Safety and Immunogenicity of Human Serum Albumin-Free MMR Vaccine in US Children Aged 12-15 Months.

BACKGROUND: M-M-R(TM)II (MMRII; Merck & Co) is currently the only measles-mumps-rubella (MMR) vaccine licensed in the United States. Another licensed vaccine would reinforce MMR supply. This study assessed the immunogenicity of a candidate vaccine (Priorix(TM), GlaxoSmithKline Vaccines [MMR-RIT]) when used as a first dose among eligible children in the United States. METHODS: In this exploratory Phase-2, multicenter, observer-blind study, 1220 healthy subjects aged 12-15 months were randomized (3:3:3:3) and received 1 dose of 1 of 3 MMR-RIT lots with differing mumps virus titers (MMR-RIT-1 [4.8 log10]; MMR-RIT-2 [4.1 log10]; MMR-RIT-3 [3.7 log10] CCID50) or MMRII co-administered with hepatitis A vaccine (HAV), varicella vaccine (VAR) and 7-valent pneumococcal conjugate vaccine (PCV7). Immune response to measles, mumps, and rubella viruses was evaluated at Day 42 post-vaccination. Incidence of solicited injection site, general, and serious adverse events was assessed. RESULTS: Seroresponse rates for MMR vaccine viral components in MMR-RIT lots were 98.3-99.2% (measles), 89.7-90.7% (mumps), and 97.5-98.8% (rubella), and for MMRII were 99.6%, 91.1%, and 100%, respectively. Immune responses to HAV, VAR, and PCV7 were similar when co-administered with any of the 3 MMR-RIT lots or MMRII. There were no apparent differences in solicited or serious adverse events among the 4 groups. CONCLUSIONS: Immune responses were above threshold levels for projected protection against the 3 viruses from MMR-RIT lots with differing mumps virus titers. MMR-RIT had an acceptable safety profile when co-administered with HAV, VAR, and PCV7. CLINICAL TRIALS REGISTRATION: NCT00861744; etrack; 111870.

Analysis of safety data in children after receiving two doses of ProQuad® (MMRV).

BACKGROUND: In randomized clinical studies, over 11,800 children, 12 months to 6 years of age, were administered ProQuad(®), a combination measles, mumps, rubella, and varicella vaccine (MMRV). This paper describes the safety following a 2-dose regimen of MMRV administered to children in the second year of life. METHODS: Safety data from five clinical studies were combined for all children who were scheduled to receive two doses of MMRV ∼3-6 months apart. All vaccinated children were followed for safety following each dose of MMRV. RESULTS: Of 3112 children who received a first dose of MMRV, 2780 (89.3%) received a second dose of MMRV. Overall, 70.5% and 57.7% of children reported ≥1 adverse experiences following first and second doses of MMRV, respectively. Injection-site redness was statistically significantly higher postdose 2 than postdose 1, while injection-site pain/tenderness was statistically significantly higher postdose 1 compared to postdose 2. Rashes were statistically significantly lower postdose 2 compared to postdose 1. Ten febrile seizures (8 postdose 1, 2 postdose 2) were reported following MMRV vaccination. The incidence of febrile seizures postdose 1 of MMRV was 0.26% (8/3019) compared to 0.07% (2/2695) postdose 2 of MMRV. CONCLUSIONS: Administration of two doses of MMRV has an acceptable safety profile in children 12 to 23 months of age. There is a small increase in the risk of febrile seizures following the first dose of MMRV as compared to the component vaccines, but the risk for any individual child is relatively low.

Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine versus one dose of monovalent varicella vaccine: a multicentre, observer-blind, randomised, controlled trial.

BACKGROUND: Rates of varicella have decreased substantially in countries implementing routine varicella vaccination. Immunisation is possible with monovalent varicella vaccine or a combined measles-mumps-rubella-varicella vaccine (MMRV). We assessed protection against varicella in naive children administered one dose of varicella vaccine or two doses of MMRV. METHODS: This study was done in ten European countries with endemic varicella. Healthy children aged 12-22 months were randomised (3:3:1 ratio, by computer-generated randomisation list, with block size seven) to receive 42 days apart (1) two doses of MMRV (MMRV group), or (2) MMR at dose one and monovalent varicella vaccine at dose two (MMR+V group), or (3) two doses of MMR (MMR group; control). Participants and their parents or guardians, individuals involved in assessment of any outcome, and sponsor staff involved in review or analysis of data were masked to treatment assignment. The primary efficacy endpoint was occurrence of confirmed varicella (by detection of varicella zoster virus DNA or epidemiological link) from 42 days after the second vaccine dose to the end of the first phase of the trial. Cases were graded for severity. Efficacy analyses were per protocol. Safety analyses included all participants who received at least one vaccine dose. This trial is registered with ClinicalTrials.gov, number NCT00226499. FINDINGS: Between Sept 1, 2005, and May 10, 2006, 5803 children (mean age 14·2 months, SD 2·5) were vaccinated. In the efficacy cohort of 5285 children, the mean duration of follow-up in the MMRV group was 36 months (SD 8·8), in the MMR+V group was 36 months (8·5) and in the MMR group was 35 months (8·9). Varicella cases were confirmed for 37 participants in the MMRV group (two moderate to severe), 243 in the MMR+V group, and 201 in the MMR group. Second cases occurred for three participants (all in the MMR+V group). Varicella cases were moderate to severe for two participants in the MMRV group, 37 in the MMR+V group (one being a second case that followed a mild first case); and 117 in the MMR group. Efficacy of two-dose MMRV against all varicella was 94·9% (97·5% CI 92·4-96·6), and against moderate to severe varicella was 99·5% (97·5-99·9). Efficacy of one-dose varicella vaccine against all varicella was 65·4% (57·2-72·1), and against moderate to severe varicella (post hoc) was 90·7% (85·9-93·9). The most common adverse event in all groups was injection-site redness (up to 25% of participants). Within 15 days after dose one, 57·4% (95% CI 53·9-60·9) of participants in the MMRV group reported fever of 38°C or more, by contrast with 44·5% (41·0-48·1) with MMR+V, and 39·8% (33·8-46·1) with MMR. Eight serious adverse events were deemed related to vaccination (three MMRV, four MMR+V, one MMR). All resolved within the study period. INTERPRETATION: These results support the implementation of two-dose varicella vaccination on a short course, to ensure optimum protection from all forms of varicella disease. FUNDING: GlaxoSmithKline Vaccines.

Immunogenicity and safety of a tetravalent measles-mumps-rubella-varicella vaccine: an open-labeled, randomized trial in healthy Korean children.

PURPOSE: This study (NCT00751348) evaluated the immunogenicity and safety of a combined measles-mumps-rubella-varicella (MMRV) vaccine compared to co-administration of measles-mumps-rubella and varicella (MMR+V) vaccines in Korean children during their second year of life. MATERIALS AND METHODS: Healthy children aged 11-24 months received one dose of MMRV or MMR+V. Antibody titers against measles, mumps and rubella were measured using enzyme-linked immunosorbent assay and against varicella using an immunofluorescence assay. Parents/guardians recorded adverse events in diary cards for up to 43 days post-vaccination. The primary objective was to demonstrate non-inferiority of MMRV to MMR+V for all antigens in terms of seroconversion rates (SCRs), defined as a group difference with a lower limit of the 95% confidence interval (CI)>-10%. RESULTS: Of 474 subjects enrolled, 458 (MMRV, 301; MMR+V, 157) were included in the according-to-protocol cohort. For measles (98.0% vs. 99.4%), rubella (99.7% vs. 100%) and varicella (98.9% vs. 100%) SCRs, the lower limits of the 95% CIs for group differences were greater than -10%; however, for mumps SCRs (88.8% vs. 94.2%), it was -10.40%. The primary objective of non-inferiority in mumps SCRs was therefore not met, although the observed group difference in a post-hoc analysis of anti-mumps antibodies using a plaque reduction neutralization assay was 0.39% with a 95% CI lower limit of -4.03%. Adverse events occurred at comparable frequencies for both groups, except for more frequent fever in MMRV recipients. CONCLUSION: Based on the pre-specified non-inferiority criterion, SCRs of the MMRV vaccine were non-inferior to that elicited by MMR+V vaccines for all antigens except mumps.

Immunogenicity and safety of two tetravalent (measles, mumps, rubella, varicella) vaccines coadministered with hepatitis a and pneumococcal conjugate vaccines to children twelve to fourteen months of age.

BACKGROUND: This study compared single-dose tetravalent measles, mumps, rubella, varicella vaccine, Priorix-Tetra, stored refrigerated (GSK+4C) or frozen (GSK-20C), with ProQuad (Merck-20C), when coadministered with hepatitis A vaccine (HAV) and 7-valent pneumococcal conjugate vaccine (PCV7). METHODS: Multicenter, observer-blind phase 2 study in 1783 healthy 12-14 month olds randomized to: GSK+4C (n = 705), GSK-20C (n = 689) or Merck-20C (n = 389), administered concomitantly with HAV (Havrix) and PCV7 (Prevnar). Seroresponse rates and antibody geometric mean concentrations/titers were determined from enzyme-linked immunosorbent assay and neutralization assays. Reactogenicity and safety were assessed. RESULTS: Seroresponse rates (day 42) were >97% for measles and rubella viruses and >92% for mumps virus, in all groups. Noninferiority of both GSK+4C and GSK-20C vaccines versus Merck-20C was demonstrated for seroresponse rates to measles, mumps and rubella viruses (lower 97.5% confidence interval above -5%, -10% and -5%, respectively). For varicella-zoster virus, seroresponse rates were 57.1%, 69.8% and 86.7% in the GSK+4C, GSK-20C and Merck-20C groups, respectively. Noninferiority was not shown for either GSK vaccine (lower 97.5% confidence intervals <-15%). Geometric mean concentration ratios for anti-varicella-zoster virus demonstrated noninferiority (lower 97.5% confidence interval ≥ 0.5) versus Merck-20C for GSK-20C only. Geometric mean concentration ratios for antibodies to HAV and to PCV7 pneumococcal serotypes also met criteria for noninferiority for both GSK groups compared with Merck-20C. GSK vaccine safety was observed comparable to Merck-20C. Localized but not generalized measles/rubella-like rash and grade 3 fever was reported slightly more frequently with GSK vaccines, but antipyretic use was similar. The incidence of subjects experiencing at least 1 serious adverse event was 2.0%, 2.9% and 1.8% in the GSK+4C, GSK-20C and Merck-20C groups, respectively. CONCLUSIONS: Noninferiority of both GSK measles, mumps, rubella, varicella vaccines versus Merck-20C was demonstrated for responses to measles, mumps and rubella viruses but was not fully demonstrated for varicella-zoster virus. The vaccines showed acceptable reactogenicity/safety when coadministered with HAV and PCV7.

Immunogenicity and safety of MMRV and PCV-7 administered concomitantly in healthy children.

OBJECTIVE: We assessed the immunogenicity and safety of a combination measles, mump, rubella, and varicella vaccine (MMRV) (ProQuad [Merck & Co, Inc, West Point, PA]) administered to healthy children concomitantly with a pneumococcal 7-valent conjugate vaccine (PCV-7) (Prevnar [Pfizer, Philadelphia, PA]). PATIENTS AND METHODS: Healthy 12- to 15-month-old children who lacked vaccination and clinical histories for measles, mumps, rubella, varicella, and zoster but had written documentation of receipt of a 3-dose primary series of PCV-7 were randomly assigned in a 2:1:1 ratio to receive either the MMRV and PCV-7 (group 1), PCV-7 followed 6 weeks later by MMRV (group 2), or MMRV followed 6 weeks later by PCV-7 (group 3). The primary safety analysis was 56 days (28 days after each visit). Immunogenicity was evaluated 6 weeks after each vaccination. RESULTS: A total of 1027 children were enrolled (group 1: 510; group 2: 258; group 3: 259). For all 3 groups, the antibody response rate was ≥96.8% for measles, mumps, and rubella, ≥88.0% for varicella-zoster virus, and ≥98.3% for all of the 7 Streptococcus pneumoniae serotypes. The immune responses to all antigens present in MMRV and PCV-7 were similar whether administered concomitantly or sequentially. The incidence of local and systemic adverse experiences (AEs) was comparable between group 1 and groups 2 and 3 combined. No vaccine-related serious AEs were reported. CONCLUSIONS: Concomitant administration of the MMRV and PCV-7 is highly immunogenic and generally well tolerated. Similar immune responses between the groups support concomitant administration of the MMRV and PCV-7 to healthy children 12 to 15 months of age.

Safety and Immunogenicity of the MRKAd5 gag HIV Type 1 Vaccine in a Worldwide Phase 1 Study of Healthy Adults.

The safety and immunogenicity of the MRK adenovirus type 5 (Ad5) HIV-1 clade B gag vaccine was assessed in an international Phase I trial. Three-hundred and sixty healthy HIV-uninfected adults were enrolled on five continents. Subjects received placebo or 1 × 109 or 1 × 1010 viral particles (vp) per dose of the MRKAd5 HIV-1 gag vaccine at day 1, week 4, and week 26. Immunogenicity was evaluated using an IFN-γ ELISPOT gag 15-mer assay with positive responses defined as ≥55 SFC/106 PBMCs and ≥4-fold over mock control. The vaccine was well tolerated. The most common adverse events were injection site reactions, headache, pyrexia, diarrhea, fatigue, and myalgia. At week 30, geometric mean ELISPOT responses were 24, 114, and 226 SFC/106 PBMCs in the placebo, 1 × 109 vp/dose, and 1 × 1010 vp/dose groups, respectively. Overall, responses to 1 × 1010 vp were 85% and 68% in subjects with low (≤200) and high (>200) baseline Ad5 titers, respectively. The MRKAd5 HIV-1 gag vaccine was immunogenic in diverse geographic regions. Gag ELISPOT responses were greater in the 1 × 1010 vp/dose groups than in the 1 × 109 vp/dose groups. Data from this first international study indicate that adenovirus-vectored vaccines are well tolerated and may be immunogenic in subjects from regions with high prevalence of preexisting Ad5 immunity.

Acute human immunodeficiency virus infection in a breast-fed infant in New York City.

Acute human immunodeficiency virus (HIV) infection in a breast-fed infant is a rare diagnosis in developed countries. We present a six-month old girl with postnatally acquired HIV infection complicated by Pneumocystis jéroveci pneumonia, cytomegalovirus pneumonitis and encephalopathy. Her mother had tested negative for HIV during pregnancy. Children infected by mothers during an acute seroconversion may have more rapid disease progression.

Predicting the Onset of Sexual and Drug Risk Behaviors in HIV-Negative Youths with HIV-Positive Mothers: The Role of Contextual, Self-Regulation, and Social-Interaction Factors.

HIV-negative, inner-city adolescents with HIV-infected parents are considered to be at high risk for acquiring HIV themselves. Using a modified theory of health behavior, this study examined the effects of maternal HIV infection and psychosocial variables on the onset of sexual and drug risk behavior in 144 HIV-negative adolescents with and without HIV-positive mothers. Adolescents and their mothers were interviewed when the youths were 10-14 years old and again when they were 13-19 years old. By follow-up, 42% of youths reported the onset of vaginal sex (vs 5% at baseline). Marijuana and alcohol use increased from 6 and 38%, respectively, at baseline to 25 and 60% at follow-up. Among those reporting risk behaviors, 40--50% reported onset prior to 14 years. Youth and family psychosocial variables, but not maternal HIV status, were associated with risk behaviour outcomes.

Cerebral abscess associated with meningococcal meningitis.

Purulent fluid collections, including brain abscess and subdural empyema, are exceedingly rare in association with meningococcal meningitis. We present a 5-month-old infant with meningococcal meningitis and sepsis complicated by an intracerebral abscess.

Nontuberculous mycobacterial infections in pediatric hematopoietic stem cell transplant recipients: case report and review of the literature.

Nontuberculous mycobacterial (NTM) infections are rarely diagnosed in hematopoietic stem cell transplant (HSCT) recipients. We describe a case of disseminated Mycobacterium avium complex with gastrointestinal tract involvement in a HSCT recipient. We reviewed NTM infections among pediatric HSCT patients at our institution from 2000-2004 and identified 2 additional cases. Fourteen published case reports of NTM disease in children are reviewed.

HIV treatment-related knowledge and self-efficacy among caregivers of HIV-infected children.

OBJECTIVE: Improvements in treatment-related knowledge and self-efficacy may improve clinical outcomes in HIV-infected populations. We examined whether caregivers' knowledge and self-efficacy was associated with better clinical outcomes and anti-retroviral therapy (ART) adherence among HIV-infected children. METHODS: Caregivers of 77 perinatally HIV-infected children were administered a semi-structured interview which included scales of HIV treatment-related knowledge, adherence self-efficacy and caregiver reports of child medication adherence. RESULTS: While caregivers correctly answered 74% of the knowledge questions, specific misconceptions were noted. Caregivers rated themselves as having high adherence self-efficacy, but were least confident in their ability to adhere to ART if it caused side effects or might result in social disclosure. Higher caregiver treatment-related knowledge and self-efficacy were associated with better clinical outcomes, as measured by viral load and CD4+ count, but not with caregiver reports of ART adherence. CONCLUSION/DISCUSSION: While additional factors may be important determinants of adherence to ART in this population, improving the HIV treatment-related knowledge and self-efficacy of caregivers may help to improve the clinical outcomes of HIV-infected children. PRACTICE IMPLICATIONS: Care providers should address both misconceptions that might serve to undermine adherence as well as factors that limit patients' self-efficacy in adhering to treatment, prior to the initiation of ART and throughout the course of treatment.