Dynamic transmission modeling of COVID-19 to support decision-making in Brazil: A scoping review in the pre-vaccine era.

Brazil was one of the countries most affected during the first year of the COVID-19 pandemic, in a pre-vaccine era, and mathematical and statistical models were used in decision-making and public policies to mitigate and suppress SARS-CoV-2 dispersion. In this article, we intend to overview the modeling for COVID-19 in Brazil, focusing on the first 18 months of the pandemic. We conducted a scoping review and searched for studies on infectious disease modeling methods in peer-reviewed journals and gray literature, published between January 01, 2020, and June 2, 2021, reporting real-world or scenario-based COVID-19 modeling for Brazil. We included 81 studies, most corresponding to published articles produced in Brazilian institutions. The models were dynamic and deterministic in the majority. The predominant model type was compartmental, but other models were also found. The main modeling objectives were to analyze epidemiological scenarios (testing interventions' effectiveness) and to project short and long-term predictions, while few articles performed economic impact analysis. Estimations of the R0 and transmission rates or projections regarding the course of the epidemic figured as major, especially at the beginning of the crisis. However, several other outputs were forecasted, such as the isolation/quarantine effect on transmission, hospital facilities required, secondary cases caused by infected children, and the economic effects of the pandemic. This study reveals numerous articles with shared objectives and similar methods and data sources. We observed a deficiency in addressing social inequities in the Brazilian context within the utilized models, which may also be expected in several low- and middle-income countries with significant social disparities. We conclude that the models were of great relevance in the pandemic scenario of COVID-19. Nevertheless, efforts could be better planned and executed with improved institutional organization, dialogue among research groups, increased interaction between modelers and epidemiologists, and establishment of a sustainable cooperation network.

Vaccination trends in people with HIV infection participanting in the hospital-based survey of patients infected with HIV, 2006-2021.

OBJECTIVE: To assess the trend in hepatitis A, hepatitis B, pneumococcal, tetanus and seasonal influenza vaccination in people with HIV infection and to analyse associated factors. METHODS: The Hospital Survey of Patients with HIV, an annual cross-sectional study conducted on a fixed day (2006-2021), was used. Inpatients and outpatients were included. Trends in vaccination and associated factors were analysed using logistic regression. RESULTS: A total of 8643 participants were included. Vaccination rates increased to 65.3% for hepatitis A, 83.7% for hepatitis B, 49.3% for tetanus, 68.9% for pneumococcal and 74.5% for seasonal influenza in 2021. Factors positively associated with vaccination were older age for pneumococcal and influenza vaccination; higher educational level for hepatitis A and tetanus; living in a closed institutions or prison for tetanus, pneumococcal and influenza; and having acquired HIV through sex between men for hepatitis A, B and pneumococcal. In addition, being on antiretroviral treatment and having a high CD4 count were positively associated with vaccination for all these diseases. Factors inversely associated with vaccination were being older (hepatitis A, B and tetanus), being an immigrant (tetanus and seasonal influenza) and being an injection drug user/ex-user for hepatitis A and B. CONCLUSIONS: Vaccination in people with HIV has increased in the study period. The results are in line with the recommendations in this population, although there is still room to reach the established vaccination indicators.

Estimates of mpox effective reproduction number in Spain, April-August 2022.

We analysed the transmission of the human mpox virus in Spain by estimating the effective reproduction number of the disease from official surveillance data. Our computations show that this decreased steadily after an initial burst phase, dropping below 1 on July 12, and thus the outbreak was expected to reduce in the following weeks. Differences in trends were found across geographical regions of the country and across MSM and heterosexual populations.

Modeling the impact of child vaccination (5-11 y) on overall COVID-19 related hospitalizations and mortality in a context of omicron variant predominance and different vaccination coverage paces in Brazil.

Background: Developing countries have experienced significant COVID-19 disease burden. With the emergence of new variants, particularly omicron, the disease burden in children has increased. When the first COVID-19 vaccine was approved for use in children aged 5-11 years of age, very few countries recommended vaccination due to limited risk-benefit evidence for vaccination of this population. In Brazil, ranking second in the global COVID-19 death toll, the childhood COVID-19 disease burden increased significantly in early 2022. This prompted a risk-benefit assessment of the introduction and scaling-up of COVID-19 vaccination of children. Methods: To estimate the potential impact of vaccinating children aged 5-11 years with mRNA-based COVID-19 vaccine in the context of omicron dominance, we developed a discrete-time SEIR-like model stratified in age groups, considering a three-month time horizon. We considered three scenarios: No vaccination, slow, and maximum vaccination paces. In each scenario, we estimated the potential reduction in total COVID-19 cases, hospitalizations, deaths, hospitalization costs, and potential years of life lost, considering the absence of vaccination as the base-case scenario. Findings: We estimated that vaccinating at a maximum pace could prevent, between mid-January and April 2022, about 26,000 COVID-19 hospitalizations, and 4200 deaths in all age groups; of which 5400 hospitalizations and 410 deaths in children aged 5-11 years. Continuing vaccination at a slow/current pace would prevent 1450 deaths and 9700 COVID-19 hospitalizations in all age groups in this same time period; of which 180 deaths and 2390 hospitalizations in children only. Interpretation: Maximum vaccination of children results in a significant reduction of COVID-19 hospitalizations and deaths and should be enforced in developing countries with significant disease incidence in children. Funding: This manuscript was funded by the Brazilian Council for Scientific and Technology Development (CNPq - Process # 402834/2020-8).

Modelling the impact of school reopening and contact tracing strategies on Covid-19 dynamics in different epidemiologic settings in Brazil.

We simulate the impact of school reopening during the COVID-19 pandemic in three major urban centers in Brazil to identify the epidemiological indicators and the best timing for the return of in-school activities and the effect of contact tracing as a mitigation measure. Our goal is to offer guidelines for evidence-based policymaking. We implement an extended SEIR model stratified by age and considering contact networks in different settings - school, home, work, and community, in which the infection transmission rate is affected by various intervention measures. After fitting epidemiological and demographic data, we simulate scenarios with increasing school transmission due to school reopening, and also estimate the number of hospitalization and deaths averted by the implementation of contact tracing. Reopening schools results in a non-linear increase in reported COVID-19 cases and deaths, which is highly dependent on infection and disease incidence at the time of reopening. When contact tracing and quarantining are restricted to school and home settings, a large number of daily tests is required to produce significant effects in reducing the total number of hospitalizations and deaths. Policymakers should carefully consider the epidemiological context and timing regarding the implementation of school closure and return of in-person school activities. While contact tracing strategies prevent new infections within school environments, they alone are not sufficient to avoid significant impacts on community transmission.

Modelling optimal vaccination strategies against COVID-19 in a context of Gamma variant predominance in Brazil.

INTRODUCTION: Brazil experienced moments of collapse in its health system throughout 2021, driven by the emergence of variants of concern (VOC) combined with an inefficient initial vaccination strategy against Covid-19. OBJECTIVES: To support decision-makers in formulating COVID-19 immunization policy in the context of limited vaccine availability and evolving variants over time, we evaluate optimal strategies for Covid-19 vaccination in Brazil in 2021, when vaccination was rolled out during Gamma variant predominance. METHODS: Using a discrete-time epidemic model we estimate Covid-19 deaths averted, considering the currently Covid-19 vaccine products and doses available in Brazil; vaccine coverage by target population; and vaccine effectiveness estimates. We evaluated a 5-month time horizon, from early August to the end of December 2021. Optimal vaccination strategies compared the outcomes in terms of averted deaths when varying dose intervals from 8 to 12 weeks, and choosing the minimum coverage levels per age group required prior to expanding vaccination to younger target populations. We also estimated dose availability required over time to allow the implementation of optimal strategies. RESULTS: To maximize the number of averted deaths, vaccine coverage of at least 80 % should be reached in older age groups before starting vaccination into subsequent younger age groups. When evaluating varying dose intervals for AZD1222, reducing the dose interval from 12 to 8 weeks for the primary schedule would result in fewer COVID-19 deaths, but this can only be implemented if accompanied by an increase in vaccine supply of at least 50 % over the coming six-months in Brazil. CONCLUSION: Covid-19 immunization strategies should be tailored to local vaccine product availability and supply over time, circulating variants of concern, and vaccine coverage in target population groups. Modelling can provide valuable and timely evidence to support the implementation of vaccination strategies considering the local context, yet following international and regional technical evidence-based guidance.

Parasitemia Levels in Trypanosoma cruzi Infection in Spain, an Area Where the Disease Is Not Endemic: Trends by Different Molecular Approaches.

Trypanosoma cruzi infection has expanded globally through human migration. In Spain, the mother-to-child route is the mode of transmission contributing to autochthonous Chagas disease (CD); however, most people acquired the infection in their country of origin and were diagnosed in the chronic phase (imported chronic CD). In this context, we assessed the quantitative potential of the Loopamp Trypanosoma cruzi detection kit (Sat-TcLAMP) based on satellite DNA (Sat-DNA) to determine parasitemia levels compared to those detected by real-time quantitative PCRs (qPCRs) targeting Sat-DNA (Sat-qPCR) and kinetoplast DNA minicircles (kDNA-qPCR). This study included 173 specimens from 39 autochthonous congenital and 116 imported chronic CD cases diagnosed in Spain. kDNA-qPCR showed higher sensitivity than Sat-qPCR and Sat-TcLAMP. According to all quantitative approaches, parasitemia levels were significantly higher in congenital infection than in chronic CD (1 × 10-1 to 5 × 105 versus >1 × 10-1 to 6 × 103 parasite equivalents/mL, respectively [P < 0.001]). Sat-TcLAMP, Sat-qPCR, and kDNA-qPCR results were equivalent at high levels of parasitemia (P = 0.381). Discrepancies were significant for low levels of parasitemia and older individuals. Differences between Sat-TcLAMP and Sat-qPCR were not qualitatively significant, but estimations of parasitemia using Sat-TcLAMP were closer to those by kDNA-qPCR. Parasitemia changes were assessed in 6 individual cases in follow-up, in which trends showed similar patterns by all quantitative approaches. At high levels of parasitemia, Sat-TcLAMP, Sat-qPCR, and kDNA-qPCR worked similarly, but significant differences were found for the low levels characteristic of late chronic CD. A suitable harmonization strategy needs to be developed for low-level parasitemia detection using Sat-DNA- and kDNA-based tests. IMPORTANCE Currently, molecular equipment has been introduced into many health care centers, even in low-income countries. PCR, qPCR, and loop-mediated isothermal amplification (LAMP) are becoming more accessible for the diagnosis of neglected infectious diseases. Chagas disease (CD) is spreading worldwide, and in countries where the disease is not endemic, such as Spain, the parasite Trypanosoma cruzi is transmitted from mother to child (congenital CD). Here, we explore why LAMP, aimed at detecting T. cruzi parasite DNA, is a reliable option for the diagnosis of congenital CD and the early detection of reactivation in chronic infection. When the parasite load is high, LAMP is equivalent to any qPCR. In addition, the estimations of T. cruzi parasitemia in patients living in Spain, a country where the disease is not endemic, resemble natural evolution in areas of endemicity. If molecular tests are introduced into the diagnostic algorithm for congenital infection, early diagnosis and timely treatment would be accomplished, so the interruption of vertical transmission can be an achievable goal.

Physical and social environmental factors related to co-occurrence of unhealthy lifestyle behaviors.

Previous work identifying determinants of co-occurrence of behavioral risk factors have focused on their association with individuals' characteristics with scant attention paid to their relationship to contextual factors. Data came from 21,007 individuals ≥15 years of age who participated in the cross-sectional 2011-2012 Spanish National Health Survey. Two indicators were defined by tobacco consumption, alcohol intake, diet, physical activity, and body mass index. The first indicator, based on dichotomized measures, ranges from 0 to 5. The second one (unhealthy lifestyle index), ranges from 0 to 15, with 0 denoting the healthiest score. Among the determinants, we examined social support, five perceived characteristics of the neighborhood, and the socioeconomic deprivation index of the census tract of residence. Data were analyzed using multilevel linear and logistic regression models adjusted for the main sociodemographic characteristics. Using the dichotomized indicator, the probability of having 3-5 risk factors versus <3 factors was associated with low social support (Odds Ratio [OR] 1.50; 95% Confidence Interval [CI]: 1.25-1.80). Issues surrounding neighborhood cleanliness (OR = 1.18; 95%CI: 1.04-1.33), air pollution (OR = 1.38; 95%CI: 1.16-1.64), and street crime (OR = 1.21; 95%CI: 1.03-1.42) were associated with determinants of co-occurrence. Risk factors co-occurrence increased as deprivation level increased: the OR for the highest deprivation quintile versus the lowest was 1.30 (95%CI: 1.14-1.48). Similar results were observed when using the unhealthy lifestyle index. Poorer physical and social environments are related to greater co-occurrence of risk factors for chronic diseases. Health promotion interventions targeting the prevention of risk factors should consider the contextual characteristics of the neighborhood environment.

Small area influences on the individual unhealthy lifestyle behaviors: A multilevel analysis of discriminatory accuracy.

We estimated the discriminatory power of area of residence (census tract) on the prevalence of main risk factors for chronic diseases. Results, based on a sample of 21,007 participants from the 2011-2012 National Health Survey of Spain, show a differential influence of the geosocial environment on the four health risk factors. Accounting for census tracts substantially increases the discriminatory power regarding at-risk alcohol consumption, unbalanced diet, and leisure-time sedentarism but not tobacco consumption. However, the socioeconomic characteristics of the tracts played a minor role. Further research on the specific geosocial contextual variables explaining variability in these risk factors is necessary.

Individual and Contextual Factors Associated With Hazardous Drinking in Spain: Evidence From a National Population-Based Study.

BACKGROUND: Heavy drinking (HD) and binge drinking (BD) exhibit marked differences in their relationships with contextual-level factors imbedded in geographical areas of residence. The objective is to identify sociodemographic factors, both at the individual and at the contextual level, associated with these 2 main hazardous consumption patterns. METHODS: Cross-sectional study using data from the 2011 to 2012 National Health Survey in Spain. The sample included 21,007 individuals ≥15 years of age. HD was defined as an alcohol intake of ≥40 g/d in men and ≥24 g/d in women. BD was defined as the consumption in the previous month of ≥6 alcoholic drinks (men) or ≥5 drinks (women) within 4 to 6 hours. Individual-level variables included sociodemographic factors, urban/rural residence, smoking, and perceived social support. Contextual-level variables covered percentage of population with no schooling, unemployment rate, and hospitality industry-related economic activity, all at the census tract level. We analyzed data using multilevel logistic regression and calculated areas under the curve (AUC). RESULTS: Being male, smoking, high-income, and low perceived social support were associated with both hazardous drinking patterns. Younger individuals were at higher risk for BD but at lower risk for HD. BD was more common among rural than urban dwellers (odds ratios [OR] = 1.35; 95% CI: 1.05 to 1.72), whereas HD was less likely in participants residing in areas with high unemployment rates (OR = 0.62; 95% CI: 0.41 to 0.93). HD was more likely in census tracts with higher levels of hospitality industry activity (OR = 1.74; 95% CI: 1.20 to 2.54). The AUC increased substantially for both HD and BD when the census tract variable was entered in the respective models (reaching 89.5 and 93.3%, respectively). CONCLUSIONS: Except for age, both drinking patterns have similar associations with individual-level variables but disparate links to contextual-level indicators. In both cases, accounting for area of residence substantially increased the ability to discriminate between high-risk drinkers from nonhazardous alcohol consumers.

Impact of an excise tax on the consumption of sugar-sweetened beverages in young people living in poorer neighbourhoods of Catalonia, Spain: a difference in differences study.

BACKGROUND: Sugar-sweetened beverage consumption is contributing to the obesity epidemic. On 28 March 2017, Catalonia enacted a law levying an excise tax on sugar-sweetened beverages for public health reasons. The purpose of this study is to assess the impact of the tax on the consumption of sugar-sweetened beverages in Catalonia (Spain). METHODS: Before-and-after study to assess changes in the prevalence of consumption of sugar-sweetened beverages among 1929 persons aged 12 to 40 years residing in low-income neighbourhoods of Barcelona (intervention) and Madrid (control). Beverage consumption frequency was ascertained via a validated questionnaire administered during the month prior to the tax's introduction (May 2017) and again at 1 year after it had come into force. The effect of the tax was obtained using Poisson regression models with robust variance weighted using propensity scores. RESULTS: While the prevalence of regular consumers of taxed beverages fell by 39% in Barcelona as compared to Madrid, the prevalence of consumers of untaxed beverages remained stable. The main reason cited by more than two-thirds of those surveyed for reducing their consumption of sugar-sweetened beverages was the increase in price, followed by a heightened awareness of their health effects. CONCLUSIONS: The introduction of the Catalonian excise tax on sugar-sweetened beverages was followed by a reduction in the prevalence of regular consumers of taxed beverages.

Changes in Alcohol Intake During Pregnancy in Spain, 1980 to 2014.

BACKGROUND: Even small amounts of alcohol consumed during pregnancy can have adverse effects on the embryo and the fetus. We estimated how alcohol intake among pregnant women in Spain changed between 1980 and 2014, and identified factors associated with alcohol use. METHODS: Data came from the Spanish Collaborative Study of Congenital Malformations (ECEMC). The sample includes ECEMC's control mothers, 40,268 pregnant women from all regions of Spain. We classified alcohol consumption during pregnancy into 3 categories: no consumption; sporadic consumption of small amounts of alcohol; and regular consumption, or sporadic but in large quantities including drunkenness. Independent variables included sociodemographic factors, planned/unplanned pregnancy, maternal chronic diseases, gestational diabetes, and tobacco and illegal drug use during pregnancy. Trend analyses were performed using data from 1980 to 2014. The multinomial logistic regression models designed to identify associated factors differentiated between 2 periods: 1994 to 2004 and 2005 to 2014. RESULTS: Prevalence of alcohol consumption declined from 29.6% (95% CI: 27.1 to 32.2) in 1980 to 5.4% (95% CI: 3.7 to 7.6) in 2014, mostly due to the reduction in regular intake. This decline was especially acute between 1980 and 1994. Sporadic and regular consumption increased among women working outside the home, born outside Spain, those whose pregnancy was unplanned, and those reporting using tobacco or other drugs. Comparing 1994 to 2004 versus 2005 to 2014, a stronger association was observed between regular alcohol consumption and tobacco consumption in the latter period (interaction p = 0.003). CONCLUSIONS: Alcohol consumption among expectant mothers has declined substantially in the last 35 years. However, it is worth highlighting the significant and substantial associations between alcohol use and consumption of tobacco, which have become stronger in the most recent years.

Impact of 2 Successive Smoking Bans on Hospital Admissions for Cardiovascular Diseases in Spain.

INTRODUCTION AND OBJECTIVES: To evaluate the impact of 2 smoking bans enacted in 2006 (partial ban) and 2011 (comprehensive ban) on hospitalizations for cardiovascular disease in the Spanish adult population. METHODS: The study was performed in 14 provinces in Spain. Hospital admission records were collected for acute myocardial infarction (AMI), ischemic heart disease (IHD), and cerebrovascular disease (CVD) in patients aged ≥ 18 years from 2003 through 2012. We estimated immediate and 1-year effects with segmented-linear models. The coefficients for each province were combined using random-effects multivariate meta-analysis models. RESULTS: Overall, changes in admission rates immediately following the implementation of the partial ban and 1 year later were -1.8% and +1.2% for AMI, +0.1 and +0.4% for IHD, and +1.0% and +2.8% for CVD (P>.05). After the comprehensive ban, immediate changes were -2.3% for AMI, -2.6% for IHD, and -0.8% for CVD (P>.05), only to return to precomprehensive ban values 1 year later. For patients aged ≥ 65 years of age, immediate changes associated with the comprehensive ban were -5.0%, -3.9%, and -2.3% for AMI, IHD, and CVD, respectively (P<.05). Again, the 1-year changes were not statistically significant. CONCLUSIONS: In Spain, smoking bans failed to significantly reduce hospitalizations for AMI, IHD, or CVD among patients ≥ 18 years of age. In the population aged ≥ 65 years, hospital admissions due to these diseases showed significant decreases immediately after the implementation of the comprehensive ban, but these reductions disappeared at the 1-year evaluation.

Smoke-Free Legislation in Spain and Prematurity.

BACKGROUND AND OBJECTIVE: Spain implemented a partial smoking ban in 2006 followed by a comprehensive ban in 2011. The objective was to examine the association between these smoke-free policies and different perinatal complications. METHODS: Cross-sectional study including all live births between 2000 and 2013. Selected adverse birth outcomes were: preterm births (<37 gestational weeks), small for gestational age (SGA; <10th weight percentile according to Spanish reference tables), and low birth weight (<2500 g). We estimated immediate and gradual rate changes after smoking bans by using overdispersed Poisson models with different linear trends for 2000 to 2005 (preban), 2006 to 2010 (partial ban), and 2011 to 2013 (comprehensive ban). Models were adjusted for maternal sociodemographics, health care during the delivery, and smoking prevalence during pregnancy. RESULTS: The comprehensive ban was associated with preterm birth rate reductions of 4.5% (95% confidence interval [CI]: 2.9%-6.1%) and 4.1% (95% CI: 2.5%-5.6%) immediately and 1 year after implementation, respectively. The low birth weight rate also dropped immediately (2.3%; 95% CI: 0.7%-3.8%) and 1 year after the comprehensive ban implementation (3.5%; 95% CI: 2.1%-5.0%). There was an immediate reduction in the SGA rate at the onset of the partial ban (4.9%; 95% CI: 3.5%-6.2%), which was sustained 1 year postimplementation. Although not associated with the comprehensive ban at the onset, the SGA rate declined by 1.7% (95% CI: 0.3%-3.1%) 1 year postimplementation. CONCLUSIONS: The implementation of the Spanish smoke-free policies was associated with a risk reduction for preterm births and low birth weight infants, especially with the introduction of the more restrictive ban.

Changes in hospitalizations for chronic respiratory diseases after two successive smoking bans in Spain.

BACKGROUND: Existing evidence on the effects of smoke-free policies on respiratory diseases is scarce and inconclusive. Spain enacted two consecutive smoke-free regulations: a partial ban in 2006 and a comprehensive ban in 2011. We estimated their impact on hospital admissions via emergency departments for chronic obstructive pulmonary disease (COPD) and asthma. METHODS: Data for COPD (ICD-9 490-492, 494-496) came from 2003-2012 hospital admission records from the fourteen largest provinces of Spain and from five provinces for asthma (ICD-9 493). We estimated changes in hospital admission rates within provinces using Poisson additive models adjusted for long-term linear trends and seasonality, day of the week, temperature, influenza, acute respiratory infections, and pollen counts (asthma models). We estimated immediate and gradual effects through segmented-linear models. The coefficients within each province were combined through random-effects multivariate meta-analytic models. RESULTS: The partial ban was associated with a strong significant pooled immediate decline in COPD-related admission rates (14.7%, 95%CI: 5.0, 23.4), sustained over time with a one-year decrease of 13.6% (95%CI: 2.9, 23.1). The association was consistent across age and sex groups but stronger in less economically developed Spanish provinces. Asthma-related admission rates decreased by 7.4% (95%CI: 0.2, 14.2) immediately after the comprehensive ban was implemented, although the one-year decrease was sustained only among men (9.9%, 95%CI: 3.9, 15.6). CONCLUSIONS: The partial ban was associated with an immediate and sustained strong decline in COPD-related admissions, especially in less economically developed provinces. The comprehensive ban was related to an immediate decrease in asthma, sustained for the medium-term only among men.

Assessing the effects of the Spanish partial smoking ban on cardiovascular and respiratory diseases: methodological issues.

OBJECTIVE: Recent research has assessed the impact of tobacco laws on cardiovascular and respiratory morbidity. In this study, we also examined whether the association between the implementation of the 2005 Spanish smoking ban and hospital admissions for cardiovascular and respiratory diseases varies according to the adjustment for potential confounders. DESIGN: Ecological time series analysis. SETTING: Residents of Madrid and Barcelona cities (Spain). OUTCOME: Data on daily emergency room admissions for acute myocardial infarction, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), and asthma derived from the 2003-2006 Spanish hospital admissions registry. METHODS: Changes in admission rates between 2006 and the 2003-2005 period were estimated using additive Poisson models allowing for overdispersion adjusted for secular trend in admission, seasonality, day of the week, temperature, number of flu and acute respiratory infection cases, pollution levels, tobacco consumption prevalence and, for asthma cases, pollen count. RESULTS: In Madrid, fully adjusted models failed to detect significant changes in hospital admission rates for any disease during the study period. In Barcelona, however, hospital admissions decreased by 10.2% (95% CI 3.8% to 16.1%) for cerebrovascular diseases and by 16.0% (95% CI 7.0% to 24.1%) for COPD. Substantial changes in effect estimates were observed on adjustment for linear or quadratic trend. Effect estimates for asthma-related admissions varied substantially when adjusting for pollen count in Madrid, and for seasonality and tobacco consumption in Barcelona. CONCLUSIONS: Our results confirm that the potential impact of a smoking ban must be adjusted for the underlying secular trend. In asthma-related admissions, pollen count, seasonality and tobacco consumption must be specified in the model. The substantial variability in effects detected between the two cities of Madrid and Barcelona lends strong support for a nationwide study to assess the overall effect of a smoking ban in Spain and identify the causes of the observed heterogeneity.

Decline in rotavirus hospitalizations following the first three years of vaccination in Castile-La Mancha, Spain.

Rotavirus is a major burden on the Spanish Healthcare System. Rotarix(®) and RotaTeq(®) were simultaneously commercialized in Spain by February, 2007. The objective is to analyze the incidence and seasonality of rotavirus hospitalizations (RH) in Castile-La Mancha (CLM), following the first 3 y of commercialization. A cross-sectional study of the hospital discharge registry's Minimum Basic Data Set (MBDS) in CLM between 2003 and 2009 was performed. We used the Poisson regression model to quantify the percentage of change in the rotavirus incidence rate (IR) for 2007-09 vs. 2003-05, adjusting for age, sex, and province. To analyze changes between epidemic seasons the chi-square test was used. The median IR in 2003-09 was 224.71 per 10(5) [interquartile range (IQR): 185.24-274.70], which represents 60% of hospital admissions due to infectious acute gastroenteritis. The median rate in 2007-09 decreased [incidence rate ratio (IRR): 0.86, 95% CI: 0.78-0.96], significantly in Toledo (IRR: 0.54, 95% CI: 0.39-0.75). An incipient decline at the beginning of the last cold season was observed, preceded by a significant decrease of 68% in the autumn season of 2009. Despite its limited coverage, the rotavirus vaccine may have contributed to decrease RH in CLM.

Liposomes containing NY­ESO­1/tetanus toxoid and adjuvant peptides targeted to human dendritic cells via the Fc receptor for cancer vaccines.

AIM: To improve the immunological response against tumors, a vaccine based on nanoliposomes targeted to the Fcg-receptor was developed to enhance the immunogenicity of tumor-associated antigens (TAAs). MATERIALS & METHODS: Using human dendritic cells in vitro, a fragment of the TAA NY-ESO-1 combined with a T-helper peptide from the tetanus toxoid encapsulated in nanoliposomes was evaluated. In addition, peptides Palm-IL-1 and MAP-IFN-g were coadministered as adjuvants to enhance the immunological response. RESULTS: Coadministration of Palm-IL-1 or MAP-IFN-g peptide adjuvants and the hybrid NY-ESO-1-tetanus toxoid (soluble or encapsulated in nanoliposomes without targeting) increased immunogenicity. However, the most potent immunological response was obtained when the peptide adjuvants were encapsulated in liposomes targeted to human dendritic cells via the Fc receptor. CONCLUSION: This targeted vaccine strategy is a promising tool to activate and deliver antigens to dendritic cells, thus improving immunotherapeutic response in situations in which the immune system is frequently compromised, as in advanced cancers.

Targeting nanosystems to human DCs via Fc receptor as an effective strategy to deliver antigen for immunotherapy.

Dendritic cells (DCs) are increasingly being explored as cellular vaccines for tumor immunotherapy, since they provide an effective system of antigen presentation both in vitro and in vivo. An additional advantage of this cell type is that it is possible to target specific antigens through the activation of receptors, such as FcR (the receptor for the IgG Fc fragment) and TLR (toll-like Receptor). Thus, the uptake capacity of DCs can be improved, thereby increasing antigen presentation. This, in turn, would lead to an enhanced immune response, and, in some instances, the tolerance/anergy of immune effector cells present in cancer patients could be reverted. Here we studied various nanotargeting systems, including liposomes and gold nanoparticles of a peptide-based immunotherapeutic vaccine for the treatment of androgen-responsive prostate cancer. Building blocks of the immunogenic peptide consisted of the luteinizing hormone-releasing hormone (LHRH), also known as gonadotropin-releasing hormone (GnRH) peptide (B- and T-cell epitope), in tandem with a T-helper epitope corresponding to the 830-844 region of tetanus toxoid. Three new peptides with several modifications at the N-terminal (palmitoyl, acetyl, and FITC) were synthesized. These peptides also contained a Cys as C-terminal residue to facilitate grafting onto gold nanoparticles. To target different antigen formulations to human DCs, the Fc was activated with a cross-linking spacer to generate a free thiol group and thus facilitate conjugation onto gold nanoparticles, liposomes, and peptide. Our results show that gold nanoparticles and liposomes targeted to FcRs of human DCs are effective antigen delivery carriers and induce a strong immune response with respect to nontargeted LHRH-TT-nanoparticle conjugates and a superior response to that of naked antigens. In addition, dual labeling using gold and FITC-peptide allowed DC tracking by flow cytometry as well as transmission electron microscopy. Nanoparticles were observed to show a homogeneous distribution throughout the cytoplasm. These results open up a new approach to the development of a novel strategy for cancer vaccines.