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Re: Is H7N9 Spreading from Human to Human in China?
Remember the H5N1 discussion about "superspreaders"? Children are regarded as somewhat of a superspreader, but didn't someone put forward a theory that people with AIDS can become superspreaders? As AIDs increases globally, might that impact the spread of influenzas for which we have no Ab, more than regular influenza?
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"The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation
Re: Is H7N9 Spreading from Human to Human in China?
Being very much interested in the development of this influenza virus, I have a question.
Reading up on influenza, I found a publication that mentioned influenza in Rattus Norvegicus and I concluded from the article that this species could carry this virus.
See this link: http://www.genome.jp/kegg-bin/show_pathway?rno05164
I read many times that this novel H7N9 virus shows signs of adaptation to mammalians and that the virus in chickens and other poultry seems to be a different one than the one found in humans.
Can it be that the source of this virus is really Rattus Norvegicus and that the oftentimes mentioned mutations have happened and are happening in this omnipresent mammalian rodent species?
Since markets where chickens are slaughtered and places like this, tend to be infested with rats, can it not be that rats are intermediate between humans and chickens?
Rats urinate everywhere they can and if infected with this virus, might sneeze all over the place as well, thereby spraying the virus into the human habitat as well.
I assume that in China, like everywhere else on the planet, Rattus Norvegicus and Homo Sapiens live together in the same habitat and as such wondered about this possibility.
Does anyone know if this is being researched?
Last edited by G.Verkerk; April 18, 2013, 03:02 AM.
Reason: Question I want an answer to.
Re: Is H7N9 Spreading from Human to Human in China?
Rats are frequent visitors to poultry houses. They eat the grain and contaminate it. I can see where it would be possible to pass the virus back and forth if they are susceptible.
The salvage of human life ought to be placed above barter and exchange ~ Louis Harris, 1918
Remember the H5N1 discussion about "superspreaders"? Children are regarded as somewhat of a superspreader, but didn't someone put forward a theory that people with AIDS can become superspreaders? As AIDs increases globally, might that impact the spread of influenzas for which we have no Ab, more than regular influenza?
.
I think it was not demonstrated that H1pdm09 was worse in HIV/AIDS patients than other chronic diseased patients.
The HIV//AIDS could also reduce some hyperinflammatory reponses because the depletion of some T cells related to cytokine storm.
Children are usually immunocompetent but they lack of an antibodies repertoire against a variety of antigens, where old people had.
It is possible that natural infection with recent human/animal flu viruses in China may have increased in some Young people an heterotypic immunity that is not present in older people (original sin, for example, may play a role too).
Children may also have a longer viral shedding period, even when symptoms have resolved.
If in China elderly people are used to take care of children (an there is need for an ethnographic proof), then it may also possible that at least a number of these infections are actually the result of children shedding.
We have zero rat-sequences but thousands poultry sequences
The maxim 'if you dont look, you won't find' may apply here.
Can anyone find any record of rats being trapped and tested for influenza strains, but influenza has not been found? However, even if that is the case, we dont know that it is true for H7N9 until the premise has been tested.
Hopefully the WHO/China expert teams will look at this to gain a definitive answer. Same goes for any mice they trap in and around wet markets where H7N9 has been found in poultry.
If the answer was 'yes' it could help to explain the geographical spread. Rodents are well known for hitch-hiking in grain transports etc. (Bubonic plague distribution is a classic example)
Low-Pathogenic Avian Influenza Viruses in Wild House Mice
Discussion
This study provides evidence that avian influenza viruses may be naturally transmitted to mice at outbreak sites and that wild house mice can efficiently replicate avian influenza viruses without prior adaptation. Even though our sample size was low and we were sampling nearly a month after the outbreak was first detected, the house mice in our mammal survey at the Idaho outbreak site showed a positive response for influenza A antibodies. We recommend that future outbreaks allow for significant rodent sampling on the premises as soon as an outbreak is detected to further our understanding of the role rodents may play in avian influenza dynamics at outbreak sites.Furthermore, low sera sample volumes for the mice prevented us from subtyping the samples, which may have provided stronger support for past avian influenza virus infection. The ELISA used in this study was type-specific for antibodies to influenza A; therefore we cannot rule out that the mice may have been infected with a mammalian influenza strain rather than an avian strain. However, the outbreak farm housed only birds so the probability of the presence of a mammalian influenza strain was likely to be lower than for an avian strain.
Few studies have explored the seroprevalence of avian influenza viruses in synanthropic wildlife at outbreak sites and active areas of infection. Exceptions are surveys by Nettles et al. [55], Henzler et al. [56], and Shortridge et al. [57]. In the first study more than 250 mice and rats from infected farms were sampled after a 1983–84 outbreak of H5N2 virus in domestic poultry in the eastern U.S. No evidence for influenza infection was found in the rodents. However, rodent sampling was conducted 2–3 months post-outbreak, which is relatively late given the monthly survival rate of mice on farms can be as low as 0.55 [58]. Henzler et al. also surveyed mice on poultry farms during an outbreak of H7N2 in poultry in Pennsylvania, U.S. from 1996–1998. Lung and intestinal tissues were tested by virus isolation and all samples were found to be negative. In the Shortridge et al. study, mice and rats associated with poultry markets in Hong Kong were surveyed for exposure to avian influenza viruses after the initial detection of Asian strain H5N1 virus. Again, no virus was isolated from either rodent species, but rats showed evidence of hemagglutination inhibition activity and the ability of both mice and rats to replicate the H5N1 virus was subsequently confirmed[30].
A potential caveat with regard to mammalian sero-surveys is that many assays developed to detect antibodies to avian influenza viruses are optimized for poultry species and may not be validated for other species. Consequently, assay sensitivity and specificity may not be consistent with published parameters. Further, a number of commercial enzyme-linked immunosorbent assays (ELISAs) developed for detection of antibodies to avian influenza viruses use anti-mouse antigens and may not be appropriate for rodents. Hemagluttination inhibition (HI) tests may also be problematic as mouse sera may cause non-specific binding that interferes with HI tests [59]. Only a third of the mice tested in this study were positive for antibodies to avian influenza virus. Further work needs to be done to elucidate whether mice lacking an ELISA response would be protected upon re-exposure to influenza virus.
Rodents could contribute to avian influenza virus transmission on and among farms in a number of ways. Mice and rats could spread virus via mechanical transmission [60]. Alternatively, they could contribute to viral spread by becoming infected via scavenging on infected poultry carcasses [2] or by contact with contaminated water sources [61] and subsequently transmitting virus if they are scavenged or predated. Mice are a very common prey species for a variety of raptors, meso-predators, and other mammalian carnivores and are also commonly eaten by barnyard chickens. The high concentrations of viral RNA detected in the lungs of experimentally infected house mice indicate that wild mice may have the potential to replicate sufficient virus for transmission to other species.
We tested five subtypes of avian influenza virus in order to compare the replication potential of subtypes derived from both wild birds and chickens. Our results indicate that wild mice were able to more efficiently replicate viruses originating from wild birds than from poultry. Viral RNA was detected in 94% of lung, 86% of nasal turbinate, and 78% of trachea tissues from mice inoculated with wild bird viruses compared with 51% of lung, 44% of nasal turbinate, and 20% of trachea tissues from mice inoculated with chicken viruses. Given the wide range of replication potential for different avian influenza virus subtypes and different strains within subtypes, this pattern of higher viral replication of wild bird viruses compared with poultry viruses may be due to chance. Further study is needed to confirm this general result, but if the pattern holds, it may indicate that mice are more likely to introduce an avian influenza strain from wild birds to poultry than to spread poultry viruses among and between farms.
Studying wild house mice rather than laboratory mice is essential to understanding the potential role that mice may play in avian influenza virus outbreak dynamics because wild house mice and laboratory mice may exhibit differential immune function [42]. Standard laboratory mice, including BALB/c mice, have a defective Mx1 gene (Mx1−) that reduces their ability to resist influenza virus infections [62], [63], [64], [65]. On the other hand, wild mice with an intact Mx1 gene (Mx1+) are resistant to influenza virus infection [63], [64]. Consequently, the results of studies based on experimental infections of laboratory mice may not accurately reflect viral replication in wild mice. In addition to differing genetics, natural populations of wild mice are likely to include a broad spectrum of heterogeneities that might influence viral replication. For example, sex, age, reproductive status, behavior, nutritional condition, disease status, and parasite load are all likely to affect immune function [42], [43], [66]. In this study, wild house mice were fed standard laboratory diets for 2–5 weeks prior to testing and were dusted for parasites, so individual differences due to nutritional status or parasite loads were likely diminished. However, we were able to evaluate sex and found that female mice exhibited higher viral replication rates compared to males. While none of the females in this study were pregnant at the time of inoculation, a few individuals gave birth during the quarantine period and a range of hormonal conditions were likely. Previous studies of influenza in mice indicate that morbidity, mortality, and viral loads are higher for pregnant females compared with non-pregnant controls [67], [68]. Differential replication rates may be important to consider in the development of risk assessment and transmission models because individuals with higher viral loads may be more likely to cause an infection post contact with a potential host. If so, the basic reproductive number, or the mean number of secondary infections caused by an infected individual, may be different for males and females and that difference might be important in epidemiologic models.
In summary, the ability of wild mice to efficiently replicate avian influenza viruses without adaptation indicates the potential role of wild house mice in avian influenza virus outbreak dynamics and warrants further investigation. In particular, studies that seek to confirm the presence of avian influenza virus antibodies, detect virus, or examine the ability of mice to transmit virus to other species would shed light on whether or not rodent control is an important strategy for avian influenza virus outbreak control.
Re: Is H7N9 Spreading from Human to Human in China?
they have been looking for these sources since decades,centuries.
Scientists are eager to find those and publish them as the first , but
... nothing. Mice are frequently used in labs, they infect them
and measure weight loss, death etc.
But in the wild it doesn't seem to happen.
It usually transmits respiratory (or waterborne in mallards) not oral-fecal
The China CDC just announced that the World Health Organization is invited to come next week with a team.
I suspect this is the official conformation of Jason Gale's
China Said to Invite Four Flu Experts as Disease Outbreak Widens
<cite class="byline">By Jason Gale - Apr 14, 2013 1:10 PM CT</cite>
Four international flu experts will arrive in China within days to help authorities respond to the country’s widening bird-flu emergency, according to two people familiar with the matter.
Nancy Cox, director of the flu division at the U.S. Centers for Disease Control and Prevention in Atlanta, Anne Kelso, director of a World Health Organization flu research center in Melbourne, Malik Peiris from the University of Hong Kong, and Angus Nicoll, head of the Stockholm-based European Centre for Disease Prevention and Control’s flu program, will arrive on about April 17 to offer technical advice, said the people, who declined to be identified because the Chinese government hasn’t announced that the experts are being invited.
posted by Pathfinder on the 14th.
I note it says they are being invited to provide 'technical advice' we shall see what that entails and if it includes suggestions like releasing sequence data. Looking at the cast list there is a wealth of talent here I hope they are not just given the guided tour.
Re. The rats
Firstly G.Verkerk welcome to FluTrackers.
I do not know if they are being tested but despite 'lab rats' being a common test model they are not usually used in flu research and, as Gs notes, absent from the sequence database. For immune response models mice are usually used - cheap and easy to work with - and for transmission studies ferrets - a more expensive mammalian model with both alpha 2,3 (Avian) & 2,6 (Mammalian) binding sites who sneeze to spread infection. I queried the GISAID database and they have a few A/pika/Qinghai/2007(H5N1) but no common rat.
Re. HIV
Immunocompromised patients are a big problem in drug resistance development. As they can be on several types of anti-biotic and anti-viral at the same time and often never come off them. They have been instrumental in the growth of MDR and XRD-TB. The only case of Relenza resistance I know of was in a immunocompromised patient who was put on Tamiflu and then developed a resistant form so was switched to Relenza to which they also developed a resistant strain. As their system never cleared the infection the virus just kept on trying combinations until it found one that worked. Release of drug resistant forms from such patients back onto the general population is a major concern in the battle to keep on top of microbial pathogens.
Re
I suspect this is the official conformation of Jason Gale'sposted by Pathfinder on the 14th.
I note it says they are being invited to provide 'technical advice' we shall see what that entails and if it includes suggestions like releasing sequence data. Looking at the cast list there is a wealth of talent here I hope they are not just given the guided tour..
I have frequently mentioned rodents as a potential vector to rule out.
There is some precedent here. Whilst this particular species is not resident in China, it does show that rats could be a vector. I dont know if all species of rats or only some have dual sialic acid receptors, but it must be worth looking at?
"I know God will not give me anything I can't handle. I just wish that He didn't trust me so much." - Mother Teresa of Calcutta
Re: Is H7N9 Spreading from Human to Human in China?
Lately, I've been thinking about La Gloria, Mexico. 《edited》
The information around the origination of the 2009 H1N1 event is sparse and usually starts with the Mexico City events, identification in the US, and the rapid spread around the world.
There was speculation the disease originated in La Rosa, Mexico in February -
1-2 months before the Mexico City fatalities that heralded something unusual was going on and 2-3 months before standard surveillance picked up cases in the US.
What happened in La Rosa? What are the epidemiological and genetic findings in humans? in nearby poultry and pigs? Did the disease rapidly spread through the town? Why didn't it reach other areas quickly? Or did it? Were there epidemics in the surrounding cities and towns before making it's way to Mexico City?
Re: Is H7N9 Spreading from Human to Human in China?
The events behind the emersion of the h1pdm09 virus had not been clarified and perhaps it will never.
At the time the virus was causing illness in humans it was already 'humanized', and no further adaptation were needed in order to sustain its spread h2h, with large community outbreaks.
The animal reservoir was never identified with certainty, even though the virus was of swine origin and its ancestors circulated for decades without trouble for humans (and pigs).
Some circumstantial records of pigs die-off in Mexican farms were never substantiated by independent investigations, and overall the interest at the time was almost totally focused on human illness and pandemic preparedness.
The surface antigen was similar to a seasonal strain circulating in the first half of XX century so that older people would have likely had some degree of immunity and the youngersters were partially covered by heterotypic immunity from current H1 strains, although with some limitations.
The pandemic was not this great deal in terms of morbidity and mortality if compared with other pandemic of XX century (1918, 57, 68).
H7N9 is an avian virus, although with some mammalian genetic signature. Clearly it needs more adaptation or mutations, even though the genetic constellation is new and a different behaviour with respect all other AIV cannot be discounted.
It is important what is doing on the ground: how many people remain infected per every new infection (R0), the susceptible population etc.
Re: Is H7N9 Spreading from Human to Human in China?
There was speculation the disease originated in La Rosa, Mexico in February
Could you be thinking of La Gloria in Veracruz, curiosity? I think there was one positive sample there in a child who recovered just fine, as did the earliest cases found by the Navy here in CA. The two children found there got the new flu in late March.
The confirmed 7 deaths in Mexico City were never explained as far as why the outcome was so bad, as far as anything being different about the virus itself.
"...there’s an obvious contest that’s happening between different sectors of the colonial ruling class in this country. And they would, if they could, lump us into their beef, their struggle." ---- Omali Yeshitela, African People’s Socialist Party
(My posts are not intended as advice or professional assessments of any kind.) Never forget Excalibur.
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