Eleanor Burnett

Global Impact of Rotavirus Vaccination on Childhood Hospitalizations and Mortality From Diarrhea

In 2006, 2 rotavirus vaccines were licensed. We summarize the impact of rotavirus vaccination on hospitalizations and deaths from rotavirus and all-cause acute gastroenteritis (AGE) during the first 10 years since vaccine licensure, including recent evidence from countries with high child mortality. We used standardized guidelines (PRISMA) to identify observational evaluations of rotavirus vaccine impact among children <5 years of age that presented at least 12 months of pre- and post-vaccine introduction surveillance data. We identified 57 articles from 27 countries. Among children <5 years of age, the median percentage reduction in AGE hospitalizations was 38% overall and 41%, 30%, and 46% in countries with low, medium, and high child mortality, respectively. Hospitalizations and emergency department visits due to rotavirus AGE were reduced by a median of 67% overall and 71%, 59%, and 60% in countries with low, medium, and high child mortality, respectively. Implementation of rotavirus vaccines has substantially decreased hospitalizations from rotavirus and all-cause AGE.

Effectiveness of Rotavirus Vaccination: A Systematic Review of the First Decade of Global Postlicensure Data, 2006–2016

Two rotavirus vaccines, Rotarix (RV1) and RotaTeq (RV5), were licensed for global use in 2006. A systematic review of 48 peer- reviewed articles with postlicensure data from 24 countries showed a median RV1 vaccine effectiveness (VE) of 84%, 75%, and 57% in countries with low, medium, and high child mortality, respectively, and RV5 VE of 90% and 45% in countries with low and high child mortality, respectively. A partial vaccine series provided considerable protection, but not to the same level as a full series. VE tended to decline in the second year of life, particularly in medium- and high-mortality settings, and tended to be greater against more severe rotavirus disease. Postlicensure data from countries across geographic regions and with different child mortality levels demonstrate that under routine use, both RV1 and RV5 are effective against rotavirus disease, supporting the World Health Organization recommendation that all countries introduce rotavirus vaccine into their national immunization program.

Catching-up with pentavalent vaccine: Exploring reasons behind lower rotavirus vaccine coverage in El Salvador.

Rotavirus vaccine was introduced in El Salvador in 2006 and is recommended to be given concomitantly with DTP–HepB–Haemophilus influenzae type b (pentavalent) vaccine at ages 2 months (upper age limit 15 weeks) and 4 months (upper age limit 8 months) of age. However, rotavirus vaccination coverage continues to lag behind that of pentavalent vaccine, even in years when national rotavirus vaccine stock-outs have not occurred. We analyzed factors associated with receipt of oral rotavirus vaccine among children who received at least 2 doses of pentavalent vaccine in a stratified cluster survey of children aged 24–59 months conducted in El Salvador in 2011. Vaccine doses included were documented on vaccination cards (94.4%) or in health facility records (5.6%). Logistic regression and survival analysis were used to assess factors associated with vaccination status and age at vaccination. Receipt of pentavalent vaccine by age 15 weeks was associated with rotavirus vaccination (OR: 5.1; 95% CI 2.7, 9.4), and receipt of the second pentavalent dose by age 32 weeks was associated with receipt of two rotavirus vaccine doses (OR: 5.0; 95% CI 2.1–12.3). Timely coverage with the first pentavalent vaccine dose was 88.2% in the 2007 cohort and 91.1% in the 2008 cohort (p = 0.04). Children born in 2009, when a four-month national rotavirus vaccine stock-out occurred, had an older median age of receipt of rotavirus vaccine and were less likely to receive rotavirus on the same date as the same dose of pentavalent vaccine than children born in 2007 and 2008. Upper age limit recommendations for rotavirus vaccine administration contributed to suboptimal vaccination coverage. Survey data suggest that late rotavirus vaccination and co-administration with later doses of pentavalent vaccine among children born in 2009 helped increase rotavirus vaccine coverage following shortages.

Potential for a booster dose of rotavirus vaccine to further reduce diarrhea mortality

Concern has grown that children vaccinated against rotavirus in developing countries may be vulnerable to rotavirus diarrhea in the second year of life due to waning immunity. Adding a booster dose of rotavirus vaccine at 9 or 12 months of age with measles vaccine has been suggested as a strategy to address this. We evaluated the hypothetical potential benefits of a booster dose on reduction of rotavirus mortality. The projected number of deaths averted were calculated using national level full series vaccination coverage, estimated national rotavirus deaths by week of age, and VE at <12 months of age and ≥12 months of age derived from the published literature. We assumed three functional forms of waning based on the VE estimates: stepwise, linear, and logarithmic. We modeled three potential boosting scenarios: (a) reduced VE waning in the second year of life by 50%, (b) reestablished second year of life VE to the levels in the first year of life, and (c) boosted first year VE by 50% of the difference between VE in the first and second years. To express uncertainty resulting from the parameters, each of the nine models were run 1000 times using a random sample of input values. Across all WHO regions, with the stepwise models we estimated a median of 9800 (95%CI: 9400, 10,200), 19,600 (95%CI: 18,800, 20,400), and 29,400 (95%CI: 28,200, 30,700) additional rotavirus deaths averted in the reduced VE waning, reestablished VE, and boosted VE scenarios. These estimates were highly sensitive to the assumed functional form of waning with approximately 65-80% fewer deaths averted if immunity waned in a linear or logarithmic fashion compared to the stepwise model. While these projections will benefit from improved input data points, our resultsinform consideration of booster doses of rotavirus vaccine.

Administering Multiple Injectable Vaccines During a Single Visit-Summary of Findings From the Accelerated Introduction of Inactivated Polio Vaccine Globally.

Abstract Background. In 2013, the World Health Organization’s (WHO’s) Strategic Advisory Group of Experts (SAGE) recommended that all 126 countries using only oral polio vaccine (OPV) introduce at least 1 dose of inactivated polio vaccine (IPV) into their routine immunization schedules by the end of 2015. In many countries, the addition of IPV would necessitate delivery of multiple injectable vaccines (hereafter, “multiple injections”) during a single visit, with infants receiving IPV alongside pentavalent vaccine (which covers diphtheria, tetanus, and whole-cell pertussis; hepatitis B; and Haemophilus influenzae type b) and pneumococcal vaccine. Unanticipated concerns emerged from countries over acceptability of multiple injections, sites of administration, and safety. We contextualized the issues surrounding multiple injections by documenting concerns associated with administration of ≥3 injections, existing evidence in the published literature, and findings of a systematic review on administration practices and techniques. Methods. Concerns associated with multiple-injection visits were documented from meetings and personal communications with immunization program managers. Published literature on the acceptability of multiple injections by providers and caregivers was summarized, and a systematic review of the literature on administration practices was completed on the following topics: spacing between injection sites (ie, vaccine spacing), site of injection, route of injection, and procedural preparedness. WHO and United Nations Children’s Fund data from 2013–2015 were used to assess multiple-injection visits included in national immunization schedules. Results. Healthcare provider and caregiver attitudes and practices indicated concerns about infant pain, potential adverse effects, and uncertainty about vaccine effectiveness with multiple-injection visits. Published literature reinforced the record of safety and acceptance of the recommended schedule of IPV by the SAGE, but the evidence was largely from developed countries. Parental acceptance of multiple injections was associated with a positive provider recommendation to the caregiver. Findings of the systematic review identified that the intramuscular route is preferred over the subcutaneous route for vaccine administration and that the vastus lateralis muscle is preferred over the deltoid muscle for intramuscular injections. Recommendations on vaccine spacing and procedural preparedness were based on practical necessities, but comparative evidence was not identified. During 2013–2015, 85 countries added IPV to their immunization schedules, 46 (55%) of which adopted a schedule resulting in 3 injectable vaccines being administered in a single visit. Conclusion. The multiple-injection experience identified gaps in guidance for future vaccine introductions. Global partner organizations quickly mobilized to assess, document, and communicate the existing global experience on multiple-injection visits. This evidence-based approach provided reassurance to opinion leaders, health workers, and professional societies, thus encouraging uptake of IPV as a second or third injection in an accelerated manner globally.

Knowledge, Attitudes, and Practices regarding Diarrhea and Cholera following an Oral Cholera Vaccination Campaign in the Solomon Islands

Background In response to a 2011 cholera outbreak in Papua New Guinea, the Government of the Solomon Islands initiated a cholera prevention program which included cholera disease prevention and treatment messaging, community meetings, and a pre-emptive cholera vaccination campaign targeting 11,000 children aged 1–15 years in selected communities in Choiseul and Western Provinces. Methodology and Principal Findings We conducted a post-vaccination campaign, household-level survey about knowledge, attitudes, and practices regarding diarrhea and cholera in areas targeted and not targeted for cholera vaccination. Respondents in vaccinated areas were more likely to have received cholera education in the previous 6 months (33% v. 9%; p = 0.04), to know signs and symptoms (64% vs. 22%; p = 0.02) and treatment (96% vs. 50%; p = 0.02) of cholera, and to be aware of cholera vaccine (48% vs. 14%; p = 0.02). There were no differences in water, sanitation, and hygiene practices. Conclusions This pre-emptive OCV campaign in a cholera-naïve community provided a unique opportunity to assess household-level knowledge, attitudes, and practices regarding diarrhea, cholera, and water, sanitation, and hygiene (WASH). Our findings suggest that education provided during the vaccination campaign may have reinforced earlier mass messaging about cholera and diarrheal disease in vaccinated communities.

Impact of rotavirus vaccine on all-cause diarrhea and rotavirus hospitalizations in Madagascar

BACKGROUND Rotavirus vaccine was introduced into the Extended Program on Immunization in Madagascar in May 2014. We analyzed trends in prevalence of all cause diarrhea and rotavirus hospitalization in children <5years of age before and after vaccine introduction and assessed trend of circulating rotavirus genotypes at Centre Hospitalier Universitaire Mère Enfant Tsaralalàna (CHU MET). METHODS From January 2010 to December 2016, we reviewed the admission logbook to observe the rate of hospitalization caused by gastroenteritis among 19619 children <5years of age admitted at the hospital. In June 2013-December 2016, active rotavirus surveillance was also conducted at CHUMET with support from WHO. Rotavirus antigen was detected by EIA from stool specimen of children who are eligible for rotavirus gastroenteritis surveillance at sentinel site laboratory and rotavirus positive specimens were further genotyped at Regional Reference Laboratory by RT-PCR. RESULTS Diarrhea hospitalizations decreased after rotavirus vaccine introduction. The median proportion of annual hospitalizations due to diarrhea was 26% (range: 31-22%) before vaccine introduction; the proportion was 25% the year of vaccine introduction, 17% in 2015 and 16% in 2016. Rotavirus positivity paralleled patterns observed in diarrhea. Before vaccine introduction, 56% of stool specimens tested positive for rotavirus; the percent positive was 13% in 2015, 12% in 2016. Diverse genotypes were detected in the pre-vaccine period; the most common were G3P[8] (n=53; 66%), G2P[4] (n=12; 15%), and G1P[8] (n=11; 14%). 6 distinct genotypes were found in 2015; the most common genotype was G2P[4] (n=10; 67%), the remaining, 5, G12[P8], G3[P8], G1G3[P4], G3G12[P4][P8] and G1G3[NT] had one positive specimen each. CONCLUSIONS Following rotavirus vaccine introduction all-cause diarrhea and rotavirus-specific hospitalizations declined dramatically. The most common genotypes detected in the pre-vaccine period were G3P[8] and G2P[4] in 2015, the post vaccine period.

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.

Estimated impact of rotavirus vaccine on hospitalizations and deaths from rotavirus diarrhea among children <5 in Asia

ABSTRACT Background: Of the 215,000 global deaths from rotavirus estimated in 2013, 41% occur in Asian countries. However, despite a recommendation for global rotavirus vaccination since 2009, only eight countries in Asia have introduced the rotavirus vaccine into their national immunization program as of September 2017. To help policy makers assess the potential value of vaccination, we projected the reduction in rotavirus hospitalizations and deaths following a hypothetical national introduction of rotavirus vaccines in all countries in Asia using data on national-level rotavirus mortality, <5 population, rotavirus hospitalizations rates, routine vaccination coverage, and vaccine effectiveness. Methods: To quantify uncertainty, we generated 1,000 simulations of these inputs. Results: Our model predicted 710,000 fewer rotavirus hospitalizations, a 49% decrease from the 1,452,000 baseline hospitalizations and 35,000 fewer rotavirus deaths, a 40% decrease from the 88,000 baseline deaths if all 43 Asian countries had introduced rotavirus vaccine. Similar reductions were projected in subanalyses by vaccine introduction status, subregion, and birth cohort size. Conclusion: Rotavirus vaccines will substantially reduce morbidity and mortality due to rotavirus infections in Asia.

Individually Linked Household and Health Facility Vaccination Survey in 12 At-risk Districts in Kinshasa Province, Democratic Republic of Congo: Methods and Metadata.

Health facility (HF) and household (HH) data can complement each other to provide a better understanding of the factors that contribute to vaccination status. In 12 zones with low vaccination coverage within Kinshasa Province, Democratic Republic of Congo, we conducted 2 surveys: (1) a linked HH and HF survey among 6-11-month-old infants, and (2) a HH survey among 12-23-month-old children. Linked survey objectives were to identify factors associated with vaccination status and to explore methodological considerations for linked survey implementation. To provide linked HH and HF data, we enrolled 6-11-month-old infants in HH clusters in each zone and then surveyed HFs located within the 12 zones and cited by caregivers of the enrolled infants as the most recent HF visited for vaccination or curative care. To provide vaccination coverage estimates for the 12-zone area, we enrolled 12-23-month-old children in every fourth HH. Of the HHs with a child aged 6-23 months, 16% were ineligible because they had resided in the neighborhood for <3 months or were unavailable to be interviewed, 4% refused, and 80% were eligible and participated. Of 1224 enrolled infants 6-11 months of age, records of 879 (72%) were linked to one of the 182 surveyed HFs. For the coverage survey, 710 children aged 12-23 months participated. Home-based vaccination cards were available for 1210 of 1934 children (63%) surveyed. The surveys were successful in assessing HH information for 2 age groups, documenting written vaccination history for a large proportion of 6-23-month-old children, linking the majority of infants with their most recently visited HF, and surveying identified HFs. The implementation of the individually linked survey also highlighted the need for a comprehensive list of HFs and an analysis plan that addresses cross-classified clusters with only 1 child.