SARS

Severe Acute Respiratory Distress Syndrome

The typical story is a patient who presents to the emergency department with fever, a cough, three to four days of malaise and mild shortness-of-breath (SOB). The patient may complain of mild pleuritic chest pain without nasal congestion and pharyngitis. Fever can be as high as 102.5 degrees F with temperatures to 101.4 degrees F. Conversational dyspnea might be obvious. Oxygen saturations can be impaired as evidenced by pulse oximetry. Chest X-rays usually demonstrate bilateral patchy air-space opacities.

Transmission of SARS is primarily through contact and large droplet (more than 5 microns and, therefore, likely to fall within 3 feet) spread of secretions. Contact with body fluids including respiratory secretions, vomitus, and stool may result in transmission of the virus. Transmission of SARS occurred most frequently in household contacts or at the hospital with infrequent occurrences of community spread. Routes of transmission for SARS include close contact (fomites, droplet, or direct contact), airborne spread (airplane, Amoy Gardens - a housing complex where a plume of SARS-contaminated virus arose from blocked sewage and was carried on air currents, and the fecal-oral route).

The incubation period the virus is from two to ten days, with most viral shedding (transmission) occurring at the tenth day after exposure.

Severity of illness may impact viral load and opportunity for transmission. Airborne (fine particulate aerosol spread of droplets smaller than 5 microns that may remain suspended in the air) transmission has occurred most commonly in the hospital setting in association with aerosol-generating procedures such as administration of nebulizer treatments and endotracheal intubation. Some have suggested the terminology of "opportunistic airborne infections" for those infections that usually cause disease outside the lung (eg, in the gastrointestinal tract), but may result in infection in distal airways if a fine-particle aerosol is generated by nebulizers or intubation. Because of the demonstrated airborne transmission of SARS and the risk of aerosol-generating procedures to healthcare workers (HCW), patients suspected of having SARS should be placed on airborne, in addition to, contact precautions.

Most patients with SARS did not transmit the virus to anyone else. However, a few patients spread the virus to more than 10 people, each. These patients were termed "super-spreaders." The explanation of the superspreading phenomenon is unclear. Most instances of superspreading occurred within the hospital through an unrecognized case or an aerosol-generating procedure. However, in some instances, only limited contact with patients was made. Further study is needed to determine whether superspreading events represent increased viral shedding in patients with advanced disease and comorbidities, lenient or late infection control, or alternative transmission routes.

No specific therapy against SARS-CoV is available at this time, though many therapeutic agents have been tried including: ribavirin and corticosteroids, lopinavir/ritonavir in patients, and interferon and monoclonal antibodies in in-vitro studies and an animal model. These regimens have not been tested in large randomized controlled trials and some medications have the potential for serious side effects.

It can be a multisystem infection, with viral gastritis, myocarditis and evidence of other systemic viral infection.

Infected usually improve after two weeks with supportive therapy. Mortality rates in the ten to twenty percentile range have been reported.

The Technical Aspects

"Bird flu" is kind of a misnomer, for, technically, all the "flu's" in this virus category technically have some connection with birds, and birds of different species, both wild, domestic, and kitchen table prepared. There are three major types of viruses, A, B, and C.

Types

The A viruses have as their source of activity, both the human, animal kingdom and the avian populations. There are many subtypes of these A viruses, some that only infect the varoius avian species, and some that have crossed over to also infect the human population. A viruses have been responsible for some serious epidemics and pandemics in the past, including the Hong Kong flu of 1968 and the Asian flu of 1957. The huge 1918 Spanish flu, which killed hundreds of thousands across the globe, was also an A virus.

B viruse typically only infect humans; they are viruses which the human species have more experience with, and therefore, more immunity (as opposed to the A viruses, which humans might have had no previous exposure to, thus no immunity or ability to fight the virus, which leads to the virus' ability to wreak massive devastation). B viruses are involved with our typical flu sypmtoms.

C viruses can cause mild illnesses in humans, and generally, are not too significant.

Viruses are subtyped according to the type of two proteins that are found on their outer shell; the hemagglutinin and neuraminadase proteins, which are denoted respectivefully as HA and NA, or, as H and N. There are 15 different types of H proteins, and 9 different types of N proteins, that are found. Different viruses have different combinations of these two H and N proteins; also, not all combinations (currently) have infectious potential.

A virus is just a strand of genetic material that is covered in a protein sheath. The protein sheath has an H and an N protein, which the body uses to identify it. If the body has been infected with a virus before, it recognizes the H and N proteins, and generates its immune response to attack and destroy these viruses before they can infect cells and do damage. If the body does not recognize the H and N proteins, then the virus can enter the animal's cells, take over the cells manufacturing processes, cause the cell to generate new virus material, all of which causes the cell to eventually die, occasionaly, by the process of swelling and rupturing. The combination of the H and N protein is referred to as the antigen. If the human has been exposed to this antigen before, it recognizes it, and eventually, fights it. If the human has not been exposed to this antigen before, it has to recognize it as "evil", and generate an immune response to it, manufacturing antibodies that can seek out and destroy the viral invader. A virus such as the HIV virus that causes AIDS is a tough one, because the virus hides within human cells for a while, without triggering an antigenic response.


Drift and Shift

Now, the problem is, viruses don't keep this all that simple. They change, they evolve, they "mutate".

The proteins on the surface can change slightly, as the infection through the population proceeds, to the point where a human, who might have been infected with virus A H1 N1, and who fights the infection easily, and subsequently develops immunity to it (because he now has the proper antibodies to fight this virus), can, later on in the epidemic (an infection in a community of people), develop a subsequent infection to the "same" virus, because its proteins have altered a bit: A H1a N1. The individual's immune system recognizes this new strain of virus because it is similar to a previous infection, and therefore generates a rapid response to fight off the new strain. How successful the response is all depends upon how good the person's antibodies are in recognizing and destroying the new strain. We call this antigenic drift; minor changes in the virus' protein coat, kind of like a "disguise", can lead to reinfection with a previously fought virus.

Antigenic shift is when the virus's protein coat undergoes major changes, such as when virus A H3 N3, previously only found as an infectious agent in birds, for example, chckens, undergoes mutation, and then becomes A H3 N4, which can infect chickens and wild fowl. The virus can then readily transmit outside of it's local original community, thus leading to a possible pandemic into other communities throughout the world. Another antigenic shift occurs when A H3 N4 turns into A H3a N4a, which can now infect wild fowl and humans. The problem is, humans might have seen infection before with various A Hx Nx viruses, but never before with a A H3 N4 type of virus, as it was never infectious in the human population (only the chicken population). Now, a variant of that original virus is floating around, and it can invade human tissue. Because there is no prior "experience" with this virus in the human population, there is no immune response, and no immediate recognition or "fight" against this viral invader. We call these major changes in viral coat protein makeup, antigenic shift.

I've "made up" the above numbers purely for demonstrative purposes. Technically, there are fifteen different H proteins as I've said before, but the H5, 7, and 9 tend to be the ones associated with potential human infection. As there are nine N proteins, there are nine potential subtypes of each of these H forms. H7 forms are usually only found in people that have close contact with infected fowl, and these infections tend to be limited both in infection rate and in severity of symptoms. H9 infections are rare, and tend to be not highly pathogenic. H5 infections have occurred in humans before, and they tend to be highly virulent and destructive.

The 1918 pandemic was caused by an A H1 virus that underwent antigenic shift. No one really knows where this A virus orignated from, but it was estimated that it had undergone antigenic shift about ten times, as it changed from its original "human non-infectious" form, to its human infectious form. As the human population had no previous experience with this brand of virus, it had a devastating effect on the population.


The "SARS Bird flu"

The current one that is of concern, A H5 N1, is of a highly virulent H5 subtype, that previously was only infectious in chickens. It has undergone antigenic shift to the point where it now not only can infect wild fowl, but also can infect humans. The problem with this virus now, and the reason why it is triggering so much concern, is because of the following two reasons:

One: The virus, unlike previous respiratory viruses that get "trapped" in the nasal cavity and sinues, upper airway, and subsequently, bronchi and bronchioles, triggering nasal congestion, bronchitis, cough, bronchial swelling, etc, for some reason, bypasses these structures and proceeds all the way down to the final unit of the lungs, the air sacs themselves, the alveoli. The alveoli are small air sacs which are surrounded by pulmonary capillaries; this is where gas exchange between the air and the blood stream take place. The A H5 N1 virus attacks the alveolar cells directly, causing them to swell and explode, thus leading to a virtual destruction of the lungs. For this reason, the death rate can be over fifty percent. This is not your typical flu by any means.

Two: The 1918 virus that triggered the world wide pandemic, though not really known where it originated from, was generally felt to have undergone antigenic shift about TEN times, before it became wildly infectious with the human population. The virus changed that significantly, and was that different, that the human population had virtually no previous experience with it. Thus, it was incredibly devastating. Now, in 1918, there was not worldwide transport system in place like we have now; nowadays, a virus could enter a plane in a host, and end up in another part of the world in a matter of hours. The transmission of a virus of this nature, throughout the world, could virtually take one day. A frightening prospect indeed.

The other frightening prospect, is the potential use of A H5 N1 as a bio terrorist weapon. Once this virus undergoes significant antigenic shift, and becomes a real threat to the human population, its use as a weapon is horrifying, to say the least.

The scary thing about A H5 N1, at this point in time, is that it has undergone antigenic shift FIVE times already.

Treatment

A virus types tend to be sensitive to the usual antiviral medications, however, this new A H5N1 seems to be resistant to the usual antiviral mainstays in current medicine, amantidine and rimantidine. Oseltamivir (Tamiflu) seems to be one of the few antiviral medications that we currently have available, that still seems to be effective in treating the A H5N1 virus, which is why, there is currently a buying spree of this medication in the various pharmacies throughout the US. It has to be taken very early during the initial infection for it to be effective.

Having been a survivor of the SARS epidemic in Asia, and, having been a frequent visitor to Asia (and, also having seen many of these people virtually living with their chickens), I find all of this interesting, and, to some degree, a bit disconcerting. The whole concept of having chickens living outside your door, living in your ramshackle house, etc, is a foreign one to those of us living in the west, but a common one in some of the poorer regions of Asia, regions which seem to be most prevalent. it is not surprising that a viral evolution of this nature is taking place, when one considers the living conditions of a very prevalent part of the population of Asia. And, having experienced the rapidity of the SARS infection first hand, I'm not pessimistic that we will have a new pandemic on our hands in the near future, but, frightful that one might erupt.