http://www.biomedcentral.com/news/20030523/05

The replacement effect
Concern over a vaccine that causes unintended increase in related infections
| By John Dudley Miller

Prevnar, a vaccine that is dramatically decreasing the number of American babies' infections from a common but serious bacterium, also increases the number of other infections the babies get, according to an Israeli researcher. No other vaccine in history has shown this unintended effect, said Ron Dagan, director of the Pediatric Infectious Disease Unit at Soroka University Medical Center in Beer-Sheva, Israel. "[Its importance] is not minor," he said, "but for the moment, we cannot estimate totally the clinical effect because we still do not have enough vaccinated people."

Hypothetically, Prevnar's disease-enabling ability might someday become as powerful as its disease-preventing capacity, rendering it effectively useless, said Dagan, and necessitating a new vaccine design. Future vaccines utilizing the same approach of targeting specific strains in a larger microbial family might also create this effect, according to other researchers.

Prevnar, a 7-valent pneumococcal conjugate vaccine marketed by Wyeth, helps prevent routine fevers, headaches, and earaches in young children as well as rarer, invasive infections with bacterial pneumonia or meningitis caused by the seven most widespread varieties of 90 types of pneumococcus bacteria. Kids and adults routinely carry all 90 strains in their noses and throats, even when they are not sick.

Prevnar vaccinations have been recommended for all American babies since mid-2000. Between 1999 and 2001, "invasive" pneumococcal infections, the most serious category, dropped 68% in babies under age 2, according to a national study conducted by the US Centers for Disease Control and Prevention (CDC).

Prevnar also lowered pneumococcal infection rates in older people who had never received the vaccine. Over the same 2 years, invasive pneumococcal infections in the United States dropped 29% in adults aged 20 to 39 and 17% in people over 65. Dagan attributes those decreases to the fact that vaccinated babies no longer carry the seven most prominent strains in their noses and throats, so they can't infect parents or grandparents.

Even so, Prevnar is already becoming somewhat less effective against infections of the middle ear, according to the CDC's Cynthia Whitney. "It's a big headache for us… the numbers just aren't as good as one would like," she said. Between 1999 and 2001, another study in the Pittsburgh area (C. McEllistrem et al., unpublished data, 2003) found the percentage of pneumococcal middle ear infections caused by strains that Prevnar doesn't protect against more than doubled, from 16 to 37%.

This shift in prevalence from one kind of infection to another is not yet much of a problem with invasive infections, although Dagan said cases are increasing. Dagan and others call the effect "replacement" because Prevnar effectively replaces infections by the seven targeted strains of pneumococci with similar infections by the other 83 strains. Prevnar vaccination also enables a slight increase in middle ear infections caused by two unrelated bacteria. These infections spread more easily because the vaccine wipes out their seven former competitors.

Dagan said the reason previous vaccines have not caused replacement is that healthy people don't harbor the bugs those vaccines protect against. With Prevnar, once it eliminates the seven selected strains, all the others proliferate inside babies' noses and throats, waiting for an opportunity to start an infection or to spread to someone else.

Steve Pelton, a pediatrician and pediatrics professor at the Boston University School of Medicine, points to an additional cause in the unexpected diversity of the 90 strains of pneumococci. Researchers had hoped that targeting the seven most common strains would provide more protection against the other 83, he explained. But if a replacement vaccine is eventually necessary, Pelton suggests a different approach: If you target something that's in all pneumococci, then you won't have this problem, he said.

Links for this article
J.D. Miller, "Unblocking the vaccine pipeline," The Scientist, May 13, 2003.
http://www.biomedcentral.com/news/20030513/02/

C.G. Whitney et al., "Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine," New England Journal of Medicine, 348:1737-1746, May 1, 2003. [PubMed Abstract]

J. Eskola et al., "Efficacy of a pneumococcal conjugate vaccine against acute otitis media," New England Journal of Medicine, 344:403-409, February 8, 2001.
[PubMed Abstract]
 

Testimony by Jerri Johnson
Health and Human Services Policy Committee
January 27, 2003

Costs to the State of Adding Vaccine Requirements

Immunization requirements are enforced by child care providers, state licensers of child care providers, and the public schools. This enforcement costs money for staff to do record-keeping and follow-up. Much of this cost is borne by the state. A study in 1998 estimated that enforcing the immunization requirements cost the state at that time around $5 million per year. Will adding new vaccines to the list increase costs to schools? It will, because many more follow-up contacts will be needed for these particular vaccines.

Currently, 35% of parents are not vaccinating their children for chickenpox. Minneapolis Public Schools estimated that each parent follow-up contact cost $18 in staff time.

Minneapolis Public Schools wrote to the Department of Health asking that no immunization requirements be added until funding is in place to enforce them. In addition to the state costs of enforcing vaccine requirements, these vaccines cost money in health care dollars.

I have included a handout in your package with medical cost analyses of pneumococcal and chickenpox vaccines. Chickenpox and pneumococcal vaccine programs actually cost more money than they save from preventing disease. The pneumococcal vaccine, for example costs around $60 per dose, or $240 per child for the four-dose series. The chickenpox vaccine also does not recover costs when looking at the cost of the vaccine compared to the cost of the disease. Only by factoring in indirect costs, such as lost wages for a parent to stay home with a child sick with chickenpox, is this vaccine deemed to be cost-effective.

But these assessments of indirect costs did not include the cost of caring for vaccine-injured children. Hospitalization and medical costs for these children are extremely high. During school years, they require special education services, costs borne by the state. These children may later be cared for in group homes the rest of their lives, incurring huge costs to the state. Twelve per cent of our children now have chronic disease of some sort, and many medical experts believe that the rapid increase in diseases such as autism, ADD, juvenile diabetes, and asthma is partially attributable to the increase in required vaccines.

A parent who stays home for 5 days when her child has chickenpox may use vacation days or may lose some income. But parents of children disabled by vaccines often must quit work permanently to stay home with their child, losing years of income, and the vaccine-injured child may never grow up to earn a productive income.

But ultimately, the question before us is not about dollars and cents. When we are preventing communicable disease, and when we are preventing vaccine injuries, the real issue is the value in human life that can't be quantified. You can't put a price on the joy of having a healthy baby, and you can't quantify the grief of a parent who loses a baby, no matter what the cause.

And so the Minnesota Natural Health Coalition is calling for the following:

1. Safer vaccines. Pharmaceutical companies need to be held accountable to produce vaccines that have fewer serious side effects.

2. The State of Minnesota should not require new vaccines if we do not know whether they are safe for our children. In the case of the pneumococcal vaccine, during the pre-licensure study, where 17,000 healthy infants with no acute or underlying chronic disease were given Prevnar, 162 infants required emergency room care and 24 were hospitalized within 72 hours of receiving the vaccine, 8 infants who had never had seizures before had seizures within 72 hours. 40 infants who had never had asthma before required doctor's care for asthma, wheezing, shortness of breath or breath-holding within 72 hours of the vaccine. One previously healthy child developed congestive heart failure within 72 hours of the vaccine. Three children developed hypotonic/hyporesponsive episodes. Were these serious situations caused by the vaccine? There is no way to determine this without following the time-honored scientific process of comparing the test group with a control group that did not receive a vaccine. This was not done. One variable, the test vaccine, was compared with another variable, another experimental vaccine.

Yet the physicians who conducted the study concluded at the end, this test "did not reveal any severe adverse events related to vaccination that resulted in hospitalization, emergency room visits, or clinic visits." This is the Vaccine Information Sheet on Prevnar given to parents at their clinics. It says, "So far, no serious reactions have been associated with this vaccine." Given the structure of the clinical study, it is not scientifically possible to say that these reactions were caused by the vaccine, nor is it possible to say that they were not.

3. If it is inherently impossible to produce a vaccine without a significant risk of serious adverse effects or death, then we need to be clear about that. If the pneumococcal vaccine effectively reduces pneumococcal disease, but at the price of death or disability to a few babies, we need to know those numbers. Our research needs to be science-based, with control groups, and parents need to know the risks so they can make an informed decision.

We are having a good debate in this country on the smallpox vaccine. This could be a great model for our infant vaccination programs. Public health officials are doing a good job of articulating the risks of smallpox and the risks of the vaccine. 1 or 2 deaths per million from the vaccine is being taken very seriously. Adults are weighing the risks and benefits.

We should afford the same courtesy to infants and their parents in the routine vaccine program.

4. Parents should be educated that if their child is ill, vaccination should be postponed. They should be told that if their child suffered a seizure or bad reaction to a previous vaccine, she is at risk for an even greater reaction to the next one. .If parents have a family history of a severe vaccine reaction, they should know that their child may be at risk. The CDC already has guidelines on this, and they are printed on the sheets given to parents when the child receives a vaccine. If parents knew this before making their appointments with the doctor, perhaps many vaccine injuries could be avoided. Again, the smallpox discussion is a good model on this - people are being informed that if you have eczema, you are at risk from the vaccine. . If you are on corticosteroids, you are at risk. Similarly, parents of infants could be advised on this at an early date.

5. If new vaccines being produced can not be safer, then perhaps we need to rethink the model which vaccinates the entire population for a disease. This model was developed in response to overwhelming epidemics like polio. However, in the case of invasive pneumococcal  disease, which affects only 0.2% of Minnesota children, this may not be an appropriate model.

6. Finally, parents who believe that their child was harmed or killed by a vaccine need to be heard and taken seriously. They should not be brushed off by being told it was not related to the vaccine. Their experience should be studied for clues to how we can have safer vaccine programs.
 

Wyeth Halts Shipments of Prevnar Vaccine

http://www.reuters.com/newsArticle.jhtml?type=healthNews&storyID=3770167

NEW YORK (Reuters) - Wyeth on Thursday said it has temporarily delayed shipping its blockbuster Prevnar vaccine against childhood pneumococcal infections because of the need to upgrade company quality-control processes. (What this really means is the plant is filthy and we had to clean it up)

Wyeth spokesman Doug Petkus declined to give further details, but said the company decided on its own to upgrade its quality-control systems for Prevnar and had not been asked to do so by the U.S. Food and Drug Administration.

 

Otitis Media Pathogens Skewed by 7-Valent Pneumococcal Vaccine

http://www.medscape.com/viewarticle/466298?mpid=22855
By David Douglas

NEW YORK (Reuters Health) Dec 22 - Certain strains of bacteria are more prevalent in children with acute otitis media who have been inoculated with the pneumococcal 7-valent protein conjugate (PNC7) vaccine, researchers report, with strains not included in the vaccine being favored.

As lead investigator Dr. M. Catherine McEllistrem told Reuters Health, "the proportion of cases of pneumococcal acute otitis media due to non-vaccine serogroup strains rapidly increased from 1999 to 2001 in children who received at least two doses of PNC7 vaccine."

Before licensure of this vaccine, about 85% of middle-ear isolates from children with the disease were of vaccine serotypes or cross-reacting serotypes. However, Dr. McEllistrem of the University of Pittsburgh School of Medicine and colleagues found that from 1999 to 2001, the proportion of non-vaccine serogroups increased from 14.8% to 36.5%.

Furthermore, they report in the December 1st issue of the Journal of Infectious Diseases, among children who received at least two doses of PNC7 vaccine, 46.7% of the isolates had non-vaccine serotypes compared with 20.8% in children who did not receive the vaccine.

Although this phenomenon is occurring among children who have acute otitis media due to Streptococcus pneumoniae, "significant serotype replacement has not been detected among children with pneumococcal invasive disease since introduction of the PNC7 vaccine," Dr. McEllistrem pointed out.

"These data," she concluded, "underscore the importance of the monitoring the epidemiology of pneumococcal infections in the PNC7 vaccine era."

J Infect Dis 2003;188:1679-1684.