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The Growing Paradigm of Preventing Disease: Vaccines To Prevent Herpes Zoster and Pertussis in Adults

Posted on: Saturday, 8 October 2005, 03:01 CDT

By Poland, Gregory A

Two recent studies have shown the safety and efficacy of vaccines designed to prevent infectious diseases occurring among adults- herpes zoster (shingles) and pertussis (1, 2). The availability of these vaccines expands the growing paradigm of active disease prevention in adults. An acellular pertussis vaccine is now approved by the U.S. Food and Drug Administration (FDA) and available for use in adults (Adacel, Sanofi Pasteur, Swiftwater, Pennsylvania); the zoster vaccine (Zostavax, Merck Research Laboratories, New York, New York) is pending licensure application.

A VACCINE TO PREVENT HERPES ZOSTER IN ADULTS

It is estimated that approximately 1 million cases of herpes zoster occur in the United States each year. As internists, it is important to note that we will often be confronted with this disease because of the ever-increasing age of the population and longer survival of people with disease- or drug-induced immunosuppression.

The risk for shingles increases with age, paralleling the concomitant waning of cell-mediated immunity to the zoster virus (3, 4); incidence rates are 2.5 to 5 per 1000 at 60 years of age and increase to 3 to 6.8 per 1000 by age 70 years (5). In the Shingles Prevention Study, the annual incidence was 11 per 1000 in the placebo group (1). The lifetime risk for herpes zoster is approximately 15% to 30%. Complications of zoster include herpes opthalmicus, myocarditis, paresis, myelopathy, vasculopathy, pneumonia, postherpetic neuralgia, and others.

Studies have suggested that restimulation with a live, attenuated varicella vaccine in adults might stimulate zoster-specific cell- mediated immunity (6-8). The Shingles Prevention Study, a large, multicenter, randomized, double-blind, placebo-controlled clinical trial done by Oxman and colleagues, investigated a zoster vaccine (1). The study enrolled 38 546 adults 60 years of age or older who were randomly assigned to receive one 0.5-mL subcutaneous injection of placebo or vaccine from 1 of 12 lots. The vaccine was an investigational live attenuated virus vaccine (zoster vaccine live [Oka/Merck]). Individual vaccine lots had an estimated potency ranging from 18 700 to 60 000 plaque-forming units (pfu) per dose (median potency, 24 600 pfu per dose). Study participants were followed on a monthly basis for a mean of 3.13 years; more than 95% of participants completed follow-up. Persons developing rashes were carefully evaluated by polymerase chain reaction assay to determine whether the varicella zoster vaccine caused the rash and whether the virus serotype was represented in the live vaccine.

Herpes zoster was confirmed in 957 cases. The vaccine was associated with a 51.3% reduction in the incidence of zoster (P<0.001), a 66.5% reduction in the incidence of postherpetic neuralgia, and a 61.1% reduction in the burden of illness caused by zoster in vaccine recipients compared with placebo recipients. Of note, the vaccine was safe, had few adverse events, and was associated with only mild local reactions at the injection site. Reassuringly, no vaccine-type virus DNA was detected in any of the rashes.

Clinicians should prepare themselves for patients who want a "shingles vaccine." The vaccine studied in this trial (trade name, Zostavax) is not yet licensed by the FDA and is thus not available. In its absence, patients may ask clinicians to provide the currently licensed vaccine (Varivax, Merck); however, the potency of Varivax is considerably lower than that of Zostavax. Varivax has an average potency of only 1350 pfu per dose compared with a range of 18 700 to 60 000 pfu per dose of Zostavax. The higher dose seems to be necessary to overcome the immunosenescence associated with aging. For this reason, the currently licensed Varivax is not recommended for zoster prevention in adults. It is expected that Zostavax will go forward to the FDA for licensing review. If it is licensed, internists will need to understand the indications and contraindications of this vaccine and offer it to their older patients (most likely those age 60 years and older) to reduce the incidence and complications of zoster and postherpetic neuralgia, although official recommendations cannot be made until the product is licensed.

A VACCINE TO PREVENT PERTUSSIS IN ADULTS

This past winter, my fully immunized 13-year-old son developed documented pertussis and, of course, the family had to submit to both sleepless nights listening to him cough and to antibiotic prophylaxis. Had I not been a physician, the case would either have gone undiagnosed or been detected late in the disease course, exposing others and continuing the outbreak.

Pertussis is a seriously underrecognized disease. Complications from pertussis infection occur in up to 28% of adults (9) and include pneumonia, urinary incontinence, cough (mean duration in adults is 12 weeks!), sinusitis, vomiting, fractured ribs, fatigue, encephalitis, and disturbed sleep (9-11). Transmission of this disease from an infected adolescent or adult to an unimmunized or underimmunized infant leads to serious morbidity and mortality (12). Unfortunately, the diagnosis of pertussis is rarely if ever considered by internists, despite clear data about its incidence and significance among adults and knowledge that adults are the reservoir of infection for susceptible children. In prospective studies of adults presenting with 1 or more weeks of cough, 10% to 25% met the serologic criteria for pertussis infection (13-16). In the United States, the incidence of pertussis has continued to increase since 1980 (17).

Internists have had nothing in their armamentarium to prevent pertussis. The only pertussis vaccines licensed in the United States are for children up to the age of 7 years because of the significant local and systemic reactions when used in adults (18, 19). Immunity starts to wane within a decade of receipt of the last pertussis- containing vaccination, causing widespread susceptibility among adolescents and adults.

Several small studies have demonstrated the immunogenicity and safety of acellular pertussis vaccines in adults (20-23). Pichichero and colleagues (2) report the results of a randomized, modified double-blind, comparative clinical trial. This study, conducted across 39 centers in the United States, answered several previously raised questions on acellular pertussis vaccines (24, 25). Overall, 4480 healthy persons 11 to 64 years of age were enrolled and received a single 0.5-mL intramuscular dose of either a licensed tetanus-diphtheria vaccine or a tetanus-diphtheria vaccine combined with a 5-component acellular pertussis vaccine (Tdap) (Adacel).

The authors showed that Tdap was both safe and immunogenic in adolescents and adults 11 to 64 years of age. In terms of efficacy, a single dose of Tdap vaccine induced antibody liters to all 5 pertussis components that were 2.1 to 5.4 times those seen in infants who had received 3 doses of a similar diphtheria-tetanus- pertussis (DTaP) vaccine (Boostrix, GlaxoSmithKline, Philadelphia, Pennsylvania) in a previous study that demonstrated significant efficacy against culture-proven pertussis (26). In light of the reactions to the pediatric formulation when used in adults, it is important to note that the adverse local and systemic adverse reactions were similar between the 2 study groups.

Why should internists adopt pertussis immunization of adults? First, the disease is increasingly being diagnosed in adults, and immunization would reduce the burden of disease in the population. Second, since adults form the reservoir of infection for unimmunized and underimmunized infants and children, vaccinating adults should reduce disease transmission to infants and children (27). Of note is that Tdap vaccine (Adacel) is now licensed by the FDA for 1-dose use in adolescents and adults age 11 to 64 years. Physicians who administer pertussis vaccines should take care to avoid using the pediatric formulation, DTaP (Boostrix), in adults. This vaccine is licensed for use in adolescents up to age 18 years but not in adults.

CONCLUSIONS

For a variety of reasons (for example, fear, ignorance, laissez- faire attitudes toward perceived "nuisance" diseases, the antivaccine movement, vaccine cost, and poor medical systems and procedures for recognizing underimmunization), all currently licensed and routinely recommended vaccines-without exception-are underutilized in adults. This partially stems from a "collusion of ignorance" between patients and providers. Providers (for example, physicians, nurses, and pharmacists) have substantial misperceptions and fears about vaccine efficacy and safety and an inadequate knowledge base about vaccine-preventable diseases. Few practices have highly developed systems for identifying and immunizing those who need vaccines. This results in low adult immunization rates, leading to tens of thousands of preventable deaths in American adults each year.

What should we do? First, it is our responsibility to educate ourselves, our colleagues, and our patients about vaccines. Next, we must develop systems and procedures to identify those who need vaccines and methods to deliver them on a timely basis. Finally, we need to audit our practices to have objective data and metrics to determine whether we are \fulfilling our duty of protecting the health of our patients and communities. The paradigm is changing. Patients are demanding preventive care. Payers are demanding data and score-carding to measure immunization rates. In this regard, the American College of Physicians has tools and information available to assist physicians who desire to improve their immunization practices (28). Although the 2 new vaccines that have been proven to be effective against pertussis and varicella zoster increase the complexity of our task in maintaining good vaccination rates, we simply must rise to the challenge.

References

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2. Pichichero ME, Rennels MB, Edwards KM, Blatter MM, Marshall GS, Bologa M, et al. Combined tetanus, diphtheria, and 5-component pertussis vaccine for use in adolescents and adults. JAMA. 2005;293:3003-11. [PMID: 15933223]

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23. Halperin SA, Smith B, Russell M, Hasselback P, Guasparini R, Skowronski D, et al. An adult formulation of a five-componenr acellular pertussis vaccine combined with diphtheria and tetanus toxoids is safe and immunogenic in adolescents and adults. Vaccine. 2000;18:1312-9. [PMID: 10618527]

24. Poland GA, Acellular pertussis vaccines: new vaccines for an old disease. Lancet. 1996;347:209-10. [PMID: 8551875]

25. Poland GA. Still more questions on pertussis vaccines. Lancet. 1997;350: 1564-5. [PMID: 9393330]

26. Gustafsson L, Hallander HO, OHn P, Reizenstein E, Storsaeter J. A controlled trial of a two-component acellular, a five- component acellular, and a whole-cell pertussis vaccine. N Engl J Med. 1996;334:349-55. [PMID: 8538705]

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28. Adult immunization initiative. Available at www.acponline.org/ aii/index.html. Accessed 6 July 2005.

2005 American College of Physicians

Gregory A. Poland, MD

Mayo Clinic and Foundation

Rochester, MN 55905

Potential Financial Conflicts of Interest: Grants received: Merck.

Requests for Single Reprints: Gregory A. Poland, MD, Mayo Vaccine Research Group, Mayo Clinic and Foundation, 611C Guggenheim Building, 200 First Street SW, Rochester, MN 55905.

Ann Intern Med. 2005:143:539-541.

Copyright American College of Physicians Oct 4, 2005

Source: Annals of Internal Medicine

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