Clinical Health Updates

Pneumococcal conjugate vaccine prevents meningitis

Clinical Question:
What is the effect of pneumococcal conjugate vaccine on pneumococcal meningitis?

Bottom Line:
Although the pneumococcal conjugate vaccine (PCV7) has reduced the overall likelihood of pneumococcal meningitis, particularly in infants and older adults, there are worrisome recent trends regarding non-PCV7 serotype disease and antibiotic resistance that bear close watching. (LOE = 2c)

Reference:
Hsu HE, Shutt KA, Moore MR, et al. Effect of pneumococcal conjugate vaccine on pneumococcal meningitis. N Engl J Med 2009;360(3):244-256.

Study Design:
Time series

Funding:
Government

Setting:
Population-based

Summary:
Invasive pneumococcal disease declined among children and adults after the introduction of the pediatric heptavalent pneumococcal conjugate vaccine (PCV7) in 2000, but its effect on pneumococcal meningitis is unclear. They examined trends in pneumococcal meningitis from 1998 through 2005 using active, population-based surveillance data from eight sites in the United States. Isolates were grouped into PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), PCV7-related serotypes (6A, 9A, 9L, 9N, 18A, 18B, 18F, 19B, 19C, 23A, and 23B), and non-PCV7 serotypes (all others). Changes in the incidence of pneumococcal meningitis were assessed against baseline values from 1998-1999. The researcher identified 1379 cases of pneumococcal meningitis. The incidence declined from 1.13 cases to 0.79 case per 100,000 persons between 1998-1999 and 2004-2005 (a 30.1% decline, P<0.001). Among persons younger than 2 years of age and those 65 years of age or older, the incidence decreased during the study period by 64.0% and 54.0%, respectively (P<0.001 for both groups). Rates of PCV7-serotype meningitis declined from 0.66 case to 0.18 case (a 73.3% decline, P<0.001) among patients of all ages. Although rates of PCV7-related-serotype disease decreased by 32.1% (P=0.08), rates of non-PCV7-serotype disease increased from 0.32 to 0.51 (an increase of 60.5%, P<0.001). The percentages of cases from non-PCV7 serotypes 19A, 22F, and 35B each increased significantly during the study period. On average, 27.8% of isolates were nonsusceptible to penicillin, but fewer isolates were nonsusceptible to chloramphenicol (5.7%), meropenem (16.6%), and cefotaxime (11.8%). The proportion of penicillin-nonsusceptible isolates decreased between 1998 and 2003 (from 32.0% to 19.4%, P=0.01) but increased between 2003 and 2005 (from 19.4% to 30.1%, P=0.03).

Hep A vaccine similar to immune globulin for postexposure prophylaxis

Clinical Question:
Is the hepatitis A vaccine an alternative to immune globulin for postexposure prophylaxis?

Bottom Line:
Hepatitis A is a reasonable alternative to immune globulin. Advantages of the vaccine include the likelihood of subsequent immunity, the fact that it is not a blood product, a less painful injection, and its wider availability, while a disadvantage is higher cost (although the authors argue that the cost of immune globulin is nearly as high as that of vaccine now).

Reference:
Victor JC, Monto AS, Surdina TY, et al. Hepatitis A vaccine versus immune globulin for postexposure prophylaxis. N Engl J Med 2007;357(17):1685-1694.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Hepatitis A vaccine administered to persons after exposure to the hepatitis A virus has not been compared directly with immune globulin, which is known to be highly effective in preventing hepatitis A when given within 2 weeks after exposure to the virus. They randomly assigned household and day-care contacts, 2 to 40 years of age, in Almaty, Kazakhstan, to receive one standard age-appropriate dose of hepatitis A vaccine or immune globulin within 14 days after exposure to patients with hepatitis A. Instances of laboratory-confirmed, symptomatic hepatitis A infection occurring between 15 and 56 days after exposure were then assessed during active follow-up of all susceptible contacts. Of 4524 contacts who underwent randomization, 1414 (31%) were susceptible to hepatitis A virus and 1090 were eligible for the per-protocol analysis. Among these contacts, 568 received hepatitis A vaccine and 522 received immune globulin. Most contacts were children (average age, 12 years), and most received prophylaxis during the second week after exposure (average interval after exposure, 10 days). The baseline characteristics of the contacts were similar in the two groups. Symptomatic infection with hepatitis A virus was confirmed in 25 contacts receiving vaccine (4.4%) and in 17 contacts receiving immune globulin (3.3%) (relative risk, 1.35; 95% confidence interval, 0.70 to 2.67).

HPV vaccine not effective in treating women with preexisting HPV infection

Clinical Question:
Is the human papillomavirus vaccine useful in the treatment of women already infected with the virus?

Bottom Line:
This study found no evidence to support the human papillomavirus (HPV) vaccine in the treatment of women already infected with HPV. Viral clearance rates were comparable in women regardless of vaccination status.

Reference:
Hildesheim A, Herrero R, Wacholder S, et al. Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection: a randomized trial. JAMA 2007;298:743-753.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
These investigators identified 2376 women, aged 18 to 25 years, initially positive for known HPV DNA. Of these, 2055 (86%) and 1671 (70%) completed follow-up at 6 and 12 months, respectively. Eligible patients randomly received (concealed allocation assignment) 3 doses of bivalent HPV 16/18 L1 protein viruslike particle vaccine or a control hepatitis A vaccine over 6 months. Measurement of HPV DNA was performed using standard laboratory procedures; samples were either self-collected or collected by a clinician during a pelvic examination. Individuals assessing outcomes remained unaware of treatment group assignment. Using intention-to-treat analysis, the clearance rate for HPV-16/18 infections were similar in the vaccine and control groups at 6 months (33.4% vs 31.6%, respectively) and at 12 months (48.8% vs 49.8%, respectively).

Varicella immunity wanes in children after 5 years

Clinical Question:
Does immunity from varicella vaccine decrease over time?

Bottom Line:
Immunity from varicella vaccination decreases over time, resulting in more cases of greater severity among older children. These data are the basis for the recommendation that children between the ages of 4 years and 6 years receive a second varicella vaccination. Thats why a second dose of varicella vaccine now recommended for all children, could improve protection from both primary vaccine failure and waning vaccine-induced immunity

Reference:
Chaves SS, Gargiullo P, Zhang JX, et al. Loss of vaccine-induced immunity to varicella over time. N Engl J Med 2007;356:1121-1129.

Study Design:
Cohort (prospective)

Synopsis:
The introduction of universal varicella vaccination in 1995 has substantially reduced varicella-related morbidity and mortality in the United States. However, it remains unclear whether vaccine-induced immunity wanes over time, a condition that may result in increased susceptibility later in life, when the risk of serious complications may be greater than in childhood. They examined 10 years (1995 to 2004) of active surveillance data from a sentinel population of 350,000 subjects to determine whether the severity and incidence of breakthrough varicella (with an onset of rash >42 days after vaccination) increased with the time since vaccination. We used multivariate logistic regression to adjust for the year of disease onset (calendar year) and the subject’s age at both disease onset and vaccination. A total of 11,356 subjects were reported to have varicella during the surveillance period, of whom 1080 (9.5%) had breakthrough disease. Children between the ages of 8 and 12 years who had been vaccinated at least 5 years previously were significantly more likely to have moderate or severe disease than were those who had been vaccinated less than 5 years previously (risk ratio, 2.6; 95% confidence interval [CI], 1.2 to 5.8). The annual rate of breakthrough varicella significantly increased with the time since vaccination, from 1.6 cases per 1000 person-years (95% CI, 1.2 to 2.0) within 1 year after vaccination to 9.0 per 1000 person-years (95% CI, 6.9 to 11.7) at 5 years and 58.2 per 1000 person-years (95% CI, 36.0 to 94.0) at 9 years.

Botulinum toxin A effective for axillary hyperhidrosis

Clinical Question:
Are botulinum toxin type A injections safe and effective in the management of adults with axillary hyperhidrosis?

Bottom Line:
Botulinum toxin type A (Botox) injections are safe and effective for the treatment of adults with axillary hyperhidrosis. The duration of effect in this study was approximately 200 days.

Reference:
Lowe NJ, Glaser DA, Eadie N, et al, for the North American Botox in Primary Axillary Hyperhidrosis Clinical Study Group. Botulinum toxin type A in the treatment of primary axillary hyperhidrosis: A 52-week multicenter double-blind, randomized, placebo-controlled study of efficacy and safety. J Am Acad Dermatol 2007;56:604-611.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
The long-term effects of botulinum toxin type A (BoNTA) on the global impairment associated with severe primary axillary hyperhidrosis have not been comprehensively assessed relative to placebo. The authors assessed the efficacy and safety of 2 dosages of BoNTA compared with placebo in subjects with primary axillary hyperhidrosis. Subjects (N = 322) were randomized to the use of BoNTA (75 U or 50 U/axilla) or placebo in this 52-week, multicenter, double-blind study. BoNTA treatment significantly reduced daily activity limitations at 4 weeks after injection. A 2-point improvement on the 4-point Hyperhidrosis Disease Severity Scale (HDSS) was reported in 75% of subjects in the 75-U and 50-U BoNTA groups and in 25% of the placebo group (P < .001). Improvements in HDSS scores were corroborated by gravimetric results. The median duration of effect was 197 days, 205 days, and 96 days in the 75-U, 50-U, and placebo groups, respectively. BoNTA was well tolerated.
LIMITATIONS: The effect of total surface area involvement on treatment efficacy was not evaluated.

Live attenuated nasal flu vaccine safe, effective for ages 1 to 5

Clinical Question:
Is live attenuated influenza vaccine safe and effective in children between the ages of 6 months and 5 years?

Bottom Line:
Live attenuated influenza vaccine delivered via nasal spray on 2 occasions 4 weeks to 6 weeks apart is more effective than inactivated injected vaccine, and appears safe in children ages 1 year to 5 years without a history of wheezing.

Reference:
Belshe RB, Edwards KM, Vesikari T, et al, for the CAIV-T Comparative Efficacy Study Group. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med 2007;356:685-696.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Universal vaccination of children 6 to 59 months of age with trivalent inactivated influenza vaccine has recently been recommended by U.S. advisory bodies. The authors evaluated alternative vaccine approaches, we compared the safety and efficacy of intranasally administered live attenuated influenza vaccine with those of inactivated vaccine in infants and young children. Children 6 to 59 months of age, without a recent episode of wheezing illness or severe asthma, were randomly assigned in a 1:1 ratio to receive either cold-adapted trivalent live attenuated influenza vaccine (a refrigeration-stable formulation of live attenuated intranasally administered influenza vaccine) or trivalent inactivated vaccine in a double-blind manner. Influenza-like illness was monitored with cultures throughout the 2004-2005 influenza season. Safety data were available for 8352 children, and 7852 children completed the study according to the protocol. There were 54.9% fewer cases of cultured-confirmed influenza in the group that received live attenuated vaccine than in the group that received inactivated vaccine (153 vs. 338 cases, P<0.001). The superior efficacy of live attenuated vaccine, as compared with inactivated vaccine, was observed for both antigenically well-matched and drifted viruses. Among previously unvaccinated children, wheezing within 42 days after the administration of dose 1 was more common with live attenuated vaccine than with inactivated vaccine, primarily among children 6 to 11 months of age; in this age group, 12 more episodes of wheezing were noted within 42 days after receipt of dose 1 among recipients of live attenuated vaccine (3.8%) than among recipients of inactivated vaccine (2.1%, P=0.076). Rates of hospitalization for any cause during the 180 days after vaccination were higher among the recipients of live attenuated vaccine who were 6 to 11 months of age (6.1%) than among the recipients of inactivated vaccine in this age group (2.6%, P=0.002).

Acellular pertussis vaccine 63% to 92% effective

Clinical Question:
Is an acellular pertussis vaccine safe and effective for adults and adolescents?

Bottom Line:
The acellular pertussis vaccine was protective among adolescents and adults, and its routine use might reduce the overall disease burden and transmission to children.

Reference:
Ward JI, Cherry JD, Chang SJ, et al, for the APERT Study Group. Efficacy of an acellular pertussis vaccine among adolescents and adults. N Engl J Med 2005;353:1555-63.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Pertussis immunization of adults may be necessary to improve the control of a rising burden of disease and infection. This trial of an acellular pertussis vaccine among adolescents and adults evaluated the incidence of pertussis, vaccine safety, immunogenicity, and protective efficacy. Bordetella pertussis infections and illnesses were prospectively assessed in 2781 healthy subjects between the ages of 15 and 65 years who were enrolled in a national multicenter, randomized, double-blind trial of an acellular pertussis vaccine. Subjects received either a dose of a tricomponent acellular pertussis vaccine or a hepatitis A vaccine (control) and were monitored for 2.5 years for illnesses with cough that lasted for more than 5 days. Each illness was evaluated with use of a nasopharyngeal aspirate for culture and polymerase-chain-reaction assay, and serum samples from patients in both acute and convalescent stages of illness were analyzed for changes in antibodies to nine B. pertussis antigens. Of the 2781 subjects, 1391 received the acellular pertussis vaccine and 1390 received the control vaccine. The groups had similar ages and demographic characteristics, and the median duration of follow-up was 22 months. The acellular pertussis vaccine was safe and immunogenic. There were 2672 prolonged illnesses with cough, but the incidence of this nonspecific outcome did not vary between the groups, even when stratified according to age, season, and duration of cough. On the basis of the primary pertussis case definition, vaccine protection was 92 percent (95 percent confidence interval, 32 to 99 percent). Among unimmunized controls with illness, 0.7 percent to 5.7 percent had B. pertussis infection, and the percentage increased with the duration of cough. On the basis of other case definitions, the incidence of pertussis in the controls ranged from 370 to 450 cases per 100,000 person-years.

Flu shots are effective in elderly

Clinical Question:
Are flu shots effective in preventing influenza and influenza-like illness??

Bottom Line:
In long-term care facilities, where vaccination is most effective against complications, the aims of the vaccination campaign are fulfilled, at least in part. However, according to reliable evidence the usefulness of vaccines in the community is modest.

Reference:
Jefferson T, Rivetti D, Rivetti A, Rudin M, Di Pietrantonj C, Demicheli V. Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review. Lancet 2005;366:1165-74.

Study Design:
Systematic review

Synopsis:
Influenza vaccination of elderly individuals is recommended worldwide. Our aim was to review the evidence of efficacy and effectiveness of influenza vaccines in individuals aged 65 years or older. We searched five electronic databases to December, 2004, in any language, for randomised (n=5), cohort (n=49), and case-control (n=10) studies, assessing efficacy against influenza (reduction in laboratory-confirmed cases) or effectiveness against influenza-like illness (reduction in symptomatic cases). We expressed vaccine efficacy or effectiveness as a proportion, using the formula VE=1-relative risk (RR) or VE*=1-odds ratio (OR). We analysed the following outcomes: influenza, influenza-like illness, hospital admissions, complications, and deaths. In homes for elderly individuals (with good vaccine match and high viral circulation) the effectiveness of vaccines against influenza-like illness was 23% (95% CI 6-36) and non-significant against influenza (RR 1.04, 0.43-2.51). Well matched vaccines prevented pneumonia (VE 46%, 30-58) and hospital admission (VE 45%, 16-64) for and deaths from influenza or pneumonia (VE 42%, 17-59), and reduced all-cause mortality (VE 60%, 23-79). In elderly individuals living in the community, vaccines were not significantly effective against influenza (RR 0.19, 0.02-2.01), influenza-like illness (RR 1.05, 0.58-1.89), or pneumonia (RR 0.88, 0.64-1.20). Well matched vaccines prevented hospital admission for influenza and pneumonia (VE 26%, 12-38) and all-cause mortality (VE 42%, 24-55). After adjustment for confounders, vaccine performance was improved for admissions to hospital for influenza or pneumonia (VE* 27%, 21-33), respiratory diseases (VE* 22%, 15-28), and cardiac disease (VE* 24%, 18-30), and for all-cause mortality (VE* 47%, 39-54).