Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life

Rotavirus gastroenteritis is one of the leading causes of diarrhea in Indian children less than 2 years of age. The 116E rotavirus strain was developed as part of the Indo-US Vaccine Action Program and has undergone efficacy trials. This paper reports the efficacy and additional safety data in children up to 2 years of age. In a double-blind placebo controlled multicenter trial, 6799 infants aged 6-7 weeks were randomized to receive three doses of an oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6, 10, and 14 weeks. The primary outcome was severe (≥11 on the Vesikari scale) rotavirus gastroenteritis. Efficacy outcomes and adverse events were ascertained through active surveillance. We randomly assigned 4532 and 2267 subjects to receive vaccine and placebo, respectively, with over 96% subjects receiving all three doses of the vaccine or placebo. The per protocol analyses included 4354 subjects in the vaccine and 2187 subjects in the placebo group. The overall incidence of severe RVGE per 100 person years was 1.3 in the vaccine group and 2.9 in the placebo recipients. Vaccine efficacy against severe rotavirus gastroenteritis in children up to 2 years of age was 55.1% (95% CI 39.9 to 66.4; p<0.0001); vaccine efficacy in the second year of life of 48.9% (95% CI 17.4 to 68.4; p=0.0056) was only marginally less than in the first year of life [56.3% (95% CI 36.7 to 69.9; p<0.0001)]. The number of infants needed to be immunized to prevent one episode of severe RVGE in the first 2 years of life was 40 (95% CI 28.0 to 63.0) and for RVGE of any severity, it was 21 (95% CI 16.0 to 32.0). Serious adverse events were observed at the same rates in the two groups. None of the eight intussusception events occurred within 30 days of a vaccine dose and all were reported only after the third dose. The sustained efficacy of the 116E in the second year of life is reassuring

Compliance of mothers following recommendations to breastfeed or withhold breast milk during rotavirus vaccination in North India: A randomized clinical trial

Background: Neutralizing antibodies in breast milk may adversely influence the immune response to live oral vaccines. Withholding breastfeeding around the time of vaccine administration has been suggested for improving vaccine performance. However, we do not know whether mothers find withholding breastfeeding around the time of vaccination acceptable and how they perceive this recommendation. Methods: In a clinical study designed to examine predictors of poor immune response to rotavirus vaccine in infants in India, Rotarix® was administered to infants at 6 and 10 weeks with other childhood vaccines. For the study, 400 mother–infant pairs were randomized into two groups in a 1:1 ratio. Mothers were either recommended to withhold breastfeeding or were encouraged to breastfeed half an hour before and after administration of Rotarix®. The mother–infant pairs were observed and the breastfeeding intervals were recorded during this period. Mothers were administered a questionnaire about their perception of the intervention after the infants received the second dose of Rotarix®. Results: Almost 98% (391/400) of the infants received both doses of Rotarix®. Adherence to the recommendations was high in both groups. All mothers in the group who were asked to withhold breastfeeding did so, except one who breastfed her infant before the recommended time after the first dose of Rotarix®. Of the mothers, 4% (7/195) reported that the recommendation to withhold breastfeeding was difficult to follow. All mothers in this group reported that they would withhold breastfeeding at the time of vaccination if they were asked to by a health-care provider. Only one mother responded that withholding breastfeeding would be a reason for not giving rotavirus vaccine to her infant. Conclusions: Withholding breastfeeding half an hour before and after vaccination appears to be acceptable to mothers in this setting. If withholding breastfeeding produces an improvement in the performance of the vaccine, it could be used to increase the public health impact of rotavirus immunization

Effect of withholding breastfeeding on the immune response to a live oral rotavirus vaccine in North Indian infants

Interference from transplacental and breast milk antibodies may impede the performance of oral livevaccines. The effect of breastfeeding on the immunogenicity of Rotarix®, a two-dose oral monova-lent rotavirus vaccine, was examined in a community-based trial in New Delhi, India. Four hundredmother–infant pairs were randomized into two equal groups. Infants were aged 6–7 weeks at enroll-ment. Mothers were encouraged to either breastfeed or to withhold breastfeeding during the 30 minprior to and after each vaccine dose was administered. We collected blood specimens from infants atenrollment and 4 weeks after the second vaccine dose. Blood and breast milk specimens were obtainedfrom mothers at baseline and breast milk specimens were collected at the time of the second vaccinedose. Seroconversion was defined as infant serum anti-VP6 IgA antibody level of ≥20 IU/mL 4 weeksafter the second vaccine dose and a ≥4-fold rise from baseline. There was no difference in the propor-tion who seroconverted between the two groups (26% vs 27%; p = 0.92). The levels of infant serum IgA,maternal serum and breast milk IgA and IgG anti-rotavirus antibodies predicted the anti-rotavirus IgAlevel in infants at end-study and explained approximately 10% of the variability of the immune response(r2= 0.10, p < 0.001). In this population, the immune response to Rotarix®was not enhanced by withholding breastfeedingaround the time of vaccination. Maternal anti-rotavirus antibodies explained little of the variability in theimmune response to the vaccine. Factors other than maternal anti-rotavirus antibodies probably explainwhy infants in low-and middle-income settings respond poorly to live oral rotavirus vaccines

Comparison of Presentation and Prognosis of Takayasu Arteritis with or without Stroke or Transient Ischemic Attack—A Retrospective Cohort Study

Takayasu arteritis (TAK) could cause a stroke or transient ischemic attack (TIA) in young individuals due to inflammatory vascular occlusion or intracerebral hemorrhage. We compared the clinical presentation, angiographic features, longitudinal patterns of disease activity, medical treatments, and survival in 34 TAK patients with stroke/TIA and 157 without stroke/TIA from a single-center retrospective cohort. TAK patients with stroke/TIA were older (p = 0.044) with a greater proportion of males (p = 0.022), more frequent vision loss (odds ratio (OR) for stroke/TIA vs. without stroke TIA 5.21, 95% CI 1.42–19.14), and less frequent pulse or blood pressure inequality (OR 0.43, 95% CI 0.19–0.96) than TAK patients without stroke/TIA. Hata’s angiographic type IIa was more common in TAK patients with stroke/TIA (OR 11.00, 95%CI 2.60–46.58) and type V in TAK patients without stroke/TIA (OR 0.27, 95% CI 0.12–0.58). Cyclophosphamide was used more often in TAK patients with stroke/TIA (p = 0.018). Disease activity at baseline, 6, 12, and 24 months of follow-up was mostly similar for both groups. Risk of mortality was similar in TAK patients with or without stroke/TIA (hazard ratio unadjusted 0.76, 95% CI 0.15–3.99; adjusted for gender, age of disease onset, delay to diagnosis, baseline disease activity, and the number of conventional or biologic/targeted synthetic immunosuppressants used 1.38, 95% CI 0.19–10.20) even after propensity score-matched analyses. Stroke or TIA does not appear to affect survival in TAK patients adversely

Impact of Geographic Location on Diagnosis and Initial Management of Takayasu Arteritis: A Tale of Two Cohorts from Italy and India

The present study compares disease characteristics, imaging modalities used, and patterns of treatment in two large cohorts of Takayasu arteritis (TAK) from Italy and India. Clinic files were retrospectively reviewed to retrieve information about initial choices of vascular imaging and immunosuppressive therapies. Unpaired t-tests compared means, and proportions were compared using Fisher&rsquo;s exact test or Chi square test [Odds ratios (OR) with 95% confidence intervals (95%CI) calculated where appropriate]. The cohorts comprised 318 patients [Italy (n = 127), India (n = 191)] with similar delays to diagnosis. Ultrasound (OR Italy vs. India 9.25, 95%CI 5.02&ndash;17.07) was more frequently used in Italy and CT angiography in India (OR 0.32, 95%CI 0.20&ndash;0.51). Corticosteroid use was more prevalent and for longer duration in Italy. TAK from Italy had been more often treated with methotrexate, leflunomide or azathioprine, as opposed to tacrolimus in TAK from India (p &lt; 0.05). Biologic or targeted synthetic disease-modifying agents were almost exclusively used in Italy. Survival on first immunosuppressive agent was longer from Italy than from India (log rank test p value 0.041). Considerable differences in the choice of initial vascular imaging modality and therapies for TAK from Italy and India could relate to prevalent socio-economic disparities. These should be considered while developing treatment recommendations for TAK