FIVE-FOLD INCREASE IN PEDIATRIC PARAPNEUMONIC EMPYEMA SINCE INTRODUCTION OF PNEUMOCOCCAL CONJUGATE VACCINE

FIVE-FOLD INCREASE IN PEDIATRIC PARAPNEUMONIC EMPYEMA SINCE INTRODUCTION OF PNEUMOCOCCAL CONJUGATE VACCINE.

Brief Reports

Pediatric Infectious Disease Journal. 27(11):1030-1032, November 2008.
Hendrickson, Debra J. MD; Blumberg, Dean A. MD; Joad, Jesse P. MD; Jhawar, Sanjay MD; McDonald, Ruth J. MD

Abstract:
A retrospective review of medical records for all pediatric parapneumonic empyema (PPE) patients admitted to our hospital from 1996 to 2006 revealed that PPE increased 5-fold in the post-heptavalent pneumococcal conjugate vaccine (PCV7) period (2001-2005) relative to the pre-PCV7 period (1996-2000), from 13 cases to 65. Most of this increase was associated with culture-negative empyema, which accounted for 61% of all post-2000 cases; 19% was culture-positive pneumococcal empyema. Our analysis indicates that non-PCV7 serotypes became more prevalent at our institution after introduction of the vaccine.

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11-valent pneumococcal vaccine comes knocking

Safety of the 11-valent pneumococcal vaccine conjugated to non-typeable Haemophilus influenzae-derived protein D in the first 2 years of life and immunogenicity of the co-administered hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio virus, Haemophilus influenzae type b and control hepatitis A vaccines.

Prymula R, Chlibek R, Splino M, Kaliskova E, Kohl I, Lommel P, Schuerman L

Department of Epidemiology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.

This randomized (1:1), double-blind, multicenter study, included 4968 healthy infants to receive either the 11-valent pneumococcal protein D (PD)-conjugate study vaccine or the hepatitis A vaccine (HAV) (control) at 3, 4, 5, and 12-15 months of age. The three-dose primary course of both vaccines was co-administered with combined hexavalent DTPa-HBV-IPV/Hib vaccine. The pneumococcal PD-conjugate study vaccine did not impact the immune response of co-administered hexavalent vaccine and the control HAV vaccine induced seropositivity (antibodies >/=15mIU/mL) in all infants. The incidence of solicited symptoms was higher with the 11-valent pneumococcal PD-conjugate study vaccine, yet similar to that induced by concomitant DTPa-HBV-IPV/Hib vaccine. Overall, the reactogenicity and safety profile of the 11-valent pneumococcal PD-conjugate vaccine when co-administered with the hexavalent DTPa-HBV-IPV/Hib vaccine, as well as the immunogenicity of the co-administered hexavalent vaccine, were consistent with previous reports for the licensed DTPa-HBV-IPV/Hib and pneumococcal conjugate vaccines.

Vaccine
Volume 26, Issue 35, 18 August 2008, Pages 4563-4570

True safety..time will tell. There doesn’t appear to be a true placebo. They compared one group given  the trial vaccine and the other group given Hep A. And then, ‘both vaccines was co-administered with combined hexavalent DTPa-HBV-IPV/Hib vaccine.’

New Generation Vaccine?

GlaxoSmithKline is touting new, late-stage data that demonstrates how its experimental pediatric vaccine Synflorix effectively protects children from pneumococcal disease. Glaxo filed Synflorix for review by the EMEA at the beginning of the year. The new data illustrates its protection against 10 strains of streptococcus pneumoniae, which includes bacteria that causes meningitis, pneumonia and ear infections. If Glaxo prevails in its quest for regulatory approval, Synflorix will go up against Wyeth’s Prevnar, which targets seven of the 10 strains.

“The data presented today are extremely encouraging and represent a major step forward to a pneumococcal conjugate vaccine formulation, specifically designed to address the global epidemiology of pneumococcal disease in both developed and developing countries,” says Jean Stéphenne, president of GlaxoSmithKline Biologicals.

Encouraging? Maybe they missed the part where babies have died during the trials. Or maybe they find those babies simply..expendable? Informed Consent, what happened to that? Read excerpts below…

Authorities in Argentina are investigating whether there is a link between the deaths of 14 children and an experimental vaccine.

The children took Synflorix as part of a clinical trial run by the British pharmaceutical company Glaxo-SmithKline.

Synflorix is also being tested in Panama, Chile and some European countries, but it is not being tested in Britain.

The company is still enrolling participants. But officials at Argentina’s food and drug administration said the agency had ‘received complaints about irregularities in the recruitment of patients’ for the drug trial and on July 31 asked that recruitment be suspended.
GSK stopped recruiting the following day, saying it had already gathered the necessary number of participants.
Ana Maria Marchesse, who heads one of two groups that notified the national food and drug administration, said that she had witnessed ‘poor ethical management’ of patient recruitment, with participants being unaware they were being given an experimental drug.

Data from other studies shows that the vaccine is about as safe and tolerable as competitor Wyeth’s Prevnar, a vaccine widely used against pneumococcal disease, Miss Alpsach added.

However, the Argentinian province of Santiago del Estero is conducting a separate inquiry into the deaths of the seven children there, local health minister Franklin Moyano said.

 

 

 

In Argentina…Did Glaxo know that many of those who signed consent forms were illiterate? They also gave the vaccine first, then a consent form afterwards. When asked to have recruitment suspended for safety reasons, they just happen to have enough ‘guinea pigs’…
I don’t know about you, but something sure smells funny to me..

 Remember the name, Synflorix, as it may be knocking on your doctor’s door soon. It is expected to go up against the present Prevnar vaccine that targets only 7 strains. Wyeth, they hope to have their new version, that targets 13 strains, out by 2009.

 

 

 

 

 

 

Pneumococcal (Prevnar)

Pneumococcal disease is caused by a common bacterium, the pneumococcus, or also known as Streptococcus pneumoniae, which can attack different parts of the body. From the CDC Pink Book

 
Pneumococci are common inhabitants of the respiratory tract and may be isolated from the nasopharynx of 5% to 70% of healthy adults. Rates of asymptomatic carriage vary with age, environment, and the presence of upper respiratory infections. Only 5%–10% of adults without children are carriers. In schools and orphanages, 27%–58% of students and residents may be carriers. On military installations, as many as 50%–60% of service personnel may be carriers. The duration of carriage varies and is generally longer in children than adults. In addition, the relationship of carriage to the development of natural immunity is poorly understood.

Prevnar (PCV7) was licensed in 2000 for children under age 2 or for older high risk children. It was marketed to prevent invasive pneumococcal infections that can cause earaches, meningitis, blood poisoning and pneumonia, even though the chance of an infant contracting invasive pneumococcal disease was determined to be about 0.15%. Prevnar was also promoted as the ‘prevention of ear infections vaccine’ even though the package insert showed the vaccine decreases ear infections by only 9%.

Prevnar covers only 7 strains out of over 90. These strains are: 4, 9V, 14, 19F, and 23F and oligosaccharide from 18C, 6B. Prevnar was invented due to the routine use of Hib vaccine. Pneumococcal infections increased by filling the void left by the Hib vaccine.

There are two vaccines for adults and children over the age of 2 called Pneumovax and Pnu-Immune which cover 23 different strains of Streptococcus pneumoniae bacteria. The conjugate vaccine is used in the children’s version, Prevnar, and the polysaccharide vaccine is used in adult version.

Pneumococcus bacteria do not generally cause severe disease. Why it does cause more severe disease in some people is not widely understood.  The high risk groups would include: persons aged 65 and older; individuals with weak immune systems due to cancer, leukemia, Hodgkin’s disease or human immunodeficiency virus (HIV); persons with sickle cell disease or without a functioning spleen; individuals who have a chronic illness such as lung, heart, and kidney disease, diabetes and alcoholism; persons living in special environments or communities, such as Alaskan Natives and certain American Indian populations; and residents of chronic or long-term care facilities. (Facts About Pneumococcal Disease)

Efficacy and Safety Studies:

 

There used to be an FDA transcript and a chart that showed the low efficacy for AOM, but it appears to have been removed.  Here is an excerpt of what it said:
 

In summary, the Committee concluded that data derived from two efficacy trials are adequate to demonstrate efficacy of Prevnar® against AOM caused by vaccine serotype.   
However, the committee expressed concern about the low efficacy (7%) of the vaccine against AOM regardless of etiology and concluded that substantial clinical benefit of Prevnar in reducing AOM regardless of etiology had not been demonstrated. The Committee cautioned against including an indication statement as proposed by the sponsor into the label and suggested using qualifying language if an indication for AOM regardless of etiology were to be added. Committee members cautioned against promoting prevention of AOM as a benefit of Prevnar in direct-to-consumer advertising because of concerns about unrealistic public expectations.  

The Committee was concerned that promoting Prevnar as an “AOM vaccine” could potentially compromise confidence in the existing recommendations for the vaccine and trust in the labeling that FDA puts on a vaccine.

 What about the safety of Prevnar? 

 

In the clinical trials, the pneumococcal vaccine was compared against an experimental meningococcal vaccine. This means the clinical trial had no real placebo because the reaction profile was unknown for both experimental vaccines, which would compromise the scientific validity of the safety trial. Children in the Prevnar trial group had more seizures, irritability, high fevers, amongst other reactions. There were 12 deaths reported in the Prevnar group but were dismissed as “Sudden Infant Death Syndrome.” (REF: Wyeth-Lederle Product Manufacturer Insert Pneumococcal 7- Valent Conjugate Vaccine (PREVNAR). Issued February 2000. www.fda.gov/cber/label/prevnarLB.pdf). Also see: Prevnar -a critical review of a new vaccine.

 

While the Pneumococcal vaccine may have reduced incidence rates, there has been a trade-off due to serotype replacement  The strains not covered in the current vaccine for children are proliferating. According to Science Daily:

The incidence of IPD caused by strains not included in the vaccine rose by 40%. One of the non-vaccine strains, 19A showed an increase of 264%… Disease caused by non-PCV7 serotypes, especially 19A, is emerging and accounts for nearly all IPD.

According to The Journal of Infectious Diseases 2008; 197:1016–1027: Emergent Streptococcus pneumoniae Serotype 19A in the United States 2005:

Conclusions.  PCV7 ineffectiveness against serotype 19A, antibiotic resistance, clonal expansion and emergence, and capsular switching have contributed to the genetic diversity of 19A and to its emergence as the predominant invasive pneumococcal serotype in the United States.

Another problem with the widespread use of Prevnar has been the emergence of antibiotic resistant bacterial strains. The introduction of Prevnar appears to have caused many strains to become highly resistant. A vaccine-resistant virulent strain of strep is causing ear infections in children that cannot be treated with antibiotics safe for use in children.

 

Michael E. Pichichero and Janet R. Casey of the University of Rochester in New York documented the emergence of an antibiotic-resistant strain of another bacterium known as Streptococcus pneumoniae, which causes common ear infections. Although all 11 children identified in the Rochester area with the microbe so far were successfully treated, five required an antibiotic approved only for adults, and one child was left with permanent hearing loss.

The researchers attributed the emergence of the strain to a combination of the overuse of antibiotics and the introduction of a vaccine that protects against the infection.

“The use of the vaccine created an ecological vacuum, and that combined with excessive use of antibiotics to create this new superbug,” Pichichero said.

 

Prevnar has not reduced the number of cases of meningitis. It has merely changed them to other types of meningitis.

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.

 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.

 What is the answer to that? A new vaccine for Meningitis for toddlers and adolescents! This will simply try and fool Mother Nature and further mess with the bacterial balance of the body. This will not just affect those who choose to vaccinate because the strains not covered by the vaccine are in higher concentrations in those vaccinated, which will facilitate the spread of the bacteria to everyone.

 

MRSA is also a strain of the bacterium that usually causes staph infections that used to be easily treatable with common antibiotics in the penicillin family. Resistant strains of the organism have been increasing.

 

Natural immunity to pneumococcus may be more important for protecting against the disease than the vaccine according to research published in 2005. The researchers found that another mechanism, other than antibody protection, confers protection against the bacteria. What provides this protection? Researchers don’t quite know.

 these observations make a strong case for the importance of one or more factors other than [the development of] antibodies” is necessary to confer protection against pneumococcal disease.” So, children have an element of natural protection, beyond the perceived benefit of the pneumococcal vaccine, we do not understand.

Interesting!

 

If we are trading one disease for another, how do we stop it, and stop the need for more and more vaccines?  Is it already too late?  Stay tuned for more on pneumococcus…

 

Cumulative weekly number of reports of Invasive Pneumococcal Disease due to any of the serotypes NOT IN Prevenar™ : Children aged < 2 Years in England and Wales by Epidemiological Year: July-June (2003- To Date)

 

Source:

http://www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPAweb_C/1207821645727?p=1203409671876