Meningococcal Meningitis Strains

N. meningitidis strains are grouped on the basis of their capsular polysaccharides. There are at least 13 serogroups, some of which are subdivided according to the presence of outer membrane protein and lipopolysaccharide antigens.

Meningococcal capsular polysaccharides provide the basis for grouping the organism. Twelve serogroups have been identified (A, B, C, H, I, K, L, X, Y, Z, 29E, and W135). The most important serogroups associated with disease in humans are A, B, C, Y, and W135. The chemical composition of these capsular polysaccharides is known. The prominent outer membrane proteins of N. meningitidis have been designated class 1 through class 5. The class 2 and 3 proteins function as porins and are analogous to gonococcal Por. The class 4 and 5 proteins are analogous to gonococcal Rmp and Opa, respectively. Serogroup B and C meningococci have been further subdivided on the basis of serotype determinants located on the class 2 and 3 proteins. A handful of serotypes are associated with most cases of meningococcal disease, whereas other serotypes within the same serogroup rarely cause disease. All known group A strains have the same protein serotype antigens in the outer membrane. Another serotyping system exists based on the antigenic diversity of meningococcal LOS (lipooligopolysaccharide).

  

Infection with N. meningitidiscan present in two ways. Either as meningococcemia, characterized by skin lesions, or as acute bacterial meningitis.

 Five predominant strains or serogroups of N. meningitidis account for most cases of meningococcal disease. These are A, B, C, Y, and W-135. The currently available capsular polysaccharide vaccines are available for four of the five strains (A, C, Y, and W-135) No vaccine is available for widespread vaccination against serogroup B.

The group B capsular polysaccharide is a homopolymer of sialic acid which is not immunogenic in humans. A group B meningococcal vaccine consisting of outer membrane protein antigens has been developed, but is not licensed in the United States. Polysaccharide vaccines are ineffective in young children. In children under 1 year old, antibody levels decline rapidly after immunization.The duration of protection is also limited in children vaccinated at 1 to 4 years of age.  Routine vaccination is not currently recommended due to the risk of infection as being classified as low.

  

There are two vaccines against N. meningitidis available in the U.S.

Meningococcal polysaccharide vaccine (MPSV4 or Menomune®) has been approved by the Food and Drug Administration (FDA) and available since 1981.

Meningococcal conjugate vaccine (MCV4 or MenactraT) was licensed in 2005. Both vaccines can prevent 4 types of meningococcal disease, including 2 of the 3 types most common in the U.S. (serogroup C, Y, and W-135) and a type that causes epidemics in Africa (serogroup A).

Meningococcal vaccines cannot prevent all types of the disease.

 MCV4 is recommended for all children at their routine preadolescent visit (11 to 12 years of age). MCV4 is the preferred vaccine for people 11 to 55 years of age in these risk groups, but MPSV4 can be used if MCV4 is not available. MPSV4 should be used for children 2 to 10 years old and adults over 55, who are at risk.

  

MPSV4: Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined

Menomune® – A/C/Y/W-135

 Menomune® – A/C/Y/W-135, Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined, for subcutaneous use, is a freeze-dried preparation of the group-specific polysaccharide antigens from Neisseria meningitidis, Group A, Group C, Group Y and Group W-135. N meningitidis are cultivated with Mueller Hinton agar1 and Watson Scherp2 media. The purified polysaccharide is extracted from the Neisseria meningitidis cells and separated from the media by procedures which include centrifugation, detergent precipitation, alcohol precipitation, solvent or organic extraction and diafiltration. No preservative is added during manufacture.

The 0.78 mL vial of diluent contains sterile, preservative-free, pyrogen-free distilled water and is used for reconstitution of product supplied in 1 mL vials. The 6 mL vial of diluent contains sterile, pyrogen-free distilled water to which thimerosal (mercury derivative) 1:10,000 is added as a preservative. The 6 mL vial is for reconstitution of product supplied in 10 mL vials.

After reconstitution with diluent as indicated on the label, the 0.5 mL dose is formulated to contain 50 μg of “isolated product” from each of Groups A, C, Y and W-135 in an isotonic sodium chloride solution.

 

 MCV4: Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine Menactra®

 

Menactra®, Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine, is a sterile, intramuscularly administered vaccine that contains Neisseria meningitidis serogroup A, C, Y and W-135 capsular polysaccharide antigens individually conjugated to diphtheria toxoid protein. N meningitidis A, C, Y and W-135 strains are cultured on Mueller Hinton agar1 and grown in Watson Scherp2 media. The polysaccharides are extracted from the N meningitidis cells and purified by centrifugation, detergent precipitation, alcohol precipitation, solvent extraction and diafiltration. To prepare the polysaccharides for conjugation, they are depolymerized, derivatized, and purified by diafiltration. Corynebacterium diphtheriae cultures are grown in a modified Mueller and Miller medium3 and detoxified with formaldehyde. The diphtheria toxoid protein is purified by ammonium sulfate fractionation and diafiltration. The derivatized polysaccharides are covalently linked to diphtheria toxoid and purified by serial diafiltration. The four meningococcal components, present as individual serogroupspecific glycoconjugates, compose the final formulated vaccine. No preservative or adjuvant is added during manufacture.

Potency of Menactra vaccine is determined by quantifying the amount of each polysaccharide antigen that is conjugated to diphtheria toxoid protein and the amount of unconjugated polysaccharide present.

Menactra vaccine is manufactured as a sterile, clear to slightly turbid liquid. Each 0.5 mL dose of vaccine is formulated in sodium phosphate buffered isotonic sodium chloride solution to contain 4 μg each of meningococcal A, C, Y, and W-135 polysaccharides conjugated to approximately 48 μg of diphtheria toxoid protein carrier.

 

 Advantages of Meningococcal Conjugate Vaccines (ACIP meeting May 27, 2005 / 54(RR07); 1-21)

Bacterial polysaccharides, including those comprising the capsule of N. meningitdis, are T-cell–independent antigens. T-cell–independent antigens do not elicit a memory response; they stimulate mature B-lymphocytes but not T-lymphocytes, thus inducing a response that is neither long-lasting nor characterized by an anamnestic response after subsequent challenge with the same polysaccharide antigen (72). Thus, meningococcal polysaccharide vaccines have inherent limitations. The serogroup C polysaccharide is poorly immunogenic among children aged <2 years (73–75). The A polysaccharide induces antibody response in infants, but vaccine efficacy declines rapidly (64). Meningococcal polysaccharide vaccines do not confer long-lasting immunity (61,64); they also do not cause a sustainable reduction of nasopharyngeal carriage of N. meningitdis (76,77) and therefore do not substantially interrupt transmission to elicit herd immunity. Finally, multiple doses of serogroup A and C polysaccharide vaccine might cause immunologic hyporesponsiveness to the group A (56,57) and C (58,59) polysaccharide, although clinical implications of this phenomenon are unknown.

Conjugation (i.e., covalent coupling) of polysaccharide to a protein carrier that contains T-cell epitopes changes the nature of immune response to polysaccharide from T-cell–independent to T-cell–dependent, leading to a substantial primary response among infants and a strong anamnestic response at re-exposure (78). Both conjugate Hib and conjugate S. pneumoniae vaccines (introduced for mass infant immunization in the United States in 1990 and 2000, respectively) have reduced incidence of disease caused by vaccine-preventable serotypes (1,79). In addition, both vaccines reduce asymptomatic carriage of respective bacteria (80–82), thus protecting unvaccinated persons through a herd immunity effect (1).

 

What was said in 1990 in regards to polysaccharide vaccine:

 Notice to Readers Availability of Meningococcal Vaccine in Single-Dose Vials for Travelers and High-Risk Persons (MMWR Weekly October 26, 1990 / 39(42);763)

The Food and Drug Administration has approved a single-dose vial of quadrivalent polysaccharide vaccine against Neisseria meningitidis serogroups A, C, Y, and W135. The single-dose vial replaces the previously available 10-dose vial, which, once reconstituted, has a 5-day shelf life. This limitation is obviated by the single-dose vial and should facilitate administration to persons at high risk.

Immunization is recommended for persons with anatomic or functional asplenia and deficiencies of the terminal components of the complement system. Additionally, travelers to areas with hyperendemic or epidemic meningococcal disease should be immunized (1). Updated travel advisories can be obtained from travelers’ clinics, county and state health departments, and CDC.

The vaccine is not recommended for routine use in the United States for three reasons: 1) meningococcal disease is infrequent (approximately 3000 cases per year); 2) no vaccine exists for serogroup B, which accounts for about 50% of cases in the United States; and 3) vaccine is not efficacious against group C disease in children less than 2 years of age (2). This age group accounts for 28% of the group C cases in the United States (CDC, unpublished data).

In adults, the protective efficacy of the vaccine is 85%-95% for disease caused by serogroups A or C (3, 4). Efficacy data are not available for serogroups Y and W135, but the vaccine is immunogenic for both of these serogroups (5-7). Side effects of the vaccine are mild and infrequent, consisting primarily of erythema and induration at the site of injection and low-grade fever. Protective immunity is achieved 10-14 days after vaccination.

Meningococcal lipopolysaccharides: virulence factor and potential vaccine component.  (Microbiol Rev. 1993 March; 57(1): 34–49. PMCID: PMC372900)

meningitsstarins

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Maintaining protection against invasive bacteria with protein–polysaccharide conjugate vaccines

Maintaining protection against invasive bacteria with protein–polysaccharide conjugate vaccines

Polysaccharide-encapsulated organisms are the leading cause of bacterial meningitis and pneumonia in children. The use of protein–polysaccharide conjugate vaccines in developed countries over the past two decades has markedly decreased the burden of disease and mortality from these organisms through direct protection of the immunized and through herd immunity. In the next decade, the widespread use of conjugate vaccines in the developing world should prevent millions of deaths. In this Science and Society article, we describe how vaccine-induced immunity wanes rapidly after vaccination in early childhood and argue that strategies that sustain protection in the population must be considered.

Meningococcal Vaccines Study

Immunogenicity, reactogenicity and persistence of meningococcal A, C, W-135 and Y-tetanus toxoid candidate conjugate (MenACWY-TT) vaccine formulations in adolescents aged 15–25 years. (Vaccine
Volume 27, Issue 1, 1 January 2009, Pages 161-168)

Abstract

Development of meningococcal serogroups A, C, W-135 and Y conjugate vaccines could expand coverage against devastating meningococcal diseases. The immunogenicity of one dose of each one of five MenACWY-TT formulations versus a licensed ACWY polysaccharide vaccine was evaluated in 175 healthy subjects of 15–25 years. Serum bactericidal titers (rSBA) were evaluated before and after vaccination.

The percentage of rSBA responders to each serogroup A, C, W-135 and Y did not statistically differ from the control for each of the five formulations except for serogroup A that was lower after administration of one formulation. In the 3-year follow-up of the first study where the latter formulation was assessed, bactericidal antibody persistence was similar to the licensed ACWY polysaccharide vaccine for MenA and MenC and higher for MenW-135 and MenY.

Our results present five investigational MenACWY-TT conjugate vaccine formulations which are well tolerated and highly immunogenic in adolescents.

1. Introduction

Meningococcal disease due to Neisseria meningitidis remains a major public health problem worldwide due to the associated high levels of morbidity and mortality [1]. In Europe, from 1999 to 2006, the overall endemic incidence rate per 1,00,000 population ranged from 1.1 to 1.9 with the highest age specific incidence rates seen in children younger than 5 years of age, adolescents and young adults [2]. High risk groups include also those who live in crowded conditions, such as college campuses [3]. Mortality rates are generally highest in infants and young children, although very high mortality has also been recorded in adolescents [4]

Five serogroups (A, B, C, W-135 and Y), identified based on capsular polysaccharide (PS) antigens, are implicated in 95% of clinical meningococcal cases [5]. There is substantial regional variation in the relative distribution of each serogroup. In Africa and Asia, serogroups B and C cause sporadic disease, whereas serogroup A, and to a lesser degree serogroup C, are responsible for large-scale epidemics, with highest magnitude in the African meningitis belt [6]. Meningococcal meningitis epidemiology is also dynamic in time: serogroup W-135 has emerged as a new threat after causing outbreaks in Muslim pilgrims in Saudi Arabia and elsewhere, and then in Burkina Faso and Chad [7], [8] and [9]. Serogroup W-135 has now been isolated in numerous countries in Africa [10]; meningococcal disease due to serogroup X has been reported in Niger, where an outbreak occurred in 2006 [11]. In North America, serogroups B, C and Y are the major disease serogroups. By the mid-1990s, serogroup Y accounted for around one-third of all cases in the United States [12]. Cases of serogroup Y invasive disease have also been reported in Canada [13]. In Europe, serogroups B and C predominate, although the latter has been drastically reduced in those countries that have introduced meningococcal serogroup C conjugate vaccination [14].

No broadly protective vaccine exists against serogroup B meningococcal disease but effective vaccines against meningococcal disease due to the other four predominant serogroups are available, including the most recently developed meningococcal conjugate vaccines. Mass vaccination with serogroup C meningococcal conjugate vaccines has proven their effectiveness in all ages [15]. MenC conjugate vaccines are now given routinely in Australia, Canada and in some European countries either as infant vaccination followed by a booster or as a single dose in toddlers. Protection conferred by a single dose in adolescents or toddlers has been shown to last for at least 4–5 years [15] and [16] although bactericidal antibodies wane overtime in those vaccinated below 10 years of age, suggesting re-vaccination in adolescence may be necessary after vaccination in childhood [17]. Substantial reduction in nasopharyngeal carriage of serogroup C (66% reduction in adolescents in the UK [18] after MenC conjugate vaccination) is thought to be a major factor contributing to herd immunity after mass vaccination [19].

A cost-effectiveness study in Canada suggested that re-vaccination with a tetravalent conjugate vaccine would benefit those countries with established MenC conjugate vaccination programmes in light of possible increases in serogroup Y incidence [20]. Only one meningococcal ACWY conjugate vaccine is licensed to date (in the United States and in Canada) and several other meningococcal ACWY conjugate candidate vaccines are in clinical development [21].

This paper presents the results of two studies that evaluated the immunogenicity and reactogenicity of five formulations of a novel, combined MenACWY conjugate candidate vaccine that varied both in the amount of PS and the conjugation method for each serogroup. The vaccine formulations were administered as a single dose to teenagers and young adults.

Continued

Meningococcal

     Meningococcal bacteria are part of our normal flora and everyone carries it at some point in their life which gives them real immunity. The carriage rates are so large that there is constant exposure. You do not need exposure to a sick person to get the bacteria if you’re not immune as you can get it from a healthy carrier. However, neither exposure nor carriage means invasive disease, which is why very few people get sick. You don’t ‘catch’ meningitis. You can acquire the bacteria but it takes an ‘off’ immune system for the bacteria to cause invasive disease. 

 

Meningitis   is brain membranes inflammation-a disease which is named after the affected organ. Meningococcal disease  is whatever the relevant bacteria may cause (which is sometimes meningitis and/or septicemia). When exposed to meningococcal bacteria, you won’t necessarily get meningitis, unless the immune system can’t stop it, and not every meningitis is meningococcal. There are various types of bacterial and viral meningitis.

 

      Hib and Prevnar vaccines are given to prevent bacterial meningitis in infants under age 5. MCV4 is a vaccine for individuals 2-55 years of age and MPSV4 is an alternative for this age group plus can be given to individuals over age 55.

 

 

  •       Menactra vaccine (Groups A, C, Y and W-135. Polysaccharide Diphtheria Toxoid Conjugate Vaccine)
  •       Menomune (polysaccharide. Groups A, C, Y, W-135)
  •       Hib (Haemophilus Influenzae typeB)
  •       Prevnar  (Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F individually conjugated to Diphtheria protein)

 

Vaccine package Inserts  

 

 

     Meningitis vaccines create a window of 14 days in which some children will get meningitis because the vaccine suppresses the immune system. Transient Enhanced Susceptibility.

 

 

 

     The medical establishment doesn’t care about meningococcal bacteria unless it’s meningitis. Why?  First, to scare you. After that, it is a way to promote the meningococcal vaccine as the ‘life saver’ without giving you all the facts. Since there are over 90 bacteria in a healthy throat of humans at any given time, we have always lived in a symbiotic relationship with them. Now we are able to destroy what is part of us. What can that possibly accomplish? The answer: new disease.

 
 

 

 

      Meningitis is spread through respiratory and throat secretions and is not as contagious as colds or the flu. There are many strains of Haemophilus influenza bacteria, but only the ‘b’ strain causes meningitis, which is why we have the Hib vaccine. Prevnar is recommended to prevent against serious invasive disease caused by Streptococcus pneumoniae, including bacteremia (bloodstream infection) and meningitis caused by the seven serotypes in the vaccine.  The vaccine for older children and adults is recommended for four serogroups of Neisseria meningitidis, which is the bacterium that causes meningococcal infection.

 
 

 

 

     Menactra was approved by the U.S. government in 2005. It has been linked with a few cases of a neurological disorder called Guillain-Barre syndrome among some individuals in their teens. The FDA then expanded the age range for the vaccine Menactra in 2007, to 2 years olds and up. The previous the age range was 11 to 55.

 

 Chart:

 

Isolates, England and Wales, by Group, 1989/1990 to 2004/2005

MENINGOCOCCAL REFERENCE UNIT, LABORATORY CONFIRMED* NEISSERIA MENINGITIDIS: England and Wales, by Group, 1989/1990 to 2004/2005

 

 

 


 

Group B

 Group C

  Other groups

 Ungrouped

   TOTAL

1989 / 1990

1019

477

40

0

1536

1990 / 1991

965

423

45

0

1433

1991 / 1992

936

330

41

0

1307

1992 / 1993

880

320

48

0

1248

1993 / 1994

822

312

52

0

1186

1994 / 1995

863

305

60

0

1228

1995 / 1996*

867

618

67

156

1708

1996 / 1997

1070

758

85

425

2338

1997 / 1998

1102

772

114

309

2297

1998 / 1999

1401

955

103

320

2779

1999 / 2000

1627

891

145

133

2796

2000 / 2001

1686

411

186

163

2446

2001 / 2002

1503

211

139

110

1963

2002 / 2003

1209

122

69

76

1476

2003 / 2004

1306

64

52

85

1507

2004/2005**

1288

43

60

71

1462

* From 95/96 data includes PCR confirmed reports in addition to culture confirmed isolates
** Provisional data
Source: PHLS Meningococcal Reference Unit
Last reviewed: 7 February 2008
 

HIB vaccine was introduced in 1992. Within 3 years, ungrouped Meningitis rates greatly increased. Prevnar (pneumococcal) vaccine was invented because of HIB. Now, meningitis vaccines have been created because of HIB and Prevnar. And now they are working on another pneumococcal vaccine which targets  11 and 24 bacteria vs. the 7 contained in the current one. We’re vaccinating against bacteria. By doing so, we’re removing relatively harmless bacteria that rarely cause disease in healthy people. When you take away one bacteria, that is supposed to be there, and rarely causes harm in the majority of people, another type will step in and take its place. Another more dangerous one than the ‘mild’ one, you took away and this has been shown repeatedly.

 

Children with Bacterial Meningitis Presenting to the Emergency Department during the Pneumococcal Conjugate Vaccine Era

Volume 15 Issue 6 Page 522-528, June 2008. Academic Emergency Medicine 15 (6) , 522–528 doi:10.1111/j.1553-2712.2008.00117.x

 

Abstract

Background: The epidemiology of bacterial meningitis in children in the era of widespread heptavalent conjugate pneumococcal vaccination (PCV7) is unknown.

Objectives: The objective was to describe the epidemiology of bacterial meningitis in children presenting to the emergency department (ED) during the era of widespread PCV7 vaccination.

Methods: The authors retrospectively reviewed the medical records of all children aged 1 month to 19 years with bacterial meningitis who presented to the EDs of 20 U.S. pediatric centers (2001–2004). Bacterial meningitis was defined by a positive cerebrospinal fluid (CSF) culture for a bacterial pathogen or CSF pleocytosis (CSF white blood cell [WBC] count ≥10 cells/mm3) in association with either a positive blood culture or a CSF latex agglutination study.

Results: A total of 231 children with bacterial meningitis were identified. The median age was 0.6 years (interquartile range [IQR] = 0.2–4.2). Eight patients (3% of all patients) died. The following bacterial pathogens were identified: Streptococcus pneumoniae (n = 77; 33.3%), Neisseria meningitidis (67; 29.0%), Group B Streptococcus (42; 18.2%), Escherichia coli (17; 7.4%), nontypeable Haemophilus influenzae (10; 4.3%), other Gram-negative bacilli (7; 3.0%), Listeria monocytogenes (5; 2.2%), Group A Streptococcus (5; 2.2%), and Moraxella catarrhalis (1; 0.4%). S. pneumoniae serotypes were determined in 37 of 77 patients; of these, 62% were due to nonvaccine serotypes (including 19A).

Conclusions: Although now a rare infectious disease in United States, bacterial meningitis still causes substantial morbidity in affected children. Despite the introduction of PCV7, S. pneumoniae remains the most common cause of bacterial meningitis in U.S. children, with approximately half of cases due to nonvaccine serotypes.

FDA O.K.’s meningitis vaccine for young children
 

 

“Approving Menactra for younger children offers another option for health-care providers and parents. Now there are two vaccines available for children between 2 and 10 years of age who may be at increased risk of meningitis,” said Dr. Jesse Goodman, director of FDA’s center for biologics… Sanofi makes the other meningitis vaccine as well.

The CDC has said it was investigating whether the vaccine caused the reaction, which has been associated with other vaccines.”

 

 

 What’s Been Reported in the News…

 

 

Meningococcal B vaccination scrapped (4/2008)

 
 

 

Health officials are scrapping the mass vaccination of New Zealanders against the deadly meningococcal b disease.

Their own evidence released today shows quite clearly that the vaccine had no impact at all,” says Ron Law, a risk and policy analyst. “And in fact if you look at the deaths which they haven’t released, the deaths from meningococcal remain static ever since the campaign was introduced.”

Forty six people have got the disease despite being fully immunized. One child died. “Two hundred and, well they say 250 million, to save one to two lives – it’s a major policy blunder,” says Law.  (Source: ONE News)

 

Meningitis vaccine commercial irks drug advertising critics (10/2007)

CBC News

A new commercial promoting a meningitis vaccine — and showing what might happen if parents don’t vaccinate their children — has Canadian critics warning parents to examine the facts and not be swayed by such ads.

“The [TV] ads for the vaccine I’ve seen are very problematic,” Dr. Barbara Mintzes, a member of the Drug Assessment Working Group at the University of British Columbia, told CBC News. “I find it really a problem because of the way it’s playing into that parental concern to protect their child and using that to sell a product.”

On Oct. 18, the U.S. Food and Drug Administration allowed sanofi pasteur, the maker of the vaccine, to expand its use to children two to 10 years of age, in addition to the current age indication of 11 to 55 years.

But the Public Health Agency of Canada’s National Advisory Committee on Immunization says that given the low incidence of the strains of meningitis covered by Menactra, it feels mass inoculations aren’t necessary.

 

Vaccine linked to syndrome

What people watching Menactra’s TV spot may not know is that the vaccine has side-effects, such as links to Guillain-Barré syndrome. According to the CDC, between March 2005 and September 2006, 17 cases of the syndrome occurred in the U.S. in 11- to 19-year-olds who had received Menactra. 

Guillain-Barré syndrome is a serious neurological disorder in which the body’s immune system attacks part of the peripheral nervous system. Symptoms include weakness or tingling sensations in the legs, which can spread to the arms and upper body. These symptoms can increase until a person is almost totally paralyzed, although the majority of patients do recover.

Sanofi pasteur warns about the risks on its website.

 

Report from the Advisory Committee on Immunization Practices (ACIP): Decision Not to Recommend Routine Vaccination of All Children Aged 2–10 Years with Quadrivalent Meningococcal Conjugate Vaccine (MCV4)

At its February 2008 meeting, the Advisory Committee on Immunization Practices (ACIP) decided not to recommend routine vaccination of children aged 2–10 years against meningococcal disease unless the child is at increased risk for the disease. This report summarizes the deliberations of ACIP and the rationale for its decision and restates existing recommendations for meningococcal vaccination among children aged 2–10 years at increased risk for meningococcal disease. ACIP continues to recommend routine vaccination against meningococcal disease for all persons aged 11–18 years and those persons aged 2–55 years who are at increased risk for meningococcal disease (13).

On October 17, 2007, the Food and Drug Administration added approval for use of quadrivalent meningococcal conjugate vaccine (MCV4) (Menactra®, Sanofi Pasteur, Swiftwater, Pennsylvania) in children aged 2–10 years to existing approval for use in persons aged 11–55 years (4). Before licensure of MCV4, quadrivalent meningococcal polysaccharide vaccine (MPSV4) (Menomune®, Sanofi Pasteur) was the only meningococcal vaccine available in the United States. MPSV4 was recommended for routine use only among persons at increased risk for meningococcal disease (1). Because clinical efficacy trials were not feasible in the United States, MCV4 licensure was based on clinical trials in which the safety and immunogenicity of MCV4 was compared with MPSV4. Immunogenicity was measured by serum bactericidal activity (SBA), a correlate of protection. Rates of most solicited local and systemic adverse events after MCV4 vaccination were comparable to rates observed after administration of MPSV4 (5). The proportion of children aged 2–10 years who did not have detectable SBA (titer <1:8) at day 0 and seroconverted (titer >1:32) by day 28 after MCV4 vaccination was 98.6% for serogroup A, 87.9% for serogroup C, 86.2% for serogroup Y, and 96.0% for serogroup W-135, similar to MPSV4 for all serogroups (Table) (5). Hence, MCV4 was found to be safe and noninferior to MPSV4 for all serogroups.

 

Summary of ACIP Deliberations and Rationale

ACIP evaluated data to determine the anticipated duration of protection from a single dose of MCV4 in children aged 2–10 years. The duration of protection of MPSV4 is considered to be short (3–5 years), especially in young children, based on substantial declines in measurable levels of antibodies against group A and C polysaccharides by 3 years after vaccination (6,7). Although SBA titers at 28 days and 6 months after vaccination were significantly higher in children aged 2–10 years who received MCV4 compared with children who received MPSV4 for all four serogroups (p<0.001) (5), the difference in magnitude of SBA titers between children in the two groups was not substantial (Table). Further, SBA activity among children aged 2–3 years who received MCV4 was lower than in children aged 4–10 years. Based on these data, ACIP concluded that evidence was insufficient to determine that 1 dose of MCV4 administered at age 2 years would provide protection against meningococcal disease through late adolescence and college entry.

ACIP also reviewed the burden of meningococcal disease among children aged 2–10 years. In the United States, during 1998–2007, overall rates of meningococcal disease were lower in children aged 2–10 years (0.68 per 100,000 population) than in infants aged <2 years and adolescents aged 11–19 years (3.9 and 0.81 per 100,000, respectively). Furthermore, 41% of cases in children aged 2–10 years occurred among children aged 2–3 years. In addition, among cases that occurred in children aged 2–10 years, 59% were caused by serogroups contained in MCV4 (A, C, Y, and W-135), compared with 77% of cases among youths aged 11–19 years. Annually, an estimated 160 cases of A/C/Y/W-135 disease and 13 deaths occur in children aged 2–10 years, compared with 250 cases and 15 deaths among youths aged 11–19 years (Active Bacterial Core Surveillance [ABCs], unpublished data, 1997–2006).

A cost-effectiveness analysis of vaccinating a cohort of U.S. children aged 2 years also was presented at the February 2008 ACIP meeting…Because approximately 75% of cases of disease in children aged 2 years occur at age 24–29 months, the effectiveness of routine MCV4 vaccination of children aged 2 years in reducing the burden of disease is dependent on achieving high coverage at age 24 months (ABCs, unpublished data, 2008). However, achieving high coverage with MCV4 at age 24 months might be challenging…

 

ACIP Decision and Continuing Recommendations

Based on reviews of safety and immunogenicity data, the epidemiology of meningococcal disease, a cost-effectiveness analysis, and programmatic considerations, ACIP decided not to recommend routine vaccination against meningococcal disease for all children aged 2–10 years at its February 2008 meeting. ACIP continues to recommend vaccination for children aged 2–10 years 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 deficiencies, and children who have anatomic or functional asplenia. Health-care providers also may elect to vaccinate children aged 2–10 years who are infected with human immunodeficiency virus (HIV).* MCV4 is preferred to MPSV4 for children aged 2–10 years in these groups at increased risk and for control of meningococcal disease outbreaks. In addition, if health-care providers or parents elect to provide meningococcal vaccination to other children in this age group, MCV4 is preferred to MPSV4. Recommendations for use of MCV4 in persons aged 11–55 years, including a recommendation for routine vaccination with MCV4 of persons aged 11–18 years, have been published previously and remain unchanged (1,3).

For children aged 2–10 years who have 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 before and remain at increased 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 monitor available data on duration of protection to determine whether recommendations for revaccination with MCV4 are indicated. Persons with a history of Guillain-Barré syndrome (GBS) might be at increased risk for GBS after MCV4 vaccination (3); therefore, a history of GBS is a precaution to administration of MCV4.
(Source: MMWR-May 2, 2008 / 57(17); 462-465)

 

 

CDC broadens age group for meningitis shot (7/2007)

Parents are being urged to have children ages 11-18 vaccinated against meningitis under new recommendations by federal health officials.

In issuing new guidelines for the meningococcal disease vaccine, the U.S. Centers for Disease Control and Prevention closed gaps in the previous recommendations. Those had targeted students entering high school and college, as well as pre-adolescents, by applying to ages 11-12, 15 and 18.

The change stems from an increase in the availability of the vaccine, not from any flare-up in reported cases…

 

Norwegian Health Minister Apologies for Vaccine Scandal

MeNZBscandal: Twelve months ago the Ministry of Health welcomed a planned independent Norwegian review of claims of misconduct surrounding their meningococcal B vaccine which the MOH hoped would provide a greater degree of reassurance to the public in Norway and in New Zealand. http://www.moh.govt.nz/moh.nsf/pagesmh/5406?Open

…These issues in New Zealand include serious conflicts of interest, ministry officials lying to the Minister, substandard trials, the use of fear and coercion of children and parents and the creation in the minds of the public of an ‘monster’ epidemic that was past its peak before the roll out of the vaccine.

In addition it has recently emerged that the Ministry has undertaken studies that show that babies are at INCREASED risk of contracting meningococcal disease following three doses of the MeNZB vaccine. Their response was to increase the number of doses to four in the hope that a miracle might occur. They continue to inject the toxin into as many babies as they can.

As evidence of a public apology by the Norwegian Minister of Health emerges following an independent inquiry revealing major cover-ups, and deceit relating to data used to justify the New Zealand MeNZB vaccine, we look forward to a similar inquiry and apology from New Zealand’s Minister of Health.

Links to Ron Law and Barbara Sumner Burstyn’s meningococcal Gold Rush, of the Norwegian documentary aired in TVNZ’s Sunday programme:

Meningococcal Gold Rush Series

Meningococcal Gold Rush I,
http://www.scoop.co.nz/stories/HL0502/S00064.htm

Meningococcal Gold Rush Quickguide
http://www.sumnerburstyn.com/vax/MeNZB-Quick-Guide-332.pdf

Meningococcal Gold Rush II, (~60 pages)
http://www.scoop.co.nz/stories/HL0607/S00284.htm

Meningococcal Gold Rush III,
http://www.scoop.co.nz/stories/HL0505/S00352.htm

Meningococcal Gold Rush IV
http://www.scoop.co.nz/stories/HL0611/S00403.htm

Norwegian documentary (3 of 4 parts only)
Part 1
http://www.youtube.com/watch?v=H6JiUwkrTNk
Part 2 http://www.youtube.com/watch?v=XLxhvSLBejs
Part 3 http://www.youtube.com/watch?v=2Nl9biRB4f4

 

Meningitis Vaccine Boosts Immune Response (5/2008)

 Excerpt:

Swiss drug maker Novartis AG said its experimental meningitis vaccine performed well in a large clinical trial and that the company expects to file for regulatory approval in the U.S. and Europe this year.
Novartis said the vaccine, called Menveo, helped trigger a strong immune response in a greater percentage of adolescents against several types of meningitis bacteria than did the currently used vaccine, Sanofi-Aventis SA’s Menactra.
 

 


Menveo is designed to protect against four types of meningitis bacteria: serotypes A, C, W-135 and Y. Sanofi’s Menactra, launched in 2005, is now the only vaccine available against those four types…


Adam Finn, a physician and meningitis expert at the University of Bristol in the United Kingdom, said Menveo’s results appear sound. But he cautioned that generating a higher immune response doesn’t necessarily mean the new vaccine will prevent more cases of meningitis.

 

Investigational Vaccine Effective Against Meningitis in Infancy

By Crystal Phend, Staff Writer, MedPage Today.Published: January 08, 2008.University of Pennsylvania School of Medicine.

OXFORD, England

, Jan. 8 — An investigational tetravalent meningococcal vaccine may be the first to provide sufficient protection for infants, the group at highest risk for the disease, researchers here said.
At least 92% of infants who received the conjugate vaccine in a two-, three-, four-month schedule developed a protective antibody level to serogroups A, C, W-135, and Y, found Matthew D. Snape, M.D., of the University of Oxford, and colleagues in a phase II, open-label, randomized study.
The two-, four-, six-month schedule most likely to be considered for the United States yielded similar results, although a lower percentage (81%) developed a protective antibody level against serogroup A, they reported in the Jan. 9/16 issue of the Journal of the American Medical Association.

 

 

Primary source:

Journal of the American Medical Association. Source reference:
Snape MD, et al
“Immunogenicity of a tetravalent meningococcal glycoconjugate vaccine in infants: a randomized controlled trial” JAMA 2008; 299: 173-184.
Additional source: Journal of the American Medical Association. Source reference:
Harrison LH, “A multivalent conjugate vaccine for prevention of meningococcal disease in infants” JAMA 2008; 299: 217-219.