By: Dr. F. Edward Yazbak
One of my favorite "Candid Camera" segments was on a new employee in a pie company whose job it was to pick up each pie arriving on a conveyor belt, slip it into a box, turn around and put the box on a second conveyor belt. He did fine for a short while; then the show's producers cranked up the first conveyor belt and the pies arrived so fast that they were falling on the floor or flying across the room. I feel the same way as that worker. I am simply unable to keep up with all the vaccines that are being released at record speed. No one really can.
I can only presume that this must be exactly what the Centers for Disease Control and Prevention (CDC) - like the "Candid Camera" producer - wanted.
The following is a sampling of what is now on the conveyor belt and "Coming Soon to a Doctor near You." (1)
ADACEL (Sanofi Pasteur) is an adult form of tetanus, diphtheria and acellular pertussis (Tdap) vaccine. Its FDA application was submitted August 2004 and the product was licensed in June 2005 for use in individuals 11 to 64 years of age. The Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) have recommended its use during adolescence (10-18 years), instead of tetanus and diphtheria (Td) boosters.
In all likelihood, the manufacturer will return to the ACIP with a request to extend the recommendation to age 64.
BOOSTRIX® (GSK) is another adult form of tetanus, diphtheria and acellular pertussis vaccine. The original FDA application was submitted in July 2004. On May 5, 2005, the vaccine was licensed for use in adolescents 10 to 18 years of age. On June 30, 2005, the ACIP voted to recommend its routine use in that age group in place of tetanus and diphtheria (Td) boosters.
Until now, the administration of any form of whooping cough vaccine was contraindicated in children older than seven, and in adults, because of the higher incidence of convulsions. It is expected that the new Tdap vaccines will "take off" in 2006.
FluMist® (Influenza Virus Vaccine Live, Intranasal) was the first live influenza virus on the U.S. market. The required freezer storage and transportation have somewhat limited its use. Liquid CAIV-T (Cold Adapted Influenza Vaccine) was developed as a second-generation, refrigerator-stable product. Wyeth collected data to demonstrate the safety and efficacy of CAIV-T in patients 6 months to 98 years of age.
MedImmune re-acquired the commercial rights to CAIV-T from Wyeth in 2004 and will be submitting its Biologics License Application (BLA) with an age indication of 6 months to 49 years to the FDA in early 2006. With all the supply problems recently encountered with the injectable influenza vaccines and because CAIV-T is thimerosal-free, FDA approval and subsequent CDC recommendations are expected.
Cervarix (GSK) is a human papilloma virus (HPV) vaccine. FDA application is pending.
GARDASIL® (Merck) is also a HPV vaccine. A BLA was submitted this month to the FDA with an age indication of 11 to 26 years. Three doses of vaccine are recommended.
The public relations program has been in full swing for months. Human Papilloma Virus vaccine is "A vaccine every woman should take" because HPV is "the leading cause of cervical cancer" and cervical cancer is "the second most common cancer among women, with more than 270,000 deaths reported each year worldwide." (2)
According to the CDC, "Genital HPV infection is a sexually transmitted disease (STD) that is caused by human papillomavirus (HPV). Human papillomavirus is the name of a group of viruses that includes more than 100 different strains or types. More than 30 of these viruses are sexually transmitted, and they can infect the genital area of men and women, including the skin of the penis, vulva (area outside the vagina) or anus, and the linings of the vagina, cervix or rectum. Most people who become infected with HPV will not have any symptoms and will clear the infection on their own." (3)
Gardasil® is designed to protect women against four strains of HPV and Cervarix protects against "the two strains responsible for cervical cancer, a disease that kills a quarter of a million women each year." (4)
According to the CDC, the following is important information about how to reduce the risk of sexually transmitted genital HPV infection: (3)
- The surest way to eliminate risk for genital HPV infection is to refrain from any genital contact with another individual.
- For those who choose to be sexually active, a long-term, mutually monogamous relationship with an uninfected partner is the strategy most likely to prevent future genital HPV infections. However, it is difficult to determine whether a partner who has been sexually active in the past is currently infected.
- For those choosing to be sexually active and who are not in long-term mutually monogamous relationships, reducing the number of sexual partners and choosing a partner less likely to be infected may reduce the risk of genital HPV infection. Partners less likely to be infected include those who have had no or few prior sex partners.
- HPV infection can occur in both male and female genital areas that are covered or protected by a latex condom, as well as in areas that are not covered. While the effect of condoms in preventing HPV infection is unknown, condom use has been associated with a lower rate of cervical cancer, an HPV-associated disease.
Havrix ® by GSK is an inactivated hepatitis A vaccine. A supplement to the original BLA was submitted to the FDA with a new age indication of 12 months or over. It was licensed in October 2005 and immediately recommended by the CDC.
VAQTA® by Merck is a similar hepatitis A vaccine. A supplement to the original Biologics License Application (BLA) was submitted to the FDA and the vaccine was approved in August 2005 for children one year and older. The CDC recommended it in October 2005.
In 1996, the ACIP recommended vaccination of children aged >24 months in populations with the highest incidence of hepatitis A such as American Indians, Alaska natives, Asian/Pacific Islanders and certain Hispanic and religious communities. In 1999, these guidelines were expanded to recommend routine vaccination for children residing in Alaska, Arizona, California, Idaho, Nevada, New Mexico, Oklahoma, Oregon, South Dakota, Utah and Washington. The average annual hepatitis A incidence in these states between 1987 and 1997 was at least 20 per 100,000 population - or twice the national average. The ACIP considered routine vaccination for children in Arkansas, Colorado, Missouri, Montana, Texas, and Wyoming, where average annual incidence was 10-20 per 100,000 population. (5)
Hepatitis A infection is mild or asymptomatic in young children and in spite of higher concentrations in 16 states, the "national average" of hepatitis A incidence is only 1:10,000 with 70 percent of subjects older than 15. Keeping that in mind, it would seem that the vaccination of toddlers and children outside of high-risk groups will not be "needed." Unfortunately, that is not guaranteed. In the early "˜90s, because a small number of experts decided that universal pediatric hepatitis B vaccination was a good idea, we started vaccinating infants in the nursery who needed the vaccine even less.
Menactra® or MCV4 is a meningococcal vaccine designed to offer protection against four of the most common meningococcus serogroups (A, C, Y, W-135). It was first licensed on Jan. 14, 2005 for individuals 11 to 55 years of age, but mostly intended for young adults in crowded quarters: Army recruits and college students in dormitories.
In early October 2005, the FDA and CDC notified consumers and health care providers of five reports of Guillain Barre Syndrome following administration of Menactra. "It is not known yet whether these cases were caused by the vaccine or are coincidental. FDA and CDC are sharing this information with the public now and actively investigating the situation because of its potentially serious nature. Guillain Barre Syndrome (GBS) is a serious neurological disorder that can occur, often in healthy individuals, either spontaneously or after certain infections. GBS typically causes increasing weakness in the legs and arms that can be severe and require hospitalization. Because of the potentially serious nature of this matter, FDA and CDC are asking any persons with knowledge of any possible cases of GBS occurring after Menactra to report them to the Vaccine Adverse Event Reporting System (VAERS) to help the agencies further evaluate the matter." (6)
Sanofi Pasteur, the vaccine manufacturer has submitted a supplement to the original BLA to include a pediatric indication (age 2 -10 years). Although logically the FDA would be expected to wait until the Guillain Barre reports are fully investigated, it is likely that the new indication will be approved and subsequently recommended by the ACIP and the CDC. It is also a safe bet that before long, Sanofi Pasteur will be requesting approval of another indication at 2, 4 and 6 months of age, citing the fact that a monovalent meningococcal vaccine is recommended for infants in the United Kingdom.
PENTACEL is a HIB, DTaP and IPV pediatric combination vaccine. A BLA was submitted to the FDA on July 25, 2005 to allow administration of four doses of the vaccine at 2, 4, 6, and 15-18 months. CDC recommendation is expected after FDA approval.
PENTACEL (Sanofi Pasteur) should not be confused with Pediarix (GSK), the first 5-in-1 pediatric vaccine that has been licensed and used for sometime in the United States, and which contains DTaP, IPV and recombinant hepatitis B vaccines
In September 2005, the European Medicines Agency suspended the use of the Hexavax vaccine because of inadequate immunogenicity of its hepatitis B component. Hexavax was marketed in Europe by Aventis Pasteur and Merck and contained diphtheria, tetanus, acellular pertussis, IPV, HIB and recombinant hepatitis B vaccine.
ProQuad® or MMR-Varicella vaccine was licensed in the fall of 2005 and promptly recommended by the CDC. It was discussed in a previous column. (7
ROTATEQ® (Merck) is a new rotavirus vaccine. An application is pending to allow the administration of a dose of the vaccine at 2, 4 and 6 months of age. The FDA approval is imminent and the CDC recommendation is certain. A detailed review will follow.
Merck, the manufacturer of the chicken pox vaccine Varivax® submitted a supplemental BLA for a second dose of the vaccine to be administered to children under age 12, after a minimum three-month interval from the first dose. The FDA issued the license in April 2005. The second dose was not recommended by the CDC at a June 2005 meeting.
It is obviously expected that Merck will request reconsideration and that the CDC will probably approve the second dose in 2006.
ZOSTAVAX by Merck is the new shingles vaccine for older adults, discussed earlier on Red Flags. (8). A BLA was submitted to the FDA in April 2005 and there is no reason to believe that it will not be approved. A prompt CDC recommendation is guaranteed.
RotaShield® and ROTATEQ®
The saga of the rotavirus vaccine RotaShield®was a sad chapter of our vaccination history. On Aug. 31, 1998, the FDA licensed the RotaShield vaccine, the first U.S. rotavirus vaccine. On July 16, 1999, on the recommendation of the FDA, Wyeth-Lederle suspended the distribution and administration of the vaccine because of reports of intussusception shortly after vaccination. The vaccine was ultimately withdrawn from the market in the fall of 1999.
Intussusception is a form of intestinal obstruction resulting from the bowel folding in on itself. Some cases occur with viral infections and often no cause is identified. The ileo-colic junction is the most common site of intussusception.
According to the CDC, five cases of intussusception occurred among 10,054 (0.05 percent) vaccines during the pre-licensure trials of RotaShield, all among infants receiving a second or a third dose of vaccine. Because one case of intussusception occurred among 4,633 (0.02 percent) infants who received a placebo vaccine, the difference was not considered statistically significant. The manufacturer listed intussusception in the package insert of the vaccine as a possible adverse reaction. (9)
By Dec. 31, 1999, a total of 112 cases of intussusception following RotaShield vaccination had been reported to VAERS. Ninety-five cases were confirmed by review of medical records, and three were confirmed by primary care providers. No cases of vaccine-associated intussusception occurred in infants vaccinated after July 16, 1999. (10)
The FDA evaluation of ROTATEQ® (RotaTeQ)is almost complete and as mentioned earlier, its licensure is expected any time.
Trial data showed a slight increase in the occurrence of seizures among vaccinated children. (11) According to the Vaccines and Related Biological Products Advisory Committee (Dec. 14, 2005), there was no demonstrated increased risk of intussusception in the Phase III clinical trials. The committee documented that there were six cases of intussusception in the RotaTeq group in the pre-specified 42-day window, compared to five cases in the placebo group. There was also one death due to intussusception and septicemia. In the extended 60-day window, the agency found eight cases of intussusception compared to six for placebo.
Some discrepancies concerning efficacy results, gastroenteritis and follow-up are still being reviewed. (12) The situation is distantly reminiscent of what happened before the release of RotaShield.
A dental caries vaccine has been in the making for years to protect those who would rather not brush or floss. It will not cost as much as the new "bird flu" vaccine now being developed and may even prove to be more useful.
Also being developed, according to the Immunization Action Coalition (Dec. 14, 2005), are vaccines against HIV/AIDS, malaria, cytomegalovirus, plague, Alzheimer's disease, drug abuse, E. coli, staphylococcus aureus, chlamydia, Lyme disease, yellow fever and the common cold. (13)
One look at the 2005 pediatric/adolescent vaccination schedule is enough to convince anyone that too many antigens - 22 - are already administered in the United States by the age of 18 months. (14) Parents have been reassured that pediatric vaccines are now safe because they do not contain the mercury preservative Thimerosal. That is not necessarily true, although vaccines are certainly safer without mercury. Parents should become very well informed about each and every vaccine that is administered to their children - particularly combination vaccines. They should also report complications to their doctors and to VAERS because so often, physicians fail to do so.
All adults should get fully informed about vaccines and vaccination practices. It is inevitable that several new vaccines will be targeting their age group and added to the present substantial schedule. (15)
Because the vaccine race has become the main health focus in the United States, it is certain that the conveyor belt will speed up even more.
- ProQuad: The new kid on the block
- Trust Me: I Have the Statistics to Prove It