on the fence with HIB-need opinions - Page 5

[luminesce]

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

Recently, there has been an increase in The Netherlands in the number of cases of invasive disease caused by Haemophilus influenzae serotype b (Hib). [snip] The strains were collected from 1983 from 2002, covering a time period of 10 years before and 9 years after the introduction of the Hib vaccine in the Dutch national vaccination program. MLVA revealed a sharp increase in genetic diversity of Hib strains isolated from neonates to 4-year-old patients after 1993, when the Hib vaccine was introduced. Hib strains isolated from patients older than 4 years in age were genetically diverse, and no significant change in diversity was seen after the introduction of the vaccine. These observations suggest that after the introduction of the Hib vaccine young children no longer constitute the reservoir for Hib and that they are infected by adults carrying genetically diverse Hib strains.

Maybe the US is headed down the same theoretical path.

[Spectrolite]

genetically diverse strains= strains not covered by the hib vax?

[mamakay]

Originally Posted by serenitii

To jump into the discussion a little late, look at Figure 5 in the following document:

http://bioinfo.bact.wisc.edu/themicr...emophilus.html

Take note, that this figure was pre 1985, so we're talking about the pre-vaccine era. Am I reading this chart right? It looks to me like it says that kids under 3 basically had no bacterial antibodies in their blood against HiB. If this was the case in the pre-vaccine era back when the bacteria was more prevalent, then maybe (with HiB at least) exposure isn't the primary key? With this bacteria, perhaps a very specific age-related immune system issue is the predominant factor?

Do you know how to find the original research that graph is based on?

I found evidence that might conflict with that graph.

http://indianpediatrics.net/april2000/april-414-417.htm

The results demonstrated that a high percentage of infants from 1.5 months to 13 months of age had an anti-PRP concentration considered to be protective and their GM anti-PRP titers were also higher than the protective level. Serum anti-PRP in the first few months of age were considered to be maternally acquired and were expected to decrease with time(1,2). In this study, at 6.5 months of age GM anti-PRP titers and the percentage of infants having anti-PRP at protective level showed a decline, but they were not significantly different from those at other ages.

The results obtained from our study suggest that the majority of the infants have high concentrations of maternally transferred anti-PRP and have also acquired the natural immunity to Hib at an early period of life

They have a Finish and a Gambian reference for conflicting evidence. Maybe those are the research that figure 5 chart comes from? I'll go see if I can find it...

[mamakay]

Ok..the indian (well, turkish, actually) study says:

In Finland, anti-PRP concentrations were not detected to be within protective level in almost all children under 6 months age(5).

Reference 5 is:

5. Peltola H, Kayty H, Sivonen MS, Makela H. Haemophilus influenzae type b capsular polysaccharide vaccine in children: A double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland. Pediatric 1977; 60: 730-737.

That's the Finnish 1977 trial the old hib polysaccharide vax was approved in the US with. They were probably just looking at the immune response to the vax. I don't have access to the fulltext, though.

Then about the Gambian study, they say:

In Gambia, 60% of infants born to mothers immunized with Hib Conjugate vaccine and 26% of infants of unvaccinated mothers had protective anti-PRP concentration at two months of age(4). In our study the percentage of infants with protective anti PRP antibody level was approximately similar to those found in Gambian infants whose mothers received the Hib vaccine during pregnancy.

Here's the Gambian study. It doesn't tell us anything because those infants were being vaccinated.

[luminesce]

Originally Posted by Spectrolite

genetically diverse strains= strains not covered by the hib vax?

No, they are saying that kids who are infected are now being infected by adults, not other kids. I think they may be speculating that the change in reservoir might be a significant finding when looking for an explanation for the increase in the number of infections.

ETA: When we suddenly change the way bacteria circulate and colonize humans, we can't always predict what will happen. Maybe when kids had and commonly shared genetically similar strains they were better able to mount an immune response but now that they are being exposed to genetically diverse strains more frequently, they are more susceptible. This, of course, also implies some level of vaccine failure but with the stuff I've been reading about DTaP being known to reduce the response to Hib when the shots are given together... who knows?

[mamakay]

Also...this is slightly off topic, but I'm going to stick this link here so I don't lose it:

http://pediatrics.aappublications.or...tract/81/6/886

In recent months much controversy has focused on interpretations of new data concerning the safety and efficacy of Haemophilus influenzae type b vaccines.1-3 These controversies led the Infectious Disease Committee (Redbook Committee) of the Academy of Pediatrics (AAP) on Nov 13, 1987, to issue by telegram a change in recommendations for the H influenzae type b polysac-charide vaccine. Then, on Dec 22, 1987, the US Food and Drug Administration (FDA) licensed a new, more immunogenic, H influenzae type b conjugate vaccine (Prohibit-Connaught).

So putting it all together for the timeline:

According to this (you have to squint to read it)
http://i45.photobucket.com/albums/f7...rion/upeB6.jpg

..in late October or early November of 1987, there was a NIH meeting where the AAP was made aware of this: (tho the study didn't pass peer review until 1988)

http://jama.ama-assn.org/cgi/content...ct/260/10/1423

November 13 of 1987: AAP issues alert

December 22: FDA approves first (not as effective as the ones we use now) conjugate vaccine

January of 1988: ACIP makes recommendation for all kids 15 months and older to be given the new conjugate vaccines instead of the scary polysaccharide ones they were getting.

[luminesce]

Originally Posted by mamakay

Do you know how to find the original research that graph is based on?

I think this might be it but I haven't read it yet (I can't nab more than a few mins at a time today to read anything. ) The chart says the data is pre-1985.

http://www.pubmedcentral.nih.gov/art...i?artid=273954

[mamakay]

Originally Posted by serenitii

No, they are saying that kids who are infected are now being infected by adults, not other kids. I think they may be speculating that the change in reservoir might be a significant finding when looking for an explanation for the increase in the number of infections.

ETA: When we suddenly change the way bacteria circulate and colonize humans, we can't always predict what will happen. Maybe when kids had and commonly shared genetically similar strains they were better able to mount an immune response but now that they are being exposed to genetically diverse strains more frequently, they are more susceptible. This, of course, also implies some level of vaccine failure but with the stuff I've been reading about DTaP being known to reduce the response to Hib when the shots are given together... who knows?

So...why did it that happen there, but not in the US? Different vaccine? You'd think it would have already happened here if it was going to, but both Hib carriage and invasive disease are at an all time low in the US in adults. Or could it be the fact that we (generally, not sure about the Netherlands) do an extra booster dose or two?
Could doing too few shots in the series have allowed circulation in kids to have continued (albeit at a lower level than prevax), and there's where the selective pressure for genetic diversity came from?

[mamakay]

Originally Posted by serenitii

I think this might be it but I haven't read it yet (I can't nab more than a few mins at a time today to read anything. ) The chart says the data is pre-1985.

http://www.pubmedcentral.nih.gov/art...i?artid=273954

The IgG goes along with that chart (sorta), but the IgM doesn't. The IgM response is more in line with the Turkish study. With the IgM, there is a slow build from age 6 months that just continually increases.

Also, on this page, there's (only one...I wish it was a larger study) a 6 month old baby with meningitis, and both the IgM and IgG increase significantly over the 6 days the baby is in the hospital.
(first patient here)
http://www.pubmedcentral.nih.gov/pag...geindex=5#page

And he says:

The greatest increase in IgG titers obtained in serum samples
from these patients was about 50-fold, which
was observed in a child who was 4 years and 8
months old, and the greatest increase in IgM
titers was about 25-fold, which was observed in
the youngest child (6 months old).

[luminesce]

Originally Posted by mamakay

Also, on this page, there's (only one...I wish it was a larger study) a 6 month old baby with meningitis, and both the IgM and IgG increase significantly over the 6 days the baby is in the hospital.

However, serodiagnosis of H. influenza type b infections might be limited to older children and adults, since it has been found that most young children do not respond with antibody formation either to natural H. influenza infections or to vaccination with purified capsular polysaccharide (12-14). The children with H. influenza infections included in this study (even the 6-month-old child) showed specific antibody responses. Furthermore, it is known that several types of bacteria possess antigens which cross-react with type b polysaccharide (5,18) (e.g., E. coli K-100 [15], pneumococci [19], and other bacteria [1]). Therefore, it is conceivable that such organisms could give rise to antibodies that cross-react with H. influenza type b polysaccharide, which might explain the initial titers, in addition to previous H. influenzae type b infections.

[mamakay]

Originally Posted by serenitii

However, serodiagnosis of H. influenza type b infections might be limited to older children and adults, since it has been found that most young children do not respond with antibody formation either to natural H. influenza infections or to vaccination with purified capsular polysaccharide (12-14). The children with H. influenza infections included in this study (even the 6-month-old child) showed specific antibody responses. Furthermore, it is known that several types of bacteria possess antigens which cross-react with type b polysaccharide (5,18) (e.g., E. coli K-100 [15], pneumococci [19], and other bacteria [1]). Therefore, it is conceivable that such organisms could give rise to antibodies that cross-react with H. influenza type b polysaccharide, which might explain the initial titers, in addition to previous H. influenzae type b infections.

2 of the three studies are looking at the response to the vaccine.
This is the only fulltext I could find.
http://www.pedresearch.org/pt/re/ped...97303000-00001

There was one study that looked at natural infection, but they didn't break it down by age in the abstract. Even assuming that study does show in the fulltext that the infants under 2 didn't respond, we're still 2:1 on studies favoring natural immunity happening in infants. 3:1 if we count the study I just linked to, where they observed an infant form antibodies after asymptomatic carriage.

[luminesce]

Originally Posted by mamakay

There was one study that looked at natural infection, but they didn't break it down by age in the abstract. Even assuming that study does show in the fulltext that the infants under 2 didn't respond, we're still 2:1 on studies favoring natural immunity happening in infants. 3:1 if we count the study I just linked to, where they observed an infant form antibodies after asymptomatic carriage.

Could you sum up the studies for reference?

[luminesce]

To complicate it even more...

http://www.pubmedcentral.nih.gov/pic...8&blobtype=pdf

The pioneering study of Fothergill and Wright (3) showed that immunity to Haemophilus influenzae type b (HIb) was age-related and associated with bactericidal (BA) antibodies. These BA antibodies were assumed to be protective against disease and were subsequently shown to be directed primarily at the HIb capsular polysaccharide antigen (1, 23). However, several lines of evidence have suggested that anticapsular (AC) antibodies are not solely responsible for protective immunity to HIb.

ETA:

It is this study by Fothergill in 1933 that established the consensus of age related immunity: http://www.jimmunol.org/cgi/content/abstract/24/4/273 The text of this paper is where that chart showing the bactericidal activity of blood came from (it was actually copied from the paper.)

This references it as well:

http://emedicine.medscape.com/article/1164916-overview

Transmissibility of Hib infection and the capacity of this organism to cause purulent meningitis was first demonstrated by Wollstein in 1911. She first drew attention to the marked tendency for Hib meningitis to occur in infants and young children. Pittman distinguished 6 serotypes (A through F) of H influenzae in 1931 and demonstrated that the B serotype accounted for almost all cases of meningitis. Fothergill and Wright enlarged the epidemiologic understanding of Hib meningitis, the protective role of passively transmitted maternal antibodies, and the inadequacy of host immune response from infancy to age 3 years in an important series of studies published in 1933

Also, reading further down in that last link:

Hib meningitis is quite rare in the first 2 months of life, accounting for 0-0.3% of all meningitis cases in this age group. Children of this age group are likely protected from infection by the passive transfer of maternal antibodies. These antibodies are considerably diminished by 2 months of life and are often completely gone by 4 months of life. This period of limited vulnerability appears to be prolonged in breastfed infants, likely because of continued passive transfer of antibodies. This effect is thought by some authorities to account for the fact that young children who develop Hib meningitis in Northern Europe do so at an older average age than children who develop Hib meningitis in North America. These authorities suggest that more Northern European mothers engage in breastfeeding of infants and that they tend to do so for longer periods than North American mothers.

[luminesce]

Originally Posted by mamakay

So...why did it that happen there, but not in the US? Different vaccine? You'd think it would have already happened here if it was going to, but both Hib carriage and invasive disease are at an all time low in the US in adults. Or could it be the fact that we (generally, not sure about the Netherlands) do an extra booster dose or two?
Could doing too few shots in the series have allowed circulation in kids to have continued (albeit at a lower level than prevax), and there's where the selective pressure for genetic diversity came from?

http://ecdc.europa.eu/documents/pdf/...032004_hib.pdf

Despite the high reported vaccine effectiveness of Hib conjugate vaccination, a resurgence of Hib disease has been seen in both UK and, to a smaller extent, Netherlands. The rise in the former, which began in 1999, about seven years after introduction of Hib conjugate vaccination, peaked in 2002, and was ascribed to a combination of factors. These included waning immunity in the absence of a booster dose in the second year of life, and use of acellular pertussis vaccine, which has been associated with lessened immunogenecity of the Hib component. Neither of these conditions apply to the Netherlands, which saw a sudden increase in Hib incidence in 2002, 3-fold greater than that seen in the 6 previous years and that has been sustained in the years following. It has been suggested that changes in population immunity may be the most important factors in both countries. For example, reduction of Hib carriage in children caused by Hib conjugate vaccination has resulted in a lack of natural boosting of immunity in adults. This in turn has led to accumulation of susceptibles sufficient to allow increased Hib transmission and thus a much greater level of exposure to potentially invasive Hib strains by highly susceptible individuals. There is evidence of an abrupt increase in the genetic diversity of Hib strains after introduction of the vaccine.

If this is the most important factor -- then, are we headed for an increase for the same reasons?

[mamakay]

Originally Posted by serenitii

http://ecdc.europa.eu/documents/pdf/...032004_hib.pdf



If this is the most important factor -- then, are we headed for an increase for the same reasons?

For example, reduction of Hib carriage in children caused by Hib conjugate vaccination has resulted in a lack of natural boosting of immunity in adults. This in turn has led to accumulation of susceptibles sufficient to allow increased Hib transmission and thus a much greater level of exposure to potentially invasive Hib strains by highly susceptible individuals. There is evidence of an abrupt increase in the genetic diversity of Hib strains after introduction of the vaccine.

We could be...

I wonder if the CDC will think to start doing large Hib carriage studies in adults here?
With the recent "outbreaks", I'm also not sure we're not on the receiving end of selective reporting. But we won't know for 18 months or so if the apparent increase is real.

[luminesce]

Originally Posted by mamakay

We could be...

I wonder if the CDC will think to start doing large Hib carriage studies in adults here?
With the recent "outbreaks", I'm also not sure we're not on the receiving end of selective reporting. But we won't know for 18 months or so if the apparent increase is real.

They should... and now but why do I doubt that will happen until retrospectively? Carriage in the adult population was very low in the pre-vaccine era. I bet that isn't the case any more. In fact, it could be this change in reservoir that allowed the relatively minor vaccine shortage to create the "outbreak" (if it is indeed a real one.)

[ACsMom]

I am now sooo neck deep in this vax issue, it's been taking over every spare moment I have for the past 3 weeks. I feel like I NEED to decide very very soon on what to do. I talked with a organic food store owner today about vaxing (she doenst vax) and ended up getting rather teary. !! I just havne't really talked face to face about this issue with another "crunchy" mama who understands how emotions/mama instinct are part of this decision...

I am SOOO right where you're at.

[paisleypowell]

OK, I've read the whole thread here. I'm looking into delaying vaccination here.

It sounds like, from what I am reading here, that vaccinating with hib prior to 2-3 years old may be meaningless as it seems to show no immune response?

So, if that is true, what is the point in doing the vaccine prior to 2-3 years old?

And, that breastfeeding has a protective effect.

Is that correct?

I'm troubled too, reading about the vaccinations and how it is completely altering how the immunity between adults/children, etc.

[carriebft]

There are some really good stuff on the dr sears page on this as well as some good info in his discussion section going on right now and a few pages back. I recommend the read there as well.

[luminesce]

Originally Posted by paisleypowell

It sounds like, from what I am reading here, that vaccinating with hib prior to 2-3 years old may be meaningless as it seems to show no immune response?

No, that is not the case. The lack of ability in children under three to fight Hib well seems to be a general consensus in the scientific community. After some digging, this was demonstrated in a pioneering study in the early 1900's. They basically took blood from kids of different ages and tested how many bacteria it could kill in a lab setting. Ultimately, they correlated the high incidence of invasive Hib in certain age groups (under 5, but really more-so under 2 or 3) with the inability of the blood in that age group to kill the organism.

This is all in no way related to a child's ability to mount an immune response to the conjugated vaccine. The conjugate vaccine works very well. The question is, are the risks of the vaccine worth the benefit? The benefit, of course being protection against Hib. The risks being: 1) Short term reactions (this vaccine does have one of the more "safe" profiles, at least.) 2) Long term risks (The jury is out on this one. There is the issue of serotype replacement. Also, some evidence has been given that Hib may be connected to a risk of Type 1 Diabetes, but this has generally been refuted. I haven't dug into this yet to know the details.)

Originally Posted by paisleypowell

And, that breastfeeding has a protective effect.

Is that correct?

Yes, breastfeeding has a protective effect. Breast milk has lots of antibodies, especially, IgA antibodies which protect mucosal linings and do all sorts of other good things.

Originally Posted by paisleypowell

I'm troubled too, reading about the vaccinations and how it is completely altering how the immunity between adults/children, etc.

The scientific community, in general, thinks it is a good trade-off. And likely, they'll continue to fight any fires they create after-the-fact with more vaccines.