Comparison of vaccination with measles-mumps-rubella vaccine at 9, 12, and 15 months of age

To determine seroconversion rates with measles-mumps-rubella vaccine administered to children at 9, 12, or 15 months of age, we undertook a prospective randomized trial. Among children vaccinated at 15 months of age, 98% seroconverted to measles, compared with 95% of those vaccinated at 12 months of age and 87% of those vaccinated at 9 months of age. In each age group, children of mothers born in or before 1963 had lower rates of seroconversion against measles, with the lowest rate in children vaccinated at 9 months. The seroconversion rate of rubella paralleled that of measles, with the lowest seroconversion rates in children vaccinated at 9 months of age whose mothers were born in or before 1963. The response to mumps varied little by age of the child or birth year of the child's mother. These results support the recommended age for first vaccination with measles-mumps-rubella at 12-15 months.     

A high incidence of asthma and respiratory symptoms in 4-11 year old children.

A study assessing the prevalence of respiratory symptoms in two primary schools in Birmingham, U.K. was performed. A questionnaire was delivered to pupils in both schools after which three open days were conducted in one of the schools, where probable asthmatics were identified and referred to their General Practitioner, Chest Clinic or a school asthma clinic. In this school 49% of responders and 52.9% in the control school were symptomless on questionnaire: 31% and 20.8%, respectively, had probable asthma, falling to 20% and 15.5% if a positive response to the question on recent recurrent wheeze was disregarded as indicating asthma. Using the total population as a denominator, the overall asthma prevalence was 20% which is significantly higher compared to previous English rates. Forty-two were seen at the Chest Clinic, 14 being followed for more than two visits. None were on regular anti-asthma treatment initially; 12/14 were taking prophylactic treatment on follow-up. In the two schools, 10.0% and 14.2% of responders were 'chesty' with 'colds' having no other typical asthmatic symptoms: these children should be studied further. This high incidence of respiratory symptoms in primary school children could represent a national trend or just a local increase.     

Immunogenicity and reactogenicity of a single dose of live attenuated varicella vaccine and a booster dose of measles-mumps-rubella vaccine given concomitantly at 12 years of age

Universal varicella-zoster virus (VZV) childhood vaccination is still debated, but adult chickenpox may be severe. It could be prevented by vaccination of seronegative adolescents. This study aimed to determine the feasibility of coadministration of a VZV vaccine and the measles-mumps-rubella (MMR) booster at 12 y of age. Guardians of 1231 12-y-old pupils where asked about the history of chickenpox in their children. 190 had no chickenpox history and 12 of 62 of them lacked VZV antibodies. Additional history-negative children were also recruited. 199 history-positive children received only MMR and 98 history-negative children received an MMR vaccine and a VZV vaccine. Serum samples were drawn before vaccination and after 8 weeks. Viral antibodies were measured by immunofluorescence (VZV) and enzyme-linked immunosorbent assays (VZV, MMR). All 184 history-positive children tested had VZV antibodies. 17/89 VZV-vaccinated and tested children (19%) lacked VZV antibodies before vaccination. 12 (71%) seroconverted after 1 dose. Cell-mediated immunity (CMI) against varicella was tested in 3/5 children who did not seroconvert after 1 dose of VZV vaccine. They seroconverted after a second dose and had measurable CMI. VZV vaccination did not affect the MMR response and there were no severe side-effects. A history of varicella infection, as reported by the guardian, is reliable, but a negative history was incorrect in 81% of the cases. This population of 12-y-old children may require 2 doses of VZV vaccine, at least when given simultaneously with the MMR vaccine.     

A randomized comparative trial in order to assess the reactogenicity and immunogenicity of a new measles mumps rubella (MMR) vaccine when given as a first dose at 12-24 months of age

An open, randomized multi-center trial, involving 700 infants, was conducted in order to compare a new measles mumps rubella (MMR) vaccine, SB MMR (containing a Jeryl Lynn derived mumps strain RIT 4385) with a widely used vaccine, Merck MMR, when given to children between 12-24 months. Infants were divided between 2 groups; group 1 received SB MMR while group 2 received Merck MMR. Solicited local and general symptoms were recorded using diary cards and antibody levels were measured using ELISA assays. There was a significantly lower incidence of redness (p < 0.001) and swelling (p = 0.03) observed in group 1 compared with group 2. The incidence of all other solicited local and general symptoms were comparable between groups. In initially seronegative subjects equivalent seroconversion rates and post-vaccination GMTs were observed between groups. In conclusion, these results demonstrate that SB MMR is safe and well tolerated when given to children at this age range, and has an equivalent immunogenic profile compared to the widely used Merck MMR vaccine.     

Phase 2 evaluation of parainfluenza type 3 cold passage mutant 45 live attenuated vaccine in healthy children 6-18 months old

A phase 2 evaluation of live attenuated parainfluenza type 3 (PIV3)-cold passage mutant 45 (cp45) vaccine was conducted in 380 children 6-18 months old; 226 children (59%) were seronegative for PIV3. Of the 226 seronegative children, 114 received PIV3-cp45 vaccine, and 112 received placebo. No significant difference in the occurrence of adverse events (i.e., runny nose, cough, or temperature > or =38 degrees C) was noted during the 14 days after vaccination. There was no difference between groups in the occurrence of acute otitis media or serous otitis media. Paired serum samples were available for 109 of the seronegative vaccine recipients and for 110 of the seronegative placebo recipients; 84% of seronegative vaccine recipients developed a > or =4-fold increase in antibody titers. The geometric mean antibody titer after vaccination was 1 : 25 in the vaccine group and <1 : 4 in the placebo group. PIV3-cp45 vaccine was safe and immunogenic in seronegative children and should be evaluated for efficacy in a phase 3 field trial.     

Excellent booster response 4-6 y after a single primary dose of an inactivated hepatitis A vaccine

We studied the immune response of an inactivated hepatitis A vaccine (Havrix 1440) given to middle-aged travellers 4-6 y after a single, primary dose. Anti-HAV antibodies in serum were checked before and 28-35 d after the booster. All 25 vaccinees showed an impressive anamnestic booster response (geometric mean titres 32 and 2993 mIU/ml before and after the booster, respectively). The study confirms experimental data indicating that I dose of inactivated hepatitis A vaccine induces a long-term proliferative T-cell response in addition to producing anti-HAV antibody. As recall memory for this vaccine is elicited several years after a single dose there is probably no need for a second vaccine dose.     

Norms and clinical correlates of echocardiographic left ventricular mass in 3-12 year old children.

To determine norms for left ventricular mass (LVM) and correlate it with various demographic and clinical parameters 213 school children were examined using two dimensional echocardiography. The data of 183 children (108 boys, 75 girls) where no cardiovascular abnormality was found has been analysed. The mean age +/- SEM was 6.79 +/- 0.15 years. The mean LVM was 40.47 +/- 1.12 gm (40.05 +/- 1.45 gm in males; 41.06 +/- 1.79 gm in females; p greater than 0.6). Mean LVM index (grams/metre height) was 34.30 +/- 0.80 (male = 33.46 +/- 1.06; female = 35.45 +/- 1.22; p = 0.9). On univariate analysis, a significant positive correlation of LVM with age, (r = 0.57), height (r = 0.57), weight (r = 0.58) and chest size (r = 0.23) was observed. No correlation was seen with resting pulse rate, or with systolic and diastolic blood pressure.     

Immunogenicity and reactogenicity of combined versus separately administered DTPw-HBV and Hib vaccines given to healthy infants at 2, 4 and 6 months of age, with a booster at 18 months.

OBJECTIVES: To determine the immunogenicity and reactogenicity of a combined DTPw-HBV/Hib vaccine, in comparison with DTPw-HBV and Hib vaccines given as separate concomitant injections. METHODS: In an open, randomized study, healthy infants were injected with either DTPw-HBV/Hib vaccine or separate DTPw-HBV and Hib vaccines at 2, 4 and 6 months of age, with a booster at 18 months. RESULTS: Both vaccination regimens were immunogenic, with seropositivity rates of 100% after the booster vaccination for all vaccine components. Even as early as 2 months after the second dose of the primary vaccination, most patients had seroprotective antibody titers, the proportion of seropositive subjects approaching 100% for tetanus, hepatitis B, and Hib. Post-primary and post-booster geometric mean titers (GMTs) were well above seroprotective thresholds for each vaccine antigen in both groups, with no clinically relevant differences in the groups. The separate and combined administrations showed comparable reactogenicity profiles, and neither showed a significant increase in reactogenicity with successive doses. CONCLUSIONS: The results of this study support the combination of Hib and DTPw-HBV vaccination in routine infant immunization at 2, 4 and 6 months of age with a booster at 18 months. Maximum benefit is obtained from compliance with the full course, but substantial benefit is likely to be achieved even in partially compliant patients, provided they receive at least two doses. Furthermore, these results demonstrate the tolerability of a fourth (booster) administration, where the addition of the Hib vaccine to DTPw-HBV did not lead to an increase in the overall reactogenicity.     

Evaluation of the immune response to a 2-dose measles vaccination schedule administered at 6 and 9 months of age to HIV-infected and HIV-uninfected children in Malawi

BACKGROUND: The World Health Organization recommends that infants at high risk for developing measles before 9 months of age, including human immunodeficiency virus (HIV)-infected infants, receive measles vaccination (MV) at 6 and 9 months of age. METHODS: Children born to HIV-infected mothers received MV at 6 and 9 months, and children of HIV-uninfected mothers were randomized to receive MV at 6 and 9 months, MV at 9 months, or routine MV without follow-up. Blood samples were obtained before and 3 months after each MV. Data were collected on adverse events for 21 days after each MV, at all clinic visits, on any hospitalization, and for subjects who died. HIV-infection status was determined by antibody assays and polymerase chain reaction; the presence of measles IgG was determined by EIA. RESULTS: Twenty-two hundred mother-infant pairs were enrolled. After the first and second doses of measles vaccine, respectively, the percentages of children who were measles seropositive were 59% (36 of 61) and 64% (29 of 45) among HIV-infected children, 68% (152 of 223) and 94% (189 of 202) among HIV-exposed but uninfected children, and 62% (288 of 467) and 92% (385 of 417) among HIV-unexposed children. Of 521 HIV-unexposed children vaccinated only at 9 months, 398 (76%) were measles seropositive at 12 months. No serious vaccine-related adverse events were identified. CONCLUSIONS: An early, 2-dose MV schedule was immunogenic, but a higher proportion of HIV-infected children remained susceptible to measles, compared with HIV-uninfected children (whether HIV exposed or HIV unexposed).     

Immunogenicity and safety of a varicella vaccine (Okavax) and a trivalent measles, mumps, and rubella vaccine (Trimovax) administered concomitantly in healthy Filipino children 12-24 months old

The immunogenicity and safety of Okavax trade mark varicella vaccine, when administered concomitantly with Trimovax trade mark measles, mumps, and rubella (MMR) vaccine, were assessed in 300 Filipino children 12-24 months old. Three groups received Okavax only, Trimovax only, or both vaccines concomitantly. In sera obtained six weeks after vaccination, high varicella antibody geometric mean titers (GMTs) (115 and 79.8 mIU/mL, respectively) and seroconversion rates (>or= 91.9%) were similar for Okavax given alone or concomitantly with Trimovax. High MMR GMTs and seroconversion rates (mumps >or= 94.6%, measles and rubella >or= 98.6%) were not affected by concomitant administration of Trimovax with Okavax. Solicited local and systemic reactions recorded by parents were slightly more numerous after concomitant administration, but the majority of all reactions were mild and transient. The good tolerance and high immunogenicity observed supports the concomitant administration of Okavax and Trimovax to children in their second year of life to protect against four life-threatening diseases while simplifying childhood immunization programs.     

Induction of cellular and humoral immunity after aerosol or subcutaneous administration of Edmonston-Zagreb measles vaccine as a primary dose to 12-month-old children

Infants were immunized by aerosol (10(3.6) plaque-forming units [pfu]/dose) or subcutaneous (sc) (10(4.27) pfu/dose) administration of Edmonston-Zagreb measles vaccine. Measles-specific T cell proliferative responses with a stimulation index of > or =3 developed in 72% of children given aerosol-administered vaccine, compared with 87% given s.c.-administered vaccine (P =.06). Seroconversion rates were 90% after aerosol-administered vaccine and 100% after s.c.-administered vaccine (P=.01), and measles geometric mean titers were 237 milli-international units (mIU) (95% confidence interval [CI], 146-385 mIU) and 487 mIU (95% CI, 390-609 mIU) in each group, respectively (P=.01). Measles-specific T and B cell responses were weaker after aerosol than after sc vaccination, indicating a need to use a higher aerosol dose to achieve optimal immunogenicity.     

Evaluation of the immunogenicity and reactogenicity of a DTPa-HBV-IPV Combination vaccine co-administered with a Hib conjugate vaccine either as a single injection of a hexavalent combination or as two separate injections at 3, 5 and 11 months of age

A combined DTPa-HBV-IPV/Hib vaccine containing diphtheria (D), tetanus (T), acellular pertussis (Pa), hepatitis B (HBV) and types 1, 2 and 3 inactivated polioviruses (IPV) extemporaneously mixed with a conjugated Haemophilus influenzae type b (Hib) vaccine (Group 1) was compared to the DTPa-HBV-IPV and Hib vaccines (Group 2) administered separately at 3, 5 and 11 months of age (n = 440). A microneutralization assay was used to detect antibodies against the 3 polio virus types (cut-off 1:8 dil), RIA for anti-HBs antibodies (cut-off 10 mIU/ml) and ELISA for antibodies against all other vaccine antigens (cut-off: 0.1 IU/ml for anti-tetanus and anti-diphtheria antibodies; 5 El.U/ml for antibodies against each of the 3 acellular pertussis antigens and 0.15 microg/ml for anti-PRP antibodies). Similar immune responses were observed in both groups 1 month after dose 2 as well as after dose 3. Six months after dose 2 however, the proportion of subjects maintaining an anti-tetanus antibody concentration > or = 0.1 IU/ml was lower in Group 2 and a slight group difference in favour of Group 1 was also observed for anti-PRP, anti-diphtheria and anti-polio type 1 antibody persistence prior to the third dose. The overall incidence of local and general solicited symptoms was similar in both groups. One subject discontinued study vaccination following an SAE considered to be related to vaccination. The DTPa-HBV-IPV/Hib combined vaccine is immunogenic and well tolerated when administered according to a 3, 5 and 11 month vaccination schedule and can therefore be considered as a feasible alternative to the separate administration of the pentavalent DTPa-HBV-IPV and the monovalent Hib vaccines.     

Effect of intrauterine growth restriction on blood pressure, glucose tolerance and sympathetic nervous system activity in the rat at 3-4 months of age.

OBJECTIVE: Epidemiological studies suggest that intrauterine growth restriction (IUGR) due to maternal undernutrition during pregnancy represents a major risk factor for hypertension and diabetes in adult age. However, placental insufficiency, rather than maternal malnutrition, is the main cause of IUGR in the Western world. We therefore studied the relationship between birth weight and adult blood pressure and glucose tolerance in an established animal model of placental insufficiency. DESIGN: IUGR was induced by uterine artery ligation in pregnant rats and the offspring were studied at 3-4 months of age. METHODS: In one subgroup of animals (n = 41, birth weight range 3.2-6.6 g) blood pressure was recorded over 72 h using telemetry and hypothalamic tissue levels of noradrenaline was measured. In another subgroup (n = 30, birth weight range 3.0-6.8 g) the activity of the sympathetic nervous system (SNS) was assessed by noradrenaline isotope dilution techniques and glucose tolerance determined by an intravenous glucose load. RESULTS: Adult blood pressure was independent of birth weight Haemodynamic responses of IUGR rats to moderate sound stress was unaltered. In male rats neither SNS activity, hypothalamic noradrenaline concentrations nor glucose tolerance was associated with birth weight In contrast, IUGR in female rats was associated with increased SNS activity, elevated fasting blood glucose as well as lower insulin and higher glucose levels in response to a glucose load. CONCLUSION: IUGR is not linked to an elevated blood pressure at 3-4 months of age in this model. However, in female rats, IUGR is associated with increased SNS activity and impaired glucose tolerance in adult life.     

Protection against severe COVID-19 after second booster dose of adapted bivalent (original/Omicron BA.4-5) mRNA vaccine in persons ≥ 60 years,by time since infection,Italy, 12 September to 11 December 2022

Effectiveness against severe COVID-19 of a second booster dose of the bivalent (original/BA.4–5) mRNA vaccine 7–90 days post-administration, relative to a first booster dose of an mRNA vaccine received ≥ 120 days earlier, was ca 60% both in persons ≥ 60 years never infected and in those infected > 6 months before. Relative effectiveness in those infected 4–6 months earlier indicated no significant additional protection (10%; 95% CI: −44 to 44). A second booster vaccination 6 months after the latest infection may be warranted.     

A phase IV open label study to assess the safety, tolerability and immunogenicity of a Haemophilus influenzae type B (Hib) CRM197 conjugated vaccine administered to healthy infants at 2, 4, and 6 months of age

The objective of this prospective clinical study was to evaluate the safety, tolerability and immunogenicity of Chiron Hib vaccine (Vaxem Hib) in Thai infants. This trial was conducted at Bhumibol Adulyadej Hospital, Bangkok, Thailand from June to November 1999. Three intramuscular injections of the vaccine were given to 119 infants at 2, 4 and 6 months of age. Reactions and adverse events after the vaccination were recorded. Blood samples for anti-PRP antibody were collected before the first immunization, and after the second and third immunizations. After the second dose, 91% and 58% of the subjects had anti-PRP antibody titers of > or =0.15 microg/ml and > or =1.0 microg/ml, respectively. After the third dose, 99% and 90% of the subjects had anti-PRP antibody titer > or =0.15 mcirog/ ml and > or =1.0 microg/ml, respectively. Local and systemic reactions were mild and transient. The study indicates that Vaxem Hib vaccine is safe and well tolerated. Three doses of the vaccine are necessary to achieve adequate protection in infants.     

Long QT syndrome due to a novel mutation in SCN5A: treatment with ICD placement at 1?month and left cardiac sympathetic denervation at 3?months of age

We describe the case of a newborn with congenital long QT syndrome, with 2:1 AV block and frequent episodes of Torsades de Pointes (TdP) requiring placement of a dual chamber ICD at 33 days and 3.63 kg, the youngest and smallest patient, thus far reported. Long QT syndrome was diagnosed due to bradycardia in the newborn nursery, with frequent episodes of TdP. The patient was initially treated with magnesium and esmolol then given lidocaine which resulted in dramatic transient normalization of the QTc with 1:1 AV nodal conduction. An attempt to transition to oral sodium channel and beta blockade was unsuccessful. An ICD was placed and dual chamber pacing was initiated which facilitated the transition to an oral medical regimen and ultimate discharge from the hospital. Soon after placement of the ICD, genetic testing revealed a novel F1473C mutation in the SCN5A gene. Episodes of TdP continued and left stellate gangliectomy was performed at 3 months of age. At 30 months follow-up, the patient has occasional, self-limited episodes of TdP and has received rare, successful, and appropriate ICD shocks.     

Ethanol enhances alpha 4 beta 3 delta and alpha 6 beta 3 delta gamma-aminobutyric acid type A receptors at low concentrations known to affect humans

gamma-Aminobutyric acid type A receptors (GABARs) have long been implicated in mediating ethanol (EtOH) actions, but so far most of the reported recombinant GABAR combinations have shown EtOH responses only at fairly high concentrations (> or = 60 mM). We show that GABARs containing the delta-subunit, which are highly sensitive to gamma-aminobutyric acid, slowly inactivating, and thought to be located outside of synapses, are enhanced by EtOH at concentrations that are reached with moderate, social EtOH consumption. Reproducible ethanol enhancements occur at 3 mM, a concentration six times lower than the legal blood-alcohol intoxication (driving) limit in most states (0.08% wt/vol or 17.4 mM). GABARs responsive to these low EtOH concentrations require the GABAR delta-subunit, which is thought to be associated exclusively with alpha 4- and alpha 6-subunits in vivo, and the beta 3-subunit, which has recently been shown to be essential for the in vivo anesthetic actions of etomidate and propofol. GABARs containing beta 2-instead of beta 3-subunits in alpha 4 beta delta- and alpha 6 beta delta-receptor combinations are almost 10 times less sensitive to EtOH, with threshold enhancement at 30 mM. GABARs containing gamma 2-instead of delta-subunits with alpha 4 beta and alpha 6 beta are three times less sensitive to EtOH, with threshold responses at 100 mM, a concentration not usually reached with social EtOH consumption. These combined findings suggest that "extrasynaptic" delta-subunit-containing GABARs, but not their "synaptic" gamma-subunit-containing counterparts, are primary targets for EtOH.