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H7N9 discussion thread: January 24, 2014 to Feb 5 2014 (closed)

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  • #61
    Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

    Thank you for your response. I am digesting it!

    Comment


    • #62
      Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

      Originally posted by Vibrant62 View Post
      Thank you for your response. I am digesting it!
      For the longer answer, you can access many of our deeply-linked, 200+ Open-Access, Full-Text pH1N1, sH3N2 and eH7N9 publications, recently with active maps, from the FT Genetic Analysis sub-forum.

      Comment


      • #63
        Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

        What's starting to worry me is: where are the children and teenagers this year? Last year, if I can count, we had 8/150 people under the age of 20 (all but one of whom were actually under 10). This year, only one (case 200, the 5yo) out of 110, so far.

        Could be chance, but could be that this year, children are less likely to be tested than they were last year. Or less likely to be positive. Or, of course, they could be genuinely less likely to be infected for some reason. I hope they aren't the missing vector...

        Comment


        • #64
          Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

          Chinese New Year is on Jan.31.

          we are in the preparation phase
          maybe children are traditionally not involved in preparation

          last year the cases only started in greater numbers in April
          (those that went into the statistics)
          I'm interested in expert panflu damage estimates
          my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

          Comment


          • #65
            Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

            New Year is all about family in China. It is the biggest human migration at any one time on earth. So, yes, it is to some degree about children. It is also about paying off any debts, and pretty much starting a new chapter of life. That means a lot family gatherings and community gatherings. Sometimes in the form of big parades.
            Please do not ask me for medical advice, I am not a medical doctor.

            Avatar is a painting by Alan Pollack, titled, "Plague". I'm sure it was an accident that the plague girl happened to look almost like my twin.
            Thank you,
            Shannon Bennett

            Comment


            • #66
              Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

              Mathematician, here is some info for you.

              Children are sent to pediatric hospitals. Many of these hospitals do not come equipped with the latest technology. Nor do they have the labs and technicians needed for a correct diagnosis. They assume H1N1 not H7N9. We have a huge number of children in China that are very sick. Clinics are overflowing. Hospitals are reported to have a great many pediatric pneumonia cases.

              The following is part of the Chinese New Year thread. The reporter explains the difficulty of diagnosing patients and he admits that cases are missed. He also states that they don't suspect H7N9 if they don't say they had contact with live birds in a questionnaire. As 30% never admit to being exposed to live birds it means that the only patients that are selected for are those who have come close to poultry. Those 30% are then not treated until they become very sick as they are not on the probable list to begin with. This in reality skews all of the data. If you only look for people who have been in contact with chickens, it then means that many who do actually have the disease and die, are never put on the list of patients. In one underlined section below the author suggests the patients may have faulty memories or perhaps have died and the family could not then be trusted to remember where the patient came into contact with live birds. The mindset is cast in concrete-only those with contact to live chickens are infected with H7N9. The rest are aberrations and just can't remember where they came into contact with live birds. Only God knows how many are actually sick.

              Expert: During the Spring Festival is not an outbreak of H7N9

              January 28, 2014 07:28:49 Source: Beijing News
                
              Yesterday, the National Health and Family Planning Commission meeting of people infected with H7N9 avian influenza interview meeting, the CDC, the National Influenza Center experts said, because there is no evidence of large-scale spread of H7N9 between man and man, does not predict the Spring Festival mobility causing the outbreak.
                
              According to Xinhua News Agency statistics, January 1 to 26, the country has confirmed cases of human infection with H7N9 avian influenza 96 cases, three provinces of Zhejiang, Guangdong and Shanghai confirmed 83 cases, 20 deaths, including Zhejiang death in 12 cases, 4 deaths in Guangdong, Shanghai 4 deaths, including a medical staff.
                
              Experts believe that the higher H7N9 fatality rate, and the current number is close to the onset of the peak levels of last year.
                
              Cases have been close to the peak levels of last year
                
              Yesterday, the State Planning Commission, David held on H7N9 avian influenza group interview. Chinese Feng Zijian, deputy director of the CDC, said although a lot of the upcoming Spring Festival will cause movement of persons, but does not increase the probability of infection of H7N9.
                
              Shu Yuelong, director of the National Influenza Center also believes that, because there is no evidence of large-scale spread of H7N9 will be between people, that this virus does not have the biological basis of interpersonal widespread. Meanwhile, there is no variation in the virus itself, as long as the prevention and control measures in place, the risk will be lower and lower. "There are sporadic cases will now see the situation will continue, but in the entire large outbreaks during the Spring Festival, the situation will not happen quickly spread."
                
              He said that at present the number of sporadic cases of H7N9 have been close to last year's peak levels. He believes that people all over the fowl of exposure measures, efforts to control the spread of the virus, the scope of the epidemic will determine the future direction.
                
              Feng Zijian said, H7N9 is relatively high in the East China region, the presence of the virus spread between levels and consumption of poultry, poultry certain relationship, in addition, after the H5N1 avian influenza virus has a high incidence in winter and spring characteristics, H7N9 seems there are some seasonal touch.
                
              He suggested that people try to avoid contact with live poultry, it is recommended to purchase, consume chicken, chilled, replace the live bird markets. Live poultry slaughter process, if unavoidable, wash your hands as soon as possible after exposure may also reduce the chances of infection. Older people with low immunity, with particular attention.
                
              Mortality or below the H5N1 virus
                
              According to Chinese Feng Zijian, deputy director of the CDC introduced since January 1, 2014, the country reported cases of human infection with H7N9 avian influenza 96 cases and 19 deaths. If you start to last year, the country has reported 240 cases, more than 60 cases of death.
                
              "Fatality rate is relatively high." Said Feng Zijian. The number of cases and deaths in the current figures, H7N9 case fatality rate of 20% -30%.
                
              According to Shu Yuelong introduced, this figure is lower than the H5N1 fatality rate, which reached 60%. He said that from the perspective of the characteristics of several viruses, H1N1 viruses belonging to interpersonal communication, and H3N2 is similar. This will cause a lot of people infected with the virus, but the mortality rate is very low.
                
              But Feng Zijian pointed out that this is not a strict 20% -30% mortality scientific sense. First, there are still patients continued treatment; Also, the patient is currently found mainly severe, and some patients the presence of light, they may not visit, or visit the doctor did not suspect, disease picture is not known. "We see the molecules, but there is no accurate information on the denominator."
                
              ■ response
                
              The CDC
                
              "Doctors infection H7N9" only confirmed one case
                
              Recently, the network continued rumors that there are doctors in different parts of the virus H7N9 infection and died. Yesterday, Feng Zijian clear response, "Dr. infection around the H7N9" is not true, the current emergency department Shanghai confirmed only one case of H7N9 infection surgeon.
                
              However, the path of infection and cause of death for doctors in Shanghai, said Feng Zijian is still under investigation. He said that did not find its onset before contact with H7N9 patients, also found no direct contact with live birds and so on. However, because this doctor had died when diagnosed only by family, colleagues asked, still need further investigation.
                
              ■ Focus
                
              1
                
              What is a limited non-sustained person to person?
                
              Experts said the man found only a few cases of human transmission, not sustained transmission
                
              National Planning Commission, the day before the release of Wei 2014 edition H7N9 treatment program that specific route of transmission of H7N9 avian influenza virus can spread through the respiratory tract or close contact with infected poultry infected secretions or excretions obtained; or through contact with virus-contaminated environments to propagate people; do not rule out limited non-sustained person to person.
                
              H7N9 spread of only 0.09 basis the number of
                
              Chinese Feng Zijian, deputy director of the CDC, said, "limited human to human transmission" is a relatively continuous and effective person to person, the occasional occurrence of secondary cases, the vast majority of patients occurs only two generations, three generations occur rarely or almost never more patient. And sustained human to human to human transmission is effectively the same meaning, that there is more on behalf of patients, such as three generations of four generations, resulting in multiple cases of infection in a community. It more professional point of Medicine will be limited measure, called a continuing basis the number of indicators spread. When active person to person, the foundation will spread more than a few, that is, a patient as a source of infection, can infect an average of more than 1 person. The index is less than 1, it will not continue to spread.
                
              Feng Zijian said, according to the H7N9 research, epidemiological investigation, mathematical model count is the number of basis spread was 0.09. At present, very few cases of H7N9 found in the second generation, and only a few cases, no one is three generations.
                
              "There is no need to over-interpret secondary cases."
                
              Shu Yuelong, director of the National Influenza Center said there was no need to read too much into secondary cases. Currently, patients in close contact with a chicken infected with H7N9 virus or contaminated environment, is a generation of cases; close contact with a patient, a second-generation cases. But from the perspective of Virology, there is no difference.
                
              2
                
              What is the difficulty to deal with H7N9?
                
              Experts say the virus prevalence among asymptomatic poultry, harder than H5N1 prevention
                
              Shu Yuelong said, and compared with H5N1, H7N9 is more likely to infect humans, highly pathogenic, but it is popular among poultry are asymptomatic, do not see any symptoms, it is relatively harder to guard against H5N1.
                
              Hospitals generally weak ability to detect H7N9
                
              People's Hospital, director of respiratory medicine accounted for a high that birds appear healthy but for people with a highly pathogenic virus, this is a big challenge. Only patients with very early symptoms of fever, clinicians make the diagnosis very difficult.
                
              He said the doctor for questioning to strengthen epidemiological history, such as live bird markets have not been to, the availability of live poultry trade, with or without contact with live poultry populations transactions, ask the doctor to improve awareness. In addition, enhancements to the screening and identification of clinical symptoms, thus strengthening the joint between medical institutions and the prevention and control of disease control agency, timely submission of samples to the CDC. Previously, the disease is often severe pneumonia talent submission for mild colds less censorship.
                
              For H7N9, medical institutions generally weak detection capabilities.

              Because it requires a very high condition, such as to have a molecular biology laboratory, have the appropriate level of protection to handle specimens. Also detects, to avoid contamination, the instrument is also more expensive and can not be clinically charges. Therefore, free testing is difficult. These issues need further discussion.
                
              Doctors said it is difficult to achieve 100% detection rate
                
              Ditan Hospital, director of infectious disease treatment center Li Xingwang said, according to 2013, 2014, treatment programs, medical institutions qualified to be detected, there are no conditions to stay specimens. Like Tamiflu and other antiviral drugs effective against the virus, but the premise is the sooner the better. For flu-like symptoms, especially fever, cough and other lower respiratory tract symptoms, even though tested negative, also advocated giving antiviral therapy. However, each patient to achieve 100% detection rate, difficult. Even if detected, there are a variety of reasons could cause results to be negative.
               
              Why no history of exposure to infected poultry?
                
              Resulting in the death of an individual patient can not determine whether contact with live poultry
                
              Feng Zijian introduction, 70% of patients had a history of exposure found in poultry. Most cases are not family autotrophic contact with infected birds, but to the town, the town's bazaars contacting live poultry. For each case found in the CDC, have made serious epidemiological investigations, but there is a problem that I am asking the patient survey is the most reliable.
                
              Feng Zijian said, but some patients when the diagnosis has been in critical condition, the individual who has died can not investigate himself, and therefore can only investigate relatives and colleagues. But difficult for outsiders to fully restore all of the patient's own life experiences. Thus, 30% of patients did not find the presence of live poultry contact history, exposure history, this is a very important reason. In addition, some patients live birds I can not recall memories of history. This is the common scenario epidemiological investigation.
                
              4
                
              H7N9 vaccine developed any progress?
                
              Not yet developed, pre-clinical studies have been completed some companies
                
              Shu Yuelong said that in vaccine research and development in this area, some companies have completed preclinical studies, to be carried out to apply to declare. Vaccine development is very important, in order to develop a vaccine to respond to crises that may arise. Our current H7N9 virus is not very understanding, such a vaccine may produce side effects such experiments should be carried out strictly.
                
              Shu Yuelong said the problem of resistance against the virus, the current monitoring point of view, H7N9 Tamiflu and other antiviral drugs also are sensitive. Encourage doctors to reduce mortality and timely use of antiviral drugs. For flu-like illness, especially high-risk groups, the elderly, pregnant women, there are flu-like symptoms have anti-viral therapy.
                
              As to whether the use of antiviral drugs can lead to drug-resistant viral longevity issues, Shu Yuelong said, you do not have anti-viral treatment, as the global epidemic of the virus, the virus also appear resistant.
                
              5
                
              Whether the H7N9 virus mutation?
                
              Experts say the virus mutation was not found no difference with last virus
                
              Shu Yuelong said, according to the epidemic analysis, the basic conclusion is that the current pandemic virus and April of last year is the same, that there was no public health significance of variation, no significant difference. From the perspective of viral sequence analysis, we did not change the risk assessment, appeal, spread of power, such as drug-resistant viruses have not found changes. Prevention and control program in accordance with the new version, stressed the importance of virus monitoring, the purpose is to monitor changes in the virus, timely monitoring of how it will change in the end, highly concerned about the possibility of variation in trends and, if the first time be able to see, is our greatest success.
                
              Shu Yuelong said relatively H5N1, H7N9 more susceptible to a number of people. In accordance with existing knowledge, can not make accurate predictions about the trend of variation of a virus, only closely monitored.
                
              6
                
              Prevention and control programs in place to adjust the new version?
                
              Areas close contact management, information reporting to adjust
                
              Feng Zijian said, the new treatment programs, prevention programs have been revised, did not make a big adjustment. Prevention and control program adjustments where there are few, some measures were emphasized, such as close contacts management, information reporting, the timely provision of strains, such as viral sequences submitted.
                
              Feng Zijian said some places for H7N9 prevention and control has taken various measures. We also evaluate the effectiveness of different control measures. Like other departments such as the Department of Agriculture, is also actively studying longer-term, more fundamental measures.
                
              Feng Zijian said, we have already put forward proposals to change consumption patterns, try not to make a habit of live poultry consumption, purchasing chicken, chilled and so on. In addition, poultry farming model, but also upgrading.
                
              ■ news
                
              AQSIQ
                
              Temperature over 38 ℃ and contacts are required sampling and testing of poultry recommended to postpone travel

              Yesterday, this AQSIQ issued an urgent notice requiring the port inspection and quarantine people infected with H7N9 should bird flu prevention and control, temperature over 38 ℃, and a history of close contact with poultry within seven days and must be sampled pathogen detection to prevent cross-border spread of the epidemic.
                
              AQSIQ emphasized that discovered or reported fever, cough, difficulty breathing and other flu-like symptoms exit personnel, timely epidemiological investigation and medical investigation. Focus on strengthening the monitoring of outgoing personnel, particularly personnel from the H7N9 cases occurred exit area.
                
              Among them, the temperature over 38 ℃, and seven days a history of close contact with poultry, must be sampled pathogen detection, it is recommended to postpone their travel, transfer the designated hospital for treatment. Refusing to postpone the trip, may be required to give reasons in writing, inform the precautions required to wear N95 masks provide and to inform transport operators to take protective measures.

              zhttp://news.xinhuanet.com/tech/2014-01/28/c_126071520.htm <!-- / message --><!-- sig -->






              http://www.flutrackers.com/forum/sho...d.php?t=216679
              Please do not ask me for medical advice, I am not a medical doctor.

              Avatar is a painting by Alan Pollack, titled, "Plague". I'm sure it was an accident that the plague girl happened to look almost like my twin.
              Thank you,
              Shannon Bennett

              Comment


              • #67
                Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

                Originally posted by Mathematician View Post
                What's starting to worry me is: where are the children and teenagers this year? Last year, if I can count, we had 8/150 people under the age of 20 (all but one of whom were actually under 10). This year, only one (case 200, the 5yo) out of 110, so far.

                Could be chance, but could be that this year, children are less likely to be tested than they were last year. Or less likely to be positive. Or, of course, they could be genuinely less likely to be infected for some reason. I hope they aren't the missing vector...
                Here is a table of approximate count of infections by age group by flu season.

                Click image for larger version

Name:	H7N9 Age Group Table 20140128.jpg
Views:	1
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                http://novel-infectious-diseases.blogspot.com/

                Comment


                • #68
                  Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

                  Thanks, Shannon and gsgs. Yes, I understand why we'd expect most cases (especially most mild cases) to be missed. What's still not quite clear to me is why the percentage of children this year is so much smaller than the percentage of children last year. If you're a child case of H7N9, are you - and if so, why? - more likely to be missed in January 2014 than in April 2013?

                  There could be any number of explanations, or it could be chance requiring no explanation. But here's a possibility that would be worrying: this year, the bounds of who gets tested are more tightly drawn than they were last year - you have to be more critically ill, or have closer poultry contact, say, for anyone to test you than you did last year. This might result in the same number of reported cases per week as last year [as we see], but picked from a much larger number of actual cases [which we don't want to be the case] - and we'd expect to be missing proportionally more of the milder cases, which might result in fewer children in the case list [as we see]. So it might be that the near-absence of children from this year's list is a sign that China is missing many more cases now than it did in 2013.

                  Comment


                  • #69
                    Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

                    last April they also tested lots of contacts.
                    That may have slowed down.
                    Now they just test at the hospital (?)
                    I'm interested in expert panflu damage estimates
                    my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

                    Comment


                    • #70
                      Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

                      Originally posted by gsgs View Post
                      last April they also tested lots of contacts.
                      That may have slowed down.
                      Now they just test at the hospital (?)
                      Could be, yes, and given that they're finding roughly the same number of cases as at the peak of last year, this would be worrying. Against any such hypothesis: in that case, other things being equal, we'd expect the case fatality rate to be higher this year than last year (because of missing mild cases who were going to recover anyway and catching only the severe ones who were more likely to die), which isn't what is being reported so far.

                      Comment


                      • #71
                        Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

                        According to reports about 5 or 6 people have recovered since December. In this 2nd wave there are 11 announced deaths. This leaves approximately 107 currently hospitalized. Most were hospitalized in critical condition so.....??

                        Comment


                        • #72
                          Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

                          Originally posted by NS1 View Post
                          Sadly, today is the baseline because most prior information has been gathered so haphazardly as to render it incomparable. If we don't modify the process soon, even today will be a poorly functioning baseline for decision makers 5 years from now.

                          Polymorphisms that move between serotypes do not always correlate to functionally equivalent outcomes. An infective flu reservoir in a certain host determines the outcome. By studying with great scrutiny the disease process, the deepest picture of the pathogen and the human genetics of the host, science will begin to build a foundation around Gain of Function research.

                          That research will show patterns of polymorphisms, sets, that travel together and correlate to specific outcomes in identifiable scenarios. Although singleton changes at times have a dramatic impact, understanding the set of related changes is much more important to predicting the system.

                          How that information is used at the policy level will turn the tide of human health, either for the benefit of the citizen or against them.
                          Great post. In full agreement.

                          The situation - as I understand it (anyone feel free to differ)- is broadly that the 144 HxNy combinations in Type A AI (I am ignoring the new bat strains as I think they are removed from this mixing pool) fall into two broad groups one group (the larger 'primary' group) mainly circulates in Anseriformes (fresh water birds - Ducks) and the secondary group in Charadriiformes (shore birds - Gulls & waders). There is mixing between the groups, and with other Aves Orders, but each of the circulating H & N combinations has a 'home base' in one (or occasionally both) of these two groups. The primary group is of greater importance to mammalian infections as 'our' HAs are mainly from this group.
                          Both groups are ideally suited to the oral-faecal transmission route as they feed in the water into which they defecate, they often congregate into dense flocks (high viral loads) and include migratory species (wide geographic spread).

                          The first thing to note is that these birds take their flu sero-types in parallel while for us we seem to take them in series, each pandemic largely killing off its predecessor (yes I know we now have two due to the reintroduction of H1N1 in the '70s). Infection in the primary hosts is normally mild or asymptomatic allowing the sub-types in each group to mix freely with no real barrier to multiple infection in one host.

                          Flu's route to genetic diversity is two fold. Firstly the sloppy polymerase allows for poor fidelity in copying the vRNA creating lots of SNPs and secondly it does not seem to care much about virion assembly and is happy to mix RNAs from different infections leading to reassorments. Human reassortment have a very limited pallet as there are only two sero-types - plus extremely rare zoonotic infections. Most changes lead to unfit viruses but, as flu is parasitic, the cost of all these duds are born by the host not the virus.

                          As we have only had a few flu pandemics recently enough for us to know how to sub-type them and we have only very recently got surveillance in place to watch human zoonotic flu infections amongst the background we do not really understand the dynamics of pandemic emergence.
                          1918, 1957, 1968 and even 2009 all look like they reassorted straight into their pandemic form - or at least we did not spot them until there was sustainable H2H. For the first time we are now sequencing enough to spot the odd zoonotic infection amongst the background. H5N1, H7N9, H5N8, H10N8 are all ongoing and many others in the past. I think it unlikely that this is new behaviour, it is just we did not have the tools to look.

                          Now thinking a little about the 'zoonotic edge' of the avian virus pool.
                          For an infection to occur in a human they need to be exposed to an AIV that, as an absolute minimum, can infect a human cell most can't.
                          How do they get to the point where they can?
                          They drift, genetically, around the strain consensus by the methods discussed above. Of all those sero-types circulating at any given moment some will be close to an infectious form (in humans) and most will be far away. Also the line is not clear and most infections occur in either people who have been exposed to a very high viral load (farmers, vets etc.) or were immunocompromised to some degree. In an earlier post I pointed out pigs could be infected with H7N9 experimental, given a high enough dose at inoculation, but would not spread the infection either by contact or aerosol transmission.

                          If we look at H7N9 as an example there seem to have been a number of reassortments leading to a virus of which A/Anhui/1/2013 is representative. Presumably the parents strains were somewhere near my 'zoonotic edge', prior to their latest changes, and their progeny is now very close to the edge.
                          What happens now?
                          More change (hey it's flu' what did you expect). As the virus is not showing efficient H2H, in it current form, the AI strain will continue its genetic meander in its primary host(s) and either drift away from my 'zoonotic edge' or over it into pandemic territory (away from the edge should be more likely as it is likely closer to the bird index). The alternative route is that one of these human infection will develop, within its quasi-species, a variant that is better adapt and successfully start a cluster. The starting virus now is already a bit better adapted and its quasi-species can then capitalise on the advantage and jump again etc. A virus replicating in a host to which its is ill adapted will be under severe selection pressure and favour mutations that improve replication in that host (but not necessarily adaptations that improve transmission to a new host).

                          I am sorry this has ended up being so long but I thought it was important to cover as many aspects as possible as they all inter-relate. I hope some one will be able to pick holes in the logic of my model - it's how I learn and improve my mental model.

                          Edit:
                          This link is to
                          Phylogenetic Diversity and Genotypical Complexity of H9N2 Influenza A Viruses Revealed by Genomic Sequence Analysis
                          the reason I have added it is the graphic on page 7 which shows the RNA segments colour coded and tracks them as they reassort, divided, die out and generally morph their way from 1966 to 2008.

                          Comment


                          • #73
                            Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

                            Short Answers
                            Need Not
                            Apply

                            As Mr. Jackson has shown, no short answers may be applied by a thoughtful person when a complex system is under investigation with so little fact gathered by the scientific community.

                            The 'zoonotic edge' is a fine term for those genotypes capable of a host-species switching event. We've characterised that 'viral work area' in the past as a type of thermocline, the point were two separate bodies (Av and Hu) meet and very slightly intersect, creating in that 'Av ∩ Hu' an entirely different dynamic than existed in either separate body.

                            'Zoonotic edge' models better for the mathematicians, doesn't it. The 'Net Set' of polymorphisms, those found at the zoonotic edge netted to the superset of each standing body, guides interaction studies and directionality evaluations at any point in time.

                            Comment


                            • #74
                              Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

                              Wow! Nicely stated. While thought was required (those little grey cells need exercise anyway), it was a nice step-by-step explanation of how flu virus changes over time.

                              Quote:
                              <TABLE cellSpacing=0 cellPadding=6 width="100%" border=0><TBODY><TR><TD class=alt2 style="BORDER-TOP: 1px inset; BORDER-RIGHT: 1px inset; BORDER-BOTTOM: 1px inset; BORDER-LEFT: 1px inset">Originally Posted by NS1
                              Sadly, today is the baseline because most prior information has been gathered so haphazardly as to render it incomparable. If we don't modify the process soon, even today will be a poorly functioning baseline for decision makers 5 years from now.

                              Polymorphisms that move between serotypes do not always correlate to functionally equivalent outcomes. An infective flu reservoir in a certain host determines the outcome. By studying with great scrutiny the disease process, the deepest picture of the pathogen and the human genetics of the host, science will begin to build a foundation around Gain of Function research.

                              That research will show patterns of polymorphisms, sets, that travel together and correlate to specific outcomes in identifiable scenarios. Although singleton changes at times have a dramatic impact, understanding the set of related changes is much more important to predicting the system.

                              How that information is used at the policy level will turn the tide of human health, either for the benefit of the citizen or against them.

                              </TD></TR></TBODY></TABLE>
                              Great post. In full agreement.

                              The situation - as I understand it (anyone feel free to differ)- is broadly that the 144 HxNy combinations in Type A AI (I am ignoring the new bat strains as I think they are removed from this mixing pool) fall into two broad groups one group (the larger 'primary' group) mainly circulates in Anseriformes (fresh water birds - Ducks) and the secondary group in Charadriiformes (shore birds - Gulls & waders). There is mixing between the groups, and with other Aves Orders, but each of the circulating H & N combinations has a 'home base' in one (or occasionally both) of these two groups. The primary group is of greater importance to mammalian infections as 'our' HAs are mainly from this group.
                              Both groups are ideally suited to the oral-faecal transmission route as they feed in the water into which they defecate, they often congregate into dense flocks (high viral loads) and include migratory species (wide geographic spread).

                              The first thing to note is that these birds take their flu sero-types in parallel while for us we seem to take them in series, each pandemic largely killing off its predecessor (yes I know we now have two due to the reintroduction of H1N1 in the '70s). Infection in the primary hosts is normally mild or asymptomatic allowing the sub-types in each group to mix freely with no real barrier to multiple infection in one host.

                              Flu's route to genetic diversity is two fold. Firstly the sloppy polymerase allows for poor fidelity in copying the vRNA creating lots of SNPs and secondly it does not seem to care much about virion assembly and is happy to mix RNAs from different infections leading to reassorments. Human reassortment have a very limited pallet as there are only two sero-types - plus extremely rare zoonotic infections. Most changes lead to unfit viruses but, as flu is parasitic, the cost of all these duds are born by the host not the virus.

                              As we have only had a few flu pandemics recently enough for us to know how to sub-type them and we have only very recently got surveillance in place to watch human zoonotic flu infections amongst the background we do not really understand the dynamics of pandemic emergence.
                              1918, 1957, 1968 and even 2009 all look like they reassorted straight into their pandemic form - or at least we did not spot them until there was sustainable H2H. For the first time we are now sequencing enough to spot the odd zoonotic infection amongst the background. H5N1, H7N9, H5N8, H10N8 are all ongoing and many others in the past. I think it unlikely that this is new behaviour, it is just we did not have the tools to look.

                              Now thinking a little about the 'zoonotic edge' of the avian virus pool.
                              For an infection to occur in a human they need to be exposed to an AIV that, as an absolute minimum, can infect a human cell most can't.
                              How do they get to the point where they can?
                              They drift, genetically, around the strain consensus by the methods discussed above. Of all those sero-types circulating at any given moment some will be close to an infectious form (in humans) and most will be far away. Also the line is not clear and most infections occur in either people who have been exposed to a very high viral load (farmers, vets etc.) or were immunocompromised to some degree. In an earlier post I pointed out pigs could be infected with H7N9 experimental, given a high enough dose at inoculation, but would not spread the infection either by contact or aerosol transmission.

                              If we look at H7N9 as an example there seem to have been a number of reassortments leading to a virus of which A/Anhui/1/2013 is representative. Presumably the parents strains were somewhere near my 'zoonotic edge', prior to their latest changes, and their progeny is now very close to the edge.
                              What happens now?
                              More change (hey it's flu' what did you expect). As the virus is not showing efficient H2H, in it current form, the AI strain will continue its genetic meander in its primary host(s) and either drift away from my 'zoonotic edge' or over it into pandemic territory (away from the edge should be more likely as it is likely closer to the bird index). The alternative route is that one of these human infection will develop, within its quasi-species, a variant that is better adapt and successfully start a cluster. The starting virus now is already a bit better adapted and its quasi-species can then capitalise on the advantage and jump again etc. A virus replicating in a host to which its is ill adapted will be under severe selection pressure and favour mutations that improve replication in that host (but not necessarily adaptations that improve transmission to a new host).

                              I am sorry this has ended up being so long but I thought it was important to cover as many aspects as possible as they all inter-relate. I hope some one will be able to pick holes in the logic of my model - it's how I learn and improve my mental model.
                              Please do not ask me for medical advice, I am not a medical doctor.

                              Avatar is a painting by Alan Pollack, titled, "Plague". I'm sure it was an accident that the plague girl happened to look almost like my twin.
                              Thank you,
                              Shannon Bennett

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                              • #75
                                Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

                                Yes - thanks JJ and NS1. Good answers to my question and has given me much to ponder.

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