Haemophilus influenzae Type b Vaccine

Mechanism of Action

The composition of the polysaccharide capsule of Hib is 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 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 recruits T-cells and leads to the formation of sufficient numbers of anti-PRP antibodies.[7] The Hib vaccines available in the U.S. as of 2019 use either tetanus toxoid conjugate or meningococcal protein conjugate.[1] 

Research has shown that 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

For routine vaccination, 2 schedules are recommended by the FDA, neither of which is more efficacious. If using monovalent, monovalent tetanus toxoid conjugate, or polyvalent DTap, inactivated poliovirus, and Hib conjugate - vaccinate at 2, 4, and 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 child's age when initiating catch-up and how many doses, if any, they received in the past.[2] Healthy children at least 5 years old who have received no previous Hib vaccinations or an incomplete Hib schedule do not require further Hib vaccination.[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 1 or fewer doses of the Hib vaccine by 1 year of age, they should receive 2 more doses 8 weeks apart. If they received at least 2 doses of the Hib vaccine by 1 year of age, they should receive 1 additional dose at least 8 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 3 months after chemotherapy is finished. Those with an elective splenectomy and at least 15 months old with no previous Hib vaccinations should receive 1 dose at least 2 weeks before the procedure. If an individual between 5 and 18 years old with HIV has never received the Hib vaccine, they should receive 1 dose. All individuals receiving hematopoietic stem cell transplants should receive 3 doses of the Hib vaccine within 6 to 12 months after a successful transplant; each dose should be 4 weeks apart.[2]

Adverse Effects

Between 1990 and 2013, 29747 cases of adverse effects following the administration of the Hib vaccine were reported to the U.S. Vaccine Adverse Event Reporting System (VAERS). No attempt was made to describe the causality of adverse effects from these reports. Adverse effects are classified as either serious or non-serious. Serious adverse effects are defined as those that result in death, life-threatening illness, require an extended hospital stay, or permanent disability—17% of the adverse effects are classified as being serious. In descending order of frequency, the 10 most common, serious adverse effects were fever, vomiting, convulsions, irritability, intussusception, diarrhea, crying, hypotonia, lethargy, and apnea. In descending order of frequency, the 10 most common, non-serious adverse effects 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 adverse effects reported to VAERS. There were 56 reported cases of anaphylaxis. Most occurred within 1 day of vaccine administration, ranging from 0 to 3 days. Eight hundred ninety-six deaths occurred after the administration of the Hib vaccine. According to the death certificate, the most common cause of death was sudden infant death syndrome. Importantly, there is abundant evidence that vaccines, in general, are not causally related to sudden infant death syndrome.[9] Although fever was the most common adverse effect associated with the Hib vaccine, and this vaccine correlates with an increased risk of febrile seizures, prophylactic antipyretics are not recommended. Prophylactic antipyretics before administering the Hib vaccine have not significantly decreased rates of febrile seizures. It may even decrease the immune response to the vaccine.[10] It is not a current recommendation to administer antipyretics to children before administering 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 at least 6 weeks old.[8]

Enhancing Healthcare Team Outcomes

The widespread use of the Hib vaccine has greatly decreased the rates of early childhood meningitis and epiglottitis.[2][3] This data may give parents the impression that the Hib vaccine is unnecessary 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 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 and parents look to the nursing staff in the doctor’s office or their neighborhood pharmacist for guidance on whether they should vaccinate their children.

All healthcare team members must be consistent regarding vaccination recommendations and 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 helpful ways to make sure everyone is aware of the recommendations. Decreasing missed visits can help ensure 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 keep children on track with their vaccinations. Providers should also carefully consider postponing vaccinations due to acute illness. Vaccinating children who attend their immunization appointments in a mild-moderately ill state is a good way to prevent them from falling behind on their vaccinations. Providers can explain to parents that this is safe and is often the better option than postponing vaccinations that protect children from more severe illnesses.[4]

It is also essential to emphasize that the basis for the vaccination schedule for preterm or very low-birth infants is chronological age, not corrected age. Preterm infants are more likely to have an immature immune system, necessitating vaccine protection from these invasive illnesses by Haemophilus influenzae. Perhaps the most crucial aspect of vaccinations to reassure parents about in this day and age is that vaccinations do not cause or increase the risk of autism.[11] These interprofessional collaborations can improve vaccination rates and patient outcomes.