Prevention of Haemophilus inuenzae infection

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Official reprint from UpToDate www.uptodate.com 2014 UpToDate

Prevention of Haemophilus influenzae infection Author Sylvia Yeh, MD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Mar 2014. | This topic last updated: Mar 20, 2014. INTRODUCTION Haemophilus influenzae serotype b (Hib) was once the most common cause of bacterial meningitis and a frequent cause of other serious bacteremic infections, particularly in early childhood. The widespread use of Hib conjugate vaccines in infancy has led to a dramatic decline in the incidence of invasive Hib disease in children [1]. However, the disease remains common in countries not using the vaccine. Other strains of H. influenzae, particularly nontypeable H. influenzae (NTHi), remain important pathogens, causing mucosal and respiratory infections throughout life. Active immunization of young infants is the most important means for prevention of Hib infection. Another means of prevention that is now less commonly used is chemoprophylaxis for susceptible contacts of patients with invasive Hib disease. Passive prophylaxis with hyperimmune globulin is no longer used, except when intravenous immune globulin (IVIG) is administered to immunocompromised individuals who have impaired responses to vaccine (eg, for agammaglobulinemia). The development of vaccines for NTHi remains an active area of research. Prevention of Hib infections will be discussed below. The microbiology and epidemiology are discussed separately, as are the clinical manifestations and treatment of disease (eg, meningitis, epiglottitis, otitis media, sinusitis) (see individual topic reviews). (See "Microbiology, epidemiology and treatment of Haemophilus influenzae".) IMMUNIZATION Active immunization is the most important means of prevention of H. influenzae type b (Hib) infection, and it has nearly eliminated disease in most countries where it is used. Type b polysaccharide and polysaccharide conjugate vaccines induce antibodies to the type b capsular polysaccharide (polyribosylribitol phosphate, PRP), which is the most important antigen in conferring protective immunity [2]. Antibodies against PRP activate complement, are opsonophagocytic, bactericidal, and protect animals from lethal Hib challenge [3-7]. In addition, the observed age-related acquisition of natural immunity is associated with lower risk of disease [8-11]. Several trials of vaccine-induced immunity, detailed below, have shown dramatic protection. The first vaccine developed for the prevention of invasive Hib was a purified Hib capsular polysaccharide vaccine (PRP). It was licensed in 1985 for use as a single injection in children 18 months of age or older. Polysaccharide vaccines are poorly immunogenic in young children, particularly those younger than 18 months, because of the polysaccharide's inability to induce T-cell-dependent memory. A clinical trial of this vaccine in Finland suggested that a single dose given to children 18 to 71 months of age had protective efficacy of 90 percent [12,13]. Reanalysis of data after several reports of vaccine failure [14] indicated that the efficacy in children 18 to 36 months of age was incomplete and ranged from 7 to 95 percent [15]. For a brief time, this vaccine was recommended for toddlers to prevent a proportion of the disease burden in older children, but effectiveness was limited [16,17]. The limited immunogenicity of PRP in young children has been overcome by conjugating the polysaccharide to a carrier Section Editor Sheldon L Kaplan, MD Deputy Editor Mary M Torchia, MD

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protein, thereby inducing a stronger T-cell response. With conjugate vaccines, protective levels of antibodies are achieved after two or three doses in young infants (the number of doses required is dependent on the conjugate carrier). However, because of waning immunity, or an incomplete maturation of antibody by memory B cells, a booster dose is needed between 12 to 18 months to maximize protection [18,19]. Conjugate vaccines Several Hib conjugate vaccines are licensed in the United States and recommended by Advisory Committee on Immunization Practices (ACIP) (table 1). After one or more doses, each of these vaccines induces protective levels of antibody in immunocompetent children and adults. These vaccines are also immunogenic in infants but, as described below, the number of doses required varies, as does the amount of antibody induced by each vaccine [20]. ! PRP-OMP PRP-outer membrane protein conjugate vaccine (PRP-OMP, PedvaxHIB) conjugates PRP to protein components of outer membrane vesicles of a strain of serogroup B Neisseria meningitis (table 1). It is intended to prevent Hib, not N. meningitidis. PRP-OMP induces high antibody responses after a single dose in young infants (around two months of age) [2025]. After two doses (given at two and four months of age), more than 94 percent of infants mount an adequate antibody response [23,26]. Interestingly, a third dose at six months of age does not elicit an additional booster response. For high-risk infants, such as American Indian/Alaskan Native children, PRP-OMP has been recommended for the first dose in the Hib conjugate vaccine series [27,28]. PRP-OMP is licensed in the United States for use in a two-dose primary series (at two and four months) and as a booster dose (at 12 to 15 months) [27]. It is also available in a combination with hepatitis B vaccine (PRP-OMP/hepatitis B, Comvax). ! PRP-T PRP-tetanus toxoid conjugate vaccine (PRP-T) conjugates PRP to tetanus toxoid. Two PRP-T conjugate vaccines are licensed in the United States: ActHIB and Hiberix [29]. ActHIB ActHIB is licensed in the United States for use in a three-dose primary series (at two, four, and six months) and as a booster dose at 12 to 15 months (table 1). ActHIB is available in a combination with diphtheria-tetanus-acellular pertussis vaccine (DTaP) and the inactivated poliovirus (IPV) vaccine (DTaP-IPV/Hib, Pentacel) for use at 2, 4, 6, and 15 through 18 months [30]. Although whole-cell pertussis vaccine (DTP) is no longer used in the United States, in other countries, PRP-T is reconstituted with whole-cell DTP vaccine and used for the primary series and booster dose. This DTP-Hib vaccine retains immunogenicity for each of the four components and is used in many developing countries [31]. Hiberix Hiberix is licensed in the United States for use as the booster dose in children aged 15 months through 4 years who have received a primary Hib vaccination series of two or three doses (depending upon the formulation) [29]. It is not licensed for the primary series. In addition, a combination conjugate vaccine against Hib and meningococcus serogroups C and Y (Hib-MenCY, MenHibrix) was approved in June 2012 for infants and children 6 weeks to 18 months of age [32,33]. In prelicensure trials involving approximately 8000 children, Hib-MenCY vaccine was safe, immunogenic, and did not interfere with immune responses to routine immunizations [34-38]. In January 2013, the CDCs ACIP recommended immunization with Hib-MenCY for infants at increased risk of meningococcal disease (ie, those with persistent complement pathway deficiencies or anatomic or functional asplenia [including sickle cell disease]) and for infants in communities with
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outbreaks of serogroup C or Y meningococcal disease [39]. The routine and catch-up schedules for Hib-MenCY are discussed below. (See 'Combination Hib-meningococcal vaccine' below.) Hib conjugate vaccine dose and route Each dose of Hib conjugate vaccine consists of 0.5 mL and is administered intramuscularly. Hib conjugate vaccine schedules In the United States, the primary series of Hib conjugate vaccine, which is administered before seven months of age, requires two or three doses, depending upon the vaccine preparation (table 2 and table 3) [27]. The minimum age for the first dose is six weeks [40]. Hib conjugate vaccines (including Hib-MenCY) can be administered at the same visit as other routine childhood immunizations [39,41,42]. (See "Standard immunizations for children and adolescents", section on 'Overview'.) It is ideal to use the same Hib conjugate vaccine to complete the primary series. However, if it is unknown which vaccine was previously administered, or if the same vaccine is not available, the vaccines can be interchanged [27]. If two different preparations are used, a three-dose primary series is required. In the United States, a booster dose is recommended at 12 to 15 months of age (or as soon thereafter as possible); 12 months is the minimum age for the final dose [40]. For preterm infants with birth weight "1500 g, timely administration may be particularly important. In a secondary analysis of data from a multicenter observational study of pneumococcal conjugate vaccine in very low birth weight infants, only 79 percent achieved polyribosylribitol phosphate (PRP) titers #1 mcg/mL (the presumed concentration for long-term protection) after the primary series [43]. Any of the Hib conjugate vaccines may be used for the booster dose (table 2); the vaccine need not be the same as the one used for the primary series. The Hib conjugate vaccine schedule varies from country to country [44]. Some countries do not administer a booster dose after 12 months of age [44]. However, several studies suggest that a booster dose may be of importance for longterm protection [45-47]. A 2013 systematic review of 21 randomized trials from 15 countries comparing different Hib vaccine schedules (eg, three primary doses with no booster, three primary doses with a booster, two primary doses with a booster) found little difference between schedules with respect to development of seroprotection [45]. However, children who received a booster dose were more likely to be seropositive than children of the same age who did not receive a booster dose. A separate 2013 systematic review of 30 observational studies of Hib vaccine effectiveness from 17 countries also found no particular schedule to be superior and some evidence to suggest that a booster dose provides additional protection [46]. Efficacy/effectiveness Prelicensure clinical studies of Hib conjugate vaccines in large numbers of infants demonstrated a protective efficacy of #95 percent against invasive Hib disease after completion of the two- or three-dose primary series as recommended [48-50]. After licensure, the public health benefit of routine Hib immunization has far exceeded what would have been expected based on the efficacy trials alone. The added benefit appears to be due to herd immunity, such that widespread immunization reduces carriage and transmission in the community, even to those not fully immunized. Invasive Hib disease has been virtually eliminated from the United States and many other countries where the use of Hib conjugate vaccine is routine [51-53]. However, because Hib conjugate vaccines are infrequently used in developing countries, the global burden of Hib remains substantial [54,55]. The World Health Organization estimates that only 42 percent of the eligible population is vaccinated against Hib in developing countries, and only 8 percent in the poorest countries [44]. In the United Kingdom, where from 1992 to 2002, Hib conjugate vaccination was routine at two, three, and four months of age, an increase in Hib disease was noted beginning in 1998, and researchers found that Hib carriage was common in school-age children [56]. They postulated that the lack of a booster vaccination may in part have contributed to
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continued circulation of Hib. In 2003, a booster campaign for children under four years of age was initiated, with a resultant decrease in Hib disease rates. Possibly related to the United States Hib shortage from 2007 to 2009 [57,58], five cases of invasive Hib disease occurred in children younger than five years in Minnesota during 2008 [59]. Of the five children, three were completely unvaccinated due to parental or guardian deferral or refusal, one child was five months of age and had received two doses of PRP-T at two and four months of age, and one child was 15 months of age and had received PRP-OMP at two and four months of age but not the booster dose, based on the recommendations following the announcement of the Hib conjugate vaccine shortage in December 2007 [57]. The 15-month-old infant was later diagnosed with hypogammaglobulinemia. Review of Hib conjugate immunization uptake in Minnesota revealed a much lower rate of Hib vaccination coverage following the vaccine shortage announcement compared with previous years, as well as compared with concurrent DTaP and pneumococcal conjugate vaccine coverage. The increased number of cases may reflect increasing carriage and transmission of Hib affecting unvaccinated children during a period of diminished Hib vaccination coverage and prolonged deferral of the booster dose, related to a vaccine shortage [59]. Consequently, the longevity of the successful impact of Hib vaccination may be limited when there is a disruption in vaccination supply and delivery. For primary care providers, an effort to maximize delivery of the complete primary series of Hib vaccines in infants is crucial and to ensure an adequate stock of Hib conjugate vaccine for each child being vaccinated in their setting [59]. Contraindications and precautions Hib-containing vaccines are contraindicated in infants younger than six weeks and individuals with a severe allergy to any vaccine component (table 1) [60]. Adverse effects Systemic reactions (eg, fever, irritability) are infrequent after Hib immunization [61]. Local reactions, consisting of pain, redness, and/or swelling at the injection site occur in approximately 25 percent of recipients [61]. Such local reactions usually are mild and resolve within 24 hours. Special uses Catch-up schedule The catch-up schedule for Hib conjugate vaccine in immune competent children depends upon the age at which the series is initiated and the number of doses previously received (table 3) [42,62]: ! Children who are <6 months of age at initiation of vaccination should receive up to three doses of Hib conjugate vaccine (up to two doses of PRP-OMP) at four week intervals before 12 months of age and a booster dose at 12 to 15 months of age and at least eight weeks after the last dose in the primary series. ! Children who are 7 through 11 months of age at initiation of vaccination should receive two doses of Hib conjugate vaccine at four-week intervals and a booster dose at 12 to 15 months of age at least 8 weeks after the second dose of the primary series. ! Children who have received "1 dose of Hib conjugate vaccine before one year of age and are now 12 to 15 months of age should receive two doses of Hib conjugate vaccine eight weeks apart. ! Children with an incomplete series of Hib conjugate vaccination who are now 15 to 59 months of age should receive a single dose of Hib conjugate vaccine. ! Children #12 months who are at increased risk for meningococcal disease and have not received any doses of Hib or meningococcal vaccine may receive either 1) two doses of Hib-MenCY, given at least eight weeks apart or 2) a single dose of Hib conjugate vaccine (other than Hib-MenCY) and two doses of quadrivalent meningococcal conjugate vaccine, given at least 12 weeks apart (if they are <24 months) or eight weeks apart (if they are #24 months). Additional caveats apply if the child has anatomic or functional asplenia and has not completed immunization with the pneumococcal conjugate vaccine [42]. (See "Meningococcal vaccines", section on 'In infants
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and toddlers'.) Impaired host defense Certain individuals may be at increased risk of invasive Hib disease because of immune deficiency or other host-defense abnormalities (eg, anatomic or functional asplenia [including sickle cell disease], human immunodeficiency virus [HIV] infection, immunoglobulin deficiency, early component complement deficiency, recipients of hematopoietic stem cell transplant, and those receiving chemotherapy or radiation therapy) [27,60]. These individuals should receive Hib conjugate vaccine 0.5 mL intramuscularly as recommended for all infants. The combination Hibmeningococcal serogroups C and Y conjugate vaccine (Hib-MenCY) may be used for children 6 weeks through 18 months who are also at risk for meningococcal disease (ie, those with persistent complement pathway deficiencies or anatomic or functional asplenia [including sickle cell disease]). For incompletely immunized children 12 to 59 months of age who are at increased risk of invasive Hib disease, the following is recommended [27,60]: ! Those who received "1 dose of Hib conjugate vaccine before 12 months of age should receive two additional doses, separated by eight weeks. ! Those who received two doses of Hib conjugate vaccine before 12 months of age should receive one additional dose (at least eight weeks after the most recent dose). For unimmunized individuals at increased risk of Hib disease who are older than 59 months, the following is recommended [60]: ! Children >59 months and adults with sickle cell disease or anatomic or functional asplenia should receive a single dose of Hib conjugate vaccine [60,63-65]. ! Children >59 months through 18 years with HIV infection should receive a single dose of Hib conjugate vaccine; Hib conjugate vaccine is not recommended for adults with HIV-infection [65,66]. ! Children >15 months and adults who are scheduled for elective splenectomy should receive a single dose of Hib conjugate vaccine at least two weeks before the procedure [66]. (See "Prevention of sepsis in the asplenic patient", section on 'Timing of immunizations'.) Recommendations for Hib conjugate immunization of individuals with cancer, hematopoietic cell transplants, and solid organ transplants are discussed separately. (See "Immunizations in patients with cancer", section on 'Haemophilus influenzae vaccine' and "Immunizations in hematopoietic cell transplant candidates and recipients", section on 'Haemophilus influenzae' and "Immunizations in solid organ transplant candidates and recipients", section on 'Haemophilus influenzae'.) Previous history of invasive Hib disease Children who have invasive Hib infection before 24 months can remain at risk of developing a second episode of disease [27,60,67]. Such children should be immunized according to the age-appropriate schedule for unimmunized children and as if they had never received prior Hib vaccine [27,60]. Immunization should be initiated one month after the onset of invasive disease, or as soon thereafter as possible. Children who have invasive Hib disease after 24 months of age virtually always develop a protective immune response and do not require immunization. Children who develop invasive Hib disease despite two to three doses of Hib conjugate vaccine and those who have recurrent invasive Hib disease should undergo immunologic evaluation, particularly for IgG2 subclass deficiency [27,68]. (See "IgG subclass deficiency", section on 'IgG2 deficiency'.) Combination Hib-meningococcal vaccine The ACIP recommends the Hib-MenCY vaccine for infants in the United States at increased risk of meningococcal disease (ie, those with persistent complement pathway deficiencies or
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anatomic or functional asplenia [including sickle cell disease]). Hib-MenCY is given at 2, 4, 6, and 12 to 15 months of age [39,42]. If an infant at increased risk for meningococcal disease is behind on Hib vaccines, Hib-MenCY may be used following the same catch-up schedule used for Hib vaccine (table 2) (see 'Catch-up schedule' above) [39]. It is particularly important for such children who receive the first dose of Hib-MenCY at or after 12 months of age to receive two doses, at least 8 weeks apart to ensure protection against serogroups C and Y meningococcal disease [42]. Infants and children who receive Hib-MenCY are not protected against meningococcal serogroups A and W135. Such children who are planning to travel to areas with high endemic rates of meningococcal disease should receive an ageappropriate quadrivalent meningococcal conjugate (MCV4) vaccine at least two weeks before departure to provide protection against serogroups A and W135. Similarly, any child who has not received meningococcal vaccination should receive an age-appropriate series of MCV4 before travel to areas with high endemic rates of meningococcal disease. The appropriate vaccine and number of doses depends upon the underlying condition (table 4) [69]. (See "Meningococcal vaccines", section on 'In infants and toddlers'.) INFECTION CONTROL Patients with known or suspected H. influenzae type b (Hib) infections should be in private rooms, and hospital personnel should wear a face mask when they are within 3 feet (1 meter) of the patient (ie, droplet precautions) for 24 hours after the initiation of parenteral antimicrobial therapy [27]. The doors of rooms used to house these patients may remain open. (See "General principles of infection control", section on 'Droplet precautions'.) ANTIBIOTIC PROPHYLAXIS OF CLOSE CONTACTS Before the routine use of H. influenzae type b (Hib) vaccines, a prospective study evaluated 4311 household contacts of 1147 patients with Hib meningitis for the development of invasive Hib disease within 30 days of the onset of illness in the index patient [70]. The risk of Hib meningitis among household contacts was 585 times the age-adjusted risk in the general population. The overall risk of invasive Hib disease among household contacts was 0. 21 percent; however, the risk varied according to age as follows: ! 0 to 11 months 6 percent ! 12 to 23 months 1.4 percent ! 24 to 47 months 1.5 percent ! 48 to 71 months 0.1 percent ! #6 years 0 percent If close contacts of the index case receive antimicrobial prophylaxis soon after the index case is diagnosed, pharyngeal carriage of Hib in the contact can be eradicated, thereby reducing the risk of developing invasive disease, and interrupting transmission. (See "Pathogenesis and pathophysiology of bacterial meningitis".) Efficacy In placebo-controlled randomized trials and observational studies, administration of rifampin (20 mg/kg per dose) eliminated oropharyngeal carriage of Hib in at least 95 percent of household or daycare contacts of patients with invasive Hib disease (compared with less than 30 percent of patients in the placebo arm or no treatment arm) [71-75]. Drugs other than ceftriaxone and cefotaxime that may be used to treat Hib infections, such as ampicillin [76-78], cefaclor [79,80], trimethoprim-sulfamethoxazole [81], and erythromycin-sulfisoxazole [79] are not effective for chemoprophylaxis because they do not reliably eradicate Hib from the nasopharynx. We recommend not using these agents for antimicrobial prophylaxis against invasive Hib disease. Indications Chemoprophylaxis may be indicated for household (or close) contacts of a child with invasive Hib disease, child-care or preschool contacts, and the index patient, depending upon individual circumstances as described below [27]. Chemoprophylaxis is not indicated for contacts of people with invasive disease caused by nontype b strains of H.
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influenzae. Close contact Close (household) contact is defined as a person who resides with the index patient or who spent #4 hours with the index patient for at least five of the seven days before the day of hospital admission of the index case [27]. Chemoprophylaxis is recommended for all household contacts (including the index case) in the following circumstances [27]: ! Household with at least one contact <4 years who has not received an age-appropriate number of doses of Hib conjugate vaccine. (See 'Hib conjugate vaccine schedules' above.) The susceptible child(ren) should receive a dose of Hib conjugate vaccine and be scheduled for completion of Hib immunization if additional doses are necessary to complete immunization. (See 'Hib conjugate vaccine schedules' above.) ! Household with a contact who is an immunocompromised child (<18 years), regardless of that child's Hib immunization status. Monitoring for illness In addition to receiving antimicrobial prophylaxis, exposed unimmunized or incompletely immunized children who are household contacts of patients with invasive Hib disease must be carefully observed for signs of illness [27]. Exposed children in whom febrile illness develops should receive prompt medical attention. The child should be examined carefully for a focus of infection, including consideration of a lumbar puncture based on clinical presentation and risk factors, such as the age of the patient. If a focus of infection is found, the infection should be treated accordingly after appropriate cultures are obtained. If occult bacteremia is suspected, parenteral antibiotics should be administered pending the culture result. Child care or preschool contacts Chemoprophylaxis for child care or school contacts after one case of invasive Hib disease is controversial. Epidemiologic studies have reached different conclusions regarding the risk among child care contacts compared with household contacts [82]. The American Academy of Pediatrics and Advisory Committee on Immunization Practices recommend chemoprophylaxis for child-care and preschool contacts (regardless of age or vaccine status) when unimmunized or incompletely immunized children attend the facility and two or more cases of Hib invasive disease have occurred among attendees within 60 days [27,60]. Exposed unimmunized or incompletely immunized children who are child-care or preschool contacts of patients with invasive Hib disease must be carefully observed for signs of illness [27]. Exposed children in whom febrile illness develops should receive prompt medical attention, as described above. (See 'Monitoring for illness' above.) Index patient If the index patient was treated with an agent other than cefotaxime or ceftriaxone, antimicrobial therapy to eradicate nasopharyngeal carriage is recommended if either of the following also is true for the index patient [27,60,83-85]: ! Is younger than two years of age, or ! Lives in a household with a child <4 years of age who has not received an age-appropriate number of doses of Hib conjugate vaccine, or an immunocompromised child. (See 'Hib conjugate vaccine schedules' above.) Recommended regimen Prophylaxis should be initiated as soon as possible in contacts; in the index case, it should

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be initiated within two weeks of the onset of disease and may be initiated in conjunction with treatment [86]. Rifampin is the drug of choice for chemoprophylaxis [27]. The regimen is as follows: ! Rifampin 20 mg/kg (maximum dose 600 mg) once per day for four days The dose of rifampin for infants <1 month of age has not been established; some experts recommend lowering the dose to 10 mg/kg [27]. Consultation with an expert in infectious diseases is recommended for contacts in whom rifampin is contraindicated. PASSIVE IMMUNIZATION A human hyperimmunoglobulin from immunized adult donors (bacterial polysaccharide immunoglobulin) was developed before H. influenzae type b (Hib) conjugate vaccines were widely available. Although this preparation was effective in preventing disease in high-risk settings [87], it is no longer available. NONTYPEABLE H. INFLUENZAE (NTHi) VACCINE CANDIDATES Although the routine use of type b vaccines has virtually eliminated invasive H. influenzae type b (Hib) disease, the burden of disease caused by other serotypes and NTHi remains unchanged. NTHi are important pathogens as a cause of acute otitis media, acute sinusitis, bronchitis, and community-acquired pneumonia. (See "Microbiology, epidemiology and treatment of Haemophilus influenzae" and "Pneumonia in children: Epidemiology, pathogenesis, and etiology", section on 'In children <5 years' and "Acute otitis media in children: Epidemiology, microbiology, clinical manifestations, and complications", section on 'Bacteria' and "Acute bacterial rhinosinusitis in children: Microbiology and treatment", section on 'Microbiology'.) The development of a vaccine that is effective against both NTHi and Hib has the potential to reduce the burden of disease due to all types of H. influenzae. Identification of the ideal immunogen(s) requires further study. In addition, it is important to determine whether the prevention of mucosal infections involves protective antibodies. Since NTHi lack a polysaccharide capsule, type b anticapsular vaccines are not effective against NTHi infections. Vaccines effective against NTHi mucosal infections employ cell wall proteins as immunogens. Bacterial proteins that have been pursued as vaccine candidates include outer membrane proteins [88-92], adhesin molecules [93-97], and lipooligosaccharide [98]. INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) ! Beyond the Basics topic (see "Patient information: Vaccines for infants and children age 0 to 6 years (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Vaccine ! Active immunization of infants is the major means of prevention of Haemophilus influenzae type b (Hib) infection. (See 'Immunization' above.) ! Active immunization also leads to herd immunity such that high immunization levels reduce disease transmission even to the unimmunized. (See 'Efficacy/effectiveness' above.)

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! We recommend immunization of all infants with a Hib conjugate vaccine (table 1) (Grade 1A). (See 'Hib conjugate vaccine schedules' above.) ! We also recommend catch-up immunization for children younger than five years who are unimmunized or underimmunized (Grade 1A). (See 'Catch-up schedule' above.) ! We recommend that children who have invasive Hib disease before 24 months of age be immunized according to the age-appropriate schedule for unimmunized children (Grade 1B). Immunization should be initiated one month after the onset of invasive disease. (See 'Previous history of invasive Hib disease' above.) Antimicrobial prophylaxis ! Chemoprophylaxis of close contacts eradicates nasopharyngeal carriage of Hib, thereby reducing the risk of developing invasive disease and/or transmission. (See 'Antibiotic prophylaxis of close contacts' above and "Pathogenesis and pathophysiology of bacterial meningitis".) ! To prevent invasive disease in susceptible children, we recommend chemoprophylaxis for close contacts of patients with invasive Hib disease who live in a household with a child who is younger than four years of age and has not received an age-appropriate number of doses of Hib conjugate vaccine, or an immunocompromised child (Grade 1A). (See 'Hib conjugate vaccine schedules' above and 'Close contact' above.) ! We recommend chemoprophylaxis for child-care and preschool contacts when unimmunized or incompletely immunized children attend the facility and two or more cases of Hib invasive disease have occurred among attendees within 60 days (Grade 1A). (See 'Child care or preschool contacts' above.) ! We recommend chemoprophylaxis for the index patient if he or she was treated with an agent other than cefotaxime or ceftriaxone and is younger than two years of age or lives in a household with a child <4 years of age who has not received an age-appropriate number of doses of Hib conjugate vaccine, or an immunocompromised child (Grade 1A). (See 'Hib conjugate vaccine schedules' above and 'Index patient' above.) ! We recommend rifampin for Hib chemoprophylaxis (Grade 1A). The dose is 20 mg/kg (maximum dose 600 mg) once per day for four days. (See 'Recommended regimen' above.) Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Centers for Disease Control and Prevention (CDC). Progress toward eliminating Haemophilus influenzae type b disease among infants and children--United States, 1987-1997. MMWR Morb Mortal Wkly Rep 1998; 47:993. 2. Robbins JB, Schneerson R, Pittman M.. H. influenzae type b infections. In: Bacterial Vaccines, Germanier R (Ed), Academic Press, Orlando, FL 1984. p.290. 3. Tosi MF, Kaplan SL, Mason EO, et al. Generation of chemotactic activity in serum by Haemophilus influenzae type b. Infect Immun 1984; 43:593. 4. Tarr PI, Hosea SW, Brown EJ, et al. The requirement of specific anticapsular IgG for killing of Haemophilus influenzae by the alternative pathway of complement activation. J Immunol 1982; 128:1772. 5. Steele NP, Munson RS Jr, Granoff DM, et al. Antibody-dependent alternative pathway killing of Haemophilus influenzae type b. Infect Immun 1984; 44:452. 6. Newman SL, Waldo B, Johnston RB Jr. Separation of serum bactericidal and opsonizing activities for Haemophilus influenzae type b. Infect Immun 1973; 8:488. 7. Myerowitz RL, Norden CW. Immunology of the infant rat experimental model of Haemophilus influenzae type b meningitis. Infect Immun 1977; 16:218.
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8. Fothergill LD, Wright J. Influenzal meningitis: the relation of age incidence to the bactericidal power of blood against the causal organism. J Immunol 1933; 24:273. 9. Johnston RB Jr, Anderson P, Rosen FS, Smith DH. Characterization of human antibody to polyribophosphate, the capsular antigen of Hemophilus influenzae, type B. Clin Immunol Immunopathol 1973; 1:234. 10. Norden CW. Prevalence of bactericidal antibodies to Haemophilus influenzae, type b. J Infect Dis 1974; 130:489. 11. Stull TL, Jacobs RF, Haas JE, et al. Human serum bactericidal activity against Haemophilus influenzae type b. J Gen Microbiol 1984; 130:665. 12. Peltola H, Kyhty H, Virtanen M, Mkel PH. Prevention of Hemophilus influenzae type b bacteremic infections with the capsular polysaccharide vaccine. N Engl J Med 1984; 310:1561. 13. Peltola H, Kyhty H, Sivonen A, Mkel H. Haemophilus influenzae type b capsular polysaccharide vaccine in children: a double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland. Pediatrics 1977; 60:730. 14. Granoff DM, Shackelford PG, Suarez BK, et al. Hemophilus influenzae type B disease in children vaccinated with type B polysaccharide vaccine. N Engl J Med 1986; 315:1584. 15. Ward JI, Broome CV, Harrison LH, et al. Haemophilus influenzae type b vaccines: lessons for the future. Pediatrics 1988; 81:886. 16. Greenberg DP, Vadheim CM, Bordenave N, et al. Protective efficacy of Haemophilus influenzae type b polysaccharide and conjugate vaccines in children 18 months of age and older. JAMA 1991; 265:987. 17. Osterholm MT, Rambeck JH, White KE, et al. Lack of efficacy of Haemophilus b polysaccharide vaccine in Minnesota. JAMA 1988; 260:1423. 18. Berrington JE, Cant AJ, Matthews JN, et al. Haemophilus influenzae type b immunization in infants in the United Kingdom: effects of diphtheria/tetanus/acellular pertussis/Hib combination vaccine, significant prematurity, and a fourth dose. Pediatrics 2006; 117:e717. 19. Lee YC, Kelly DF, Yu LM, et al. Haemophilus influenzae type b vaccine failure in children is associated with inadequate production of high-quality antibody. Clin Infect Dis 2008; 46:186. 20. Granoff DM, Anderson EL, Osterholm MT, et al. Differences in the immunogenicity of three Haemophilus influenzae type b conjugate vaccines in infants. J Pediatr 1992; 121:187. 21. Bulkow LR, Wainwright RB, Letson GW, et al. Comparative immunogenicity of four Haemophilus influenzae type b conjugate vaccines in Alaska Native infants. Pediatr Infect Dis J 1993; 12:484. 22. Vella PP, Staub JM, Armstrong J, et al. Immunogenicity of a new Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) (PedvaxHIB). Pediatrics 1990; 85:668. 23. Shapiro ED, Capobianco LA, Berg AT, Zitt MQ. The immunogenicity of Hemophilus influenzae type B polysaccharide-Neisseria meningitidis group B outer membrane protein complex vaccine in infants and young children. J Infect Dis 1989; 160:1064. 24. Campbell H, Byass P, Ahonkhai VI, et al. Serologic responses to an Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine in very young Gambian infants. Pediatrics 1990; 86:102. 25. Ahonkhai VI, Lukacs LJ, Jonas LC, Calandra GB. Clinical experience with PedvaxHIB, a conjugate vaccine of Haemophilus influenzae type b polysaccharide--Neisseria meningitidis outer membrane protein. Vaccine 1991; 9 Suppl:S38. 26. Yogev R, Arditi M, Chadwick EG, et al. Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate): immunogenicity and safety at various doses. Pediatrics 1990; 85:690. 27. American Academy of Pediatrics. Haemophilus influenzae infections. In: Red Book: 2012 Report of the Committee on Infectious Diseases, 29th, Pickering LK. (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2012. p.345. 28. Galil K, Singleton R, Levine OS, et al. Reemergence of invasive Haemophilus influenzae type b disease in a wellvaccinated population in remote Alaska. J Infect Dis 1999; 179:101. 29. Centers for Disease Control and Prevention (CDC). Licensure of a Haemophilus influenzae type b (Hib) vaccine
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Prevention of Haemophilus inuenzae infection

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(Hiberix) and updated recommendations for use of Hib vaccine. MMWR Morb Mortal Wkly Rep 2009; 58:1008. 30. Centers for Disease Control and Prevention (CDC). Licensure of a diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated poliovirus, and haemophilus B conjugate vaccine and guidance for use in infants and children. MMWR Morb Mortal Wkly Rep 2008; 57:1079. 31. Miller MA, Meschievitz CK, Ballanco GA, Daum RS. Safety and immunogenicity of PRP-T combined with DTP: excretion of capsular polysaccharide and antibody response in the immediate post-vaccination period. Pediatrics 1995; 95:522. 32. US Food and Drug Administration. News & Events. FDA approves new combination vaccine that protects children against two bacterial diseases. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm308350.htm? utm_campaign=Google2&utm_source=fdaSearch&utm_medium=website&utm_term=Menhibrix&utm_content=1 (Accessed on June 15, 2012). 33. GSK receives FDA approval for MenHibrix. http://www.gsk.com/media/pressreleases/2012/2012-pressrelease1134059.htm (Accessed on June 15, 2012). 34. Bryant KA, Marshall GS. Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine for infants and toddlers. Expert Rev Vaccines 2011; 10:941. 35. Marchant CD, Miller JM, Marshall GS, et al. Randomized trial to assess immunogenicity and safety of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in infants. Pediatr Infect Dis J 2010; 29:48. 36. Marshall GS, Marchant CD, Blatter M, et al. Co-administration of a novel Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine does not interfere with the immune response to antigens contained in infant vaccines routinely used in the United States. Hum Vaccin 2011; 7:258. 37. Bryant K, McVernon J, Marchant C, et al. Immunogenicity and safety of measles-mumps-rubella and varicella vaccines coadministered with a fourth dose of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in toddlers: a pooled analysis of randomized trials. Hum Vaccin Immunother 2012; 8:1036. 38. Bryant KA, Marshall GS, Marchant CD, et al. Immunogenicity and safety of H influenzae type b-N meningitidis C/Y conjugate vaccine in infants. Pediatrics 2011; 127:e1375. 39. Centers for Disease Control and Prevention (CDC). Infant meningococcal vaccination: Advisory Committee on Immunization Practices (ACIP) recommendations and rationale. MMWR Morb Mortal Wkly Rep 2013; 62:52. 40. American Academy of Pediatrics. Active Immunization. In: Red Book: 2012 Report of the Committee on Infectious Diseases, 29th, Pickering LK. (Ed), American Academy of Pediatrics, Elk Grove Village, IL p.11. 41. Trofa AF, Klein NP, Paul IM, et al. Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age. Pediatr Infect Dis J 2011; 30:e164. 42. Cohn AC, MacNeil JR, Clark TA, et al. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013; 62:1. 43. D'Angio CT, Murray TE, Li L, et al. Immunogenicity of Haemophilus influenzae Type b Protein Conjugate Vaccines in Very Low Birth Weight Infants. Pediatr Infect Dis J 2013; 32:1400. 44. Morris SK, Moss WJ, Halsey N. Haemophilus influenzae type b conjugate vaccine use and effectiveness. Lancet Infect Dis 2008; 8:435. 45. Low N, Redmond SM, Rutjes AW, et al. Comparing Haemophilus influenzae type b conjugate vaccine schedules: a systematic review and meta-analysis of vaccine trials. Pediatr Infect Dis J 2013; 32:1245. 46. Jackson C, Mann A, Mangtani P, Fine P. Effectiveness of Haemophilus influenzae type b vaccines administered according to various schedules: systematic review and meta-analysis of observational data. Pediatr Infect Dis J 2013; 32:1261. 47. Perrett KP, John TM, Jin C, et al. Long-term Persistence of Immunity and B-Cell Memory Following Haemophilus influenzae Type b Conjugate Vaccination in Early Childhood and Response to Booster. Clin Infect Dis 2014; 58:949.
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Prevention of Haemophilus inuenzae infection

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48. Fritzell B, Plotkin S. Efficacy and safety of a Haemophilus influenzae type b capsular polysaccharide-tetanus protein conjugate vaccine. J Pediatr 1992; 121:355. 49. Black SB, Shinefield HR, Fireman B, et al. Efficacy in infancy of oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine in a United States population of 61,080 children. The Northern California Kaiser Permanente Vaccine Study Center Pediatrics Group. Pediatr Infect Dis J 1991; 10:97. 50. Santosham M, Wolff M, Reid R, et al. The efficacy in Navajo infants of a conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex. N Engl J Med 1991; 324:1767. 51. Centers for Disease Control and Prevention (CDC). Progress toward elimination of Haemophilus influenzae type b invasive disease among infants and children--United States, 1998-2000. MMWR Morb Mortal Wkly Rep 2002; 51:234. 52. Cowgill KD, Ndiritu M, Nyiro J, et al. Effectiveness of Haemophilus influenzae type b Conjugate vaccine introduction into routine childhood immunization in Kenya. JAMA 2006; 296:671. 53. Scheifele DW, Bettinger JA, Halperin SA, et al. Ongoing control of Haemophilus influenzae type B infections in Canadian children, 2004-2007. Pediatr Infect Dis J 2008; 27:755. 54. Peltola H. Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates. Clin Microbiol Rev 2000; 13:302. 55. Watt JP, Wolfson LJ, O'Brien KL, et al. Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates. Lancet 2009; 374:903. 56. Oh SY, Griffiths D, John T, et al. School-aged children: a reservoir for continued circulation of Haemophilus influenzae type b in the United Kingdom. J Infect Dis 2008; 197:1275. 57. Centers for Disease Control and Prevention (CDC). Interim recommendations for the use of Haemophilus influenzae type b (Hib) conjugate vaccines related to the recall of certain lots of Hib-containing vaccines (PedvaxHIB and Comvax). MMWR Morb Mortal Wkly Rep 2007; 56:1318. 58. Centers for Disease Control and Prevention (CDC). Updated recommendations for use of Haemophilus influenzae type b (Hib) vaccine: reinstatement of the booster dose at ages 12-15 months. MMWR Morb Mortal Wkly Rep 2009; 58:673. 59. Centers for Disease Control and Prevention (CDC). Invasive Haemophilus influenzae Type B disease in five young children--Minnesota, 2008. MMWR Morb Mortal Wkly Rep 2009; 58:58. 60. Briere EC, Rubin L, Moro PL, et al. Prevention and Control of Haemophilus influenzae Type b Disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2014; 63:1. 61. Decker MD, Edwards KM, Bradley R, Palmer P. Comparative trial in infants of four conjugate Haemophilus influenzae type b vaccines. J Pediatr 1992; 120:184. 62. Akinsanya-Beysolow I, Advisory Committee on Immunization Practices (ACIP), ACIP Child/Adolescent Immunization Work Group, Centers for Disease Control and Prevention (CDC). Advisory Committee on Immunization Practices recommended immunization schedules for persons aged 0 through 18 years - United States, 2014. MMWR Morb Mortal Wkly Rep 2014; 63:108. 63. Kaplan SL, Duckett T, Mahoney DH Jr, et al. Immunogenicity of Haemophilus influenzae type b polysaccharidetetanus protein conjugate vaccine in children with sickle hemoglobinopathy or malignancies, and after systemic Haemophilus influenzae type b infection. J Pediatr 1992; 120:367. 64. Frank AL, Labotka RJ, Rao S, et al. Haemophilus influenzae type b immunization of children with sickle cell diseases. Pediatrics 1988; 82:571. 65. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014; 58:e44. 66. Schlaudecker EP, Englund JA, Kimberlin DW. Update from the Advisory Committee on Immunization Practices. J Pediatric Infect Dis Soc 2013; 2:97. 67. Edmonson MB, Granoff DM, Barenkamp SJ, Chesney PJ. Outer membrane protein subtypes and investigation of
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recurrent Haemophilus influenzae type b disease. J Pediatr 1982; 100:202. 68. Holmes SJ, Lucas AH, Osterholm MT, et al. Immunoglobulin deficiency and idiotype expression in children developing Haemophilus influenzae type b disease after vaccination with conjugate vaccine. The Collaborative Study Group. JAMA 1991; 266:1960. 69. Centers for Disease Control and Prevention (CDC). Recommendation of the Advisory Committee on Immunization Practices (ACIP) for use of quadrivalent meningococcal conjugate vaccine (MenACWY-D) among children aged 9 through 23 months at increased risk for invasive meningococcal disease. MMWR Morb Mortal Wkly Rep 2011; 60:1391. 70. Ward JI, Fraser DW, Baraff LJ, Plikaytis BD. Haemophilus influenzae meningitis. A national study of secondary spread in household contacts. N Engl J Med 1979; 301:122. 71. Band JD, Fraser DW, Ajello G. Prevention of Hemophilus influenzae type b disease. JAMA 1984; 251:2381. 72. Glode MP, Daum RS, Halsey NA, et al. Rifampin alone and in combination with trimethoprim in chemoprophylaxis for infections due to Haemophilus influenzae type b. Rev Infect Dis 1983; 5 Suppl 3:S549. 73. Granoff DM, Gilsdorf J, Gessert C, Basden M. Haemophilus influenzae type B disease in a day care center: eradication of carrier state by rifampin. Pediatrics 1979; 63:397. 74. Glode MP, Daum RS, Boies EG, et al. Effect of rifampin chemoprophylaxis on carriage eradication and new acquisition of Haemophilus influenzae type b in contacts. Pediatrics 1985; 76:537. 75. Shapiro ED, Wald ER. Efficacy of rifampin in eliminating pharyngeal carriage of Haemophilus influenzae type b. Pediatrics 1980; 66:5. 76. Gessert C, Granoff DM, Gilsdorf J. Comparison of rifampin and ampicillin in day care center contacts of Haemophilus influenzae type b disease. Pediatrics 1980; 66:1. 77. Mason EO Jr, Kaplan SL, Lamberth LB, et al. Serotype and ampicillin susceptibility of Haemophilus influenzae causing systemic infections in children: 3 years of experience. J Clin Microbiol 1982; 15:543. 78. Ginsburg CM, McCracken GH Jr, Rae S, Parke JC Jr. Haemophilus influenzae type b disease. Incidence in a daycare center. JAMA 1977; 238:604. 79. Horner DB, McCracken GH Jr, Ginsburg CM, Zweighaft TC. A comparison of three antibiotic regimens for eradication of Haemophilus influenzae type b from the pharynx of infants and children. Pediatrics 1980; 66:136. 80. Yogev R, Melick C, Kabat K. Nasopharyngeal carriage of Haemophilus influenzae type b: attempted eradication by cefaclor or rifampin. Pediatrics 1981; 67:430. 81. Yogev R, Lander HB, Davis AT. Effect of TMP-SMX on nasopharyngeal carriage of ampicillin-sensitive and ampicillin-resistant hemophilus influenzae type B. J Pediatr 1978; 93:394. 82. Daum RS, Granoff DM, Gilsdorf J, et al. Haemophilus influenzae type b infections in day care attendees: implications for management. Rev Infect Dis 1986; 8:558. 83. Ogle JW, Rabalais GP, Glode MP. Duration of pharyngeal carriage of Haemophilus influenzae type b in children hospitalized with systemic infections. Pediatr Infect Dis 1986; 5:509. 84. Murphy TV, Del Rio MA, Chrane D. Persistent pharyngeal colonization during therapy in patients with meningitis caused by Haemophilus influenzae type b. J Infect Dis 1985; 152:849. 85. Goldwater PN. Effect of cefotaxime or ceftriaxone treatment on nasopharyngeal Haemophilus influenzae type b colonization in children. Antimicrob Agents Chemother 1995; 39:2150. 86. Li KI, Wald ER. Use of rifampin in Haemophilus influenzae type b infections. Am J Dis Child 1986; 140:381. 87. Santosham M, Reid R, Ambrosino DM, et al. Prevention of Haemophilus influenzae type b infections in high-risk infants treated with bacterial polysaccharide immune globulin. N Engl J Med 1987; 317:923. 88. Pittman M. THE ACTION OF TYPE-SPECIFIC HEMOPHILUS INFLUENZAE ANTISERUM. J Exp Med 1933; 58:683. 89. Barenkamp SJ, Munson RS Jr, Granoff DM. Subtyping isolates of Haemophilus influenzae type b by outermembrane protein profiles. J Infect Dis 1981; 143:668. 90. Murphy TF, Dudas KC, Mylotte JM, Apicella MA. A subtyping system for nontypable Haemophilus influenzae
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Prevention of Haemophilus inuenzae infection

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based on outer-membrane proteins. J Infect Dis 1983; 147:838. 91. Murphy TF, Nelson MB, Dudas KC, et al. Identification of a specific epitope of Haemophilus influenzae on a 16,600-dalton outer membrane protein. J Infect Dis 1985; 152:1300. 92. DeMaria TF, Murwin DM, Leake ER. Immunization with outer membrane protein P6 from nontypeable Haemophilus influenzae induces bactericidal antibody and affords protection in the chinchilla model of otitis media. Infect Immun 1996; 64:5187. 93. St Geme JW 3rd. The pathogenesis of nontypable Haemophilus influenzae otitis media. Vaccine 2000; 19 Suppl 1:S41. 94. Barenkamp SJ, Leininger E. Cloning, expression, and DNA sequence analysis of genes encoding nontypeable Haemophilus influenzae high-molecular-weight surface-exposed proteins related to filamentous hemagglutinin of Bordetella pertussis. Infect Immun 1992; 60:1302. 95. Winter LE, Barenkamp SJ. Human antibodies specific for the high-molecular-weight adhesion proteins of nontypeable Haemophilus influenzae mediate opsonophagocytic activity. Infect Immun 2003; 71:6884. 96. Barenkamp SJ, St Geme JW 3rd. Identification of a second family of high-molecular-weight adhesion proteins expressed by non-typable Haemophilus influenzae. Mol Microbiol 1996; 19:1215. 97. Cutter D, Mason KW, Howell AP, et al. Immunization with Haemophilus influenzae Hap adhesin protects against nasopharyngeal colonization in experimental mice. J Infect Dis 2002; 186:1115. 98. Gu XX, Sun J, Jin S, et al. Detoxified lipooligosaccharide from nontypeable Haemophilus influenzae conjugated to proteins confers protection against otitis media in chinchillas. Infect Immun 1997; 65:4488. Topic 6022 Version 18.0

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GRAPHICS Comparison of conjugate vaccines against Haemophilus influenzae type b licensed in the United States
Vaccine (commercial name)
Monovalent Hib vaccines PRP-OMP* (PedVaxHIB) PRP-T (ActHIB) PRP-T (Hiberix) Outer membrane protein complex of Neisseria meningitidis Tetanus toxoid Tetanus toxoid 2, 4, and 12 through 15 months 2, 4, 6, and 12 through 15 months 12 through 15 months (following primary series with PRP-OMP or ActHIB) Vial stoppers contain natural rubber latex Vial stoppers contain natural rubber latex Tip caps of prefilled syringes may contain natural rubber latex

Recommended Carrier protein age of administration

Allergy considerations

Combination Hib vaccines PRP-OMP-Hepatitis B* (Comvax) DTaP-IPV/PRP-T (Pentacel) Hib-MenCY ! (Menhibrix) Outer membrane protein complex of N. meningitidis Tetanus toxoid 2, 4, and 12 through 15 months 2, 4, 6, and 15 through 18 months 2, 4, 6, and 12 through 15 months Vial stoppers contain natural rubber latex; vaccine contains yeast Vial stoppers do not contain natural rubber latex Vial stoppers do not contain natural rubber latex Hib: Haemophilus influenzae type b; PRP-OMP: polyribosylribitol phosphate conjugated to outer membrane protein complex of N. meningitidis; PRP-T: polyribosylribitol phosphate conjugated to tetanus toxoid; DTaP: diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine; IPV: inactivated polio vaccine; Hib-MenCY: combination Hib and meningococcus serogroups C and Y conjugate vaccine. ! * Preferred for Native Americans and Alaskan natives. May be given as early as age 12 months of age, provided at least six months have elapsed since the third dose of DTaP. ! ! Recommended for use in infants at increased risk for meningococcal disease (ie, those with persistent complement pathway deficiencies or anatomic or functional asplenia [including sickle cell disease]). Data from: Briere EC, Rubin L, Moro PL, et al. Prevention and control of Haemophilus influenzae type b disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2014; 63:1. Graphic 64312 Version 7.0

Tetanus toxoid

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Recommended routine schedule of administration of conjugate Haemophilus influenzae type b vaccine for children in the United States
Primary series (<12 months of age)
2, 4, and 6 months for ActHIB, DTaP-IPV/PRP-T, or HibMenCY* 2 and 4 months for PRP-OMP or PRP-OMP-HepB

Booster (!12 months of age)

12 through 15 months for PRP-OMP, PRP-T (ActHIB or Hiberix), PRP-OMP-HepB, and HibMenCY* 15 through 18 months for DTaP-IPV/PRP-T

DTaP: diphtheria tetanus-toxoid-acellular pertussis vaccine; IPV: inactivated polio vaccine; PRP-T: polyribosylribitol phosphate conjugated to tetanus toxoid; HibMenCY: combination Haemophilus influenzae type b and meningococcus serogroups C and Y conjugate vaccine; PRP-OMP: polyribosylribitol phosphate conjugated to the outer membrane protein complex of Neisseria meningitidis; HepB: hepatitis B. * The Advisory Committee on Immunization Practices recommends HibMenCY for infants at increased risk for meningococcal disease (ie, those with persistent complement pathway deficiencies or anatomic or functional asplenia [including sickle cell disease]). May be given as early as age 12 months of age, provided at least six months have elapsed since the third dose of DTaP. Data from:! 1. Briere EC, Rubin L, Moro PL, et al. Prevention and Control of Haemophilus influenzae Type b Disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2014; 63:1. 2. Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, CDC. Prevention and control of meningococcal disease. MMWR Recomm Rep 2013; 62:1. Graphic 77170 Version 12.0

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Catch-up schedule for Haemophilus influenzae type b (Hib) immunization for children (<5 years) in the United States who are not at high-risk of invasive Hib disease
Current age
<6 months

Catch-up regimen
Up to three doses of PRP-T* or two doses of PRP-OMP "4 weeks apart before age 12 months and one dose of Hib conjugate vaccine at 12 through 15 months of age at least 8 weeks after the previous dose Up to two doses of PRP-T* or PRP-OMP "4 weeks apart before age 12 months and one dose of Hib conjugate vaccine at 12 through 60 months of age at least 8 weeks after the previous dose Two doses of Hib conjugate vaccine "8 weeks apart, up to 60 months of age Single dose of Hib conjugate vaccine ! up to 60 months of age

7 through 11 months

12 through 14 months 15 months through 5 years

PRP-T: polyribosylribitol phosphate conjugated to tetanus toxoid; PRP-OMP: polyribosylribitol phosphate conjugated to the outer membrane protein complex of Neisseria meningitidis. ! * ActHIB is the only PRP-T Hib conjugate vaccine approved for this age group. Combination Haemophilus influenzae type b and meningococcus serogroups C and Y conjugate vaccine (Hib-MenCY) is only approved for children 6 weeks through 18 months of age. ! ! If Hib-MenCY is used, two doses should be given at least eight weeks apart. Data from: 1. Briere EC, Rubin L, Moro PL, et al. Prevention and Control of Haemophilus influenzae Type b Disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2014; 63:1. 2. Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, CDC. Prevention and control of meningococcal disease. MMWR Recomm Rep 2013; 62:1. 3. Akinsanya-Beysolow I, Immunization Services Division, National Center for Immunization and Respiratory Diseases, CDC. Advisory committee on immunization practices recommended immunization schedules for persons aged 0 through 18 years - United States, 2014. MMWR Morb Mortal Wkly Rep 2014; 63:108. Graphic 94432 Version 1.0

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Meningococcal vaccination recommendations in the United States by age and/or risk factor
Targeted group by age and/or risk factor
People ages 11 through 18 years

Primary dose(s)
Give patients without HIV infection 1 dose of Menactra or Menveo, preferably at age 11 or 12 years; give HIV-infected patients 2 doses of Menactra or Menveo at least 2 months apart

Booster dose(s)
Give booster at age 16 years if primary dose given at age 12 years or younger Give booster at age 16 through 18 years if primary dose given at age 13 through 15 years* Give booster if previous dose given at age younger than 16 years

People ages 19 through 21 years who are first year college students living in residence halls

Give patients without HIV infection 1 dose of Menactra or Menveo; give HIV-infected patients 2 doses of Menactra or Menveo at least 2 months apart

Travelers to or residents of countries where meningococcal disease is hyperendemic or epidemic , people present during outbreaks caused by a vaccine serogroup "# and other people with prolonged increased risk for exposure (eg, microbiologists routinely working with Neisseria meningitidis) For children age 2 through 18 months For children age 7 through 23 months who have not initiated a series of Menveo or MenHibrix For age 2 through 55 years Give Menveo at ages 2, 4, 6, and 12 to 15 months Give 2 doses, separated by 3 months of Menveo (if age 7 to 23 months) or Menactra (if age 9 to 23 months) Give patients without HIV infection 1 dose of Menactra or Menveo; give HIV-infected patients 2 doses of Menactra or Menveo at least 2 months apart Give patients without HIV infection and no previous Menactra or Menveo dose and either short-term travel or outbreak-related 1 dose of Menomune; give HIV-infected patients two doses of Menactra or Menveo at least 2 months apart; all others, give 1 dose of Menactra or Menveo People with persistent complement component deficiencies ""
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If risk continues, give initial booster after 3 years followed by boosters every 5 years

Boost every 5 years with Menactra or Menveo **

For age 56 years and older

Boost every 5 years with Menactra or Menveo**

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For age 2 through 18 months

Give Menveo or MenHibrix at ages 2, 4, 6, and 12 to 15 months Give 2 doses, separated by 3 months, of Menveo (if age 7 to 23 months) or Menactra (if age 9 to 23 months) Give 2 doses of Menactra or Menveo, 2 months apart Give 2 doses of Menactra or Menveo, 2 months apart

Give Menactra or Menveo booster after 3 years followed by boosters every 5 years thereafter

For children age 7 through 23 months who have not initiated a series of Menveo or MenHibrix For ages 2 through 55 years For age 56 years and older

Boost every 5 years with Menactra or Menveo ## Boost every 5 years with Menactra or Menveo ##

People with functional or anatomic asplenia, including sickle cell disease For age 2 through 18 months Give Menveo or MenHibrix at ages 2, 4, 6, and 12 to 15 months Give 2 doses of Menveo, 3 months apart Give Menactra or Menveo booster after 3 years followed by boosters every 5 years thereafter

For children age 19 through 23 months who have not initiated a series of Menveo or MenHibrix For ages 2 through 55 years For age 56 years and older

Give 2 doses of Menactra or Menveo, 2 months apart Give 2 doses of Menactra or Menveo, 2 months apart

Boost every 5 years with Menactra or Menveo ## Boost every 5 years with Menactra or Menveo ##

This table was adapted from the recommendations of the United States Centers for Disease Control and Prevention's (CDC's) Advisory Committee on Immunization Practices (ACIP) for the use of meningococcal vaccines [1,2,3]. The quadrivalent meningococcal conjugate vaccines (MenACWY) are Menactra (MenACWY-D) and Menveo (MenACWY-CRM). The quadrivalent meningococcal polysaccharide vaccine is Menomune (MPSV4). MenHibrix (HibMenCY) is a combination conjugate vaccine against meningococcus serogroups C and Y and Haemophilus influenzae type b.
* The minimum interval between doses of Menactra or Menveo is eight weeks. Prior receipt of MenHibrix is not sufficient for children traveling to the Hajj or African meningitis belt as it doesn't provide protection against serogroups A or W. ! Seek advice of local public health authorities to determine if vaccination is recommended. # Given the outbreak of meningococcal disease (first reported in the fall of 2012) in men who have sex with men (MSM) in New York City, we recommend meningococcal vaccination for MSM, especially if HIV-infected, if their residence, travel, or social interactions put them in close contact with other MSM from New York City [4,5,6]. Children ages 2 through 18 months who are present during outbreaks caused by serogroups C or Y may be given an age-appropriate series of MenHibrix. If a child age 7 through 23 months will enter an endemic area in less than three months, give doses as

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close as two months apart. If using Menveo, dose 2 should be given no younger than age 12 months. If primary dose(s) given when younger than age 7 years, give initial booster after three years, followed by boosters every five years. ** Booster doses are recommended if the person remains at increased risk. Only the quadrivalent meningococcal polysaccharide vaccine (Menomune, MPSV4) has been approved by the US Food and Drug Administration for individuals "56 years of age. However, a quadrivalent meningococcal conjugate vaccine (Menactra or Menveo) is preferred by the ACIP for individuals in this age group who are expected to require revaccination since limited data demonstrate a higher antibody response after a subsequent dose of a quadrivalent meningococcal conjugate vaccine compared with a subsequent dose of the quadrivalent meningococcal polysaccharide vaccine. Please refer to the associated topic review for additional details. !! Persistent complement component deficiencies include C3, C5 to C9, properdin, factor H, and factor D. ## If the person received a one-dose primary series, give booster at the earliest opportunity, then boost every five years. Children with functional or anatomic asplenia should complete an age-appropriate series of the pneumococcal conjugate vaccine (PCV13) before vaccination with Menactra; Menactra should be given at least four weeks following the last dose of PCV13. Menveo or MenHibrix may be given at any time before or after PCV13. Adapted from the Immunization Action Coalition (www.immunize.org). Data from: 1. Cohn AC, MacNeil JR, Clark TA, et al. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013; 62:1. 2. Akinsanya-Beysolow I, Immunization Services Division, National Center for Immunization and Respiratory Diseases, CDC. Advisory Committee on Immunization Practices recommended immunization schedules for persons aged 0 through 18 years - United States, 2014. MMWR Morb Mortal Wkly Rep 2014; 63:108. 3. Bridges CB, Coyne-Beasley T. Advisory Committee on Immunization Practices recommended immunization schedule for adults aged 19 years or older - United States, 2014. Ann Intern Med 2014; 160:190. 4. Notes from the field: serogroup C invasive meningococcal disease among men who have sex with men - New York City, 2010-2012. MMWR Morb Mortal Wkly Rep 2013; 61:1048. 5. New York State Department of Health. New York State Department of Health expands vaccination recommendation in response to meningococcal disease outbreak among high risk HIV positive men in New York City. http://www.health.ny.gov/press/releases/2012/2012-10-05_meningitis.htm (Accessed on October 26, 2012). 6. Commonwealth of Massachusetts Department of Public Health. Health Advisory: Meningococcal vaccine recommendations for men who have sex with men. October 25, 2012. http://www.mass.gov/eohhs/docs/dph/cdc/immunization/alerts-meningococcal-msm.pdf (Accessed on October 26, 2012). Graphic 71265 Version 47.0

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