Stanley Prusiner

There's also an interview with Prusiner at the Nobel Prize website.

The rise and fall of kuru

Historical research carried out by Michael Alpers (see below) on the Fore suggests that the epidemic may have originated around 1900 from a single individual who lived on the edge of Fore territory, who is thought to have spontaneously developed Creutzfeldt-Jakob Disease (CJD).

Cannibalism, and possibly other funeral practices then led this single case to become an epidemic.

When cannibalism was outlawed in the 1950's Kuru began to decline although cases continued to appear for several decades more - suggesting a potentially very long incubation period.

The last kuru sufferer died in 2005 and active field surveillance was continued until 2010. It appears that Kuru has died out and the epidemic is finally over.

In recent years scientists have been studying the survivors of the Kuru epidemic and have found that some individuals have a strong genetic resistance to the disease. This could be very valuable in suggesting treatments for other prion diseases.

"Kuru comes from the same disease family as CJD, so the discovery of this powerful resistance factor opens up new areas for research taking us closer to understanding, treating and hopefully preventing of a range of prion diseases."

The Science and the Sorcery

Kuru: The Science and the Sorcery

Australian scientist Michael Alpers dedicated over 50 years to researching Kuru, an obscure and incurable brain disease unique to the Fore people of New Guinea. Kuru was once thought to be a psychosomatic illness, an infection, a genetic disorder, even a sorcerer's curse, but Alpers' findings pointed to cannibalism as the culprit. Yet a recent discovery has proven to be even more disturbing: the malady is linked to mad cow disease and its human equivalent, variant CJD. With a decades-long incubation period, could a larger outbreak be on its way?

Disease Sleuths

I've posted about Google's flu tracker and how Twitter is being used to track diseases before but I thought NPR's little animation was nice. The article: Disease Sleuths Surf for Outbreaks Online expands on it and is also interesting. This type of tracking is not suitable for all diseases:

In the early days of the cholera outbreak, Twitter and HealthMap data closely matched official reports. After 100 days online activity dropped off even though the epidemic raged on. Disease is easiest to detecte when it is out of the ordinary. Regularly recurring maladies like malaria are hard to follow online.

But it's a hot topic at the moment and even has a new name 'Webidemiology'. I hadn't realized that Google had expanded its surveillance to include Dengue Fever.

Suicide rats

I found this video from the Australian Broadcasting Corporation (ABC - nothing to do with the ABC network in America). It looks like Catalyst is a regular science show on the network. This show on Toxoplasmosis is from 2007. The tone is a little odd for something so horrific but they get quite a bit of interesting science across in 5 minutes.

Toxoplasmosis, suicide and brain cancer

In addition to the effects I mentioned in class Toxoplamsosis has also been linked to increased rates of suicide: Toxoplasma gondii Seropositivity and Suicide Rates in Women
In conclusion, the results suggest that a positive relationship between rates of infection with T. gondii and suicide is apparent in women of postmenopausal age. Prospective studies are necessary to further confirm this association predictively and to explore mechanisms mediating this relationship.

and brain cancer -
Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common.
Infection with T. gondii was associated with a 1.8-fold increase in the risk of brain cancers across the range of T. gondii prevalence in our dataset (4–67%). These results, though correlational, suggest that T. gondii should be investigated further as a possible oncogenic pathogen of humans.

Both these papers are from 2011. It's pretty clear there's something going on even if we don't know exactly what it is.

Illusory superiority

I was curious what proportion of road accidents were caused by driver error rather than, say, brake failure. Although I suspected the proportion would be high I was surprised it was as high as 93%. In fact the majority of accidents are solely due to driver error.

What is alarming is that numerous surveys have revealed that whilst, in reality we are all only human (and get distracted, make mistakes and fall asleep), most of us believe we are brilliant drivers.

In the United States for example, when asked to compare their driving safety and skill to other people 93% of people put themselves in the top 50%. This is apparently known as 'Illusory Superiority'.

I wonder how long it will be before someone tries to use Toxoplasmosis infection as a defense against a charge or reckless driving or something similar. It's really not that different to the Twinkie defence.

How your cat is making you crazy

Toxoplasmosis, the subject of today's lecture, is cropping up on news websites lately as people pick up on an article published in the Atlantic magazine:
How Your Cat Is Making You Crazy

Jaroslav Flegr is no kook. And yet, for years, he suspected his mind had been taken over by parasites that had invaded his brain. So the prolific biologist took his science-fiction hunch into the lab. What he’s now discovering will startle you. Could tiny organisms carried by house cats be creeping into our brains, causing everything from car wrecks to schizophrenia? 

Amerithrax

The American Anthrax attacks of 2001, which the FBI itself have named 'Amerithrax', provide an insight into how we might respond to a major bioterror threat.

UCLA's department of epidemiology in the School of Public Health has gathered together virtually every piece of publicly available information to create an incredibly detailed timeline with information on every single case.

Epidemiologists are often called "disease detectives," using many of the same methods as regular detectives to determine the cause of disease outbreaks, epidemics (i.e., larger excess in disease cases), or even pandemics (i.e., worldwide excess in disease cases). The anthrax outbreak in the United States which occurred during the latter part of 2001 has many of the same characteristics as a typical outbreak. What is different, however, is that there was no transmission from infected to susceptible persons that linked one case with another. Instead, all of the cases were generated by a terrorist or group of terrorists who sent letters containing anthrax spores through the postal system.

Bioterrorism in Japan

Spraying scenes from the Aum Shinrikyo headquarters building (photographs taken July 1, 1993, by the Department of Environment, Koto-ward).

I've posted this before but I think this odd tale is worthy of repeat.

Terrorists and microbiology don't seem to mix well. The meticulous and laborious work involved in microbiology seems challenging for the average terrorist who would probably rather be blowing something, someone, or themselves, up.

From the pages of 'epic fail' I bring you the surprisingly little known story of Aum Shinrikyo and anthrax. I am not making this up, everything that follows is fairly well documented (eg. this CDC report), it just isn't very well reported.

Aum Shinrikyo, who have apparently changed their name to Aleph, are a Japanese religious movement, or cult depending on where you draw the line. They are most notorious for their Sarin attack on the Japanese subway in 1995 that killed 12 commuters, seriously injured 54 and affected about a thousand more.

Two years before this, in July 1993, Aum Shinrikyo members dispersed a liquid suspension of Bacillus anthracis (anthrax) from the roof of an eight-story building in Tokyo. Although residents complained of foul odors the spraying went on for at least four days until demands from local residents forced Aum Shinrikyo to stop. There were no known human cases and, at the time, no-one realized an attack had even taken place. The incident was largely forgotten until the 1995 subway sarin gas attacks. Confessions of Aum Shinrikyo members revealed the plot and samples collected in 1993 were eventually analyzed in 1999 and found to be anthrax. The obvious question is why the anthrax attack plot had failed. The consensus seems to be that the would be bioterrorists did just about everything wrong.

• Spraying during the day was a bad move, sunlight inactivates the spores and heat radiating from concrete and asphalt makes the spores rise rather than fall.
• The spore concentration that was sprayed was about 10⁴/mL - many orders of magnitude less than the 10⁹ to 10¹⁰ organisms/mL considered to be optimal.
• The spraying device was very inefficient and apparently the nozzles clogged repeatedly and the device itself broke down several times.
• But I saved the best for last. The strain of anthrax used was an attenuated (weakened) strain used to vaccinate animals in Japan. This strain is generally regarded as nonpathogenic for immunocompetent people.

Bioterrorism - it's not as easy as they make it look in the movies.

Papers in limbo

We won't talk about influenza until week 10 but the theme of a paper in Science this week is very pertinent to the biosafety topic this week -
Does Forewarned = Forearmed With Lab-Made Avian Influenza Strains?

H5N1 Influenza has a human mortality rate of over 50% but does not yet spread among humans. Two groups of scientists in investigating why this is have created strains that DO spread easily among ferrets (a common model for human drug strains). Should they be able to publish the results of their work?

Papers about the studies, stuck in limbo at Science and Nature, remain unpublished while scientists, journal editors, and public health officials weigh the benefits and risks of full disclosure.

Proponents of full disclosure, including the researchers who conducted the work, contend that knowing the genetic signatures of these potentially devastating viruses might prove pivotal to shoring up surveillance measures and controlling an emerging threat.

Maybe, say opponents in the other camp, but they stress that in the predominantly poor countries where H5N1 circulates, surveillance and control systems are too rudimentary, or nonexistent, to take advantage of the new knowledge. They worry that if published, that data could provide a recipe for bioterrorists to unleash a doomsday scenario.

Outbreak

'Many people are dying and are going to continue to die unless we catch this monkey!'- Dustin Hoffman. Classic.

NBAF

I spoke too soon. Just two days ago the government cut all construction funding for the new billion dollar National  Biological and Agricultural Defense Laboratory that was planned for Manhattan, Kansas.

Although the cut has occurred largely for budget reasons the
National Research Council will continue its congressionally-mandated study of the facility’s safety. It's actually the second study - an earlier study by National Research Council scientists determined, based largely on the federal government’s data, that there was a 70 percent chance of an accidental release of foot-and-mouth disease from the lab sometime in its projected 50-year lifespan.

Read more here: http://www.kansascity.com/2012/02/13/3427825/budget-puts-kansas-lab-on-shaky.html#storylink=cpy

Speaking of fomites

Do mobile phones of patients, companions and visitors carry multidrug-resistant hospital pathogens?

Short answer: Yes

Long answer: Significantly higher rates of pathogens (39.6% vs 20.6%, respectively; P = .02) were found in mobile phones of patients' (n = 48) versus the health care workers' (n = 12). There were also more multidrug pathogens in the patients' mobile phones including methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase-producing Escherichia coli, and Klebsiella spp, high-level aminoglycoside-resistant Enterococcus spp, and carabepenem-resistant Acinetobacter baumanii. Our findings suggest that mobile phones of patients, patients' companions, and visitors represent higher risk for nosocomial pathogen colonization than those of health care workers. Specific infection control measures may be required for this threat.

 

Seething cauldron

 
Restaurants are inspected for cleanliness but not hospitals. Not even operating rooms. You can go home and make your own dinner...

Hospital acquired infection from the PBS Second Opinion series.

Bonus viral hemorrhagic fever

Although it is the Filoviruses such as Ebola that leap to mind when people hear the phrase 'viral hemorrhagic fever' (VHF) there are actually four different families of viruses that can lead to the classic symptoms of VHF's - capilliary leak leading to high temperature, shock (loss of blood pressure) and death.

This is rather important because whilst the Ebolavirus is really very rare some of the other VHF's are far more common. We'll talk about Yellow Fever in the penultimate week but another disease in the same group is Dengue Fever. Although 50-100 million people are estimated to contract this mosquito borne disease every year only a minority get a severe hemorrhagic fever. Maybe 5%. But 5% of 50-100 million is still several million people per year! In the severe form  Dengue Fever causes a very high fever (over 104) and generalized muscle and joint pain (hence the common name 'breakbone fever').

It is the most common viral disease transmitted by arthropods and it is deemed second in importance to malaria in terms of tropical diseases. The World Health Organization currently counts dengue as one of sixteen neglected tropical diseases and it is found in a wide range of tropical countries across South America, Africa and Asia.

In 2008 I'd been using up some gift cards from amazon.com and had bought several items. Probably some music, but I don't remember what, and some books on disease including one on Yellow Fever. Some time later I got an e-mail highlighting items they thought I might like. I was amused to see they'd combined my viral hemorrhagic fever book with music to come up with the conclusion I'd like music by a band called Dengue Fever. The sort of stupid conclusion only a computer could reach. Except they were right.

In contrast to most bands with disease related names (eg Anthrax, Cholera, Bubonic Plague and Ebola) Dengue Fever are not only not a heavy metal band but play 'Southeast Asian pop, Vietnam-war-era lounge music, klezmer, ska, surf rock, and Ethiopian jazz'. One of the band apparently caught Dengue Fever which is where the band got their name. I suspect Anthrax, Cholera, Bubonic Plague and Ebola can't say that. Dengue Fever (the band) are based in LA and so play in Santa Barbara quite freqeuntly, usually at SoHo - twice last year for some reason. 1000 tears of a tarantula is the first song link I clicked on and is still my favorite song of theirs.

Ebola in apes

Caregiver at Congo's Virunga National Park wearing a facemask to limit danger of orphan ape being exposed to human diseases.

Originally it was suspected that primates such as gorillas might be the natural reservoir of the ebola virus. It is now thought that this is unlikely and that the reservoir is probably bats. One reason we think that apes are an unlikely reservoir is that they suffer fairly severe outbreaks that can kill a high proportion of the animals, (making it difficult for the virus for persist in this population). (eg Ebola Outbreak Killed 5000 Gorillas in the journal Science in 2006). In other words the virus is spilling over into the ape populations in the same way it occasionally spills over into human populations. Over the last two decades the Zaire strain of Ebola has killed roughly one third of the world's gorilla population and only a slightly smaller proportion of the world's chimpanzees

Just last December a paper in PLoS ONE: Consequences of Non-Intervention for Infectious Disease in African Great Apes highlighted the potentially dire consequences of diseases such as Ebola and SIV's for African Great Apes.

Why can't mosquitoes transmit HIV?

In a recent survey of young Australians (18 to 29) 43 per cent believed they could get HIV from mosquito bites.

Although this is NOT the case, it does raise the question of exactly why not given that mosquitoes do vector a range of other diseases. I found this website at Rutgers that provides a very clear description of three possible mechanisms for transmission and then clearly describes why each one is simply not possible or is beyond the bounds of likely probablity. For example:

Many people think of mosquitoes as tiny, flying hypodermic syringes, and if hypodermic needles can successfully transmit HIV from one individual to another then mosquitoes ought to be able to do the same. We have already seen that HIV-infected individuals do not circulate enough virus particles to result in infection by contamination. However, even if HIV-positive individuals did circulate high levels of virus, mosquitoes could not transmit the virus by the methods that are employed in used syringes. Most people have heard that mosquitoes regurgitate saliva before they feed, but are unaware that the food canal and salivary canal are separate passageways in the mosquito. The mosquito's feeding apparatus is an extremely complicated structure that is totally unlike the crude single-bore syringe. Unlike a syringe, the mosquito delivers salivary fluid through one passage and draws blood up another. As a result, the food canal is not flushed out like a used needle, and blood flow is always unidirectional. The mechanics involved in mosquito feeding are totally unlike the mechanisms employed by the drug user's needles. In short, mosquitoes are not flying hypodermic needles and a mosquito that disgorges saliva into your body is not flushing out the remnants of its last blood meal.

The only thing we have to fear...

It is notoriously difficult to change people's behavior. However it is quite easy to frighten people.

Is it acceptable to exaggerate a risk in order to frighten people into changing their behavior?

Watch the following video and discuss.

Pneumocystis Pneumonia --- Los Angeles

Julio sent me this CDC report, from June 5 1981, about 5 cases of Pneumocystis Pneumonia in Los Angeles, which was the first published report about what would, a year later, be known as AIDS and would, thirty years later, have killed 25 million people.

All the above observations suggest the possibility of a cellular-immune dysfunction related to a common exposure that predisposes individuals to opportunistic infections such as pneumocystosis and candidiasis. 

If you would like to read more about this period in history when AIDS was first being discovered and invesitagted  then Randy Shilts book, And the Band Played On, is thoroughly recommended:

"An exhaustive account of the early years of the AIDS crisis, this outlines the medical, social and political forces behind the epidemic's origin and rapid spread. The book stands as a definitive reminder of the shameful injustice inflicted on this nation by the institutions in which we put our trust."  Publishers Weekly

Viral chatter

Virus hunter Nathan Wolfe is outwitting the next pandemic by staying two steps ahead: discovering deadly new viruses where they first emerge -- passing from animals to humans among poor subsistence hunters in Africa -- before they claim millions of lives.

Check out Nathan Wolfe's talk at the 2009 TED conference last year. TED (Technology, Entertainment, Design) invite some of the world's most fascinating thinkers and doers, and challenge them to give the talk of their lives. The best talks and performances are available on their website. You should all check out this talk, it is very interesting, very well presented and hugely relevant to this class.

Davis sent me a link to a New Yorker article from 2010 that covers Nathan Wolfe's work:

Sandrine had just finished preparing the meat for dinner. I asked her if she understood how risky it was to plunge her hands into the intestines of a dead monkey. “Yes,” she said. “I know that bushmeat is dangerous. That it can kill my children.” She was also aware that there had been an outbreak of Ebola recently in Congo. I wondered whether she or her husband had ever seen dead monkeys or gorillas in the forest. She nodded, gazing at the dark foliage as night began to fall. “What did you do when you saw them?” I asked. She turned to me and smiled. “I thanked God, picked them up, and brought them home for dinner,” she said.

Black Death - the Movie

I'm not sure how extensive the 'historical adventure horror' genre is but I guess this  movie is firmly within it. Not really my cup of tea - I felt obliged to watch it given the title - but it does make you glad to be living in the 21st century.

From the Director:

It's a 'medieval guys on a mission' movie. The period of the black death – what's fantastical and rich about that period? I said, 'What if we took a realistic approach?' The people of the time believe the plague was sent by God to punish them for their sins, or by the Devil to torment them. I wanted to find out what the characters felt and posit them on a journey of 'is it real? Or is it not real?' What would a necromancer be like if he existed? We added this fundamentalist knight, so it touches on fundamentalism. It's a super dark film but it's exciting. It's like a dark parable about how things haven't really moved on in the last 600 years.

Nom Nom Nom

Following on from the post below, here's the Black-footed ferret who likes to snack on prairie dogs and can also succumb to bubonic plague. The black footed ferret is a federally endangered species though and one of the rarest mammals in North America. In 2008 when bubonic plague broke out in the prairie dog colonies ferrets were vaccinated:


In mid-May, the Centers for Disease Control confirmed sylvatic plague in black-tailed prairie dog colonies in the Conata Basin area of Buffalo Gap National Grasslands in southwestern South Dakota. As of late June, about 9,000 acres of prairie dog habitat — including colonies occupied by vulnerable black-footed ferrets — have been infected by the disease, according to U.S. Forest Service mapping. Black-tailed prairie dogs are also being reconsidered for listing under the Endangered Species Act.

To help increase ferret survival during this outbreak, biologists are vaccinating wild ferrets to provide immunity if they become exposed to plague. The plague vaccine was developed for humans by the U.S. Army Medical Research Institute for Infectious Disease and is being tested and modified for animals at the USGS National Wildlife Health Center (NWHC) in Madison, Wisc.

nom nom nom

Prairie dogs are:

a) cute little critters and an important part of the prairie ecosystem

b) a damaging pest of pastures and fields with their digging and such.

Of course the correct answer is c) all of the above. Unfortunately Prairie Dogs are also a host of bubonic plague which gives the anti-prairie dog campaigners (mainly farmers and ranchers) a pretty powerful argument:

"They need to be managed when they are overpopulated, you want to remember, when they get overpopulated, they have a tendency to have bubonic plague. And bubonic plague is contagious to people."

Hence Bill LB473 before the Nebraska Legislature that would give counties the power and duties to carry out a management program to help control the animals.

What is missing from the disease argument though is whether an increase in the levels of bubonic plague in prairie dog populations ever actually leads to cases in humans.

Vaccine efficacy

Fear of vaccination is nothing new. This famous cartoon by James Gillray is from 1802 and refers to the fears people had against being vaccinated by Cowpox, which was used to give protection to the far more deadly smallpox.


Today the internet gives a voice to everyone. But you need to be critical of what you read. Here's a popular argument against vaccines you'll find. I copied this verbatim from an anti-vaccine website.


Meanwhile, in the real world vaccines are failing miserably. A recent outbreak of mumps in the New Jersey / New York area occurred almost entirely among children who had already been vaccinated against mumps. Clearly if vaccines really worked, then an outbreak should have only occurred among those who were NOT vaccinated against mumps, right? But as I reported, 77 percent of the children who got infected had already been vaccinated!

Sounds convincing? Can you work out what's going on?

Let's consider the numbers. Imagine we have a vaccination rate of 90%. Now, most vaccines only have a certain efficacy, in some cases they just don't work. Let's imagine our mumps vaccine has an efficacy of, say 80%. If you get the vaccine you have an 80% chance of getting immunity, and a 20% chance that you won't. (Which is why we actually need a vaccine coverage in excess of that predicted from R0 in order to establish herd immunity).

So in a population of 100 children we have 10 children who have not been vaccinated and are susceptible. But we also have 20% of the 90 vaccinated children who are susceptible, that's 18.


Assuming our outbreak hits these two groups equally then 18 out of every 28 of those infected (65%) will have been vaccinated. This is an argument for MORE vaccination to protect the fragile herd immunity and for MORE research to increase the efficacy of our vaccines. One of the reasons vaccines are given to children, (apart from giving them protection!) is that their efficacy is usually greatest. I believe this is the case with the HPV vaccines I mentioned. You can get it later in life but there is a greater chance it will not lead  to immunity.

The head and the heart

I just discovered Missouri Medicine - an award winning publication from the Missouri Medicine Association. As a person with some science background but no medical training I find their articles pitched at just the right level.

There's a nice article in the current issue advising doctors how to respond to parents fears of vaccinations.

We in the medical community must acknowledge that, for parents, the idea of allowing their child to be
injected with an agent that might cause harm and will definitely cause pain is, at the very least, unsettling to even the most educated, most rational parent. The genius of the anti-vaccine forces is that they are passionately empathetic toward parents who want only to protect their kids – and they are not shy about the sacrifices that they have personally made in standing up to uncaring physicians and greedy pharmaceutical companies. And how do we respond? Often with a well reasoned, evidence-based argument that dismisses vaccination concerns as unfounded and uninformed.


If we do express emotion about vaccination, it often comes across as either as anger at parents who just do not care enough to do what is best for their children or annoyance on our part for having to waste our time with such nonsense.


The science is clearly, unequivocally, powerfully on our side when it comes to the safety and effectiveness of vaccination, and we must share this information which is at the core of our efforts to prevent disease in children. But we have to remember that parents make decisions about their kids, not from the head, but from the heart.

Terminology

I have added a list of the glossary terms included in the midterm.
It's also linked to on the right hand side with the lecture slides.

Draft genome

Here is the latest paper on bubonic plague and the Black Death, from just a few months ago:
A draft genome of Yersinia pestis from victims of the Black Death
Although the study confirmed the basic story from last year - that the bacteria that caused the Black Death was the ancestor of all modern bubonic plague strains - it did not find any obvious change in virulence genes that might account for the huge mortality that the Black Death caused.

'(W)e posit that molecular changes in pathogens are but one component of a constellation of factors contributing to changing infectious disease prevalence and severity, where genetics of the host population, climate, vector dynamics, social conditions and synergistic interactions with concurrent diseases should be foremost in discussions of population susceptibility to infectious disease and host–pathogen relationships with reference to Y. pestis infections.'

Reanimated post

It seems appropriate to reanimate this blog post from the graveyard

I introduced the basic SIR model for a simple epidemic to you. This model actually has a long history and was first described by Kermack and McKendrick in 1927.

As I indicated this model has since been expanded to include virtually every disease scenario you can imagine.

Last year a group of Canadian mathematicians used this SIR format as the basis for an analysis of a zombie epidemic. Their paper: WHEN ZOMBIES ATTACK!: MATHEMATICAL MODELLING OF AN OUTBREAK OF ZOMBIE INFECTION ) - somehow it seemed appropriate to keep that in capitals) - describes a model that should look basically familiar to you.

Notice in their S Z R model (Z for Zombie of course) there are two extra transitions - from R back to Z (reanimation of the dead is well established in the zombie movie genre) and a movement directly from S to R (non zombie related death which can be quite high in this genre and so worth taking account of).

This is, perhaps unsurprisingly, the first mathematical analysis of an outbreak of zombie infection. While the scenarios considered are obviously not realistic, it is nevertheless instructive to develop mathematical models for an unusual outbreak. This demonstrates the flexibility of mathematical modelling and shows how modelling can respond to a wide variety of challenges in ‘biology’.

In summary, a zombie outbreak is likely to lead to the collapse of civilisation, unless it is dealt with quickly. While aggressive quarantine may contain the epidemic, or a cure may lead to coexistence of humans and zombies, the most effective way to contain the rise of the undead is to hit hard and hit often. As seen in the movies, it is imperative that zombies are dealt with quickly, or else we are all in a great deal of trouble.