Continuing Education Activity

The Haemophilus influenzae type b (Hib) vaccine is used to prevent invasive H. influenzae infections (usually caused by H. influenzae type b). It is in the vaccine class of medications. This activity describes the indications, mechanism of action, and contraindications for the Hib vaccine. Hib vaccine's role as a valuable agent in preventing early childhood meningitis and other complications of H. influenzae. This activity will also highlight the adverse event profile and other key factors (e.g., off-label uses, dosing, relevant interactions) pertinent for interprofessional healthcare team members in preventing H. influenzae type b infections.

Objectives:

• Describe the mechanism of action of the Hib vaccine.

• Identify the common adverse effects of the Hib vaccine.

• Review the appropriate timeframe for monitoring for adverse effects of the Hib vaccine.

• Summarize strategies for improving interpersonal coordination and communication to advance the use of the Haemophilus influenzae type b (Hib) vaccine and improve outcomes.

Indications

In the United States, the first Haemophilus influenzae type b (Hib) vaccine received approval in 1985 as a pure polysaccharide CPS vaccine, demonstrating 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 more robust protection against invasive Haemophilus type b infections leading to exclusive use of the conjugated form of Haemophilus influenzae type b vaccines in the USA.[1] In the 1980s, just before developing 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 USA 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, the FDA has no current recommendation for or against vaccination with Hib during pregnancy.[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] 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, 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 child's age when initiating catch-up and how many doses, if any, they received in the past.[2] Healthy children at least five years old and 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 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. Those with an elective splenectomy and at least 15 months old with no previous Hib vaccinations should receive one dose at least two weeks before the procedure. If an individual between 5 and 18 years old with HIV has never received the Hib vaccine, they should receive one dose. All individuals receiving hematopoietic stem cell transplants 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 and 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 adverse effects was made from these reports. Adverse effects are classified as either serious or non-serious. Serious AEs are defined as those which result in death, life-threatening illness, require an extended hospital stay, or permanent disability. 17% of the AEs classified as being serious. In descending order of frequency, the ten most common, serious AEs were fever, vomiting, convulsions, irritability, intussusception, diarrhea, crying, hypotonia, lethargy, and apnea. In descending order of frequency, the ten most common, non-serious AE’s 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. According to the death certificate, the most common cause of death 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 administering the Hib vaccine has not been shown to significantly decrease 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 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 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/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.

All healthcare team members need to 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 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 more severe illnesses.[4] [Level 5]

It is also 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 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]