Toward more specific and transparent research and development costs: The case of seasonal influenza vaccines

Background

The ability to calculate the development costs for specific medicines and vaccines is important to inform investments in innovation. Unfortunately, the literature is predominated by non-reproducible studies only measuring aggregate level drug research and development (R&D) costs. We describe methodology that improves the transparency and reproducibility of primary indication expected R&D expenditures.

Methods

We used publically accessible clinical trial data to investigate the fate of all seasonal influenza vaccine candidates that entered clinical development post year 2000. We calculated development times and probabilities of success for these candidates through the various phases of clinical development. Clinical trial cost data obtained from university based clinical researchers were used to estimate the costs of each phase of development. The cost of preclinical development was estimated using published literature.

Results

A vaccine candidate entering pre-clinical development in 2011 would be expected to achieve licensure in 2022; all costs are reported in 2022 Canadian dollars (CAD). After applying a 9% cost of capital, the capitalized total R&D expenditure amounts to $474.88 million CAD.

Conclusion

Clinical development costs for vaccines and drugs can be estimated with increased specificity and transparency using public sources of data. The robustness of these estimates will only increase over time due to public disclosure incentives first introduced in the late 1990s. However, preclinical development costs remain difficult to estimate from public data.     

Status of vaccine research and development for Helicobacter pylori

Gastric adenocarcinoma is globally the third leading cause of death due to malignancy, with the bulk of this disease burden being suffered by low and middle income countries (LMIC), especially in Asia. The majority of these cancers develop as a result of a chronic gastritis that arises in response to infection with the stomach-dwelling bacterium, Helicobacter pylori. A vaccine against this pathogen would therefore be a powerful tool for preventing gastric adenocarcinoma. However, notwithstanding a proof-of-concept that vaccination can protect children from acquisition of H. pylori infection, there are currently no advanced vaccine candidates with only a single vaccine in Phase I clinical trial. Further, the development of a vaccine against H. pylori is not a current strategic priority of major pharmaceutical companies despite the large global disease burden. Given the involvement of such companies is likely to be critical for late stage development, there is therefore a need for an increased appreciation of the burden of this disease in LMIC and more investment to reinvigorate research in H. pylori vaccine Research and Development.     

Effectiveness of monovalent and pentavalent rotavirus vaccines in Japanese children

BackgroundRotavirus (RV) vaccination has been available in Japan since November 2011, but is not yet part of Japan’s national immunisation programs. There are insufficient data on vaccine effectiveness (VE) among Japanese children.MethodsBetween the months of January and May in 2014 and 2015, we conducted active surveillance of gastroenteritis among children at 14 medical facilities. Rectal swabs from all patients with diarrhoea or vomiting were tested for RV by immunochromatography, and positive specimens were genotyped. Demographic data and immunisation records were obtained from a questionnaire completed by their parents/guardians or medical records. A test-negative case-control design was used to examine vaccine effectiveness (VE) using unconditional logistic regression analysis adjusted for possible confounding factors.ResultsAmong the 1519 eligible subjects (children with acute gastroenteritis symptoms aged ≥2 months to <3 y visiting medical facilities) recruited, 487 cases and 925 controls were enrolled. Cases had more severe symptoms than controls, requiring more intensive treatment, including intravenous rehydration or hospitalisation. VE against all rotavirus gastroenteritis (RVGE) was 80.0% (95% confidence interval [CI], 72.8–85.5%), and VEs against RV1 and RV5 were similar, at 80.6% (95%CI, 70.7–87.1%) for RV1 and 80.4% (95% CI, 69.1–87.6%) for RV5. Although VEs of both vaccines decreased with age, VEs against all RVGE were >70% up to 2 years after vaccination. VEs increased with severity of RVGE, and VE against severe RVGE, requiring intravenous rehydration or hospitalisation, was 97.3% (95% CI, 88.8–99.3%). VEs of RV1 and RV5 against G1P[8] and G2P[4] were comparable, at RV1, 89.8% (95% CI, 78.2–95.5%) and 78.3% (95% CI, 23.6–93.8%); and RV5, 85.8% (95% CI, 72.8–92.6%) and 88.1% (95% CI, 10.1–98.4%), respectively.ConclusionsRotavirus vaccines were effective in preventing mild to severe RVGE, irrespective of vaccine type, time since vaccination, or RV genotype.     

Effectiveness of rotavirus vaccines in an Australian population: A case-control study

ObjectiveTwo rotavirus vaccines (RV1 and RV5) were included in the publicly funded National Immunisation Program in Australia from July 2007. The programme in Western Australia initially provided RV1 (at ages 2 and 4 months) and then switched to RV5 (at ages 2, 4 and 6 months) from July 2009. This retrospective case-control study was conducted to assess the effectiveness of rotavirus vaccine against laboratory confirmed and notified cases of rotavirus infection among children aged <5 years.MethodsCase-subjects were identified as vaccine-eligible children (born from 1 May 2007) who were notified as having rotavirus infection during the period 2009–2011. The control group was vaccine-eligible children notified as having Campylobacter or Salmonella infection during the same period. Individual rotavirus immunisation status was ascertained from a population-based immunisation register. Full-dose and partial-dose vaccine effectiveness (VE) were calculated for both vaccines using the adjusted odds ratio (OR) of vaccination for cases versus controls (VE = (1 − OR)*100%).ResultsOverall, 282 cases and 883 controls were included. The adjusted VE for a full course of either rotavirus vaccine was 72% (95% CI: 56–82) and 71% (95% CI: 50–84) for partial vaccination (one dose of RV1 or one/two doses of RV5). The VE for a complete 3-dose course of RV5 was 82% (95% CI: 59–92) and for a full 2-dose course of RV1 was 73% (95% CI: 55–83).ConclusionsRV1 and RV5 were both effective in preventing laboratory confirmed and notified rotavirus infections among children aged <5 years. Even incomplete courses of vaccination conferred good protection.     

Impact of the introduction of rotavirus vaccine on the timeliness of other scheduled vaccines: The Australian experience

Strict age limits for receipt of rotavirus vaccines and simultaneous use of vaccines requiring two (Rotarix^®) and three (RotaTeq^®) doses in Australia may impact on coverage and timeliness of other vaccines in the infant schedule. Using data from the Australian Childhood Immunisation Register (ACIR), coverage and timeliness of rotavirus vaccines and changes in timeliness of other infant vaccines following rotavirus vaccine introduction was examined, with particular emphasis on Indigenous infants in whom coverage is less optimal. Final dose rotavirus coverage reached 83% within 21 months of program commencement but remained 7% lower than other vaccines due in infancy. Coverage was 11–17% lower in Indigenous infants. Adherence to the first dose upper age limits for rotavirus vaccine was high with >97% of children vaccinated by the recommended age, but for subsequent rotavirus doses, receipt beyond the upper age limits was more common, especially in Indigenous children. Following rotavirus vaccine introduction, there were improvements in timeliness of receipt of all doses of DTPa-containing and 7-valent pneumococcal conjugate vaccines. High population coverage can be attained with rotavirus vaccines, even with adherence to strict upper age restrictions for vaccine dose administration. Rotavirus vaccine introduction appears to have impacted upon the timeliness of other concomitantly scheduled vaccines. These factors should be considered when rotavirus programs are introduced.     

Global economic evaluations of rotavirus vaccines: A systematic review

Introduction: World Health Organization (WHO) recommends Rotavirus vaccines to prevent and control rotavirus infections. Economic evaluations (EE) have been considered to support decision making of national policy. Summarizing global experience of the economic value of rotavirus vaccines is crucial in order to encourage global WHO recommendations for vaccine uptake. Therefore, a systematic review of economic evaluations of rotavirus vaccine was conducted.Methods: We searched Medline, Embase, NHS EED, EconLit, CEA Registry, SciELO, LILACS, CABI-Global Health Database, Popline, World Bank - e-Library, and WHOLIS. Full economic evaluations studies, published from inception to November 2015, evaluating Rotavirus vaccines preventing Rotavirus infections were included. The methods, assumptions, results and conclusions of the included studies were extracted and appraised using WHO guide for standardization of EE of immunization programs.Results: 104 relevant studies were included. The majority of studies were conducted in high-income countries. Cost-utility analysis was mostly reported in many studies using incremental cost-effectiveness ratio per DALY averted or QALY gained. Incremental cost per QALY gained was used in many studies from high-income countries. Mass routine vaccination against rotavirus provided the ICERs ranging from cost-saving to highly cost-effective in comparison to no vaccination among low-income countries. Among middle-income countries, vaccination offered the ICERs ranging from cost-saving to cost-effective. Due to low- or no subsidized price of rotavirus vaccines from external funders, being not cost-effective was reported in some high-income settings.Conclusion: Mass vaccination against rotavirus was generally found to be cost-effective, particularly in low- and middle-income settings according to the external subsidization of vaccine price. On the other hand, it may not be a cost-effective intervention at market price in some high-income settings. This systematic review provides supporting information to health policy-makers and health professionals when considering rotavirus vaccination as a national program.     

Effectiveness of rotavirus vaccines in preventing cases and hospitalizations due to rotavirus gastroenteritis in Navarre, Spain

Two rotavirus vaccines have been available since 2006. This study evaluates the effectiveness of these vaccines using a test-negative case-control design in Navarre, Spain. We included children 3-59 months of age who sought medical care for gastroenteritis and for whom stool samples were taken between January 2008 and June 2011. About 9% had received the pentavalent vaccine (RotaTeq) and another 8% received the monovalent vaccine (Rotarix). Cases were the 756 children with confirmed rotavirus and controls were the 6036 children who tested negative for rotavirus. Thirty-five percent of cases and 9% of controls had required hospitalization (p < 0.0001). The adjusted effectiveness of complete vaccination was 78% (95% CI: 68-85%) in preventing rotavirus gastroenteritis and 83% (95% CI: 65-93%) in preventing hospitalization for rotavirus gastroenteritis. No differences between the two vaccines were detected (p = 0.4523). Both vaccines were highly effective in preventing cases and hospital admissions in children due to rotavirus gastroenteritis.     

Analysis of rotavirus genotypes in Korea during 2013: An increase in the G2P[4] genotype after the introduction of rotavirus vaccines

Background

Group A rotavirus is the leading cause of acute gastroenteritis in children worldwide. We investigated G and P genotypes of group A rotavirus strains isolated from patients during 2013 and investigated which genotypes were identified from vaccinated patients.

Methods

From January to December 2013, 2235 fecal specimens were tested for rotavirus antigen, of which 374 specimens (16.7%) showed positive results. Strains from 288 rotavirus-positive specimens were genotyped using PCR and sequencing, and individual patients’ corresponding vaccine histories were investigated through the Korean Center for Disease Control website.

Results

G2 (22.6%) and P[4] (24.0%) were the most frequently identified G and P genotypes, respectively; accordingly, G2P[4] (19.8%) was the most prevalent G/P genotype observed in this period. G4P[6] (10.1%) was the second most prevalent G/P genotype and was mostly detected in neonates. Other genotypes, G1P[8], G9P[8], G1P[6], and G3P[6], were also detected. Of 288 rotavirus-positive specimens, 48 specimens were obtained from previously vaccinated patients. G2P[4] was also the genotype most frequently isolated from vaccinated patients. VP7 epitope analysis of G1P[8] and G2P[4] strains showed at least one amino acid differences in comparison with Rotarix and RotaTeq vaccine strains. The genotypic distribution of rotavirus strains in Korea has been shown temporal and geographical differences.

Conclusion

This study showed that G2P[4] was the genotype most frequently isolated from both vaccinated and unvaccinated patients in Korea during 2013. However, it is unclear whether the change of predominant genotype is due to the effect of vaccination or due to natural variation.     

Status of vaccine research and development of vaccines for malaria

Despite recent progress in reducing deaths attributable to malaria, it continues to claim approximately 500,000 lives per year and is associated with approximately 200 million infections. New tools, including safe and effective vaccines, are needed to ensure that the gains of the last 15 years are leveraged toward achieving the ultimate goal of malaria parasite eradication. In 2015, the European Medicines Agency announced the adoption of a positive opinion for the malaria vaccine candidate most advanced in development, RTS,S/AS01, which provides modest protection against clinical malaria; in early 2016, WHO recommended large-scale pilot implementations of RTS,S in settings of moderate-to-high malaria transmission. In alignment with these advancements, the community goals and preferred product characteristics for next-generation vaccines have been updated to inform the development of vaccines that are highly efficacious in preventing clinical malaria, and those needed to accelerate parasite elimination. Next-generation vaccines, targeting all stages of the parasite lifecycle, are in early-stage development with the most advanced in Phase 2 trials. Importantly, progress is being made in the definition of feasible regulatory pathways to accelerate timelines, including for vaccines designed to interrupt transmission of parasites from humans to mosquitoes. The continued absence of financially lucrative, high-income markets to drive investment in malaria vaccine development points to continued heavy reliance on public and philanthropic funding.     

Status of vaccine research and development of vaccines for dengue

This review on the dengue vaccine pipeline was a solicited article and drafted based on the pre-defined template for PD-VAC.     

Impact of rotavirus vaccine on rotavirus diarrhoea in countries of East and Southern Africa

BackgroundEstablished in 2006 with four countries conducting hospital-based rotavirus surveillance, the African rotavirus surveillance network has expanded over subsequent years. By 2015, 14 countries in the World Health Organization (WHO) East and Southern Africa sub-region (Eritrea, Ethiopia, Kenya, Lesotho, Madagascar, Mauritius, Namibia, Rwanda, Seychelles, Swaziland, Tanzania, Uganda, Zambia and Zimbabwe) were participating in the rotavirus surveillance network coordinated by WHO. We monitored the proportion of rotavirus diarrhoea among children under five years of age who were hospitalized for diarrhoea in the sentinel hospitals from 2010 to 2015 among countries that introduced rotavirus vaccine during or before 2013 (Rwanda, Tanzania, Zambia and Ethiopia) and compared with the other countries in the network.MethodsChildren under the age of five years hospitalized due to acute diarrhoea were enrolled into the sentinel surveillance system and had stool samples collected and tested for rotavirus antigens by enzyme immunoassay. We described trends in rotavirus positivity among tested stool samples before and after rotavirus vaccine introduction.ResultsIn countries that introduced rotavirus vaccine by 2013 (Rwanda, Tanzania, Zambia and Ethiopia), average rotavirus vaccine coverage from 2010 to 2015 improved from 0% in 2010 and 2011, 13% in 2012, 46% in 2013, 83% in 2014 to 90% in 2015. Annual average rotavirus positivity from 2010 to 2015 was 35%, 33%, 38%, 28%, 27%, and 19%, respectively. In countries that introduced rotavirus vaccine after 2013 or had not introduced by 2015, average rotavirus vaccine coverage was 0% in 2010–2013, 13% in 2014 and 51% in 2015. In these countries, rotavirus positivity was 44% in 2010, 32% in 2011, 33% in 2012, 41% in 2013, 40% in 2014 and 25% in 2015.ConclusionCountries that introduced rotavirus vaccine by 2013 had a lower proportion of rotavirus positive hospitalizations in 2013–2015 as compared to those that had not introduced rotavirus vaccine by 2013. The decrease in rotavirus positivity was inversely related to increase in rotavirus vaccine coverage showing impact of rotavirus vaccines.     

Detection of rotavirus before and after monovalent rotavirus vaccine introduction and vaccine effectiveness among children in mainland Tanzania

BackgroundMonovalent rotavirus vaccine (RV1) was introduced in Tanzania in January 2013 under the Reach Every Child initiative, to be given at ages 6 and 10 weeks. We used the sentinel hospital rotavirus surveillance system to examine the rotavirus detection rate before and after vaccine introduction and estimate vaccine effectiveness.MethodsBefore vaccine introduction, rotavirus surveillance was established at two mainland hospitals; children admitted for acute diarrhea were eligible for enrollment and stools were tested for rotavirus antigen. We compared the rotavirus positivity rate in the pre-vaccine period (Tanga Hospital, 2009 and 2011; Bugando Medical Centre, 2012) to that from post-introduction years, 2014–2015. In 2013, surveillance was established at 9 additional hospitals. We examined rotavirus positivity among infants at these sites for 2014–2015. We obtained vaccine records and calculated vaccine effectiveness at 3 sites using case-test-negative control design.ResultsAt Tanga Hospital, the rotavirus positivity rate among infants was 41% (102/251) pre-vaccine and 14% (28/197) in post-vaccine years (rate ratio: 0.35 [95% CI 0.22–0.54]). At Bugando, the positivity rate was 58% (83/143) pre-vaccine, and 18% (49/277) post-introduction (rate ratio 0.30 [95% CI 0.210.44]). Results were similar among children <5 years. At the new sites, the median site rotavirus positivity rate among infants was 26% in 2014 (range 19–44%) and 18% in 2015 (range 16–33%). The effectiveness of ≥1 RV1 dose against rotavirus hospitalization among children 5–23 months was 53% (95% CI: −14, 81), and 66% (95% CI: 9–87) against hospitalization with intravenous rehydration. Following introduction, peak rotavirus activity occurred later in the year and appeared more concentrated in time.ConclusionRotavirus surveillance data from Tanzania indicate that the rotavirus positivity rate among children hospitalized with diarrhea that were enrolled was substantially reduced after vaccine introduction. Low positivity rates among infants were detected at hospitals across the country. Overall, the data support that rotavirus vaccine has been successfully introduced and is effective in Tanzanian children.     

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.     

Dynamic model of rotavirus transmission and the impact of rotavirus vaccination in Kyrgyzstan

New rotavirus vaccines show promise to reduce the burden of severe diarrhea among children in developing countries. We present an age-specific dynamic rotavirus model to assess the effect of rotavirus vaccination in Kyrgyzstan, a country in Central Asia that is eligible for funds from the GAVI Alliance. A routine rotavirus vaccination program at 95% coverage and 54% effectiveness against severe infection is estimated to lead to a 56% reduction in rotavirus-associated deaths and a 50% reduction in hospital admissions, while outpatient visits and homecare episodes would decrease by 52% compared to baseline levels after 5 years of intervention. A 10% reduction in vaccine efficacy due to incomplete 3-dose regimen is estimated to increase the numbers of severe cases by 6-8%. Herd immunity was found to account for 1% or less of averted cases of severe gastroenteritis, while an extra 7-8% of all rotavirus infections would be avoided due to reduced transmission. Conclusion: Rotavirus vaccines would reduce the burden of rotavirus disease substantially, but the results are sensitive to delay in age-appropriate vaccination.     

Cost-effectiveness and budget impact analyses for the prioritisation of the four available rotavirus vaccines in the national immunisation programme in Thailand

BackgroundRotavirus is a major cause of diarrhoea in children less than five years old in Thailand. Vaccination has been shown to be an effective intervention to prevent rotavirus infections but has yet to be enlisted in the national immunisation programme. This study aimed to assess the cost-utility of introducing rotavirus vaccines, taking all WHO-prequalified vaccines into consideration.MethodsA cost-utility analysis was performed using a transmission dynamic model to estimate, from a societal perspective, the costs and outcomes of four WHO-prequalified rotavirus vaccines: Rotarix®, RotaTeq®, ROTAVAC® and ROTASIIL®. The model was used to simulate the impact of introducing the vaccines among children aged < 1 year and compare this with no rotavirus vaccination. The vaccination programme was considered to be cost-effective if the incremental cost-effectiveness ratio was less than a threshold of USD 5,110 per QALY gained.ResultsOverall, without the vaccine, the model predicted the average annual incidence of rotavirus to be 312,118 cases. With rotavirus vaccination at a coverage of more than 95%, the average number of rotavirus cases averted was estimated to be 144,299 per year. All rotavirus vaccines were cost-saving. ROTASIIL® was the most cost-saving option, followed by ROTAVAC®, Rotarix® and RotaTeq®, providing average cost-savings of USD 32, 31, 23 and 22 million per year, respectively, with 999 QALYs gained. All vaccines remained cost-saving with lower QALYs gained, even when ignoring indirect beneficial effects. The net saving to the healthcare system when implementing any one of these vaccines would be between USD 13 and 33 million per year.ConclusionRotavirus vaccines should be included in the national vaccination programme in Thailand. Implementing any one of these four WHO-prequalified vaccines would reduce government healthcare spending while yielding health benefits to the population.     

Impact of non-routine rotavirus vaccination on hospitalizations for diarrhoea and rotavirus infections in Spain

This study shows hospital discharges related to all-cause diarrhoea and rotavirus infection in children up to five years of age from 2005 to 2009 in Spain. Rotavirus vaccines have been available in Spain since late 2006 and early 2007. They are neither funded nor reimbursed by the National Health Care System. However, they are recommended by the Spanish Association of Pediatricians and prescribed by paediatricians. The vaccination coverage was 17% in 2007, 35% in 2008 and 38% in 2009. Among a total of 111,738 hospitalizations recorded, 24% (N = 26,500) were coded as rotavirus and 14% (N = 16,217) as diarrhoea of undetermined aetiology. The overall annual incidence of hospitalization was 991,235 and 144 per 100,000 children up to five years of age for all-causes diarrhoea, rotavirus infection and diarrhoea of undetermined aetiology respectively. The annual rate significantly decreased during the study period.     

Manufacturing costs of HPV vaccines for developing countries

BackgroundNearly all of the 500,000 new cases of cervical cancer and 270,000 deaths occur in middle or lower income countries. Yet the two most prevalent HPV vaccines are unaffordable to most. Even prices to Gavi, the Vaccine Alliance, are unaffordable to graduating countries, once they lose Gavi subsidies. Merck and Glaxosmithkline (GSK) claim their prices to Gavi equal their manufacturing costs; but these costs remain undisclosed. We undertook this investigation to estimate those costs.MethodsSearches in published and commercial literature for information about the manufacturing of these vaccines. Interviews with experts in vaccine manufacturing.FindingsThis detailed sensitivity analysis, based on the best available evidence, finds that after a first set of batches for affluent markets, manufacturing costs of Gardasil for developing countries range between $0.48 and $0.59 a dose, a fraction of its alleged costs of $4.50. Because volume of Cervarix is low, its per unit costs are much higher, though at comparable volumes, its costs would be similar.InterpretationGiven the recovery of fixed and annual costs from sales in affluent markets, Merck’s break-even price to Gavi could be $0.50–$0.60, not $4.50. These savings could support Gavi programs to strengthen delivery and increase coverage. Outside Gavi, prices to lower- and middle-income countries, with profit, could also be lowered and made available to millions more adolescents at risk. These estimates and their policy implications deserve further discussion.     

Reduction in hospitalizations for diarrhea and rotavirus infections in New York state following introduction of rotavirus vaccine

Objectives

To monitor trends and costs of diarrhea and rotavirus-associated hospitalizations in New York before and after rotavirus vaccine implementation in 2006. To examine rotavirus test results from sentinel hospital-associated laboratories.

Methods

Hospital discharge data and laboratory rotavirus testing data were analyzed for children 1 month up to 18 years of age for 10 sentinel and all statewide hospitals from January 1, 2003 through December 31, 2008.

Results

Among children 1–23 months of age, a 40% reduction in diarrhea-associated hospitalizations and 85% decrease in rotavirus-coded hospitalizations at the 10 sentinel hospitals was observed in 2008 compared with the average of pre-vaccine seasons from 2003 through 2006. For both sentinel and statewide hospitals, the percent of diarrhea admissions due to rotavirus was reduced at least 83% among children 1–23 months (vaccine eligible) and 70% for older unimmunized children. Statewide hospital costs for rotavirus hospitalizations in children <2 years of age were reduced $10 million. Sentinel hospital laboratory data validated the declining trends seen in hospitalizations.

Conclusions

In 2008, New York hospital data showed significant reductions in rotavirus hospitalizations and costs among children aged 1–23 months who were eligible for vaccine. Reductions also occurred among unimmunized older children suggesting the importance of continue monitoring in future seasons to fully assess vaccine impact.     

Impact of rotavirus vaccination on rotavirus and all-cause gastroenteritis in peri-urban Kenyan children

A monovalent rotavirus vaccine (RV1) was introduced into the National Immunization Program in Kenya in July 2014. We examined the impact of the vaccine on hospitalization for all-cause acute gastroenteritis (AGE) and rotavirus-specific AGE and strain distribution at a large referral hospital which serves a predominantly peri-urban population in Central Kenya. Data on rotavirus AGE and strain distribution were derived from ongoing hospital-based AGE surveillance. Hospital administrative data were used to compare trends in all-cause AGE. Pre-vaccine (July 2009–June 2014) and post-vaccine (July 2014–June 2016) periods were compared for changes in hospitalization for all-cause AGE and rotavirus AGE and strain distribution. Following the vaccine introduction, the proportion of children aged <5 years hospitalized for rotavirus declined by 30% (95% CI: 19–45%) in the first year and 64% (95% CI: 49–77%) in the second year. Reductions in rotavirus positivity were most pronounced among the vaccine-eligible group (<12 months) in the first year post-vaccination at 42% (95% CI: 28–56%). Greater reductions of 67% (95% CI: 51–79%) were seen in the second year in the 12–23 months age group. Similarly, hospitalizations for all-cause AGE among children <5 years of age decreased by 31% (95% CI: 24–40%) in the first year and 58% (95% CI: 49–67%) in the second year of vaccine introduction. Seasonal peaks of rotavirus and all-cause AGE were reduced substantially. There was an increased detection of G2P[4], G3P[6] and G3P[8], which coincided temporally with the timing of the vaccine introduction. Thus, introducing the rotavirus vaccine into the routine immunization program in Kenya has resulted in a notable decline in rotavirus and all-cause AGE hospitalizations in Central Kenya. This provides early evidence for public health policy makers in Kenya to support the sustained use of the rotavirus vaccine in routine immunizations.