Risk Of Meningococcal Disease Research Articles

Meningococcal carriage in Dutch adolescents and young adults; a cross-sectional and longitudinal cohort study

ObjectivesCurrent information on rates and dynamics of meningococcal carriage is essential for public health policy. This study aimed to determine meningococcal carriage prevalence, its risk factors and duration in the Netherlands, where meningococcal C vaccine coverage is >90%. Several methods to identify serogroups of meningococcal carriage isolates among adolescent and young adults were compared. MethodsOropharyngeal swabs were collected from 1715 participants 13–23 years of age in 2013–2014; 300 were prospectively followed over 8 months. Cultured isolates were characterized by Ouchterlony, real-time (rt-) PCR or whole-genome sequencing (WGS). Direct swabs were assessed by rt-PCR. Questionnaires on environmental factors and behaviour were also obtained. ResultsA meningococcal isolate was identified in 270/1715 (16%) participants by culture. Of MenB isolates identified by whole genome sequencing, 37/72 (51%) were correctly serogrouped by Ouchterlony, 46/51 (90%) by rt-PCR of cultured isolates, and 39/51 (76%) by rt-PCR directly on swabs. A sharp increase in carriage was observed before the age of 15 years. The age-related association disappeared after correction for smoking, level of education, frequent attendance to crowded social venues, kissing in the previous week and alcohol consumption. Three participants carried the same strain identified at three consecutive visits in an 8-month period. In these isolates, progressively acquired mutations were observed. ConclusionsWhole genome sequencing of culture isolates was the most sensitive method for serogroup identification. Based upon results of this study and risk of meningococcal disease, an adolescent meningococcal vaccination might include children before the age of 15 years to confer individual protection and potentially to establish herd protection.

Effect of Complement Inhibition By Anti-C5 (Eculizumab) or a Small Molecule Inhibitor of Factor D (ACH-4471) on Survival of Meningococci in Blood from Vaccinated Adults

Background. Complement pathways are important targets for treatment of paroxysmal nocturnalhemoglobinuria (PNH) and autoimmune diseases. Because complement is essential in host defense against Neisseria, patients treated with complement inhibitors are at increased risk of life-threatening meningococcal disease. Meningococcal vaccination is recommended. However, the ability of vaccine-induced antibodies to confer protection when different complement pathways are blocked is poorly understood. Inhibiting formation of the membrane attack complex, C5b-C9, blocks serum bactericidal activity (SBA). In the absence of SBA, antibodies can prevent meningococcal disease byopsonophagocytosis (OPA) by binding of antibody to bacteria and activation of C4b and C3b via the classical pathway (CP). When antibody is limited, or the antigenic target is sparse, amplification of C3b deposition via the alternative pathway (AP) is required. OPA killing also depends on activation of phagocytic cells and up-regulation of Fc- and CR3 receptors, which is stimulated by C5a. In this study, we used a whole blood meningococcal killing assay to investigate blocking terminal pathway components C5 or C7 on bacterial survival. We also investigated the effect of blocking the AP using a small molecule factor D inhibitor.Methods. Bloodanticoagulated withlepirudin was obtained from five adults previously immunized with a meningococcal polysaccharide or conjugate vaccine. Four subjects also had completed serogroup B vaccination within 10 months. At time 0, ~5000cfu/ml of serogroup B or C bacteria were added to blood. Meningococcal killing was measured after incubation for 1 and 3hrs in the presence or absence of 50 µg/ml of anti-C5 (eculizumab) or a mouse anti-C7 mAb, both of which blocked SBA, or by 1 to 8 µM of a factor D inhibitor (ACH-4471,Achillion) that inhibited Factor D. By ELISA, 1 µM of the factor D inhibitor completely blocked the AP at 1 µM (the lowest concentration tested) and at 8 µM (the highest concentration tested) had no effect on CP.Results. In the absence of inhibitor, blood from all five subjects incubated with bacteria showed no growth after 1 hr (<50 colony forming units (cfu)/mL). For the serogroup C strain, addition of the C5 inhibitor abolished bacterial killing, as evidenced by lack of decrease in cfu/mL at 1 hr relative to time 0, and an increase of >1 log10 cfu/mL at 3 hr (geometric mean, 74,200, Figure, left Panel). With the C7 inhibitor, cfu/mL decreased at 1 hr (p=0.04) and 3 hr (p=0.07) relative to time 0, and at both time points cfu/mL was significantly lower than with the anti-C5 inhibitor (p<0.007). In blood from four subjects tested, addition of the Factor D inhibitor had less effect on inhibiting serogroup C bacterial killing than anti-C5 or anti-C7 as evidence by an average of 1 log10 decreased cfu/mL at 1 hr with the Factor D inhibitor relative to time 0, and <50 cfu/mL at 3 hr. Similar results were obtained with the serogroup B strain by the addition of the C5 or C7 inhibitor to the blood from the three vaccinated subjects tested, and the addition of the Factor D inhibitor did not interfere with bacterial killing (<50 cfu/mL at 1 hr and 3 hr, Figure, right Panel). When tests were done with blood from a serogroup B unvaccinated subject, the Factor D inhibitor blocked killing (42,000 cfu/mL at 3 hr). In experiments with blood from two vaccinated subjects and serogroup B and C strains, the addition of a C5a receptor antagonist to blood containing anti-C7 increased cfu/mL by >1 log10 at 3 hr, compared to anti-C7 alone.Conclusions. Blocking C5 cleavage and release of C5a by a C5 inhibitor impairs both SBA and OPA killing of meningococci in whole blood, which provides a biologic basis for reports of failure of vaccination in preventing meningococcal disease in some patients treated witheculizumab. Blocking C7 impairs SBA but has less effect on impairing whole blood OPA killing than with anti-C5, since release of C5a, which stimulates phagocytic cell activity, is not inhibited by anti-C7. Effective killing of meningococci by blood from vaccinated subjects was seen at 3 hr (< 50cfu/mL) in the presence of ACH-4471. However, ACH-4471 impaired killing of serogroup B strain by blood from an unvaccinated adult, in which bacterial killing depended on the AP. These data suggest that vaccination may be more effective in decreasing the risk of meningococcal disease in the presence of an AP inhibitor as compared to a C5 inhibitor. [Display omitted] DisclosuresGranoff:Achillion Pharmaceuticals: Other: Consultant, ended May 1, 2016, Research Funding.

Recommendations for Use of Meningococcal Conjugate Vaccines in HIV-Infected Persons - Advisory Committee on Immunization Practices, 2016.

At its June 2016 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of meningococcal conjugate vaccine (serogroups A, C, W, and Y; including MenACWY-D [Menactra, Sanofi Pasteur] or MenACWY-CRM [Menveo, GlaxoSmithKline]) for persons aged ≥2 months with human immunodeficiency virus (HIV) infection. ACIP has previously recommended routine vaccination of persons aged ≥2 months who have certain medical conditions that increase risk for meningococcal disease (1), including persons who have persistent (e.g., genetic) deficiencies in the complement pathway (e.g., C3, properdin, Factor D, Factor H, or C5-C9); persons receiving eculizumab (Soliris, Alexion Pharmaceuticals) for treatment of atypical hemolytic uremic syndrome or paroxysmal nocturnal hemoglobinuria (because the drug binds C5 and inhibits the terminal complement pathway); and persons with functional or anatomic asplenia (including persons with sickle cell disease). Routine vaccination with meningococcal conjugate vaccine is also recommended for all healthy adolescents in the United States (1). This report summarizes the evidence considered by ACIP in recommending vaccination for HIV-infected persons, and provides recommendations and guidance for use of meningococcal conjugate vaccines (serogroups A, C, W, and Y) among HIV-infected persons aged ≥2 months; the majority of meningococcal disease among HIV-infected persons is caused by these four serogroups.

Control of invasive meningococcal disease: is it achievable?

Neisseria meningitidis still leads to deaths and severe disability in children, adolescents and adults. Six different capsular groups of N. meningitidis cause invasive meningococcal disease in the form of meningitis and septicaemia in humans. Although conjugate meningococcal vaccines have been developed to provide protection against four of the capsular groups causing most diseases in humans, vaccines against capsular group B, which causes 85% of cases in Australia and the United Kingdom, have only recently been developed. A capsular group B meningococcal vaccine - 4CMenB (Bexsero) - has recently been licensed in the European Union, Canada and Australia. In Australia, a submission for inclusion of 4CMenB in the funded national immunization programme has recently been rejected. The vaccine will now be introduced into the national immunization programme in the United Kingdom following negotiation of a cost-effective price. With the current low incidence of invasive meningococcal disease in many regions, cost-effectiveness of a new capsular group B meningococcal vaccine is borderline in both the United Kingdom and Australia. Cost-effectiveness of an infant programme is determined largely by the direct protection of those vaccinated and is driven by the higher rate of disease in this age group. However, for an adolescent programme to be cost-effective, it must provide both long-term protection against both disease and carriage. The potential of vaccination to reduce the rate of severe invasive disease is a real possibility. A dual approach using both an infant and adolescent immunization programme to provide direct protection to those age groups at highest risk of meningococcal disease and to optimize the potential herd immunity effects is likely to be the most effective means of reducing invasive meningococcal disease. This commentary aims to describe the known disease burden and consequences of meningococcal disease, and the development and potential effectiveness of new capsular group B meningococcal vaccines.

Meningococcal disease among men who have sex with men - United States, January 2012-June 2015.

Since 2012, three clusters of serogroup C meningococcal disease among men who have sex with men (MSM) have been reported in the United States. During 2012, 13 cases of meningococcal disease among MSM were reported by the New York City Department of Health and Mental Hygiene (1); over a 5-month period during 2012–2013, the Los Angeles County Department of Public Health reported four cases among MSM; and during May–June 2015, the Chicago Department of Public Health reported seven cases of meningococcal disease among MSM in the greater Chicago area. MSM have not previously been considered at increased risk for meningococcal disease. Determining outbreak thresholds* for special populations of unknown size (such as MSM) can be difficult. The New York City health department declared an outbreak based on an estimated increased risk for meningococcal infection in 2012 among MSM and human immunodeficiency virus (HIV)–infected MSM compared with city residents who were not MSM or for whom MSM status was unknown (1). The Chicago Department of Public Health also declared an outbreak based on an increase in case counts and thresholds calculated using population estimates of MSM and HIV-infected MSM. Local public health response included increasing awareness among MSM, conducting contact tracing and providing chemoprophylaxis to close contacts, and offering vaccination to the population at risk (1–3). To better understand the epidemiology and burden of meningococcal disease in MSM populations in the United States and to inform recommendations, CDC analyzed data from a retrospective review of reported cases from January 2012 through June 2015.

Background Paper for the update of meningococcal vaccination recommendations in Germany: use of the serogroup B vaccine in persons at increased risk for meningococcal disease.

In December 2013 Bexsero® became available in Germany for vaccination against serogroup B meningococci (MenB). In August 2015 the German Standing Committee on Vaccination (STIKO) endorsed a recommendation for use of this vaccine in persons at increased risk of invasive meningococcal disease (IMD). This background paper summarizes the evidence underlying the recommendation. Bexsero® is based on surface protein antigens expressed by about 80% of circulating serogroup B meningococci in Germany. The paper reviews available data on immunogenicity and safety of Bexsero® in healthy children and adolescents; data in persons with underlying illness and on the effectiveness in preventing clinical outcomes are thus far unavailable.STIKO recommends MenB vaccination for the following persons based on an individual risk assessment: (1) Persons with congenital or acquired immune deficiency or suppression. Among these, persons with terminal complement defects and properdin deficiency, including those under eculizumab therapy, are at highest risk with reported invasive meningococcal disease (IMD) incidences up 10,000-fold higher than in the general population. Persons with asplenia were estimated to have a ~ 20-30-fold increased risk of IMD, while the risk in individuals with other immune defects such as HIV infection or hypogammaglobulinaemia was estimated at no more than 5-10-fold higher than the background risk. (2) Laboratory staff with a risk of exposure to N. meningitidis aerosols, for whom an up to 271-fold increased risk for IMD has been reported. (3) Unvaccinated household (-like) contacts of a MenB IMD index case, who have a roughly 100-200-fold increased IMD risk in the year after the contact despite chemoprophylaxis. Because the risk is highest in the first 3 months and full protective immunity requires more than one dose (particularly in infants and toddlers), MenB vaccine should be administered as soon as possible following identification of the serogroup of the index case.

MenHibrix

To review the immunogenicity and safety of the Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (Hib-MenCY-TT) for infants and toddlers. Studies conducted in humans and limited to publication in English were identified through a MEDLINE (January 2000 to September 2013) search using the terms Hib-MenCY-TT, MenHibrix, and Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine. Clinical trial registries, Web sites, and reference citations from publications identified were reviewed for additional sources. Randomized controlled trials were included to evaluate the safety and immunogenicity of Hib-MenCY-TT. Epidemiological data and recommendations from the Advisory Committee on Immunization Practices (ACIP) were also reviewed. Hib-MenCY-TT is available for primary vaccination of infants as a 4-dose series at 2, 4, 6, and 12 to 15 months of age. Hib-MenCY-TT has comparable immunogenicity to licensed Hib vaccines and produces high levels of N meningitidis antibodies against serogroups C and Y. The most common adverse events were pain and redness at the injection site, drowsiness, and irritability. Hib-MenCY-TT has been demonstrated to be a safe and immunogenic vaccination for prevention of disease caused by N meningitidis serogroups C and Y and H influenzae type b in healthy infants and toddlers. Currently, the ACIP recommends the use of Hib-MenCY-TT specifically in high-risk infants aged 6 weeks to 18 months. Hib-MenCY-TT provides the first therapeutic option for vaccination of infants as young as 6 weeks of age who are at increased risk for meningococcal disease.

Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age

Background: Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR).Results: Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76–98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines.Conclusion: MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations.Methods: Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period.

Prevention and Control of Meningococcal Disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP).

In January 2005, a tetravalent meningococcal polysaccharide-protein conjugate vaccine ([MCV4] Menactra, manufactured by Sanofi Pasteur, Inc., Swiftwater, Pennsylvania) was licensed for use among persons aged 11-55 years. CDCns Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of young adolescents (defined in this report as persons aged 11-12 years) with MCV4 at the preadolescent health-care visit (at age 11-12 years). Introducing a recommendation for MCV4 vaccination among young adolescents might strengthen the role of the preadolescent visit and have a positive effect on vaccine coverage among adolescents. For those persons 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. Routine vaccination with meningococcal vaccine also is recommended for college freshmen living in dormitories and for other populations at increased risk (i.e., military recruits, travelers to areas in which meningococcal disease is hyperendemic or epidemic, microbiologists who are routinely exposed to isolates of Neisseria meningitidis, patients with anatomic or functional asplenia, and patients with terminal complement deficiency). Other adolescents, college students, and persons infected with human immunodeficiency virus who wish to decrease their risk for meningococcal disease may elect to receive vaccine. This report updates previous reports from ACIP concerning prevention and control of meningococcal disease. It also provides updated recommendations regarding use of the tetravalent meningococcal polysaccharide vaccine (MPSV4) and on antimicrobial chemoprophylaxis.

On the Trail of Preventing Meningococcal Disease: A Survey of Students Planning to Travel to the United States

College freshmen living in dormitories are at increased risk for meningococcal disease. Many students become a high-risk population when they travel to the United States. This study surveyed the knowledge, attitudes toward, and behavior surrounding the disease among Taiwanese college students planning to study in the United States, and to identify factors that may affect willingness to accept meningococcal vaccination. A cross-sectional survey of college students going to study in the United States was conducted in a medical center-based travel medicine clinic. Background information, attitudes, general knowledge, preventive or postexposure management, and individual preventive practices were collected through a structured questionnaire. A total of 358 students were included in the final analysis. More than 90% of participants believed that preventing meningococcal disease was important. However, fewer than 50% of students accurately answered six of nine questions exploring knowledge of the disease, and only 17.3% of students knew the correct management strategy after close contact with patients. Logistic regression analysis showed that students who understood the mode of transmission (odds ratio: 3.21, 95% CI = 1.117-9.229), medication management (1.88, 1.045-3.38), and epidemiology (2.735, 1.478-5.061) tended to be vaccinated. Despite an overall positive attitude toward meningococcal vaccination, there was poor knowledge about meningococcal disease. Promoting education on the mode of transmission, epidemiology, and pharmacological management of the disease could increase vaccination rates. Both the governments and travel medicine specialists should work together on developing an education program for this high-risk group other than just requiring vaccination.

A Licensed Combined Haemophilus influenzae Type b-Serogroups C and Y Meningococcal Conjugate Vaccine.

The highest incidence of meningococcal disease occurs in infants younger than 1 year of age. However, in the US, prior to June 2012, there was no meningococcal vaccine licensed for use in this age group. In the US, where both serogroups C and Y contribute substantially to the overall epidemiology of invasive meningococcal disease, a vaccine combining these capsular polysaccharides was developed. We review the newly licensed HibMenCY-TT (MenHibrix™, GlaxoSmithKline Biologicals, Rixensart, Belgium), a novel vaccine containing Haemophilus influenzae type b (Hib) and serogroups C and Y Neisseria meningitidis conjugated to tetanus toxoid. We describe the vaccine, summarize the clinical trial data, and describe the patient populations recommended to receive HibMenCY-TT as their primary vaccination against Hib. Phase II and III clinical trials found HibMenCY-TT to be well tolerated, safe, and immunogenic when administered at 2, 4, 6, and 12–15 months of age for primary vaccination against both Hib and serogroups C and Y meningococcal disease. In October 2012, the Advisory Committee on Immunisation Practice in the US recommended HibMenCY-TT vaccination for infants at increased risk of meningococcal disease. HibMenCY-TT may be given concomitantly with other routine infant vaccines. It induces antibodies against Hib as well as bactericidal activity against meningococcal serogroup C and Y without increasing the number of injections required. As meningococcal disease epidemiology is dynamic, global surveillance remains essential. In the future, other countries may also benefit from the addition of HibMenCY-TT into their vaccine armamentarium against meningococcal disease.

Prolonged University Outbreak of Meningococcal Disease Associated With a Serogroup B Strain Rarely Seen in the United States

College students living in residential halls are at increased risk of meningococcal disease. Unlike that for serogroups prevented by quadrivalent meningococcal vaccines, public health response to outbreaks of serogroup B meningococcal disease is limited by lack of a US licensed vaccine. In March 2010, we investigated a prolonged outbreak of serogroup B disease associated with a university. In addition to case ascertainment, molecular typing of isolates was performed to characterize the outbreak. We conducted a matched case-control study to examine risk factors for serogroup B disease. Five controls per case, matched by college year, were randomly selected. Participants completed a risk factor questionnaire. Data were analyzed using conditional logistic regression. Between January 2008 and November 2010, we identified 13 meningococcal disease cases (7 confirmed, 4 probable, and 2 suspected) involving 10 university students and 3 university-linked persons. One student died. Ten cases were determined to be serogroup B. Isolates from 6 confirmed cases had an indistinguishable pulsed-field gel electrophoresis pattern and belonged to sequence type 269, clonal complex 269. Factors significantly associated with disease were Greek society membership (matched odds ratio [mOR], 15.0; P = .03), >1 kissing partner (mOR, 13.66; P = .03), and attending bars (mOR, 8.06; P = .04). The outbreak was associated with a novel serogroup B strain (CC269) and risk factors were indicative of increased social mixing. Control measures were appropriate but limited by lack of vaccine. Understanding serogroup B transmission in college and other settings will help inform use of serogroup B vaccines currently under consideration for licensure.

A New Vaccine for Preventing Invasive Hib and Serogroups C and Y Meningococcal Disease in Young Children

Background: Polysaccharide-protein conjugated vaccines for protection against Neisseria meningitidis (Nm) and Haemophilus influenzae type b (Hib) are in routine use in the U.S. and many other countries. Hib vaccine is part of the U.S. childhood immunization program, and Nm vaccines are approved for routine administration in children aged 11 to 18 years and for immunization of children aged ≥9 months who are at increased risk for meningococcal disease. On June 14, 2012, the FDA licensed a combined meningococcal (serogroups C and Y) and Hib vaccine, Hib-MenCY-TT (MenHibrix; GlaxoSmithKline Biologicals). At its October 2012 meeting, the CDC's Advisory Committee on Immunization Practices (ACIP) recommended this vaccine for …

Passive smoking, invasive meningococcal disease and preventive measures: a commentary

Active smoking is a recognized risk factor of various infectious diseases. In a systematic review published in BMC Public Health, Murray et al. demonstrated that exposure to passive smoking significantly increased the risk of meningococcal disease among children. Their review especially highlights that the risk remains high even if the exposure occurs during pregnancy or after birth, although the authors could not disentangle the independent effects of smoking during pregnancy from those in the postnatal period. How passive smoking increases the risk of childhood meningococcal disease is not precisely known. Both exposure to 'smoke', or 'smokers' (who are highly susceptible to pharyngeal carriage of meningococci) are postulated mechanisms, but unfortunately very few studies have examined the risk of exposure by considering these two variables separately, and this therefore remains a research priority. Quitting may well be the mainstay of preventing tobacco-related hazards but the available global data suggest that most smokers are reluctant to quit. Among other interventions, immunizing children with a meningococcal conjugate vaccine could, theoretically, reduce the risk of meningococcal disease among children and their smoker household contacts through herd immunity.See related article http://www.biomedcentral.com/1471-2458/12/1062

Meningococcal disease in travelers

Invasive meningococcal disease is a rare but potentially devastating disease in travelers. In the past 5 years, significant progress in vaccine development has been made. The purpose of this review is to provide up-to-date information on the current status of risk of meningococcal disease in travelers and vaccine recommendations. More evidence on cases of meningococcal disease in travelers is now available. The main areas of highest risk for travelers continue to be the Hajj pilgrimage and travel to the meningitis belt. Two new tetravalent conjugate vaccines against serogroups A, C, W135 and Y have been licensed in North America, Europe and other countries. Significant progress has been made in the development of serogroup B vaccines. The vaccine of choice for travelers at risk of invasive meningococcal disease is a tetravalent conjugate meningococcal vaccine. Data on the need for re-vaccination schedules are still lacking, and so are data on immunogenicity in very young children and the elderly. The first vaccine against serogroup B may become available in early 2013 thus expanding the options of broadening the protection against more serogroups for travelers. Furthermore, the development of pentavalent vaccines will increase the uptake of meningococcal vaccines in the future.

Using the Internet to Trace Contacts of a Fatal Meningococcemia Case—New York City, 2010

In August 2010, the New York City Department of Health and Mental Hygiene (DOHMH) conducted an investigation to identify and provide antibiotic prophylaxis to close contacts of a patient who had died of invasive meningococcal disease. Traditional contact tracing, which relies on interviews with the patient's close associates, identified 3 persons meeting prophylaxis criteria. In addition, DOHMH learned of an Internet site used by the patient to arrange anonymous sexual encounters. By working with the Internet site administrator through a liaison, DOHMH sent notification to 15 additional persons potentially at risk for meningococcal disease; of those, at least 1 met prophylaxis criteria. The Internet has been used previously for partner notification by sexually transmitted disease control programs. This case report illustrates how the Internet can aid contact investigations for other communicable diseases, especially when identifying potential contacts is urgent, patients have died, or contacts are unknown to the patient's associates.

Genetic susceptibility to invasive meningococcal disease: MBL2 structural polymorphisms revisited in a large case–control study and a systematic review

Invasive infection caused by Neisseria meningitidis is a worldwide public health problem. Previous reports have indicated that carriage of common 'defective' structural polymorphisms of the host mannose-binding lectin gene (MBL2) greatly increases an individual's risk of developing the disease. We report the largest case-control study so far to investigate the effect of these polymorphisms in meningococcal disease (296 PCR-positive cases and 5196 population controls, all of European ancestry) and demonstrate that no change in risk is associated with the polymorphisms overall or in any age-defined subgroup. This finding contrasts with two smaller studies that reported an increase in risk. A systematic review of all studies of MBL2 polymorphisms in people of European ancestry published since 1999, including 24,693 individuals, revealed a population frequency of the combined 'defective'MBL2 allele of 0.230 (95% confidence limits: 0.226-0.234). The past reported associations of increased risk of meningococcal disease were because of low 'defective' allele frequencies in their study control populations (0.13 and 0.04) that indicate systematic problems with the studies. The data from our study and all other available evidence indicate that MBL2 structural polymorphisms do not predispose children or adults to invasive meningococcal disease.

Carriage Rates and Serogroups ofNeisseria meningitidisamong Freshmen in a University Dormitory in Korea

PurposeNeisseria meningitidis is a leading cause of bacterial meningitis in young adults. University students, especially those living in dormitories, have been known to be at increased risk of meningococcal disease. We performed a longitudinal study to determine the carriage rates of N. meningitidis and the changes thereof.Materials and MethodsWe recruited Inha University freshmen who were, at that time, admitted to a student dormitory. A pharyngeal swab was taken from all participant who were also asked to complete a questionnaire. This was repeated four weeks later.ResultsA total of 136 students were enrolled at the first culture. After four weeks, 128 students were enrolled, including 106 re-participants. The overall carriage rates changed from 11.8% to 14.1%. In analysis of the 106 re-participants, "visiting to pubs" was associated with carriage of N. meningitis for both the first (p=0.047) and second cultures (p=0.026). Serogroup C was found to be the most frequent serogroup (5 isolates), while 3 isolates were found from serogroup B. The most prevalent PorA types were P1.22,14-6 (4 isolates) and P1.19,15 (3 isolates). The DNA sequences of PorA VR2 were changed in 2 students during prolonged carriage.ConclusionThe meningococcal carriage rate among first year university students who resided in a dormitory did not significantly increase over 4-week interval between cultures, which is markedly different from those reported in Western studies. Close social contact appeared to be related with carriage. Our data also revealed diversity in PorA types, suggesting the possibility of rapid mutation of the PorA gene during the 4-week interval.

Meningococcal Conjugate Vaccines Policy Update: Booster Dose Recommendations

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention and the American Academy of Pediatrics approved updated recommendations for the use of quadravalent (serogroups A, C, W-135, and Y) meningococcal conjugate vaccines (Menactra [Sanofi Pasteur, Swiftwater, PA] and Menveo [Novartis, Basel, Switzerland]) in adolescents and in people at persistent high risk of meningococcal disease. The recommendations supplement previous Advisory Committee on Immunization Practices and American Academy of Pediatrics recommendations for meningococcal vaccinations. Data were reviewed pertaining to immunogenicity in high-risk groups, bactericidal antibody persistence after immunization, current epidemiology of meningococcal disease, meningococcal conjugate vaccine effectiveness, and cost-effectiveness of different strategies for vaccination of adolescents. This review prompted the following recommendations: (1) adolescents should be routinely immunized at 11 through 12 years of age and given a booster dose at 16 years of age; (2) adolescents who received their first dose at age 13 through 15 years should receive a booster at age 16 through 18 years or up to 5 years after their first dose; (3) adolescents who receive their first dose of meningococcal conjugate vaccine at or after 16 years of age do not need a booster dose; (4) a 2-dose primary series should be administered 2 months apart for those who are at increased risk of invasive meningococcal disease because of persistent complement component (eg, C5-C9, properdin, factor H, or factor D) deficiency (9 months through 54 years of age) or functional or anatomic asplenia (2-54 years of age) and for adolescents with HIV infection; and (5) a booster dose should be given 3 years after the primary series if the primary 2-dose series was given from 2 through 6 years of age and every 5 years for persons whose 2-dose primary series or booster dose was given at 7 years of age or older who are at risk of invasive meningococcal disease because of persistent component (eg, C5-C9, properdin, factor H, or factor D) deficiency or functional or anatomic asplenia.

Decreased Response After Conjugated Meningococcal Serogroup C Vaccination in Children With Down Syndrome

To the Editors: Meningococcal serogroup C conjugate (MenC) vaccine is a part of the Dutch immunization program since 2002. In the MenC vaccine, the polysaccharide antigen is linked to the protein carrier tetanus toxoid with the aim to achieve an adequate immune response at an early age, which would not be possible with a pure polysaccharide vaccine. The immune response to a conjugate vaccine is characterized by T-cell-dependent isotype switching to IgG-antibodies, especially IgG1, and induction of immunologic memory. In a catch-up campaign, all children (1–18 years) were offered a single dose of MenC in the Netherlands in 2002. Blood samples were obtained from 19 children (mean age, 10.6; range, 5.3–17.4 years) with Down syndrome (DS) during regular hospital visits 3 months (n = 7; mean, 13 weeks; range, 39–107 days), or around 1 year (n = 12; mean, 50 weeks; range, 275–447 days), after this single dose of MenC vaccination. MenC polysaccharide (PS)-specific IgG, IgM, and IgA concentrations were measured using an antibody capture enzyme-linked immunosorbent assay.1 Results were compared with reference values of healthy adults from the same laboratory, 1 month (n = 12) and 1 year (n = 11) after single MenC vaccination. At 3 months postvaccination, geometric mean MenC/PS-specific IgG, IgA, and IgM serum values were 5.5 (range, 1.4–41), 0.71 (0.03–11), and 0.61 (0.10–7.5) μg/mL, compared with 26 (5.6–59), 5.6 (2.1–11), and 5.2 (1.7–35) μg/mL in healthy controls (P = 0.014, 0.028, and 0.12 were assessed by Mann-Whitney U test, respectively). One year after vaccination, geometric mean MenC/PS-specific IgG, IgA, and IgM values were 2.7 (0.78–15), 0.19 (0.02–1.2), and 0.28 (0.15–0.76) μg/mL, whereas reference values were 4.5 (0.68–19), 0.79 (0.13–3.8), and 0.71 (0.16–5.1) μg/mL (P = 0.204, 0.019, <0.001 were assessed by Mann-Whitney U test, respectively). The 19 children with DS did reach protective, but lower levels of vaccine protection after a single MenC vaccination, in comparison with healthy adults, despite the fact that 9 of them showed hypergammaglobulinemia according to age-matched reference values.2 Assaying specific antibody production against well-defined antigens can be used as a model to assess T-cell-dependent (antiprotein) and T-cell-independent (antipolysaccharide) antibody responses; conjugated protein-polysaccharide vaccines like MenC show aspects of both the types of responses. Impaired specific antibody responses to unconjugated pneumococcal polysaccharide have been described in DS, suggesting a B-lymphocyte problem.3 Impaired responses to influenza, hepatitis B, and tetanus (protein prototype) have been described as well, suggesting an additional T-lymphocyte or T-B interaction problem.3 Not unexpectedly, therefore, our data show that protein conjugation does not fully overcome the impaired antibody production to this polysaccharide antigen in DS. Of course, decreased antibody production upon vaccination may have clinical implications as well. Children with DS have frequent respiratory infections, but an increased frequency of meningococcal disease has not been described in recent surveys, either in the pre-4 or post-MenC5 era, but specific attention was not given to this subject. Thus, it is as yet unclear whether children with DS are at greater risk of meningococcal disease, or whether they would benefit from an additional dose of conjugated meningococcal vaccination. Further studies are needed to elucidate this. Maaike A. Kusters, MD Department of Pediatrics Jeroen Bosch Hospital Els C. M. Jol-Van Der Zijde, BASC Department of Pediatrics Leiden University Medical Center Leiden, The Netherlands Rianne H. J. M. Gijsbers, MSc Esther de Vries, MD, PhD Department of Pediatrics Jeroen Bosch Hospital ′s-Hertogenbosch, The Netherlands