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In a previous randomized phase 2 study in adolescents, a CRM197 meningococcal conjugate vaccine against serogroups A, C, W-135 and Y (MenACWY-CRM) was well tolerated and immunogenic, compared with a plain polysaccharide vaccine (MenACWY-PS).This extension study assessed antibody persistence 5 years after primary vaccination with MenACWY-CRM (n = 50) or MenACWY-PS (n = 51), and the immunogenicity and reactogenicity of a dose of MenACWY-CRM given 5 years after primary vaccination; antibody response was also compared with vaccine-naive controls (n = 54). The primary endpoints were the percentage of subjects with titers ≥8 by serum bactericidal activity assay using human complement (hSBA) 5 years after primary vaccination and hSBA geometric mean titers 1 month after the MenACWY-CRM dose given in the current study.Five years after primary vaccination, over 70% of subjects who had received MenACWY-CRM were seropositive (hSBA titers ≥8) for serogroups C, W-135 and Y; for serogroups C and Y, the percentages of seropositive subjects were significantly higher in subjects previously vaccinated with MenACWY-CRM than in subjects previously vaccinated with MenACWY-PS. The MenACWY-CRM dose given 5 years postprimary vaccination elicited an anamnestic response across serogroups in those previously vaccinated with MenACWY-CRM. Responses in those previously vaccinated with MenACWY-PS were less robust but adequate and similar to that seen in the vaccine-naive group, both in magnitude and kinetics. MenACWY-CRM was well tolerated in all 3 groups.MenACWY-CRM provided a broad and persistent immune response in adolescents. A subsequent dose of MenACWY-CRM elicited an adequate antibody response, regardless of vaccine history.

Because of the well-documented increased risk of meningococcal disease among adolescents, vaccination is recommended for this population in many countries, including the United States. This study compared the tolerability and immunogenicity in adolescents of a candidate quadrivalent meningococcal CRM197 glycoconjugate vaccine against serogroups A, C, W-135, and Y (MenACWY-CRM) with that of the licensed unconjugated quadrivalent polysaccharide vaccine (MPSV4).This phase II study was conducted in the United States among 524 adolescents aged 11-17 years in 2 stages, with different randomization schemes. The first 334 participants, enrolled in Stage 1, were randomized (1:1) to receive either MenACWY-CRM(+) (with adjuvant) or MPSV4. The next 190 participants, enrolled in Stage 2, were randomized (4:1) to receive either MenACWY-CRM(-) (without adjuvant) or MPSV4. Safety data were collected using diary cards and active surveillance. Human complement serum bactericidal activity (hSBA) titers were measured 1 and 12 months postvaccination.MenACWY-CRM and MPSV4 vaccines were well tolerated (local reactions, 63%-71% vs. 60%-62%; systemic reactions, 44%-56% vs. 46%-59%, respectively). One month postvaccination, similar hSBA titers were observed with the adjuvanted and nonadjuvanted MenACWY-CRM. The immunogenicity of MenACWY-CRM(-), measured by geometric mean titer, was significantly (P0.05) greater than that of MPSV4 for all 4 vaccine serogroups at 1 month. The percentage of subjects with hSBA titersor =1:4 was also significantly greater (P0.01) for MenACWY-CRM(-) recipients for serogroups A, C, and Y and noninferior for W-135. The proportions of MenACWY-CRM(-) recipients with hSBA titersor =1:4 to the vaccine serogroups at 1 month were 84% to 96% and geometric mean titers were 34 to 100. The percentage of subjects with hSBA titersor =1:4 was significantly (P0.01) greater than MPSV4 for serogroups C, W-135, and Y 12 months postvaccination.MenACWY-CRM was well tolerated and immunogenic, with evidence of persistence of bactericidal antibodies for at least 12 months postvaccination.

Objective To evaluate whether the varicella vaccine virus is detected in breast milk after vaccination of breast-feeding women and whether there is serologic evidence of exposure of the infant to varicella virus after maternal vaccination. Methods We enrolled women identified as varicella seronegative during routine prenatal screening at Group Health Cooperative. Participants received the first dose of varicella vaccine at least 6 weeks postpartum and the second dose at least 4 weeks later. They collected ten breast milk samples after each vaccine dose. Breast milk samples were tested for varicella zoster virus by polymerase chain reaction (PCR). Serum specimens were collected from the mothers 1 month after each vaccine dose, and peripheral blood from their infants was collected onto filter spots 1 month after the mother's second dose. These samples were tested for varicella immunoglobulin (Ig) G by whole-virus enzyme-linked immunosorbent assay (ELISA), or by the more sensitive glycoprotein ELISA. When possible, filter spots from the infants were also tested by PCR for the presence of varicella zoster virus deoxyribonucleic acid (DNA). Results Twelve women were enrolled; all seroconverted after the first vaccine dose. Varicella DNA was not detected by PCR in any of the 217 postvaccination breast milk specimens. None of the infants was seropositive. Samples from six infants were tested for varicella zoster virus DNA by PCR, and all were negative. Conclusion We found no evidence of varicella vaccine virus excretion in breast milk. These findings suggest that postpartum vaccination of varicella-susceptible women need not be delayed because of breast-feeding.

A few previous studies have suggested that childhood vaccines, particularly whole cell pertussis vaccine, may increase the risk of asthma. We evaluated the suggested association between childhood vaccinations and risk of asthma.Cohort study involving 167,240 children who were enrolled in 4 large health maintenance organizations during 1991 to 1997, with follow-up from birth until at least 18 months to a maximum of 6 years of age. Vaccinations were ascertained through computerized immunization tracking systems, and onset of asthma was identified through computerized data on medical care encounters and medication dispensings.In the study 18,407 children (11.0%) developed asthma, with a median age at onset of 11 months. The relative risks (95% confidence intervals) of asthma were: 0.92 (0.83 to 1.02) for diphtheria, tetanus and whole cell pertussis vaccine; 1.09 (0.9 to 1.23) for oral polio vaccine; 0.97 (0.91 to 1.04) for measles, mumps and rubella (MMR) vaccine; 1.18 (1.02 to 1.36) for Haemophilus influenzae type b (Hib); and 1.20 (1.13 to 1.27) for hepatitis B vaccine. The Hib result was not consistent across health maintenance organizations. In a subanalysis restricted to children who had at least 2 medical care encounters during their first year, the relative risks decreased to 1.07 (0.71 to 1.60) for Hib and 1.09 (0.88 to 1.34) for hepatitis B vaccine.There is no association between diphtheria, tetanus and whole cell pertussis vaccine, oral polio vaccine or measles, mumps and rubella vaccine and the risk of asthma. The weak associations for Hib and hepatitis B vaccines seem to be at least partially accounted for by health care utilization or information bias.

Objective: To evaluate economic and clinical outcomes of a program of routine prenatal serotesting for varicella and postpartum vaccination of seronegative women. Methods: An analytic cost-effectiveness model was constructed to compare the current strategy of no serotesting with 1) selective serotesting of pregnant women without a prior history of chickenpox and 2) serotesting of all pregnant women. In both serotesting strategies, seronegative women were vaccinated postpartum. The model followed a hypothetical cohort of 4 million women over 20 years. Costs and chickenpox disease outcomes during and outside of subsequent pregnancies were considered. The incremental cost-effectiveness (cost per adult chickenpox case prevented) of selective serotesting compared with the current strategy was measured. Results: Compared to no testing, selective serotesting would prevent 43% (48,577 of 112,654) of adult chickenpox cases, save $21.8 million in discounted medical and work loss costs from the societal perspective, and cost $1126 per case prevented from the health payer’s perspective (medical costs only). The model was sensitive to varicella seroprevalence and incidence of chickenpox among susceptible women but was relatively insensitive to the cost of serologic testing and vaccination. Compared with selective serotesting, the serotest-all strategy would prevent an additional 15,645 cases, at a societal cost of $7653 per additional case prevented. Conclusion: The selective serotesting strategy could prevent nearly half of chickenpox cases among this cohort and is cost-saving from the societal perspective. From the health payer’s perspective, it compares favorably with other generally accepted preventive practices. It should be considered for prevention of chickenpox among women of childbearing age.

Between July 7 and 18, 1991, five boys from a small town in rural Illinois experienced the onset of an acute febrile illness subsequently confirmed as leptospirosis by serologic tests. A cohort study found that swimming in a small swimming hole, Steel Tunnel Pond, was associated with disease (P < 0.01), the attack rate being 28%. Leptospira interrogans serovar grippotyphosa was isolated from urine cultures from two of the case patients and from a culture of Steel Tunnel Pond water. A high seroprevalence for grippotyphosa was found in animals near the pond. Drought conditions had been present in the month before the outbreak, creating an environment in the pond which probably facilitated transmission of the organism from area animals to humans. Although leptospirosis is infrequently reported in humans in the United States, it is endemic in animals and the potential for outbreaks exists, especially when environmental conditions are favorable.

Reply from the Authors: We appreciate the interest of Caron et al. in our article concerning "Clinical evidence of genomic imprinting in Tourette's syndrome"1 and their effort to replicate these findings. Unfortunately, there are some serious limitations of the study by Caron et al., which differs from ours in several important respects. First, probable autosomal dominant transmission of TS in their study was based solely on family history of the tic disorder, neglecting obsessive compulsive disorder(OCD) as a possible expression of the Tourette syndrome (TS) gene(s)7,8 and ignoring its possible influence as a co-inherited disorder.9 …