Haemophilus Influenzae

Haemophilus Influenzae

 

The HIB vaccine is solely for capsulated Haemophilus B, not non encapsulated Hib.  The HIB vaccine is solely for invasive Hib disease caused by capsular Hib. It has no effect on any other type of Hib disease. You can’t make a Hib vaccine for non-encapsular HIB. Due to the recommended and rountine use of Hib conjugate vaccine, at least half of invasive H influenzae infections are now caused by the nonencapsulated strains.

 

There are six strains of H. influenzae that have been classified (types a through f) and other non-typeable strains. Type b is responsible for 95 percent of all strains causing invasive disease. Invasive Hib disease usually manifests itself clinically as meningitis, accounting for 50 to 65 percent of all cases.

 

HIB vaccines are available as a single vaccine or in combination vaccines and four conjugate Hib vaccines are currently available:

Monovalent Hib vaccines:

PedvaxHIB® [Merck] [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)] PedvaxHIB* [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)] is a highly purified capsular polysaccharide (polyribosylribitol phosphate or PRP) of Haemophilusinfluenzae type b (Haemophilus b, Ross strain) that is covalently bound to an outer membrane protein complex (OMPC) of the B11 strain of Neisseria meningitidis serogroup B. Each 0.5 mL dose of Liquid PedvaxHIB is a sterile product formulated to contain: 7.5 mcg of Haemophilus b PRP, 125 mcg of Neisseria meningitidis OMPC and 225 mcg of aluminum as amorphous aluminum hydroxyphosphate sulfate (previously referred to as aluminum hydroxide), in 0.9% sodium chloride, but does not contain lactose or thimerosal.

 

 

 

 ActHib [sanofi pasteur] The vaccine consists of the Haemophilus b capsular polysaccharide (polyribosyl-ribitol-phosphate, PRP), a high molecular weight polymer prepared from the Haemophilus influenzae type b (HiB) strain 1482 grown in a semi-synthetic medium, covalently bound to tetanus toxoid.1 The lyophilized ActHIB vaccine powder and saline diluent contain no preservative. The tetanus toxoid is prepared by extraction, ammonium sulfate purification, and formalin inactivation of the toxin from cultures of Clostridium tetani (Harvard strain) grown in a modified Mueller and Miller medium.

 

Combination vaccines:

COMVAX® (Hib/hepatitis B vaccine) [Merck] [HAEMOPHILUS b CONJUGATE (MENINGOCOCCAL PROTEIN CONJUGATE) and HEPATITIS B (RECOMBINANT) VACCINE]

COMVAX* [Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine] is a sterile bivalent vaccine made of the antigenic components used in producing PedvaxHIB* [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)] and RECOMBIVAX HB* [Hepatitis B Vaccine (Recombinant)]. These components are the Haemophilus influenzae type b capsular polysaccharide [polyribosylribitol phosphate (PRP)] that is covalently bound to

an outer membrane protein complex (OMPC) of Neisseria meningitidis and hepatitis B surface antigen (HBsAg) from recombinant yeast cultures. Haemophilus influenzae type b and Neisseria meningitidis serogroup B are grown in complex

fermentation media.

 

The PRP-OMPC conjugate is prepared by the chemical coupling of the highly purified PRP (polyribosylribitol phosphate) of Haemophilus influenzae type b (Haemophilus b, Ross strain) to an OMPC of the B11 strain of Neisseria meningitidis serogroup B. The coupling of the PRP to the OMPC is necessary for enhanced immunogenicity of the PRP. This coupling is confirmed by analysis of the components of the conjugate following chemical treatment which yields a unique amino acid. After conjugation, the aqueous bulk is then adsorbed onto an amorphous aluminum hydroxyphosphate sulfate adjuvant (previously referred to as aluminum hydroxide).

 TriHIBit® (diphtheria and tetanus toxoids and acellular pertussis [DTaP]/Hib vaccine) [sanofi pasteur]

When Tripedia vaccine is used to reconstitute ActHIB® [Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate)

manufactured by Aventis Pasteur SA] the combination vaccine is TriHIBit®. Each single 0.5 mL dose of TriHIBit vaccine for the

fourth dose only, is formulated to contain 6.7 Lf of diphtheria toxoid, 5 Lf of tetanus toxoid (both toxoids induce at least 2 units

of antitoxin per mL in the guinea pig potency test), 46.8 μg of pertussis antigens (approximately 23.4 μg of inactivated PT and

23.4 μg of FHA), 10 μg of purified Haemophilus influenzae type b capsular polysaccharide conjugated to 24 μg of inactivated tetanus toxoid, and 8.5% sucrose. (Refer to ActHIB vaccine package insert.)

 

 

HibTITER  HAEMOPHILUS b CONJUGATE VACCINE  (Diphtheria CRM197 Protein Conjugate)

 

Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate) HibTITER is a sterile solution of a conjugate of oligosaccharides of the capsular antigen of Haemophilus influenzae type b (Haemophilus b) and diphtheria CRM197 protein (CRM197) dissolved in 0.9% sodium chloride. The oligosaccharides are derived from highly purified capsular polysaccharide,

polyribosylribitol phosphate, isolated from Haemophilus b strain Eagan grown in a chemically defined medium (a mixture of mineral salts, amino acids, and cofactors).

 

Three conjugate Hib vaccines are licensed for use in infants as young as 6 weeks of age (see below). All three vaccines

utilize different carrier proteins. Two combination vaccines that contain Hib conjugate vaccine are also available.

 

 hibbrands1

 

 

 hibbrands2

 

 

 

 

HIB Vaccine Timeline and History Tidbits:

 

1970-1st hib vaccine

 

1980’s Conjugate vaccine for hib

 

1985-polysaccharide vaccine

Provoked Hib in rats (by causing transient immune suppression for 7 – 14 days) and also in humans.  
The polysaccharide vaccine was quietly swept under the rug. It continued to be used after 1987, but was rapidly replaced with the conjugate vaccine.

 

In 1985, the first Hib polysaccharide vaccines were licensed for use in the United States. These vaccines contained purified polyribosylribitol phosphate (PRP) capsular material from the type b serovar. Antibody against PRP was shown to be the primary component of serum bactericidal activity against the organism. PRP vaccines were ineffective in children less than 18 months of age because of the T-cell-independent nature of the immune response to PRP polysaccharide.

Conjugation of the PRP polysaccharide with protein carriers confers T-cell-dependent characteristics to the vaccine and substantially enhances the immunologic response to the PRP antigen. In 1989, the first Hib conjugate vaccines were licensed for use among children 15 months of age or older. In 1990, two new vaccines were approved for use among infants.

Haemophilus influenzae type b Polysaccharide-Protein Conjugate Vaccines

 

Conjugation is the process of chemically bonding a polysaccharide (a somewhat ineffective antigen) to a protein “carrier,” which is a more effective antigen. This process changes the polysaccharide from a T-independent to a T-dependent antigen and greatly improves immunogenicity, particularly in young children. In addition, repeat doses of Hib conjugate vaccines elicit booster responses and allow maturation of class-specific immunity with predominance of IgG antibody. The Hib conjugates also cause carrier priming and elicit antibody to “useful” carrier protein. The first Hib conjugate vaccine (PRP-D, ProHIBIT) was licensed in December 1987. This vaccine was not consistently immunogenic in children younger than 18 months of age.

 

PRP-D is no longer available in the United States.

 

 

 

Haemophilus influenzae is a small, nonmotile Gram-negative bacterium in the family Pasteurellaceae,  on the level with the Vibrionaceae and the Enterobacteriaceae. The family also includes Pasteurella and Actinobacillus, two other genera of bacteria that are parasites of animals.  Encapsulated strains of Haemophilus influenzae isolated from cerebrospinal fluid are coccobacilli, 0.2 to 0.3 to 0.5 to 0.8 um, similar in morphology to Bordetella pertussis, the agent of whooping cough. Non encapsulated organisms from sputum are pleomorphic and often exhibit long threads and filaments. The organism may appear Gram-positive unless the Gram stain procedure is very carefully carried out. Furthermore, elongated forms from sputum may exhibit bipolar staining, leading to an erroneous diagnosis of Streptococcus pneumoniae.

 

 

 

hib1

 

 

 

 

Seven serotypes of the bacterium have been identified on the basis of capsular polysaccharides. Until the implementation of widespread vaccination programs, type b H. influenzae was the most common cause of meningitis in children between the ages of 6 months and 2 years (see Figure 4 below), resulting in 12,000 to 20,000 cases annually in the U.S. It would be interesting to view comparative data since the era of vaccination against H. influenzae meningitis, which began in 1985. Certainly, there are fewer than 100 cases annually of bacterial meningitis caused by H. influenzae type b.

 

*bloggers note..type g has since been identified.

 

 

hib2

 

 

 

 

Two variants among Haemophilus influenzae serotype b strains with distinct bcs4, hcsA and hcsB genes display differences in expression of the polysaccharide capsule

 

Background

Despite nearly complete vaccine coverage, a small number of fully vaccinated children in the Netherlands have experienced invasive disease caused by Haemophilus influenzae serotype b (Hib). This increase started in 2002, nine years after the introduction of nationwide vaccination in the Netherlands. The capsular polysaccharide of Hib is used as a conjugate vaccine to protect against Hib disease. To evaluate the possible rise of escape variants, explaining the increased number of vaccine failures we analyzed the composition of the capsular genes and the expressed polysaccharide of Dutch Hib strains collected before and after the introduction of Hib vaccination.

 

Differences in Genetic and Transcriptional Organization of the glpTQ Operons between Haemophilus influenzae Type b and Nontypeable Strains

 

Haemophilus influenzae is a common pathogen, especially among children, but the clinical manifestations are largely type specific. The encapsulated H. influenzae serotype b (Hib) usually causes invasive infections, such as meningitis and septicemia (2), whereas the much more common nonencapsulated, or nontypeable, H. influenzae (NTHi) is a major cause of otitis media, sinusitis, and pneumonia (8). General vaccination against Hib has reduced the incidence of Hib infection to a near minimum (10), while attempts to construct a vaccine against the costly NTHi infections have as yet been unsuccessful due to a high genetic heterogeneity among NTHi strains.

 

 

hib5

 

 

CDC: Better Tracking of Hib Needed

CDC: Better Tracking of Hib Needed

haemophilus_influenzae_cdc

Federal health officials are urging doctors and state agencies to be more careful in suspected cases of invasive Haemophilus influenzae type B (HiB) in children younger than 5, largely due to a continuing vaccine shortage that is expected to continue until the middle of 2009.

The vaccine protects against Hib disease (Haemophilus influenza type b) a bacterium estimated to be responsible for some three million serious illnesses and an estimated 386,000 deaths every year, mainly through meningitis and pneumonia.

There are varying forms of serotypes of H. influenzae, says Michael Jackson, an epidemiologist with the U.S. Centers for Disease Control and Prevention (CDC). The current vaccine helps to prevent type B, at one time the most common cause of bacterial meningitis in children.

But the reporting of serotypes to the CDC has been inconsistent with an estimated 40 percent of cases lacking such information, Dr. Jackson said.

“Without the serotype,” says Dr. Jackson, “we are unable to know if it’s type B, which is the type we are most concerned about, or another type that is less worrisome.”

The vaccine shortage began in December 2007 when Merck recalled 1.2 million doses of the vaccine. The voluntary recall began after the Merck found a bacterial contamination, Bacillus cereus on vaccine manufacturing equipment at its Pennsylvania plant.

The company has recently modified its manufacturing process, delaying vaccine availability until the middle of next year, said a spokeswoman for Merck.

While there is enough Hib vaccine to supply infants with a first series of shots, the shortage means children are going longer without the booster shots usually given after their first birthday, said CDC officials.

Agency officials encourage state and hospital laboratories, health departments and doctors to do serotyping of blood or spinal fluid specimens in a timely manner and report findings to the CDC.

The full report is published in the CDC’s weekly MMWR report on November 21, 2008.

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.
 

 

HIB Vaccines

Package Inserts

ActHib and OmniHib are conjugated with tetanus toxoid.

Hib Titer is conjugated with mutant diphtheria protein.

PedvaxHib and Comvax are conjugated with meningococcal group B outer membrane protein.

 

 Efficacy? The information varies based on the brand of vaccine. Table 2 at the end of this page http://www.cdc.gov/mmwr/preview/mmwr…m#00001680.htm tells how effective each dose number is.

Efficacy:

Results of efficacy trials among infants are available for the three conjugate vaccines. The first efficacy trial of an Hib conjugate vaccine among infants was completed in Finland using the PRP-D vaccine. In a systematic, unblinded trial involving 60,000 infants (30,000 of whom received the vaccine at 3, 4, and 6 months of age), the point estimate of efficacy was 87% (95% CI = 50%-96%) (10). In a randomized, double-blind, placebo-controlled study of 2,102 Alaskan Natives, however, the point estimate of efficacy was 35% (95% CI = (-57%)-73%) (11). Immunogenicity of the vaccine was limited in both trials. In the Finnish trial, less than 40% of infants had attained an antibody level of greater than 1 ug/mL 1 month after receiving the third of three doses (geometric mean titer (GMT) = 0.42 ug/mL). In Alaska, infants with a similar vaccination schedule had lower mean titers (GMT = 0.2 ug/mL) 3 months after receiving the third dose. A subsequent immunogenicity study documented antibody responses that were similar to those in the Alaskan and Finnish efficacy trials.

ActHib (Sanofi): ActHib was tested for safety by giving one group ActHib w/ DTP and the control group was given Hepatitis B w/ DTP. Here is an excerpt from the product insert:

 In a randomized, double-blind US clinical trial, ActHIB® was given concomitantly with DTP to more than 5,000 infants and Hepatitis B vaccine was given with DTP to a similar number.
In this large study, deaths due to sudden infant death syndrome (SIDS) and other causes were observed but were not different in the two groups.
In the first 48 hours following immunization, two definite and three possible seizures were observed after ActHIB® and DTP in comparison with none after Hepatitis B vaccine and DTP. This rate of seizures following ActHIB® and DTP was not greater than previously reported in infants receiving DTP alone. (Refer to product insert for AvP DTP.) Other adverse reactions reported with administration of other Haemophilus b conjugate vaccines include urticaria, seizures, hives, renal failure and Guillain-Barré syndrome (GBS). A cause and effect relationship among any of these events and the vaccination has not been established.

Children are at more risk of getting Hib disease right after vaccination.  

Studies from Science News warn of increased susceptability to the disease during the first 7 days after vaccination. The AAP has warned doctors to look for signs of the disease following vaccination (AAP policy statement.) Several studies have found that that Hib vaccinated children are up to 6 times more likely than non Hib vaccinated children to contract Hib during the first week following vaccination. (Pediatric Infectious Disease Journal and JAMA). 
 
In one study of children who got Hib at least 3 weeks after their vaccination, 70% developed meningitis. Additional research shows that antibody levels DECLINE rather than increase immediately following Hib vaccination, even with the newer conjugated vaccines. (Journal of Pediatrics, Pediatrics, and Pediatric Infectious Disease Journal.) 
 

Who are the highest risks?

 Children from lower socioeconomic families are at highest risk for getting Hib disease. (Physicians Desk Reference, 53rd edition, 1999 pg 3072)

Thirty-two percent of children aged 6–59 months with confirmed type b disease had received three or more doses of HIB vaccine, including 22 who had received a booster dose 14 or more days before onset of their illness. The cause of Hib vaccine failure in these children is not known.

Vaccine Linked with Diabetes:

 The British Medical Journal warns about the dangers of childhood vaccines. Investigators pooled data on roughly 116,000 Finnish children who received Heamophisis Influenza type b vaccine at either 3 or 24 months of age. These children were compared with 128,5000 children who did not receive the vaccine.
Subjects were reevaluated at age 10. The study’s author found that “immunizations starting after the age of 2 months is associated with an increased risk of diabetes. Our analysis is further associated with a similar rise in diabetis after immunization with H influenzae type b vaccine in the US and UK. Furthermore, the increased risk of of diabetes in the vaccinated group exceeds the expected decreased risk of complication of H influenzae meningitis.

Research into immunisation has been based on the theory that the benefits of immunisation far outweigh the risks from delayed adverse events and so long term safety studies do not need to be performed. When looking at diabetes only one potential chronic adverse event we found that the rise in the prevalence of diabetes may more than offset the expected decline in long term complications of H influenzae meningitis. Thus diabetes induced by vaccine should not be considered a rare potential adverse event. The incidence of many other chronic immunological diseases, including asthma, allergies, and immune mediated cancers, has risen rapidly and may also be linked to immunisation. Classen JB, Claussen DC. Public should be told that vaccines may have long term adverse effects. (Brit Med Journal 1999 (Jan 16);   318 (7177):193 full text)

 

 

 

The Hib vaccine can cause adverse reactions such as convulsions, allergic reactions such as anaphylaxis, vomiting, and serum sickness-like reactions. The FDA did not recognize these reactions when licensure was granted. Incidence of Hib type meningitis peaks between 6-11 months.
Daum RS, Sood SK, Osterholm, MT et. al.   Decline in serum antibody to the capsule of Haemophilus influenzae type b in the immediate postimmunization period   J Pediatr. 1989 (May);   114 (5):   742-747
Milstien JB, Gross TP, Kuritsky JN  
Adverse reactions reported following receipt of Haemophilus influenzae type b vaccine: an analysis after 1 year of marketing   Pediatrics 1987 (Aug);   80 (2):   270-274.

The “Finnish” study, upon which license was granted, showed the vaccine was  ineffective for infants 3-17 months of age.
Peltola H, Kayhty H, Sivonen A, Makela H   Haemophilus influenzae type b capsular polysaccharide vaccine in children: a double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland.   Pediatrics 1977 (Nov);   60 (5):   730-737.
Shinefield HR, Hiatt RA, Fireman BH   Efficacy of Haemophilus influenzae type b capsular polysaccharide vaccine.   Pediatr Infect Dis J. 1988 (Mar);   7 (3):   149-156
Shapiro ED, Murphy TV, Wald ER, Brady CA   The protective efficacy of Haemophilus b polysaccharide vaccine.   JAMA. 1988 (Sep 9);   260 (10):   1419-1422
Harrison LH, Broome CV, Hightower AW, Hoppe CC, Makintubee S, Sitze SLA day care-based study of the efficacy of Haemophilus b polysaccharide vaccine.   JAMA 1988 (Sep 9);   260 (10):   1413-1418

Other studies showed the vaccine has no efficacy at all:
Ward JI, Broome CV, Harrison LH, Shinefield H, Black S   Haemophilus influenzae type b vaccines: lessons for the future   Pediatrics 1988 (Jun);   81 (6):   886-893.
Osterholm MT, Rambeck JH, White KE, Jacobs JL, Pierson LM, Neaton JD, Hedberg   Lack of efficacy of Haemophilus b polysaccharide vaccine in Minnesota   JAMA 1988 (Sep 9);   260 (10):   1423-1428.
Ward J, Brenneman G, Letson GW, Heyward WL   Limited efficacy of a Haemophilus influenzae type b conjugate vaccine in Alaska Native infants. The Alaska H. influenzae Vaccine Study Group   N Engl J Med 1990 (Nov 15);   323 (20):   1393-1401

 

 

 

The C.D.C. stated “Efficacy of the conjugate vaccine (currently being used) has not been determined in field trials. MMWR 1988, Vol. 37, RR-37, pp. 13-16.

Your baby will actually become more susceptible to meningitis for up to 3 weeks following vaccination.  Daum RS, Sood SK, Osterholm, MT et. al.   Decline in serum antibody to the capsule of Haemophilus influenzae type b in the immediate postimmunization period.   J Pediatr. 1989 (May);   114 (5):   742-747.
Ward J, Brenneman G, Letson GW, Heyward WL   Limited efficacy of a Haemophilus influenzae type b conjugate vaccine in Alaska Native infants. The Alaska H. influenzae Vaccine Study Group.   N Engl J Med 1990 (Nov 15);   323 (20):   1393-1401
Sood SK, Schreiber JR, Siber GR, Daum RS.   Postvaccination susceptibility to invasive Haemophilus influenzae type b disease in infant rats.   J Pediatr 1988 (Nov);   113 (5):   814-819.
Hiner EE, Frasch CE   Spectrum of disease due to Haemophilus influenzae type b occurring in vaccinated children.   J Infect Dis 1988 (Aug);   158 (2):   343-348.
Granoff DM, Shackelford PG, Suarez BK, Nahm MH et. al. Hemophilus influenzae type B disease in children vaccinated with type B polysaccharide vaccine. N Engl J Med 1986 Dec 18;315(25):1584-1590. Ward J   Newer Haemophilus influenzae type b vaccines and passive prophylaxis.   Pediatr Infect Dis J. 1987 (Aug);   6 (8):   799-803.
 The risk of contracting meningitis one week after vaccination is 6.4-1.8 times greater than unvaccinated children.
Sood SK, Schreiber JR, Siber GR, Daum RS   Postvaccination susceptibility to invasive Haemophilus influenzae type b disease in infant rats   J Pediatr 1988 (Nov);   113 (5):   814-819.

41% of cases of Hib occurred in vaccinated individuals. The vaccine’s protective efficacy is about negative 58%.  You are more likely to get Hib if you are vaccinated.
Osterholm MT, Rambeck JH, White KE, Jacobs JL, Pierson LM, Neaton JD, Hedberg   Lack of efficacy of Haemophilus b polysaccharide vaccine in Minnesota.   JAMA 1988 (Sep 9);   260 (10): 1423-1428.

The widespread use of the Hemophilus influenza vaccine in 1986 was followed by a 62% rise (16 cases/100,000 children to 29.2 cases/100,000) in the incidence of diabetes in the 0-4 age group between the years 1980-1982 and 1990-1992.
Tuomilehto J, Virtala E, Karvonen M, Lounamaa R, Pikaniemi J et. al.   Increase in incidence of insulin-dependent diabetes mellitus among children in Finland   Int J Epidemiol 1995 (Oct);   24 (5):   984-992.

The incidence of IDDM also rose in the young children 2-3 year olds after the first dose of HiB was introduced.
Classen DC, Classen JB   The timing of pediatric immunization and the risk of insulin-dependent diabetes mellitus   Infectious Diseases in Clinical Practice 1997;   6:   449-454.
Drastic rises in the incidence of IDDM have been reported in the US and the UK after the introduction of the HiB vaccine.
 An epidemic of diabetes in the 0-4 age group occurred during the years 1985-1989 in Allegheny County at the time when the Hemophilus influenza vaccine was being incorporated into the immunization schedule. The annual incidence of IDDM in 0-4 year  olds living in Allegheny county rose 60% from the years 1980-1984 (10 cases/100,000) to 1985-1989 (16 cases/100,000). The incidence of diabetes in  0-4 year olds had been consistently below 10 cases/100,000 from 1965-1984.  The incidence of IDDM in this age group is expected to rise even higher since  the maximum effect of the HiB vaccine on IDDm is not seen until 4 years after  immunization.
 India appears to have a high rate of natural immunity:

 Studies from the early 1970’s might hold an explanation for this phenomenon. It is known that other bacteria have cross-reactive antigens to the Hib capsular polysaccharide. In an elegant experiment with burros, Bradshaw et al demonstrated the development of serologically specific precipitate antibodies to Hib after immunization of animals with Stephylococcus aureas and Bacillus subtillis. Strains of Staphylococci, Group D. Streptococci, Diphtheroids and Escherichia coli have been found with cross-reactive antigens to Hib. Robbins et al have demonstrated that infants show enhanced immune response to H influenzae capsular polysaccharide when they have concurrent cross reacting E. coli infection of the gut. Under these circumstances, a rapid and sustained rise in antibody to Hib was noted. E. Coli are ubiquitous in developing countries like India and their presence in the gut may have helped to stimulate antibody to Hib in the subjects reported….. There is thus a great potential for savings to be made in vaccination us in developing countries, if this finding is further substantiated. (Puliyel JM, Agarwal KS, Abass FA. Natural immunity to haemophilus b in infancy in Indian children. Vaccine 2001; 19: 4592-4594.)

 

 Hib and E Coli are not killers in undeveloped countries because the people can’t afford antibiotics. When you use antibiotics, the gut flora becomes unbalanced and causes E. Coli numbers to explode; making them very dangerous. Antibiotics kill E.Coli, and by doing so, can kill. The bacterial cell walls become endotoxin which cannot be processed by the liver and thus the person dies from antibiotic-induced endotoxic shock. Since 70% of the immune system resides in the gut, if you use antibiotics too much, not only do you create imbalances, you also create situations where you wouldn’t get good levels of diverse ‘good’ flora, so that they can make good levels of immunity to Hib.