Most evil software company

[Prof.Wizard]

Symantec: Symantec buys a piece of software, and its next release goes from useful to brown and stinky. Ghost will be a lot less cool when it doesn't fit on a floppy disk. We won't even talk about NAV.

Symantec.
I happen to believe that anti-virus software companies are the same which create the viruses. (Some say this also about pharmaceutical companies...)

 

[Adcadet]

Using the patented Adcadet Evil Scale (AES; where the evilness of the act (evil points)*frequency=AES value), I figure that automatically installing a monopolist's product (50 evil points) onto 95% of PCs is worth 47.5 AES's. The monkey's secret install is really evil (99 evil points), but it only happens on a fraction of machines, say 5% to get an AES of nearly 5.

Andy, did you see this post?

How does that rate on your scale?

I'm sorry, the AES becomes pretty non-linear at that level of evil. When the scale was designed back in 1981 that level of evil was just not thought possible.

 

[Adcadet]

Symantec: Symantec buys a piece of software, and its next release goes from useful to brown and stinky. Ghost will be a lot less cool when it doesn't fit on a floppy disk. We won't even talk about NAV.

Symantec.
I happen to believe that anti-virus software companies are the same which create the viruses. (Some say this also about pharmaceutical companies...)

PW - what are you saying about pharmaceutical companies? I know they can be pretty sleazy, but are you suggesting that they create disease intentionally?

 

[Mercutio]

It's been suggested for many, many years. Personally I think nature probably does a fine job on its own, but for the conspiracy minded it is a possibility.

 

[Prof.Wizard]

PW - what are you saying about pharmaceutical companies? I know they can be pretty sleazy, but are you suggesting that they create disease intentionally?

I'm not saying that they release stems of Ebola virus purposely, but this usual thingy of the mild winter-time flu (and the usual vaccination of the elders which means lots of $$$...) is a little bit... too weird.

Moreover, sometimes drugs can be made with an easier and simpler manufacturing and the pharmaceutical companies prefer the complex one because of the larger profit margin. (You know... they want to make up for the money of the research search, especially if the second procedure is invented only some months later!)

I believe Intel and AMD do it as well. Why rush their newest products to the market if there is still gain by selling slower CPUs?

 

[Adcadet]

PW - what are you saying about pharmaceutical companies? I know they can be pretty sleazy, but are you suggesting that they create disease intentionally?

I'm not saying that they release stems of Ebola virus purposely, but this usual thingy of the mild winter-time flu (and the usual vaccination of the elders which means lots of $$$...) is a little bit... too weird.

Moreover, sometimes drugs can be made with an easier and simpler manufacturing and the pharmaceutical companies prefer the complex one because of the larger profit margin. (You know... they want to make up for the money of the research search, especially if the second procedure is invented only some months later!)

I believe Intel and AMD do it as well. Why rush their newest products to the market if there is still gain by selling slower CPUs?

Ya lost me. Mid-winter flu. Not sure about the seasonal variation in influenza in Europe, but in the US winter influenza epidemics have been a fact of life for as long as anybody can remember. At least since 1918. How on earth is a pharmaceutical company going to alter flu patters, unless you think they're creating, or isolating and releasing strains of influenza so as to get people sick? And how are they going to profit from viral infections that are rarely treated with drugs? (other than if some people, usually the elderly, get very sick and develop secondary infections which can be treated with antibiotics....unfortunately, those antibiotics tend to be cheap, relatively speaking).

A private company will use whatever manufacturing process it sees as costing it the least amount of money. So if a new, easier, cheaper process is developed, yet requires a large initial investment in the factory, why should they switch if they figure it won't actually save them any money?

Don't get me wrong, I think the pharmaceutical industry does many slimy things, but I don't think they intentionally raise their costs and promote disease. PW, I hope you're joking.

 

[Fushigi]

Ya lost me. Mid-winter flu. Not sure about the seasonal variation in influenza in Europe, but in the US winter influenza epidemics have been a fact of life for as long as anybody can remember. At least since 1918. How on earth is a pharmaceutical company going to alter flu patters, unless you think they're creating, or isolating and releasing strains of influenza so as to get people sick? And how are they going to profit from viral infections that are rarely treated with drugs? (other than if some people, usually the elderly, get very sick and develop secondary infections which can be treated with antibiotics....unfortunately, those antibiotics tend to be cheap, relatively speaking).

<cynicism>Flu shots are cheap. But, if a new strain was making the rounds, you might need a new vaccine that costs a lot more to fight it. And, my, itn't it coincidental that company X just so happens to have a vaccine available. And for the bargain price of only 5x the regular vaccine.</cynicism>

I'm not saying it happens. Just that it wouldn't be that difficult to manipulate the market away from a drug where cheap generics are available and onto a new, high-margin variant that only one or two manufacturers can offer.

 

[Prof.Wizard]

Ya lost me. Mid-winter flu. Not sure about the seasonal variation in influenza in Europe, but in the US winter influenza epidemics have been a fact of life for as long as anybody can remember. At least since 1918. How on earth is a pharmaceutical company going to alter flu patters, unless you think they're creating, or isolating and releasing strains of influenza so as to get people sick?

The drug IS ALWAYS ready by November-December. And it's ready to counter most strains of this year's influenza BEFORE it even breaks out.

And how are they going to profit from viral infections that are rarely treated with drugs? (other than if some people, usually the elderly, get very sick and develop secondary infections which can be treated with antibiotics....unfortunately, those antibiotics tend to be cheap, relatively speaking).

In our post-industrial world, elders make a great part of the population. And vaccines cost you know.

A private company will use whatever manufacturing process it sees as costing it the least amount of money. So if a new, easier, cheaper process is developed, yet requires a large initial investment in the factory, why should they switch if they figure it won't actually save them any money?

Someone has to pay for the research you know. As you said, they are private companies. Like the ones which make Q-results every trimester.

Don't get me wrong, I think the pharmaceutical industry does many slimy things, but I don't think they intentionally raise their costs and promote disease. PW, I hope you're joking.

They're not promoting diseases like releasing viruses and the likes. But they deliberately maintain the prices high, that's for sure. Gains are gains, everybody pays for his health.

 

[Adcadet]

Ya lost me. Mid-winter flu. Not sure about the seasonal variation in influenza in Europe, but in the US winter influenza epidemics have been a fact of life for as long as anybody can remember. At least since 1918. How on earth is a pharmaceutical company going to alter flu patters, unless you think they're creating, or isolating and releasing strains of influenza so as to get people sick? And how are they going to profit from viral infections that are rarely treated with drugs? (other than if some people, usually the elderly, get very sick and develop secondary infections which can be treated with antibiotics....unfortunately, those antibiotics tend to be cheap, relatively speaking).

<cynicism>Flu shots are cheap. But, if a new strain was making the rounds, you might need a new vaccine that costs a lot more to fight it. And, my, itn't it coincidental that company X just so happens to have a vaccine available. And for the bargain price of only 5x the regular vaccine.</cynicism>


I'm not saying it happens. Just that it wouldn't be that difficult to manipulate the market away from a drug where cheap generics are available and onto a new, high-margin variant that only one or two manufacturers can offer.

Ok, the last part there I *do* think happens with many drugs. Take hypertensive medications over the last few years. More and more docs have shifted away from using diuretics (cheap) and to ACE inhibitors and calcium channel blockers (expenstive) to manage hypertension. It can be argued that the only reason they did this is pharmaceutical company pressure. A study just came out, showing the cheaper diuretics are actually better. See the CBS story here: http://www.cbsnews.com/stories/2002/12/17/earlyshow/contributors/emilysenay/main533320.shtml

OK, now back to influenza:
Oh good lord. We're talking about influenza vaccination, not drugs (there actually are a few influenza drugs, though they are rarely used). Where to begin (re: Fushigi and PW). PW - aren't you a med student or something? Shouldn't you know better? Have either of you actually read up on the epidemiology of influenza? Familiar with genetic drift and genetic shift? If not, I'd be happy to refer you to a few references, including a paper I wrote on the subject last year.

 

[Adcadet]

Introduction

In the winter of 1918-1919, a disease killed 21 million people worldwide. Despite the continued morbidity of this disease, today most people don’t understand the true public health impact of the “common cold.” Influenza virus, the cause of “the flu,” is an infectious virus that causes significant death and disease each year in the United States. While in most healthy individuals influenza causes a self-limiting disease, influenza is capable of causing serious and life threatening illness.

The influenza virus is a member of the genus Orthomyxoviridae (2). Influenza, which takes its name from the Latin and Italian words for “bad influence,” is often simply called “the flu.” However, one must be careful to distinguish between the “stomach flu,” usually a food-born gastrointestinal illness, from the respiratory infection caused by influenza virus. There are three strains of influenza. Influenza A causes moderate to severe infection in both humans and animals and has great public health impact. Influenza B causes a more mild illness, primarily infects children, and does not infect animals. Influenza C is though to only produce sub-clinical illness and is rarely reported in humans (2).

Influenza virus contains an outer envelope, a lipid bilayer derived from the previous host cell that is studded with viral proteins (see Figure 1). The two most important surface proteins are hemagglutinin (H or HA) and neuraminidase (N or NA) (8). Influenza viruses are categorized on the basis of their hemagglutinin and neuraminidase genes. For example, H3N2 is currently the dominant Influenza A virus in circulation in the United States. The genome of influenza is composed of eight segments of negative stranded RNA. Genetic variation can occur by antigenic drift, the change in nucleic acid sequence of a gene, or antigenetic shift, or the substitution of an entire gene between subtypes. Genetic drift generally produces subtle changes in the virus, whereas genetic shift often produces a novel virus in which large numbers of people may be susceptible.





Figure 1: Electron Micrograph of three influenza virus particles. Picture taken from the National Center for Infectious Disease, CDC. (URL: http://www.virology.net/Big_Virology/BVRNAortho.html)





Life Cycle and Replication

During an infection cycle, influenza first needs to bind to a target cell. Hemagglutinin located on the outside of the virus is synthesized as a precursor called HA0 and needs to be cleaved, usually at a single site, by the enzyme tryptase Clara to form two subunits called HA1 and HA2. This cleaved hemagglutinin can then bind to sialic acid located on the surface of epithelial and immune cells in the respiratory tract (16). The specificity of influenza for the lungs thus comes mainly from the fact that tryptase Clara is produced from Clara cells in the respiratory tract epithelium. Some influenza viruses carry an HA0 contains multiple sites that can be cleaved by a wide range of proteases and thus can infect cells located throughout the body (26). Hemagglutinin can also sometimes by cleaved by proteases produced in the endoplasmic reticulum or even by various bacteria such as Staphylococcus areus, Haemophilus influenzae, and Streptococcus pneumoniae, leading to a great increase in influenza pathogenicity in people infected with these bacteria.

Once influenza is bound to a host cell, it is endocytosed into a vesicle that is progressively acidified. The acidic environment triggers a series of events that allow the viral genome and associated proteins (ribonucleoprotein) to disassociate from the capsid, and allows the fusion of the viral envelope with the vesicle membrane. These two processes allow the viral nucleoprotein to escape from the vesicle into the cell cytoplasm. Once in the cell cytoplasm, the viral nucleoprotein moves into the host cell nucleus with the aide of a nuclear localization signal (8).

Once influenza ribonucleoprotein is in the cell nucleus, it can begin the process of making viral proteins and replicating its genome. An interesting feature of influenza is that it uses a process called “cap snatching” in which the viral endonuclease cleaves 5’ capped fragments from newly synthesized host cell mRNA and uses these as a primer to make viral PB1, the viral transcriptase (2). This viral transcriptase produces mRNA, which is transported to the cytoplasm to make more viral proteins. The termination of transcription and addition of poly(A) tails to influenza transcripts occurs by a stuttering of the transcription machinery that copies a series of U residues (which code for a poly(A) tail). When a high concentration of viral nucleocapsid protein (NP) has been made, the stuttering process is inhibited, and full length genomes are copied. These genomes enter the cell’s secretory pathway along with viral proteins. Some viral proteins, namely HA and NA, are incorporated into the plasma membrane. New virions are assembled and bud from the apical surface of epithelial cells. Because of the directionality of budding, it is rare to isolate influenza outside of the respiratory system (21).



Pathology

Host pathology occurs by a number of mechanisms. The production of new virions within host epithelial cells disrupts the apical surface of epithelial cells, destroys host cell mRNAs by “cap snatching,” inhibits translation of host proteins, and kills the host cell either by inducing programmed cell death (apoptosis) (19) or by rupturing the plasma membrane during budding (20). However, during infection, some infected cells respond by production interferon, a chemical which has anti-proliferative and immunomodulatory properties, and chemicals which attract immune cells and promote an inflammatory immune response (1, 28). Taken together, these various changes trigger an immune response, affect the integrity of the mucosal layer and mucocilliary clearance, and interfere with the removal of other pathogens from the lungs which often leads to secondary bacterial pneumonia and produces cough (13).

Influenza infections usually manifest a rapid onset of symptoms following a one- to five-day incubation period. These symptoms include a fever, chills, body aches, sore throat, non-productive cough, runny nose, and headache. Illness usually resolves after several days, although symptoms can persist for two weeks or longer. An infected person typically sheds virus for 5-10 days after infection (2). Influenza can cause serious medical complications among people with underlying medical conditions and can lead to secondary infections with other pathogens.

Influenza is usually diagnosed on the basis of symptoms alone, although there are a variety of laboratory tests that can confirm a diagnosis or be used in research. These include enzyme linked immunosorbant assay, reverse-transcription polymerase chain reaction, hemagglutination, and radioimmunoassay (see table 1). Most rapid tests will give results within 24 hours with >70% sensitivity and >90% specificity. Because of the low sensitivity, positive rapid influenza tests are usually followed with viral culture. When serum samples are used for antibody detection, one sample is usually taken within the first week of illness and a second sample is taken two to four weeks later. A positive result is considered a significant rise in serum antibody levels between the two tests (17).

























Table 1: Laboratory Diagnostic Procedures for Influenza.

Laboratory Diagnostic Procedures for Influenza1

Procedure
Influenza
types
Detected
Acceptable
Specimens
Time for
Results
Point-of-care
market

Viral culture
A and B
NP Swab2
Throat Swab
Nasal Wash
Bronchial Wash
Nasal Aspirate
Sputum
5-10
days3
No

Immuno-
fluorescence
A and B
NP Swab2
Nasal Wash
Bronchial Wash
Nasal Aspirate
Sputum
2-4
hours
No

Influenza A
Enzyme Immuno
Assay (EIA)
A and B
NP Swab2
Throat Swab
Nasal Wash
Brochial Wash
2
hours
No

Directigen A
(Becton-
Dickinson)
A
NP Swab2
Throat Swab
Nasal Wash
Nasal Aspirate
<30
minutes
Yes

Directigen
Flu A and B
(Becton-
Dickinson)
A and B
NP Swab2
Throat Swab
Nasal Wash
Nasal Aspirate
Bronchial Wash
<30
minutes
Yes

FLU OIA
(Biostar)
A and B4
NP Swab2
Throat Swab
Nasal Aspirate
Sputum
<30
minutes
Yes

Quick Vue
(Quidel)
A and B4
NP Swab2
Nasal Wash
Nasal Aspirate
<30
minutes
Yes

Zstat Flu
(ZymeTx)
A and B4
Throat Swab
<30
minutes
Yes

RT-PCR
A and B
NP Swab2
Throat Swab
Nasal Wash
Bronchial Wash
Nasal Aspirate
Sputum
1-2
days
No

Serology
A and B
Paired Acute and
Convalescent
Serum
Samples5
>2
weeks
No


1 List may not include all test kits approved by the U.S. Food and Drug Administration as of September 1, 2001
2 NP = nasopharyngeal
3 Shell vial culture, if available, may reduce time for results to 2 days
4 Does not distinguish between influenza A and B types
5 A fourfold or greater rise in antibody titer from the acute- (collected within the 1st week of illness) to the
convalescent-phase (collected 2-4 weeks after the acute sample) samples is indicative of recent infection.

Table 1: comparison of various methods used clinically to detect influenza A and B. Taken from the Detection & Control of Influenza Outbreaks in Acute Care Facilities. (URL: http://www.cdc.gov/ncidod/hip/INFECT/flu_acute.htm)





Children and teenagers infected with influenza are at risk of developing a rare complication called Reye’s syndrome if given salicylates such as aspirin. Reye’s syndrome affects the central nervous system and liver and can be fatal (13). Thus, it is important that young people who show flu-like symptoms are not given aspirin.



Epidemiology

Influenza is a major cause of morbidity and mortality in the United States and globally. The level of influenza activity can be categorized as endemic, epidemic, or pandemic. Endemic refers to the “normal” or baseline rate of disease. An epidemic is a level of disease greater than expected, and a pandemic is a world-wide epidemic (see Figure 2). During epidemic years, influenza can increase hospitalization rates two- to five-fold, lead to more than 10,000 excess deaths, and cause 80% of all deaths in persons over age 65 (15). During the 1997 epidemic, influenza was the 6th leading cause of death. It has been estimated that between 1972 and 1992, influenza was responsible for 426,000 deaths in the U.S. alone (20).


Figure 2. Diagram showing the percent of deaths due to influenza and pneumonia over time. The lower curve shows the endemic level and the upper curve shows the “epidemic threshold.” Overlaid is the pneumonia and influenza mortality rate for 122 U.S. cities for the week ending 3/23/02. Taken from the 1999-2000 Influenza Season Summary, CDC. (URL: http://www.cdc.gov/ncidod/diseases/flu/weekly.htm)



Influenza epidemics are thought to typically originate in Asia where the interaction of aquatic birds, pigs, and humans allows the periodic generation and introduction of novel strains. Waterfowl are the natural reservoirs of influenza, where the virus replicates while causing no disease. These birds then excrete the virus in high concentration in feces into the water. While avian influenza is in evolutionary stasis with nearly no major changes occurring in the past 60 years (24), each year a new group of young ducks hatch and serve as a new susceptible population. Furthermore, migrating birds serve as a means of transmitting the virus over long distances. This process makes aquatic birds a very efficient means of transmitting virus. Phylogenic analysis of nucleic acid sequences of influenza A viruses from around the world suggests that all mammalian influenza viruses derive from the avian reservoir (9). Live bird markets may also be an important source of influenza viruses (24). Fecal contamination of water is probably responsible for the transmission of avian influenza viruses to mammal such as pigs, horses, and humans. Influenza outbreaks of avian origin have been implicated in outbreaks in various mammals including seals (10), whales (11), pigs and domestic poultry (9). Once humans have been infected, transmission of influenza is thought to occur rapidly primarily between people by respiratory means such as sneezing and coughing, and global spread is likely, especially for extremely virulent strains.

Since novel influenza strains are first seen in avian, and to a lesser extent, porcine species, the World Health Organization has established a sentinel program that tracks changes in circulating influenza viruses and notes the emergence of novel strains in an attempt to predict what the dominant strains will be in the upcoming flu season. Each year, the 110 centers and 180 laboratories located in 83 countries send isolates to the Centers for Disease Control and Prevention (CDC) in Atlanta where they are analyzed in an attempt to gauge their likelihood of causing outbreaks and severe illness. Between January and March, the CDC, together with the Food and Drug Administration, decide which strains should be used for vaccine production. The pharmaceutical companies licensed to produce vaccine then attempt to produce a sufficient quantity in time for the major vaccination campaigns beginning in late September (15). If all goes well, the majority of high-risk individuals will have been vaccinated and had time to form an immune response before influenza infection peaks in December through March (see figure 3).




























Figure 3. A plot of the number of isolates from clinical laboratories during the current flu season (2001-2002). Graph taken from the National Respiratory Virus Surveillance System, WHO/CDC. (URL: http://www.cdc.gov/ncidod/diseases/flu/weekly.htm)





Immunization and Antiviral Treatment

Immunization is the primary method of limiting the public health impact of influenza. The vaccine is either whole or split inactivated vaccine that contains antigens from the three strains of influenza (two influenza A strains, and one influenza B strain) that are predicted to have the greatest impact in that year. Since novel influenza strains are constantly being introduced (or reintroduced) into human populations, previous years’ vaccines are not very effective. Efficacy is highly correlated with the match between the predicted virus strains and what actually circulates, and in most years the vaccine is a very good match with the major circulating viruses. For example, the typical vaccine is (15):

· up to 90% effective in preventing clinical illness in young, healthy people

· 30-40% effective in preventing illness in frail, elderly people

· 50-60% effective in preventing hospitalization

· 80% effective in preventing death



It is important to realize that while the vaccine may not be able to completely protect individuals from clinical infection (especially among the elderly who are thought to mount an incomplete or poor response to the vaccine), it is still effective in preventing the more serious complications of infection which result in hospitalization and death.

The vaccine is not only efficacious, but it is also extremely safe. Therefore, it is highly recommended that the following individuals receive the vaccine (4):

· all people over 65

· persons under 6 months with chronic illness

· all persons with various chronic illnesses (pulmonary, cardiovascular, metabolic, renal, hemoglobinopathies, immunosuppression)

· HIV-positive individuals

· Providers of essential services

· Foreign travelers

· Residents of long-term care facilities

· 6-18 year olds receiving aspirin therapy

· Pregnant women

· Health care providers

· Employees of long-term care facilities

· Household members of high-risk persons

· Anyone who wishes to reduce their risk of influenza



However, there are a some individuals to whom the vaccine should not be given, including those who are allergic to a vaccine component, including eggs, and those with moderate to severe illness. There is also a range of adverse effects associated with the vaccine, including (18):

· Local reactions such as arm soreness (less than 30%)

· Fever or malaise (less than 1%)

· Severe allergic reactions (rare)

· Neurological reactions (very rare)



Due to the difficulty in producing the vaccine, and the critical issues of timing, the vaccine supply sometimes fails to meet the perceived need in a timely manner. In years in which that occurs, the vaccine may only initially be offered to those who are highest risk of morbidity and mortality from influenza, and health care workers.

The cost effectiveness of the influenza vaccine varies based upon what population received the vaccine, the severity of the circulating influenza viruses, and the match between the vaccine and the dominant viruses. A study examining the cost effectiveness of influenza vaccination among healthy workers found a net societal loss both when the match was poor (net societal cost of $65.59 per person) and when the match was very good (net societal loss of $11) (7). A study of Medicare recipients found that the net societal cost of administering the influenza vaccine to the Medicare population was approximately zero, although the cost per year of life gained were significantly lower compared to other prevention programs. Specifically, if we assume a vaccination rate of 40% and reduction in reducing hospitalizations and deaths, the influenza vaccine would cost $145 per year life gained. This compares favorably against other preventive measures, such as the pneumococcal vaccine ($1853 per year of healthy life gained) and cervical cancer screening ($1600-2900 per year of healthy life gained) (3).

While antibiotics are ineffective against viruses, four drugs have been developed and licensed for the prevention and treatment of infections (see table 2). The first two to market, amantadine and rimantadine, seem to interfere with the replication of the virus, and are 70-90% effective in preventing clinical illness when used within 48 hours of infection. An important point is that while these drugs reduce clinical illness, it is thought that they still allow sub-clinical infection and an active immune response for long-term protection.

In 1999, zanamivir and oseltamivir, two neuraminidase inhibitors were licensed for the reduction in severity of influenza infections. Like amantadine and rimantidine, these drugs must be given within 48 hours of the onset of symptoms to be effective. Unlike the amantadine and rimantidine, these two drugs are generally not used prophylacticly, are generally used in older individuals, and are effective in treating both influenza A and B infections (16).



Table 2: Comparison of Antiviral Drugs for Influenza Treatment.

Comparison of Antiviral Drugs for Influenza Table

Drug
Trade Name
Influenza Virus Type
Approved Use
Treatment Age
Prevention Age

amantadine
Symmetrel®
A
Treatment and Prevention
>1 year
>1 year

rimantadine
Flumadine®
A
Treatment and Prevention
Adults
>1 year

zanamivir
Relenza®
A and B
Treatment
>7 years
n/a

oseltamivir
Tamiflu®
A and B
Treatment
and
Prevention
>1 years
>13 years


Table 2: a comparison on the four FDA approved drugs used in the treatment of influenza. Taken from MMWR, April 20, 2001. (URL: http://www.cdc.gov/ncidod/diseases/flu/fluviral.htm)



Summary

Influenza virus is a major public health concern. The ubiquitous “common cold” can be anything but mild and is capable of turning regional epidemics into global pandemics. By utilizing a large and dynamic reservoir and constantly changing its antigenic profile, influenza remains an ever-present threat. Through vigilant immunization and the selected use of antiviral therapies, we can hope to significantly reduce the burden of this disease.









References*



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26. Skehel, J.J., D.C. Wiley. 2000. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Ann. Rev. Biochem 69:531-69.

27. Webster, R.G. 1998. Influenza: An Emerging Disease. Emerging Infectious Disease 4:436-441.

28. Zlotnik, A., O. Yoshire. 2000. Chemokines: a new classification system and their role in immunity. Immunity 12:121-7.

 

[Adcadet]

sorry that came out so messy. If you want a cleaner version, with nifty pictures, let me know and I can email it to ya.

Adcadet
acalvin@mmrf.org

 

[Adcadet]

Ya lost me. Mid-winter flu. Not sure about the seasonal variation in influenza in Europe, but in the US winter influenza epidemics have been a fact of life for as long as anybody can remember. At least since 1918. How on earth is a pharmaceutical company going to alter flu patters, unless you think they're creating, or isolating and releasing strains of influenza so as to get people sick?

The drug IS ALWAYS ready by November-December. And it's ready to counter most strains of this year's influenza BEFORE it even breaks out.

And how are they going to profit from viral infections that are rarely treated with drugs? (other than if some people, usually the elderly, get very sick and develop secondary infections which can be treated with antibiotics....unfortunately, those antibiotics tend to be cheap, relatively speaking).

see the paper I posted above. In a nutshell, the reason the vaccines are always ready is becaue the next year's predominate strains first appear in ducks. The CDC keeps ducks in China to monitor the strains. Each season they select three strains that they think are most likely to go global, and send these into production. If all goes well, we'll have a plentiful supply of vaccine by the time the virus hits us (us being the US specifically. Not sure about Europe).

They're not promoting diseases like releasing viruses and the likes. But they deliberately maintain the prices high, that's for sure. Gains are gains, everybody pays for his health.

 

[Adcadet]

oh, sorry. One last thing: yes, I absolutely agree that drug companies try to make as much profit as they can get away with. I also think they often use slimy methods that range from normal business practices, to questionable, to outright immoral.

 

[Buck]

Nicely explained Adcadet.

Can Influenza lead to other illnesses, such as sinus infections. Everytime I get a cold, I end up with a sinus infection. It's been that way since I was a boy.

 

[time]

Yes.

Taken together, these various changes trigger an immune response, affect the integrity of the mucosal layer and mucocilliary clearance, and interfere with the removal of other pathogens from the lungs which often leads to secondary bacterial pneumonia and produces cough

AFAIK, sinusitis sets in with the combination of increased discharge and poorer drainage resulting from inflammation - but it would be really great to hear Adcadet expand on this, because exactly the same thing happens to me.

 

[Handruin]

Holy good lord, that has to be a record for the longest single post Adcadet.

 

[Cliptin]

Holy good lord, that has to be a record for the longest single post Adcadet.

Don't we need to get that disertation reduced to a link to a web page?

 

[Adcadet]

Nicely explained Adcadet.

Can Influenza lead to other illnesses, such as sinus infections. Everytime I get a cold, I end up with a sinus infection. It's been that way since I was a boy.

Sorry for the length. I was actually going for the greatest number of consecutive posts in a thread.

What's the relation between influenza and other infections? I actually looked this up about a year ago, when it seemed I got influenza followed by a sinus infection (sinusitis) and was working in an infectious disease lab focusing on streptococcus pneumonia. Influenza disturbs the normal flow of mucus, and can also damage the cilliated cells that line the nasopharyngeal mucosa, making it easier for other things (other viruses and bacteria) to land and colonize the host. The most common cause of sinus infections is streptococcus pneumonia, which most kids are now being immunized against (at least the most common strains), mainly to prevent ear infections. As as been touched upon before, it's these secondary infections that cause most of the mortality (and possibly morbidity, but I'm not sure about this) from influenza.

 

[Adcadet]

Yes.

Taken together, these various changes trigger an immune response, affect the integrity of the mucosal layer and mucocilliary clearance, and interfere with the removal of other pathogens from the lungs which often leads to secondary bacterial pneumonia and produces cough

AFAIK, sinusitis sets in with the combination of increased discharge and poorer drainage resulting from inflammation - but it would be really great to hear Adcadet expand on this, because exactly the same thing happens to me.

For the record, sinusitis is simply inflammation of the sinuses. But usually when people refer to sinusitis they are refering to an infection. When refering to an allergy some people make a point of saying "allergic xxxx-itis (i.e.-allergic rhinitis)." Time is exactly right about the increased discharge (although discharge usually refers to what comes out...I think Time means "increased mucus production") and disturbed flow. But there's also a good deal of an inflammatory immune response involved. This would include release of interferons, inflammatory mediators such as serotonin (yes, the same serotonin found in the brain), histamine (the one us allergy sufferers tend to focus on), leukotrienes, kinnins, and cyclooxygenase metablolites. Just like an inflammatory immune response developes at other sites under other conditions (me being allergic to rats, of all things, swelling up wherever I've been scratched by their cute little paws; somebody developing horrible diahhrea after eating a bad hamburger; a cut on your hand swelling up and getting red and tender), so too can one develop in your nose. (the inflammatory immune response in the gut used to be my specialty; in fact, I've got a paper coming out in J. Pharmacology and Experimental Therapeutics on Kinnin in the gut).


By the way, sorry I didn't link that to my webpage, but I was at work and couldn't remember the settings to FTP it up to it. I'll work on getting my act together.

 

[Adcadet]

Aight, I figured out how to FTP stuff up to my webpage. In case anybody is interested, I've got some goodies for ya'all.

Adcadet's regular webpage: www.tc.umn.edu/~calv0016

Flu paper: www.tc.umn.edu/~calv0016/flu

Paper on Kinin-induced secretion in the gut: www.tc.umn.edu/~calv0016/kinin.pdf (just accepted today to J. Pharmacology and Experimental Therapeutics)

Paper on what I'm currently working on, just in case I've got a really lazy stalker: www.tc.umn.edu/~calv0016/fetal.pdf (also accepted for publication in J. Pharmacology and Experimental Therapeutics)

By the way, does anybody know of a good, free FTP program?

 

[Adcadet]

Aight, I figured out how to FTP stuff up to my webpage. In case anybody is interested, I've got some goodies for ya'all.

Adcadet's regular webpage: www.tc.umn.edu/~calv0016

Flu paper: www.tc.umn.edu/~calv0016/flu

Paper on Kinin-induced secretion in the gut: www.tc.umn.edu/~calv0016/kinin.pdf (just accepted today to J. Pharmacology and Experimental Therapeutics)

Paper on what I'm currently working on, just in case I've got a really lazy stalker: www.tc.umn.edu/~calv0016/fetal.pdf (also accepted for publication in J. Pharmacology and Experimental Therapeutics)

By the way, does anybody know of a good, free FTP program?

make that www.tc.umn.edu/~calv0016/flu.html

Don't know why the .html part is important, but i guess it is. Speaking of which, where's the edit botton?

 

[Buck]

Thanks for the links Dr.

 

[Prof.Wizard]

Nice links Adcadet, but may I remind you I'm a med student myself?! I admit I didn't "know" the history of the Influenza virus back to 1918, but bear with me, ALL diseases can be eradicated with good control and right vaccination the right moment.

I could go on and do the search and post you a thesis (as you did!) about the slime underworld of pharmaceutical companies, but since you seem so interested (and since I'm in exam period!) I'll leave you do the search alone.

Interesting topic to search as well: AIDS drugs and 3rd-world countries. Then we'll see if the pharmaceutical companies care ONLY about profits or what.

 

[Prof.Wizard]

And I repeat: I didn't say the pharmaceutical companies release viruses or other pathogen agents. They just help to make them survive for next year.

 

[jtr1962]

It can be argued that the overuse of antibiotics is helping to create more resistant strains of bacteria and virii. And guess who produces antibiotics? No doubt in my mind the drug companies, aided by doctors, are helping to create these resistant bugs on purpose. They get more money now for antibiotics, and more money in the future for the stronger strains that current antibiotics can't combat. In time one could imagine germs so strong that you'll need to receive a steady supply of anitbiotics from birth.

Not to mention the overuse of all sorts of drugs like Ritalin for imaginary social disorders like ADHD, social anxiety disorder, plus a few others whose exact names escape me now. These drugs mask the symptoms of these so-called disorders-they don't get to the root causes, if in fact most of them could even be considered disorders by any reasonable person. ADHD in particular is the biggest farce perpetuated on us. These are mostly perfectly normal children whose parents and teachers just can't be bothered with them, so they get zombified with drugs.

BTW, what on earth does this have to do with most evil software companies? Maybe we should vote on most evil drug companies instead. :evil:

 

[Prof.Wizard]

BTW, what on earth does this have to do with most evil software companies? Maybe we should vote on most evil drug companies instead. :evil:

Hehe, you're right.
It all started by a post of mine somewhere further up where I speculate that the Antivirus companies produce the antivirus-definitions along with some viruses as well! I believe the same happens with pharmaceutical companies. In the name of profit, they're not really interested in completely eradicating a pathogen agent-based disease. And this, I presume is one of the reason we still have global pandemics and expensive drugs.

 

[Adcadet]

Nice links Adcadet, but may I remind you I'm a med student myself?! I

I don't care if you're the secretary general of the World Health Organization. I believe Time had some great points here, and I seem to remember him not having any formal training in the health sciences (forgive me if I'm wrong Time).

I admit I didn't "know" the history of the Influenza virus back to 1918, but bear with me, ALL diseases can be eradicated with good control and right vaccination the right moment.

Disease eradication requires a number of key points. First, you must have an effective method of preventing infection, usually a vaccine. Note that no all diseases are effectively prevented by vaccines. Note that many diseases can persist as latent infections (i.e.-HIV). Note that many diseases have many large, poorly-defined reservoirs and non-human hosts (what are you going to do, vaccinate every bat to erradicate rabies?). Note that not every vaccine given will prevent the disease. Polio is a disease that meets these requirements, and we're still trying to erradicate polio. And, just to be technically correct, not all diseases are caused by infection with, or intoxication by, another organism. How on earth are you going to eradicate heart disease?

I could go on and do the search and post you a thesis (as you did!) about the slime underworld of pharmaceutical companies, but since you seem so interested (and since I'm in exam period!) I'll leave you do the search alone.

I'm not interested in defending the pharmaceutical companies except against cases that are absolutely absurd. As students of medicine, let's at least get the facts right.

Interesting topic to search as well: AIDS drugs and 3rd-world countries. Then we'll see if the pharmaceutical companies care ONLY about profits or what.

Yeah. Agreed.

 

[Adcadet]

It can be argued that the overuse of antibiotics is helping to create more resistant strains of bacteria and virii. And guess who produces antibiotics? No doubt in my mind the drug companies, aided by doctors, are helping to create these resistant bugs on purpose. They get more money now for antibiotics, and more money in the future for the stronger strains that current antibiotics can't combat. In time one could imagine germs so strong that you'll need to receive a steady supply of anitbiotics from birth.

Agreed. And from what I've seen, the vast majority of people who study this topic believe the evidence that antibiotic resistance is a problem and is being made worse by the pharmaceutical industry. In fact, this topic is a staple topic in infectious disease courses in schools of public health now.

 

[Prof.Wizard]

I don't care if you're the secretary general of the World Health Organization. I believe Time had some great points here, and I seem to remember him not having any formal training in the health sciences (forgive me if I'm wrong Time).

And I'm not impressed by your cut&paste posting of the Influenza-virus history. I'm not a layman, and yes I still believe that pharmaceutical companies are NOT helping full-steam as I believe there are doctors who don't do their job right and as I believe America will bomb and invade Iraq to lay its hand on its petroleum fields.

OK, now you can post me (cut & paste me to be technically correct, as you said, because you're good in this) about the minimum requisites to become a licensed MD, including being ethic and caring practitioner, but now don't come and tell me all doctors are nice and good. Do the analogy for the SmithKline now.

Disease eradication requires a number of key points. First, you must have an effective method of preventing infection, usually a vaccine. Note that no all diseases are effectively prevented by vaccines. Note that many diseases can persist as latent infections (i.e.-HIV). Note that many diseases have many large, poorly-defined reservoirs and non-human hosts (what are you going to do, vaccinate every bat to erradicate rabies?). Note that not every vaccine given will prevent the disease. Polio is a disease that meets these requirements, and we're still trying to erradicate polio. And, just to be technically correct, not all diseases are caused by infection with, or intoxication by, another organism. How on earth are you going to eradicate heart disease?

First you defeat pandemics, then epidemics, and then you try to confine endemics and other hosts. I don't say it's easy, but the "common cold" gives "common profits" to the pharmaceutical kartel.
And since we're talking about microbe-related diseases, forgive me about my use of the term disease.
Polio is fairly defeated in respect to the past.

I'm not interested in defending the pharmaceutical companies...

I doubt that. You know, you're so naive you remind me tobacco-company sponsored research about lung cancer. Pharmaceutical companies are for-profit companies. Only that they can't go out shouting it because of the public outcry.

Yeah. Agreed.

I'm happy you agree here. For you're pleasure:
http://www.commondreams.org/views01/0212-01.htm

 

[Adcadet]

I'm not interested in defending the pharmaceutical companies...

I doubt that. You know, you're so naive you remind me tobacco-company sponsored research about lung cancer. Pharmaceutical companies are for-profit companies. Only that they can't go out shouting it because of the public outcry.

Please explain how I'm being so naive? So far I've only tried to debunk your idea that somehow the pharmaceutical industry is behind the winter influenza epidemics and the coincidence of the appearance of each year's vaccine right before the epidemic hits, in addition to a few of your comments that are factually incorrect. To compare this to the tobacco industry's coverup of the link between disease and smoking is odd, if not insulting.

We seem to agree that the pharmaceutical industry seeks to maximize their profits, and are not really interested in eradicating a disease that makes them money.

 

[Prof.Wizard]

Please explain how I'm being so naive? So far I've only tried to debunk your idea that somehow the pharmaceutical industry is behind the winter influenza epidemics and the coincidence of the appearance of each year's vaccine right before the epidemic hits, in addition to a few of your comments that are factually incorrect. To compare this to the tobacco industry's coverup of the link between disease and smoking is odd, if not insulting.

We seem to agree that the pharmaceutical industry seeks to maximize their profits, and are not really interested in eradicating a disease that makes them money.

My whole speculation (repeat: speculation) about winter-time influenza and other pathogen-related diseases and the involvement of pharmaceutical companies comes from the part you said in bold, which we happen to agree.

Everyone can believe what he wants. You'll never find a Symantec paper (like you influenza-history) where it says they deliberately develop and administer virii either. But then again you'll never find a Bush-administration official admitting the war is all about the black gold. It's all about constructing a theory (more or less evidence-based) to advocate the other side and explain suspect facts.

Speculations arise from small coincidences, small facts that are too much disturbing (or outright weird) to pass unnoticed. I'm not a fan of "X-Files" nor "Conspiracy Theory" of Mel Gibson is my favorite movie. My favorite philosopher is Descartes just to make you understand I'm not prone to gossip and unnecessary blah-blah. But damn it, pharmaceutical companies don't help this world as we would love them do. Fact.

PS. The most well-respected scientific journals (ie. Nature, etc.) now require the authors to disclose the sponsoring source. Scientists are (and should be!) nowdays skeptical about results sponsored by pharmaceutical companies.

 

[Cliptin]

My cats breath smells like cat food.

PS. AD, I can be your editor. Just ask. Just don't punch me too hard or too often.

 

[Adcadet]

My cats breath smells like cat food.

PS. AD, I can be your editor. Just ask. Just don't punch me too hard or too often.

Thanks. But why would I punch?

So, can I just start emailing you stuff for you to edit and post? That would be great. Two years ago I wrote this 40 page paper on vaccines...think you could read it over and post it here for PW?

 

[Mercutio]

My cats breath smells like cat food.

I thought CityK had the Ralph Wiggum avatar...

 

[Prof.Wizard]

Two years ago I wrote this 40 page paper on vaccines...think you could read it over and post it here for PW?

Cut&Paste Cut&Paste Cut&Paste
:stpd:

 

[e_dawg]

Nicely explained Adcadet.

Can Influenza lead to other illnesses, such as sinus infections. Everytime I get a cold, I end up with a sinus infection. It's been that way since I was a boy.

I think you are confusing the flu with the common cold. 80% of the time people say the have "the flu" (flu = infected with influenza), they really mean they have a "cold". Most of the time people are not infected with the influenza virus, but rather with the Rhinovirus, which is responsible for the bulk of the "colds/flus" that humans get. Sinus infections are part of the pathology of rhinoviral infections (i.e., it's part of the progression of getting "a cold").

Having said that, if you do get infected with influenza first, that could predispose you to getting a secondary rhinoviral infection, and vice-versa.

And FYI, very few people actually need or could possibly benefit from flu vaccines. Like I said, 80% of the "colds" out there are due to rhinovirus. And of the influenza infections out there, chances are maybe a third of them could never have been prevented by getting a vaccine anyways. The vaccines usually concentrate on a single strain that's predicted by the WHO to be dominant over the next year, but they are not always right, nor is there any assurance that the influenza strain you will be exposed to will be the same as the strain the vaccine was created for.

I'll let everyone else get the flu vaccine. I'll just practice good hygeine (washing my hands frequently, not rubbing my eyes or nose), stay away from sick people, and take my chances.

 

[Adcadet]

Nicely explained Adcadet.

Can Influenza lead to other illnesses, such as sinus infections. Everytime I get a cold, I end up with a sinus infection. It's been that way since I was a boy.

I think you are confusing the flu with the common cold. 80% of the time people say the have "the flu" (flu = infected with influenza), they really mean they have a "cold". Most of the time people are not infected with the influenza virus, but rather with the Rhinovirus, which is responsible for the bulk of the "colds/flus" that humans get. Sinus infections are part of the pathology of rhinoviral infections (i.e., it's part of the progression of getting "a cold").

Having said that, if you do get infected with influenza first, that could predispose you to getting a secondary rhinoviral infection, and vice-versa.

And FYI, very few people actually need or could possibly benefit from flu vaccines. Like I said, 80% of the "colds" out there are due to rhinovirus. And of the influenza infections out there, chances are maybe a third of them could never have been prevented by getting a vaccine anyways. The vaccines usually concentrate on a single strain that's predicted by the WHO to be dominant over the next year, but they are not always right, nor is there any assurance that the influenza strain you will be exposed to will be the same as the strain the vaccine was created for.

I'll let everyone else get the flu vaccine. I'll just practice good hygeine (washing my hands frequently, not rubbing my eyes or nose), stay away from sick people, and take my chances.

Good points. But there is good evidence that infection with influenza does predisponse one to getting other infections due to the changes in mucocilliary clearance at least. And each year's influenza vaccine is actually a trivalent vaccine, though often two of the three are the same as the year before. And as cited above, the net societal cost (dollars) is about zero for immunizing the general population. Hence the focus on immunizing those most at risk. However, in terms of dollars spent per disability-adjusted life year saved, the influenza vaccine (not that there is just one exactly; of course this all depends on the match between what's in the vaccine and the year's circulating influenza viruses) is one of the more economical methods of reducing morbidity and mortality. So, should you get your influenza vaccine each year? Well, if you're an otherwise healthy individual, it probably won't save you any money. But for extending your healthy life, it is probably one of the better things you can do. Generally the three most cost-effective interventions a physician can provide are birth control pills, immunization, and smoking cessation counseling.

 

[e_dawg]

You left out genetic profiling and engineering, but that's a whole other can of worms

 

[Buck]

What are the difference in symptom between something as a rhinoviral infection or influenza?

 

[e_dawg]

Flu (influenza) = severe muscle aches, extreme tiredness, chills, fever
Cold (rhinovirus) = typical sore throat, runny nose, cough, chills, fever, but you can actually get out of bed if you really wanted to (influenza kicks your ass so bad and is sometimes debiliatating to the point where you can't get out of bed)