Pediatric Haemophilus Influenzae Infection Follow-up

• Inpatient care should concentrate on the disease syndrome associated with invasive Haemophilus influenzae type b (Hib) disease.
• As already noted, airway management, careful management of fluid and electrolyte problems (in particular, syndrome of inappropriate secretion of antidiuretic hormone [SIADH]), and use of seizure precautions may be appropriate with invasive infections, depending on the extent of disease.

Long-term neurodevelopmental evaluation, in particular audiologic assessment for possible deafness, is important in outpatient follow-up care of children with H influenzae meningitis.

• Chemoprophylaxis is 1 of 2 modalities for the prevention of Hib disease.

  • Chemoprophylaxis is used to prevent secondary disease.
  • With the widespread success of immunization, chemoprophylaxis now is of mostly historical interest.
  • Many reports have documented the increased risk of invasive disease among household contacts in the month after the onset of disease in the index patient. The rate is a function of age, approaching 4% in children younger than 2 years.
  • Rifampin is the most effective antibiotic for eradicating Hib from the nasopharynx, primarily because of its exquisite ability to penetrate respiratory secretions. Children younger than 12 years should receive 20 mg/kg once daily for 4 days, and adults should receive 600 mg once daily for 4 days.
  • Quinolones may also be effective, although they have not been studied sufficiently, and they are not approved for use in children.
  • Prophylaxis should be initiated as soon as possible, because the risk of secondary disease is greatest during the few days after disease onset in the index patient. Also, prophylaxis is recommended only if it can be administered within 2 weeks of disease onset.
  • Because therapeutic antibiotics do not consistently eradicate Hib from the nasopharynx, rifampin should be given to the index patient before discharge from the hospital.
  • The use of rifampin chemoprophylaxis in daycare settings remains controversial, primarily because the risk of secondary disease in this setting is not well defined. Coordination with the local health department and consultation with an expert are warranted. Fortunately, most daycare attendees now are immunized and, therefore, are at low risk of secondary disease.
• Active immunization is another modality for the prevention of Hib disease (ie, endemic disease). Polysaccharide vaccines once were used in active immunization.

  • The first vaccine used in an effort to prevent Hib invasive disease was a purified type b capsular polysaccharide vaccine that was introduced in the United States in 1985. However, the polyribosyl ribitol phosphate (PRP) vaccine was not consistently immunogenic or protective when administered to children younger than 2 years. Infants rarely responded to PRP vaccine, but both the proportion of responders and resultant antibody levels improved dramatically in those aged 1-2 years. Hence, the vaccine was initially licensed for use in children aged 18-24 months or older.
  • Although the vaccine could not protect infants and young children at greatest risk, it was licensed for use in older children to reduce at least a proportion of disease. After licensure, findings from most studies suggested that protection afforded by this vaccine was, at best, marginal.
  • By 1988, this vaccine was replaced by the more immunogenic conjugate vaccines.
• Conjugate vaccines are now used in active immunization.^[5]

  • These vaccines were developed in an effort to enhance immune responses to the PRP antigen. These vaccines consisted of a covalently linked PRP (in the process of conjugation) to an immunogenic carrier protein; a semisynthetic carrier-hapten was created. The predominant antibody is immunoglobulin G (IgG).
  • Findings from numerous studies in animals and children demonstrate that the HiB conjugate vaccines have immunologic properties characteristic of T-cell–dependent antigens. With these vaccines, much higher levels of antibodies are induced, particularly in infants and young children; booster responses occur with subsequent injections.
  • Four Hib conjugate vaccines have undergone extensive evaluation in humans, and they have been licensed for use in infants aged 2 months or older (see below).
  • A covalent linkage between the PRP molecule and a carrier protein is common to all of the Hib conjugate vaccines but is the only similarity because the vaccines differ in composition, structure, and resultant immune responses.
    • PRP-D vaccine, the first HiB conjugate vaccine licensed for use in older children, is the least immunogenic vaccine in infants. In efficacy trials, it protected infants and children in Finland but failed to protect young infants in Alaska. In both trials, only approximately one half of the infants had levels of antibody that were considered protective. PRP-D is licensed in the United States only for use in children aged 12 months or older.
    • HbOC vaccine, the first HiB conjugate vaccine licensed for use in infants, does not induce a significant antibody response with the first dose, which is administered to infants aged 2 months. After a second dose is administered in those aged 4 months, some, but not all, have protective levels of antibody. With a third dose, given to infants aged 6 months, essentially all have a high level of antibody. The protective effect of the vaccine was proven in a trial involving the Northern California Kaiser Health Plan. Follow-up findings in Northern California and throughout the United States have confirmed its protective effect. Doses are recommended for infants aged 2 months, 4 months, and 6 months, with a booster dose for those aged 12-15 months.
    • PRP-OMP vaccine appears to be the most immunogenic HiB conjugate vaccine in young infants. In contrast to the other vaccines, a first dose of PRP-OMP induces a good antibody response in most 2-month-old infants. Further doses in 4-month-old and 6-month-old infants increase the proportion of those who respond, but these do not lead to marked booster responses. Therefore, the use of only 2 doses is recommended: one in infants aged 2 months and one in those aged 4 months; a booster dose is administered at age 12-15 months.
    • PRP-T vaccine is similar to HbOC. The first dose given to 2-month-old infants causes little response, if any. Not all infants who receive a second dose when aged 4 months have protective levels of antibody, but after 3 doses, nearly all infants have high antibody levels. This vaccine is recommended for use in infants aged 2 months, 4 months, and 6 months; a booster dose is administered to those aged 12-15 months.
    • The PRP-T formulation approved most recently (Hiberix) is indicated only for use in children aged 15 months to 4 years.^[6]
  • The proliferation of newly licensed vaccines in the United States, with a shift away from the use of oral polio vaccine (OPV) to the use of inactivated polio vaccine (IPV), has resulted in the need to administer multiple injections at well-baby visits. In an effort to minimize the number of injections, strategies to mix vaccines in a single syringe have evolved.
    • Once such vaccine contains diphtheria-tetanus-pertussis (DTP) and HbOC (Tetramune). This product was licensed in 1995 for use as the primary series. However, the increased reactogenicity of whole-cell pertussis vaccine compared with that of the newer acellular pertussis vaccines has limited the usefulness of this product.
    • One combination vaccine consists of PRP-T and the Connaught diphtheria-tetanus-acellular pertussis (DTaP) vaccine (TriHIBit), which is licensed for administration as the fourth dose in the primary series. Unfortunately, current data are insufficient to support licensure of the DTaP-Hib combination vaccines for use in the primary series for infants. Clinical trials of some mixed Hib conjugate and acellular pertussis revealed a decrease in the anti-PRP antibody titer in some children, rendering problematic the licensure of such combination products for use in the primary series.
    • Another Hib combination vaccine, PRP-OMP and hepatitis B (Comvax) vaccine, does not appear to have this same degree of interference with anti-PRP responses, and this product is licensed for use in the primary series.
    • The combination of Dtap-Hib-IPV (Pentacel) is the latest combination vaccine to be approved in the United States. This vaccine is recommended at age 2 months, 4 months, and 6 months, with a booster at age 12-15 months.
    • A Hib conjugate and meningococcal YC conjugate combination vaccine is also under consideration by the FDA for approval for use in infants.
  • Combination vaccines require cautious evaluation, particularly in high-risk populations. In a high-risk Alaskan Native American population, change from the PRP-OMP vaccine to the DTP-HbOC vaccine resulted in a resurgence of invasive HiB disease, and children immunized with DTP-HbOC had demonstrable nasopharyngeal colonization with HiB. This finding indicated the existence of a reservoir of the organism in an immunized population.
  • The incidence of invasive Hib disease has declined dramatically in recent years; however, the experience in high-risk Native Americans is a reminder that Hib, though largely forgotten, is not yet eradicated. Diligence must be maintained to ensure that widespread immunization continues to prevent the reemergence of this serious pediatric infection.
  • The recent shortage of Hib conjugate vaccines in the United States resulted in an increased number of cases of invasive Hib disease and death in some children who were unimmunized or underimmunized against Hib. This recent experience clearly indicates that continued immunization against Hib diseases is necessary to keep the disease in check and keep children protected.^[7]

Even with prompt diagnosis and supportive care, the mortality rate with Hib meningitis is approximately 5%. Long-term sequelae occur in 15-30% of survivors and include sensorineural hearing loss, language disorders, mental retardation, and developmental disorders. In epiglottis, the mortality rate of 5-10% is invariably related to poor early airway control.

For excellent patient education resources, visit eMedicine's Cold and Flu Center. Also, see eMedicine's patient education article Flu in Children.