Heterogeneity and Hierarchy of Immune Response to Primary Immunization in HIV-Infected Children on HAART and the Impact of an Additional Dose of Vaccine.

The nature of vaccine response inferiority is not well studied in children living with HIV (CLHIV). The authors investigated Hepatitis B Virus (HBV) and Diphtheria/Pertussis/Tetanus toxoid (DPT) vaccination responses following primary immunization in CLHIV (n = 42) and healthy controls (HC) (n = 38) and the effect of an additional vaccine dose. Antibody responses, CD4 and HBV-specific T/B cells were analysed using CMIA/ELISA and flow-cytometry. CLHIV had significantly lower baseline median antibody titres for all vaccines than HC (p <0.02). Differential seroprotection rates observed in CLHIV were, 4.8% for pertussis; 9.5% for HBV; 26.2% for diphtheria and 66.7% for tetanus. WHO staging significantly influenced anti-HBs levels (p = 0.0095). HBsAg-specific CD4+T-cells were significantly higher in CLHIV than HC (p = 0.042). An additional vaccine dose (HBV and Tdap) conferred a higher protection rate for tetanus and diphtheria (p <0.040) in CLHIV. These findings suggest that CLHIV exhibit a hierarchy of vaccine responses affecting antibody levels and protection rate, which was rescued by administering additional vaccine dose.

Stories to Take the Edge Off Pain During Immunization for Preschoolers: A Randomized Controlled Trial.

IMPORTANCE: Fear and distress during immunization may lead to long-term preprocedural anxiety and nonadherence to immunization schedules. Pictorial stories provide a way of educating the parent and child about the procedure. OBJECTIVE: To determine the efficacy of pictorial stories in reducing pain perception among children and anxiety among mothers during immunization. DESIGN: Three-arm randomized controlled trial Setting: Immunization clinic of a tertiary care hospital in South India. PARTICIPANTS: Fifty children ages 5 to 6 yr, who reported to the hospital for measles, mumps, and rubella and typhoid conjugate virus vaccines. Inclusion criteria were that the child was accompanied by the mother and maternal knowledge of either Tamil or English. Exclusion criteria were child hospitalization in the past year or neonatal intensive care unit admission in the neonatal period. INTERVENTION: Pictorial story regarding immunization before the procedure that contained information related to immunization, coping strategies, and distraction techniques. OUTCOMES AND MEASURES: Pain perception was evaluated using the Sound, Eye, Motor Scale; the Observation Scale of Behavioral Distress; and the Wong-Baker FACES Pain Rating Scale (FACES). Maternal anxiety was measured using the General Anxiety-Visual Analog Scale. RESULTS: Of 50 children recruited, 17 were in the control group, 15 were in the placebo group, and 18 were in the intervention group. Children in the intervention group reported lower pain scores on the FACES (p = .04) compared with the placebo and control groups. CONCLUSIONS AND RELEVANCE: A pictorial story is a simple and cost-effective intervention to reduce pain perception among children. What This Article Adds: Pictorial stories may be a feasible, simple, and cost-effective intervention to reduce pain perception during immunization.

Vaccination coverage and the factors influencing routine childhood vaccination uptake among communities experiencing disadvantage in Vellore, southern India: a mixed-methods study.

BACKGROUND: In 2015, the Vellore district in southern India was selected for intensified routine immunization, targeting children from communities experiencing disadvantage such as migrant, tribal, and other hard-to-reach groups. This mixed-methods study was conducted to assess routine immunization coverage and the factors influencing childhood vaccination uptake among these communities in Vellore. METHODS: We conducted a cross-sectional household survey (n = 100) and six focus group discussions (n = 43) among parents of children aged 12-23 months from the known communities experiencing disadvantage in Vellore during 2017 and 2018. Multivariate logistic regression was conducted to examine associations between the parental characteristics and children's vaccination status in the household survey data; the qualitative discussions were analyzed by using the (previously published) "5As" taxonomy for the determinants of vaccine uptake. RESULTS: In the household survey, the proportions of fully vaccinated children were 65% (95% CI: 53-76%) and 77% (95% CI: 58-88%) based on information from vaccination cards or parental recall and vaccination cards alone, respectively. Children whose mothers were wage earners [Adjusted prevalence odds ratio (aPOR): 0.21, 95% CI = 0.07-0.64], or salaried/small business owners [aPOR: 0.18, 95% CI = 0.04-0.73] were less likely to be fully vaccinated than children who had homemakers mothers. In the focus group discussions, parents identified difficulties in accessing routine immunization when travelling for work and showed knowledge gaps regarding the benefits and risks of vaccination, and fears surrounding certain vaccines due to negative news reports and common side-effects following childhood vaccination. CONCLUSIONS: Vaccination coverage among children from the surveyed communities in Vellore was suboptimal. Our findings suggest the need to target children from Narikuravar families and conduct periodic community-based health education campaigns to improve parental awareness about and trust in childhood vaccines among the communities experiencing disadvantage in Vellore.

A phase III randomized, open-label, non-inferiority clinical trial comparing liquid and lyophilized formulations of oral live attenuated human rotavirus vaccine (HRV) in Indian infants.

The human rotavirus vaccine (HRV; Rotarix, GSK) is available as liquid (Liq) and lyophilized (Lyo) formulations, but only Lyo HRV is licensed in India. In this phase III, randomized, open-label trial (NCT02141204), healthy Indian infants aged 6-10 weeks received 2 doses (1 month apart) of either Liq HRV or Lyo HRV. Non-inferiority of Liq HRV compared to Lyo HRV was assessed in terms of geometric mean concentrations (GMCs) of anti-RV immunoglobulin A (IgA), 1-month post-second dose (primary objective). Reactogenicity/safety were also evaluated. Seroconversion was defined as anti-RV IgA antibody concentration ≥20 units [U]/mL in initially seronegative infants (anti-RV IgA antibody concentration <20 U/mL) or ≥2-fold increase compared with pre-vaccination concentration in initially seropositive infants. Of the 451 enrolled infants, 381 (189 in Liq HRV and 192 in Lyo HRV group) were included in the per-protocol set. The GMC ratio (Liq HRV/Lyo HRV) was 0.93 (95% confidence interval [CI]: 0.65-1.34), with the lower limit of the 95% CI reaching ≥0.5, the pre-specified statistical margin for non-inferiority. In the Liq HRV and Lyo HRV groups, 42.9% and 44.3% (baseline) and 71.4% and 73.4% (1-month post-second dose) of infants had anti-RV IgA antibody concentration ≥20 U/mL, and overall seroconversion rates were 54.5% and 50.0%. Incidences of solicited and unsolicited adverse events were similar between groups and no vaccine-related serious adverse events were reported. Liq HRV was non-inferior to Lyo HRV in terms of antibody GMCs and showed similar reactogenicity/safety profiles, supporting the use of Liq HRV in Indian infants.

PLAIN LANGUAGE SUMMARYWhat is the context?Rotavirus is the most common cause of acute gastronenteritis and contributes to the high number of hospitalizations and deaths in young children worldwide.Vaccination against rotavirus has led to a significant decrease in rotavirus-related infections.The human rotavirus vaccine Rotarix (GSK) is currently used as a liquid or lyophilized formulation.In clinical trials conducted in European and North American infants, the liquid vaccine showed ability to induce immune response and safety comparable to the lyophilized formulation.Only the lyophilized vaccine is currently marketed in india.What is new?We compared the 2-dose liquid and lyophilized human rotavirus vaccines in indian infants in a phase III clinical trial:The ability to induce immune response for thw liquid formulation was not inferior to that observed for the lyophilized vaccine.The safety profiles of the 2 formulations were comparable.Why is this important?This study shows that the liquid human rotavirus vaccine can be administrated to infants from india.

Vaccination coverage and factors associated with routine childhood vaccination uptake in rural Vellore, southern India, 2017.

BACKGROUND: Vellore district in southern India was selected for intensified immunization efforts through India's Mission Indradhanush campaign based on 74% coverage in the National Family Health Survey in 2015. As rural households rely almost entirely on the Universal Immunization Program (UIP), we assessed routine immunization coverage and factors associated with vaccination status of children in rural Vellore. METHODS: We conducted a cross-sectional household survey among parents or primary caretakers of children aged 12-23 months during August-September 2017 using two-stage, EPI cluster sampling. We verified vaccination histories from vaccination cards and collected data on sociodemographic and non-socio-demographic characteristics by using mobile data capture. Associations with vaccination status were examined with univariate and multivariate logistic regression models. RESULTS: A total of 643 children were included. Coverage of BCG, third dose pentavalent/DPT, measles/MR vaccines and full vaccination (BCG, three doses of polio and pentavalent/DPT and measles/MR vaccines) among children with vaccination cards (n = 606) was 94%, 96%, 93% and 84%, respectively. Of children with vaccination cards, 70.8% had received all recommended doses according to the UIP schedule. No socio-demographic differences were identified, but parents' familiarity with the schedule (Adjusted Prevalence Odds Ratio (aPOR): 2.06, 95%CI = 1.26-3.38) and receiving information on recommended vaccinations during antenatal visits (aPOR: 2.16, 95% CI = 1.13-4.12) were significantly associated with full vaccination status of the children. CONCLUSIONS: We found higher UIP antigen coverage and proportion of fully vaccinated children than previously reported from rural Vellore. However, adherence to the recommended schedule was still not optimal. Our study highlights the potential of improving parental awareness of vaccination schedule and targeting health education interventions at pregnant women during antenatal visits to sustain and improve routine immunization coverage.

Immunogenicity and safety of an intramuscular split-virion quadrivalent inactivated influenza vaccine in individuals aged ≥ 6 months in India.

A quadrivalent split-virion inactivated influenza vaccine (IIV4; Fluzone® Quadrivalent, Sanofi Pasteur) has been available in the US since 2013 for individuals aged ≥ 6 months. Here, we describe the results of an open-label, multicenter trial (WHO Universal Trial Number U1111-1143-8370) evaluating the immunogenicity and safety of IIV4 in Indian children aged 6-35 months and 3-8 years, adolescents aged 9-17 years, and adults aged ≥ 18 years (n = 100 per group). Post-vaccination hemagglutination inhibition titers for all strains in all age groups were ≥ 8 fold higher than at baseline (range, 8-51). At least 70% of participants in all age groups seroconverted or had a significant increase in titer for each strain. The most common solicited reactions were injection-site pain and tenderness, plus fever in participants 6-23 months and myalgia in older children and adolescents. All injection-site reactions and most systemic reactions were grade 1 or 2 and resolved within 3 days. Only three vaccine-related unsolicited adverse events were reported, all of which were grade 1 or 2 and transient. No immediate adverse events, adverse events leading to study discontinuation, adverse events of special interest, or serious adverse events were reported. This study showed that IIV4 was well tolerated and highly immunogenic in all age groups. This adds important data on the safety, tolerability, and immunogenicity of influenza vaccines in India.

Safety and Immunogenicity of Two Doses of a Quadrivalent Meningococcal Polysaccharide Diphtheria Toxoid Conjugate Vaccine in Indian and Russian Children Aged 9 to 17 Months.

OBJECTIVE: Evaluation of tolerability, safety and immunogenicity of a two-dose series of a quadrivalent meningococcal polysaccharide diptheria toxoid conjugate (ACYW-D) vaccine in Indian and Russian infants/toddlers. DESIGN: Open-label, single-arm, phase III multi-national trial. STUDY PARTICIPANTS: 300 children aged 9-17 months, previously unvaccinated against meningococcal disease from four sites each in India (n=200) and the Russian Federation (n=100). INTERVENTION: Two 0.5 mL doses of ACYW-D by intramuscular injection, 3-6 months apart. MAIN OUTCOME MEASURES: Meningococcal antibody titers to serogroups A, C, W-135 and Y, determined using a serum bactericidal assay in the presence of human complement before vaccination and 28 days after the second vaccination. Titers ≥1:8 against either/all of the A, C, W-135 or Y were considered sero-protective. RESULTS: After dose 2, 95.7-99.5% and 92.9-99.0% of infants/toddlers achieved seroprotection across the four serogroups in India and the Russian Federation, respectively. No immediate adverse events were reported after any dose of ACYW-D. Solicited reactions were reported in 49.2% of participants, and were mainly of Grade 1 severity, and resolved within three days. Unsolicited adverse events were reported in 19.1% of infants: one event (Grade 3 diarrhea, resolving within one day) was considered related to study vaccine. No non-serious adverse events led to premature withdrawal from the study. Four serious adverse events were reported; none were considered related to study vaccine. No deaths occurred during the study. CONCLUSIONS: A two-dose series of ACYW-D vaccine in Indian and Russian children (9-17 month) was well-tolerated with no safety concerns, and induced robust bactericidal antibody responses against the meningococcal serogroups contained in the vaccine.

Direct and Indirect Costs of Pediatric Gastroenteritis in Vellore, India.

OBJECTIVE: To determine costs of pediatric gastroenteritis in out-patient and in-patient facilities. METHODS: Cross-sectional survey of children with acute gastroenteritis attending out-patient clinic (n=30) or admitted in the ward (n=30) for management in the Christian Medical College, Vellore, India from July-September 2014 to estimate direct (drugs, tests, consultation/hospitalization) and indirect (travel, food, lost wages) costs associated with the episode. RESULTS: Median direct and indirect costs were Rs 590 and Rs 190 for out-patient management and Rs 7258 and Rs. 610 for hospitalization, constituting 1.1% and 11% of median annual household income, respectively. CONCLUSIONS: Escalating healthcare costs need tracking for evaluation of interventions.

Immunogenicity of a three dose and five dose oral human rotavirus vaccine (RIX4414) schedule in south Indian infants.

AIM: This study was undertaken to compare the immunogenicity of a three dose and five dose schedule of an oral live-attenuated human rotavirus vaccine, Rotarix in south Indian infants. METHOD: Healthy infants (N=90), six to seven weeks of age were enrolled to receive three doses (n=45) or five doses of Rotarix vaccine (n=45) along with other scheduled vaccines, each dose separated by a four week interval. Blood samples were taken before vaccination and one month post-dose three in the Rotarix three dose group and one month post-dose five in the Rotarix five dose group; all were tested for anti-rotavirus IgA by an antibody sandwich enzyme immunoassay. RESULTS: At baseline, >50% of infants had >20 units of anti-rotavirus IgA. The seroconversion rates after three and five doses were low and not significantly different in the two groups. However, among vaccine responders, children seropositive at baseline showed a much greater absolute increase in IgA antibody levels than children seronegative at baseline. CONCLUSIONS: Rotarix vaccine showed low immunogenicity in south Indian children and increasing the number of doses did not increase the proportion of infants seroconverting after vaccination.