Vaccine Update Selection from: Highlights of ACPM 2007

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Vaccine Update  CME/CE
Roy Hoffman, MD, MPH   
Disclosures


Primary prevention, exemplified through the process of immunization, is an action that prevents a disease or condition from developing in an otherwise susceptible host. Such interventions are favored tools in the fields of preventive medicine, public health, and primary healthcare because of the high potential impact in reducing both individual and population-wide morbidity and mortality.

Thanks to advancements in the field of vaccine research, the number of vaccine-preventable diseases continues to increase steadily -- along with the concomitant body of knowledge that the prevention-minded provider must learn. It was very fitting then that the American College of Preventive Medicine (ACPM) 2007 Annual Conference provided a venue for much-needed vaccine updates.

Since 2005, the following developments have occurred in the field of vaccinology:

Two infectious agents (human papillomavirus [HPV] and herpes zoster) were added to the list of vaccine-preventable diseases;


One infectious agent (rotavirus) returned, after a more than 5-year hiatus, to the list of vaccine-preventable diseases;


Two new formulations of vaccines for infectious agents (meningococcal disease and pertussis) now allow provision of broader coverage to more age groups;


A new vaccine combination (measles-mumps-rubella with varicella vaccine -- MMRV [ProQuad], Merck) was released;


A form of cancer (cervical) can now be largely prevented by a vaccine against 4 strains of HPV; and


New emphasis has been placed on vaccination of males and females aged 11-12 years and older against meningococcal disease and pertussis, and for females against HPV, in turn potentially strengthening the role of the preadolescent healthcare visit.
Vaccine updates are important for healthcare providers to remain current on the latest recommendations and contraindications for the safe and effective use of available immunizations. The following summary focuses on recently licensed vaccines against 4 diseases: HPV, herpes zoster, meningococcal disease, and pertussis. The primary target of 3 of these vaccines is adolescents, a relatively new target group for immunization.

HPV Vaccines
At the conference, updates on HPV vaccination were provided during 2 separate sessions by Eileen Dunne, MD, MPH,[1] Division of STD Prevention, Centers for Disease Control and Prevention (CDC), and Eileen Yamada, MD, MPH,[2] Immunization Branch, California Department of Health Services.

Background of Disease. HPV is estimated to be the most common sexually transmitted disease in the United States. Approximately 20 million people are currently infected,[3] and overall HPV prevalence is estimated to be 26.8% among US females aged 14-59 years.[4]

HPV exists in many different strains; there are more than 100 types in all. Over half of the HPV types cause cutaneous infections (common warts on the hands and feet), while the remaining 40-plus mucosal types cause genital infections. Mucosal HPV types are further classified as either "high-risk" for being associated with cervical cancers (eg, types 16, 18, 53, and others) or "low-risk" (eg, types 6, 11, 62, and others).[5]

Background of Vaccine. One way to reduce the disease burden of HPV, and thus prevent a major source of cervical cancer, is to vaccinate females before they have ever engaged in any sexual activity.

Two types of HPV vaccines have recently been licensed. Gardasil (Merck) received Food and Drug Administration (FDA) licensure in June 2006. It is a quadrivalent vaccine made from HPV types 6, 11, 16, and 18. Cervarix (GlaxoSmithKline) is currently pending FDA licensure. It is a bivalent vaccine made from HPV types 16 and 18. Both vaccines are made from the HPV viral capsid proteins using recombinant yeast technology. Both are given in a series of 3 doses, spread over a 6-month period.

These vaccines are the first ever to be marketed as being able to (partially) prevent a particular type of cancer. Although types 16 and 18 are not necessarily the most prevalent HPV types of the high-risk category, they do account for approximately 70% of cervical cancers worldwide.[6]

Current Advisory Committee on Immunization Practices (ACIP) Recommendations. General: The vaccine is indicated only for females aged 9-26 years. Adolescents: In March 2007, ACIP officially recommended routine HPV vaccination for girls aged 11-12 years, with the option to vaccinate those as young as age 9. In addition, females aged 13-26 are eligible for catch-up immunizations -- ideally provided before the onset of sexual activity because vaccinees will not get the full benefit if already infected with a vaccine-included HPV type.

Contraindications. The only contraindication to the HPV vaccines is a history of immediate hypersensitivity to yeast or to any of the vaccine components.

Special Considerations. Women who are lactating or immunocompromised are eligible to receive the vaccine. In addition, vaccine is still recommended for females aged 9-26 years, even if they already have a history of genital warts, a positive HPV test, or an equivocal or abnormal Pap test. Vaccination is not recommended for use in women who are pregnant.

*An important note of caution for women who do receive the HPV vaccine: There should be no changes to the current recommendations for the screening of cervical cancers.

The Vaccine for Children (VFC) program covers the cost of HPV vaccine for eligible children. In order to be eligible for VFC, children must be 18 years or younger and be eligible for Medicaid, uninsured, American Indian/Alaska Native, or underinsured (ie, health insurance does not cover immunizations). More information about VFC is available online.[7]

Future Developments. Both Gardasil and Cervarix are currently being tested for safety and efficacy in females older than age 26 years. Additionally, Gardasil is being tested for safety and efficacy in males.[1]

Herpes Zoster Vaccine
Rafael Harpaz, MD, MPH,[8] National Center for Immunization and Respiratory Diseases ,CDC, provided an update on Zostavax (Merck), the vaccine which targets the herpes zoster manifestation of the varicella-zoster virus (VZV).

Background of Disease. Herpes zoster (also known as shingles) is caused by a reactivation of VZV, and can occur years to decades after initial infection with chickenpox virus. Herpes zoster appears as a vesicular crop of rashes/blisters in a dermatomal pattern, typically accompanied by pain, which often may be intense.

Approximately 1 million cases of herpes zoster are diagnosed annually in the United States, translating to 3-4 cases per 1000 persons each year. Americans have about a 20% to 30% risk of developing herpes zoster at some point during their lives.[8,9]

As burdensome as herpes zoster itself may be, up to 25% of afflicted patients will go on to develop the severe complication of postherpetic neuralgia (PHN).[10] PHN is a chronic neuropathic pain syndrome that has an impact on quality of life comparable to that of congestive heart failure, diabetes, and depression.[8] Increasing age, particularly age greater than 50-60 years, is the predominant risk factor in the development and severity of (acute) herpes zoster, as well as (chronic) PHN.[9]

In addition to the disease burden borne by the individual, herpes zoster exacts a burden on public health resources and on society, causing approximately 12,000-19,000 hospitalizations with an average length of 5-7 days annually,[8] as well as indirect costs from loss of work for patients and/or caregivers.

Background of Vaccine. Zostavax, the only herpes zoster vaccine on the market, received FDA licensure in May 2006. The vaccine is a live, attenuated version of VZV -- identical to the strain found in the chickenpox vaccine Varivax but at a 14-fold higher concentration.

In a clinical trial involving thousands of participants older than age 60, Zostavax prevented herpes zoster in approximately 50% and PHN in approximately two thirds of the study participants.[9]

Current ACIP Provisional Recommendation. General: The vaccine is indicated only for persons aged 60 years or older for the prevention of herpes zoster and PHN. A single dose of vaccine is all that is needed for full immunization, and it should be given regardless of history of chickenpox and/or previous episode of herpes zoster. Adolescents: The vaccine is not recommended for any persons younger than age 60.

These ACIP recommendations are provisional, but will become official once published in CDC's MMWR. This is expected to occur sometime around June 2007.

Contraindications. Immunodeficiency, immunosuppressive therapy, active untreated tuberculosis, and pregnancy are all contraindications to receipt of Zostavax, as is a history of anaphylaxis/anaphylactoid reaction to neomycin, gelatin, or any other component of the vaccine.

Special Considerations. The vaccine is not indicated for the treatment of herpes zoster or PHN. The vaccine must be stored at freezer temperature (+5° F or colder) and used within 30 minutes of being reconstituted.

It is anticipated that Zostavax will not be covered under the Medicare Part B program (which covers influenza and pneumococcal polysaccharide vaccine). Instead, the vaccine will be reimbursed through the Medicare Part D program.[11]

Meningococcal Disease Vaccines
A review of the currently available formulations for immunization against meningococcal disease and uptake patterns of use (Menactra, sanofi pasteur) among US adolescents was provided by Daniel Fishbein, MD,[12] a member of the Vaccine Safety Datalink Team, CDC.

Background of Disease. Meningococcal disease is caused by the bacterium Neisseria meningitidis, a gram-negative diplococcus whose only natural reservoir is the human nasopharyngeal mucosa, and which colonizes approximately 10% of the population.[13]

Despite the high rates of colonization of N meningitidis, not all strains of the bacterium are pathogenic, and a series of conditions must be fulfilled in order for serious infection in the host to occur. Therefore, invasive meningococcal disease is a relatively uncommon event in the United States, with approximately 2500 cases occurring per year. However, the morbidity and mortality of the disease yield a very high price: an approximate 10% case fatality rate and serious neurologic and other permanent sequelae in 10% to 20% of survivors.[14]

Although there are 13 known serogroups of N meningitidis, only 5 serogroups are responsible for more than 90% of invasive disease worldwide (types A, B, C, W-135, and Y).[15] In the United States, 3 serogroups (B, C, and Y) each account for approximately 33% of total cases.[16] Invasive disease occurs most commonly in the (seronegative) young. Another high-risk factor is new entry into crowded living conditions, such as a military barracks or college dormitories.

Background of the Vaccines. There are 2 meningococcal vaccines currently on the market. Menomune (Sanofi Pasteur) has been licensed for use by the FDA since 1981. It is a quadrivalent polysaccharide vaccine, which combines the purified bacterial capsular polysaccharide of serogroups A, C, W-135, and Y. Menactra (Sanofi Pasteur) received FDA licensure in January 2005.[17] It is a quadrivalent conjugate vaccine, also covering serogroups A, C, W-135, and Y. However, this vaccine is made by conjugating the bacterial capsular polysaccharides to the protein carrier of diphtheria toxoid, creating a T-cell-dependent immune response. This confers the advantage of longer-lasting immunity and a good response to booster doses in the host. Another advantage of the conjugate vaccine is that it may reduce asymptomatic carriage of N meningitidis, thus providing secondary protection to the surrounding unvaccinated population.[14]

Current ACIP Recommendations. General: Menactra is indicated only for persons aged 11-55 years. Adolescent: A single dose of Menactra is recommended for routine vaccination of 11- to 12-year-olds at the preadolescent healthcare visit.[17] In addition, for those adolescents not yet vaccinated, Menactra is recommended "before high school entry," or at approximately age 15. The rationale for the temporary plan of a "catch-up" shot before high school entry is because of the recent licensure of the vaccine and the attempt to not have demand surpass supply. By 2008, the goal is routine vaccination of all adolescents at age 11-12 years.[17]

Other Groups: A single dose of Menactra is recommended for the following groups considered at high risk for invasive meningococcal disease:

college freshmen living in dormitories;


certain travelers;


certain microbiologists;


military recruits;


certain populations experiencing outbreaks of meningococcal disease; and


persons with increased susceptibility to meningococcal disease (ie, having complement deficiency and/or functional asplenia).
For those persons outside the approved age ranges but at increased risk for invasive meningococcal disease, there still is Menomune. Menomune is recommended as a single dose for those aged 19 months to 10 years and for those older than 55 years of age; it is recommended as a series of 2 doses for those aged 3-18 months. More information on the official ACIP recommendations on meningococcal disease prevention and control is available online.[17]

Contraindications. Any history of severe allergic reaction to diphtheria toxoid; dry, natural latex rubber; or any other component of the vaccine is a contraindication to receipt of Menactra.

Special Considerations. When indicated, immunosuppressed persons are still eligible to receive the vaccine. There are no current data on the safety of Menactra's use in pregnant women.

There were 8 confirmed cases of Guillain-Barré syndrome associated with Menactra immunization reported to the CDC from March 2005 to February 2006. CDC views these findings with caution, but continues to recommend routine vaccination with Menactra for adolescents and other populations at increased risk.

Future Development. It is hoped that a meningococcal vaccine will eventually be developed to cover serogroup B, which accounts for approximately one third of invasive meningococcal disease in the United States.[12]

Pertussis Vaccine
The new acellular pertussis vaccine indicated for adolescents and the general adult population was covered by Elise Beltrami, MD, MPH,[18] Division of Healthcare Quality Promotion, CDC.

Background of Disease. Pertussis (whooping cough) is caused by the bacterium Bordetella pertussis, a gram-negative coccobacillus. Pertussis causes a protracted respiratory illness characterized by a catarrhal stage (generally lasting 1-2 weeks), a paroxysmal stage (4-6 weeks), and finally a convalescent stage (2-4 weeks). It is during the paroxysmal stage that coughing attacks occur, usually followed by the characteristic whooping sound.

Although pertussis in older adolescents and adults is often manifested as a mild-to-moderate persistent cough illness, disease in younger children can be much more severe. Rates of complications (such as pneumonia) and hospitalizations increase rapidly with decreasing age, particularly in infants younger than 1 year. In young infants, coughing paroxysms are often followed by emesis and even cyanosis, and usually require admission to an intensive care unit. Infants younger than age 1 year accounted for approximately 19% of cases recorded in the United States from 2000 to 2004 but for 92% of the pertussis-related deaths.[19]

Background of Vaccine. Pertussis immunity is thought to wane by 5-10 years after the completion of the pediatric DTaP (diphtheria, tetanus, and acellular pertussis) series. This fact, along with the recent rise in infantile pertussis, contributed to rationale for the reformulation of pertussis vaccine to make an immunization suitable for adolescents and adults.[20]

Two vaccines for Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) are currently licensed and approved for use in the United States. BOOSTRIX (GlaxoSmithKline) received FDA licensure in May 2005 and is indicated only for persons aged 10-18 years. ADACEL (Aventis Pasteur) received FDA licensure in June 2005, and is indicated only for persons aged 11-64 years.

Both vaccines contain the same tetanus and diphtheria toxoids and pertussis antigens as their manufacturers' pediatric DTaP counterparts. However, the reformulated vaccines reduce the quantity of tetanus toxoid by 50%, the quantity of diphtheria toxoid by approximately 90%, and the amount of the individual pertussis antigens from less than 1% to 75%.[19]

Current ACIP Recommendations. General: Tdap should be used in place of the recommended Td boosters for persons aged 11-64 years. Adolescent: A single dose of Tdap booster (either BOOSTRIX or ADACEL) is recommended for routine vaccination of all adolescents aged 11-18 years, with the preferred time for vaccination being given during the preadolescent healthcare visit to the 11- or 12-year-old. More information on the ACIP recommendations for preventing pertussis among adolescents is available online.[20] Adults: A single dose of ADACEL is recommended in adults aged 19-64 years in place of a single dose of Td booster if they received their last Td dose 10 or more years previously. Healthcare workers: Healthcare personnel with direct patient contact should receive a single dose of ADACEL as soon as feasible, as long as at least 2 years have elapsed since their last Td booster dose. Priority should be given to vaccination of those with direct contact with infants younger than 1 year.

Contraindications. Tdap is contraindicated in persons with any history of anaphylaxis/anaphylactoid reaction to any component of the vaccine. In addition, any person with a history of encephalopathy not attributable to any other cause within 7 days of administration of a vaccine with pertussis components should not receive Tdap.

A full list of precautions to and special considerations for Tdap use can be found online.[19,20]

Conclusion
Immunizations are an important part of the healthcare provider's arsenal, and they are more effective when the provider is up-to-date on the most current vaccine information. A number of new vaccines have entered the market within the past 2 years and luckily more are in store for the future. More information about the latest status of licensure of new vaccines, as well as the ACIP and American Academy of Pediatrics immunization recommendations, are also available on the Web.[21]

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ACPM：Annual Meeting of the American College of Preventive Medicine