First Dose Of Rotavirus Vaccine Research Articles

Safety of Rotavirus Vaccination in Preterm Infants Admitted in Neonatal Intensive Care Units in Sicily, Italy: A Multicenter Observational Study.

Rotavirus (RV) is among the most common vaccine-preventable diseases in children under five years of age. Despite the severity of rotavirus pathology in early childhood, rotavirus vaccination for children admitted to the neonatal intensive care unit (NICU), who are often born preterm and with various previous illnesses, is not performed. This multicenter, 3-year project aims to evaluate the safety of RV vaccine administration within the six main neonatal intensive care units of the Sicilian Region to preterm infants. Methods: Monovalent live attenuated anti-RV vaccination (RV1) was administered from April 2018 to December 2019 to preterm infants with gestational age ≥ 28 weeks. Vaccine administrations were performed in both inpatient and outpatient hospital settings as a post-discharge follow-up (NICU setting) starting at 6 weeks of age according to the official immunization schedule. Any adverse events (expected, unexpected, and serious) were monitored from vaccine administration up to 14 days (first assessment) and 28 days (second assessment) after each of the two scheduled vaccine doses. Results: At the end of December 2019, 449 preterm infants were vaccinated with both doses of rotavirus vaccine within the six participating Sicilian NICUs. Mean gestational age in weeks was 33.1 (±3.8 SD) and the first dose of RV vaccine was administered at 55 days (±12.9 SD) on average. The mean weight at the first dose was 3388 (SD ± 903) grams. Only 0.6% and 0.2% of infants reported abdominal colic and fever above 38.5 °C in the 14 days after the first dose, respectively. Overall, 1.9% EAEs were observed at 14 days and 0.4% at 28 days after the first/second dose administration. Conclusions: Data obtained from this study confirm the safety of the monovalent rotavirus vaccine even in preterm infants with gestational age ≥ 28 weeks, presenting an opportunity to improve the vaccination offer both in Sicily and in Italy by protecting the most fragile infants who are more at risk of contracting severe rotavirus gastroenteritis and nosocomial RV infection.

Missed Opportunities for Vaccination and Associated Factors among Children Attending Primary Health Care Facilities in Cape Town, South Africa: A Pre-Intervention Multilevel Analysis.

Despite the substantial efforts at ensuring universal access to routine immunisation services among children in South Africa, major gaps in immunisation coverage remain. This study assessed the magnitude of missed opportunities for vaccination (MOV) and associated factors among children aged 0–23 months attending primary health care (PHC) facilities in Cape Town. We used multilevel binomial logistic regression models to explore individual and contextual factors associated with MOV, with children aged 0–23 months at Level 1, nested within PHC facilities (Level 2). A total of 674 children and their caregivers were enrolled. MOV prevalence was 14.1%, ranging from 9.1% to 18.9% across sub-districts. Dose-specific MOV prevalence was highest for the second dose of measles vaccine (9.5%) and lowest for the first dose of rotavirus vaccine (0.6%). The likelihood of a child experiencing MOV was significantly associated with caregivers’ low level of education (Odds ratio (OR) = 3.53, 95% credible interval (CrI): 1.13–11.03), recent receipt of immunisation messages (OR = 0.46, 95%CrI: 0.25–0.87), shared immunisation decision making by both parents (OR = 0.21, 95%CrI: 0.07–0.62) and health facility staff number (OR = 0.18, 95%CrI: 0.06–0.61). The burden of MOV among children in Cape Town is influenced by individual and contextual factors, which provide important opportunities for quality improvement and broader strategies to improve routine immunisation service delivery.

Impact and effectiveness of monovalent rotavirus vaccine in Tajik children

BackgroundIn 2015, Tajikistan became the second country in Central Asia to introduce rotavirus vaccine into its national immunization program. Before vaccine introduction, rotavirus was estimated to cause > 40% of pediatric diarrhea hospitalizations in Tajikistan. We aimed to assess the impact of rotavirus vaccine introduction on rotavirus disease burden and estimate rotavirus vaccine effectiveness (VE). MethodsUsing surveillance data from 2013 through 2019, we examined trends in monthly hospital admissions among children < 5 years old, before and after rotavirus vaccine introduction. Poisson regression was used to quantify decreases. VE was estimated using a test-negative case control design, with data from admissions during 2017 – 2019. Immunization records were obtained from clinics. ResultsAmong enrolled children, rotavirus positivity declined from 42% to 25% in the post-vaccine introduction period, a decrease of 41% (95% Confidence Interval [CI]: 36 – 45%). Declines were greatest in children < 12 months of age. Estimated VE of a complete course of rotavirus vaccine was 55% (95% CI: 21 – 73%) among children 5 – 59 months of age and 64% (95% CI: 36 – 80%) among children 5 – 23 months of age. VE point estimates were higher among children receiving both doses of rotavirus vaccine non-concurrently with OPV and among children receiving their first dose of rotavirus vaccine at 4 – 11 months of age, but CIs were wide and overlapping. ConclusionsOur data demonstrate that rotavirus vaccine introduction was associated with a substantial reduction in pediatric rotavirus hospitalization burden in Tajikistan, and that rotavirus vaccination is effective in Tajik children.

Timeliness of rotavirus vaccination at sentinel sites in four early-adopter African countries

BackgroundThe majority of countries with the highest rotavirus-associated death rates are in sub-Saharan Africa. In 2009, the World Health Organization (WHO) recommended routine vaccination against rotavirus worldwide, with unique age recommendations to administer the first dose before 15 weeks of age and last dose by 32 weeks of age. These age restrictions were relaxed in January 2013, but they may still lead to lower rotavirus vaccine coverage. MethodsChildren age-eligible to have received rotavirus vaccine that were enrolled in Ghana, Zimbabwe, Rwanda or Burkina Faso′s active rotavirus surveillance platforms from 2013 to 2017 and had a stool specimen that tested rotavirus-negative were included in the analysis. Proportion vaccinated and timeliness of rotavirus vaccine versus DTPw-HepB-Hib (pentavalent) first dose and last dose were compared at weeks 15 and 32, respectively, using Chi-square analyses. Odds ratios were calculated using logistic regression. ResultsAmong children who received rotavirus vaccine dose 1, 96–99% received this dose by 15 weeks of age and among children who received the last dose, 98–99% received it by 32 weeks of age. In all four countries, there was no significant difference in the proportion of children who received first dose rotavirus versus pentavalent vaccine by week 15, or last dose rotavirus versus concordant pentavalent vaccine by week 32. Delayed administration of first dose pentavalent vaccine was significantly associated with missing first dose of rotavirus vaccine in 3 of the 4 countries studied, although delays in administration were rare (1–4%). ConclusionsRotavirus vaccination was timely among sentinel sites in these four early rotavirus vaccine-introducing countries in Africa. Late presentation for vaccination may have resulted in some children with access to care missing first dose of rotavirus vaccine; however, vaccination delays were infrequent and therefore the potential impact of the age restrictions on overall proportion vaccinated was minimal.

A case-control study of risk factors for intussusception among infants in eastern France after the introduction of the rotavirus vaccine

ObjectiveThe objective of the present study was to investigate the risk factors for intussusception (IS) among infants, including vaccination against rotavirus. MethodsCase-control study with systematic inclusion of all infants aged <1 year with suspected IS admitted to emergency departments in the eastern region of France between 1 April 2008 and 31 March 2012. All cases classed level 1 according to the Brighton classification were matched to 4 hospital controls. Two exposure windows were examined; exposure to the first dose of rotavirus vaccine in the 7 and in the 14 days prior to the occurrence of IS. ResultsA total of 115 cases were matched with 457 controls. The average vaccination coverage rate over the 4 years of study was 8.6%. Rotavirus vaccine was not found to be significantly associated with the occurrence of IS in the 7 days (odds ratio (OR) not calculated; p = 0.99) and in the 14 days after administration of one dose vaccine (OR 1.33, 95% confidence interval (CI) 0.14–12.82). Infant formula alone or combined with breastfeeding was associated with an excess risk of IS (OR 2.74, 95% CI 1.10–6.79). A history of gastroenteritis within 2 weeks prior to hospitalisation was also associated with an increased risk (OR 2.24, 95% CI 1.07–4.67). ConclusionOur study indicates that infant formula alone or combined with breastfeeding is a risk factor for IS. A small, non-significant increase in the risk of IS was observed after rotavirus vaccination, although the low vaccine coverage rate likely precluded detection of a significant increase in risk.

Detailed analysis of BALB/c mice challenged with wild type rotavirus EDIM provide an alternative for infection model of rotavirus

Mouse is one of the infection animal models for rotavirus. Since the optimal age of mouse sensitive to rotavirus infection thus far has not been unified, we elucidated clinical symptoms, immune responses and pathological changes of mice in different ages after challenged by murine rotavirus wild strain EDIM (Epidemic Diarrhea of Infant Mice) to provide data for the estimation. One-week-old, two-week-old, and three-week-old BALB/c mice were inoculated with EDIM in the challenge dose of 235 ID50, 470 ID50 and 705 ID50 respectively and were compared to mock-infected controls. Diarrhea illness, mobility, bodyweight were recorded, viral shedding and immune responses including serum IgA, fecal sIgA were detected, and small intestine tissue was evaluated for virus distribution and pathological changes. All the mice in one-week-old and two-week-old groups were completely unavoidable to be infected by EDIM and have been found to be malaise, activity reduced and even diarrhea, while three-week-old mice partly resist the challenge with 40% mice free from diarrhea. Meanwhile, EDIM infection has greater impact to the bodyweight of two-week-old group than those of one-week-old, three-week-old (0.9860 vs 1.2340, 1.2375g/day). One peak of virus shedding in three groups was observed in day 1–2 post infection, but the duration shortened with age increase. Feces sIgA in both two-week-old and three-week-old groups began to increase in day 4, 2–3days earlier than that in one-week-old group, and grow to the peak in day 8, which is about 2 fold of that in one-week-old group. Stronger serum IgA response was found in two-week-old group, it increased to the peak in day 15 and the level was 2 fold of three-week-old group and 4 fold of one-week-old group. The pathological changes included vacuolar degeneration, edema and congestion of intestinal wall, integrity destruction of enteric epithelium, and the changes relieved with the increase of age. Besides, rotavirus particles were found in small intestine tissues, especially in the surface and crypt of villi. In conclusion, the two-week-old mice were more sensitive to EDIM infection and initiated more effective immune response. In combination with that 14days old mice equals to 2 months infant when the first dose of rotavirus vaccine should be administrated, two-week-old mice is preferred to be used as infection model for the study of pathogenicity and immunogenicity of rotavirus.

Review of Naturally Occurring Intussusception in Young Children in the WHO African Region prior to the Era of Rotavirus Vaccine Utilization in the Expanded Programme of Immunization.

Rotavirus vaccines, Rotarix and RotaTeq, are increasingly being introduced in national immunization programmes in Africa to prevent severe dehydrating acute gastroenteritis. A low-level risk of intussusception has been associated with rotavirus vaccines. We reviewed published data on intussusception in children <2 years of age in Africa. PubMed electronic database search was used to retrieve papers published on intussusception. The search was further refined to identify surveillance reports and case series conducted from 1980 to 2014, with at least 25 cases. The initial search identified 34 studies, and the refined search yielded 16. Intussusception occurred naturally in infants 2-4 months and peaked around 5-8 months of age. Delayed presentation was common and required surgical intervention in 87% (1008 of 1158) of cases with a high CFR, 10-33.7%. In African children, intussusception has been reported infrequently at a young age when the first dose of rotavirus vaccine is administered.

The composition of demand for newly launched vaccines: results from the pneumococcal and rotavirus vaccine introductions in Ethiopia and Malawi.

Understanding post-launch demand for new vaccines can help countries maximize the benefits of immunization programmes. In particular, low- and middle-income countries (LMICs) should ensure adequate resource planning with regards to stock consumption and service delivery for new vaccines, whereas global suppliers must produce enough vaccines to meet demand. If a country underestimates the number of children seeking vaccination, a stock-out of commodities will create missed opportunities for saving lives. We describe the post-launch demand for the first dose of pneumococcal conjugate vaccine (PCV1) in Ethiopia and Malawi and the first dose of rotavirus vaccine (Rota1) in Malawi, with focus on the new birth cohort and the ‘backlog cohort’, comprised of older children who are still eligible for vaccination at the time of launch. PCV1 and Rota1 uptake were compared with the demand for the first dose of pentavalent vaccine (Penta1), a routine immunization that targets the same age group and immunization schedule. In the first year, the total demand for PCV1 was 37% greater than that of Penta1 in Ethiopia and 59% greater in Malawi. In the first 6 months, the demand of Rota1 was only 5.9% greater than Penta1 demand in Malawi. Over the first three post-introduction months, 70.7% of PCV1 demand in Ethiopia and 71.5% of demand in Malawi came from children in the backlog cohort, whereas only 28.0% of Rota1 demand in Malawi was from the backlog cohort. The composition of demand was impacted by time elapsed since vaccine introduction and age restrictions. Evidence suggests that countries’ plans should account for the impact of backlog demand, especially in the first 3 months post-introduction. LMICs should request for higher stock volumes when compared with routine needs, plan social mobilization activities to reach the backlog cohort and allocate human resources and cold chain capacity to accommodate high demand following vaccine introduction.

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Potential impact of accelerating the primary dose of rotavirus vaccine in infants

We estimated the potential impact of administering the first dose of rotavirus vaccine at 6 weeks (42 days of life) instead of 2 months of age, which is permissible for all U.S. vaccines recommended at 2 months of age, on rotavirus hospitalization rates. We used published data for hospitalization rates, vaccine coverage, and vaccine efficacy after one dose and assumed a two-week delay in seroconversion after vaccine administration in the United States. Administering the first dose of rotavirus vaccine at 6 weeks instead of 8 weeks of age should have prevented 1110, 1660, and 2210 rotavirus hospitalizations among U.S. infants <3 months of age in 2006 when the vaccine was first introduced. This estimated benefit represents a 2–4% reduction in rotavirus hospitalizations among children <5 years of age.

Prevention of Rotavirus Disease: Updated Guidelines for Use of Rotavirus Vaccine

This statement updates and replaces the 2007 American Academy of Pediatrics statement for prevention of rotavirus gastroenteritis. In February 2006, a live oral human-bovine reassortant rotavirus vaccine (RV5 [RotaTeq]) was licensed as a 3-dose series for use in infants in the United States. The American Academy of Pediatrics recommended routine use of RV5 in infants in the United States. In April 2008, a live, oral, human attenuated rotavirus vaccine (RV1 [Rotarix]) was licensed as a 2-dose series for use in infants in the United States. The American Academy of Pediatrics recommends routine immunization of infants in the United States with rotavirus vaccine. The American Academy of Pediatrics does not express a preference for either RV5 or RV1. RV5 is to be administered orally in a 3-dose series with doses administered at 2, 4, and 6 months of age; RV1 is to be administered orally in a 2-dose series with doses administered at 2 and 4 months of age. The first dose of rotavirus vaccine should be administered from 6 weeks through 14 weeks, 6 days of age. The minimum interval between doses of rotavirus vaccine is 4 weeks. All doses should be administered by 8 months, 0 days of age. Recommendations in this statement also address the maximum ages for doses, contraindications, precautions, and special situations for administration of rotavirus vaccine.

European Society for Paediatric Infectious Diseases/European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Evidence‐Based Recommendations for Rotavirus Vaccination in Europe: Executive Summary

European Society for Paediatric Infectious Diseases/European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Evidence‐Based Recommendations for Rotavirus Vaccination in Europe: Executive Summary

Effect of rotavirus vaccination programme on trends in admission of infants to hospital for intussusception

Studies have reported a temporal association between a first dose of rotavirus vaccine (Rotashield) and infant intussusception. We investigated the effect of Rotashield vaccination use on intussusception admissions in ten US states. We analysed electronic databases containing 100% hospital discharge records for 1993-99 from ten US states, where an estimated 28% of the birth cohort had received Rotashield (based on manufacturer's net sales data). We examined records of infants admitted to hospital (<365 days old) with any mention of intussusception (International Classification of Diseases, ninth revision, clinical modification code 560.0). Excess admissions for intussusception during the period of Rotashield availability (October 1998 to June 1999) were estimated by direct comparison with the corresponding period of October 1997 to June 1998 (before Rotashield was available) and with adjustment for secular trends during 1993-98 by Poisson regression. Hospital admission for intussusception among infants younger than 365 days of age during the Rotashield period compared with previously was 4% lower (10 cases) by direct comparison and 10% lower (27 cases) by trend comparison, corresponding to a negative population attributable risk. Among infants aged 45-210 days (target age range for a first Rotashield dose), we estimated an increase in intussusception admissions of 1% (one excess admission) by direct comparison and 4% (4.6 excess admissions) by trend comparison, corresponding to a population attributable risk range of one excess admission in 66000-302000. We found no evidence of increased infant intussusception admissions during the period of Rotashield availability. The total intussusception admission risk attributable to Rotashield was substantially lower than previous estimates based on studies focusing on the immediate postvaccination weeks.