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Haemophilus Influenza Type B Vaccine


Haemophilus Influenza Type B Vaccine

Article Author:
Hannah Brundage
Article Editor:
Santosh Mukka
Updated:
4/14/2020 7:28:08 PM
For CME on this topic:
Haemophilus Influenza Type B Vaccine CME
PubMed Link:
Haemophilus Influenza Type B Vaccine

Indications

In the United States, the first Haemophilus influenzae type b (Hib) vaccine received approval in 1985 as a pure polysaccharide CPS vaccine, which demonstrated ineffectiveness due to the young age at which this vaccine must be administered and was soon replaced by conjugated forms of the vaccine. The conjugated vaccines conferred longer and stronger protection against invasive Haemophilus type b infections leading to exclusive use of the conjugated form of Haemophilus influenzae type b vaccines in the US.[1] In the 1980s, just before the development of the Hib conjugate vaccine, Hib was the most common cause of meningitis in children less than five years old. By the early 1990s, the use of the Hib conjugate vaccine caused a 99% drop in infections caused by Hib.[2] Widespread use of the Hib vaccine has also been shown to significantly decrease rates of epiglottitis, which usually occurs in children.[3]  

Recommendations are that all infants receive the Hib vaccine. The FDA recommends one of two vaccine schedules for parents to choose from, both involve the first dose of the vaccine at two months of age. The earliest the first dose can be as early as six weeks of age. The schedules vary based on the brand of the vaccine.[2] The schedules themselves will be discussed further in the “Administration” section of the paper. Indications for the H. influenzae vaccine include children with mild illness (e.g., afebrile or low-grade fever) at the time of immunization visit. If the child has a fever, the physician should use clinical judgment, based on the severity of the fever and other symptoms, to determine if the child should receive the Hib vaccine at that visit. Ideally, immunizations should be given on time to prevent deviation from the vaccine schedule and the risk of missed doses over long periods.[4]

Other at-risk populations recommended to receive at least one booster of the Hib vaccine, depending on age and previous Hib vaccination status include: 

  • Chemotherapy
  • Hematopoietic stem cell transplant
  • Anatomic or functional asplenia
  • Elective splenectomy
  • HIV infection 
  • Immunoglobulin or early component complement deficiency

Research has shown that preterm and low-weight infants benefit from the same Hib vaccination schedule as at-term and average weight infants when using the hexavalent vaccine specifically.[5] 

Maternal immunization during the third trimester is not currently an FDA recommendation but has been studied in the U.S. and was shown to increase serum and cord blood antibody titers. Vaccination at this time was shown to be safe and did not harm the infants’ immune response to the vaccine, compared to infants whose mothers did not receive the vaccine.[6] Though this demonstrates the safety and potential benefit of vaccination during the third trimester of pregnancy, there is no current recommendation for or against vaccination with Hib during pregnancy by the FDA.[2]

Mechanism of Action

The composition of the polysaccharide capsule of Hib is of polyribosyl ribitol phosphate (PRP), which like other polysaccharide capsules, acts as an antigen that does not recruit T-cells. Therefore, the polysaccharide form of the vaccine is not immunogenic before the age of 2 years old because only small numbers of antibodies form via the T-cell independent immune process. The conjugate form of the vaccine is made by covalently attaching the PRP capsule to a protein, which will recruit T-cells and lead to the formation of sufficient numbers of anti-PRP antibodies.[7] Hib vaccines that are available in the U.S. as of 2019 use either tetanus toxoid conjugate or meningococcal protein conjugate.[1] The use of the Hib vaccine in combination with the acellular pertussis vaccine, as is the case in diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated poliovirus and Haemophilus b conjugate (tetanus toxoid conjugate) vaccine (DTaP-IPV/Hib) has been shown to decrease the immunogenicity and possibly contribute to the Hib vaccine failures.[1] Importantly, administration of the Hib vaccine and DTap (which contains acellular pertussis) at the same appointment but in different injection sites has shown no evidence of decreased Hib immunogenicity or increased Hib vaccine failures.[7]

Administration

The polysaccharide capsule of Hib is made of polyribosyl ribitol phosphate (PRP), which like other polysaccharide capsules, acts as an antigen that does not recruit T-cells. Therefore, the polysaccharide form of the vaccine is not immunogenic before the age of 2 years old because only small numbers of antibodies form via the T-cell independent immune process. The conjugate form of the vaccine is made by covalently attaching the PRP capsule to a protein, which will recruit T-cells and lead to the formation of sufficient numbers of anti-PRP antibodies.[7] Hib vaccines that are available in the U.S. as of 2019 use either tetanus toxoid conjugate or meningococcal protein conjugate.[1] The use of the Hib vaccine in combination with the acellular pertussis vaccine, as is the case in the Research has shown that diphtheria, Haemophilus B, pertussis, polio, tetanus vaccine to decrease the immunogenicity and possibly contribute to the Hib vaccine failures.[1] Importantly, administration of the Hib vaccine and DTaP (which contains acellular pertussis) at the same appointment but in different injection sites has shown no evidence of decreased Hib immunogenicity or increased Hib vaccine failures.[7]

For routine vaccination, two different schedules are FDA recommended, neither of which is more efficacious than the other. If using monovalent, monovalent tetanus toxoid conjugate, or polyvalent DTap, inactivated poliovirus, and Hib conjugate - vaccinate at 2, 4, 6 months and then a booster between 12 to 15 months. If using monovalent; meningococcal protein conjugate - vaccinate at 2 and 4 months with a booster between 12 to 15 months.[2][1] 

The catch-up schedule for the Hib vaccine depends on the age of the child when initiating catch-up and how many doses if any, they received in the past.[2] Healthy children who are at least five years old and have received no previous Hib vaccinations or an incomplete Hib schedule do not require further vaccination for Hib.[8]   

Children between the ages of 1 and 5 years old who are receiving chemotherapy or radiation, have anatomic or functional asplenia, have an HIV infection, or are immunoglobulin/complement deficient, are also recommended to be revaccinated with the Hib vaccine. If they received one or fewer doses of the Hib vaccine by one year of age, they should receive two more doses, eight weeks apart. If they received at least two doses of the Hib vaccine by one year of age, they should receive one additional dose, at least eight weeks after the most recent dose. Any dose given less than 14 days after the initiation of chemotherapy or radiation should be readministered greater than three months after chemotherapy is finished. For those with an elective splenectomy and at least 15 months old with no previous Hib vaccinations, they should be given one dose at least two weeks before the procedure. If an individual between 5 and 18 years old has with HIV has never received the Hib vaccine, they should receive one dose. All individuals receiving hematopoietic stem cell transplant should receive three doses of the Hib vaccine, within six to twelve months after a successful transplant; each dose should be four weeks apart [2].

Adverse Effects

Between 1990-2013, 29747 cases of adverse effects (AEs) following administration of the Hib vaccine were reported to the U.S. Vaccine Adverse Event Reporting System (VAERS). No attempt at describing the causality of AEs was made from these reports. AEs classified as either serious or non-serious. Serious AE’s defined as those which resulted in death, life-threatening illness, required a(n) extended hospital stay, or permanent disability. 17% of the AEs classified as being serious. The ten most common, serious AEs, in descending order of frequency were fever, vomiting, convulsions, irritability, intussusception, diarrhea, crying, hypotonia, lethargy, and apnea. The ten most common, non-serious AE’s, in descending order of frequency were fever, erythema at the injection site, crying, rash, irritability, screaming, hives, swelling of the injection site, agitation, and erythema.

One day after vaccine administration was the median time for onset of AEs reported to VAERS. There were fifty-six reported cases of anaphylaxis. Most occurred within one day of vaccine administration, with a range of 0 to 3 days. Eight hundred ninety-six deaths occurred after the administration of the Hib vaccine. The most common cause of death, according to the death certificate, was sudden infant death syndrome (SIDS). Importantly, there is abundant evidence that vaccines, in general, are not causally related to SIDS.[9] Although fever was the most common AE associated with the Hib vaccine, and this vaccine correlates with an increased risk of febrile seizures, prophylactic antipyretics are not recommended. The use of prophylactic antipyretics before the administration of the Hib vaccine has not been shown to decrease rates of febrile seizures significantly. It may even decrease the immune response to the vaccine.[10] It is not a current recommendation to administer antipyretics to children before the administration of the Hib vaccine.

Contraindications

Although there are reported cases of adverse events after receiving the Hib vaccine, these events are considered rare, and most are not considered contraindications for future doses of the Hib vaccine. The only current contraindication to receiving future doses of the Hib vaccine is when an individual has had a prior severe hypersensitivity reaction (such as anaphylaxis) to the vaccine or its constituents.[1] Individuals with known severe allergies to natural rubber latex should not receive [Haemophilus b Conjugate Vaccine (Tetanus Toxoid. Conjugate)], Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate), or [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)]. The combination vaccine [diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated poliovirus and Haemophilus b conjugate (tetanus toxoid conjugate)] has its own set of several relative contraindications that merit consideration because it is a pertussis-containing vaccine. The only other absolute contraindication to the Hib vaccine is age less than six weeks old.[8]

Enhancing Healthcare Team Outcomes

The widespread use of the Hib vaccine has greatly decreased the rates of early childhood meningitis, as well as epiglottitis.[2][3] This data may give parents the impression that the Hib vaccine is not necessary or is not worth the risk of possible adverse effects. For this reason, providers should emphasize to parents how dangerous meningitis and epiglottitis can be for their children and also about the low probability of significant adverse effects occurring because of the vaccine. Once parents understand that the disease processes that vaccines prevent are much more dangerous than almost all of the possible side effects, which are very rare, they may be more open to vaccinating their children. Often patients/parents may look to the nursing staff in the doctor’s office or their neighborhood pharmacist for guidance on whether they should vaccinate their children. It is essential for all members of the healthcare team to be consistent as far as vaccination recommendations and to educate the patients about how important the Hib vaccine (as well as any other vaccine) is to their child’s health and well-being. Staying up to date on current vaccine recommendations and having recommended vaccine schedules hanging up in the office or easily accessible to the staff are all helpful ways to make sure everyone is aware of what the recommendations are. Decreasing missed visits can help make sure that children receive their vaccinations on time. Calling parents to remind them that their child has an upcoming visit for immunizations and calling after missed appointments to reschedule immunizations could help with keeping children on track with their vaccinations. Providers should also carefully consider postponing vaccinations due to acute illness. Vaccinating children who present to their immunization appointments in a mild-moderately ill state is a good way to prevent children from falling behind on their vaccinations. Providers can explain to parents that this is safe to do and is often the better option than postponing vaccinations which protect children from much more severe illnesses.[4] [Level 5] Also, it is essential to emphasize the basis for the vaccination schedule for preterm or very low birth infants is on chronological age, not corrected age. Preterm infants are more likely to have an immature immune system, thereby necessitating the protection through vaccines from these invasive illnesses by Haemophilus influenzae. Perhaps the most crucial aspect of vaccinations to be able to reassure parents about in this day and age is that vaccinations do not cause or increase the risk of autism.[11] [Level 3] These interprofessional collaborations can improve vaccination rates and patient outcomes. [Level 5]


References

[1] Zarei AE,Almehdar HA,Redwan EM, Hib Vaccines: Past, Present, and Future Perspectives. Journal of immunology research. 2016;     [PubMed PMID: 26904695]
[2] Ventola CL, Immunization in the United States: Recommendations, Barriers, and Measures to Improve Compliance: Part 1: Childhood Vaccinations. P     [PubMed PMID: 27408519]
[3] Takala AK,Peltola H,Eskola J, Disappearance of epiglottitis during large-scale vaccination with Haemophilus influenzae type B conjugate vaccine among children in Finland. The Laryngoscope. 1994 Jun;     [PubMed PMID: 8196448]
[4] Lapphra K,Scheifele D, Can children with minor illnesses be safely immunized? Paediatrics     [PubMed PMID: 23024581]
[5] Omeñaca F,Vázquez L,Garcia-Corbeira P,Mesaros N,Hanssens L,Dolhain J,Puente Gómez I,Liese J,Knuf M, Immunization of preterm infants with GSK's hexavalent combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine: A review of safety and immunogenicity. Vaccine. 2018 Feb 8;     [PubMed PMID: 29336924]
[6] Chu HY,Englund JA, Maternal immunization. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2014 Aug 15;     [PubMed PMID: 24799324]
[7] Kelly DF,Moxon ER,Pollard AJ, Haemophilus influenzae type b conjugate vaccines. Immunology. 2004 Oct;     [PubMed PMID: 15379976]
[8] Briere EC,Rubin L,Moro PL,Cohn A,Clark T,Messonnier N, Prevention and control of haemophilus influenzae type b disease: recommendations of the advisory committee on immunization practices (ACIP). MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports. 2014 Feb 28;     [PubMed PMID: 24572654]
[9] Moro PL,Jankosky C,Menschik D,Lewis P,Duffy J,Stewart B,Shimabukuro TT, Adverse events following Haemophilus influenzae type b vaccines in the Vaccine Adverse Event Reporting System, 1990-2013. The Journal of pediatrics. 2015 Apr;     [PubMed PMID: 25598306]
[10] Monfries N,Goldman RD, Prophylactic antipyretics for prevention of febrile seizures following vaccination. Canadian family physician Medecin de famille canadien. 2017 Feb;     [PubMed PMID: 28209678]
[11] Taylor LE,Swerdfeger AL,Eslick GD, Vaccines are not associated with autism: an evidence-based meta-analysis of case-control and cohort studies. Vaccine. 2014 Jun 17;     [PubMed PMID: 24814559]