Prevnar's risk
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http://www.wfaa.com/wfaa/articledisplay/0,1002,20489,00.html
News 8 Investigates: Prevnar-Part 1

DALLAS, Feb 21  - By the time our children are old enough to go to school in this country we have given them nearly 40 doses of vaccines. In 1940, children received just nine doses of vaccines. News 8's Valeri Williams begins an investigation into the questionable science behind the federal government's vaccine approval process. And what parents should know about the latest vaccine on the market, Prevnar.

"He-man took it with a smile as they participated in the experiment that could end the menace of polio," said a clip from an old film. This is NOT a report about vaccines being bad.  In the past 50 years, they have helped us to eradicate polio, small pox and whooping cough just to name a few dreaded childhood diseases. But as the number of vaccines grows in this country so do the profits for the pharmaceutical companies who manufacture them.

Consumer advocates say here's what getting government approval for just one vaccine can mean:

"The vaccine manufacturer of a new vaccine that's added to the universal use list has an assured stable market of three-and-a-half to four million babies born in this country every year. As of 1986, the manufacturer has virtually no liability for adverse events that may occur as do the doctors who administer the vaccine as of 1986. No liability. Stable-made market. No liability. A stockholder's dream," said Barbara Loe Fisher of the National Vaccine Information Center.

This little vial holds one of the latest vaccines to be licensed by the FDA.

It's called Prevnar and since last March, there have been 10-million doses distributed.  At about $60-per-injection, there are a series of four shots, this is one of the most expensive vaccines in history. "I had a baby that was perfectly healthy, happy, okay until she got a shot, until she got her vaccine, remembered parent Ray Graves.

Hayley Graves was nine months old when she received her second dose of Prevnar. This picture was taken the day she got her injection. "Thirty, forty hours later, she's in the hospital having seizures that they can't stop. You're not gonna tell me it's not related to the vaccine somehow," said Graves. Hayley slipped in and out of a coma for 45 days until she died in September. Tremors shook her little body almost the entire time. "It's hard, it's very hard," said Graves.

Like many parents, Ray and Lisa Graves were told by their pediatrician that Prevnar would help to prevent "otitis media"-- or in layman's terms-- ear infections.  But News 8 has discovered during a four-month investigation that Prevnar was never licensed for that use.  In fact, clinical trials showed that overall Prevnar decreased a child's chance of getting an ear infection by only 6% as compared to children who did not get the vaccine.

"I don't think anybody believes the vaccine was developed to prevent otitis," said Dr. John Modlin, chairman of the CDC Vaccine Advisory Committee.  Dr. Modlin confirmed that he knew this to be the case during an interview last week.  So 'why' we wondered had the Centers for Disease Control put out this fact sheet last March telling parents that among those who benefited most from Prevnar were:

"Children who have frequent or serious ear-aches." "I think what you're focusing on here is um.. is um ... I think you're creating basically a tempest in a teapot here," said Dr. Modlin.  But the misinformation from federal regulators doesn't stop there. Doctors who log onto the CDC's website for Continuing Education Credit are given this test question which asks:

"Which type of pneumococcal disease is the Prevnar vaccine effective in preventing? The correct answer according to the CDC is "all of the above"... including "acute otitis media".  Dr. Erdem Cantekin is one of the nation's leading experts on ear aches. "It is an ineffective and toxic vaccine," said medical researcher Dr. Cantekin.

Cantekin says not only are federal regulators putting out bad information, they're also not revealing some of Prevnar's dangerous side effects. Like seizures, which Cantekin says a study by the vaccine's manufacturer shows happened four times more often in infants given vaccines with Prevnar than children in a control group.

"I think the FDA approval of this vaccine is an act of irresponsibility. I think the FDA is following their regular course. They ignore the warnings until many people die, and then, it becomes such a public outrage and public problem, they say, "Oops, we will take this thing off the market," said Dr. Cantekin. Before licensing Prevnar last year, vaccine committees from both the FDA and the CDC dismissed the data on seizures as not signficant. However, as part of our investigation, News 8 reviewed nearly 800 adverse reaction reports filed with the FDA during past nine months.

What we found is that one of out 10 children who had suspected side effects suffered some sort of seizure. "I'm angry..or I'm not angry, I'm mad.. that's all there is to it. You know, I guess I'm a little bitter about losing a child. I'm not a little, I'm a lot bitter," said Graves.  The Graves have no absolute proof that Prevnar killed their daughter.. just a string of medical coincidences.

Wyeth Laboratories, which makes Prevnar, says it has received a small number of reports about seizures among patients who've received the vaccine. The company declined to interview with News 8, but it did fax us this letter which says:

"These reports are consistent with data from clinical trials documenting seizures in children who did not receive Prevnar. While there have also been a small number of deaths coincident with Prevnar administration, there is no reason to conclude that there is any association between these deaths and the administration of Prevnar. Prevnar... was tested in hundreds of thousands of children prior to its approval by the FDA." Once you assume that a certain number of children are expendible, it is a very slippery slope. Because then, how many, how many can you sacrifice? Is it five? Is it a 100? Is it 5,000? It's very dangerous to employ that kind of utilitarian rational," said Fisher.

So if Prevnar was not licensed for ear infections... exactly what was it approved for?  To fight some strains of pneumococcal meningitis, pneumonia, and bacterimia. But last year, there were only 1500 cases of pneumococcal meningitis in infants in this country.

Critics say not enough of a threat to scare parents into getting the vaccine, but tell parents that this ear ache vaccine... and there are five million cases of ear infections in children each year ... suddenly that produces a lot more interest.  Thursday night News 8's Valeri Williams will look into the stocks, grants or contracts that the people who sit on the vaccine committees have with the pharmaceutical industry.

It's called "conflict of interest".

By: Valeri Williams
Copyright:  2001 by WFAA-TV Co. All Rights Reserved.

http://www.immunizationinfo.org/pressroom/newsbriefs_detail.cfv?id=9835

Lawsuit Alleges Irregularities With Vaccine

Wall Street Journal C1
Hensley, Scott ; McKay, Betsy

03/31/2004

Since its introduction to the market in 2000, the pneumococcal vaccine Prevnar has grown in popularity as a protective barrier against the bacteria, which  can cause brain infections and even death, yet its maker Wyeth has run into a string of production problems that have left the company unable to meet demand and prompting the Centers for Disease Control and Prevention to recommend delays in children's four-dose immunization schedules so that infants can have at least some protection with two doses.

The vaccine takes a year to produce, so any improvement in Wyeth's production abilities is delayed on the market for a year, leading to continued shortages that are expected through the summer of 2004, though the company claims that at that time, the troubles will be over. In a twist, however, former Wyeth manufacturing manager Mark Livingston has filed a lawsuit against the company and two employees, saying that in its drive to get Prevnar to the market, Wyeth cut production corners that violate Food and Drug Administration (FDA) rules and which could leave the vaccine vulnerable to problems with quality control. Livingston brought up his concerns at an FDA meeting in July 2003, but he said that because he had not heard any development from the agency since that time, he would go ahead with a civil lawsuit to bring more attention to the matter, claiming that Wyeth's actions amount to  fraud against its shareholders by not revealing problems with Prevnar production.
 

http://abclocal.go.com/wtvd/news/050704_NW_prevnar.html
WTVD Raleigh Durham
May 7, 2004

Pharmaceutical Plant Employee Fired After Raising Alarm Over Vaccine Production

Eyewitness News Investigates
By Steve Daniels

Prevnar prevents a potentially fatal illness in children called pneumococcal meningitis, the most common bacterial infection. Prevnar is a multi-billion dollar product for Wyeth in Sanford. But a local man who used to work there claims profits were more important to his bosses than proper training on the production line. Elizabeth is just 14 months old. She's at Triangle Pediatrics in Cary getting her latest round of shots and she's not happy about it.  The federal government says every baby in America should get a vaccine called Prevnar. It's made at the Wyeth Pharmaceutical plant in Sanford.

Mark Livingston used to work at the Sanford plant. He was a manager who was supposed to make sure all the workers had the proper training. "If there are major deviations or problems or issues, the FDA can come in and ask for me and handcuff me and take me out," Livingston said. Eyewitness News asked Livingston what he could say about the quality control of the vaccine leaving the Sanford plant. "Quality control is suspect," he said. That's why he says he came forward with allegations claiming Wyeth was cutting corners when it came to worker training inside the Prevnar plant, which he claims violated federal regulations. "The potential for contaminated product, a mislabeled, or an outright failure of part of the vaccine, or the total vaccine goes up dramatically," Livingston said. In a federal whistleblower lawsuit, Livingston says he was fired in 2002 for raising questions about worker training on the Prevnar production line. The problems he says he saw could have meant big trouble for Wyeth, because in 2000 it paid a $30 million fine for violating FDA regulations at another plant.

"Mark Livingston is a hero, whistle blowers are heroes," said Joanne Royce, an attorney with the Government Accountability Project. Royce is also Mark Livingston's lawyer. "Mr. Livingston cared more about the babies than he did about his own job," she said. "He knew he was going to be fired. But he had the courage to come forward and tell the truth." Wyeth wouldn't talk on camera, but the company says the lawsuit has no merit and the company will defend itself vigorously. Wyeth also says all the employees have the requisite training, background and experience. Wyeth says Livingston's a disgruntled former employee. "That's what employers always say about whistle blowers," said attorney Joanne Royce. "But the evidence will show when we take it to trial, there was one reason Mark Livingston was fired, and that's because he blew the whistle on corporate corruption and gross non-compliance in the manufacture of Prevnar."

Livingston feels he had become, in Wyeth's view, a troublemaker who had to go. "Probably from Wyeth's point of view yes, I was too aggressive, too assertive challenging the status quo too much." But Mark Livingston says he did it for the babies. "Babies have no voice and so we're giving them four shots of this chemical soup within the first year of their life. They're looking at us. They're trusting us completely." Wyeth says there are no safety problems with Prevnar connected to production at the Sanford plant. Mark Livingston says he'd like to get his job back at Wyeth. He hopes a judge agrees with his claim and orders Wyeth to re-hire him.

Online producer: Shaun Chavis Benchi

 
 

Doctors decry lack of Wyeth vaccine

Health policy officials urge rationing of Prevnar, which prevents meningitis
Sunday, May 30, 2004
BY ED SILVERMAN

Star-Ledger Staff

When Barry Prystowsky heard last November about a sudden shortage of the Prevnar vaccine for meningitis, he was frustrated and alarmed.

"It was very aggravating. The explanation was never clear," said the Nutley pediatrician. "But I had to tell parents that I couldn't protect their babies against this horrible bacteria."

He was even more upset during February, when Wyeth, the only company to make the vaccine, said supplies were still hampered by unspecified production problems. Today, the medicine is being rationed, and many doctors say Wyeth should have disclosed the full extent of a series of manufacturing problems that caused the shortage.

Wyeth experienced numerous manufacturing issues for several years before the shortage was announced, according to the Food and Drug Administration. The two plants that make Prevnar were annually cited for extensive shortcomings -- most recently last September and October. And one plant avoided taking steps to improve quality control, according to a whistleblower lawsuit filed by a former employee.

A number of doctors say they were upset by the lack of timely information, because it forced them to grapple with both an unexpected shortage and an inability to plan. Doctors are rationing the widely praised vaccine, which is supposed to be administered to children four times by the age of 15 months. Instead, children are given just two shots.

"Being kept in the dark for a protracted period of time really does wreak havoc," said Tom Saari, a University of Wisconsin pediatrics professor and member of the infectious diseases committee at the American Academy of Pediatrics. "My concern is if they're going to shut down, they should've had a pretty good idea how long it would take to get up and running."

WIDER IMPLICATIONS

Beyond the immediate shortage, the episode may have wider implications for Wyeth. Prevnar is one of the Madison-based drug maker's biggest-selling products, generating nearly $1 billion in revenue last year.

Wyeth officials acknowledged manufacturing problems, but maintain they took steps to fix them. And they stressed the plant problems didn't pose a safety issue. "We're as frustrated as anybody else," said Peter Paradiso, Wyeth's vice president of scientific affairs. "We want to make sure we maximize coverage of this vaccine."

The Centers for Disease Control and Prevention, which establishes national health policy, had to issue two different advisories about Prevnar rationing during less than four months. This caused confusion and anxiety among doctors and patients, according to the federal agency.

"Had we known that the shortage was going to get much worse, we wouldn't have done things the way we did," said Lance Rodewald, director of the immunization division at the CDC, which recommended the reduction in the number of shots.

At issue is whether Wyeth should have disclosed more information sooner about manufacturing problems that may cause shortages. Although disclosure wasn't required, Wyeth didn't reveal that a team of FDA inspectors last October found numerous quality-control failings at its Pearl River, N.Y., plant. Prevnar is made at a Sanford, N.C., facility, but is packaged in Pearl River. A production shutdown occurred at the Pearl River site late last year.

 

BAD REPORT

The FDA inspection report, which was obtained by The Star- Ledger, detailed sloppy operating procedures, dirty work areas, instances of contamination, improper environmental monitoring and insects in a hallway outside a room where the vaccine was filled in vials. Wyeth's own internal investigations also took longer than expected and were incomplete, the report said.

"Manufacturing investigation reports are not always completed in a timely manner," the FDA inspectors wrote in reviewing Wyeth's follow-up to problems noted previously by the agency. "Further, there is a lack of evidence that product impact is addressed in a timely manner and that all batches/processes are fully investigated."

Bruce Burlington, a Wyeth executive vice president in charge of quality, regulatory and safety matters, said FDA inspectors found significant shortcomings during the inspection at the Pearl River plant last October,

Detailed inspections are routine in the pharmaceutical industry, which must adhere to strict manufacturing practices. But lengthy inspection reports aren't the norm. In this case, FDA inspectors chronicled 59 problems in their 15-page account. But FDA spokeswoman Lenore Gelb said any serious problems would be conveyed to the medical community.

In a brief interview last month, Bernard Poussot, a Wyeth executive vice president, said the stoppage at the Pearl River plant late last year took place because "the FDA shut us down." Such a step would indicate the company had no choice but to interrupt production. However, the FDA spokeswoman said the agency never took such action. A Wyeth spokesman didn't make Poussot available for further comment.

 

SECOND INSPECTION

This was the second time the FDA inspected the facility since October 2000, when Wyeth signed a consent decree with the federal government. As part of the decree, Wyeth agreed to correct manufacturing problems and relinquish $30 million in profit. The company still faces as much as $5 million in fines for failing to improve operations.

A consent decree results when a company repeatedly fails to comply with FDA standards. Repeated citations by FDA inspectors reflect an ongoing inability to satisfy the decree requirements, according to Suggy Chrai, a drug-industry manufacturing consultant.

Wyeth officials have repeatedly said the safety or effectiveness of the vaccine was never compromised. They said deficiencies were willingly disclosed to FDA inspectors and that last year's Pearl River shutdown was part of a scheduled maintenance procedure. The stoppage ran longer than expected due to ongoing manufacturing problems, they said.

"We shut it down to do a routine maintenance and because of the issues that arose, we had a pronounced shutdown," said Wyeth's Paradiso. He added the CDC and doctor groups were alerted to an impending shortage very quickly last fall, but the extent of the plant problems weren't disclosed.

In addition, Wyeth's Burlington defended the company's efforts and also noted Prevnar is a difficult product to make.

"At this point, we're where we want to be," he said. "We sent a remediation plan to the FDA and the response we received indicates our action appears to be adequate. And we'll be on a full production schedule, hopefully, later this year."

SHARED PRODUCTION

To do so, Wyeth has enlisted two companies, Cardinal Health and Baxter Healthcare, to assume part of the production process that was previously handled at Pearl River.

Normal production would cheer Wall Street. Despite the difficulties, which include a previous shortage, Prevnar has been a shot in the arm for Wyeth. Approved by the FDA during 2000, Prevnar quickly filled a medical void. Until then, pneumococcal infection each year killed 200 children under the age of 5 and caused more than 700 meningitis cases.

Last year, the vaccine generated $946 million in sales. That was much-needed revenue for a drug maker plagued by a pair of serious setbacks -- costly diet-pill litigation and plunging sales of hormone replacement treatments.

To capitalize, Wyeth has wanted to produce as much vaccine as possible, even while grappling with the consent decree. But Chrai, the manufacturing consultant, said drug makers that don't quickly fix mistakes run the risk of a financial hit and losing investor confidence.

"Prevnar is an important product for Wyeth. It's an earnings driver," said David Moskowitz, an industry analyst at Friedman Billings Ramsey. "At this point, it's a show-me story. It's very unfortunate they haven't been able to supply the product. They really need to show the marketplace they can supply it in sufficient quantities by the end of the year."

One former Wyeth employee maintains shareholders have already suffered.

In a whistleblower lawsuit filed last December in U.S. District Court in Greensboro, N.C., Mark Livingston, a quality-control expert, charged Wyeth managers at the Sanford, N.C., plant cut corners to boost Prevnar production. He also charged that his suggestions for meeting FDA standards were deliberately ignored and that he was wrongly fired during 2002.

The company's practices, according to the lawsuit, amounted to fraud and violated the Sarbanes- Oxley Act, which was designed to improve corporate governance and financial disclosure to shareholders. For instance, filings with the Securities and Exchange Commission didn't mention a negative FDA inspection report at the Sanford plant during September 2003.

MISREPRESENTATIONS

"They misrepresented the real state of manufacturing," said Joanne Royce, an attorney with the Government Accountability Project, which represents Livingston. "And so there was misrepresentation of Wyeth's financial condition. When noncompliance goes on so long, shareholders have a right to know. It's bound to reflect on the bottom line at some point."

A Wyeth spokesman, Doug Petkus, said the lawsuit was filed by a disgruntled employee and was without merit. He also said Prevnar remains safe and effective. Despite the ongoing shortage, Margaret Rennels, a University of Maryland pediatrics professor and chair of the American Academy of Pediatrics infectious diseases committee, praised Wyeth for providing weekly inventory updates, creating an effective rationing system and opening a hot line for doctors.

"They're trying to ensure that every doctor has enough vaccine to administer, and in an equitable way," she said. Yet she and other doctors say the episode is worrisome, and are concerned another shortage may occur unless Wyeth improves its manufacturing procedures. "With Wyeth, there's a pattern here, and it concerns me," said Saari of the University of Wisconsin. "The fact that these issues are still going on is disturbing, because of the impact on kids who can't get the vaccine. There are some real risks in terms of disease prevention."

Ed Silverman can be reached at (973) 392-1542 or esilverman@starled ger.com.

Copyright 2004 NJ.com. All Rights Reserved.

http://www.medalerts.org/

Prevnar is PNC Lederle in VAERS
There have been 217 deaths reported since 5/2000 (22 pages) The following are some interesting cases from the first FIVE pages, where the baby received Prevnar alone and died shortly thereafter "coincidentally" The reports are copied as they appear..

===================================================
Found 217 records with Vaccine contains 'PNC' and Patient Died

Result page: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 

============
VAERS ID 158751 Vaccination Date: 2000-07-27
Age 0.8 Date filed: 2000-08-15
Sex M Where Administered: PVT
State WI Purchased by: PVT
Life Threatening Illness? No
Died? Yes (date died: 2000-07-28)
Disability? No
Recovered? No
ER or Doctor Visit? No
Hospitalized? No
Current Illness: Sinusitis
Diagnostic Lab Data:
Previous Vaccinations:
Other Medications:
Preexisting Conditions: Walker-Warburg syndrome

Vaccinations Manufacturer Lot Dose Route Site
1 PNC LEDERLE 475228 1 IM LL

Onset Date: 2000-07-28    Number of Days: 1
Symptoms: REACT UNEVAL
Death. Doubt any relationship other than temporal.

==============================================
VAERS ID 161756 Vaccination Date: 2000-07-03
Age 0.8 Date filed: 2000-11-10
Sex M Where Administered: PVT
State KY Purchased by:
Life Threatening Illness? Yes
Died? Yes (date died: 2000-07-22)
Disability? No
Recovered? No
ER or Doctor Visit? Yes
Hospitalized? Yes (days in hospital: 2)
    Prolonged Hospitalization? No
Current Illness:
Diagnostic Lab Data: sepsis work-up, CSF culture showed strep pneumoniae;
CSF was sent to CDC where it was sterotyped as #14, which is a sterotyped
contained in Prevnar
Previous Vaccinations:
Other Medications: Tylenol, Motrin
Preexisting Conditions:

Vaccinations Manufacturer Lot Dose Route Site
1 PNC LEDERLE 4712149 0 IM LL

Onset Date: 2000-07-19    Number of Days: 16
Symptoms: DYSPNEA FEVER HYPOXIA INFECT BACT INTRACRAN HYPERTENS MYDRIASIS
PNEUMONIA RASH STUPOR VOMIT
On 7/19, the pt developed a fever and rash on face. On 7/20, the fever
continued. On 7/21, the pt developed vomiting and fever. Then later on
7/21, seen at physician's office with unresponsiveness, forced
respirations, bulging fontanelle, dilated left pupil. Pt transferred by
ambulance to hospital where pt was intubated. En route to CT, the pt was
coded and eventually expired on 7/22.

===================================
VAERS ID 165790 Vaccination Date: 2001-01-11
Age 0.2 Date filed: 2001-02-13
Sex M Where Administered:
State SC Purchased by:
Life Threatening Illness? No
Died? Yes (date died: 2001-01-14)
Disability? No
Recovered? No
ER or Doctor Visit? No
Hospitalized? Yes (days in hospital: )
    Prolonged Hospitalization? No
Current Illness:
Diagnostic Lab Data:
Previous Vaccinations:
Other Medications:
Preexisting Conditions: prematurity (29 weeks), ROP

Vaccinations Manufacturer Lot Dose Route Site
1 PNC LEDERLE IM

Onset Date: 2001-01-11    Number of Days: 0
Symptoms: APNEA CYANOSIS SHOCK
This patient presented to ED in shock. The patient was then transported to
PICU. The patient in shock requiring cardiopulmonary resuscitation. The
patient expired approximately 72 hours after admission. The patient had
received Prevnar the day prior to admission. Autopsy shows baby was
cyanotic, not breathing

=============================
VAERS ID 166725 Vaccination Date: 2001-01-08
Age 4.0 Date filed: 2001-03-08
Sex F Where Administered: PVT
State WA Purchased by: PVT
Life Threatening Illness? No
Died? Yes (date died: 2001-01-22)
Disability? No
Recovered? No
ER or Doctor Visit? No
Hospitalized? No
Current Illness: NONE
Diagnostic Lab Data: NONE
Previous Vaccinations:
Other Medications: Ranitidine, Fluoride, Prednisone, Reglan, multivitamins
Preexisting Conditions: microcephaly, undiagnosed endocrine abnormality, GE
reflux, G-tube fed

Vaccinations Manufacturer Lot Dose Route Site
1 PNC LEDERLE 473825 1 IM RL

Onset Date: 2001-01-22    Number of Days: 14
Symptoms: DYSPNEA ENDO DIS SUDDEN DEATH
The pt had an undiagnosed metabolic/endocrine problem had gradual
deterioration in the last few months of life. A week before death had
"strange" breathing pattern, like gasping. Died 15 days post vax. PMD
doesn't think it is causally related. Sudden death, no fever.

====================================
VAERS ID 167703 Vaccination Date: 0000-00-00
Age 0.3 Date filed: 2001-03-23
Sex F Where Administered: OTH
State CA Purchased by: OTH
Life Threatening Illness? No
Died? Yes (date died: 0000-00-00)
Disability? No
Recovered? No
ER or Doctor Visit? No
Hospitalized? No
Current Illness: UNK
Diagnostic Lab Data: UNK
Previous Vaccinations:
Other Medications: UNK
Preexisting Conditions: gastroesophageal reflux

Vaccinations Manufacturer Lot Dose Route Site
1 PNC LEDERLE 0 IM

Onset Date: 0000-00-00    Number of Days:
Symptoms: SIDS
Information has been received from an investigator regarding a 3 month old
female who received her first dose of Prevnar as part of a post-marketing
safety surveillance trial. At 39 days, post vax, the infant died due to
Sudden Infant Death Syndrome. Both the medical monitor and the investigator
agree that this event was not related to the vaccine.

========================
VAERS ID 169943 Vaccination Date: 2001-04-24
Age 0.3 Date filed: 2001-05-21
Sex M Where Administered: PVT
State CA Purchased by: PUB
Life Threatening Illness? No
Died? Yes (date died: 2001-04-25)
Disability? No
Recovered? No
ER or Doctor Visit? No
Hospitalized? No
Current Illness: NONE
Diagnostic Lab Data:
Previous Vaccinations:
Other Medications: NONE
Preexisting Conditions: NONE

Vaccinations Manufacturer Lot Dose Route Site
1 PNC LEDERLE 473343 1 IM LL

Onset Date: 2001-04-25    Number of Days: 1
Symptoms: PNEUMONIA INTERSTIT STUPOR
Infant died in sleep.

http://www.thecouriermail.news.com.au/common/story_page/0,5936,11008696%255E
421,00.html

Pneumococcal jab fails to stop disease

08oct04


TWO children developed the deadly pneumococcal disease despite receiving very expensive vaccinations meant to prevent it. Another 41 children have reported minor reactions to the vaccine which will become available free to all children aged under two from January next year. And an elderly woman has died from septic shock after she and 14 others developed serious blood problems after using the oral antifungal drug Lamisil used to treat tinea.

The cases were reported in the Adverse Drug Reactions Bulletin yesterday. Drug company Novartis, which makes Lamisil, yesterday refused to comment on the death. A spokesman said the adverse blood reactions, which leave a person vulnerable to infection, were detailed on its patient information sheet and occurred in just 0.1 per cent of cases. The company was negotiating with the Therapeutic Goods Administration about whether any changes were needed to the drug's labelling, he said.

The bulletin reported that of the two children affected by the pneumococcal vaccine, one, a two-year-old girl, developed pneumococcal pneumonia two months after being given a single dose of the product. A seven-month-old baby also developed a pneumococcal infection four months after being given the vaccine. Both recovered from the infections.

Drug company Wyeth, which manufacturers the vaccine, said it appeared from the case notes that the vaccine had not been properly administered to the baby. Official guidelines recommend children be vaccinated at two, four and six months but this child appeared to have received three doses in her first three months of life. The two-year-old child had developed a less serious form of the disease, a Wyeth spokesman said.

 

http://jama.ama-assn.org/cgi/content/abstract/292/14/1702

Postlicensure Safety Surveillance for 7-Valent Pneumococcal Conjugate Vaccine


Robert P. Wise, MD, MPH; John Iskander, MD, MPH; R. Douglas Pratt, MD, MPH; Scott Campbell, RN, MPH; Robert Ball, MD, MPH, ScM; Robert P. Pless, MD, MSc; M. Miles Braun, MD, MPH


JAMA. 2004;292:1702-1710.

Context  Clinical trials evaluate a vaccine’s safety before approval, but some risks may escape detection or adequate characterization until larger population exposures occur after licensure.  Objective  To summarize reports of events occurring after vaccination with 7-valent pneumococcal conjugate vaccine (PCV), including those that may warrant further investigation to assess possible causation by PCV.

Design  Descriptive epidemiology of reports submitted to the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance database. Setting and Patients  United States during first 2 years after licensure of PCV (February 2000 through February 2002). Reports studied were for children younger than 18 years and vaccinated with PCV.

Main Outcome Measures  Numbers and proportional distributions of reports.

Results  A total of 4154 reports of events following PCV were submitted to VAERS, for a rate of 13.2 reports per 100 000 doses distributed. Multiple vaccines were given in 74.3% of reports.The most frequently reported symptoms and signs included fever, injection site reactions, fussiness, rashes, and urticaria. Serious events were described in 14.6% of reports. There were 117 deaths, 23
reports of positive rechallenges, and 34 cases of invasive pneumococcal infections possibly representing vaccine failure. Immune-mediated events occurred in 31.3% of reports. All 14 patients with anaphylactic or anaphylactoid reactions survived. Thrombocytopenia developed in 14 patients and serum sickness in 6 others. Neurologic symptoms occurred in 38% of reports. Seizures described in 393 reports included 94 febrile seizures.

Conclusions  The majority of reports to VAERS in the first 2 years after licensure of PCV described generally minor adverse events previously identified in clinical trials. The proportion of reports portraying serious events was similar to that for other vaccines. Although there are important limitations in passive surveillance data, and caution in their interpretation is necessary, symptoms experienced by a few children more than once after successive PCV doses, including allergic reactions, prolonged or abnormal crying, fussiness, dyspnea, and gastrointestinal distress, warrant continued surveillance, as do reports of rare but potentially serious events, such as seizures, anaphylactic or anaphylactoid reactions, serum sickness, and thrombocytopenia.


Author Affiliations: Division of Epidemiology, Office of Biostatistics and Epidemiology (Drs Wise, Ball, and Braun), and Division of Vaccines and Related Products Applications, Office of Vaccines Research and Review (Dr Pratt), Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Md; Immunization Safety Branch, Epidemiology and Surveillance Division, National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Ga (Drs Iskander and Pless and Mr Campbell); and Immunization Safety Unit, Immunization and Respiratory Infections Division, Centre for Infectious Disease Prevention and Control Health Canada, Ottawa, Ontario (Dr Pless).

Corresponding Author: Robert P. Wise, MD, MPH, Center for Biologics Evaluation and Research, Food and Drug Administration, HFM-225, 1401 Rockville Pike, Rockville, MD 20852-1448 (R.P.Wise@cber.fda.gov).

 

"Report Calls for More Study on Children's Vaccine"
Wall Street Journal (10/13/04) P. D17; Dooren, Jennifer Corbett    

http://www.immunizationinfo.org/pressroom/newsbriefs_detail.cfv?id=10650

A two-year post-licensing study of Wyeth's childhood pneumococcal vaccine, Prevnar, shows that most adverse side effects associated with the vaccine are minor, but a few reported cases in which children had post-vaccination seizures have led researchers to recommend additional studies on the safety of the vaccine. In a report published in the current Journal of the American Medical Association, researchers led by Dr. Robert Wise of the U.S. Food and Drug Administration assert that of the first 98 reported seizures associated with the vaccine, the majority occurred in children who had either experienced a high fever or had a history of seizures. Still, the researchers recommend more studies on the seriousness of reactions associated with Prevnar.
 

Childhood vaccine saves lives, but may lead to other infections

Since it was put on the market in February 2000, a childhood vaccine called Prevnar has reduced the rates of certain serious bacterial infections by 75 percent in American children.

But the bacterium it protects against -- pneumococcus, which causes bloodstream infections, meningitis, pneumonia, ear infections and other diseases -- is a wily organism. It comes in over 90 different strains, and Prevnar covers just the seven most common. Since the introduction of Prevnar, there has been a slow but definite rise in infections caused by strains not covered by the vaccine, and there are concerns that this trend may continue.

''I think this is a very good vaccine," said Dr. Gordon Schutze, a professor of pediatrics at the University of Arkansas for Medical Sciences. ''But I'm concerned because we're seeing a rise in disease caused by strains not covered by the vaccine." Pneumococcus -- which is also referred to as Streptococcus pneumoniae -- was first identified in 1881, and has been a scourge of humanity since long before that. Studies have shown that roughly half of all children carry pneumococcus in their noses and throats at any one time. It's mostly harmless, but when the bacterium is inhaled into the lungs, or gets into the bloodstream, it can cause serious illness.

Prior to 2000, pneumococcus was responsible for close to 200,000 hospitalizations and several thousands deaths annually in the United States in both children and adults. The rates have dropped since the introduction of Prevnar -- one recent study in Michigan showed a 50 percent reduction in hospitalizations in young children since 2002 due to the vaccine -- but pneumococcus continues to be one of the most important causes of infectious disease worldwide.

Children receive Prevnar in three doses at 2 months, 4 months and 6 months of age, followed by a booster dose at about a year old. The latest federal data shows that about two-thirds of American infants are receiving all of their doses on time.

The only previously approved vaccine against pneumococcus -- called the pneumococcal polysaccharide vaccine, which is still given to high-risk adults -- is not effective in infants and young children. While Prevnar is very effective in infants and young children, it only protects against a limited number of strains because it stimulates an immune response against pneumococci's outer shell, which varies from strain to strain.

Prevnar seems to be reducing pneumococcal disease not just in children but in adults as well because children are now less likely to pass on the bacterium to others. This so-called ''herd effect" has been a somewhat unexpected benefit of the vaccine.

According to Dr. Cynthia Whitney of the US Centers for Disease Control and Prevention, serious diseases such as meningitis and bloodstream infections due to strains of pneumococci not covered by Prevnar have risen by about 50 percent since its introduction, though the amount of disease due to these strains is still low. The rise has been more substantial for less-serious diseases such as ear infections and pneumonia. The strains not covered by Prevnar seem to be better at causing these less-serious diseases for reasons that are not entirely clear.

Recent studies have also found that strains of pneumococci not covered by Prevnar multiply in the noses and throats of children after they are given the vaccine. Although Prevnar reduces the amount of the seven strains it covers, other strains completely fill in the gap -- so the total amount of pneumococcus found in children's noses and throats is not reduced by vaccination.

This ''replacement" phenomenon is something that occurs commonly throughout nature. For example, when timber companies chop down the largest trees in a forest, it creates room for smaller trees and bushes to increase in number. Likewise, when doctors give antibiotics to treat an infection, new bacteria that are resistant to the antibiotic quickly fill in the space left by the susceptible bacteria.

And it is not just other strains of pneumococcus that are filling in the gaps. New evidence is showing that ear infections due to other species of bacteria are on the rise now that ear infections caused by pneumococcus have decreased. This may make it necessary to treat ear infections with different antibiotics than those currently used because the bacteria filling in the gaps are not always susceptible to the currently used antibiotics.

According to experts, extensive replacement has not happened with other widely used vaccines, likely because many other bacteria exist in only a small number of disease-causing varieties. The rise in nonvaccine strains of pneumococci has been especially concerning in high-risk patients -- those with HIV or sickle-cell disease, for instance -- whose immune systems are weaker.

Dr. Stephen Pelton, a pediatric infectious disease physician at Boston Medical Center, explained that the strains not covered by Prevnar are weaker than the strains that are covered. Therefore, high-risk patients -- who have weaker immune systems -- are most susceptible to these less-virulent strains that healthy people usually can fight off.

The rise in nonvaccine strains of pneumococcus is likely to continue. ''We do need to keep our eyes on the nonvaccine type disease in case it starts becoming more of a problem," Whitney said.

Experts say that the best way to curb such a rise would be to develop new vaccines to cover more strains. This will be especially important for the developing world where, according to Pelton, pneumococcal strains not included in Prevnar have always been a more important cause of disease than in the United States.

Wyeth Pharmaceuticals, which makes Prevnar, is currently working on a product that would cover 13 total strains of pneumococci -- six more than the current version. And GlaxoSmithKline has new vaccines in development as well.

According to Pelton, researchers are also developing vaccines that would cover all 90 strains of pneumococci. Several groups are working on a vaccine that would stimulate a response against a protein common to all strains. The best candidate proteins are hidden inside the outer shell, however, and the immune system has trouble recognizing these proteins when pneumococcus enters the body. ''I think we can ultimately win the race [against pneumococci]," Schutze said. ''But I think we'll probably have to do better than covering seven strains. I think we'll have to find a vaccine that covers 20 strains or so." 

© Copyright 2005 The New York Times Company
 

1: JAMA. 2004 Oct 13;292(14):1702-10. Links
Postlicensure safety surveillance for 7-valent pneumococcal conjugate vaccine.Wise RP, Iskander J, Pratt RD, Campbell S, Ball R, Pless RP,
Braun MM. Division of Epidemiology, Office of Biostatistics and Epidemiology,  Center for Biologics Evaluation and Research, Food and Drug
Administration, Rockville, Md 20852-1448, USA. R.P.Wise@cber.fda.gov

CONTEXT: Clinical trials evaluate a vaccine's safety before approval, but some risks may escape detection or adequate characterization until larger population exposures occur after licensure. OBJECTIVE: To summarize reports of events occurring after vaccination with 7-valent pneumococcal conjugate vaccine (PCV), including those that may warrant further investigation to assess possible causation by PCV. DESIGN: Descriptive epidemiology of reports submitted to the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance database. SETTING AND PATIENTS: United States during first 2 years after licensure of PCV (February 2000 through February 2002). Reports studied were for children younger than 18 years and vaccinated with PCV. MAIN OUTCOME MEASURES: Numbers and proportional distributions of reports. RESULTS: A total of 4154 reports of events following PCV were submitted to VAERS, for a rate of 13.2 reports per 100,000 doses distributed. Multiple vaccines were given in 74.3% of reports.The most frequently reported symptoms and signs included fever, injection site reactions, fussiness, rashes, and urticaria. Serious events were described in 14.6% of reports. There were 117 deaths, 23 reports of positive rechallenges, and 34 cases of invasive pneumococcal infections possibly representing vaccine failure. Immune-mediated events occurred in 31.3% of reports. All 14 patients with anaphylactic or anaphylactoid reactions survived. Thrombocytopenia developed in 14 patients and serum sickness in 6 others. Neurologic symptoms occurred in 38% of reports. Seizures described in 393 reports included 94 febrile seizures. CONCLUSIONS: The majority of reports to VAERS in the first 2 years after licensure of PCV described generally minor adverse events previously identified in clinical trials. The proportion of reports portraying serious events was similar to that for other vaccines. Although there are important limitations in passive surveillance data, and caution in their interpretation is necessary, symptoms experienced by a few children more than once after successive PCV doses, including allergic reactions, prolonged or abnormal crying,fussiness, dyspnea, and gastrointestinal distress, warrant continued surveillance, as do reports of rare but potentially serious events, such as seizures, anaphylactic or anaphylactoid reactions, serum sickness, and thrombocytopenia.
PMID: 15479935 [PubMed - indexed for MEDLINE]


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