Economic Evaluation of Universal Varicella Vaccination in Mexico.

BACKGROUND: Universal varicella vaccination has proven to be cost-effective (CE) in countries where implemented. However, this has not been evaluated for Mexico. METHODS: The yearly disease burden (varicella cases/deaths, outpatient visits, and hospitalizations) was derived from Mexican seroprevalence data adjusted to the 2020 population. The yearly economic burden was calculated by combining disease with Mexican unit cost data from both health care and societal perspectives. Four different vaccination strategies were evaluated: (1) 1 dose of varicella vaccine at 1 year old; (2) 2 doses at 1 and 6 years; (3) 1 dose of varicella vaccine at 1 year, and quadrivalent measles-mumps-rubella-varicella vaccine at 6 years; (4) 2 doses of measles-mumps-rubella-varicella vaccine at 1 and 6 years. We developed an economic model for each vaccination strategy where 20 consecutive birth cohorts were simulated. Vaccination impact (number of avoided cases/deaths) was evaluated for a 20-year follow-up period based on vaccine effectiveness (87% and 97.4% for 1 and 2 doses), and assuming a 95% coverage. We estimated annual costs saved, incremental cost-effectiveness ratio, and costs per life year gained. RESULTS: Avoided cases during the 20-year follow-up with 1, and 2 doses were 20,570,722 and 23,029,751, respectively. Strategies 1 and 2 were found to be cost saving, and strategy 3 to be CE. Strategy 4 was not CE. Strategies 1 and 2 would allow saving annually $53.16 and $34.41 million USD, respectively, to the Mexican society. CONCLUSIONS: Universal varicella vaccination, using 1 dose or 2 doses, would result in a cost-beneficial and CE public health intervention in Mexico.

Real-world impact and effectiveness assessment of the quadrivalent HPV vaccine: a systematic review of study designs and data sources.

INTRODUCTION: Vaccine effectiveness and impact studies are typically observational, generating evidence after vaccine launch in a real-world setting. For human papillomavirus (HPV) vaccination studies, the variety of data sources and methods used is pronounced. Careful selection of study design, data capture and analytical methods can mitigate potential bias in such studies. AREAS COVERED: We systematically reviewed the different study designs, methods, and data sources in published evidence (1/2007-3/2020), which assessed the quadrivalent HPV vaccine effectiveness and impact on cervical/cervicovaginal, anal, and oral HPV infections, anogenital warts, lesions in anus, cervix, oropharynx, penis, vagina or vulva, and recurrent respiratory papillomatosis. EXPERT OPINION: The rapid growth in access to real-world data allows global monitoring of effects of different public health interventions, including HPV vaccination programs. But the use of data which are not collected or organized to support research also underscore a need to develop robust methodology that provides insight of vaccine effects and consequences of different health policy decisions. To achieve the WHO elimination goal, we foresee a growing need to evaluate HPV vaccination programs globally. A critical appraisal summary of methodology used will provide timely guidance to researchers who want to initiate research activities in various settings.

Norovirus Gastroenteritis among Hospitalized Patients, Germany, 2007-2012.

We estimated numbers of hospitalizations for norovirus gastroenteritis (NGE) and associated medical costs in Germany, where norovirus testing is high because reimbursement is affected. We extracted aggregate data for patients hospitalized with a primary or secondary code from the International Classification of Diseases, 10th Revision (ICD-10), NGE diagnosis during 2007-2012 from the German Federal Statistics Office. We assessed reliability of the coding system in patient records from a large academic hospital. Approximately 53,000-90,000 NGE hospitalizations occurred annually in Germany (21,000-33,000 with primary and 32,000-57,000 with secondary ICD-10-coded NGE diagnoses). Rates of hospitalization with NGE as primary diagnosis were highest in children <2 years of age; rates of hospitalization with NGE as secondary diagnosis were highest in adults >85 years of age. The average annual reimbursed direct medical cost of NGE hospitalizations was €31-43 million. Among patients with a NGE ICD-10 code, 87.6% had positive norovirus laboratory results.

Vaccine safety surveillance in pregnancy in low- and middle-income countries using GAIA case definitions: A feasibility assessment.

BACKGROUND: Global efforts to adequately monitor safety of new vaccines for pregnant women in low and middle-income countries (LMICs) are needed. The Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) project recently published case definitions based on levels of diagnostic certainty for pregnancy- and neonatal outcomes and maternal vaccination. As a preliminary step to assessing the applicability of these definitions in LMICs, WHO selected sites and conducted a feasibility assessment to evaluate their ability to identify and classify selected outcomes (preterm birth, neonatal death, neonatal invasive bloodstream infection (NI-BSI), stillbirth) and maternal vaccination. METHODS: Candidate sites were initially screened using a questionnaire. For each outcome, eligible sites were asked to retrospectively identify and collect information for three individuals born in 2016. Subsequently, outcomes were classified by level of diagnostic certainty. RESULTS: Fifty-one sites (15 countries) were screened; 32 of them (9 countries) participated in the assessment and identified 315 subjects with the outcomes of interest. Twenty-four sites (8 countries) identified at least one subject per outcome and agreed to continue participating. The majority (80%) of preterm births, neonatal deaths, and NI-BSI subjects, but only 50% of stillbirths, could be assessed for diagnostic certainty. The main reasons for not classifying stillbirths were insufficient information to distinguish between antepartum and intrapartum stillbirth (29%); or that not all data for one subject fit into a single level of diagnostic certainty (35%). Forty-nine percent of mothers were considered vaccinated, 6% not-vaccinated, and vaccination status could not be assessed in 44% of them. DISCUSSION: GAIA case definitions for four neonatal outcomes and maternal vaccination were successfully piloted in 24 sentinel sites across four WHO regions. Our assessment found that modification of the stillbirth definition could help avoid potential misclassification. Vaccine safety monitoring in LMICs will benefit from systematic recording of all vaccinations during pregnancy.

The incidence of medically-attended norovirus gastro-enteritis in Japan: Modelling using a medical care insurance claims database.

BACKGROUND: The burden of medically-attended acute gastro-enteritis (MA-AGE) that can be attributed to norovirus is not well established in Japan. Using a nationwide database of medical care insurance claims, we estimated the incidence of medically-attended norovirus-attributable gastroenteritis (MA-NGE) in Japan. METHODS: The incidences of MA-NGE outpatient consultations or hospitalization in Japan were modelled on seasonal patterns of MA-AGE for unspecified causes derived from the Japan Medical Data Center (JMDC) database for the period July 2007 to June 2015. RESULTS: Mean age-adjusted annual incidence rates (per 10,000 person-years) of MA-NGE associated with outpatient care or hospitalization were 389 (95% CI 269-558) and 13 (95% CI 9-20), respectively. Highest rates were in children under 5 years of age: 1,569 (95% CI 1,325-1,792) for outpatient consultations and 48 (95% CI 39-56) for hospitalizations. Of all gastroenteritis episodes associated with outpatient care or hospitalization, 29% and 31% were attributed to norovirus, respectively. Norovirus was estimated to be responsible for 4,964,000 outpatient visits (95% CI 3,435,000-7,123,000) and 171,000 hospitalizations (95% CI 110,000-251,000) per year across Japan. CONCLUSIONS: Incidence rates of MA-AGE are high in Japan, and norovirus-attributable disease is at least as high as in some other developed countries.

Rapid assessment of the reactogenicity of a 2016-2017 seasonal influenza vaccine: results from a feasibility study.

BACKGROUND: ​​The European Medicines Agency (EMA) calls for a strategy for enhanced safety surveillance of seasonal influenza vaccines. OBJECTIVE: We assessed the feasibility of collecting reactogenicity data within one month of the start of the vaccination campaign in Belgium. METHODS: One hundred subjects aged 18 to 65 years who had received inactivated seasonal influenza vaccine in occupational setting were enrolled. For 7 days after vaccination, subjects received a daily SMS with a link to a web-based questionnaire where reactogenicity events and their severity were solicited. RESULTS: Data collection was completed by October 13th, 2016, before the peak of the vaccination campaign in Belgium. 68% of participants reported a local reaction and 65% a general reaction; 51% reported both a local and a general reaction. CONCLUSION: Here we show that it has been possible to collect reactogenicity data in adults for enhanced safety surveillance in Belgium in a timely manner. The observed reactogenicity is higher compared to previous observations for this vaccine measured in clinical trials.

Quantitative benefit-risk assessment by MCDA of the quadrivalent HPV vaccine for preventing anal cancer in males.

OBJECTIVES: To quantify the benefit-risk (BR) balance of the quadrivalent human papillomavirus (qHPV) vaccine for use in males, including anal cancer prevention, by using the multicriteria decision analysis (MCDA). METHODS: Value tree and an effect table were compiled using relevant qHPV vaccine efficacy/safety data. An expert panel validated the final model inputs. RESULTS: On a scale of 0-100, the MCDA qHPV vaccine score (66) was superior to the no vaccination score (46), indicating a more favorable BR balance for the qHPV vaccine. Significant changes in weight of individual outcomes were needed to change BR balance in sensitivity analyses. The qHPV vaccine maintained a better BR profile in all alternative models. CONCLUSIONS: MCDA can be used to transparently evaluate BR balance of vaccines. The qHPV vaccine had a favorable BR balance in males. Including anal cancer as a new indication further improves the BR profile of the qHPV vaccine.

Postmarketing surveillance of intussusception following mass introduction of the attenuated human rotavirus vaccine in Mexico.

BACKGROUND: Mexico initiated mass vaccination with the attenuated human rotavirus vaccine (Rotarix) in 2006. This postlicensure study aimed to assess any potential temporal association between vaccination and intussusception in Mexican infants. METHODS: Prospective, active surveillance for intussusception among infants aged less than 1 year was conducted in 221 hospitals across Mexico from the Mexican Institute of Social Security between January 2008 and October 2010. The temporal association between vaccination and intussusception was assessed by self-controlled case-series analysis. RESULTS: Of the 753 episodes of intussusception reported in 750 infants, 701 were in vaccinated infants (34.5% post-dose 1, 65.5% post-dose 2). The relative incidence of intussusception within 31 days of vaccination was 1.75 (95.5% confidence interval [CI]: 1.24-2.48; P=0.001) post-dose 1 and 1.06 (95.5% CI: 0.75-1.48; P=0.75) post-dose 2. The relative incidence of intussusception within 7 days of vaccination was 6.49 post-dose 1 (95.5% CI: 4.17-10.09; P<0.001) and 1.29 post-dose 2 (95.5% CI: 0.80-2.11; P=0.29). Clustering of intussusception within 7 days of vaccination was observed post-dose 1. An attributable risk of 3 to 4 additional cases of intussusception per 100,000 vaccinated infants was estimated. CONCLUSION: This is the largest surveillance study for intussusception after rotavirus vaccination to date. A temporal increase in the risk for intussusception was seen within 7 days of administration of the first vaccine dose. It is still uncertain whether rotavirus vaccination has any impact on the overall incidence of intussusception. This finding has to be put in perspective with the well-documented substantial benefits of rotavirus vaccination.

Safety of thimerosal-containing vaccines: a two-phased study of computerized health maintenance organization databases.

OBJECTIVE: To assess the possible toxicity of thimerosal-containing vaccines (TCVs) among infants. METHODS: A 2-phased retrospective cohort study was conducted using computerized health maintenance organization (HMO) databases. Phase I screened for associations between neurodevelopmental disorders and thimerosal exposure among 124 170 infants who were born during 1992 to 1999 at 2 HMOs (A and B). In phase II, the most common disorders associated with exposure in phase I were reevaluated among 16 717 children who were born during 1991 to 1997 in another HMO (C). Relative risks for neurodevelopmental disorders were calculated per increase of 12.5 micro g of estimated cumulative mercury exposure from TCVs in the first, third, and seventh months of life. RESULTS: In phase I at HMO A, cumulative exposure at 3 months resulted in a significant positive association with tics (relative risk [RR]: 1.89; 95% confidence interval [CI]: 1.05-3.38). At HMO B, increased risks of language delay were found for cumulative exposure at 3 months (RR: 1.13; 95% CI: 1.01-1.27) and 7 months (RR: 1.07; 95% CI: 1.01-1.13). In phase II at HMO C, no significant associations were found. In no analyses were significant increased risks found for autism or attention-deficit disorder. CONCLUSIONS: No consistent significant associations were found between TCVs and neurodevelopmental outcomes. Conflicting results were found at different HMOs for certain outcomes. For resolving the conflicting findings, studies with uniform neurodevelopmental assessments of children with a range of cumulative thimerosal exposures are needed.

Vaccinations and risk of central nervous system demyelinating diseases in adults.

BACKGROUND: Several case reports of the onset or exacerbation of multiple sclerosis or other demyelinating conditions shortly after vaccination have suggested that vaccines may increase the risk of demyelinating diseases. OBJECTIVE: To evaluate the association between vaccination and onset of multiple sclerosis or optic neuritis. DESIGN: Case-control study involving cases of multiple sclerosis or optic neuritis among adults 18 to 49 years of age. Data on vaccinations and other risk factors were obtained from computerized and paper medical records and from telephone interviews. SETTING: Three health maintenance organizations. PARTICIPANTS: Four hundred forty case subjects and 950 control subjects matched on health maintenance organization, sex, and date of birth. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Onset of first symptoms of demyelinating disease at any time after vaccination and during specified intervals after vaccination (<1 year, 1-5 years, and >5 years). RESULTS: Cases and controls had similar vaccination histories. The odds ratios (95% confidence intervals), adjusted for potential confounding variables, of the associations between ever having been vaccinated and risk of demyelinating disease (multiple sclerosis and optic neuritis combined) were 0.9 (0.6-1.5) for hepatitis B vaccine; 0.6 (0.4-0.8) for tetanus vaccination; 0.8 (0.6-1.2) for influenza vaccine; 0.8 (0.5-1.5) for measles, mumps, rubella vaccine; 0.9 (0.5-1.4) for measles vaccine; and 0.7 (0.4-1.0) for rubella vaccine. The results were similar when multiple sclerosis and optic neuritis were analyzed separately. There was no increased risk according to timing of vaccination. CONCLUSION: Vaccination against hepatitis B, influenza, tetanus, measles, or rubella is not associated with an increased risk of multiple sclerosis or optic neuritis.