Welcome Math and Biology Folks to the 2008 BioMath Connect (BMC) Pre-Program on Epidemiology!

What is epidemiology anyway?

Epidemiology is a branch of medicine that deals with the study of the causes, distribution and control of disease. In particular, at BMC we are interested in infectious diseases.

What is an infectious disease?

An infectious disease is any disease caused by microbes such as viruses or bacteria. An example would be influenza (the flu).

Below is a table of various bacterial and viral conditions along with the associated microbe. Don't worry about memorizing any of the condtions or microbes, this is just to give you an idea of some bacterial vs. viral conditions. Most viral conditions are caused by a virus named from the condition (ie. measles virus, mumps virus etc...)

Are viruses and bacteria the same thing?

No, bacteria and viruses are two different organisms. A bacteria is a single-celled living organism. It has the things living things have (cell wall, cell membrane, genetic material) and does the things that living things do - eats, drinks, makes stuff and reproduces - all on its own. A virus, on the other hand, is not constructed like other living things and can not reproduce on its own. A virus is made of genetic material (DNA or RNA) surrounded by a protein coat (rather than a cell membrane or cell wall) and requires a host to live in and reproduce.

bacterial image courtesy of http://peer.tamu.edu	types of viruses

Does that really matter?

Yep, it kinda does. Since epidemiology is the study of diseases, and we are interested in ways to control those diseases, it is important to understand what these microbes are made of and how they behave. Since bacteria are living entities that actually need food and undergo metabolic processes, we can use that knowledge to our advantage when we want to destroy them. Antibiotics are designed to attack bacteria either structurally or by attacking particular metabolic processes that happen in bacterial cells that do not happen in our human cells. For example, some antibiotics block the production of a specific protein in bacteria so they can not grow. Others attack the bacterial cell wall which destroys the bacteria (human cells have a cell membrane but do not have a cell wall).

So have we solved our bacterial problems?

Not quite. Like all other creatures, bacteria evolve. And in doing so they have evolved resistance to various antibiotics. And since we only know of a limited number of ways to attack the bacteria without harming its host (ie. humans) we are running out of new antibiotics and starting to become seriously concerned about antibiotic resistant strains. If you want to truly see nature's sense of humor (and be a little scared), read this news item.

Are viruses this big of a problem?

Yes - even moreso in some ways. Since viruses don't do much but replicate it is hard to find ways to attack them without damaging the host. For example, antibiotics are useless against viruses. The major weapon we have is our own immune system - which does a phenomenal job at protecting us.

How does our immune system protect us?

When we are first infected with a particular virus our immune system goes on alert and builds an army (antibodies - see picture to the right) to combat the viral invaders. Unfortunately, building that army takes some time and so the first time you are infected the virus may do serious damage before it is defeated. However, if you are ever infected again then your army is ready to go and quickly wins the battle. This is why it is very unlikely to 'get' the measles or mumps more than once in your lifetime. It would be nice though to avoid the potentially serious damage or death that the initial infection may cause. To try and overcome this, scientists developed vaccines.

How does a vaccine work?

Vaccines are basically weakened forms of the actual virus that are injected into your blood stream. The viruses are weakened so that they do not cause you to become sick but still give your immune system a chance to recognize the virus and build an army against it. Then, if you ever encounter that virus later 'in the wild' your immune system will be ready. Unfortunately, sometimes things don't go as planned and the vaccine actually gives the person the disease it was trying to prevent - but that is quite rare. This happened with the live polio vaccine but doctors have now switched over to a dead version. Vaccines also don't seem to confer the lifelong immunity that actually getting the disease does. This is why they keep adding more and more 'booster' shots for various diseases.

So have we solved our virus problems?

Not quite. It turns out that viruses evolve quite rapidly too. These mutations counteract vaccinations and your own immune system. This is why there is a new flu shot every year and why we can repeatedly 'catch' a cold. It is really a newly evolved form of the virus. The other problem is that a virus can remain dormant or latent. HIV is a great example of this - one can harbor the virus for years before it becomes active. In doing so people do not even know they are infected and yet may be actively spreading the virus.

Let's demonstrate with a timely topic...

The Avian Influenza Virus (Bird Flu)

Viruses tend to infect a particular type of host and, conversely, different organisms tend to have their own set of viruses. There are viruses that only infect pigs and others that only infect horses and others that only infect primates etc... In this case we are dealing with a virus that infects and kills birds. The particular virus in this case of bird flu is named H5N1, which is a classification given to it based on two different proteins (H and N) on its outer coat. (The H1N1 virus caused the Spanish Flu in 1918 killing over 50 million people)

image courtesy of the University of Delaware

With 16 'H' proteins and 9 'N' proteins, the virus can obviously present itself in many forms - you can do the math :-) This is one of the problems the immune system has in recognizing a virus like the flu from year to year.

Why are we worried about a virus that infects birds?

Once again we run into that pesky little problem of evolution. As the virus mutates it may gain the ability to infect cells in a different host - ie. humans. The virus also needs to mutate to find a way to spread from human to human - ie. through sneezing or contact. Thus far there have been human cases of bird flu but mostly in people with very close contact with infected birds. The virus does not spread easily from human to human. In fact, there have only been a few cases and only with prolonged close contact.

Colorized transmission electron micrograph of Avian influenza A H5N1 viruses (seen in gold) grown in MDCK cells (seen in green).

How does a virus mutate and infect us?

You may recall from your own biology class that DNA codes for proteins (for more background on DNA and cells click here). Changes in the DNA sequence will change the proteins on the surface of the virus. If the correct changes occur, the virus can match up to proteins on our cells and trick our cells into letting the viral RNA or DNA inside. Then the virus uses our own cells to grow more copies of itself - quite clever really. An animation of the HIV virus infecting a cell can be seen here. You will notice that the HIV virus will only enter a cell if it finds a particular protein (CD-4) to bind to. This is why HIV infects the T-cells of your immune system and not other cells in your body; T-cells have the CD-4 protein on their surface. The same concept holds true for H5N1 - it needs to match up to a receptor on the cell - if an organism does not have that receptor then the virus can not infect it. Unless, of course, the virus mutates to match a receptor the new host already has. And this is exactly what concerns us.

So why don't we just vaccinate everyone and stop worrying about it?

Three reasons....

1. We don't have a vaccine. Vaccines are difficult to make because you have to create a very specific serum with enough of the virus to create an immune response but not too much that will make you sick. And if your vaccine doesn't exactly match it will create the wrong immune response and offer little to no protection. Here is a recent news item regarding this year's flu shots. Finally, the vaccine carries some health risks.

2. Even if a vaccine is created there won't be enough of it to go around!

3. In cases of bioterrorism we won't know ahead of time what disease to be looking for.

How can we predict if a disease will be an epidemic?
What do we do to stop the spread once it does infect humans?
Who do we vaccinate if we don't have enough for everyone?
How do we track who is spreading the disease?
How accurate are the tests that detect a disease in a person?

These are exactly the types of questions that biologists need mathematicians to help answer. And these are the kinds of questions we will be dealing with in our summer workshop.

We look forward to seeing you in July!

* images courtesy of Wikimedia Commons unless otherwise noted