Update on infectious disease prevention: Human papillomavirus, hepatitis A
ABSTRACTKey studies on the prevention of human papillomavirus and hepatitis A published during the past year found that:
A quadrivalent vaccine against human papillomavirus prevents cervical intraepithelial neoplasia, vulvar and vaginal intraepithelial neoplasia, and anogenital disease in young women. The vaccine is likely cost-effective when given to girls, but perhaps not when given to boys.
Although hepatitis A immune globulin is modestly better than hepatitis A vaccine for postexposure prophylaxis against hepatitis A, both are highly effective. Hepatitis A vaccine is now recommended by the Advisory Committee on Immunization Practices as the preferred agent in healthy individuals between the ages of 2 and 40.
HPV VACCINE LIKELY COST-EFFECTIVE IN GIRLS, BUT NOT BOYS
Newall AT, Beutels P, Wood JG, Edmunds WJ, MacIntyre CR. Cost-effectiveness analyses of human papillomavirus vaccination. Lancet Infect Dis 2007; 7:289–296.
The study. In a review, Newall et al6 looked at four studies that examined the cost-effectiveness of the HPV vaccine. These studies were not perfect and had methodologic limitations because of uncertainty about vaccine efficacy, duration of protection, and the contribution of herd immunity. The studies nevertheless suggested that immunization of young girls but not young boys may be cost-effective, though they suggested the need for further research.
Findings. Three of the studies showed an incremental cost-effectiveness ratio of $14,000 to $24,000 per quality-adjusted year of life gained, which is well within the range for many preventive strategies that we employ in this country.
One of the studies examined the cost-effectiveness of immunizing males, and in that study it was found not to be cost-effective.
TAKE-HOME POINTS ON HPV VACCINATION
Quadrivalent vaccine does indeed reduce the incidence of HPV-associated cervical intra-epithelial neoplasia, vulvar and vaginal intra-epithelial neoplasia, and anogenital diseases in young women, and it is likely cost-effective.
The vaccine works only against HPV types 6, 11, 16, and 18, and 30% of cervical cancers are due to types other than HPV-16 and HPV-18. Also, vaccination is much more effective in patients not yet exposed to HPV, so it would be best to vaccinate them before they become sexually active.
The Advisory Committee on Immunization Practices voted to recommend that girls ages 11 to 12 in this country should receive vaccine.
Regrettably, many third-party payers do not yet pay for the vaccine, and the cost (around $375) must be paid out of pocket. Also, this issue remains politically charged and controversial. Some states have mandated vaccination and another 15 are presently considering legislation mandating vaccination. Such legislation has been defeated in four states.
My own practice is to offer the vaccine to 11- and 12-year old girls, and to older girls and young women (not to boys), especially if the health insurance plan covers it or if the patient or the patient’s family can afford it.
HEPATITIS A VACCINE IS AS GOOD AS IMMUNE GLOBULIN AFTER EXPOSURE
Victor JC, Monto AS, Surdina TY, et al. Hepatitis A vaccine versus immune globulin for postexposure prophylaxis. N Engl J Med 2007; 357:1685–1694.
Before 1995, when the first hepatitis A vaccine was introduced, about 30,000 cases of hepatitis A were reported each year in the United States. This was thought to be the tip of the iceberg: since this infection is often subclinical, estimates of up to 300,000 cases per year were given.
At first, immunization against hepatitis A in this country was confined to children over age 2 in states in which hepatitis A occurred more often than the norm. In 2005, after it had become clear that the vaccine was highly effective, the Advisory Committee on Immunization Practices revised its recommendations to include immunization of children between the ages of 12 and 23 months,7 so that they would complete this two-stage vaccination procedure by the time they reached the age of 2 years. With that strategy, the annual occurrence of hepatitis A in the United States fell dramatically, to about 4,000 cases per year in 2005, the lowest number of cases reported in the last 40 years. At present, most hepatitis A infections in this country are not from casual idiosyncratic transmission but rather are food-borne.
Still, hepatitis A remains a major problem in many parts of the world. Moreover, the availability of immune globulin, the traditional recommended agent for postexposure pro-phylaxis, has been limited because only one company manufactures it and the price has steadily escalated.
The study. Investigators at the University of Michigan and in Kazakhstan compared conventional doses of immune globulin vs hepatitis A vaccine as postexposure prophylaxis, given within 14 days of exposure to index cases of hepatitis A.8 Excluded were persons under the age of 2 years or over the age of 40, those with a history of hepatitis A or vaccination, those with liver disease, and those with other contraindications. The primary end point was the development of symptomatic, laboratory-confirmed hepatitis A, defined as a positive test for immunoglobulin M antibodies to hepatitis A; transaminase levels greater than two times the upper limit of normal; and symptoms consistent with hepatitis A in the absence of another identifiable disease that occurred within 15 to 56 days of exposure to the index case.
Findings. Of 4,524 contacts randomized, only 1,414 (31%) were susceptible to hepatitis A, suggesting that the prevalence of hepatitis A in Kazakhstan was high at that time. Of these, 1,090 completed the immunization and follow-up protocol and were eligible for the final analysis. Of these, 568 received vaccine and 522 received globulin. The average age was 12 years, the average time to vaccination after exposure was 10 days; 16% of the exposures occurred in the day-care setting, and 84% of the exposures occurred from household contacts.
Symptomatic hepatitis A occurred in 4.4% of vaccine recipients vs 3.3% of immunoglobulin recipients. The authors concluded that hepatitis A vaccine met the test of noninferiority, that both strategies were highly protective, but that immunoglobulin was modestly better. Thus, in June 2007, the Advisory Committee on Immunization Practices recommended hepatitis A vaccine as the preferred regimen for postexposure prophylaxis.9
This approach has several advantages:
- Hepatitis A vaccine confers immunity and long-term protection, which globulin does not
- The supply of vaccine is abundant
- Vaccine is relatively cheap
- Vaccine is easy to give.
This study, however, does not apply to people younger than 2 years or older than 40, those who are immunocompromised, or those who have chronic liver disease. In these groups, the recommendation is still to use immunoglobulin in postexposure prophylaxis.
