Uncertainty and sensitivity of the sexual behavior changes to the current human papillomavirus vaccination campaign in Spain

Taking into account the public health importance of the human papillomavirus (HPV) control in the future, it is mandatory to assess the effect of the vaccination campaigns on the control of HPV spread and the associated diseases using reliable mathematical models. We propose a computational random network model with the aim of studying the transmission dynamics of HPV infections. This model reflects the herd immunity effect in the heterosexual network more accurately than the classical models. We perform a sensitivity analysis of the sexual behavior changes consisting of increasing the number of men who have sex with men (MSM), increasing the frequency of the intercourses and increasing the number of sexual partners. We find that large changes in the sexual behavior, in some extent, only have minor effects on the decline of the HPV infections in women and men in the current vaccination campaign in Spain (vaccination of young girls with a coverage of 70%). Therefore, the current vaccination program in Spain is robust for the heterosexuals. However, we cannot say the same for MSM, where they do not benefit by the herd immunity effect of the vaccination of girls, and consequently, the circulation of the virus among them remains unchanged. A consequence of the present study is that the effect of other external factors that may affect the transmission dynamics of the HPV, for instance, the tourism or the immigration, does not influence the protection provided by the current Spanish vaccination program.This work has been supported by the Spanish Ministerio de Economía, Industria y Competitividad (MINECO), the Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER UE) grant MTM2017-89664-P. This paper has been supported by the European Union through the Operational Program of the [European Regional Development Fund (ERDF) / European Social Fund (ESF)] of the Valencian Community 2014-2020. Files: GJIDI/2018/A/010 and GJIDI/2018/A/009

Optimizing strategies for meningococcal C disease vaccination in Valencia (Spain)

BackgroundMeningococcal C (MenC) conjugate vaccines have controlled invasive diseases associated with this serogroup in countries where they are included in National Immunization Programs and also in an extensive catch-up program involving subjects up to 20 years of age. Catch-up was important, not only because it prevented disease in adolescents and young adults at risk, but also because it decreased transmission of the bacteria, since it was in this age group where the organism was circulating. Our objective is to develop a new vaccination schedule to achieve maximum seroprotection in these groups.MethodsA recent study has provided detailed age-structured information on the seroprotection levels against MenC in Valencia (Spain), where vaccination is routinely scheduled at 2 months and 6 months, with a booster dose at 18 months of age. A complementary catch-up campaign was also carried out in n for children from 12 months to 19 years of age. Statistical analyses of these data have provided an accurate picture on the evolution of seroprotection in the last few years.ResultsAn agent-based model has been developed to study the future evolution of the seroprotection histogram. We have shown that the optimum strategy for achieving high protection levels in all infants, toddlers and adolescents is a change to a 2 months, 12 months and 12 years of age vaccination pattern. If the new schedule were implemented in January 2014, high-risk subjects between 15-19 years of age would have very low seroprotection for the next 6 years, thereby threatening the program.ConclusionsHigh protection levels and a low incidence of meningococcal C disease can be achieved in the future by means of a cost-free change in vaccination program. However, we recommend a new catch-up program simultaneous to the change in regular vaccination program

Random Network Models to Predict the Long-Term Impact of HPV Vaccination on Genital Warts

[EN] The Human papillomaviruses (HPV) vaccine induces a herd immunity effect in genital warts when a large number of the population is vaccinated. This aspect should be taken into account when devising new vaccine strategies, like vaccination at older ages or male vaccination. Therefore, it is important to develop mathematical models with good predictive capacities. We devised a sexual contact network that was calibrated to simulate the Spanish epidemiology of different HPV genotypes. Through this model, we simulated the scenario that occurred in Australia in 2007, where 12¿13 year-old girls were vaccinated with a three-dose schedule of a vaccine containing genotypes 6 and 11, which protect against genital warts, and also a catch-up program in women up to 26 years of age. Vaccine coverage were 73% in girls with three doses and with coverage rates decreasing with age until 52% for 20¿26 year-olds. A fast 59% reduction in the genital warts diagnoses occurred in the model in the first years after the start of the program, similar to what was described in the literature.We are grateful for the support from Sanofi Pasteur. The authors would also like to thank M. Diaz-Sanchis from the Institut Catala d'Oncologia (ICO) for her useful comments and the data provided on HPV prevalence. We would also like to thank the ICO for the HPV information centre at http://hpvcentre.net.Diez-Domingo, J.; Sánchez-Alonso, V.; Villanueva Micó, RJ.; Acedo Rodríguez, L.; Moraño Fernández, JA.; Villanueva-Oller, J. (2017). Random Network Models to Predict the Long-Term Impact of HPV Vaccination on Genital Warts. Viruses. 9(10). doi:10.3390/v9100300S91

Clinical and economic burden of respiratory syncytial virus in Spanish children: the BARI study

Respiratory syncytial virus (RSV) infection is a major cause of morbidity in children. However, its disease burden remains poorly understood, particularly outside of the hospital setting. Our study aimed to estimate the burden of medically attended acute lower respiratory infection (ALRI) cases potentially related to RSV in Spanish children. Longitudinal data from September 2017 to June 2018 of 51,292 children aged < 5 years old from the National Health‑ care System (NHS) of two Spanish regions were used. Three case definitions were considered: (a) RSV‑specific; (b) RSV‑specific and unspecified acute bronchiolitis (RSV‑specific and Bronchiolitis), and; (c) RSV‑specific and unspecified ALRI (RSV‑specific and ALRI). A total of 3460 medically attended ALRI cases potentially due to RSV were identified, of which 257 (7.4%), 164 (4.7%), and 3039 (87.8%) coded with RSV‑specific, unspecific bronchiolitis, and unspecific ALRI codes, respectively. Medically attended RSV‑specific and ALRI cases per 1000 children was 134.4 in the first year of life, 119.4 in the second, and 35.3 between 2 and 5 years old. Most cases were observed in otherwise healthy children (93.1%). Mean direct healthcare cost per medically attended RSV‑specific and ALRI case was €1753 in the first year of life, €896 in the second, and €683 between 2 and 5 years old. Hospitalization was the main driver of these costs, accounting for 55.6%, 38.0% and 33.4%, in each respective age group. In RSV‑specific cases, mean direct healthcare cost per medically attended case was higher, mostly due to hospitalization: €3362 in the first year of life (72.9% from hospitalizations), €3252 in the second (72.1%), and €3514 between 2 and 5 years old (74.2%). These findings suggest that hospitalization data alone will underestimate the RSV infections requiring medical care, as will relying only on RSV‑specific codes. RSV testing and codification must be improved and preventive solutions adopted, to protect all infants, particularly during the first year of life.The BARI study was funded by Sanofi.Medicin

Intussusception following rotavirus vaccination in the Valencia Region, Spain

Studies have shown high intussusception rates in Spain. We performed a hospital-based retrospective observational study of the intussusception risk following rotavirus vaccinations among infants in Valencia, a region of Spain with an annual birth cohort of approximately 48,000 children, during 2007–2011, using a self-controlled case series design. We performed medical record review of all cases using Brighton Collaboration´s case definition and assessed the positive predictive value (PPV) of the intussusception diagnosis code. Among 151 hospitalized cases discharged as intussusception, we confirmed 136 as Brighton Collaboration's Levels 1 or 2, resulting in a PPV of 93% (95% CI: 87%–96%). Three confirmed cases occurred within days 1–7 following the first rotavirus vaccination. The incidence rate ratio was 9.0 (95% CI: 0.9–86.5) (crude) and 4.7 (95% CI:0.3–74.1)(age adjusted). In this first study in Europe, the intussusception risk point estimate was comparable to other studies, although results were not statistically significant, maybe due to limited power. The high PPV found will facilitate implementation of a larger study without requiring medical record review. Our finding of very few vaccinated cases despite a thorough 5-year investigation in a country that, according to previous studies, may have a large background rate of intussusception is reassuring and should contribute to deliberations about the need to include rotavirus vaccines in the official Spanish calendars

Quality-of-Life Impact of an Investigational Subunit-Adjuvanted Herpes Zoster Vaccine in Adults ≥50 Years of Age

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Burden of paediatric Rotavirus Gastroenteritis (RVGE) and potential benefits of a universal Rotavirus vaccination programme with a pentavalent vaccine in Spain

<p>Abstract</p> <p>Background</p> <p>Rotavirus is the most common cause of gastroenteritis in young children worldwide. The aim of the study was to assess the health outcomes and the economic impact of a universal rotavirus vaccination programme with RotaTeq, the pentavalent rotavirus vaccine, versus no vaccination programme in Spain.</p> <p>Methods</p> <p>A birth cohort was followed up to the age of 5 using a cohort model. Epidemiological parameters were taken from the REVEAL study (a prospective epidemiological study conducted in Spain, 2004-2005) and from the literature. Direct and indirect costs were assessed from the national healthcare payer and societal perspectives by combining health care resource utilisation collected in REVEAL study and unit costs from official sources. RotaTeq per protocol efficacy data was taken from a large worldwide rotavirus clinical trial (70,000 children). Health outcomes included home care cases, General Practioner (GP)/Paediatrician, emergency department visits, hospitalisations and nosocomial infections.</p> <p>Results</p> <p>The model estimates that the introduction of a universal rotavirus vaccination programme with RotaTeq (90% coverage rate) would reduce the rotavirus gastroenteritis (RVGE) burden by 75% in Spain; 53,692 home care cases, 35,187 GP/Paediatrician visits, 34,287 emergency department visits, 10,987 hospitalisations and 2,053 nosocomial infections would be avoided. The introduction of RotaTeq would avoid about 76% of RVGE-related costs from both perspectives: €22 million from the national health system perspective and €38 million from the societal perspective.</p> <p>Conclusions</p> <p>A rotavirus vaccination programme with RotaTeq would reduce significantly the important medical and economic burden of RVGE in Spain.</p

Efficacy, Immunogenicity and Safety of an Investigational Subunit Adjuvanted Herpes Zoster Vaccine in Adults Aged 60 Years and Older: Results From the ZOE-50 and ZOE-70 Efficacy Studies

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Incidence rates of narcolepsy diagnoses in Taiwan, Canada, and Europe: The use of statistical simulation to evaluate methods for the rapid assessment of potential safety issues on a population level in the SOMNIA study

BACKGROUND & OBJECTIVES: Vaccine safety signals require investigation, which may be done rapidly at the population level using ecological studies, before embarking on hypothesis-testing studies. Incidence rates were used to assess a signal of narcolepsy following AS03-adjuvanted monovalent pandemic H1N1 (pH1N1) influenza vaccination among children and adolescents in Sweden and Finland in 2010. We explored the utility of ecological data to assess incidence of narcolepsy following exposure to pandemic H1N1 virus or vaccination in 10 sites that used different vaccines, adjuvants, and had varying vaccine coverage.METHODS: We calculated incidence rates of diagnosed narcolepsy for periods defined by influenza virus circulation and vaccination campaign dates, and used Poisson regression to estimate incidence rate ratios (IRRs) comparing the periods during which wild-type virus circulated and after the start of vaccination campaigns vs. the period prior to pH1N1 virus circulation. We used electronic health care data from Sweden, Denmark, the United Kingdom, Canada (3 provinces), Taiwan, Netherlands, and Spain (2 regions) from 2003 to 2013. We investigated interactions between age group and adjuvant in European sites and conducted a simulation study to investigate how vaccine coverage, age, and the interval from onset to diagnosis may impact the ability to detect safety signals.RESULTS: Incidence rates of narcolepsy varied by age, continent, and period. Only in Taiwan and Sweden were significant time-period-by-age-group interactions observed. Associations were found for children in Taiwan (following pH1N1 virus circulation) and Sweden (following vaccination). Simulations showed that the individual-level relative risk of narcolepsy was underestimated using ecological methods comparing post- vs. pre-vaccination periods; this effect was attenuated with higher vaccine coverage and a shorter interval from disease onset to diagnosis.CONCLUSIONS: Ecological methods can be useful for vaccine safety assessment but the results are influenced by diagnostic delay and vaccine coverage. Because ecological methods assess risk at the population level, these methods should be treated as signal-generating methods and drawing conclusions regarding individual-level risk should be avoided

SARS-CoV-2 Omicron BA.1 variant breakthrough infections in nursing home residents after an homologous third dose of the Comirnaty® COVID-19 vaccine: Looking for correlates of protection

8 páginas, 2 figuras. Texto completo en PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348298/pdf/JMV-94-4216.pdfWe investigated whether peripheral blood levels of SARS-CoV-2 Spike (S) receptor binding domain antibodies (anti-RBD), neutralizing antibodies (NtAb) targeting Omicron S, and S-reactive-interferon (IFN)-γ-producing CD4+ and CD8+ T cells measured after a homologous booster dose (3D) with the Comirnaty® vaccine was associated with the likelihood of subsequent breakthrough infections due to the Omicron variant. An observational study including 146 nursing home residents (median age, 80 years; range, 66-99; 109 female) evaluated for an immunological response after 3D (at a median of 16 days). Anti-RBD total antibodies were measured by chemiluminescent immunoassay. NtAb were quantified by an Omicron S pseudotyped virus neutralization assay. SARS-CoV-2-S specific-IFNγ-producing CD4+ and CD8+ T cells were enumerated by whole-blood flow cytometry for intracellular cytokine staining. In total, 33/146 participants contracted breakthrough Omicron infection (symptomatic in 30/33) within 4 months after 3D. Anti-RBD antibody levels were comparable in infected and uninfected participants (21 123 vs. 24 723 BAU/ml; p = 0.34). Likewise, NtAb titers (reciprocal IC50 titer, 157 vs. 95; p = 0.32) and frequency of virus-reactive CD4+ (p = 0.82) and CD8+ (p = 0.91) T cells were similar across participants in both groups. anti-RBD antibody levels and NtAb titers estimated at around the time of infection were also comparable (3445 vs. 4345 BAU/ml; p = 0.59 and 188.5 vs. 88.9; p = 0.70, respectively). Having detectable NtAb against Omicron or SARS-CoV-2-S-reactive-IFNγ-producing CD4+ or CD8+ T cells after 3D was not correlated with increased protection from breakthrough infection (OR, 1.50; p = 0.54; OR, 0.0; p = 0.99 and OR 3.70; p = 0.23, respectively). None of the immune parameters evaluated herein, including NtAb titers against the Omicron variant, may reliably predict at the individual level the risk of contracting COVID-19 due to the Omicron variant in nursing home residents.Ignacio Torres (Río Hortega Contract; CM20/00090), Estela Giménez (Juan Rodés Contract, JR18/00053), and Eliseo Albert (Juan Rodés Contract; JR20/00011) hold contracts funded by the Carlos III Health Institute (cofinanced by the European Regional Development Fund, ERDF/FEDER). Ron Geller holds a Ramon y Cajal fellowship from the Spanish Ministerio de Economía y Competitividad (RYC‐2015‐17517). This study work was supported by Instituto de Salud Carlos III, Madrid, Spain (FIS, PI21/00563) to David Navarro, and by the European Commission NextGenerationEU fund (EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global) to Ron Geller.Peer reviewe