A look back at the year 2006

December 2006

We have a slew of new vaccines for adolescents: rotavirus, human papillomavirus and combined tetanus-diphtheria-acellular pertussis (Boostrix, GlaxoSmithKline; Adacel, Sanofi Pasteur). In addition we have a recommendation for a second varicella vaccine, which can now be given in combination with measles-mumps-rubella as MMRV (ProQuad, Merck).

We have had our usual supply problems, including a curtailment of the use of conjugate meningococcal vaccines because of shortages; this has now been rescinded and the vaccine can now be offered to 11 to 12-year-olds. One of the major problems that arose from this plethora of new vaccines is how physicians can afford to stock them. The cost of the new vaccines has increased logarithmically compared with the older ones, and there are more vaccines to give. Thus, it may be necessary to lay out tens of thousands of dollars to stock our offices with vaccines. This is a problem that will be discussed in these pages during the next couple of months.

We had expected live vaccines to produce an infection, which would result in immunity similar to that of natural infection, i.e. permanent immunity. This generally appeared to be the case in the past. A second dose of MMR is recommended to protect those who might not have been immunized successfully with the initial dose. If one assumed a vaccine failure rate of only 1% from one dose, then 40,000 susceptible patients (1% of 4 million births) would accrue annually, or 400,000 in a decade. It is essential to keep the pool of susceptible patients as small as possible, thus the importance of giving multiple doses.

Now there is concern that some of these vaccines may not confer durable immunity. In the case of varicella, the second dose, which may be given as MMRV, was recommended because of the number of partially protected vaccinees following one dose, but with an eye to waning immunity. Varicella-zoster is a live herpes virus that produces latent infection with cellular immunity that clearly diminished with age, thus the need for boosting immunity with a vaccine against zoster at age 60; that vaccine was also licensed this year. For this herpes virus, cellular immunity may be more critical than immunity to the older vaccines we have been using. The durability of the immunity achieved with this vaccine is being carefully watched. As a greater proportion of children get vaccinated, we expect to see more cases of modified varicella in the future. This does not imply a loss of vaccine-induced immunity.

The second vaccine to arouse concern about waning immunity is mumps. During the past year we have had about 5,000 cases, which far exceeds what we have seen for many decades. Outbreaks of mumps have occurred sporadically, mainly in educational settings, in the past. What is most disconcerting is a large number of recent cases occurred in people in their 20s, many of whom had received the recommended two doses of MMR. The predominance of cases in these people rather than younger individuals certainly suggests there may be waning immunity. In retrospect, earlier estimates of the effectiveness of this vaccine may have been overly optimistic. The proportion of subclinical cases obfuscates the calculation of vaccine efficacy and may make it more difficult to appreciate virus spread. Diminishing immunity to these childhood diseases is of great concern as these diseases tend to be much more severe in adulthood.

One example of a disease in which immunity seems to have diminished following vaccination is pertussis. For reasons that are complex and as yet unclear, we have witnessed a striking increase in cases most of which are attributable to cases in adolescents and adults. Thus, TDaP has replaced dT as the vaccine of choice. It is too soon to tell whether this has had an effect on pertussis in the United States, but in Canada, where vaccinating adolescents began in 2004, there is some suggestion that it may be working. Although there appeared to be an opportunity to test effectiveness in a suspected outbreak of pertussis, PCR results used for diagnosis could not be confirmed and thus the planned intervention program was not carried out. There continues to be a problem in laboratory confirmation as we still lack an approved serologic test and continue to be plagued with unreliable PCR.

We now have a newly licensed rotavirus vaccine, with a second on the way. These have been tested extensively and there has been no evidence of increased risk of intussusception, which led to the recall of the first rotavirus vaccine a few years ago. In clinical trials, these vaccines have been shown to reduce the risk of severe diarrhea and are expected to decrease hospitalization for gastroenteritis, a major cause of hospitalization in infants.

Probably the most important new vaccine is HPV. This has been approved for girls as young as 9 years of age and recommended for those women up to 26 years of age. It is important to immunize at a young age, before sexual activity begins as acquisition of HPV occurs rapidly after sexual debut. In extensive field trials, the vaccine has been shown to decrease the risk of infection with the strains contained in both vaccines, 16 and 18, which are the two strains most commonly involved in cervical cancer. The vaccine now licensed contains additional strains, 6 and 11, which are the principal ones causing genital warts. A second vaccine has been submitted for licensure, which contains only the two cancer-producing strains. The vaccines have been found to be immunogenic, decrease the risk of infection and the development of early stages of malignancy.

The major story of the year is the continuing epidemic of methicillin-resistant Staphylococcus aureus. What is more, the resistance to clindamycin, although variable geographically, appears to be increasing. One should know the resistance rate in one’s own community before using it as a first choice. Testing for inducible resistance using the D-test should be routine as well as testing additional antibiotics for sensitivity. What has been most troubling is the appearance of the disease in newborns. Both community and hospital-associated disease are on the rise.

This has been an exciting year in infectious disease research. Let’s hope an influenza epidemic does not make 2007 even more exciting … a reminder to get ourselves, our families, our office staff and out patients immunized. Have a happy holiday season and a great (but not too exciting) New Year.