Cost analysis of a vaccination startegy for respiratory syncytial virus (RSV) in a network model

[EN] In this paper an age-structured mathematical model for respiratory syncytial virus (RSV) is proposed where children younger than one year old, who are the most affected by this illness, are specially considered. Real data of hospitalized children in the Spanish region of Valencia are used in order to determine some seasonal parameters of the model. Once the parameters are determined, we propose a complete stochastic network model to study the seasonal evolution of the respiratory syncytial virus (RSV) epidemics. In this model every susceptible individual can acquire the disease after a random encounter with any infected individual in the social network. The edges of a complete graph connecting every pair of individuals in the network simulate these encounters and a season dependent probability, beta(t), determines whether the healthy susceptible individual becomes infected or not. We show that the prediction of this model is compatible with the above mentioned age-structured model based upon differential equations, but sharper peaks are obtained in the case of the network. Then, on the network model, we propose the vaccination of children at 2 months, 4 months and 1 year old, and we study the cost of this vaccination strategy, which is emerging as the most plausible one to be applied when the vaccine hits the market. It is worth to note that this vaccination strategy is simulated in the network model because to implement it in the continuous model is very difficult and increases its complexity. (C) 2010 Elsevier Ltd. All rights reserved.Acedo Rodríguez, L.; Moraño Fernández, JA.; Diez-Domingo, J. (2010). Cost analysis of a vaccination startegy for respiratory syncytial virus (RSV) in a network model. Mathematical and Computer Modelling. 52(7):1016-1022. doi:10.1016/j.mcm.2010.02.041S1016102252

Influence of health literacy on acceptance of influenza and pertussis vaccinations: a cross-sectional study among Spanish pregnant women.

OBJECTIVES: Immunisations against influenza and Bordetella pertussis infection are recommended to pregnant women in Valencia (Spain), yet vaccination rates remain low. Health literacy (HL) appears as a crucial factor in vaccination decision-making. We explored the relation between HL of pregnant women and decisions to receive influenza and pertussis immunisations. SETTING: University hospital in Valencia (Spain). PARTICIPANTS: 119 women who gave birth at a hospital in Valencia (Spain) between November 2015 and May 2016. Women in the immediate postpartum period (more than 27 weeks of gestation), between November 2015 and May 2016 were included in the study. Women with impairments, language barriers or illiteracy which prevented completion of the questionnaires, or those who were under 18 years were excluded from enrolment. PRIMARY AND SECONDARY OUTCOME MEASURES: HL level; influenza and pertussis immunisation rate; reasons for rejection of vaccination. RESULTS: 119 participants were included (mean age 32.3±5.5 years, 52% primiparous, 95% full-term deliveries). A higher education level was associated with Short Assessment of Health Literacy for Spanish Adults _50 (adjusted R2=0.22, p=0.014) and Newest Vital Sign (adjusted R2=0.258, p=0.001) scores. Depending on the scale, 56%-85% of participants had adequate HL. 52% (62/119) and 94% (112/119) of women received influenza and pertussis immunisation, respectively. Women rejecting influenza vaccine had a higher HL level (measured by SALHSA_50 tool) than those accepting it (Kruskal-Wallis test p=0.022). 24% of women who declined influenza vaccination felt the vaccine was unnecessary, and 23% claimed to have insufficient information. CONCLUSIONS: Influenza vaccination rate was suboptimal in our study. Women with high HL were more likely to decline immunisation. Information from professionals needs to match patients' HL levels to reduce negative perceptions of vaccination

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

Intradermal and virosomal influenza vaccines for preventing influenza hospitalization in the elderly during the 2011–2012 influenza season: A comparative effectiveness study using the Valencia health care information system

AbstractBackgroundThe use of intradermal vaccination or virosomal vaccines could increase protection against influenza among the vulnerable population of older adults. Studies assessing the comparative effectiveness of these two influenza vaccine types in this age group are lacking.MethodsWe conducted a retrospective cohort study to estimate the comparative effectiveness of intradermal seasonal trivalent-influenza vaccine (TIV) delivered by a microneedle injection system and a virosomal-TIV intramuscularly delivered for prevention of influenza hospitalization in non-institutionalized adults aged ≥65 years. We obtained administrative data on immunization status and influenza hospitalization for the 2011–2012 influenza season, and used Cox regression models to assess comparative effectiveness. We estimated crude and adjusted (age, sex, comorbidity, pharmaceutical claims, recent pneumococcal vaccination and number of hospitalizations for all causes other than influenza between the previous and current influenza seasons) hazard ratios (HR).ResultsOverall, 164,021 vaccinated subjects were evaluated. There were 127 hospitalizations for influenza among 62,058 subjects, contributing 914,740 person-weeks at risk in the virosomal-TIV group, and 133 hospitalizations for influenza among 101,963 subjects, contributing 1,504,570 person-weeks at risk in the intradermal-TIV group. The crude HR of intradermal-TIV relative to virosomal-TIV was 0.64 (95% confidence interval (CI): 0.50–0.81), and the adjusted Cox estimated HR was 0.67 (95% CI: 0.52–0.85).ConclusionsDuring the 2011–2012 influenza season the risk of hospitalization for influenza was reduced by 33% in non-institutionalized elderly adults who were vaccinated with intradermal-TIV compared with virosomal-TIV

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

Clonal hematopoiesis is not prevalent in Hutchinson-Gilford progeria syndrome.

Clonal hematopoiesis of indeterminate potential (CHIP), defined as the presence of somatic mutations in cancer-related genes in blood cells in the absence of hematological cancer, has recently emerged as an important risk factor for several age-related conditions, especially cardiovascular disease. CHIP is strongly associated with normal aging, but its role in premature aging syndromes is unknown. Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare genetic condition driven by the accumulation of a truncated form of the lamin A protein called progerin. HGPS patients exhibit several features of accelerated aging and typically die from cardiovascular complications in their early teens. Previous studies have shown normal hematological parameters in HGPS patients, except for elevated platelets, and low levels of lamin A expression in hematopoietic cells relative to other cell types in solid tissues, but the prevalence of CHIP in HGPS remains unexplored. To investigate the potential role of CHIP in HGPS, we performed high-sensitivity targeted sequencing of CHIP-related genes in blood DNA samples from a cohort of 47 HGPS patients. As a control, the same sequencing strategy was applied to blood DNA samples from middle-aged and elderly individuals, expected to exhibit a biological age and cardiovascular risk profile similar to HGPS patients. We found that CHIP is not prevalent in HGPS patients, in marked contrast to our observations in individuals who age normally. Thus, our study unveils a major difference between HGPS and normal aging and provides conclusive evidence that CHIP is not frequent in HGPS and, therefore, is unlikely to contribute to the pathophysiology of this accelerated aging syndrome.This work was supported by Fundación “la Caixa” (grant number LCF/PR/HR17/52150007 to VF, and JJF). JJF is supported by a Ramón y Cajal award (RYC2016–20026) from the Spanish Ministerio de Ciencia e Innovación (MICIN)/Agencia Estatal de Investigación (AEI)/10.13039/501100011033 and Fondo Social Europeo “El FSE invierte en tu futuro”. VA’s lab is supported by MICIN/ AEI/10.13039/501100011033 and Fondo Social Europeo “El FSE invierte en tu futuro” (grant number PID2019-108489RBI00), the Progeria Research Foundation (Award PRF 2019–77), and a donation from Asociación Progeria Alexandra Peraut. LBG is supported by The Progeria Research Foundation. MDD is supported by a predoctoral FPI fellowship from the Spanish MICIN/AEI/10.13039/501100011033 and Fondo Social Europeo “El FSE invierte en tu futuro” (PRE2019-087463), and MA-P is supported by a predoctoral FPU contract from the Ministerio de Educación, Cultura y Deporte (FPU18/02913). The CNIC is supported by the MICIN, the Instituto de Salud Carlos III, the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant number CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033).S

Using random networks to study the dynamics of respiratory syncytial virus (RSV) in the Spanish region of Valencia

[EN] Seasonal fluctuations in the incidence of several respiratory infections are a feature of epidemiological surveys all around the world. This phenomenon is characteristic of influenza and respiratory syncytial virus pandemics. However, the explanation of the seasonal outbreaks of these diseases remains poorly understood. Many statistical studies have been carried out in order to provide a correlation of the outbreaks with climatic or social factors without achieving a definitive conclusion. Here we show that, in a random social network, self-sustained seasonal epidemics emerge as a process modulated by the infection probability and the immunity period after recovering from the infection. This is a purely endogenous phenomenon that does not require any exogenous forcing. Assuming that this is the dominant mechanism for seasonal epidemics, many implications for public health policies for infectious respiratory diseases could be drawn. (C) 2010 Elsevier Ltd. All rights reserved.Supported by a grant from the Universidad Politecnica de Valencia PAID-06-09 ref: 2588.Acedo Rodríguez, L.; Moraño Fernández, JA.; Villanueva Micó, RJ.; Villanueva Oller, FJ.; Díez Domingo, J. (2011). Using random networks to study the dynamics of respiratory syncytial virus (RSV) in the Spanish region of Valencia. Mathematical and Computer Modelling. 54(7-8):1650-1654. https://doi.org/10.1016/j.mcm.2010.11.068S16501654547-

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

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