Final

Good luck tomorrow. 12 noon. The usual room (1640 Broida).
The format is not just similar to the midterm it's identical but the final is worth 50% more than the midterm.
As far as possible questions are based on material covered since the midterm BUT I have used some of the terminology that we introduced in the first half. However this should be pretty familiar by now since it is terminology we kept using (vector, prevalence, epidemic, antibiotic etc)
We'll be grading the exams pretty quickly so grades should be available before the end of the weekend but PLEASE write clearly to make our job easier

Forward harvesting

One of the grimmer terms I have come across in epidemiology is 'forward harvesting' - referring to the possibility that events like heatwaves may cause a high mortality rate but only by bringing forward the deaths of those who would have died in the short term anyway.

Although this seems likely, given that events like heatwaves and cold spells primarily affect the elderly there does not not seem to be much evidence for it. In fact there seems to be no evidence for it in cold spells and only a weak effect in some studies on hot spells. Because we have large data sets the effect, if there is one, cannot be large.

eg for the 2003 heatwave in Europe and especially France:
Impact of the 2003 Heatwave on All-Cause Mortality in 9 French Cities
There was no evidence to suggest that the extras deaths associated with the heatwave were simply brought forward in time.
and for a series of heatwaves and cold spells in Holland:
The Impact of Heat Waves and Cold Spells on Mortality Rates in the Dutch Population
The results concerning the forward displacement of deaths due to heat waves were not conclusive. However, looking at the relation between the ambient temperature and mortality over the whole period studied, our results showed compensatory effects on mortality in the longer lag periods after warm weather (average temperature above optimum temperature level). This could be an indication of a harvesting effect of warmer temperatures. However, as previously discussed, this was not clearly shown by the analysis of heat waves. We found no cold-induced forward displacement of deaths.

Acronymorama

What do the following acronyms stand for and what do they have to do with infectious disease?

• AIDS
  
• BSL
• BSE
• VRSA
• HIV
• HAART
• MDR-TB

Thirteen diseases

Consider the following thirteen diseases, all of which we discussed, although some of them only briefly.

1. AIDS
2. Bubonic plague
3. Lyme disease
4. Cholera
5. Ebola hemorrhagic fever
6. Hantavirus cardiopulmonary syndrome
7. Measles
8. Marburg hemorrhagic fever
9. Tuberculosis
10. Malaria
11. Polio
12. Influenza
13. Yellow fever

• Four of these disease have vectors. Which are they and what are the vectors?
• Three of these diseases have rodent reservoirs. Which are they?
• Which three of these diseases have exhibited a series of truly global pandemics?
• Which of these disease are essentially incurable? What do these incurable diseases have in common?
• Which of these diseases is caused by neither a bacteria nor a virus? What is it caused by?
• Which two of these disease are transmitted by the fecal-oral route?
• Which two of these diseases are a particular problem to immunocompromised people? Why?
• Which of these disease can be vertically transmitted?
  

Whale snot

Sandwiched between 'How to make a toddlers guitar hero controller' and 'How to make a cardboard horse to hide a paper tiger' (huh?) on the Make Magazine blog is the equally fascinating 'How to collect whale snot using an RC helicopter'.

With a growing interest in wildlife diseases and a desire to non-destructively collect samples from whales scientists have been interested in collecting the exudates from whale blowholes.

At the simplest level, as they explain this involves three steps:

• Find whale.
• Hold petri dish over blowhole to intercept spout.
• Return to lab, enjoy sample.

Of course holding the petri dish over the blowhole is the tricky step. Enter the RC helicopter.

Scientific report here:
"A novel non-invasive tool for disease surveillance of free-ranging whales and its relevance to conservation programs"

I've said this before, but I'll say it again, how can you not be a biologist when you could get to do things like this for a living?

HIV vaccine?

Okay, how about a review question AND an interesting news article?

There are four fundamentally different ways of making vaccines. What are they and what are the advantages and disadvantages of each?

Reported in New Scientist this week: Fight HIV with HIV: 'safe' virus proposed as vaccine from results reported last month at the 2010 annual Conference on Retroviruses and Opportunistic Infections.

Review part 1

Thank you to everyone who has posted here this quarter and thanks for being a great class. Seriously, I have enjoyed teaching the class this quarter, I thought the lectures were nicely interactive - lots of good questions from the audience.

I'll continue to post here up until the final next Friday and I'll be posting some questions for review. I will eventually post some additional exam format questions in the links on the right but I'll also post more general review type questions here. Let's see, here's some simple definitions to get you started. For best value try explaining these to someone else.

What's the difference between:

• A dead end host and a definitive host?
• Reassortment and transformation
• An antibiotic and an antibody?
• A vector and a vaccine?
• A viral swarm and a cytokine storm?
• Antigen shift and antigen drift?
  

MMWR

Morbidity and Mortality Weekly Report (MMWR) is a weekly epidemiological digest for the United States published by the Centers for Disease Control and Prevention.

You can sign up to receive it in your e-mail weekly or access the current version and the archives at the website. There's often something interesting there that isn't getting picked up by the mainstream media and when something does hit the media it's a good place to go for the plain facts.

The writing is aimed at a medical audience so there is quite a lot of jargon but there is always something interesting going on. Here are just a few items that caught my attention in the most recent reports:

• Progress Toward Poliomyelitis Eradication --- Afghanistan and Pakistan, 2009
• Jimsonweed Poisoning Associated with a Homemade Stew --- Maryland, 2008
• Outbreaks of 2009 Pandemic Influenza A (H1N1) Among Long-Term--Care Facility Residents --- Three States, 2009

Safe Patients, Smart Hospitals

This relates to the topic of nosocomial infections from a few weeks back but I thought this interview with Dr. Peter J. Pronovost, medical director of the Quality and Safety Research Group at Johns Hopkins Hospital in Baltimore, in the New York Times on Monday was interesting. Click the link for the full interview, I've just posted some snippets below. Even something as simple as making sure supplies are together and at hand can reduce infections:

At Hopkins, we tested the checklist idea in the surgical intensive care unit. It helped, though you still needed to do more to lower the infection rate. You needed to make sure that supplies — disinfectant, drapery, catheters — were near and handy. We observed that these items were stored in eight different places within the hospital, and that was why, in emergencies, people often skipped steps. So we gathered all the necessary materials and placed them together on an accessible cart. We assigned someone to be in charge of the cart and to always make sure it was stocked.

Q. WHAT CAN CONSUMERS DO TO PROTECT THEMSELVES AGAINST HOSPITAL ERRORS?

A. I’d say that a patient should ask, “What is the hospital’s infection rate?” And if that number is high or the hospital says they don’t know it, you should run. In any case, you should also ask if they use a checklist system.

Once you’re an in-patient, ask: “Do I really need this catheter? Am I getting enough benefit to exceed the risk?” With anyone who touches you, ask, “Did you wash your hands?” It sounds silly. But you have to be your own advocate.

Herd Immunity

A nice study, reported in the New York Times, demonstrating herd immunity in a Hutterite community in Canada.

Toxoplasmosis and the Future of Medicine

Toxoplasmosis killed with gold nanoparticles and lasers
Yes! This is great! This will be a great precursor to eliminating other illnesses, especially eukaryote-based diseases. Hopefully in the future, we will be able to use nanoparticles to destroy bacteria without having to use antibiotics. Then we will probably have won our battle with disease because we will not have to be constantly developing new anitbiotics, and can focus on treating infections where they occur in the body, instead of flooding a person's body with medicine or radiation. Looking good for humanity, I just wish we do not die of something extreme before we develop better technology,
But...I cannot help from being slightly skeptical, because even though we can now eliminate toxoplasmosis cysts from the brain, millions of people (and animals) are infected, and using lasers and nanoparticles can seem like an expensive waste for a non-fatal disease. But if we can develop a way to remove toxoplasmosis permanently, then I am sure it would be adopted more quickly.
My idea: nanobots with built in lasers for hunting down disease causing parasites, bacteria and viruses. For prions? Perhaps have nanobots with some storage capability as to contain the prion within itself, rendering it harmless withing the nanobots walls. If everyone has nanobots that destroy diseases as you are infected, what will happen to the human race?

ps. My favorite part of writing science-fiction is speculating, obviously.

Flu Attack! How A Virus Invades Your Body

This is a pretty nice animation. I did cringe though when he said that 'all viruses want to spread'. In terms of natural selection it is much better to think of selection as favoring those viruses that spread most successfully therefore favoring those that spread most efficiently. They've also made a very clear decision to avoid virtually all terminology and use familiar terms (locks, keys, noodly things, factories, copying machines, little chefs).

Notice all the antibodies swirling around the virus at the very end. It is the fact that these antibodies latch onto the virus (via the same lock and key mechanism) that marks the virus for destruction via the white blood cells (actual white blood cells may not actually make a slurping noise).

The answer to the final question - of why you don't usually drop dead is also rather weak. The fact you have so many cells won't keep you alive for long if a virus multiplied this fast. They actually have a better answer at the NPR website:

In our video we ask, if a flu virus inside your body can multiply by the millions within seconds, why don't we topple over and die quickly?

Here's a better, longer answer than the one in the video. First, some new viruses get caught in mucus and other fluids inside your body and are destroyed. Other viruses get expelled in coughs and sneezes. Second, lots of those new viruses are lemons. They don't work that well. Some don't have the right "keys" to invade healthy cells so they can't spread the infection. And third, as the animation shows, your immune system is busy attacking the viruses whenever and wherever possible.

Blood groups and immunology

Although agglutination is a mechanism by which your body destroys attacking microorganisms, when this happens on a larger scale it can be dangerous. The human blood groups are a good illustration of the way that antibodies and antigens interact and this is well illustrated at the Nobel prize website (Karl Landsteiner's work made it possible to determine blood groups and thus paved the way for blood transfusions to be carried out safely. For this discovery he was awarded the Nobel Prize in Physiology or Medicine in 1930.)

Note that the example of human blood groups also illustrates that you do not generally have antibodies against antigens that are normally present in your body. This makes a lot of sense and this distinction between self and non-self is crucial. We see the importance of it, and the power of our immune system, when it breaks down in so-called auto-immune diseases (originally known by the splendidly gothic name of “horror autotoxicus”).

Beautiful and deadly

Deborah sent me a link to the glass artwork of Luke Jerram - transparent glass sculptures of viruses that push the boundaries of both biological knowledge and glassblowing. His website has lots of examples and a video. Everything but the cost. I'm guessing that if you have to ask, you can't afford them... Not that I need one, I was just curious.

These transparent glass sculptures were created to contemplate the global impact of each disease and to consider how the artificial colouring of scientific imagery affects our understanding of phenomena. Jerram is exploring the tension between the artworks' beauty, what they represent and their impact on humanity.

The question of pseudo-colouring in biomedicine and its use for science communicative purposes, is a vast and complex subject. If some images are coloured for scientific purposes, and others altered simply for aesthetic reasons, how can a viewer tell the difference? How many people believe viruses are brightly coloured? Are there any colour conventions and what kind of ‘presence’ do pseudocoloured images have that ‘naturally’ coloured specimens don’t? See these examples of HIV imagery. How does the choice of different colours affect their reception?

Latent AIDS infections

Researchers at the University of Michigan believe they have pinpointed the reason as to why people infected with HIV eventually develop AIDS if they cease taking medication. Scientists have found that the AIDS virus can hide in bone marrow, avoid drugs during the course of treatment, and become active later. The HIV virus can infect other cells in the bone marrow that live longer than most cells. When infected bone marrow cells are converted to blood cells, the virus reactivates and starts infecting other cells. This discovery is a crucial step toward finding a cure for HIV/AIDS; eliminating the source that is responsible for latent infections would allow HIV patients to stop treatment after the infection is over. Those in rural and poor countries where many are unable to afford medication would greatly benefit from new medications that destroy the cells responsible for latent infections. To read more about latent HIV infections click here.

Smallpox 2002

I've posted this before and I thought it worthy of repeat but I saved it for the weekend because it is a bit of a potential time sink. Smallpox 2002 is a FICTIONAL 'documentary' made in 2001 by the BBC. It was commissioned and largely completed before both the 9/11 attacks and the anthrax attack that followed. The film has been shown in the US as "Smallpox", on FX. Although the program has some flaws, on the whole I thought it was well done. If it gets people to think in advance about what will happen in the next pandemic, whether it is influenza or bioterror, then that's a good thing. What parts of the program did you find unrealistic? Do you think events would have played out differently? Do you think this program is unnecessarily fear-mongering or do you think it is a valuable warning? The tagline for the movie was, "Drama, until it happens". Good one.

The program is rather addictive and lasts 90 minutes so don't start watching if you have other things to do!

For those whose history is shaky, let me repeat, this is fiction. There wasn't a smallpox epidemic in 2002 that killed 60 million people! For reference though, the 1918 influenza pandemic killed somewhere between 20 and 100 million people worldwide.

The embedded video above is just part 1 of 9. Here's a link to the complete Playlist.

Smallpox questions

Parchment signed at Geneva on 9 December 1979, by the members of the Global Commission for Certification of Smallpox Eradication.

A couple of interesting questions during and after class that I had to look up the answers to but thought would be of enough general interest to post here.

1) Where did smallpox come from?

Human disease likely attributable to variola virus (VARV), the etiologic agent of smallpox, has been reported in human populations for >2,000 years. VARV is unique among orthopoxviruses in that it is an exclusively human pathogen....Our results show two primary VARV clades, which likely diverged from an ancestral African rodent-borne variola-like virus either ≈16,000 or ≈68,000 years before present (YBP), depending on which historical records (East Asian or African) are used to calibrate the molecular clock.
From: On the origin of smallpox: Correlating variola phylogenics with historical smallpox records
But see also: How long ago did smallpox virus emerge?

2) When was smallpox officially declared eradicated?

Both the WHO and CDC have information on their respective websites. Here is an account from the CDC website of the final years of the eradication project and the final certification of eradication which occurred two years later.

By the end of 1975, smallpox persisted only in the Horn of Africa.

Conditions were very difficult in Ethiopia and Somalia, where there were few roads. Civil war, famine, and refugees made the task even more difficult. With the interruption of smallpox transmission in Asia, more resources were made available in Africa, including more staff and transport.

An even more intensive surveillance and containment and vaccination program was initiated in the spring and summer of 1977. As a result, the world’s last indigenous patient with smallpox on earth was a hospital cook in Merka, Somalia, on October 26, 1977 with variola minor.

Searches for additional cases continued in Africa for more than 2 years, during which time thousands of rash illnesses were investigated. None proved to be smallpox.

Although 2 cases of smallpox occurred in England in 1978 as a result of a laboratory accident, smallpox was gone as a naturally transmitted disease.

The World Health Organization officially certified that smallpox had been eradicated on December 9, 1979, 2 years after the last case in Somalia. In 1980 the World Health Assembly recommended that all countries cease routine vaccination.

Private Snafu vs. Malaria Mike

A US-army sponsored instructional film aimed at military personnel.Produced by the US Army Signal Corps and distributed by Warner Bros Pictures. Although none of the key production personnel are credited onscreen there are some famous characters associated with this short film. If Snafu sounds like Bugs Bunny that's because he IS Bugs Bunny, well, Bug Bunny's voice - Mel Blanc (check out the sound he makes when he tosses the repellent away). Also, the supervising producer was Theodore Geisel - better known as Dr Seuss.

I'm not going to mention the frequent depiction of naked buttocks in this army sponsored film....

Panama Canal and Malaria

As Professor Latto explained in class, the Panama Isthmus was the ideal breeding habitat for malaria carrying mosquitoes: no dramatic seasonal changes, the rainy season last ¾ of the year, and most of the area was rural jungle. 1/6 of the 80,000 people that lived in the region before the canal was built were infected with malaria. When it was decided that the canal would be constructed, the US army intervened to prevent workers from becoming infected with malaria by following seven crucial rules:

1. Drainage: all standing water within 100 yards of the construction site was drained

2. Brush and grass cutting: all grasses were kept at a height of less than 1 foot

3. Oiling: when drainage was not possible, oil was added to kill mosquito larvae

4. Larviciding: when oiling was not sufficient, they used larviciding

5. Prophylactic quinine: provided without charge to all workers and ½ of the workers took a dose each day

6. Screening: all government building were to be screened against mosquitoes

7. Adult killing: mosquitoes generally stay within the same room after they are done feeding and workers collected them

By following these seven rules, yellow fever was eradicated and cases of malaria dramatically declined in the Panama Isthmus. Click here to read more about eradicating malaria in the Panama Isthmus

Malaria Action Plan

"I believe that if you show people a problem, and then you show them the solution, they will be moved to act. The Global Malaria Action Plan lays out an achievable blueprint for fighting malaria – now it's time for the world to take action." Bill Gates, Co-Chair, Bill & Melinda Gates Foundation

The Roll Back Malaria (RB M) Partnership has developed the Global Malaria Action Plan (GMAP) to provide a global framework for action around which partners can coordinate their efforts. It consolidates the collective input of 30 endemic countries and regions, 65 international institutions and 250 experts from a wide range of fields.

The GMAP outlines the RBM Partnership’s vision for a substantial and sustained reduction in the burden of malaria in the near and mid-term, and the eventual global eradication of malaria in the long term, when new tools make eradication possible.

You can further information at the RBM website including a lot of information on the Global Malaria action Plan and some interesting videos.

Gram-negative infections

Deborah sent me this link to a New York Times article from last week Rising Threat of Infections Unfazed by Antibiotics .

The article describes the problems caused by the rising prevalence of some gram-negative infections like Acinetobacter.

Doctors treating resistant strains of Gram-negative bacteria are often forced to rely on two similar antibiotics developed in the 1940s — colistin and polymyxin B. These drugs were largely abandoned decades ago because they can cause kidney and nerve damage, but because they have not been used much, bacteria have not had much chance to evolve resistance to them yet.

“You don’t really have much choice,” said Dr. Azza Elemam, an infectious-disease specialist in Louisville, Ky. “If a person has a life-threatening infection, you have to take a risk of causing damage to the kidney.”

Zinduka! and Prevent Malaria

Malaria affects many areas around the world, but currently the disease has especially devastated Africa. In order to combat malaria in Africa, African countries have worked together to educate their citizens about malaria prevention. The main goal of many of anti-malaria organizations has been to guarantee universal access to insecticide-treated mosquito “bed nets.” These efforts have been met with some success, but the African country that has been making headlines lately for its anti-malaria campaign is Tanzania.

Tanzania has planned an aggressive campaign to provide access to mosquito nets and malaria care for its people. To spread the word and help garner support for the cause, Tanzania’s most popular musicians and artists have banned together as ambassadors for the cause and put out a pop song “Zinduka!” meaning “wake up!” to be performed at a large concert to benefit the cause. Tanzania’s president Kikiwete has signed on to head the “Malaria Haikubaliki: Tushirikiane Kuitokomeza” awareness campaign, which translates to “Malaria is unacceptable: working together we can eliminate malaria.” To begin the 2010 campaign, President Kikiwete hosted the nationally broadcast Zinkduka! Concert on February 13^th with the aim of reaching millions of Tanzanians via radio or television and thereby informing them about their personal responsibility in preventing the spread of malaria. Clearly, it’s a bit too early to determine the effects of this campaign against malaria, but Tanzania has taken serious initiative in malaria control and prevention in recent years. I thought this article was informative and best of all, inspiring. Here’s the link if you would like to read more:http://www.malarianomore.org/index.php?cID=659

Also, go to the Malaria No More website if you would like to view news on all things malaria around the world.

A Bug's Death

A bacterial strain of Wolbachia has been adapted to infect the mosquito vector that transmits dengue virus to humans. The bacterial infections (red) are only transmitted through females to offspring, and cut mosquito life span by up to 50%. This may block disease transmission to humans.

One way to shorten mosquito lifespans is to infect them with the bacterium, Wolbachia. In the laboratory, infection with this bacterium halved the lifespan of the insects, potentially reducing the spread of diseases like Dengue fever and Malaria that must incubate in the mosquitoes for two weeks or so.

This is relatively recent work and was reported in the journal Science at the start of last year: Stable Introduction of a Life-Shortening Wolbachia Infection into the Mosquito Aedes aegypti. There is also an editorial summary: Mosquitoes cut short.

For a different approach, and some interesting ethical questions, consider Olivia Judson's article
A Bug's Death in the New York Times.