BACKGROUND:Since 1990, most schoolchildren in the United States have received a second dose of measles-mumps-rubella vaccine (MMR2) at kindergarten entry. Elimination of endemic rubella virus circulation in the United States was declared in 2004. The objective of the current study was to evaluate the short- and long-term rubella immunogenicity of MMR2.METHODS:At enrollment in 1994-1995, children (n = 307) in a rural Wisconsin health maintenance organization received MMR2 at age 4-6 years. A comparison group of older children (n = 306) was vaccinated at age 9-11 years. Serum specimens were collected during a 12-year period. Rubella antibody levels were evaluated by plaque-reduction neutralization (lowest detectable titer, 1:10).RESULTS:Before administration of MMR2 in the kindergarten group, 9% of subjects were seronegative, 60% had the lowest detectable titer, and the geometric mean titer (GMT) was 1:13. One month after administration of MMR2, 1% were seronegative, 6% had the lowest detectable titer, and the GMT was 1:42. Four-fold boosts occurred in 62% of subjects, but only 0.3% were immunoglobulin M positive. Twelve years after MMR2 administration, 10% were seronegative, 43% had the lowest detectable titer, and the GMT was 1:17. The middle-school group showed similar patterns.CONCLUSIONS:Rubella antibody response to MMR2 was vigorous, but titers decreased to pre-MMR2 levels after 12 years. Because rubella is a highly epidemic disease, vigilance will be required to assure continued elimination.

The American Telemedicine Association (ATA) held the Global Forum on Telemedicine: Connecting the World Through Partnerships in September 2007 with sponsorship by the Telemedicine and Advanced Technology Research Center (TATRC), U.S. Army Medical Research and Materiel Command (USAMRMC). The goal was to bring together key stakeholders in global healthcare outreach to explore a flexible framework and sustainable business model that can leverage telemedicine and information technology (IT) to expand healthcare services internationally. Dr. Hon S. Pak, President of the ATA, opened the forum with a call for collaboration and partnership, and encouraged continued international dialogue to create a framework that leverages the telemedicine community to improve global disparity in healthcare. Keynote addresses included speakers from the World Health Organization (UN) and United Nations (UN) Global Alliance for Information and Communities Technologies and Development (GAID). Presentations from 15 government and nongovernment aid organizations (NGOs) and 12 international programs covered 5 key areas: (1) NGO perspective; (2) governmental/military programs; (3) financial sustainability; (4) disaster response; and (5) emerging opportunities. The forum resulted in an International Roadmap for Action that was developed by the authors based on the presentations and interactions from the 335 attendees and establishing a set of priorities and actions to improve healthcare using telemedicine and IT. Recommendations include: (1) continued dialogue in creating a telemedicine framework; (2) identification and leverage of resources; (3) provision of education to funding organization and expand training programs to build competency in the healthcare workforce; (4) alignment of international policy to support integration of telemedicine into country plans and support cross-country partnerships; (5) development of communications infrastructure; and (6) integration of telemedicine into disaster relief programs.

Recent mumps outbreaks in older vaccinated populations were caused primarily by genotype G viruses, which are phylogenetically distinct from the genotype A vaccine strains used in the countries affected by the outbreaks. This finding suggests that genotype A vaccine strains could have reduced efficacy against heterologous mumps viruses. The remote history of vaccination also suggests that waning immunity could have contributed to susceptibility. To examine these issues, we obtained consecutive serum samples from children at different intervals after vaccination and assayed the ability of these samples to neutralize the genotype A Jeryl Lynn mumps virus vaccine strain and a genotype G wild-type virus obtained during the mumps outbreak that occurred in the United States in 2006. Although the geometric mean neutralizing antibody titers against the genotype G virus were approximately one-half the titers measured against the vaccine strain, and although titers to both viruses decreased with time after vaccination, antibody induced by immunization with the Jeryl Lynn mumps vaccine strain effectively neutralized the outbreak-associated virus at all time points tested.

OBJECTIVE:To evaluate the persistence of measles antibodies after 2 doses of measles vaccine in a setting where exposure to wild-type measles was unlikely. Measles was declared eliminated from the United States in 2000, an achievement attributed to effective implementation of a routine 2-dose vaccination policy. Some have questioned whether measles transmission could resume if immunity wanes in the absence of boosting from wild-type measles.DESIGN:Prospective, observational, volunteer cohort study.SETTING:Rural Wisconsin health maintenance organization.PARTICIPANTS:Children who received the second measles vaccine dose at kindergarten (aged 4-6 years) or middle school (aged 10-12 years) in 1994 or 1995. Serum samples were collected periodically during a 10-year period for the kindergarten group and a 5-year period for the middle school group.INTERVENTION:Second dose of measles vaccine.MAIN OUTCOME MEASURE:Measles antibody levels were assessed by plaque-reduction neutralization: titers less than 8 mIU/mL were considered seronegative and suggestive of susceptibility to measles, and titers of 120 mIU/mL or less were considered low and suggestive of potential susceptibility.RESULTS:During the study period, no measles was reported in the study area. Voluntary attrition reduced the study population from 621 at enrollment to 364 (58.6%) by study end. Before the second dose, 3.1% (19/621) had low titers, of whom 74% (14/19) were antibody-negative, with geometric mean titers being significantly higher in kindergarteners (1559 mIU/mL) than in middle schoolers (757 mIU/mL) and rates of negativity significantly lower (1.0% [3/312] vs 3.6% [11/309]). One month after the second dose, 0.2% (1/612) had low titers and none was seronegative, with geometric mean titers being significantly higher in kindergarteners (2814 mIU/mL) than in middle schoolers (1672 mIU/mL). By study end, 4.9% (18/364) had low titers and none was seronegative, with no significant difference in geometric mean titers between kindergarteners (641 mIU/mL) and middle schoolers (737 mIU/mL) when both groups were aged 15 years. Projections suggest that the proportion of persons with low antibody levels may increase over time.CONCLUSIONS:Measles antibody persisted in all vaccinees available for follow-up 10 years after a second dose of vaccine, with no seronegative results detected. Declining titers suggest the need for vigilance in ensuring disease protection for the vaccinated population.

Background: A combination measles, mumps, rubella, and varicella vaccine (ProQuad®, Merck & Co., Inc, West Point, PA) was evaluated in 5 clinical trials. Use of ProQuad® would result in fewer injections for children and would facilitate universal immunization against all 4 diseases. Objective: To describe the combined results obtained from the studies conducted during the clinical development program for ProQuad®. Methods: A total of 5833 healthy children, 12-23 months of age, and 399 healthy children, 4-6 years of age, received 1 or 2 doses of ProQuad® in 5 controlled clinical trials. M-M-R®II and VARIVAX® were used as the control for most studies. Safety was evaluated for 6 weeks postvaccination and immunogenicity was assessed 6 weeks after each dose by a sensitive assay (ELISA or gpELISA). Results: A single dose of ProQuad® in 12- to 23-month-old children was shown to be as immunogenic as a single dose of M-M-R®II and VARIVAX® and was generally well tolerated. ProQuad® can be used concomitantly with other vaccines (hepatitis B and Haemophilus influenzae b). A higher rate of fever was reported after 1 dose of ProQuad® compared to M-M-R®II and VARIVAX®, but fever episodes were transient without long-term sequelae. Both a 2-dose regimen of ProQuad® in 12- to 23-month-olds and use of ProQuad® in place of M-M-R®II at 4-6 years were shown to be immunogenic and well tolerated. The incidence of adverse experiences following a second dose of ProQuad® was lower than that following the initial dose. Conclusions: A single dose of ProQuad® is as immunogenic as M-M-R®II and VARIVAX® and is well tolerated in a 1- or 2-dose schedule. ProQuad® should easily fit into the routine immunization schedule.

BACKGROUND. In the United States, children receive primary doses of M-M-RII (Merck & Co, Inc, West Point, PA) and Varivax (Merck & Co, Inc) beginning at 12 months, often at the same health care visit. Currently a second dose of M-M-RII is given to 4- to 6-year-old children, to increase vaccination rates and to reduce the number of individuals without detectable antibodies. A second dose of a varicella-containing vaccine may result in similar benefits. OBJECTIVES. To demonstrate that ProQuad (measles, mumps, rubella, and varicella virus vaccine live; Merck & Co, Inc) may be given in place of a second dose of M-M-RII or second doses of M-M-RII and Varivax for 4- to 6-year-old children. METHODS. Four- to 6-year-old children who had been immunized previously with M-M-RII and Varivax were assigned randomly to receive either ProQuad and placebo (N = 399), M-M-RII and placebo (N = 195), or M-M-RII and Varivax (N = 205) and were then monitored for safety and immunogenicity. RESULTS. ProQuad was generally well tolerated. Similarity (noninferiority) was demonstrated in postvaccination antibody responses to measles, mumps, and rubella between recipients of ProQuad and all recipients of M-M-RII and in responses to varicella between recipients of ProQuad and recipients of Varivax. Postvaccination seropositivity rates for antibodies against all 4 viruses were nearly 100% in all 3 groups. Small fold increases were observed for measles, mumps, and rubella antibody titers. In contrast, substantial boosts in varicella antibody titers were observed among recipients of a second dose of varicella vaccine, administered as ProQuad or Varivax. CONCLUSIONS. ProQuad may be used in place of a second dose of M-M-RII or second doses of M-M-RII and Varivax for 4- to 6-year-old children.

BACKGROUND/OBJECTIVES. In 1989, the American Academy of Pediatrics and the Advisory Committee on Immunization Practices recommended that school children receive 2 doses of measles-mumps-rubella vaccine. With measles and rubella eliminated from the United States, measles-mumps-rubella vaccine adverse events have come under scrutiny, but no study has compared the reactogenicity of the first (measles-mumps-rubella vaccine dose 1) and second (measles-mumps-rubella vaccine dose 2) doses at the most common ages of administration in the United States. METHODS. From a health maintenance organization, 3 groups of children were recruited: (1) toddlers aged 12 to 24 months receiving measles-mumps-rubella vaccine dose 1; (2) kindergartners aged 4 to 6 years receiving measles-mumps-rubella vaccine dose 2; and (3) middle schoolers aged 10 to 12 years receiving measles-mumps-rubella vaccine dose 2. From 2 weeks before measles-mumps-rubella vaccine administration until 4 weeks afterward, families recorded in diaries the occurrence of potentially common symptoms. Postvaccination symptom rates were compared with the prevaccination baseline, with significance assessed by testing incidence rate ratios estimated by Poisson regression. RESULTS. Of 2173 children enrolled, 373 (17%) were lost to attrition, producing a study population of 1800. Compared with the prevaccination baseline, rates of fever, diarrhea, and rash were significantly elevated postvaccination among 535 toddlers receiving measles-mumps-rubella vaccine dose 1. An estimated net 95 (18%) experienced measles-mumps-rubella vaccine-associated events (median onset 5–10 days postvaccination, duration 2–5 days), with high fever (temperature ≥39.5°C) occurring in 33 (6%). None required medical attention. For 633 kindergartners and 632 middle schoolers, symptom rates were not significantly elevated after measles-mumps-rubella vaccine dose 2 compared with baseline. CONCLUSIONS. Vaccination-associated adverse events occur in ∼1 of every 6 toddlers receiving measles-mumps-rubella vaccine dose 1, with high fever occurring in 1 of 20. Adverse events are infrequent for measles-mumps-rubella vaccine dose 2 administered to school-aged children.

Background. The study was done to verify that concomitant administration of a bivalent Haemophilus influenzae type b-hepatitis B vaccine (Comvax), measles-mumps-rubella vaccine (M-M-R-II) and varicella vaccine (Varivax) would be well-tolerated and suitably immunogenic with respect to all vaccine antigens.Methods. We randomized 822 healthy 12- to 15-month-old children (1:1) to receive concomitant injections of Comvax, M-M-RI, and Varivax (concomitant group) or Comvax followed 6 weeks later by injections of M-M-R-II and Varivax (nonconcomitant group). Blood samples taken before and 6 weeks after vaccination were tested for antibodies to all vaccine antigens.Results. Vaccinations were generally well-tolerated. Children in the concomitant and nonconcomitant treatment groups were similar with respect to the safety endpoint of primary interest (16.1 and 19.5%, respectively, had a fever greater than or equal to103degreesF rectally at any time within 14 days after either of two clinic visits). Fifteen serious adverse events were reported (eight in the concomitant group and seven in the nonconcomitant group); all resolved. Elements of two serious adverse events (fever, fever and measles-like rash; both in concomitant group children) were considered possibly related to vaccination. One child was withdrawn from the study because of a nonserious adverse event subsequently judged to be unrelated to vaccination. Similar proportions of vaccinees in the concomitant and nonconcomitant groups developed satisfactory antibody responses to the H. influenzae polysaccharide, polyribosylribitol phosphate (97.8 to 98.7%), hepatitis B surface antigen (99.2 to 100%), measles virus (99.4 to 99.6%), mumps virus (98.4 to 99.2%), rubella virus (100%) and varicella virus (93.2 to 94.6%).Conclusion. Concomitant administration of Comvax, M-M-RI, and VARIVAX at the 12- or 15-month clinic visit is one satisfactory way of delivering some of the multiple vaccines indicated during the second year of life.

OBJECTIVE Inappropriate use of antibiotics is common in primary care, and effective interventions are needed to promote judicious antibiotic use and reduce antibiotic resistance. The objective of this study was to assess the impact of parent and clinician education on pediatric antibiotic prescribing and carriage of penicillin-nonsusceptible Streptococcus pneumoniae in child care facilities. METHODS A nonrandomized, controlled, community intervention trial was conducted in northern Wisconsin Clinicians. Clinic staff received educational materials and small-group presentations; materials were distributed to parents through clinics, child care facilities, and community organizations. Prescribing data were analyzed for 151 clinicians who provided primary pediatric care; nasopharyngeal carriage of penicillin-nonsusceptible S pneumoniae was assessed for 664 children in the baseline period (January-June 1997) and for 472 children in the postintervention period (January-June 1998). RESULTS The median number of solid antibiotic prescriptions per clinician declined 19% in the intervention region and 8% in the control region. The median number of liquid antibiotic prescriptions per clinician declined 11% in the intervention region, compared with an increase of 12% in the control region. Retail antibiotic sales declined in the intervention region but not in the control region. Among participating children in child care facilities, there were no significant differences in antibiotic use or penicillin-nonsusceptible S pneumoniae colonization between the intervention and control regions. CONCLUSIONS A multifaceted educational program for clinicians and parents led to community-wide reductions in antibiotic prescribing, but in child care facilities, there was no apparent impact on judicious antibiotic use or colonization with drug-resistant S pneumoniae. Longer follow-up time or greater reductions in antibiotic use may be required to identify changes in the pneumococcal susceptibility.

The antibody response to three Haemophilus influenzae type b vaccines was examined in 134 infants 17 to 22 months of age. Sera were collected from each subject before and 1 month after vaccination with either purified H. influenzae type b capsular polysaccharide (polyribosyl-ribitol phosphate (PRP) or one of two protein-conjugated vaccines (PRP-D or HbOC). Comparison of the two conjugate vaccines revealed that HbOC produced an antibody response ± 1.0 μg/ml in 96% compared with 72% who were vaccinated with PRP-D (P < 0.05). The isotype distribution of the antibodies produced by the two vaccines was similar. While all of the vaccines resulted in higher concentrations of anticapsular IgG1 than IgG2, the IgG1:IgG2 ratio was significantly higher in subjects immunized with HbOC. The IgG1:IgG2 ratio was similar in subjects immunized with PRP or PRP-D. The clinical significance of these observations remains to be determined.

Psychosis in a child is a problem that demands urgent diagnosis and, when appropriate, treatment Steroid therapy is an unusual cause of such a disturbance. There are few reports in the adult literature and none in the pediatric literature concerning steroid-associated personality disturbances We describe a child receiving steroid therapy who had an organic psychosis that progressed to catatonia. CASE REPORT A previously healthy 11-year-old boy, who was examined initially at another institution, had a facial rash and reported weakness of the proximal limb muscles. A clinical diagnosis of dermatomyositis was made by a dermatologist, although no electromyogram (EMG), muscle biopsy, or lupus erythematosus (LE) preparation was obtained.