HiB Vaccine (Meningitis)

This is a continuation of a weekly series I’ve been helping to write for an education forum. This is the long version. For the short version, click here.

H. influenzae type B, (c) NHS

H. influenzae type B, (c) NHS

What are the “meningitis vaccines”?

There are two basic types of meningitis: viral and bacterial. There are no vaccines targeting viral meningitis. There are three vaccines targeting causes of bacterial meningitis: HiB, pneumococcal, and meningococcal. Meningococcal was Weekly Topic 03, HiB will be discussed here, and pneumococcal will be discussed in a future Weekly Topic.

According to the CDC Vaccination Schedule (2015), HiB vaccination occurs at 2 mo, 4 mo, 6 mo, and 12/15 mo. No further doses are recommended after the 15 mo dose, even if it was the only dose ever received. It is not recommended after age 5 years in healthy children. It is only available as a combination vaccine, not alone [1, 2]. In Canada, depending on province/territory, a HiB combination vaccine is typically recommended at 2 mo, 4 mo, 6 mo, and 18 mo [3].

 

What is HiB?

Haemohpilus influenzae type B is a bacterium that normally lives in the respiratory tracts of healthy people without causing disease. Up to 5% of the population is infected at a given time, and most children become infected by H. influenzae bacteria by the age of 5, whereby they develop immunity. Infection is more common in crowded housing and settings such as daycare; in fact, in daycare, the infection rate is approximately 15%, 3-15 times the proportion of the general population. Asymptomatic carriers remain infected and contagious for months at a time and the bacteria may easily pass from one person with disease through a long line of asymptomatic carriers before causing disease in another. It is present in the nose and throat and thus is passed by coughing or contact with mucus. However, cribs and toys of daycare children known to be asymptomatic carriers test negative for the bacteria, so contact with contagious children’s belongings is not believed to be a route of transmission. [4]

Because H. influenzae bacteria are a normal part of our respiratory tracts, probably 100% of the population becomes infected at some point, and most infections are asymptomatic, HiB disease is relatively very rare. However, when it does occur, HiB disease may result in sepsis, meningitis, and even death. Among those with HiB disease, approximately 3-6% die and 15-35% suffer permanent neurological sequelae (the most common being partial hearing loss). The most common symptoms of HiB disease include fever, decreased mental status, and stiff neck. [4, 5, 6]

 

How can I prevent or treat HiB in my child?

Conditions that make an individual more susceptible to HiB disease include recent viral infection, smoking or other respiratory irritants, immune suppression (e.g., sickle-cell anemia, absence of a spleen, antibody deficiency disorders, cancer, chemotherapy, etc.), and crowded housing or environment. [4] Avoid exposing your child to these triggers as much as possible by smoking cessation, avoiding crowded living spaces if possible, boosting the immune system, etc., and engaging in a generally healthy lifestyle. If your child has a known exposure to HiB, prompt evaluation by a physician for prophylactic antibiotics may be prudent.

Breastfeeding offers significant protection against HiB, lasting years after weaning [4, 7]. If breastfeeding is not possible due to adoption or other issues, look into relactation, pumping, or donor milk.

Note as discussed later in this post that there is an increased risk of HiB disease in the first week following vaccination. Therefore, if you choose to vaccinate and your child develops symptoms of HiB following vaccination, take it seriously.

 

How effective are the vaccines at preventing asymptomatic carriage?

Several studies have found HiB carriage to be reduced (but not eliminated) by vaccination. [4] Other studies have shown that when HiB vaccination was introduced to a population, HiB disease rates in both vaccinated and unvaccinated infants decreased, but were not eliminated in spite of very high vaccination rates [4]. Because it does not eliminate asymptomatic carriage, and the bacteria can jump from asymptomatic carrier to asymptomatic carrier regardless of the carrier’s vaccine status before causing disease in a susceptible individual, the vaccine cannot be relied upon for herd immunity, as evidenced by continued HiB disease in highly vaccinated populations.

 

How effective is the HiB vaccine?

Prior to the introduction of the vaccine, HiB caused over 80% of all invasive H. influenzae disease among children [8]. The incidence of HiB began to drop before the introduction of the vaccine [9, 10] and continued to drop after vaccination.

The HiB vaccine is of questionable efficacy, with some studies finding it not to be protective in children younger than 18 months, others finding variable efficacy in children over the age of 2, and others finding an increased risk of meningitis immediately following vaccination, with efficacy ranging from 88% to -69%. [6, 11] Newer conjugate vaccines have widely ranging efficacy depending on the population in which it they are tested. For example, the diphtheria-HiB (PRP-D) vaccine ranged from 35% efficacy (in producing an antibody response) in Alaskan Natives and <40% in Finnish children to 87% in another group of Finnish children [12]. Even across a single country, the same vaccine may be associated with vastly varying efficacy, as in one study that found a HiB vaccine that was effective in other areas of the U.S. was not associated with increased antibody response or decreased disease rate in Minnesota [13]. Another study found that HiB-vaccinated children with HiB disease had significantly lower HiB antibody levels than unvaccinated children with HiB disease. This was in spite of appropriate antibody response to other vaccines they had received. It’s thought to be partly due to a genetic defect that affects their ability to produce antibodies specifically to HiB [14].

All of the above estimates of efficacy depend on assumptions regarding what antibody level will be effective at preventing HiB disease, though the CDC states, “the precise level of antibody required for protection against invasive disease is not clearly established.” [15] However, the change in HiB incidence following vaccination can give us an idea of the vaccine’s efficacy.

The introduction of the HiB vaccine was followed by a shift in the dominant strains of H. influenzae from type B (HiB) to predominately nontypeable and type F (HiF)—that is to say, the incidence of infections and invasive disease caused by type B dropped while the incidence of infections and invasive disease caused by other strains increased. The overall incidence of H. influenzae invasive disease and death increased after the introduction of the vaccine. In other words, the introduction of the vaccine was followed by a net increase in H. influenzae-related morbidity and mortality in spite of the decrease in type B disease and death. [8]

This suggests that the HiB vaccine increases the overall risk of H. influenzae morbidity and mortality by increasing one’s risk particularly to non-B H. influenzae. This goes back to the theory of original antigenic sin. In short, people who are vaccinated against one strain are able to produce antibodies only to the antigens included in the vaccine, which handicaps them in fighting other viruses or bacteria that are similar enough to trigger their body’s antibody response but different enough that they don’t have antibodies against the primary antigens. In the case of pertussis, we see how vaccination against PRN-positive B. pertussis increases the risk of PRN-negative B. pertussis, B. parapertussis, and sometimes B. holmesii [16]. In the case of N. meningitidis, we see how the meningococcal vaccine increases the risk of infection with serogroups not included in the vaccine [17]. And here we see that the HiB vaccine increases the risk of H. influenzae strains not included in the vaccine, as discussed above.

The majority of H. influenzae invasive disease occurs in those aged 65 years or older. Furthermore, the introduction of the vaccine in children was followed by a rise in H. influenzae invasive disease and death in adults, especially the vulnerable elderly, demonstrating a negative herd effect. The introduction of the vaccine in children was followed by a net increase in H. influenzae-related morbidity and mortality in those too old to be vaccinated and in the vulnerable. In other words, the vaccine seems to have the opposite effect on the herd—a harmful rather than a helpful effect. [8]

 

Are there other infectious diseases related to HiB vaccination?

The use of other bacterial vaccines, particularly pertussis, seems to have contributed to the sudden increase in HiB infections in the 1970s and 1980s. [18] This led to the creation of the HiB vaccine. However, the introduction of the HiB vaccine also seems to have caused the sudden increase in pneumococcal infections, which are more dangerous and less treatable than HiB. This led to the introduction of the pneumococcal vaccine. However, the introduction of the pneumococcal vaccine seems to have caused the sudden increase in meningococcal infections, which are more dangerous and less treatable than pneumococcal infections. This led to the introduction of the meningococcal vaccine. There is concern that meningococcal vaccination will also be followed by the sudden increase of another more dangerous and less treatable bacterial disease. [5, 19]

 

What are the risks of the vaccine?

Type 1 Diabetes. The HiB vaccine is associated with a 25% increased incidence of type 1 diabetes as compared to vaccinated children who did not receive the HiB vaccine [5, 20, 21, 22; 23, p. 872; 24]. The risk increases with just one dose of HiB vaccine, but is highest in children who received all four doses [25]. In fact, the long-term complications from HiB-vaccine-induced type 1 diabetes alone outweigh the long-term complications from HiB disease if no children were vaccinated against HiB [26].

H. influenzae non-B Invasive Disease. As discussed above, the vaccine is associated with an overall increased incidence in H. influenzae infections and deaths. This is because the increase in non-B infections is more than the decrease in type B infections. The increase in non-B H. influenzae disease and death alone outweighs the drop in type B disease and death.

HiB Invasive Disease. Many studies have found an increased incidence of HiB invasive disease in the first week following vaccination with some types of HiB vaccine. “The evidence favors acceptance of a causal relation between unconjugated PRP vaccine and early-onset Hib disease.” [11] It’s said that this risk is only present with unconjugated vaccines (which we no longer use in the U.S.) [11], but it’s actually more common with conjugated vaccines (which we currently use in the U.S.) [27]. At times, this has occurred as early as 3 hours after HiB vaccination [28] and after a second HiB vaccine when there was no reaction to the first [29]. It’s important to note that this is not due to injection with live bacteria—that is, the contents of the vaccine do not directly cause the infection. Rather, it may be due to two related issues. One is that a dramatic decrease in antibody levels occurs in the first few days after vaccination due to the antibodies already present in the child pre-vaccination being quickly used up in fighting the antigens found in the vaccine, leaving the child susceptible to HiB in the environment due to inadequate antibody levels [28]. Another is the vaccine causing a briefly suppressed immune system, which makes the recipient more susceptible to disease. This is called “provocation disease” and was first recorded in medical literature in the 1960s in relation to polio, tuberculosis, and a few other diseases occurring secondary to vaccination [30, pp. 179-188].

Transverse Myelitis. There may be an association between the vaccine and transverse myelitis. This association is based on VAERS reports, not on medical literature. “The evidence is inadequate to accept or reject a causal relation between Hib vaccines and transverse myelitis.” [11]

Guillain-Barré Syndrome (GBS). There may be an association between the vaccine and transverse myelitis. This association is based on a published case series and VAERS reports. “The evidence is inadequate to accept or reject a causal relation between Hib vaccines and GBS.” [11]

Thrombocytopenia. This possible association is based on data from a HiB vaccine trial conducted in adults, as well as VAERS reports. “The evidence is inadequate to accept or reject a causal relation between Hib vaccines and thrombocytopenia.” [11]

SIDS. There are VAERS reports of SIDS cases occurring in close temporal association to HiB vaccination. [31] The association does not seem to have been studied in depth.

Asthma and Allergies. A Swiss study found HiB-vaccinated children to have a higher incidence of asthma and allergies as compared to HiB-unvaccinated children [32]. Studies in guinea pigs found asthmatic reactions to begin as early as four days following HiB vaccination [33].

Epiglottitis. The same Swiss study referenced above [32] found that an increase in epiglottitis was associated with the HiB-vaccine-associated increase in asthma and allergies.

Autism. The autism rate did not change significantly after the introduction of the MMR and DTP vaccines. However, it began to rise significantly after the introduction of the HiB and Hep B vaccines. Many parents have noted autistic regression following the MMR, which used to be given at the same time as the HiB vaccine. [34] Correlation does not equal causation, but a study comparing the autism rates in children who did and children who did not receive the HiB vaccine would be interesting. To my knowledge, such a study has not been conducted.

Encephalitis. There is at least one report of encephalitis occurring after HiB vaccination, but the child was simultaneously vaccinated against DPT (known to be associated with encephalitis) and OPV, so it’s uncertain whether the HiB vaccine can be blamed in this case. [35]

Others. Convulsions (seizures) and allergic reactions to the vaccine (including anaphylaxis) have also been reported. [36]

 

What vaccines are offered against HiB?

In the U.S. and Canada, there are no HiB-only vaccines. All HiB vaccines are combo shots. (NOTE: These ingredients lists are not complete; they only list the most alarming ingredients.)

  • ActHIB: tetanus-HiB (tetanus and HiB antigens, ammonium sulfate, formaldehyde, casein [milk protein]) [37]
  • Pentacel: DTaP-IPV-HiB (contains ActHIB; diphtheria, tetanus, acellular pertussis, 3 strains of inactivated poliovirus, and HiB antigens, aluminum, polysorbate 80, formaldehyde, cow serum, 2-phenoxyethanol, neomycin, polymyxin B, ammonium sulfate, casein [milk protein], and MRC-5 [aborted fetus cells]) [38]
  • MenHibrix: Men C/Y-tetanus-HiB (meningococcal C/Y, HiB, and tetanus antigens, formaldehyde) [39]
  • PedvaxHiB: Men B-HiB (meningococcal B and HiB antigens, aluminum) [40]
  • Hiberix: tetanus-HiB (tetanus toxoid and HiB antigens, formaldehyde, lactose) [41]
  • Comvax: Hep B-Men B-HiB (contains PedvaxHiB; hepatitis B, meningococcal B, and HiB antigens, yeast cells, soy, aluminum, and formaldehyde) [42]

 

So what’s the bottom line?

The bottom line is that HiB is so common that 100% of the population carries it at some point and virtually 100% of the population is immune to it by age 5. The vaccine does not prevent asymptomatic carriage and so cannot be relied upon for herd immunity. The vaccine simultaneously decreases the risk of H. influenzae type B, which makes up a minority of strains today, and increases the risk of all other H. influenzae strains. Vaccination of children is associated with an overall increased risk of H. influenzae invasive disease and death in both children and adults, especially the elderly. HiB vaccination is also associated with increased incidence of other more dangerous and less treatable bacterial infections. The vaccine is associated with type 1 diabetes, and the complications of vaccine-induced type 1 diabetes when vaccinated alone outweighs the risk of HiB disease when not vaccinated. The vaccine is also associated with other adverse events such as asthma, allergies, epiglottitis, an increased incidence of HiB disease in the first week after vaccination, and more. The bottom line is the risk of death is higher with the vaccine than without.

 

References

[1] http://www.cdc.gov/vaccines/schedules/downloads/child/0-18yrs-child-combined-schedule.pdf

[2] http://www.cdc.gov/vaccines/vpd-vac/hib/vac-faqs-hcp.htm

[3] http://healthycanadians.gc.ca/healthy-living-vie-saine/immunization-immunisation/children-enfants/schedule-calendrier-table-1-eng.php

[4] Evans, A.S. & Brachman, P.S. (2013). Bacterial Infections of Humans: Epidemiology and Control (Fifth Ed.). (pp. 315-316) New York: Springer-Verlag New York Inc.

[5] https://www.youtube.com/watch?v=QVE2l2RJ8lY

[6] http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/hib.pdf

[7] http://www.ncbi.nlm.nih.gov/pubmed/10569222

[8] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322072/

[9] http://www.ncbi.nlm.nih.gov/pubmed/8417239

[10] http://www.unboundmedicine.com/medline/citation/8143010/Eradication_of_Haemophilus_influenzae_type_b_disease_in_southern_California__Kaiser_UCLA_Vaccine_Study_Group_

[11] http://www.ncbi.nlm.nih.gov/books/NBK236299/

[12] http://www.cdc.gov/mmwr/preview/mmwrhtml/00041736.htm

[13] http://www.ncbi.nlm.nih.gov/pubmed/2785147

[14] http://www.ncbi.nlm.nih.gov/pubmed/3491315

[15] http://www.cdc.gov/mmwr/preview/mmwrhtml/00023705.htm

[16] https://schaabling.wordpress.com/2015/12/18/pertussis-whooping-cough/

[17] Weekly Topic 03: Meningococcal Vaccine (Meningitis)

[18] “Several factors indicate that mass immunisation with pertussis and other non-Hib vaccines may have been responsible for the unprecedented epidemics of invasive bacterial infections such as Hib, during the 1970’s and 1980’s.” (p. 315) Miller, N.Z. (2008). Vaccine Safety Manual.

[19] http://www.wellwithin1.com/HibPneuButler1993to2006letters.pdf

[20] http://www.ncbi.nlm.nih.gov/pubmed/14679101

[21] http://www.ncbi.nlm.nih.gov/pubmed/12482192

[22] http://www.ncbi.nlm.nih.gov/pubmed/12793601

[23] http://care.diabetesjournals.org/content/23/6/872.long

[24] Shoenfeld, Y., Agmon-Levin, N., & Tomljenovic, L. (2015). Vaccines and Autoimmunity (pp. 185-190). Hoboke, NJ: Wiley Blackwell.

[25] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1116914/

[26] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1114674/

[27] http://www.ncbi.nlm.nih.gov/pubmed/1669664

[28] http://www.ncbi.nlm.nih.gov/pubmed/8762955

[29] http://www.ncbi.nlm.nih.gov/pubmed/9133234

[30] http://soilandhealth.org/wp-content/uploads/02/0201hyglibcat/020152.vac.haz/vac.haz.pdf

[31] http://www.ncbi.nlm.nih.gov/books/NBK236284/

[32] http://www.ncbi.nlm.nih.gov/pubmed/9027536

[33] http://www.ncbi.nlm.nih.gov/pubmed/6335351

[34] https://web.archive.org/web/20041029232155/http://mothering.com/articles/growing_child/vaccines/biochemistry.html

[35] http://www.ncbi.nlm.nih.gov/pubmed/8103131

[36] http://www.ncbi.nlm.nih.gov/pubmed/3497381

[37] http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM109841.pdf

[38] http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM109810.pdf

[39] http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM308577.pdf

[40] http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM253652.pdf

[41] http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM179530.pdf

[42] http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM109869.pdf

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2 thoughts on “HiB Vaccine (Meningitis)

  1. Pingback: HiB Vaccine (Meningitis) SHORT | Schaabling Shire Shoppe

  2. Pingback: Pneumococcal Vaccine (Pneumonia, Meningitis) | Schaabling Shire Shoppe

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