CDC reports that hepatitis A virus vaccine escapes variants & potential new serotype emergence ...

[miriam]

... so the solution?  More vaccination?  

http://www.cdc.gov/eid/content/17/4/pdfs/10-1169.pdf

[PlayaMama]

that's because the new variants arose from a situation of partial vaccination.

this is likely because the wild-type variant strongly out-competes these variants in an non-vaccinated person. in the situation described, only eight had been vaccinated, (out of 186) and only one of those had been completely vaccinated. five had HIV, which also shows lower levels of responsiveness to the vaccine.

the conclusion of encouraging people to complete the series of vaccination, especially if they are likely to have a low level of responsiveness, is based upon the data they collected.

it seemed that you were implying that the suggestion was for "more" vaccination (rather than completing the currently recommended amount) in response to potential (have not actually developed yet) new serotypes. though you did use a question mark after "more vaccination?" so i could be misinterpreting your statement.

[miriam]

I am referring to the definition of insanity which is to keep doing the same thing even though we know something does not work.  

[PlayaMama]

the article says nothing about the vaccination not working when properly administered according to the recommended schedule. in fact, it is the partial vaccination that offered the grounds for the new variants to emerge.

they are saying is that people need to finish the series to AVOID situations that would likely lead to new variants. so, we are UNLIKELY to get a new serotype if people either don't get vaccinated (wild-type out competes) OR if you finish your series. i fail to see the insanity. 

Edited by PlayaMama - 3/23/11 at 10:46am

[miriam]

If a person avoids situations that lead to new variants in the first place, why get the vaccine?  

Are there any studies that show this to be the case?  

[PlayaMama]

i want to be sure i'm understanding your question correctly. are you suggesting that if people avoid situations that lead to the development of new variants (meaning, people should avoid partial vaccination) then they shouldn't get vaccinated?

in the absence of vaccination the wild-type virus out competes the variants. this just means that the type of Hep A that you get is the wild-type, not a new variant.

i'm not really sure what type of study you are asking for, i'm only responding to the article that you posted and the conclusions that you seemed to draw from it.

[miriam]

If this is preventative medicine, I am willing to take my chances with disease. 

[PlayaMama]

i don't understand how that statement is related to the findings of the article that you posted (which concluded that partial vaccination is what is causing new variants to arise) but it's certainly well within your rights to choose not to vaccinate.

i would think, though, that your point might be better served by a different article than the one you posted.

[miriam]

There are and have been many concerns with vaccines as to changing serotypes, boosters and waning immunities for some time.  The answer should be to build a healthier immune system, but I guess when one is in the business of selling a product, that product has all of the answers . 

http://www.medbroadcast.com/health_news_details_pf.asp?news_id=15245&news_channel_id=1000

Once upon a time, doctors and the CDC believed and wanted us to believe that just one shot would do the trick.  Now doctors do a series of three and are looking for room for a fourth or fifth booster.

http://insidevaccines.com/wordpress/2008/05/20/for-the-good-of-the-herd/

And I am old enough to recall quarantines and county trucks driving up and down the streets telling everyone to vaccinate, NOW.  The government and the medical profession were arrogant enough to think that they could coerce everyone into getting vaccinated and ALL childhood diseases could be wiped out in one generation.  After all of these years I look forward to collecting Social Security soon and enjoying grandchildren, I know that is NOT true.  

http://www.time.com/time/magazine/article/0,9171,836830-1,00.html

[PlayaMama]

i'm sorry, but i guess i'm unsure of why you would post an article for discussion and then discuss topics that are not relevant to the article?

i thought the point of posting an article was to discuss the content of the article?

not being critical, but i was interested in discussing the article.

Edited by PlayaMama - 3/24/11 at 5:07am

[amnesiac]

I will be very interested to see future hep A research regarding escape mutants. The article does indeed seem to indicate that, in a situation where you have immunocompromised hosts in an area of low endemicity, you have the potential for selection of escape variants. Perhaps some of the confusion about the article is related to the statement that 4% of the cases were vaccinated & 5/8 of these vaccinated patients were HIV+. I wonder if increased vaccination in that population would compensate for their poor immune function. I did not see immune/HIV status described for the remaining 96% of cases. And since I know so few adults who have been vaxed for hep A, I also wonder how many contacts there might have been and what their immune status might have been. It has been noted with Hep B that antiviral therapy contributes to escape mutants as well & I wonder if antiviral treatment for HIV plays any role in Hep A mutants. I suppose that overall, I wonder if we really know enough about the mechanisms involved to make accurate assumptions about the role of vaccination on the emergence and proliferation or prevention of these escape variants. Very interesting - thanks for sharing the article!

[PlayaMama]

Originally Posted by amnesiac 

I will be very interested to see future hep A research regarding escape mutants. The article does indeed seem to indicate that, in a situation where you have immunocompromised hosts in an area of low endemicity, you have the potential for selection of escape variants. Perhaps some of the confusion about the article is related to the statement that 4% of the cases were vaccinated & 5/8 of these vaccinated patients were HIV+. I wonder if increased vaccination in that population would compensate for their poor immune function. I did not see immune/HIV status described for the remaining 96% of cases.

And since I know so few adults who have been vaxed for hep A, I also wonder how many contacts there might have been and what their immune status might have been. It has been noted with Hep B that antiviral therapy contributes to escape mutants as well & I wonder if antiviral treatment for HIV plays any role in Hep A mutants. I suppose that overall, I wonder if we really know enough about the mechanisms involved to make accurate assumptions about the role of vaccination on the emergence and proliferation or prevention of these escape variants. Very interesting - thanks for sharing the article!

thanks for your thoughtful response!

in regards to the bolded, the article did cite two studies that discuss this topic.

it's interesting that you would look to the immune status of the subjects rather than the vaccination status. the majority of the article was discussing the limited ways in which the structure of the Hep A virus could mutate and still be viable. they also showed how the locations of these mutations were similar in the lab (in conditions in which the virus was placed in vaccine serum) as it was from the population.

there is also the additional data that shows that the phylogeny of four of the variants indicate that they came from one source. as the population charts (on page 8) indicate, it is highly likely that this person was partially vaccinated.

oh jeez, the three year old will not go to sleep! i'm sorry if this isn't as clear as i had hoped.

[amnesiac]

Quote:

Originally Posted by PlayaMama 

thanks for your thoughtful response!

in regards to the bolded, the article did cite two studies that discuss this topic.

it's interesting that you would look to the immune status of the subjects rather than the vaccination status. the majority of the article was discussing the limited ways in which the structure of the Hep A virus could mutate and still be viable. they also showed how the locations of these mutations were similar in the lab (in conditions in which the virus was placed in vaccine serum) as it was from the population.

there is also the additional data that shows that the phylogeny of four of the variants indicate that they came from one source. as the population charts (on page 8) indicate, it is highly likely that this person was partially vaccinated.

oh jeez, the three year old will not go to sleep! i'm sorry if this isn't as clear as i had hoped.

I guess I wouldn't say that I am looking at immune status rather than vaccination status, but at all aspects of the situation. I just have an interest in hepatitis is all.

In thinking about why there might be confusion as to how partial vaccination might be the basis for the problem, my initial thought was that of the 186 cases, one completed the vax series, 7 had received only one dose and the remaining 96% of cases were not vaxed at all. So it's hard for people to conceive how partial vaxing is the instigating factor when partial vaxers constituted only 3.7% of these cases.

The authors comment that

An incomplete vaccination schedule in an immunocompromised host could lead to a situation of only partial protection, providing suitable conditions for the emergence of an antigenic variant

So I do think a natural question is, if this immunocompromised population does not respond well to vaccination, why would we expect to see significant improvement even with series completion? They can be expected to have only partial protection anyway so what impact does complete vaccination truly have for them where these mutants are concerned?

It seems amazing to think that you suddenly have 4 mutants appear in a single host in such a remarkably stable virus. It would most definitely be interesting to know what all was going on with that host. Perhaps you could elaborate on how the lab growth competition graphs on page 8 indicate anything about this specific index case?

A big part of what they mentioned repeatedly is that this was happening in an area where not much wild virus was circulating. Definitely interesting to think about when we're talking about the role of vaccines vs the role of sanitation in "VPD" control.

The article seems very full of assumptions and inferrences without direct evidence which is why I say I will certainly be curious to see how the complete picture is investigated in the future.

[PlayaMama]

Originally Posted by amnesiac 

Quote:

I guess I wouldn't say that I am looking at immune status rather than vaccination status, but at all aspects of the situation. I just have an interest in hepatitis is all.

In thinking about why there might be confusion as to how partial vaccination might be the basis for the problem, my initial thought was that of the 186 cases, one completed the vax series, 7 had received only one dose and the remaining 96% of cases were not vaxed at all. So it's hard for people to conceive how partial vaxing is the instigating factor when partial vaxers constituted only 3.7% of these cases.

The authors comment that

An incomplete vaccination schedule in an immunocompromised host could lead to a situation of only partial protection, providing suitable conditions for the emergence of an antigenic variant

So I do think a natural question is, if this immunocompromised population does not respond well to vaccination, why would we expect to see significant improvement even with series completion? They can be expected to have only partial protection anyway so what impact does complete vaccination truly have for them where these mutants are concerned?

It seems amazing to think that you suddenly have 4 mutants appear in a single host in such a remarkably stable virus. It would most definitely be interesting to know what all was going on with that host. Perhaps you could elaborate on how the lab growth competition graphs on page 8 indicate anything about this specific index case?

A big part of what they mentioned repeatedly is that this was happening in an area where not much wild virus was circulating. Definitely interesting to think about when we're talking about the role of vaccines vs the role of sanitation in "VPD" control.

The article seems very full of assumptions and inferrences without direct evidence which is why I say I will certainly be curious to see how the complete picture is investigated in the future.

in response to the bolded and blue- the reasons that it is likely that the partial status of these few subjects is important for two reasons.

1- the population data, which shows that mutants ONLY out-compete the wild-type in the presence of the vaccine, indicates that these would ONLY have arisen in a partially vaxed person. if the person was not vaxed, then the mutants would have been out-competed by the wild-type.

2- the fact that at least four of the mutants evolved from one ancestor indicate that they likely came from the same host.

in response to the bolded italics- according to the articles cited, 48% of those HIV patients that completed a full vaccination series (two vaccines) responded and the other one found that 88.2% of HIV patients responded. this is quite a bit of variation and it would seem that this is an area that could use more study. the responders without HIV were 100%, so the recommendation (from one of the articles) to vaccinate early in the progress of the HIV disease makes sense.
 

in response to the bolded- the population charts show that the wild-type virus (HM175/43c) out competes the resistant mutants (C6 and P29)in an environment that does not contain the serums. this means, that in an unvaccinated subject, the is very little chance of a mutant developing because the wild-type is much more fit and the mutant would not be able to survive if it were to appear..

in an environment in which there is a portion of the vaccination serum, the mutants were able to out-compete the wild-type virus. this means, that in an environment where there was some protection from the vaccine, the wild-type virus would be neutralized, and the mutants would be capable of survival. kind of like antibiotic resistant bacteria.

it's basically just natural selection. the scientists have recreated similar mutations in the lab under the hypothetical situation of partial vaccination. the lab results align with what was observed in the field. therefore, the evidence that they found (mutants in a very stable virus) supports their hypothesis.

i mean, sure, it's possible that the new mutants could have arisen in someone that wasn't vaccinated, but why would it not have been out competed by the wild-type? it just doesn't align with the laboratory evidence that they found.

[miriam]

More CDC serotypes. http://www.cdc.gov/eid/content/17/4/584.htm?source=govdelivery

QUOTE  "What is carriage?   A carrier is a person who harbors a specific infectious agent in the absence of clinical illness with or without a detectable immune response. The carrier state may reflect carriage of the organism in the incubation period before clinical symptoms appear, during an illness, or after recovery from illness. The carrier state may be short or long, and it may be intermittent or continuous. Carriers may spread infection to others. Latency should be distinguished from the carrier state, in that a latent organism is not transmissible. Hib carriage can be synonymous with Hib colonization and is defined as the presence of viable Hib organisms in the human pharyngeal mucosa. This definition depends on the sensitivity and specificity of the process used to identify viable bacteria in a healthy host."  /UNQUOTE

[amnesiac]

The article tells us that a big issue is that of immunosuppression in areas where wild Hep A has low endemicity, so there is little opportunity for species competition. I don't think that the evidence is definitive in saying "this person only received one of the 2 recommended vaccine doses" so much as it might say "this person's antibody titer wasn't likely to have been very high" which could well mean "this immunosuppressed person didn't respond well to the 2 vaccine doses s/he received" in addition to living in an area where little wild virus circulated.  Like I said, "could", "may", "likely to" & such inferrences are interesting but I think it's early yet to say this is definative evidence that vaccine series completion would halt escape mutants in this population.

[PlayaMama]

it might not in an individual with HIV. the results of less than 50% from the one study aren't terribly high, though almost 90% sounds a lot better! so, if they were to achieve an immunity status that was somewhere in the middle (3 out of 4 say) then that would be helpful for decreasing the likelihood of a new variant happening. of course it's not going to completely prevent it, but an increase in the odds isn't bad. and combined with safer sexual practices it's likely to decrease transmission.

the article's recommendation was not only for those with HIV though, and i think in those cases where there is a much higher chance of immunity developing, the laboratory evidence that they've found indicates that a partial vaccination status is likely to increase the chances of a new serotype.

good discussion though! i agree with you that the ability of HIV positive subjects to achieve immunity through vaccination is important in the decision to recommend vaccination in this particular population. though i would suppose, that even if there are only half that achieve immunity after two doses, it might be worth examining if this would increase with additional doses. which is funny since the article did not mention that, but miriam was talking about it.

in this specific population it might be a supported area of inquiry.