Impact of rotavirus vaccine on paediatric rotavirus hospitalisation and intussusception in New Zealand: A retrospective cohort study

BackgroundRotavirus results in a significant burden of hospitalisations and deaths globally. Rotavirus vaccine has been used in New Zealand since July 2014. The aim of this study was to assess the safety and effectiveness of RotaTeq® vaccine in New Zealand between 2006 and 2016.MethodsA national cohort study of 723,695 children aged less than 6 years was carried out using linked administrative datasets. Study outcomes were hospitalisation for intussusception, rotavirus, and all-cause gastroenteritis. Intussusception hospitalisation rates were calculated from 2006 to 2016, and rotavirus and all-cause gastroenteritis hospitalisation rates from 2011 to 2016. We examined the effect of RotaTeq® vaccination on rotavirus and all-cause gastroenteritis hospitalisation rates using Poisson regression. Adjusted incidence rate ratios controlled for sex, year of birth, ethnicity, socioeconomic deprivation, and district health board area.ResultsSignificant reductions in the incidence of rotavirus hospitalisation were seen in all age groups, ethnicities, and deprivation following the introduction of RotaTeq®. There was a 92.6% reduction in hospitalisation incidence in the vaccinated cohort (p < 0.0001). There was also a 48% reduction in all-cause gastroenteritis hospitalisation incidence in the vaccinated cohort (p < 0.0001). The average annual intussusception rate in children aged less than 3 years was 26.2 per 100,000, with no significant change over time (p = 0.847).ConclusionsIn New Zealand the introduction of RotaTeq® resulted in a significant reduction in rotavirus hospitalisation, and a halving in all-cause gastroenteritis hospitalisation. There has been no change in the overall incidence of intussusception or clear change in patterns of cases, although intussusception cases did occur within risk period immediately post vaccine.     

Validation of parental reports of rotavirus vaccination of their children compared to the national immunization registry

BackgroundThe introduction of rotavirus vaccines into national immunization programs necessitates vaccine effectiveness evaluations. Parental report of vaccination status is a simple and accessible source of information; however, its validity is unclear.AimsTo validate parental reports of rotavirus immunization compared to documentation of vaccination in national immunization registry, and to assess vaccine effectiveness by each method.MethodsParents of 1272 children aged 2–59 months from northern Israel hospitalized for gastroenteritis in 2011–2015 were interviewed on the sociodemographics and rotavirus vaccination status of their child. Rotavirus immunization status based on parental report was compared to that documented in the national immunization registry, which was considered the gold standard. Stool samples collected from patients were tested for rotavirus antigen by immunochromotgraphy. In a rotavirus test-negative case-control study, vaccination history was compared between children found positive for rotavirus and those who tested negative. Vaccine effectiveness for ≥ 1 dose vs. zero doses was calculated as: (1-adjusted odds ratio) * 100.ResultsThe sensitivity and specificity of parental report of their child's immunization with a rotavirus vaccine were 97% (95% CI 96–98), and 75% (95% CI 65–82), respectively. Kappa coefficient was 0.69 (p < 0.001) for the agreement between the two methods. Rotavirus vaccine effectiveness was 72% (95% CI 54–84) when using parental report of rotavirus immunization and 79% (95% CI 62–88) when using the registry.ConclusionParental report of their child's immunization with a rotavirus vaccine demonstrated high sensitivity, although the specificity was relatively low. Vaccine effectiveness was similar regardless of method used to determine rotavirus immunization status. Parental report of vaccination status can be useful in vaccine effectiveness assessment.     

Cost-effectiveness analysis of the implementation of a National Immunization Program for rotavirus vaccination in a country with a low rotavirus gastroenteritis-related mortality: A South Korean study

Rotavirus is a leading cause of severe gastroenteritis among children younger than 5 years in South Korea. Two rotavirus vaccines (RVs), pentavalent human-bovine reassortant vaccine (Rotateq®; RV5) and attenuated human strain originated monovalent vaccine (Rotarix®; RV1), have been available for voluntary vaccination using out-of-pocket payment since 2007 and 2008, respectively. Yet, RVs are not included in the National Immunization Program (NIP), partly because of the low associated mortality rate. We assessed the cost-effectiveness of RVs to assist the evidence-based decision-making process for NIP implementation in South Korea. Using a transparent age-structured static cohort model, we simulated the experience of ten annual birth cohorts of South Korean children from 2018 to 2027. Model inputs included rotavirus gastroenteritis (RVGE) incidence and mortality rates, RVGE treatment costs, vaccine coverage and timeliness, and vaccine effectiveness and price. The incremental costs of including RVs in the NIP compared to no vaccination were 59,662,738 USD and 152,444,379 USD for RV1 and RV5, respectively. The introduction of RV1 and RV5 can prevent 4799 disability-adjusted life years (DALYs) and 5068 DALYs. From the societal perspective, the incremental cost-effectiveness ratios (ICERs) for adopting RV into the NIP versus no vaccination were 12,432 USD per DALY averted for RV1 and 30,081 USD per DALY averted for RV 5. The weighted average for the ICERs of the two vaccines computed using the market share of each vaccine in the current voluntary use as a weight, was 21,698 USD per DALY averted. The estimated ICER was below 1 × gross domestic product per capita (30,000 USD), which has been a commonly used willingness-to-pay threshold for health care technology assessment in South Korea, suggesting that introducing RVs into the NIP would be cost-effective.     

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.     

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.     

Identifying signatures of the impact of rotavirus vaccines on hospitalizations using sentinel surveillance data from Latin American countries

BackgroundPassive surveillance data are often the only available source of data that can be used to evaluate the population-level impact of vaccination, but such data often suffer from important limitations such as changes in surveillance efforts. This study provides an example of how to identify important signatures of rotavirus vaccine impact, including evaluating the overall effectiveness and changes in rotavirus seasonal dynamics.MethodsWe used data from a standardized sentinel rotavirus surveillance network in six Latin American countries (Bolivia, El Salvador, Guatemala, Honduras, Paraguay, and Venezuela) from 2004 to 2017. A random-effects model was used to evaluate changes in the proportion of rotavirus-associated hospitalizations following vaccine introduction. Harmonic regression models were used to estimate vaccine impact on the number of rotavirus hospitalizations, controlling for trends in rotavirus-negative cases. Changes to rotavirus seasonality were evaluated using center of gravity analysis, wavelet analysis, and harmonic regression.ResultsAll countries observed declines in the proportion of rotavirus-positive acute diarrhea samples with a mean reduction of 16% (95% confidence interval: 10–22%). We estimate that each 10% increase in vaccine coverage was associated with declines in the number of rotavirus-positive cases, ranging from 4.3% (1.3–7.2%) in Honduras to 21.4% (16.8–25.9%) in Venezuela. The strength of the seasonal peak in rotavirus incidence became smaller after vaccine introduction in Guatemala, Honduras, and Venezuela. Seasonal peaks also shifted later in the surveillance year, especially in higher-mortality countries.ConclusionsThe combination of methods we applied have different strengths that allow us to identify common signatures of rotavirus vaccine impact.     

Risk of intussusception after monovalent rotavirus vaccine (Rotavac) in Indian infants: A self-controlled case series analysis

BackgroundAn association between rotavirus vaccination and intussusception has been documented in post-licensure studies in some countries. We evaluated the risk of intussusception associated with monovalent rotavirus vaccine (Rotavac) administered at 6, 10 and 14 weeks of age in India.MethodsActive prospective surveillance for intussusception was conducted at 22 hospitals across 16 states from April 2016 through September 2017. Data on demography, clinical features and vaccination were documented. Age-adjusted relative incidence for 1–7, 8–21, and 1–21 days after rotavirus vaccination in children aged 28–364 days at intussusception onset was estimated using the self-controlled case-series (SCCS) method. Only Brighton Collaboration level 1 cases were included.ResultsOut of 670 children aged 2–23 months with intussusception, 311 (46.4%) children were aged 28–364 days with confirmed vaccination status. Out of these, 52 intussusception cases with confirmed receipt of RVV were included in the SCCS analysis. No intussusception case was observed within 21 days of dose 1. Only one case occurred during 8–21 days after the dose 2. Post-dose 3, two cases in 1–7 days and 7 cases during 8–21 days period were observed. There was no increased risk of intussusception during 1–7 days after the doses 1 and 2 (zero cases observed) or dose 3 (relative incidence [RI], 1.71 [95% confidence interval {CI} 0.0–5.11]). Similarly, no increased risk during 8–21 days after the dose 1 (zero cases observed), dose 2 (RI, 0.71 [95% CI, 0.0–3.28]) or dose 3 (RI, 2.52 [95% CI, 0.78–5.61]). The results were similar for 1–21 day periods after the doses separately or pooled.ConclusionsThe risk of intussusception during the first 21 days after any dose of rotavirus vaccine (Rotavac) was not higher among the Indian infants than the background risk, based on limited SCCS analysis of 52 children.     

Long-term effectiveness of pentavalent and monovalent rotavirus vaccines against hospitalization in Taiwan children

BackgroundTwo rotavirus vaccines (RV1 and RV5) are available on the private market in Taiwan, not included in national immunization program. Scanty reports evaluated the rotavirus vaccine effectiveness (VE) in Asian countries.MethodsFrom February 2014-July 2017, we conducted a prospective case-control study in ten hospitals in Taiwan. Case-patients included children aged 8–59 months, and hospitalized with laboratory-confirmed rotavirus acute gastroenteritis (AGE). For each case patient, up to four controls, rotavirus-negative AGE or non-AGE illnesses, respectively, were matched by gender, age and enrolled date. Vaccination history was confirmed through vaccination card or hospital record. VE was calculated as (1 − odds ratio of vaccination) × 100%.ResultsTotally 4248 AGE patients and 2242 non-AGE controls were enrolled. A total of 330 case-patients with rotavirus AGE, 1226 rotavirus-negative AGE controls and 1122 non-AGE controls were included for analysis. Unvaccinated rate was 85.15% for rotavirus-positive cases, 42.9% for rotavirus-negative controls, and 34.31% for non-AGE controls. VE of two-dose RV1 was 84.9% (95% confidence interval [CI]:77.7%, 90.1%) for rotavirus-negative AGE and 88.9% (95% CI: 83.4%, 92.8%) for non-AGE controls, while VE of three-dose RV5 was 92.5% (95% CI: 85.1%, 96.7%) and 96.4% (95% CI: 91.9%, 98.6%), respectively. For respective vaccine, VEs were not significantly different in term of rotavirus genotypes. VEs of both vaccines declined <80% in children aged three years by combined controls.ConclusionsBoth vaccines provided excellent and sustained protection against rotavirus AGE hospitalization in children in Taiwan, but the effectiveness declined slightly in children aged three years.     

Immunogenicity and safety of a liquid Pentavalent (DTwP-Hb-Hib) combination vaccine manufactured by Human Biologicals Institute in 6–8 weeks old healthy infants: A phase III,randomized, single blind,non-inferiority study

BackgroundA liquid Pentavalent (DTwP-Hb-Hib) combination vaccine, developed by Human Biologicals Institute, underwent a Phase III clinical study in India. In this randomized, single blind, non-inferiority study, the immunogenicity and safety of this Investigational vaccine was compared with Pentavac SD® vaccine in 6–8 weeks old healthy infants.MethodsA total of 405 healthy infants aged 6–8 weeks old were randomized in 2:1 ratio to receive three doses of either the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine or Pentavac SD® vaccine at four to six weeks interval. Immunogenicity was compared by estimation of antibody titers before the first dose and 4–6 weeks after the third dose of vaccination. Safety of each vaccine was assessed and compared by collection of data on solicited and unsolicited adverse events throughout the study period.ResultsOut of a total of 405 enrolled subjects, 387 subjects completed the study. The seroconversion rates, seroprotection rates and geometric mean titres of the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine group were found to be comparable and non-inferior to the Pentavac SD® vaccine group at 4–6 weeks after the third dose of vaccination. Pain, erythema and swelling at the site of injection were found to be the most common local adverse events whereas fever, irritability and unusual crying were found to be the most common systemic adverse events in both the vaccine groups. No vaccine related serious adverse event was reported. In this study, both the Investigational vaccine as well as the Comparator vaccine were found to be immunogenic and well tolerated.ConclusionAfter assessment of the results of the study it was concluded that the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine developed by Human Biologicals Institute was immunogenic and safe when administered to infants aged 6–8 weeks and was non-inferior in immunogenicity and safety to Pentavac SD® vaccine.Clinical Trial Registry of India Identifier: CTRI/2016/01/006541.     

Timeliness and factors associated with rotavirus vaccine uptake among Australian Aboriginal and non-Aboriginal children: A record linkage cohort study

ObjectivesRotavirus vaccines (RV), included in Australia’s National Immunisation Program from mid-July 2007, are unique in strict time limits for administration. Here, we report on timeliness of RV uptake, compare cumulative RV coverage to age 12 months with DTPa, and assess factors associated with receipt of RV among Aboriginal and non-Aboriginal children.MethodsBirth records for 681,456 children born in two Australian states in 2007–2012 were probabilistically linked to national immunisation records. We assessed on-time coverage (defined as receipt of vaccine dose between 4 days prior to scheduled date and the recommended upper limit) for RV and compared this to diphtheria-tetanus-pertussis (DTPa) vaccine. Logistic regression modelling was used to assess independent determinants of receipt of RV.ResultsCompared to non-Aboriginal infants, on-time RV coverage was lower for all doses among Aboriginal infants. Post the upper age limit of RV dose2, DTPa dose2 coverage increased by 9–16% to ≥90%, whereas RV coverage remained around 77% (Aboriginal) and 85% (non-Aboriginal). Compared to first-born children, the adjusted odds of receiving ≥1 RV dose if born to a mother with ≥3 previous births was 0.30 (95%CI: 0.27–0.34) among Aboriginal, and 0.53 (95%CI: 0.51–0.55) among non-Aboriginal children. Prematurity (<33 weeks), low birthweight (<1500 g), maternal age <20 years, maternal smoking during pregnancy and living in a disadvantaged area were independently associated with decreased vaccine uptake.ConclusionsAboriginal children are at greater risk of rotavirus disease than non-Aboriginal children and delayed vaccine receipt is substantially higher. Although specific programs targeting groups at risk of delayed vaccination might improve RV coverage, relaxation of upper age restrictions is most readily implementable, and its overall risk-benefit should be evaluated.     

Potential impact and cost-effectiveness of rotavirus vaccination in Afghanistan

IntroductionDespite progress made in child survival in the past 20 years, 5.9 million children under five years died in 2015, with 9% of these deaths due to diarrhea. Rotavirus is responsible for more than a third of diarrhea deaths. In 2013, rotavirus was estimated to cause 215,000 deaths among children under five years, including 89,000 in Asia. As of April 2017, 92 countries worldwide have introduced rotavirus vaccination in their national immunization program. Afghanistan has applied for Gavi support to introduce rotavirus vaccination nationally. This study estimates the potential impact and cost-effectiveness of a national rotavirus immunization program in Afghanistan.MethodsThis study examined the use of Rotarix® (RV1) administered using a two-dose schedule at 6 and 10 weeks of age. We used the ProVac Initiative’s UNIVAC model (version 1.2.09) to evaluate the impact and cost-effectiveness of a rotavirus vaccine program compared with no vaccine over ten birth cohorts from 2017 to 2026 with a 3% annual discount rate. All monetary units are adjusted to 2017 US$.ResultsRotavirus vaccination in Afghanistan has the potential to avert more than one million cases; 660,000 outpatient visits; approximately 50,000 hospital admissions; 650,000 DALYs; and 12,000 deaths, over 10 years. Not accounting for any Gavi subsidy, rotavirus vaccination can avert DALYs at US$82/DALY from the government perspective and US$80/DALY from the societal perspective. With Gavi support, DALYs can be averted at US$29/DALY and US$31/DALY from the societal and government perspective, respectively. The average yearly cost of a rotavirus vaccination program would represent 2.8% of the total immunization budget expected in 2017 and 0.1% of total health expenditure.ConclusionThe introduction of rotavirus vaccination would be highly cost-effective in Afghanistan, and even more so with a Gavi subsidy.     

Explaining the formation of a plateau in rotavirus vaccine impact on rotavirus hospitalisations in Belgium

BackgroundObservational data on the reduction in hospitalisations after rotavirus vaccine introduction in Belgium suggest that vaccine impact plateaued at an unexpectedly high residual hospitalisation rate. The objective of this analysis was to identify factors that influence real-world vaccine impact.MethodsData were collected on hospitalisations in children aged ≤ 5 years with rotavirus disease from 11 hospitals since 2005 (the RotaBIS study). The universal rotavirus vaccination campaign started late in 2006. A mathematical model simulated rotavirus hospitalisations in different age groups using vaccine efficacy and herd effect, influenced by vaccine coverage, vaccine waning, and secondary infection sources. The model used optimisation analysis to fit the simulated curve to the observed data, applying Solver add-in software. It also simulated an ‘ideal’ vaccine introduction maximising hospitalisation reduction (maximum coverage, maximum herd effect, no waning), and compared this with the best-fit simulated curve. Modifying model input values identified factors with the largest impact on hospitalisations.ResultsCompared with the ‘ideal’ simulation, observed data showed a slower decline in hospitalisations and levelled off after three years at a higher residual hospitalisation rate. The slower initial decline was explained by the herd effect in unvaccinated children. The higher residual hospitalisation rate was explained by starting the vaccine programme in November, near the rotavirus seasonal peak. This resulted in low accumulated vaccine coverage during the first rotavirus disease peak season, with the consequential appearance of secondary infection sources. This in turn reduced the herd effect, resulting in a diminished net impact.ConclusionsOur results indicate that countries wishing to maximise the impact of rotavirus vaccination should start vaccinating well ahead of the rotavirus seasonal disease peak. This maximises herd effect during the first year leading to rapid and high reduction in hospitalisations. Secondary infection sources explain the observed data in Belgium better than vaccine waning.     

Effects of rotavirus vaccine on all-cause acute gastroenteritis and rotavirus hospitalizations in Israel: A nationwide analysis

BackgroundIn December 2010, the pentavalent rotavirus vaccine (RotaTeq) was added to the national immunization program in Israel. The study aim was to examine national reductions in all-cause acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) hospitalizations among children aged 0–59 months following the introduction of universal rotavirus immunization in Israel.MethodsWe extracted data from the Israel National Hospital Discharge Database. Hospitalization rates were calculated by dividing the annual number of all-cause AGE and RVGE hospitalizations by the number of children aged 0–59 months residing Israel. To assess rate reductions, we compared the mean hospitalization rate for the pre-vaccine years (2002–2008) with that for the universal vaccination years (2011–2017). Interrupted time-series analyses were undertaken. During 2008–2010 rotavirus vaccines were partially available.ResultsA total of 131,116 AGE hospitalizations were reported, of which 13,111 (10.0%) were coded as RVGE hospitalizations. The average annual all-cause AGE hospitalization rate during the pre-vaccine period was 147.9 (95% CI 146.7–149.0) per 10,000 children aged 0–59 months, and declined by 38.7–53.0% during the universal vaccination years. The average annual pre-vaccine RVGE hospitalization rate was 16.9 (95% CI 16.5–17.3) per 10,000 children, and declined by 89.1% during 2016–2017.Findings from interrupted time-series analyses showed significant impact of introducing universal rotavirus immunization on the declines of all-cause AGE and RVGE hospitalizations rates. A multivariable Autoregressive Integrated Moving Average model showed that the variable “immunization period” was a significant predictor of RVGE hospitalizations (t = 7.3, p < 0.001) for the universal vaccination years.The declines in hospitalizations rates of all-cause AGE were lower among Arab children compared to Jewish children, but the declines in RVGE rates were similar between the groups.ConclusionsNational hospitalization data demonstrated substantial and consistent reductions in all-cause AGE and RVGE hospitalizations following the implementation of universal rotavirus vaccination program.     

Cost-benefit analysis of a national influenza vaccination program in preventing hospitalisation costs in Australian adults aged 50–64 years old

IntroductionInfluenza causes a significant burden among Australian adults aged 50–64, however, vaccine coverage rates remain suboptimal. The National Immunisation Program (NIP) currently funds influenza vaccinations in this age group only for those at high risk of influenza complications.AimsThe main aim of this study was to determine whether a strategy of expanding the government-funded vaccination program to all adults 50–64 in preventing influenza-related hospitalisations will be cost beneficial to the government.MethodsA cost-benefit analysis from a governmental perspective was performed using parameters informed by publicly available databases and published literature. Costs included cost of vaccinations and general practitioner consultation while benefits included the savings from averted respiratory and acute myocardial infarction (AMI) hospitalisations.ResultsIn the base-case scenario, the proposed policy would prevent 314 influenza/pneumonia, 388 other respiratory and 1482 AMI hospitalisations in a year. The government would save $8.03 million with an incremental benefit-cost ratio of 1.40. Most savings were due to averted AMI hospitalisations. In alternative scenarios cost savings ranged from saving of $31.4 million to additional cost to the government of $15.4 million, with sensitive variation in vaccine administration practices (through general practitioner or pharmacists) and vaccine effectiveness estimates.DiscussionExtension of the NIP to include adults 50–64 years of age is likely to be cost beneficial to the government, although this finding is sensitive to vaccine administration cost, which varies if provided through general practitioners or pharmacists; and to variation in vaccine effectiveness. An increased role of pharmacists in immunisation programs would likely result in cost savings in an expanded adult immunisation program.     

Cost-effectiveness of human papillomavirus vaccination in girls living in Latin American countries: A systematic review and meta-analysis

BackgroundCervical cancer is a major public health problem in Latin America. Cost-effectiveness studies help stakeholders with decisions regarding human papillomavirus (HPV) vaccination programs, one of the main prevention measures. Our objective was to synthesize the results of cost-effectiveness studies of HPV vaccination in girls, to understand factors influencing cost-effectiveness in the region.MethodsWe systematically searched databases as well as repositories from conferences, Ministries of Health and Health Technology Assessment offices. Incremental cost-effectiveness ratios (ICERs) were extracted, with data converted to international dollars (I$) and inflated to 2019 values. We used the gross domestic product per capita as threshold for judging the cost-effectiveness of vaccination. We calculated the geometric mean ICER by type of vaccine, whether screening (cytology or HPV test) was used as comparator, effectiveness measure, perspective, source of funding, year of cost, and country.ResultsWe found 24 studies. Despite the methodological differences, most studies concluded that HPV vaccination of girls in Latin American countries was either cost-saving or cost-effective. The mean ICER was I$ 3,804 for the bivalent vaccine, I$ 640 for the quadrivalent and I$ 358 for a generic HPV-16/18 vaccine. The mean ICER was lower in the studies that used HPV DNA test instead of cytology (I$ 122 vs I$ 1,841) as comparator; used the societal perspective (I$ 235 vs. I$ 1,986); were funded by non-profit sources instead of by pharmaceutical industry (I$ 421 vs. I$ 2,676); and used costs obtained prior to 2008 (I$ 365 vs I$ 1,415). We observed great variation in the mean ICERs by effectiveness measure (I$ 402 for per disability adjusted life years, I$ 461 for life year saved, and I$ 1,795 for quality adjusted life years).ConclusionsMost studies concluded that HPV vaccination of girls in Latin America countries was cost-saving or cost-effective, despite heterogeneity between models.     

Cost-effectiveness of introducing an MF59-adjuvanted trivalent influenza vaccine for older adults in Argentina

IntroductionInfluenza surveillance in Argentina reported influenza-like illness at a rate of 3500/100,000, a hospitalization rate of 15.5/100,000, and a death rate of 0.32/100,000 annually in adults aged over 65 years. The high burden of disease may be due to a combination of immunosenescence and the suboptimal clinical effectiveness of conventional, non-adjuvanted influenza vaccines in this age group. There is a clinical need for more effective influenza vaccines in this population. This study evaluated the cost-effectiveness of an MF59®-adjuvanted trivalent influenza vaccine (aTIV) in adults aged over 65 years in Argentina compared with the non-adjuvanted trivalent influenza vaccine (TIV) used under the current national vaccination policy.MethodsA decision tree cost-effectiveness model was developed to estimate the cost-effectiveness of switching from TIV to aTIV in Argentinian older adults. The model compared cost and health benefits of vaccination in one influenza season from the payer perspective. The main predictions included survival, quality-adjusted survival, and costs. Model inputs were sourced from Argentina or internationally where local data was considered inaccurate. Vaccine efficacy assumptions were extracted from recently published, peer-reviewed scientific literature.ResultsSwitching from TIV to aTIV would result in 170 deaths averted and 1310 incremental quality-adjusted life years (QALYs) gained. The incremental cost-effectiveness ratio per QALY was US $2660.59 from the payer perspective. In all sensitivity analyses, aTIV remained highly cost-effective. The probabilistic sensitivity analyses showed a 95% CI per QALY of US $113.74–7721.67.ConclusionIntroducing an adjuvanted influenza vaccine in Argentina is potentially beneficial and cost-effective relative to the currently-used TIV through the reduction of disease burden and utilization of healthcare resources.     

Cost-effectiveness analysis of quadrivalent and nonavalent human papillomavirus vaccines in Ethiopia

BackgroundIn Ethiopia, cervical cancer is the second most common cancer among women of the reproductive age group. Since 2018, the quadrivalent human papillomavirus (4vHPV) vaccine targeting four HPV types (6/11/16/18) has been introduced in the national immunization program in Ethiopia. Currently, however, a nonavalent HPV (9vHPV) vaccine which provides broader protection against nine HPV types (?6/11/16/18/31/33/45/52/58) is available for global use. Our study, therefore, aims to estimate the cost-effectiveness of 9vHPV vaccine compared to the current HPV vaccination program in Ethiopia.MethodA static Markov cohort model was used to simulate the progression of HPV infection to cervical cancer for a cohort of 12-years-old girls (N = 100,000) in Ethiopia. The model ran up to the age of 100 years, with a cycle length of 1 year. One-way and probabilistic sensitivity analyses were used to explore the robustness of the model and uncertainties around the parameters included in the model. Cost-effectiveness thresholds of one and three times gross domestic product (GDP) per quality-adjusted life-year (QALY) gained were considered.ResultsAt a price of US$ 6.9, the incremental cost-effectiveness ratio (ICER) per QALY gained for the 9vHPV vaccine was US$ 454 compared to the 4vHPV vaccine, which is less than one times GDP per capita of Ethiopia. The ICER was most sensitive to the change in the discount rate of QALYs. Compared to 4vHPV vaccine, for 9vHPV vaccine to remain very cost-effective and cost-effective, its price per dose should not exceed US$ 8.4 and US$ 15, respectively, at a threshold of one and three times GDP per capita.ConclusionCompared to the 4vHPV vaccine, the 9vHPV vaccine is a cost-effective option in Ethiopia, given that its price per dose does not exceed US$15.     

Individual factors influencing COVID-19 vaccine acceptance in between and during pandemic waves (July–December 2020)

BackgroundA year after the start of the COVID-19 outbreak, the global rollout of vaccines gives us hope of ending the pandemic. Lack of vaccine confidence, however, poses a threat to vaccination campaigns. This study aims at identifying individuals’ characteristics that explain vaccine willingness in Flanders (Belgium), while also describing trends over time (July–December 2020).MethodsThe analysis included data of 10 survey waves of the Great Corona Survey, a large-scale online survey that was open to the general public and had 17,722–32,219 respondents per wave. Uni- and multivariable general additive models were fitted to associate vaccine willingness with socio-demographic and behavioral variables, while correcting for temporal and geographical variability.ResultsWe found 84.2% of the respondents willing to be vaccinated, i.e., respondents answering that they were definitely (61.2%) or probably (23.0%) willing to get a COVID-19 vaccine, while 9.8% indicated maybe, 3.9% probably not and 2.2% definitely not. In Flanders, vaccine willingness was highest in July 2020 (90.0%), decreased over the summer period to 80.2% and started to increase again from late September, reaching 85.9% at the end of December 2020. Vaccine willingness was significantly associated with respondents’ characteristics: previous survey participation, age, gender, province, educational attainment, household size, financial situation, employment sector, underlying medical conditions, mental well-being, government trust, knowing someone with severe COVID-19 symptoms and compliance with restrictive measures. These variables could explain much, but not all, variation in vaccine willingness.ConclusionsBoth the timing and location of data collection influence vaccine willingness results, emphasizing that comparing data from different regions, countries and/or timepoints should be done with caution. To maximize COVID-19 vaccination coverage, vaccination campaigns should focus on (a combination of) subpopulations: aged 31–50, females, low educational attainment, large households, difficult financial situation, low mental well-being and labourers, unemployed and self-employed citizens.     

Cost-effectiveness of routine catch-up hepatitis a vaccination in the United States: Dynamic transmission modeling study

BackgroundDespite routine vaccination of children against hepatitis A (HepA), a large segment of the United States population remains unvaccinated, imposing a risk of hepatitis A virus (HAV) to adolescents and adults. In July of 2020, the Advisory Committee on Immunization Practices recommended that all children and adolescents aged 2–18 years who have not previously received a HepA vaccine be vaccinated. We evaluated the public health impact and cost-effectiveness of this HepA catch-up vaccination strategy.MethodsWe used a dynamic transmission model to compare adding a HepA catch-up vaccination of persons age 2–18 years to a routine vaccination of children 12–23 months of age with routine vaccination only in the United States. The model included various health compartments: maternal antibodies, susceptible, exposed, asymptomatic infectious, symptomatic infectious (outpatient, hospitalized, liver transplant, post- liver transplant, death), recovered, and vaccinated with and without immunity. Using a 3% annual discount rate, we estimated the incremental cost per quality-adjusted life year (QALY) gained from a societal perspective over a 100-year time horizon. All costs were converted into 2020 US dollars.FindingsCompared with the routine vaccination policy at 12–23 months of age over 100 years, the catch-up program for unvaccinated children and adolescents aged 2–18 years, prevented 70,072 additional symptomatic infections, 51,391 outpatient visits, 16,575 hospitalizations, and 413 deaths. The catch-up vaccination strategy was cost-saving when compared with the routine vaccination strategy. In scenario analysis allowing administering a second dose to partially vaccinated children, the cost-effectiveness of was not favorable at a higher vaccination coverage ($196,701/QALY at 5% and $476,241/QALY at 50%).InterpretationHepA catch-up vaccination in the United States is expected to reduce HepA morbidity and mortality and save cost. The catch-up program would be optimized when focusing on unvaccinated children and adolescents and maximizing their first dose coverage.     

Socioeconomic disadvantage and human papillomavirus (HPV) vaccination uptake

ImportanceDespite availability of safe and effective human papillomavirus (HPV) vaccines, vaccination uptake remains low in the U.S. Research examining the impact of neighborhood socioeconomic status on HPV vaccination may help target interventions.ObjectiveTo examine the association between area deprivation and HPV vaccine initiation and completion.Design, setting, participantsRetrospective cohort study of individuals aged 11–18 years residing in the upper Midwest region. Receipt of HPV vaccination was examined over a three-year follow-up period (01/01/2016–12/31/2018).Main outcomes and measuresOutcomes of interest were initiation and completion of HPV vaccination. Demographic data were collected from the Rochester Epidemiology Project (REP). Area-level socioeconomic disadvantage was measured by calculating an Area Deprivation Index (ADI) score for each person, a measure of socioeconomic disadvantage derived from American Community Survey data. Multivariable mixed effect Cox proportional hazards models were used to examine the association of ADI quartiles (Q1-Q4) with HPV vaccine series initiation and completion, given initiation.ResultsIndividuals residing in census block groups with higher deprivation had significantly lower likelihood of HPV vaccine initiation (Q2: HR = 0.91, 0.84–0.99 Q3: HR = 0.83, 0.76–0.90; Q4: HR = 0.84, 0.74–0.96) relative to those in the least-deprived block groups (Q1). Similarly, those living in block groups with higher deprivation had significantly lower likelihood of completion (Q2: HR = 0.91, 0.86–0.97; Q3: HR = 0.87, 0.81–0.94; Q4: HR = 0.82, 0.74–0.92) compared to individuals in the least-deprived block groups (Q1).Conclusions and relevanceLower probability of both HPV vaccine-series initiation and completion were observed in areas with greater deprivation. Our results can inform allocation of resources to increase HPV vaccination rates in our primary care practice and provide an example of leveraging public data to inform similar efforts across diverse health systems.