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13th International Congress on Infectious Diseases

Kuala Lumpur, Malaysia / June 19-22, 2008

Immunization to prevent vaccine-preventable illnesses in adults is increasingly vital because the population is aging and is thus more vulnerable to infection. The increasing prevalence of comorbidities in the elderly, including diabetes and chronic cardiac and renal disease, also contributes to their vulnerability. As Dr. Jeffrey Hanna, Medical Director of Communicable Disease Control, Queensland Health, Australia, emphasized, “We want to keep our elderly citizens as healthy as possible for as long as possible.” In order to achieve this, the important vaccines for adults to be considered are the influenza vaccine, adult dTpa, the herpes zoster (HZ) vaccine and the 23-valent pneumococcal polysaccharide vaccine (23vPPV). “But how are we faring with adult vaccination? Unfortunately, not nearly as well as we should be,” Dr. Hanna observed.

Low Uptake

According to Dr. Hanna, there needs to be more emphasis on getting the message across to physicians and the general public of the importance of adult immunization, just as there has been emphasis for many years on making childhood vaccination a priority. He quoted previous research on the uptake of the pneumococcal polysaccharide vaccine in adults, which compared patients with a positive attitude to vaccination to those with a more casual attitude. When they saw a physician who did not actively recommend the vaccine, the former group had an uptake of about 40% compared with <20% in the latter group. But with a brief intervention that involved a positive recommendation from the physician and perhaps a written leaflet, uptake rose to more than 80% in both groups.

Another recently published report on the uptake of the 23vPPV in Ontario from 1995 to 2001 showed that in 2001, the uptake was only about 50% in those over the age of 65 with chronic underlying illness (Al-Sukhni et al. Vaccine 2008; 26(11):1432-7). “These are people who really should have the vaccine because they are aged and they have an underlying comorbidity,” Dr. Hanna noted. In the population >65 years of age who were healthy, the uptake was only about 39%. In those <65 years of age with chronic underlying illness, a very large group of patients whose comorbidity was almost certainly an indication for the vaccine, the uptake was only about 15%.

Dr. Murali Mohan, Head, Departments of Medicine and Pulmonology, Trinity Hospital, Bengaluru, India, reported that World Health Organization data from 2003 revealed there were about 1.6 million deaths in all age groups from pneumococcal disease. Mortality from serious complications, such as pneumococcal bacteremia and pneumococcal meningitis, was much higher in the very young, the elderly and those with serious comorbidities; however, resistance to antibiotics was increasing and up to 40% of infections were resistant to a single antibiotic.

The Cochrane Review published a meta-analysis this year of 15 randomized controlled trials with more than 48,000 participants which showed that the 23vPPV was efficacious in reducing the mortality rate from invasive pneumococcal disease. The vaccine was not associated with a significantly increased reduction in all-cause mortality and appeared to be slightly less effective in adults with chronic illness. “What that means to me is that if you take people who are already very ill and vaccinate them, it is less effective,” Dr. Mohan suggested. “You need to catch them when they are healthy before they develop comorbidities and vaccinate them.”

The vaccine, which covers more than 90% of clinically important infections, has been shown to be cost-effective in many countries. “It should form part of any immunization schedule for adults,” Dr. Mohan concluded.

Preventing Shingles

Similarly, because the burden of illness (BOI) caused by HZ and its serious complication, post-herpetic neuralgia (PHN), is substantial, the HZ vaccine is now deemed to be an essential component in an adult immunization regimen. The vaccine should be available in all countries because of the universality of chickenpox and the potential for reactivation of the HZ virus with waning cellular immunity. “We have all been exposed to the chickenpox virus, which means we may all one day get zoster,” Dr. Hanna pointed out to delegates.

The main barrier to uptake of the HZ vaccine appears to be failure by the primary care physician or specialist to suggest vaccination during a consultation. “As soon as a clinician, general practitioner or specialist recommends this vaccine, particularly if they have it on site and it is in the vaccine fridge in the [office], then we know the uptake can be optimized,” Dr. Hanna commented.

HZ: A Function of Age

Dr. Myron Levin, Professor of Pediatrics and Medicine, University of Colorado School of Medicine, Denver, said 96% of adults worldwide had contracted chickenpox in childhood and were therefore at risk for HZ. About one in four people develop HZ in their lifetime and this increases to one in two of those who live to 80 years of age. Moreover, PHN is common and in those >60 years of age, one in three suffers pain for 30 days, one in five for 60 days and one in seven for 90 days. “That pain has a particularly profound effect on older people and on younger people who are working,” Dr. Levin said.

Six studies from four countries confirmed that contracting HZ is a function of age. “Something happens around the age of 40 to 50 years that makes it much more likely that we get HZ,” Dr. Levin remarked. In fact, what happens is that cell-mediated immunity to the varicella-zoster virus (VZV)—the virus that causes chickenpox in childhood and then becomes latent until it is reactivated to cause HZ—declines with age, he added. “We reach a certain threshold below which we do not have enough immunity to prevent reactivation of the virus causing disease,” he explained. “But if we had a VZV vaccine that could boost VZV cell-mediated immunity, then we ought to be able to prevent HZ, or attenuate it, or do both.”

This was borne out by the SPS (Shingles Prevention Study), a double-blind, placebo-controlled trial of a live, attenuated HZ vaccine in 38,546 adults. Approximately 20,750 were aged 60 to 69 years and almost 17,800 were aged <u>></u>70 years (Oxman et al. N Engl J Med 2005;352 (22):2271-84). The study cohort was followed for 3.1 years. Results showed that compared with placebo, the vaccine prevented 61.1% of the BOI due to HZ, 66.5% of PHN and 51.3% of cases of HZ. Breaking the results down by age, 65.5% of the BOI was prevented in 60- to 69-year-olds compared with 55.4% in those aged <u>></u>70 years. “As these people got older, the effect on the BOI was a little bit less,” Dr. Levin noted.

The effect of age was more striking when looking at the effect of the vaccine on HZ incidence, with results showing there were 64% of cases prevented in those aged 60 to 69 years and 37% in those aged <u>></u>70 years. However, the vaccine prevented 65.7% of PHN in 60- to 69-year-olds and 66.8% in those aged <u>></u>70 years. “Here we see severity of disease is attenuated just as much in older people,” Dr. Levin said. “The zoster vaccine maintained its efficacy regardless of the age of the subject. The effect in the younger subjects is mediated mostly by preventing HZ and the effect in the older subjects is mediated mostly by attenuating HZ.”

A current trial of 6800 participants is following patients for up to 10 years; data to date shows vaccine efficacy is maintained for at least five years. Dr. Levin added that it did not appear possible to improve the early accurate diagnosis and appropriate treatment of HZ in order to prevent prolonged pain. “You do much better to prevent the disease than to worry about how to treat it,” he concluded.