Attitudes toward a future norovirus vaccine among members of an integrated healthcare delivery system in Portland, Oregon, 2016-2017.

With recent advances in U.S. clinical trials for norovirus vaccines, it is an opportune time to examine what is known about the public receptivity to this novel vaccine. From October 2016-September 2017, we surveyed Kaiser Permanente Northwest members in Portland, Oregon, to ask their level of agreement on a 5-point scale with statements about the need for and willingness to get a potential norovirus vaccine for themselves or their child and analyzed their responses according to age, occupational status, prior vaccine uptake, and history of prior norovirus diagnoses. The survey response rate was 13.5% (n = 3,894); 807 (21%) responded as legal guardians, on behalf of a child <18 y of age and 3,087 (79%) were adults aged 18+ y. The majority of respondents were in agreement about getting the norovirus vaccine, if available (60% of legal guardians, 52% of adults aged 18-64 y, and 55% of adults aged 65+ y). Prior vaccination for influenza and rotavirus (among children) was the only correlate significantly associated with more positive attitudes toward receiving norovirus vaccine. Pre-pandemic attitudes in our all-ages study population reveal generally positive attitudes toward willingness to get a norovirus vaccine, particularly among those who previously received influenza or rotavirus vaccines.

Rotavirus Vaccine Impact Within an Integrated Healthcare Delivery System in the United States.

We assessed rotavirus vaccine impact using data on acute gastroenteritis (AGE) encounters within an integrated healthcare delivery system during 2000-2018. Following rotavirus vaccine introduction, all-cause AGE rates among children <5 years declined by 36% (95% confidence interval [CI]: 32%-40%) for outpatient and 54% (95% CI: 46%-60%) for inpatient encounters.

Characteristics of intussusception in the period of arbitrary Rotavirus vaccination.

BACKGROUND: In November 2011, rotavirus (RV) vaccine was launched in Japan as a voluntary vaccination to prevent RV-associated gastroenterocolitis. We examined the characteristics of intussusception following RV vaccination in our two centers. METHODS: We investigated intussusception patients <16 years old from January 2006 to September 2020. Patients were categorized according to the period (before [Group A] or after the introduction of arbitrary RV vaccination [Group B]). The patient characteristics and treatment of intussusception were retrospectively investigated. RESULTS: During the study period, 560 patients (group A, n = 233; group B, n = 327) were identified. The distribution of patients who were 0-6 months old was not significantly different between the groups (group A, n = 12, 5.2%; group B, n = 18, 5.5%). Among these 18 patients in Group B, 7 were vaccinated against RV, and 10 were not. One patient was excluded due to incomplete data. On comparing patients with and without RV vaccination, the mean age at the onset of intussusception was 3.3 ± 0.4 versus 4.0 ± 0.3 months (P = 0.19), the mean interval from the onset to treatment was 7.5 ± 2.4 versus 16.0 ± 2.2 h (P = 0.03), the time of the contrast enema for treatment was 9.1 ± 3.3 versus 7.7 ± 2.8 min (P = 0.76), and the final pressure of the contrast enema was 92.5 ± 4.4 versus 92.2 ± 4.4 cmH2 O (P = 0.97). CONCLUSIONS: Arbitrary RV vaccination did not influence the age distribution of intussusception, and the interval from the onset to treatment was significantly shorter in the patients with RV vaccination than in those without it. Recognizing the presence of intussusception following RV vaccination enables accurate treatment.

Intussusception among infants in Tanzania: findings from prospective hospital-based surveillance, 2013-2016.

INTRODUCTION: intussusception surveillance was initiated in Tanzania in 2013 after monovalent rotavirus vaccine was introduced, as part of the 7-country African evaluation to assess whether the vaccine was associated with an increased risk of intussusception. An increased risk from vaccine was not identified. Published data on intussusception in Tanzanian infants are limited. METHODS: prospective intussusception surveillance was conducted at 7 referral hospitals during 2013-2016 to identify all infants with intussusception meeting Brighton Level 1 criteria. Demographic, household and clinical data were collected by hospital clinicians and analyzed. RESULTS: a total of 207 intussusception cases were identified. The median age of cases was 5.8 months and nearly three-quarters were aged 4-7 months. Median number of days from symptom onset to admission at treatment hospital was 3 (IQR 2-5). Seventy-eight percent (152/195) of cases had been admitted at another hospital before transfer to the treating hospital. Enema reduction was not available; all infants were treated surgically and 55% (114/207) had intestinal resection. The overall case-fatality rate was 30% (62/206). Compared with infants who survived, those who died had longer duration of symptoms before admission to treatment hospital (median 4 vs 3 days; p < 0.01), higher rate of intestinal resection (81% [60/82] vs 44% [64/144], p < 0.001), and from families with lower incomes (i.e., less likely to own a television [p < 0.01] and refrigerator [p < 0.05). CONCLUSION: Tanzanian infants who develop intussusception have a high case-fatality rate. Raising the index of suspicion among healthcare providers, allocating resources to allow wider availability of abdominal ultrasound for earlier diagnosis, and training teams in ultrasound-guided enema reduction techniques used in other African countries could reduce the fatality rate.

Investigating barriers to the protective efficacy provided by rotavirus vaccines in African infants.

Julie Bines discusses an accompanying study by Sheila Isanaka and colleagues on nutrient supplementation and immune responses to rotavirus vaccination.

Immunogenicity of an oral rotavirus vaccine administered with prenatal nutritional support in Niger: A cluster randomized clinical trial.

BACKGROUND: Nutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine. METHODS AND FINDINGS: We nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron-folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6-8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear. CONCLUSIONS: This study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02145000.

Incidence of pediatric inflammatory bowel disease within the Vaccine Safety Datalink network and evaluation of association with rotavirus vaccination.

BACKGROUND: Recent studies have reported an increase in Inflammatory bowel disease (IBD) incidence in young children, highlighting the need to better understand risk factors for the development of IBD. Licensed for use in infants in 2006, the oral, live-attenuated rotavirus vaccine has biologic plausibility for instigating inflammation of the gut mucosa as a pathway to immune dysregulation. METHODS: Over a ten-year period, we evaluated incidence of IBD within a cohort of children under the age of ten, enrolled in seven integrated healthcare delivery systems. We conducted a nested case-control study to evaluate the association between rotavirus vaccination and IBD using conditional logistic regression. Cases were confirmed via medical record review and matched to non-IBD controls on date of birth, sex, and study site. RESULTS: Among 2.4 million children under the age of 10 years, 333 cases of IBD were identified with onset between 2007 and 2016. The crude incidence of IBD increased slightly over the study period (p-value for trend = 0.046). Of the 333 cases, 227 (68%) were born prior to 2007. Forty-two cases born in 2007 or later, with continuous enrollment since birth were included in the case-control study and matched to 210 controls. The adjusted odds ratio for any rotavirus vaccination in IBD cases, compared to matched controls, was 0.72 (95% confidence interval 0.19-2.65). CONCLUSIONS: Data from this large pediatric cohort demonstrate a small overall increase in IBD incidence in young children over a ten-year period. The data suggest that rotavirus vaccination is not associated with development of IBD.

Estudio clínico-epidemiológico de invaginación intestinal en el Hospital Pediátrico Docente Centro Habana, previo a la introducción de la vacuna contra rotavirus / Clinical and epidemiology characterization of intussusception at the Centro Habana Paediatric Hospital before rotavirus vaccine introduction

Contar con datos confiables de la incidencia de la invaginación intestinal en la población infantil cubana es un paso necesario previo a la introducción de la vacuna contra el rotavirus. Con el objetivo de profundizar en el conocimiento de los hallazgos clínicos y epidemiológicos de la invaginación intestinal en niños menores de 1 año, se realizó un estudio epidemiológico en el servicio de cirugía pediátrica del Hospital Pediátrico Docente Centro Habana entre noviembre de 2017 a abril de 2018. El estudio constituye el precursor de un sistema de vigilancia centinela de base hospitalaria que será parte del proyecto Vacuna contra rotavirus promovido por el Instituto Finlay de Vacunas. Los datos de todos los casos notificados se recolectaron por los cirujanos a través de la Ficha de vigilancia centinela de la invaginación intestina. Se notificaron un total de nueve casos con diagnóstico de invaginación intestinal, principalmente a los 5 meses de edad (44,4 por ciento), todos confirmados por ecografía de abdomen. La incidencia de invaginación intestinal en este período fue estimada de 1,41 por ciento. Los síntomas y signos más frecuentes fueron las deposiciones con sangre (77,8 por ciento), la irritabilidad (66,7 por ciento) y el vómito (55,6 por ciento). La desinvaginación por técnicas no quirúrgicas fue empleada en ocho casos y de ellas, el enema con aire fue la más usada (62,5 por ciento). Los resultados presentados aportan información necesaria para la construcción de la línea base de la invaginación intestinal en niños menores de 1 año de edad, antes de la introducción de la vacunación contra rotavirus en Cuba(AU)

The knowledge of the baseline incidence rates of intussusception among infants in Cuba are necessary to introduce the rotavirus vaccine into the Cuban immunization schedule. With the aim of characterizing the clinical presentation and epidemiology of intussusception a surveillance study was performed in children less than 1 years old with intussusception, in the pediatric surgery service at the Centro Habana Pediatric Hospital in Havana city between November 2017 and April, 2018. This study is the precursor of an active sentinel hospital surveillance for intussusception in children under 1 year of age, as a part of the project Rotavirus vaccine promoted by Instituto Finlay de Vacunas. Data were collected for each notified case by surgeons using a brief study questionnaire (Sentinel surveillance file for intussusception). A total of nine patients were diagnosed with intussusception, most cases presented at 5 months of age (44.4 percent), and all cases were confirmed by abdominal ultrasonography. The incidence of intussusception was 1.41 percent. The most frequent symptoms were rectal bleeding (77.8 percent), irritability (66.7 percent) and vomiting (55.6 percent). Intussusceptions reduction by non-surgical methods was used in eight cases, mainly air enema (62.5 percent). These results are now available to build the body of scientific evidence for baseline rates of intussusception in children less than 1 year of age, prior to the introduction of the rotavirus vaccine in Cuba(AU)

Holistic process development to mitigate proteolysis of a subunit rotavirus vaccine candidate produced in Pichia pastoris by means of an acid pH pulse during fed-batch fermentation.

To meet the challenges of global health, vaccine design and development must be reconsidered to achieve cost of goods as low as 15¢ per dose. A new recombinant protein-based rotavirus vaccine candidate derived from non-replicative viral subunits fused to a P2 tetanus toxoid CD4(+) T cell epitope is currently under clinical development. We have sought to simplify the existing manufacturing process to meet these aims. To this end, we have taken a holistic process development approach to reduce process complexity and costs while producing a product with the required characteristics. We have changed expression system from Escherichia coli to Pichia pastoris, to produce a secreted product, thereby reducing the number of purification steps. However, the presence of proteases poses challenges to product quality. To understand the effect of fermentation parameters on product quality small-scale fermentations were carried out. Media pH and fermentation duration had the greatest impact on the proportion of full-length product. A novel acidic pH pulse strategy was used to minimize proteolysis, and this combined with an early harvest time significantly increased the proportion of full-length material (60-75%). An improved downstream process using a combination of CIEX and AIEX to further reduce proteases, resulted in maintaining product quality (95% yield).

Socioeconomic Impact of the Rotavirus Vaccine in Korea: Comparing the Epidemiologic and Economic Characteristics of Rotavirus Gastroenteritis Before and After the Introduction of Vaccines.

BACKGROUND: Since the introduction of 2 rotavirus (RV) vaccines in Korea, the vaccination rate has reached over 80% with out-of-pocket spending in the private market. We investigated the socioeconomic impact of RV vaccines in Korea to assess their value and public health contribution. METHODS: By using National Health Insurance Service claims data, we compared the epidemiologic and economic characteristics of rotavirus gastroenteritis (RVGE) before and after the introduction of RV vaccines. For each year of the study period, the annual prevalence and national costs of RVGE were estimated based on children under 5 years with at least 1 National Health Insurance Service claims record with a diagnosis of RVGE. RESULTS: Compared with the prevaccination period, the prevalence of RVGE decreased in the postvaccination period by 48.9% from 2097 per 100,000 children in 2006 to 1072 per 100,000 children in 2015, implying an increase in the vaccination rate and the prevention effect of the vaccines. The highest reduction was observed among those 12 to <24 months of age (-73.4%), presumably due to the benefit of full vaccination, while children under 2 months, ineligible for the RV vaccine, showed an increase (41.7%). The number of hospitalized RVGE cases per year decreased by 69.0%. The national economic burden of RVGE decreased by 28.6%. CONCLUSIONS: The substantial reduction in the socioeconomic burden of RVGE after the introduction of RV vaccines confirms their benefit to society. This study would help health policy makers make empirical decisions on incorporating the vaccination into national immunization programs.

Colostrum from cows immunized with a veterinary vaccine against bovine rotavirus displays enhanced in vitro anti-human rotavirus activity.

Human rotaviruses represent a major cause of severe diarrheal disease in infants and young children. The limited impact of oral vaccines on global estimates of rotavirus mortality and the suboptimal use of oral rehydration justify the need for alternative prophylactic and therapeutic strategies, especially for immunocompromised hosts. The protective effects of colostrum-the first milk produced during the initial 24 to 48 h after parturition-are well documented in the literature. In particular, the ingestion of hyperimmune bovine colostrum has been proposed as an alternative preventive approach against human rotavirus gastroenteritis. Although the immunization of pregnant cows with human rotavirus boosts the release of specific immunoglobulin G in bovine colostrum, it raises regulatory and safety issues. In this study, we demonstrated that the conventional bovine rotavirus vaccine is sufficient to enhance the anti-human rotavirus protective efficacy of bovine colostrum, thus providing a conservative approach to produce hyperimmune bovine colostrum, making it exploitable as a functional food.

Epidemiology study of pediatric primary intussusception aged ≤24 months in pre-rotavirus vaccine era of Jinan, China.

INTRODUCTION: Few studies have reported on the epidemiological characteristics of pediatric primary intussusception in the pre-rotavirus vaccine era of China. It is important to complementary baseline data before rotavirus vaccine introduction in China. This study conduct a retrospective investigation and evaluated the incidence rate, described the epidemiology of pediatric primary intussusception aged ≤24 months. METHODS: We conducted a retrospective investigation in all secondary- and tertiary-hospitals in Jinan. Pediatric primary intussusception inpatients aged ≤24 months were identified depending on ICD-10 discharge code from a total of 63 hospitals from 2011 to 2015. Demographic and clinical information were extracting from the electronic clinical record systems. RESULTS: A total of 575 pediatric primary intussusception inpatients were identified with average annual incidence of 86.5 per 100,000. A significantly higher incidence was observed in males (χ2 = 13.8, P < 0.01), in the ≤12 months old age group (χ2 = 19.5, P < 0.01) and from the urban areas (χ2 = 63.31, P < 0.001). No clear seasonality found. Abdominal pain (80.9%) and vomiting (63.3%) were the most frequently reported. Most intussusception cases occurred in ileo-cecum. Over 92% of intussusception cases were diagnosed by ultrasound alone and 77.4% was successfully treated by air enema. 99.7% were cured. The median time of hospitalization was 2 days (range: 0-35 days). CONCLUSION: This retrospective study provides baseline information of incidence, epidemiologyand clinical characteristics of pediatric primary intussusception in Jinan City during 2011-2016 before the introduction of rotavirus vaccine. It will be important for evaluating safety of rotavirus vaccine if it will be introduced to the routine immunization program in China.

[False beliefs about vaccines]. / Falsas creencias sobre las vacunas.

Vaccines are an essential tool for the prevention of infectious diseases. However, false ideas and rumours with no scientific foundation about their possible negative effects may dissuade people from being vaccinated, with the consequent risks for the health of the population. The objective of this article is to evaluate the origin and the arguments of some of the most frequent mistaken ideas and rumours about the possible adverse effects of vaccines. Some clearly established adverse effects are presented, as well as false beliefs about various vaccines and potential harm to health. Vaccines, like any drug, can cause adverse effects, but the possible adverse effects of vaccination programs are clearly lower than their individual (vaccinated) and collective benefits (those vaccinated and those who cannot be vaccinated for medical reasons). The possible adverse effects attributable to vaccines should be detected by powerful and well-structured pharmacovigilance systems.

Retinoic acid elicits a coordinated expression of gut homing markers on T lymphocytes of Zambian men receiving oral Vivotif, but not Rotarix, Dukoral or OPVERO vaccines.

All-trans retinoic acid (ATRA) up-regulates, in laboratory animals, the expression of the gut homing markers α4ß7 integrin and CCR9 on lymphocytes, increasing their gut tropism. Here, we show that, in healthy adult volunteers, ATRA induced an increase of these gut homing markers on T cells in vivo in a time dependent manner. The coordinated increase of α4ß7 and CCR9 by ATRA was seen in 57% (12/21) of volunteers and only when given together with an oral Vivotif vaccine. When this coordinated response to ATRA and Vivotif vaccine was present, it was strongly correlated with the gut immunoglobulin A (IgA) specific response to vaccine LPS (ρ = 0.82; P = 0.02). Using RNA-Seq analysis of whole blood transcription, patients receiving ATRA and Vivotif in conjunction showed transcriptomic changes in immune-related pathways, particularly including interferon α/ß signaling pathway, membrane-ECM interactions and immune hubs. These results suggest that exogenous ATRA can be used to manipulate responses to a subclass of oral vaccines, so far limited to a live attenuated Vivotif vaccine.

Incidence and epidemiology of intussusception among children under 2 years of age in Chenzhou and Kaifeng, China, 2009-2013.

INTRODUCTION: In China, rotavirus is the leading cause of diarrhea hospitalizations among children aged <5 years. A locally manufactured rotavirus vaccine is available for private market use, but little is known about its coverage. Given the impending availability of newer rotavirus vaccines, we evaluated intussusception rates among children aged <2 years to better understand intussusception epidemiology for future vaccine safety monitoring. METHODS: We conducted a retrospective review at 4 hospitals in Chenzhou City of Hunan Province and Kaifeng City of Henan Province. We identified intussusception cases admitted during 2009-2013 by reviewing medical records with the ICD-10 discharge code for intussusception and extracting demographic and clinical information from the electronic clinical record systems. RESULTS: During 2009-2013, 1715 intussusception hospitalizations among 1,487,215 children aged <2 years occurred in both cities. The average annual intussusception hospitalization incidence was 112.9 per 100,000 children aged <2 years (181.8 per 100,000 children <1 year; 56 per 100,000 children 1 to <2 years). Intussusception incidence was low among infants aged <3 months and peaked at age 6-8 months. No clear seasonality was observed. Ultrasound was used to diagnose 95.9% of cases. Enema reduction was performed in 80% cases; 25% of cases in Chenzhou and 16% in Kaifeng required surgical intervention. No deaths were reported. The median time between symptom onset and admission was 1 day. CONCLUSIONS: This study provides information on intussusception incidence and epidemiology in two cities of China during 2009-2013. Monitoring intussusception rates in this population will be important in the post-rotavirus vaccine era.

Recurrent intussusception among infants less than 2 years of age in Vietnam.

In some settings, rotavirus vaccines have been associated with a low-level risk of intussusception, the most common cause of bowel obstruction in infants. As Vietnam prepares to introduce rotavirus vaccine into the national immunization program, we sought to better characterize the epidemiology of recurrent intussusception. We enrolled children <2 years of age who were hospitalized for intussusception retrospectively from January 2013 through December 2014 and prospectively from January 2015 through December 2016 at 2 hospitals in Vietnam. We enrolled 2477 children. Nearly all children were successfully treated by enema with low surgery rate (1%). We found 10% of children (n = 254) experienced at least once recurrence (range: 1-6) and 57% of first recurrences happened within the first 12 weeks after treatment of the first episode. The median age at first intussusception was 13 months for children without a recurrent episode and 10 months for children with a recurrence. The symptoms of the recurrent cases were milder with less vomiting (67%), bloody stool (7%) and fever (10%) compared to the initial cases (p < 0.01). We found the rate of recurrences following enema reduction of intussusception to be similar to that reported from other countries. Due to the high rate of intussusception and recurrent episodes in Vietnam, a better understanding of the cause of recurrent intussusception will be critical in assessing intussusception cases after rotavirus introduction.

Rotavirus Genotypes Circulating in Brazil Before and After the National Rotavirus Vaccine Program: A Review.

BACKGROUND: Rotavirus vaccines created the opportunity to control diarrhea in children. We describe the rotavirus genotypes before and after the rotavirus vaccine introduction in Brazil. METHODS: We reviewed the distribution of rotavirus genotypes in Brazil before and after vaccine introduction by searching publication. RESULTS: Eighty-six studies reported 6884 (15.2%) rotavirus episodes among 45,305 children. Rotavirus caused 22.4% and 11.6% of cases before and after vaccine introduction. G1P[8], G9P[8] and G2P[4] heterotypic strains were most common before and after vaccine introduction. CONCLUSIONS: The vaccines may have selected heterotypic strains in this highly vaccinated population.

Challenges to Developing a Rotavirus Vaccine.

Rotavirus is the most important cause of gastroenteritis worldwide. In developing countries, the virus is a major cause of death in infants and young children. In the United States, before the licensure of vaccines, rotavirus infections accounted for ∼2.7 million cases of gastroenteritis annually. Here are described the history and challenges surrounding the development of a rotavirus vaccine.

The effect of probiotics and zinc supplementation on the immune response to oral rotavirus vaccine: A randomized, factorial design, placebo-controlled study among Indian infants.

BACKGROUND: Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function. METHODS: Infants 5weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5mg), probiotic (1010Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14weeks of age based on detection of VP6-specific IgA at ≥20U/ml in previously seronegative infants or a fourfold rise in concentration. RESULTS: The study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): -1.4%, 16.2%), p=0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: -4.4%, 13.2%), p=0.272). 16 serious adverse events were recorded, none related to study interventions. CONCLUSIONS: Zinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation. TRIAL REGISTRATION: The trial was registered in India (CTRI/2012/05/002677).

Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand.

BACKGROUND: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. METHODS: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0-5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. RESULTS: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). CONCLUSIONS: The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or stool excretion following 3 doses of RV3-BB Rotavirus Vaccine administered using either a neonatal or infant schedule in New Zealand infants.