Rethinking Replacement and Resistance

Rethinking Replacement and Resistance  (The Journal of Infectious Diseases 2009;199:771–773)

 

Before 2000, the year in which the 7‐valent pneumococcal conjugate vaccine (PCV7; Prevnar, Wyeth) was introduced into the US infant immunization schedule, most antibiotic‐resistant strains of Streptococcus pneumoniae belonged to serotypes included in PCV7. During just the first 3 years after vaccine introduction, we observed profound reductions in the incidence of invasive pneumococcal disease (e.g., bacteremia and meningitis) caused by vaccine serotypes and their associated antibiotic‐resistant strains, not only among vaccinated children but also among persons too young [1] and too old [2] to receive the vaccine. The dramatic success of PCV7 in reducing pneumococcal disease in wealthy countries [36]—and the potential benefits to poor countries [7, 8]—have led to World Health Organization recommendations for the global introduction of conjugate vaccines [9] and to extraordinary efforts to finance vaccine purchase and delivery to the poorest countries of the world [10].

At the same time we were heralding the benefits of PCV7, we were alert to the unintended consequence of serotype replacement. This phenomenon, demonstrated convincingly in randomized, controlled trials [11], occurs when serotypes not included in a conjugate vaccine colonize the nasopharynx and “replace” the vaccine serotypes whose colonization is prevented by the vaccine. The net effect is that PCV7 does not reduce the overall prevalence of nasopharyngeal colonization. PCV7 serotypes are, on average, better suited to causing invasive disease than non‐PCV7 serotypes [12, 13]; therefore, vaccine‐induced elimination of PCV7 serotypes from the nasopharynx leads to a net reduction in invasive disease and antibiotic resistance. Of all the serotypes, 19A may come closest to having certain characteristics that make it a successful replacement serotype. First, serotype 19A has relatively high propensities for colonizing the nasopharynx (to maximize transmissibility) and for causing invasive disease. Second, serotype 19A was associated with antibiotic resistance even before the introduction of PCV7; therefore, when exposed to antibiotics prescribed for upper respiratory tract infections, it had a selective advantage over other, more susceptible serotypes. Finally, PCV7 has no efficacy against serotype 19A.

Increases in the incidence of serotype 19A associated with otitis [14], mastoiditis [15], and invasive disease [1618] have been described in multiple US settings since 2000, making it impossible to ignore the temporal association between the introduction of PCV7 and the emergence of serotype 19A. It seemed safe to assume that PCV7 had caused replacement with serotype 19A. There were hints, however, that we might have been presumptuous in attributing the rise of serotype 19A exclusively to the use of PCV7. In multiple studies conducted before PCV7 introduction, serotype 19A was identified as an antibiotic‐resistant serotype, not only in the United States [19] but in other parts of the world as well [20, 21]. Until now, the strongest evidence against PCV7‐induced serotype replacement was that the incidence of serotype 19A seemed to be increasing in Korea [22], France, and Belgium [23] before the introduction of PCV7. The article by Dagan et al. [24] in this issue of the Journal pushes us to question our assumptions about serotype replacement even more forcefully.

The authors describe the emergence of serotype 19A as a cause of otitis media among Bedouin children in southern Israel who, along with their Jewish counterparts, had not received PCV7. During 1999–2006, the proportion of otitis media cases among Bedouin children caused by serotype 19A increased from 8% to 14%. Among Jewish children over the same time period, the prevalence of serotype 19A varied between 8% and 14% without a clear upward or downward trend. These findings are not particularly striking until one examines the susceptibility patterns and clones of serotype 19A strains in these 2 groups. A stable 38% of serotype 19A strains causing otitis in Jewish children from 2002 to 2006 were resistant to penicillin, with very few isolates resistant to macrolides or multiple agents. In contrast, the Bedouin population experienced a dramatic increase in the prevalence of 2 multidrug‐resistant pneumococcal clones (ST‐276 and ST‐2928) of serotype 19A over the same time period. Why the difference?

One hypothesis is that Bedouin children may have had greater exposure to antibiotics than Jewish children. In fact, in the 20% of both populations for whom data were available, modest reductions in overall antibiotic use, including amoxicillin and cephalosporins, were observed. Azithromycin prescriptions, on the other hand, increased markedly in both groups—antibiotic replacement, so to speak. This is important for 2 reasons. First, azithromycin may promote macrolide resistance better than other macrolides because of its long half‐life and low extracellular concentrations [25]. Macrolide resistance often travels with other resistance determinants, so it is plausible that the dramatic increase in multidrug resistance can be attributed to increased azithromycin use. Second, azithromycin use increased dramatically in the United States after its licensure in 1991 at the same time that overall antibiotic use was declining [26] and the prevalence of multidrug‐resistant S. pneumoniae was increasing [27]. This pattern suggests that the appearance of multidrug‐resistant serotype 19A in the United States and southern Israel may somehow have been a response to the introduction and increased use of azithromycin. However, if Bedouin and Jewish children both experienced important increases in azithromycin use, why were the increases in multidrug‐resistant serotype 19A confined to the Bedouin population? A careful look at differences between these populations may shed light on this question.

One important difference relates to seasonal patterns of antibiotic use. Antibiotic prescribing among Jewish children declines substantially in warm months and is accompanied by reductions in antibiotic resistance, whereas, among Bedouins, antibiotic prescribing and the prevalence of antibiotic resistance are more consistent year‐round [28]. This more stable antibiotic pressure may force strains colonizing Bedouin children to maintain multidrug‐resistance determinants despite the fitness costs required to do so [29]. There are also important socioeconomic disparities to consider. According to Dagan et al., Jews and Bedouins live side by side without intermingling. Bedouins have lower family incomes, but their birth rates and family sizes are more than double those of their Jewish counterparts. If living conditions among Bedouins favor more intense transmission, this may be sufficient to overcome any growth costs paid by the organism to sustain multiple resistance determinants [30]. Similar relationships between socioeconomic factors and pneumococcal colonization and transmission have been described in other settings [18, 3134].

Is the emergence of serotype 19A in the PCV7 era entirely attributable to antibiotic use, and is the introduction of PCV7 pure coincidence? It is hard to imagine that increases in serotype 19A causing otitis and invasive disease are not in some way related to the introduction of PCV7, and evidence of increased genetic diversity within serotype 19A, including some antibiotic‐susceptible clones, suggests that a serotype‐specific selection process is at work [16]. But Dagan et al.’s study reminds us to consider how other important factors, such as antibiotics, contribute to well‐documented trends in individual pneumococcal serotypes in the absence of PCV7 [3537]. It is a cautionary note to resist the temptation to attribute all increases in nonvaccine serotypes to the introduction of PCV7, as biologically plausible as that relationship may be. As we prepare for the availability of pneumococcal conjugate vaccines with expanded valency and as the introduction of conjugate vaccine moves forward among vulnerable populations of the world’s poor, Dagan et al. remind us that vaccines do not cause antibiotic resistance, antibiotics do.

 

See Also:

Introduction and Proliferation of Multidrug‐Resistant Streptococcus pneumoniae Serotype 19A Clones That Cause Acute Otitis Media in an Unvaccinated Population

(The Journal of Infectious Diseases 2009;199:776–785)
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Emergence of Streptococcus pneumoniae Serotypes

Emergence of Streptococcus pneumoniae Serotypes 19A, 6C, and 22F and Serogroup 15 in Cleveland, Ohio, in Relation to Introduction of the Protein-Conjugated Pneumococcal Vaccine

Clinical Infectious Diseases 2008;47:1388–1395    2008

Background.  A 7-valent conjugate pneumococcal vaccine (PCV7) was introduced in 2000.

Methods.  We determined serotypes and assessed antimicrobial susceptibility of 1235 invasive and noninvasive isolates of Streptococcus pneumoniae recovered from children and adults at University Hospitals Case Medical Center (Cleveland, OH) during the period 1999–2007.

Results.  The annual number of cases of S. pneumoniae infection decreased from 218 in 2000 to 86–130 during the period 2002–2007, with the number of cases involving invasive strains decreasing from 96 to 18–35. For 1999 versus 2005–2007, the annual incidence of vaccine serotypes decreased by 92% (95% confidence interval [CI], −96.3% to −87.0%), whereas that of vaccine-related and nonvaccine serotypes increased 207.4% (95% CI, 135.0%–297.7%) and 18.4% (95% CI, −10.0% to 52.3%), respectively. Serotypes 19A, 6C, and 22F and serogroup 15 accounted for most of these increases. For the period 2005–2007, antimicrobial susceptibility testing revealed that ceftriaxone was the most active parenteral β-lactam for both meningeal and nonmeningeal infections (72% and 88% of isolates, respectively, were susceptible to this agent); only 52% were susceptible to penicillin G at the meningeal breakpoint, whereas 77% were susceptible at the new nonmeningeal breakpoint of 2 μg/mL. Amoxicillin was the most active oral β-lactam (72% of isolates were susceptible), whereas 53% of isolates were susceptible to azithromycin, 69% to clindamycin, 63% to trimethoprim-sulfamethoxazole, and 100% to levofloxacin.

Conclusions.  This study documents decreases in the incidence of infections involving vaccine serotypes, increases in infections involving other serotypes, and decreases in the activity of macrolides and clindamycin after conjugate vaccine introduction.

Is GlaxoSmithKline Behaving Badly in Argentina?

Parents Allege Pharmaceutical Giant Tricked Them With Experimental Vaccine

Protocol Compas is the name of the study designed to test the efficacy of Synflorix, GSK’s experimental pediatric pneumonia vaccine, which can also ward off the bacteria that causes meningitis and ear infections. Synflorix is still in the preapproval stage.

 

 

GSK compares Synflorix with Wyeth’s hugely successful Prevnar vaccine, which has proved effective in the United States. Besides Argentina, trials are also being conducted in Panama, Chile and Colombia.

 

In 1997, the United States conducted 5 percent of its clinical studies outside of the United States and Western Europe, according to a study conducted by Tufts Center for Drug Development. By 2007, that number had climbed to 29 percent.

Because of the multinational business of major drug companies, and how Americans fit in as U.S.-based employees and stockholders of GSK, as well as consumers of drugs that will be available in the U.S. market, there are global ramifications of clinical testing being conducted around the world.

The lion’s share of drug studies has gone to regions with “emerging markets”: Eastern Europe and Central Europe, Latin America, and south and Southeast Asia. In order for a region to be of use to a legitimate drug company, the country has to maintain a minimal level of infrastructure, says Mary Jo Lamberti, director of market research at the Boston-based Center Watch, a consulting firm that bills itself as the “Global Destination for Clinical Trials Information.”

Some parents say they didn’t know that their children were participating in a study at all. Others claim to have been coerced into participating — a suggestion rebutted by Ruttiman, who told ABCNews.com that participation is always voluntary and that parents “are informed, clearly and in a language they can understand, by experienced medical investigators.”

They are informed not only about the benefits, he says, such as round-the-clock access to medical care and vaccinations against diseases such as diphtheria, tetanus and hepatitis, but about potential risks.

He adds that “the vaccines used in this study may cause adverse reactions unknown up to now. … As with any vaccine, unexpected adverse events can arise, including allergic reactions.”

Trading participation in a medical trial for health care has become the standard operating procedure for drug companies and/or their medical contractors, according to Shah. Some see it as win-win, but Shah views the trade as nearly as coercive as the dramatic threat Ester alleges she received.

“The argument I make is that the drug companies are going [abroad] because people have less access to health care,” said Shah. “So they offer incentives and the choice is, ‘participate in the trial or your children won’t get health care.’ That’s not a choice. Being in an experiment is not the same as standard care. In an experiment [the drug] might work, you might get a placebo or it might be worse than nothing. They might suffer some terrible unforeseen consequence.”

It’s impossible to say whether the 12 babies’ deaths are due to the vaccine or not, because half of the [total number of] children were given a placebo,” the pediatrician told ABCNews.com through a translator. “But the way the study has been conducted is reprehensible.”

A large part of the problem lies in the consent form, says Marchese. The language in the 12-page document is so convoluted, she charges, that even she had to read it more than once to fully grasp its meaning. Another problem is how subjects say they were recruited, Marchese says.

Ovejero, who works as a part-time disc jockey, alleges the couple was misled by the “agente saniterio,” a kind of nurse’s aide, who told them about the study. “She did not say it was a test. She said it was a vaccine for his lungs that would keep him from getting worse.”

The Nigerian state of Kano is one well-publicized example. In 2004, Kano’s government refused to take part in the Global Polio Eradication Initiative sponsored by the World Health Organization out of fears that the immunizations constituted a plot to reduce the country’s Muslim population.

According to The Associated Press, the boycott was initiated after Pfizer faced accusations made by families and human rights groups of putting about 200 children at risk during what they claimed was a poorly managed meningitis study 11 years ago.

Eleven children died, while others suffered brain damage, according to the Nigerian government, which this summer filed suit against the London- and Connecticut-based pharmaceutical company. The case is still pending.

 

More

 

 

 

 

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.