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PUBH 3100 Human Disease and Prevention

Week 6 – Emerging Diseases: Prions and Viruses

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NARRATOR: It had been another hot, long, miserable day. Just when you think you're ahead of the curve, you find out you're way behind the eight-ball. I've been hitting the pavement all day; all day yesterday, and all day the day before.

I had four cases on the run, each one as confusing as the last: the CJD case, the zoonose case, the avian flu case and the SARS case. We're in the business of emerging diseases, and it's a back alley fistfight we can't win.

It had all started a heck of a long time ago. Millions of years of human evolution led to the development of natural defenses against disease. Our immune system is constantly facing new challenges as organisms mutate to get the upper hand. Just when we think we've got them licked, they change their ways and we're back to square one. Some of these diseases are very old. Over time they have evolved into new and more dangerous forms, and some are completely new to science. I started questioning the usual suspects.

DR. JENNIFER MCKIMM-BRESCHKIN: An emerging disease is a disease that has increased in incidence over about the last 20 years. Now these diseases can arise either from a completely new organism. They can arise from an organism that's now spreading into a new ecological area. So for example, with clearing of the rainforests in the Amazon, you're driving animals and insects out of the forests into urban areas, so you're now seeing new diseases in some of these urban areas. It can be through evolution of an existing disease that used not to be a very nasty disease, but is now emerging to become quite severe. It can be due to reemergence of a disease that was under control, but now may have drug resistance. So things like that are TB, where it was well under control, but we are now seeing drug resistant types of TB.

NARRATOR: CJD, zoonose, avian flu and SARS; emerging diseases at their worst. I'm tired. I'm beat. But I have to get onto these cases as fast as a bookie collecting a debt. A sudden outbreak of any one of these diseases will lead to a severe and devastating effect. An outbreak can lead to an epidemic, and an epidemic can lead to a pandemic. If that happens, the results would be catastrophic.

An emerging disease is one that appears in a number of cases for the first time. It may have existed previously, but signs show its rapid increase. Although human evolution has led to the development of a natural defense against disease, many pathogens are

able to co-evolve ways around these defenses. The disease organisms are constantly evolving alongside our defenses. Though some diseases are very old, over time they can evolve into new and more dangerous forms. An outbreak can lead to an epidemic.

The first case, CJD, Creutzfeldt-Jakob disease; CJD is a rare and incurable brain disease that is fatal in virtually all its victims. It is believed to be caused by prions, short for proteinaceous infectious particles, an infectious agent that infects mammals, including humans.

DR. JENNIFER MCKIMM-BRESCHKIN: A prion disease is a disease that appears to be caused by a protein only. A lot of the diseases we are familiar with that are caused by viruses are viruses that are made up of genetic material of a gene and a protein, which covers that gene, whereas prions appear to only be the protein.

NARRATOR: It promotes the refolding of normal cellular proteins, destroying their original function. This causes cell disruption, particularly in nerve cells of the brain, leading to severe dementia and inevitably death. There are many symptoms of CJD, the first being a rapidly advanced state of dementia. This is categorized by memory loss, personality changes and hallucinations.

DR. JENNIFER MCKIMM-BRESCHKIN: It could also affect you physically. So you get seizures, what they call myoclonic jerks, where you get sort of jerking of the muscle. So there is sort of the diagnostic features, and it is all because of accumulation of these mutant protein in the brain.

NARRATOR: The majority of people affected by CJD are between the ages of 55 and 65, although there have been cases reported of people outside this age group. Although the duration of the disease can vary, in 80% of cases it is fatal within 12 months of being diagnosed. The symptoms can continue for years. These symptoms are caused by the progressive deterioration of the brain's nerve cells, which is associated with the buildup of abnormal prion proteins. When brain tissue from a CJD patient is examined under a microscope, many tiny holes can be seen where nerve tissue once appeared.

DR. JENNIFER MCKIMM-BRESCHKIN: And this is called spongiform appearance. And these groups are called the spongiform encephalopathies, because they make the brain turn to sponge.

NARRATOR: Transmission of CJD can be byproducts containing human growth hormone, corneal grafts, dual grafts or electrode implants. CJD can also be inherited, although it frequently appears in patients who have no family history of it.

DR. JENNIFER MCKIMM-BRESCHKIN: Now it's still extremely rare. You're looking at one in a million people. But this part of the population are the ones that generally are associated with the inherited CJD.

NARRATOR: It has been speculated that humans can contract the disease by consuming the meat of beef cattle infected from the bovine form, mad cow disease.

DR. JENNIFER MCKIMM-BRESCHKIN: And that's what has been seen in the UK primarily, about the last 5 to 10 years, where they had animals that actually had BSE. And people were exposed to the BSE from those infected animals. And they had a disease that's called variant CJD, as opposed to the normal CJD.

NARRATOR: Although no firm evidence exists to confirm this, is still a fear amongst the general public.

DR. JENNIFER MCKIMM-BRESCHKIN: The main means of controlling is preventing infection. So for the variant CJD, they've actually had to slaughter millions of cattle that were infected to try and prevent that being spread any further.

The human and animal prions are essentially the same, so that what they call the PRP protein is essentially the same in humans and animals. But there seems to be this variant of the PRP that actually causes the disease, and that can be found in either humans or animals. But they cause different diseases, so in animals you might see scrapie or BSE. In humans, you might see the Creutzfeldt-Jakob or perhaps Kuru.

NARRATOR: Through the once prevalent custom of cannibalism, the Fore tribe in Papua New Guinea were found to contract a form of the disease known as Kuru. Interestingly, although men were also involved in these rituals, only women and children of the tribe were found to have the disease.

The diagnosis of CJD is suspected when the typical signs of dementia and muscle deterioration are present. Further investigation to support the diagnosis is made when one or more of the following tests is confirmed positive. Electroencephalography: the measurement of the electrical activity produced by the brain. Cerebrospinal fluid analysis: when the clear bodily fluid that occupies a subarachnoid space in the ventricular system around and inside the brain is tested for particular protein markers that become increased in CJD. And a MRI: Magnetic Resonance Imaging of the brain, which detects alterations in brain activity. Biopsy of brain tissue from the patient may also be examined histologically in some situations.

DR. JENNIFER MCKIMM-BRESCHKIN: There's currently no treatment for CJD. They've tried a number of other broad-spectrum anti-virals, such as ribavirin, but they've had no effect. So, generally the outcome is fatal.

NARRATOR: In 2003, an experimental treatment was given to a teenager in Ireland using the medication pentosan polysulfide. While it failed to stop the progression of the disease, it allegedly slowed the symptoms. CJD is fatal, and a search for a viable treatment continues as well as further investigation of the causative agent.

NARRATOR: CJD is a rare and incurable brain disease that is fatal. The main symptoms are dementia and coordination dysfunction. To diagnose CJD, electroencephalography, cerebrospinal fluid sampling, and MRIs are employed. Currently, there is no cure for CJD.

NARRATOR: Case number two, zoonotic disease. This case has been on my desk for a long, long time. Some cases come, get solved, and then go. But this one, I just can't seem to get rid of it.

NARRATOR: Zoonosis are infectious diseases that can be transmitted from animal to humans.

DR. JENNIFER MCKIMM-BRESCHKIN: Normally diseases are limited to one species. They may only be limited to animals or limited to humans. But a zoonosis is one when it can spread from animals to humans.

NARRATOR: Many serious diseases fall under this category, like Anthrax, Bubonic Plague, Ebola fever and Rift Valley fever. And the carriers for these types of diseases are endless. Any animal you can think of could potentially be a carrier of Zoonotic disease.

Rift Valley fever is a common form of Zoonosis that is caused by a virus. The mosquito is the main carrier of the disease.

DR. JENNIFER MCKIMM-BRESCHKIN: And the mosquitoes bite the infected carcasses or infected animals and then can transmit it to humans. Interestingly, the mosquitoes actually pass it on to their own eggs. And those eggs can maintain that virus over several years. So if there's a dry season for several years, they can still be infectious. So, when water comes and the mosquitoes start hatching, they can still be infected with that virus.

NARRATOR: Rift Valley fever was first identified in 1931 during an outbreak in Kenya. With the first known instance of the disease starting in the Rift Valley, the disease was soon tracked to other parts of Africa and even as far as Europe. It didn't take long for the Rift Valley fever to cross the species boundary and begin infecting humans, usually in the form of mosquito bites.

DR. JENNIFER MCKIMM-BRESCHKIN: The other source of infection for humans is handling of infected carcasses. So they can either get it through aerosol infection from handling a dead carcass, or from actually a cut, in which you might get contaminated liquids, contaminated blood. Or Rift Valley fever causes abortion, so if you're handling an aborted fetus, there's going to be a lot of blood and liquid, and you may get infected from that liquid.

NARRATOR: There have been no reports of human-to-human transmission of the disease to date. People at high risk include those who work with animals and anyone who enters the area of an outbreak where they may have been exposed to animal products or biting insect vectors.

Generally, the symptoms of RVF are mild in comparison to CJD. Patients of RVF will experience symptoms similar to a flu-like illness with fever, weakness, back pain, dizziness and weight loss occurring. In the more serious cases, other complications may arise. These can include inflammation of the brain and infection of the retina, causing varying degrees of permanent blindness.

There's not a lot that can be done in terms of treatment for an infected patient. In less serious cases, the patient is given supportive therapeutic treatment to assist them in recovering naturally. There are vaccines for animals and insecticide spray for waterways available, which are extremely helpful. But with mosquitoes being the main carrier of the disease, it is extremely difficult, if not impossible, to vaccinate every animal in the infectious areas.

DR. JENNIFER MCKIMM-BRESCHKIN: In terms of humans, there are some experimental human vaccines. But at this stage, there is nothing really approved for humans. So, probably the best means of controlling is actually controlling the vectors. So you need to control the mosquitoes, and that has to be done by trying to eradicate areas of water where the mosquitoes are breeding.

NARRATOR: Vaccines for humans have been developed but are pretty much only used by veterinarians and people who are classed as high risk.

NARRATOR: No readily available vaccine, no way to stop the spread; at least this one isn't killing people.

NARRATOR: A zoonotic disease is one that is transmitted from animals to humans. The symptoms are usually flu-like illnesses with a fever and muscle pain. There are vaccinations for animals, but for humans they are mostly used for those at high risk, such as veterinarians.

NARRATOR: The third case I have sitting on my desk, Avian Influenza, AKA "Bird Flu." Every year this seasonal disease comes around. While this disease kills thousands of birds each year, it's human relative, influenza, kills 250 to 300,000 people each and every year.

NARRATOR: As time goes by and nature evolves, new and deadlier strains of Avian Flu emerge. Concerns have been raised that if a variant Avian Flu crosses the species barrier, it may pose a serious threat to humans. There are two main forms of Avian Flu, a high virulence and a low virulence form.

DR. JENNIFER MCKIMM-BRESCHKIN: So what is happening with Avian Flu is that it has been around for many, many years in aquatic birds. They're a normal carrier of influenza A. But it hasn't actually killed the birds.

Recently, there's been changes in some of these strains that have suddenly made the virus start killing these aquatic birds. With intensive farming of chickens and turkeys, some of these aquatic birds are now spreading this newer form of the disease into the domestic poultry.

NARRATOR: The high virulent form, although rare, is extremely fatal. Generally, it kills up to 100% of infected poultry within 48 hours of contamination. This form has also been responsible for a small number of human deaths. It only takes one or two changes in the virus for it to mutate from a low virulent strain into a high virulent strain. Outbreaks of the low virulence form must therefore be taken very seriously.

The transmission of Avian Flu from birds to humans is generally through direct contact with infected poultry or surfaces and objects contaminated by their feces.

DR. JENNIFER MCKIMM-BRESCHKIN: So the way to sort of control that is to try to educate people about how it's spread and not to come in close contact with dead animals. And people need to eat these dead animals, because many of them, it's their only source of food. So this is a big problem, if that's your only source of food. You're not going to throw away this animal because it has died. You will try and cook it and have a meal. So it's generally in the preparation that you can get infected.

The original highly pathogenic "Bird Flu" was first seen through China and in through Southeast Asia. It's now spread to parts of Africa, and it's also been seen in parts of Europe. So it is becoming a global disease.

NARRATOR: The first symptoms of Avian Flu in humans include sore throat, fever, muscle pains, severe headaches, coughing, weakness and general discomfort.

DR. JENNIFER MCKIMM-BRESCHKIN: And ultimately what we see is about a 60 to 70% mortality rate of people currently infected with "Bird Flu." So, it's a very severe disease.

MALE SPEAKER: Although these symptoms are sometimes confused with the common cold, this influenza is a severe disease with much harsher consequences.

DR. JENNIFER MCKIMM-BRESCHKIN: And the particular strain we're talking about at the moment is an H5N1. What does the H mean, what does the N mean? These are two little spikes that are on the surface of a flu virus, and that's how we name every type of flu virus. There is 16 different types of H and 9 different types of N. So we have an H of one type and an N of another type. So what we're currently seeing in the "Bird Flu," as everyone is calling it, is the H5 type, and the N1 type. So we call it H5N1.

NARRATOR: Since 2003, the highly virulent H5N1 strain of the virus has infected small numbers of humans throughout the world. The highest number of deaths occurred from outbreaks in Indonesia, Vietnam and Egypt.

DR. JENNIFER MCKIMM-BRESCHKIN: The major concern now is that this H5N1, or perhaps one or the other avian viruses, might now adapt to infect humans more readily. And then you start to see human-human spread of this new type of virus. Because humans haven't been exposed to it before, this virus will now be able to spread rapidly through the population, causing probably a high rate of death or certainly a high rate of very ill people.

NARRATOR: However, disease control centers around the world are making Avian Flu the top priority.

DR. JENNIFER MCKIMM-BRESCHKIN: But the problem is at this stage we don't really know which strain of "Bird Flu" it may be that's going to cause the pandemic. So vaccine manufacturers are making what they call a pre-pandemic vaccine. So this is a vaccine that's based on the current strains of "Bird Flu" that are circulating, so the H5N1. And they're getting those ready and testing those on people to make sure that they do actually make us make antibodies that could protect us.

NARRATOR: Experience with the common seasonal flu has shown that it is possible to be vaccinated and still get the disease. It is therefore likely that vaccines for H5N1 will also be less than a 100% effective.

NARRATOR: The biggest problem we have with this one is that it's a suspect that is constantly changing. The moment we think we have it cornered, it changes into something else and we have to start all over again.

NARRATOR: Avian Influenza is commonly known as the "Bird Flu." Although it affects mainly birds, it can also infect humans. There are a number of different strains that are constantly changing. It has many symptoms including fever, sore muscles and throat and general weakness.

NARRATOR: SARS: severe, acute respiratory syndrome. It's a respiratory disease.

DR. JENNIFER MCKIMM-BRESCHKIN: It's caused by a virus, which is a member of the virus family called coronaviruses. Now we actually have all been infected with coronaviruses before because they're common viruses of humans and animals. And they cause common respiratory and enteric diseases. So there is a human cold-like virus that is a coronavirus. So as coronaviruses are such, and not an unknown sort of virus. But the SARS coronavirus was a new type of coronavirus.

NARRATOR: There's been one near-pandemic case to date: China, 2002. Eight thousand and ninety-six infected cases and 774 deaths. That's a mortality rate of 9.6%.

NARRATOR: SARS impedes the flow of air into the lungs and reduces the capacity of air that the lungs can hold. SARS is another example of a viral zoonose. Its natural host is the masked palm civet, a relative of the mongoose. It is believed to be contracted to humans through contact with blood or animal tissue during the butchering and ingesting of the animal, which is a delicacy in China. Once within the human host it was able to spread more rapidly.

DR. JENNIFER MCKIMM-BRESCHKIN: Subsequently, they've also found SARS coronavirus in bats. So they're really not quite sure whether the civet cats have spread it to humans through bats, or whether they have spread it directly. So the real spread of infection is really not very clear at this case because it mostly seems to have died out.

NARRATOR: The transmission of SARS became a huge problem. It could be caught very easily, such as by touching a door handle or breathing infected air molecules. The disease has an incubation period of up to 10 days. This means that the infected patient who doesn't know they're infected can travel to other parts of the globe spreading the disease.

DR. JENNIFER MCKIMM-BRESCHKIN: SARS infection generally looks like a flu-like infection. So people get fever, muscle aches, maybe sore throat, cough. So it's probably very difficult to distinguish originally from flu.

NARRATOR: Symptoms usually appear between 2 and 10 days, but up to 13 days have been reported. In most cases, 10 to 20% of patients require mechanical ventilation to help them breathe. There are three different tests used to diagnose SARS, each one having their drawbacks.

The first is an enzyme-linked immunosorbent assay test, or a ELISA. This test detects antibodies that might have been produced in a patient to fight off SARS. Unfortunately, this test can only be used after 21 days following the onset of symptoms.

The second is an immunofluorescence assay that detects antigens or proteins that make up the SARS virus itself. It is time consuming and requires an experienced operator.

The third test used to diagnose SARS is a polymerase chain reaction, or PCR. This test can detect genetic material of the virus in specimens such as blood and tissue samples. The PCR tests have been proven not to be reliable.

Patients suspected of SARS should be isolated, preferably in a negative pressure room with a barrier in place that protects the nurses and staff treating the patients. This prevents infected air from reaching people.

To treat SARS, general antibiotics are ineffective. What has worked so far are antipyretics, which are fever reducers, supplemented by oxygen and ventilation support systems. A major issue with SARS is the body's own immune system overreacting to the virus. Steroids are sometimes used, which modulate the immune system and help prevent the body going into hyper-drive and damaging itself.

DR. JENNIFER MCKIMM-BRESCHKIN: China has now made some experimental vaccines, which I understand have been tested in healthy people, just to make sure that the people make antibodies. But because there's not been SARS around, they haven't actually used these vaccines as a means of protecting people against infection.

NARRATOR: Luckily for us, there haven't been any reported cases since 2004. But there is something about this one. I can tell we haven't seen the end of it yet.

MALE SPEAKER: SARS stands for severe acute respiratory syndrome, and is a respiratory disease. The symptoms of SARS include fever, lethargy and shortness of breath. Currently, there are no vaccinations available.

NARRATOR: These four cases, CJD, Rift Valley fever, avian flu and SARS are only a handful. There's so many more out there.

DR. JENNIFER MCKIMM-BRESCHKIN: We are seeing new diseases emerging all the time. There's been recent viruses, which have emerged through other parts of Asia, through Northern parts of Australia called Nipah and Hendra. So these were not known 20 years ago. We're seeing spread of viruses that were limited to animals in the jungles. So I think we are going to continue to see new diseases emerging, which are going to provide a challenge because to treat virus infections, we have no generic antibiotics like we do for bacteria. And we need to understand every individual virus in order to be able to make a treatment or a vaccine for that virus.

NARRATOR: I've been working on these cases all my life. I'm not the only one. There are many of us out there, searching for clues, looking for answers. And who knows? Maybe one day we'll solve a case or two. Fingers crossed.