then took this further and looked at how viruses like these grew in bats, whether they caused disease and were the excreted and transmitted within and between bat populations. Instead of exploring what viruses were simply present, this group was more interested in establishing whether bats acted as an animal reservoir as knowing this would be excellent from a public health perspective. For example, what areas/species should be protecting and avoided from human contact.

Also from a purely biological perspective, if we assume that these closely related viruses (for example the 'bat mumps' virus) are well adapted to bats and not to humans and then vice versa for the human viruses, then the similarities and differences in functions of each component of the virus should be illuminating understanding how viruses jump species.

#Microtwjc 1 - bacterial cell shape and pathogenesis

This is new ground for me as a virologist, writing about bacterial genetics and pathogenesis. But it's for a good cause - the cause of Microbiology Twitter Journal Club or #microtwjc. Set up by Zoonotica and encompassing a number of other microbiologists. This post serves background reading for the discussion on this paper on Tuesday the 8th May at 20:00 BST.

This paper aims to determine the role of bacterial shape/structure in how micro-organisms cause disease. I don't think they actually succeed in doing this as it's going to be a pretty complicated picture. But it does highlight a number of interesting points in bacterial genetics and pathogenesis, especially for an organism in which very little is really known.

Two very different structures - ultimately a single genetic change. But how?

A Jedi and vaccination

Last week was World Immunisation Week, celebrating and raising awareness for one of the greatest medical interventions known to mankind: the vaccine. But vaccination has a lot of problems, one being the cold chain.

The cold chain refers to the physical supply of refrigerated vaccines from the manufacturer to the person being immunised. This constant controlled temperature is required to limit any damage done to the vaccine components, which themselves are biological samples. 

For example, the live-attenuated measles vaccine used across the world will rapidly lose it's ability to protect you if it is stored at 37 degree celsius; it can be stored for much longer at 4 degrees. This makes the cold chain essentially one of the most important components of global health strategies. For another take on the cold chain and developments to make it better, read Vincent Racaniello's post over at Virology Blog last year. 

The cost of getting the flu

I've come across this neat infographic that explores the cost of influenza infection to the individual and to the country as a whole (here's the WHO factsheet on flu for more info). It really sends home the message of necessity of preventative and therapeutic options for treating these respiratory viruses.


 Of course this can also be extended worldwide and to the other viruses that cause the same roughly the same symptoms as influenza, like Respiratory Syncytial Virus. There's a couple of differences when you extend this to other countries, namely the UK, thanks to our National Health Service where Doctor's visits and prescriptions are free. 


Also in some countries it is good to remember that in some countries the fu season extends throughout the whole year. Despite some questions arising on the effectiveness of the seasonal flu vaccines, they are better and safer than nothing so remember to get protected if you're at risk!



Source: FrugalDad.com

So how does Respiratory Syncytial Virus infect your lungs?

This post is hopefully the beginning of a new series of stories on this blog covering the thinking behind the papers I cover from the point of view of those scientists doing the work. 

The first up is from Remi Villenave, a post-doc in my department at Queen's University, Belfast Centre for Infection & Immunity. Remi is currently working on understanding how Respiratory Syncytial Virus (RSV) infects and causes disease in humans. He studies this by using an in vitro culture of primary differentiated bronchial epithelial cells taken from children. This work is reported in a PNAS paper published a couple of weeks ago. 

In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

Here is some answers he gave to a couple of questions I put to him last week:

Single mumps vaccine jab (versus MMR) in the UK - back again?

The "Children's Immunisation Centre" has recently announced that it plans to start administering the single mumps vaccine sometime in the 2nd quarter of this year in the UK. When I rang them up asked at the helpdesk, the very helpful receptionist told me they were scheduling vaccinations for July. Their website details:

"Currently Mumps single vaccine is not available due to Merck stopping the manufacture of it about 3 years ago. However we are working with our suppliers (who have an MHRA -Medicines and  Healthcare products Regulatory Agency - Wholesale license and who are regularly inspected) to source a Jeryl Lynn Strain (the safest strain) of Mumps vaccine." 

They continue,

"M-M-R single vaccines are manufactured by, France, India, and in some European countries and also China, Russia and in future the  UK. Our suppliers in the UK are working with UK manufacturers and are looking to produce the single mumps vaccine  for our patients."

The internet has picked up on this as well, here.

The curious case of Wipfelkrankheit "disease"

Baculovirus particles

I am sure you have heard of Wipfelkrankheit disease. If you haven't heard of this name at least you must have heard what it's symptoms are. Wipfelkrankheit - or in English, tree-top disease, is a fatal viral infection of caterpillars, an infection that causes them to climb up high, hang upside down and liquify themselves raining down millions upon millions of viral particles to the forest floor below. 

Here they are easily ingested by unsuspecting and uninfected insects. The question of how they do so has been consuming researchers for 100 years. But we may now have the full story. 

Your top 10 questions in virology? Here's some of mine:

Do you want to help organise a virology meeting? Paul Duprex, the chair of the Society for General Microbiology's Virology Division (and also my current PhD supervisor) is asking you guys to help him and the committee set-up the virology symposium in 2014. 

This event will be: "Top 10 questions in Virology". The aim of this is for ordinary people (scientists and non-scientists alike) to put forward a question that they really would like answered. Something which has been niggling at them for sometime now. Something they think is important and needs to be answered soon.