December 7, 2007 Addendum
On October 17, 2007, the U.S. Food and Drug Administration approved quadrivalent meningococcal conjugate vaccine (MCV4) (Menactra®, Sanofi Pasteur, Swiftwater, Pennsylvania) for use in children aged 2 to 10 years, in addition to its prior approval for use in persons aged 11 to 55 years. Previous Advisory Committee on Immunization Practices (ACIP) recommendations called for routine vaccination with meningococcal polysaccharide vaccine (MPSV4) (Menomune®, Sanofi Pasteur) of children aged 2 to 10 years who are at increased risk for meningococcal disease. These children include travelers to or residents of countries in which meningococcal disease is hyperendemic or epidemic, children who have terminal complement component deficiencies, and children who have anatomic or functional asplenia. This notice provides updated recommendations for meningococcal vaccination among children aged 2 to 10 years at increased risk for meningococcal disease.
In anticipation of possible licensure of MCV4 for children aged 2 to 10 years, during February 2007--October 2007, the ACIP meningococcal vaccine workgroup reviewed data on MCV4 immunogenicity and safety in children in that age group. On the basis of these data, opinions of workgroup members, and feedback from partner organizations, the workgroup proposed recommendations for use of MCV4 among children aged 2 to 10 years who are at increased risk for meningococcal disease. The recommendations were approved by ACIP at its October 24, 2007, meeting.
In a single, randomized, modified double-blind, controlled study of healthy U.S. children aged 2 to 10 years that compared MCV4 with MPSV4, serum bactericidal antibody geometric mean titers against all four serogroups were significantly higher at both 28 days and 6 months after vaccination in the children who received MCV4. In the same study, rates of most solicited local and systemic adverse events after vaccination with MCV4 were comparable to rates observed after vaccination with MPSV4. Although duration of protective immunity from MCV4 is not yet known, conjugate vaccines generally have a longer duration of protection than polysaccharide vaccines.
At its October meeting, ACIP revised its recommendation to state that MCV4 is preferable to MPSV4 for vaccination of children aged 2 to 10 years who are at increased risk for meningococcal disease. These children include travelers to or residents of countries in which meningococcal disease is hyperendemic or epidemic, children who have terminal complement component deficiencies, and children who have anatomic or functional asplenia. Additionally, MCV4 is preferred to MPSV4 for use among children aged 2 to 10 years for control of meningococcal disease outbreaks. Providers may elect to vaccinate children aged 2 to 10 years who are infected with human immunodeficiency virus (HIV).* For children aged 2 to 10 years who have previously received MPSV4 and remain at increased risk for meningococcal disease, ACIP recommends vaccination with MCV4 at 3 years after receipt of MPSV4. Children who last received MPSV4 more than 3 years ago and remain at risk for meningococcal disease should be vaccinated with MCV4 as soon as possible. For children at lifelong increased risk for meningococcal disease, subsequent doses of MCV4 likely will be needed. ACIP will make recommendations for revaccination with MCV4 as more data on duration of protection become available.
*Children with HIV infection likely are at increased risk for meningococcal disease, although not to the extent that they are at risk for invasive Streptococcus pneumoniae infection. The efficacy of MCV4 among HIV-infected children is unknown.
Persons with a history of Guillain-Barré syndrome (GBS) might be at increased risk for GBS after MCV4 vaccination; therefore, a history of GBS is a precaution to administering MCV4. For children with a history of GBS, MPSV4 is an acceptable alternative for short-term (i.e., 3 to 5 years) protection against meningococcal disease.
The ACIP meningococcal vaccine workgroup is considering options for general use of MCV4 among children aged 2 to 10 years. Recommendations will be presented at a future ACIP meeting. Recommendations for use of MCV4 in persons aged 11 to 55 years, including a recommendation for routine vaccination with MCV4 of persons aged 11 to 18 years, have been published previously and remain unchanged.
August 10, 2007 Addendum
In January 2005, a quadrivalent meningococcal polysaccharide-protein conjugate vaccine (MCV4) (Menactra™, Sanofi Pasteur, Inc., Swiftwater, Pennsylvania) was licensed for use among persons aged 11-55 years. In May 2005, the Advisory Committee on Immunization Practices (ACIP) recommended routine vaccination with 1 dose of MCV4 for persons aged 11-12 years, persons entering high school (i.e., at approximately age 15 years) if not previously vaccinated with MCV4, and other persons at increased risk for meningococcal disease, including college freshmen living in dormitories. Background information regarding meningococcal disease and the vaccine, including a discussion of duration of protection and use of the vaccine for outbreak control, has been published previously.
In June 2007, ACIP revised its recommendation to include routine vaccination of all persons aged 11 to 18 years with 1 dose of MCV4 at the earliest opportunity. Persons aged 11-12 years should be routinely vaccinated at the 11 to 12 years health-care visit as recommended by ACIP. ACIP continues to recommend routine vaccination for persons aged 19-55 years who are at increased risk for meningococcal disease: college freshmen living in dormitories, microbiologists routinely exposed to isolates of Neisseria meningitidis, military recruits, travelers to or residents of countries in which N. meningitidis meningitis is hyperendemic or epidemic, persons with terminal complement component deficiencies, and persons with anatomic or functional asplenia.
The ACIP goal is routine vaccination of all adolescents with MCV4 beginning at age 11 years. ACIP and partner organizations, including the American Academy of Pediatrics, American Academy of Family Physicians, American Medical Association, and Society for Adolescent Medicine, recommend a health-care visit for children aged 11-12 years to receive recommended vaccinations and indicated preventive services. This visit is the optimal time for adolescents to receive MCV4. In addition, because the incidence of meningococcal disease increases during adolescence, health-care providers should vaccinate previously unvaccinated persons aged 11-18 years with MCV4 at the earliest possible health-care visit. College freshmen living in dormitories are at increased risk for meningococcal disease and should be vaccinated with MCV4 before college entry if they have not been vaccinated previously. Because of difficulties in targeting freshmen in dormitories, colleges may elect to target their vaccination campaigns to all matriculating freshmen.
The ACIP meningococcal vaccine workgroup reviewed updated data on MCV4 use and supply projections and data presented previously on the epidemiology of meningococcal disease, safety, and the cost-effectiveness of MCV vaccination strategies. On the basis of these data, expert opinion of the workgroup members, and feedback from partner organizations, the workgroup revised the MCV4 recommendations, which were approved by ACIP at the June 2007 meeting.
The 2005 ACIP MCV4 recommendation was influenced by concern that implementation of MCV4 recommendations might be hindered by reduced vaccine supply during the first few years of production. In 2005 and 2006, peaks in demand were observed during the months when children were returning to school after summer vacation, leading to limited vaccine availability. However, as of June 2007, ACIP expects supply of MCV4 to be sufficient to meet increased vaccine demand resulting from the revised recommendations. ACIP anticipates that recommending vaccination of all persons aged 11-18 years will improve MCV4 vaccination coverage in this age group and simplify provider decisions to vaccinate.
ACIP encourages health-care providers to vaccinate with MCV4 throughout the year to minimize seasonal increases in demand during July and August when students prepare to return to school from summer vacation. Vaccine providers should administer MCV4 and Tdap (tetanus toxoid, reduced diphtheria toxoid and acellular pertussis) vaccine to persons aged 11-18 years during the same visit if both vaccines are indicated and available. If simultaneous vaccination is not feasible (e.g., a vaccine is not available), MCV4 and Tdap can be administered using any order of administration. When making decisions about timing of vaccination, providers should consider that eligibility for the Vaccines for Children Program ends at age 19 years.
Guillain-Barré syndrome (GBS) has been associated with receipt of MCV4. Persons with a history of GBS might be at increased risk for postvaccination GBS; therefore, a history of GBS is a relative contraindication to receiving MCV4. Persons recommended to receive meningococcal vaccination who have a history of GBS (or their parents) should discuss the decision to be vaccinated with their health-care provider. Meningococcal polysaccharide vaccine (MPSV4) is an acceptable alternative for short-term protection against meningococcal disease (3-5 years). Providers who have questions about ordering MCV4 or MPSV4 may contact Sanofi Pasteur by telephone at 1-800-VACCINE or online at http://www.vaccineshoppe.com.
May 2005 Recommendations for Use of Meningococcal Vaccines
Routine Vaccination of Adolescents
The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of young adolescents (defined in this report as persons aged 11-12 years) with meningococcal conjugate vaccine (MCV4) at the preadolescent health-care visit (i.e., a visit to a health-care provider at age 11-12 years, at which time ACIP and other professional organizations [e.g., the American Academy of Pediatrics and the American Medical Association] recommend that persons aged 11-12 years receive appropriate vaccinations and other preventive services). Introducing a recommendation for MCV4 vaccination among persons aged 11-12 years might strengthen the role of the preadolescent health-care visit and have a positive effect on vaccine coverage during adolescence. For those adolescents who have not previously received MCV4, ACIP recommends vaccination before high school entry (at approximately age 15 years) as an effective strategy to reduce meningococcal disease incidence among adolescents and young adults. By 2008, the goal will be routine vaccination with MCV4 of all adolescents beginning at age 11 years. Other adolescents who wish to decrease their risk for meningococcal disease may elect to receive vaccine.
Other Populations at Increased Risk for Meningococcal Disease
Routine vaccination also is recommended for certain persons who have increased risk for meningococcal disease (see Table below). Use of MCV4 is preferred among persons aged 11-55 years; however, use of the meningococcal polysaccharide vaccine (MPSV4) is recommended among children aged 2-10 years and persons aged >55 years. If MCV4 is unavailable, MPSV4 is an acceptable alternative for persons aged 11-55 years.
The following populations are at increased risk for meningococcal disease:
- College freshmen living in dormitories
- Microbiologists who are routinely exposed to isolates of Neisseria meningitidis
- Military recruits
- Persons who travel to or reside in countries in which N. meningitidis is hyperendemic or epidemic, particularly if contact with the local population will be prolonged
- Persons who have terminal complement component deficiencies
- Persons who have anatomic or functional asplenia
Because of feasibility constraints in targeting freshmen in dormitories, colleges can elect to target their vaccination campaigns to all matriculating freshmen. The risk for meningococcal disease among nonfreshmen college students is similar to that for the general population of similar age (age 18-24 years). However, the vaccines are safe and immunogenic and therefore can be provided to nonfreshmen college students who want to reduce their risk for meningococcal disease.
For travelers, vaccination is especially recommended to those visiting the parts of sub-Saharan Africa known as the "meningitis belt" during the dry season (December-June). Vaccination is required by the government of Saudi Arabia for all travelers to Mecca during the annual Hajj. Advisories for travelers to other countries will be issued when epidemics of meningococcal disease caused by vaccine-preventable serogroups are detected. Travelers' health information is available from the Centers for Disease Control and Prevention (CDC) at 877-FYI-TRIP (toll-free) or at http://www.cdc.gov/travel. Further information concerning geographic areas for which vaccination is recommended can be obtained from international health clinics for travelers and state health departments.
Patients with human immunodeficiency virus (HIV) are likely at increased risk for meningococcal disease, although not to the extent that they are at risk for invasive Streptococcus pneumoniae infection. Although the efficacy of MCV4 among HIV-infected patients is unknown, HIV-infected patients may elect vaccination. For persons aged 11-55 years who have been previously vaccinated with MPSV4, revaccination with MCV4 is not indicated unless vaccination occurred 3-5 years previously and the person still remains at increased risk for meningococcal disease (see Revaccination Section below).
Adults Aged 20-55 Years
MCV4 is licensed for use among adults aged 20-55 years. It is safe, immunogenic, and likely to provide relatively long-lasting protection against meningococcal disease caused by serogroups A, C, Y, and W-135. The rates of meningococcal disease are low in this age group, and vaccination will decrease but not eliminate risk. Therefore, routine vaccination is not recommended; however, persons who wish to decrease their risk for meningococcal disease may elect to be vaccinated.
Children <11 Years and Adults Aged >55 Years
MCV4 is not licensed for use among children aged <11 years or adults aged >55 years. Routine vaccination with MPSV4 is not recommended for children aged <2 years because it is relatively ineffective and offers a short duration of protection. Routine vaccination with MPSV4 is not recommended for children aged 2-10 years and adults aged >55 years who are not identified as being at increased risk for meningococcal disease.
Note: See the December 7, 2007 addendum, above, for updated recommendations for children 2 to 10 at increased risk.
Outbreaks of Meningococcal Disease
Both MPSV4 and MCV4 are recommended for use in control of meningococcal outbreaks caused by vaccine-preventable serogroups (A, C, W-135, and Y) of N. meningitidis. An outbreak is defined by the occurrence of at least three* confirmed or probable primary** cases of serogroup C meningococcal disease in <3 months, with a resulting primary attack rate of >10 cases/100,000 population. For calculation of this threshold, population-based rates are used rather than age-specific attack rates. These recommendations are based on experience with serogroup C meningococcal outbreaks, but these principles might be applicable to outbreaks caused by the other vaccine-preventable meningococcal serogroups, including Y, W-135, and A. Both MCV4 and MPSV4 can be used for outbreak control, although use of MCV4 is preferred if the population targeted for vaccination includes age groups for which MCV4 is licensed. Detailed recommendations on evaluation and management of suspected outbreaks of meningococcal disease have been published previously.
*Calculation of attack rates for organization-based outbreaks is most useful for sizable organizations (e.g., certain universities). However, for the majority of organization-based outbreaks with three cases of disease, the rate will be >10 cases/100,000 population. Thus, occurrence of three cases in these settings should prompt consideration of vaccination. In certain situations, public health officials also might consider vaccination after only two primary cases are identified.
**To calculate a primary attack rate, sum all confirmed cases; exclude secondary cases, and count each set of co-primary cases as one case. A primary case is one that occurs in the absence of previous known close contact with another patient. A secondary case is one that occurs among close contacts of a primary patient >24 hours after onset of illness in the primary patient. If two or more cases occur among a group of close contacts with onset of illness separated by<24 hours, these cases are considered to be co-primary.
Administration
For persons aged 11-55 years, MCV4 is administered intramuscularly as a single 0.5-mL dose. MPSV4 is administered subcutaneously as a single 0.5-mL dose to persons aged >2 years. MCV4 and MPSV4 can be administered concomitantly with other vaccines, but at a different anatomic site. Protective levels of antibodies are usually achieved within 7-10 days of vaccination.
Revaccination
Revaccination might be indicated for persons previously vaccinated with MPSV4 who remain at increased risk for infection (e.g., persons residing in areas in which disease is epidemic), particularly children who were first vaccinated at age <4 years. Such children should be considered for revaccination after 2-3 years if they remain at increased risk. Although the need for revaccination among adults and older children after receiving MPSV4 has not been determined, antibody levels decline rapidly after 2-3 years, and, if indications still exist for vaccination, revaccination might be considered after 5** years. Repeated vaccination with serogroup A and C polysaccharide vaccine might induce immunologic hyporesponsiveness, although clinical implications of such hyporesponsiveness are not known. Hyporesponsiveness to serogroup C polysaccharide can be overcome by vaccination with serogroup C conjugate vaccine. MCV4 is recommended for revaccination of persons aged 11-55 years; however, use of MSPV4 is acceptable.
ACIP expects that MCV4 will provide longer protection than MPSV4; however, studies are needed to confirm this assumption. More data will likely become available within the next 5 years to guide recommendations on revaccination for persons who were previously vaccinated with MCV4.
**Certain sources recommend revaccination after 3 years.
Precautions and Contraindications
Refer to the "Potential Harms" and "Contraindications" fields in this summary for information.
Table: Recommendations for the Use of Meningococcal Vaccines Among Persons Not Vaccinated Previously
| Population Group |
Age Group (yrs) |
| <2 |
2-10 |
11-19 |
20-55 |
>55 |
| General population |
Not recommended |
Not recommended |
A single dose of MCV4 is recommended at age 11-12 years (at preadolescent assessment visit) or at high school entry (at approximately age 15 years) |
Not recommended |
Not recommended |
Groups at increased risk:
- College freshmen living in dormitories
- Certain travelers2
- Certain microbiologists3
- Certain populations experiencing outbreaks of meningococcal disease4
- Military recruits
- Persons with increased susceptibility5
|
Not usually recommended1 |
A single dose of MPSV4 |
A single dose of MCV4 is preferred (MPSV4 is an acceptable alternative) |
A single dose of MCV4 is preferred (MPSV4 is an acceptable alternative) |
A single dose of MPSV4 |
1MPSV4 (2 doses, 3 months apart) can be considered for children aged 3-18 months to elicit short-term protection against serogroup A disease (a single dose should be considered for children aged 19-23 months).
2Persons who travel to or in areas where N. meningitidis is hyperendemic or epidemic are at increased risk of exposure, particularly if contact with the local population will be prolonged. Vaccination is especially recommended to those visiting the "meningitis belt" of sub-Sahara Africa during the dry season (December-June), and vaccination is required by the government of Saudi Arabia for all travelers to Mecca during the annual Hajj. Advisories for travelers are available at http://wwwn.cdc.gov/travel/notices.aspx, http://www.cdc.gov/travel, or by calling CDC's Travelers' Health Hotline at 877-FYI-TRIP (toll-free).
3Microbiologists who are routinely exposed to isolates of N. meningitidis should be vaccinated.
4The use of vaccination in outbreak settings has been described previously.
5Includes persons who have terminal complement component deficiencies and persons with anatomic or functional asplenia.
*See the December 7, 2007 addendum, above, for updated recommendations for children 2-10 at increased risk.
Antimicrobial Chemoprophylaxis
In the United States, the primary means for prevention of sporadic meningococcal disease is antimicrobial chemoprophylaxis of close contacts of a patient with invasive meningococcal disease (see Table below). Close contacts include 1) household members, 2) child-care center contacts, and 3) anyone directly exposed to the patient's oral secretions (e.g., through kissing, mouth-to-mouth resuscitation, endotracheal intubation, or endotracheal tube management). For travelers, antimicrobial chemoprophylaxis should be considered for any passenger who had direct contact with respiratory secretions from an index-patient or for anyone seated directly next to an index-patient on a prolonged flight (i.e., one lasting >8 hours). Guidelines for chemoprophylaxis of travelers have been published previously. The attack rate for household contacts exposed to patients who have sporadic meningococcal disease was estimated to be four cases/1,000 persons exposed, which is 500-800 times greater than the rate for the total population. In the United Kingdom, the attack rate among health-care workers exposed to patients with meningococcal disease was determined to be 25 times higher than among the general population.
Because the rate of secondary disease for close contacts is highest immediately after onset of disease in the index patient, antimicrobial chemoprophylaxis should be administered as soon as possible (ideally <24 hours after identification of the index patient). Conversely, chemoprophylaxis administered >14 days after onset of illness in the index patient is probably of limited or no value. Oropharyngeal or nasopharyngeal cultures are not helpful in determining the need for chemoprophylaxis and might unnecessarily delay institution of this preventive measure.
Rifampin, ciprofloxacin, and ceftriaxone are 90-95% effective in reducing nasopharyngeal carriage of N. meningitidis and are all acceptable antimicrobial agents for chemoprophylaxis. Systemic antimicrobial therapy of meningococcal disease with agents other than ceftriaxone or other third-generation cephalosporins might not reliably eradicate nasopharyngeal carriage of N. meningitidis. If other agents have been used for treatment, the index patient should receive chemoprophylactic antibiotics for eradication of nasopharyngeal carriage before being discharged from the hospital.
One recent study has reported that a single 500-mg oral dose of azithromycin was effective in eradicating nasopharyngeal carriage of N. meningitidis. Azithromycin, in addition to being safe and easy to administer, is also available in a suspension form and is approved for use among children. Further evaluation is warranted of both the effectiveness of azithromycin in eradicating carriage of N. meningitidis and potential for development of microbial resistance to this drug if it is widely used for chemoprophylaxis.
Table: Schedule for Administering Chemoprophylaxis Against Meningococcal Disease
| Drug |
Age Group |
Dosage |
Duration and Route of Administration1 |
| Rifampin2 |
Children aged <1 mo |
5 mg/kg body weight every 12 hrs |
2 days |
| Children aged >1 mo |
10 mg/kg body weight every 12 hrs |
2 days |
| Adults |
600 mg every 12 hrs |
2 days |
| Ciprofloxacin3 |
Adults |
500 mg |
Single dose |
| Ceftriaxone |
Children aged <15 yrs |
125 mg |
Single IM4 dose |
| Ceftriaxone |
Adults |
250 mg |
Single IM dose |
1Oral administration unless indicated otherwise.
2Not recommended for pregnant women because it is teratogenic in laboratory animals. Because the reliability of oral contraceptives might be affected by rifampin therapy, consideration should be given to using alternative contraceptive measures while rifampin is being administered.
3Not usually recommended for persons aged <18 years or for pregnant and lactating women because it causes cartilage damage in immature laboratory animals. Can be used for chemoprophylaxis of children when no acceptable alternative therapy is available. Recent literature review identified no reports of irreversible cartilage toxicity or age-associated adverse events among children and adolescents.
4Intramuscular.
