Microbio Takehome Exam #6
May. 17th, 2008 02:44 pm![[personal profile]](https://www.dreamwidth.org/img/silk/identity/user.png){kind=small}
liveonearthQ1: Many people in infectious disease circles are concerned about animal housing practices in countries such as China, where pigs and chickens are housed in close proximity. What are the primary concerns based on generation of new strains of flu? Are these concerns valid and why?
Because people, swine and fowl live in close proximity in Chinese farms, and because all of the aforementioned can carry or contract the virus, the virus has ample opportunity to recombine in China. Influenza is especially suited to making great evolutionary jumps in this situation because its genetic information is contained in segmented (-) strand RNA, which can easily reassort just by switching segments, in a process known as antigenic shift. Historically all of the great flus can be traced back to China, and it is known by some epidemiologists as the Epicenter of Influenza. Interestingly, each of the great flus to arise in SE China has not caused any great outbreak there, presumably because the population there has been previously exposed and developed immunity to the new strain.
The concern is that a bird flu will evolve to match an old but effective neurminidase protein with a brand new hemagluttinin. This would generate an H5N1 or H5N2, or H5N3 flu. The entire population of the planet earth would be naive to the H5 antigen, and the majority would be naive to an older N antigen (having never been exposed to it because the last round was long ago), so the virus could possibly have incredible virulence and kill far more people than the 1918 flu did.
The risk is uncertain but the concern is certainly valid. The flu kills quite a few every year. But the new flu would also have to evolve such that it was easily transmissible among humans, as all of the destructive flus have. The odds of this happening are incalculable. It is unlikely in any given year, but like a flood, eventually the big one will come. All who are concerned with Public Health would be wise to consider the possibility of such an outbreak and plan accordingly. Previous vaccination programs have had mixed results. Thankfully, naturopathic medicine provides us with excellent tools for treating flu that substantially reduce mortality.
Q2: Regarding the "crazyborat" virus, which must be entirely invented. My plan to control the spread of crazyborat virus in Kazakhistan would depend substantially on the local public health system and its capacities. Of course it would be necessary to educate the public about the virus, its signs and symptoms, and the really bring home the importance of handwashing (because the virus seems to be transmitted via the fecal-oral route, and because it is a + stranded RNA virus which is able to immediately infect cells because it acts like mRNA). Knowing what I know about Kazakhistan, I suspect that it would be difficult to mount an effective educational campaign, but this would be my primary effort. The public would be instructed on proper handwashing and if facilities or water were not available for such washing, they need to be provided. Infected individuals need to have somewhere to eliminate. I imagine that with many people infected with diarrhea in the 3rd world, there could be infectious fecal matter EVERWHERE. If this is the case, some effort at cleanup might be attempted. The public would also need to know the treatment protocol should someone show the preliminary symptoms in the initial several weeks. If individuals can be treated before the virus goes into the nervous system, many lives might be saved. A quarantine is not likely to be useful unless there is a way to identify asymptomatic carriers. If the virus can be isolated and analyzed and an appropriate vaccine devised, it may be advisable to vaccinate those at risk, but vaccination will only stop or slow future outbreaks, it won't help with the current one.
Q3: Find herbal alternatives for rimantadine or amantadine. First I'd like to point out that this question steers us in the direction of "green allopathy" which is based on the assumption that natural medicine involves finding a herbal treatment to replace a drug treatment. The herb is expected to have some component that has similar actions to the pharmaceutical. This view is short sighted because naturopathy includes many modalities besides herbs that are highly effective for treating pneumonia, including but not limited to hydrotherapy, diathermy, enemas and fasting.
MECHANISMS (RIMANTADINE)
--from http://gsm.about.com/compact/showmono.asp?cpnum=547&r=6078&monotype=full
--rimantadine's exact mechanism of action is unknown
--appears to block uncoating of virus
--may occur via interference with fusion of the virion envelope to vacuolar membranes (virustatic effect)
--from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=89245
--action is pH dependent based on experience with treating Trypanosoma brucei, and is consistent with a mechanism involving inhibition of the ability to regulate internal pH
--from www.hhs.gov/nvpo/meetings/ PowerPoints/ShayIntroAntiviralsNVAC.ppt
--interferes w/ fx of the transmembrane domain of the M2 protein of influenza A viruses
--interferes with virus assembly during replication of influenza A viruses
--http://www.nature.com/nature/journal/v451/n7178/full/nature06531.html has the best info on the M2 proton channel that I found, and the exact biochemical mechanism
MECHANISMS (AMANTADINE)
--in antiparkinsonic effect it appears to be releasing dopamine from the nerve endings of the brain cells, together with stimulation of norepinephrine response
--appears to be a weak NMDA receptor antagonist and an anticholinergic
--antiviral mechanism seems to be unrelated
--interferes with M2 viral protein (an ion channel) involved in uncoating
--above according to http://en.wikipedia.org/wiki/Amantadine
--confirmed here http://www.medicinenet.com/amantadine/article.htm
OTHER INFO ON RIMANTADIN0E
--from http://gsm.about.com/compact/showmono.asp?
--effective against most strains of influenza A
--has little or no activity against influenza B
--ineffective against all strains of herpes and HIV
--oral administration, protein binding is approximately 40%, with extensive metabolism by the liver to three distinct hydroxylated metabolites and one conjugated metabolite
--half-life 13—65 hours
--urinary excretion of unchanged rimantadine accounts for ~ 20% of dose in healthy subjects
--not appreciably removed by hemodialysis
--from http://www.medicinenet.com/rimantadine/article.htm below
--start before exposure to the virus to prevent infection
--take within 24-48 hours of onset to decrease the severity of the flu
--chemically related to amantadine (Symmetrel), but fewer side effects on the nervous system --no studies on safety with pregnancy or nursing
--side effects incl: nausea, vomiting, sleep disturbances, dizziness, loss of appetite and dry mouth
A few natural treatments for pneumonia:
--fenugreek tea, during acute stage helps produce sweat, dispel toxicity and shorten fever. OK to add lemon but no food may be taken during acute fever.
--garlic, taken raw and internally or applied on the chest in a paste, irritant and rubefacient (and my personal favorite, so far)
--sesame seed infusion plus linseed, salt and honey helps remove mucus
--parsnip juice contains phosphorus and chlorine (use cultivated not wild)
--carrot, spinach, beet and cucumber juices
--turpentine oil rubbed on rib cage with warm cotton plus wool wrap for chest pain
--raw foods diet for 5-10 days, until fever subsides, then juicy fruits for 3-4 days
--the above from http://www.home-remedies-for-you.com/remedy/Pneumonia.html
--mucurita, onions and garlic contain sulfide compounds with antiseptic, antibiotic and antiviral properties
--astragalus aka huang qi, immune booster, OK to use with echinacea
--baikal skullcap (Scutellaria baicalensis), root has shown broad-spectrum antimicrobial activity including flu viruses and pneumo-causing fungi! Chinese med: mix with goldthread, amur cork tree extract.
--barberry, goldthread
--Oregon grape aka. yellowroot
--dandelion (Taraxacum officinale). Numerous clinical trials have demonstrated dandelion's effectiveness against pneumonia, bronchitis and upper respiratory infections, according to pharmacognosist (natural product pharmacist) Albert Leung, Ph.D. (eat cooked greens and roots, and drink the water from cooking)
--echinacea
--goldenseal has two broad-spectrum antimicrobial constituents, hydrastine and berberine.
--honeysuckle flower extract or tea
--forsythia tea
--onion (Allium cepa) similar to garlic (not quite as good) also has sulfur-containing compound
--osha (Lomatium dissectum) = tribal remedy, chew on root for all resp ailments
--sundew (Drosera, various species) contains plumbagin which inhibits bacteria that cause pneumo. This is relevant because most pneumo infections include a bacterial component, even if the infection was initiated by a virus. sundew also contains cough suppressant
--the above from http://www.mothernature.com/Library/Bookshelf/Books/41/93.cfm
--mao-to, Japanese herb, antipyretic
ON MECHANISMS OF HERBS
Upon searching for the mechanisms of herbal treatments it quickly became apparent that there has been little research and less repeated/confirmed research. There is very little consensus among users of herbs as to what each herb does, and how it works. The most effective remedies known are those that have been used for centuries and proven to work. The primary purposes of further study are to build credibility for the users of herbs, and also to be able to predict possible interactions when giving multiple remedies. This is not going to happen any time soon, as the exact mechanisms of many pharmaceuticals including rimantadine and amantadine are not known. We have a long way to go.
Because people, swine and fowl live in close proximity in Chinese farms, and because all of the aforementioned can carry or contract the virus, the virus has ample opportunity to recombine in China. Influenza is especially suited to making great evolutionary jumps in this situation because its genetic information is contained in segmented (-) strand RNA, which can easily reassort just by switching segments, in a process known as antigenic shift. Historically all of the great flus can be traced back to China, and it is known by some epidemiologists as the Epicenter of Influenza. Interestingly, each of the great flus to arise in SE China has not caused any great outbreak there, presumably because the population there has been previously exposed and developed immunity to the new strain.
The concern is that a bird flu will evolve to match an old but effective neurminidase protein with a brand new hemagluttinin. This would generate an H5N1 or H5N2, or H5N3 flu. The entire population of the planet earth would be naive to the H5 antigen, and the majority would be naive to an older N antigen (having never been exposed to it because the last round was long ago), so the virus could possibly have incredible virulence and kill far more people than the 1918 flu did.
The risk is uncertain but the concern is certainly valid. The flu kills quite a few every year. But the new flu would also have to evolve such that it was easily transmissible among humans, as all of the destructive flus have. The odds of this happening are incalculable. It is unlikely in any given year, but like a flood, eventually the big one will come. All who are concerned with Public Health would be wise to consider the possibility of such an outbreak and plan accordingly. Previous vaccination programs have had mixed results. Thankfully, naturopathic medicine provides us with excellent tools for treating flu that substantially reduce mortality.
Q2: Regarding the "crazyborat" virus, which must be entirely invented. My plan to control the spread of crazyborat virus in Kazakhistan would depend substantially on the local public health system and its capacities. Of course it would be necessary to educate the public about the virus, its signs and symptoms, and the really bring home the importance of handwashing (because the virus seems to be transmitted via the fecal-oral route, and because it is a + stranded RNA virus which is able to immediately infect cells because it acts like mRNA). Knowing what I know about Kazakhistan, I suspect that it would be difficult to mount an effective educational campaign, but this would be my primary effort. The public would be instructed on proper handwashing and if facilities or water were not available for such washing, they need to be provided. Infected individuals need to have somewhere to eliminate. I imagine that with many people infected with diarrhea in the 3rd world, there could be infectious fecal matter EVERWHERE. If this is the case, some effort at cleanup might be attempted. The public would also need to know the treatment protocol should someone show the preliminary symptoms in the initial several weeks. If individuals can be treated before the virus goes into the nervous system, many lives might be saved. A quarantine is not likely to be useful unless there is a way to identify asymptomatic carriers. If the virus can be isolated and analyzed and an appropriate vaccine devised, it may be advisable to vaccinate those at risk, but vaccination will only stop or slow future outbreaks, it won't help with the current one.
Q3: Find herbal alternatives for rimantadine or amantadine. First I'd like to point out that this question steers us in the direction of "green allopathy" which is based on the assumption that natural medicine involves finding a herbal treatment to replace a drug treatment. The herb is expected to have some component that has similar actions to the pharmaceutical. This view is short sighted because naturopathy includes many modalities besides herbs that are highly effective for treating pneumonia, including but not limited to hydrotherapy, diathermy, enemas and fasting.
MECHANISMS (RIMANTADINE)
--from http://gsm.about.com/compact/showmono.asp?cpnum=547&r=6078&monotype=full
--rimantadine's exact mechanism of action is unknown
--appears to block uncoating of virus
--may occur via interference with fusion of the virion envelope to vacuolar membranes (virustatic effect)
--from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=89245
--action is pH dependent based on experience with treating Trypanosoma brucei, and is consistent with a mechanism involving inhibition of the ability to regulate internal pH
--from www.hhs.gov/nvpo/meetings/ PowerPoints/ShayIntroAntiviralsNVAC.ppt
--interferes w/ fx of the transmembrane domain of the M2 protein of influenza A viruses
--interferes with virus assembly during replication of influenza A viruses
--http://www.nature.com/nature/journal/v451/n7178/full/nature06531.html has the best info on the M2 proton channel that I found, and the exact biochemical mechanism
MECHANISMS (AMANTADINE)
--in antiparkinsonic effect it appears to be releasing dopamine from the nerve endings of the brain cells, together with stimulation of norepinephrine response
--appears to be a weak NMDA receptor antagonist and an anticholinergic
--antiviral mechanism seems to be unrelated
--interferes with M2 viral protein (an ion channel) involved in uncoating
--above according to http://en.wikipedia.org/wiki/Amantadine
--confirmed here http://www.medicinenet.com/amantadine/article.htm
OTHER INFO ON RIMANTADIN0E
--from http://gsm.about.com/compact/showmono.asp?
--effective against most strains of influenza A
--has little or no activity against influenza B
--ineffective against all strains of herpes and HIV
--oral administration, protein binding is approximately 40%, with extensive metabolism by the liver to three distinct hydroxylated metabolites and one conjugated metabolite
--half-life 13—65 hours
--urinary excretion of unchanged rimantadine accounts for ~ 20% of dose in healthy subjects
--not appreciably removed by hemodialysis
--from http://www.medicinenet.com/rimantadine/article.htm below
--start before exposure to the virus to prevent infection
--take within 24-48 hours of onset to decrease the severity of the flu
--chemically related to amantadine (Symmetrel), but fewer side effects on the nervous system --no studies on safety with pregnancy or nursing
--side effects incl: nausea, vomiting, sleep disturbances, dizziness, loss of appetite and dry mouth
A few natural treatments for pneumonia:
--fenugreek tea, during acute stage helps produce sweat, dispel toxicity and shorten fever. OK to add lemon but no food may be taken during acute fever.
--garlic, taken raw and internally or applied on the chest in a paste, irritant and rubefacient (and my personal favorite, so far)
--sesame seed infusion plus linseed, salt and honey helps remove mucus
--parsnip juice contains phosphorus and chlorine (use cultivated not wild)
--carrot, spinach, beet and cucumber juices
--turpentine oil rubbed on rib cage with warm cotton plus wool wrap for chest pain
--raw foods diet for 5-10 days, until fever subsides, then juicy fruits for 3-4 days
--the above from http://www.home-remedies-for-you.com/remedy/Pneumonia.html
--mucurita, onions and garlic contain sulfide compounds with antiseptic, antibiotic and antiviral properties
--astragalus aka huang qi, immune booster, OK to use with echinacea
--baikal skullcap (Scutellaria baicalensis), root has shown broad-spectrum antimicrobial activity including flu viruses and pneumo-causing fungi! Chinese med: mix with goldthread, amur cork tree extract.
--barberry, goldthread
--Oregon grape aka. yellowroot
--dandelion (Taraxacum officinale). Numerous clinical trials have demonstrated dandelion's effectiveness against pneumonia, bronchitis and upper respiratory infections, according to pharmacognosist (natural product pharmacist) Albert Leung, Ph.D. (eat cooked greens and roots, and drink the water from cooking)
--echinacea
--goldenseal has two broad-spectrum antimicrobial constituents, hydrastine and berberine.
--honeysuckle flower extract or tea
--forsythia tea
--onion (Allium cepa) similar to garlic (not quite as good) also has sulfur-containing compound
--osha (Lomatium dissectum) = tribal remedy, chew on root for all resp ailments
--sundew (Drosera, various species) contains plumbagin which inhibits bacteria that cause pneumo. This is relevant because most pneumo infections include a bacterial component, even if the infection was initiated by a virus. sundew also contains cough suppressant
--the above from http://www.mothernature.com/Library/Bookshelf/Books/41/93.cfm
--mao-to, Japanese herb, antipyretic
ON MECHANISMS OF HERBS
Upon searching for the mechanisms of herbal treatments it quickly became apparent that there has been little research and less repeated/confirmed research. There is very little consensus among users of herbs as to what each herb does, and how it works. The most effective remedies known are those that have been used for centuries and proven to work. The primary purposes of further study are to build credibility for the users of herbs, and also to be able to predict possible interactions when giving multiple remedies. This is not going to happen any time soon, as the exact mechanisms of many pharmaceuticals including rimantadine and amantadine are not known. We have a long way to go.
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