Analysis of Hospitalized and Severe Dengue Cases Over the 6 years of Follow-up of the Tetravalent Dengue Vaccine (CYD-TDV) Efficacy Trials in Asia and Latin America.

BACKGROUND: CYD-TDV, a live, attenuated, tetravalent dengue vaccine, has been approved for the prevention of symptomatic dengue in previously dengue exposed individuals. This post hoc analysis assessed hospitalized and severe virologically confirmed dengue (VCD) over the complete 6-year follow-up of 3 CYD-TDV efficacy studies (CYD14, CYD15, and CYD23/CYD57). METHODS: The main outcomes were hazard ratios (HRs) for hospitalized or severe VCD by baseline dengue serostatus, focusing on those who were seropositive, and by age at immunization (<9 years/≥9 years). Baseline dengue serostatus was measured or inferred using several methods. Hospitalized VCD cases were characterized in terms of clinical signs and symptoms and wild-type viremia level. Antibody persistence was assessed up to 5 years after the last injection. RESULTS: In those aged ≥9 years and baseline seropositive, CYD-TDV protected against hospitalized and severe VCD over 6 years compared to placebo (HR [95% confidence interval] multiple imputation from month 0 method, .19 [.12-.30] and .15 [.06-.39]; other methods were consistent). Vaccine protection was observed over the different study periods, being highest during the first 2 years. Evidence for a decreased risk of hospitalized and severe VCD was also observed in seropositive participants aged 6-8 years. Clinical signs and symptoms, and quantified dengue viremia from participants with hospitalized VCD were comparable between groups. CONCLUSIONS: CYD-TDV demonstrated robust protection against hospitalized and severe VCD over the entire 6-year follow-up in participants who were seropositive and ≥9 years old. Protection was also observed in seropositive 6-8 year-olds. Clinical Trials Registration: NCT00842530, NCT01983553, NCT01373281, NCT01374516.

Impact of Dengue Vaccination on Serological Diagnosis: Insights From Phase III Dengue Vaccine Efficacy Trials.

Background: We previously reported that vaccination with the tetravalent dengue vaccine (CYD-TDV; Dengvaxia) may bias the diagnosis of dengue based on immunoglobulin M (IgM) and immunoglobulin G (IgG) assessments. Methods: We undertook a post hoc pooled analysis of febrile episodes that occurred during the active surveillance phase (the 25 months after the first study injection) of 2 pivotal phase III, placebo-controlled CYD-TDV efficacy studies that involved ≥31000 children aged 2-16 years across 10 countries in Asia and Latin America. Virologically confirmed dengue (VCD) episode was defined with a positive test for dengue nonstructural protein 1 antigen or dengue polymerase chain reaction. Probable dengue episode was serologically defined as (1) IgM-positive acute- or convalescent-phase sample, or (2) IgG-positive acute-phase sample and ≥4-fold IgG increase between acute- and convalescent-phase samples. Results: There were 1284 VCD episodes (575 and 709 in the CYD-TDV and placebo groups, respectively) and 17673 other febrile episodes (11668 and 6005, respectively). Compared with VCD, the sensitivity and specificity of probable dengue definition were 93.1% and 77.2%, respectively. Overall positive and negative predictive values were 22.9% and 99.5%, respectively, reflecting the much lower probability of correctly confirming probable dengue in a population including a vaccinated cohort. Vaccination-induced bias toward false-positive diagnosis was more pronounced among individuals seronegative at baseline. Conclusions: Caution will be required when interpreting IgM and IgG data obtained during routine surveillance in those vaccinated with CYD-TDV. There is an urgent need for new practical, dengue-specific diagnostic algorithms now that CYD-TDV is approved in a number of dengue-endemic countries. Clinical Trials Registration: NCT01373281 and NCT01374516.

Paediatric cardiopulmonary resuscitation training program in Latin-America: the RIBEPCI experience.

BACKGROUND: To describe the design and to present the results of a paediatric and neonatal cardiopulmonary resuscitation (CPR) training program adapted to Latin-America. METHODS: A paediatric CPR coordinated training project was set up in several Latin-American countries with the instructional and scientific support of the Spanish Group for Paediatric and Neonatal CPR. The program was divided into four phases: CPR training and preparation of instructors; training for instructors; supervised teaching; and independent teaching. Instructors from each country participated in the development of the next group in the following country. Paediatric Basic Life Support (BLS), Paediatric Intermediate (ILS) and Paediatric Advanced (ALS) courses were organized in each country adapted to local characteristics. RESULTS: Five Paediatric Resuscitation groups were created sequentially in Honduras (2), Guatemala, Dominican Republican and Mexico. During 5 years, 6 instructors courses (94 students), 64 Paediatric BLS Courses (1409 students), 29 Paediatrics ILS courses (626 students) and 89 Paediatric ALS courses (1804 students) were given. At the end of the program all five groups are autonomous and organize their own instructor courses. CONCLUSIONS: Training of autonomous Paediatric CPR groups with the collaboration and scientific assessment of an expert group is a good model program to develop Paediatric CPR training in low- and middle income countries. Participation of groups of different countries in the educational activities is an important method to establish a cooperation network.

Detection of vaccine-derived polioviruses in Mexico using environmental surveillance.

BACKGROUND: Early detection and control of vaccine-derived poliovirus (VDPV) emergences are essential to secure the gains of polio eradication. METHODS: Serial sewage samples were collected in 4 towns of Mexico before, throughout, and after the May 2010 oral poliovirus vaccine (OPV) mass immunization campaign. Isolation and molecular analysis of polioviruses from sewage specimens monitored the duration of vaccine-related strains in the environment and emergence of vaccine-derived polioviruses in a population partially immunized with inactivated poliovirus vaccine (IPV). RESULTS: Sabin strains were identified up to 5-8 weeks after the campaign in all towns; in Aguascalientes, 1 Sabin 3 was isolated 16 weeks after the campaign, following 7 weeks with no Sabin strains detected. In Tuxtla Gutiérrez, type 2 VDPV was isolated from 4 samples collected before and during the campaign, and type 1 VDPV from 1 sample collected 19 weeks afterward. During 2009-2010, coverage in 4 OPV campaigns conducted averaged only 57% and surveillance for acute flaccid paralysis (AFP) was suboptimal (AFP rate<1 per 100,000 population<15 years of age) in Tuxtla Gutierrez. CONCLUSIONS: VDPVs may emerge and spread in settings with inadequate coverage with IPV/OPV vaccination. Environmental surveillance can facilitate early detection in these settings.

Immunobridging efficacy of a tetravalent dengue vaccine against dengue and against hospitalized dengue from children/adolescents to adults in highly endemic countries.

BACKGROUND: The recombinant tetravalent live-attenuated dengue vaccine based on the YF 17D vaccine virus backbone (CYD-TDV) demonstrated vaccine efficacy (VE) against symptomatic, virologically confirmed dengue of any serotype from month 13 to month 25 (VCD-DENV-AnyM13→M25) in the CYD14 (2-14-y-olds) and CYD15 (9-16-y-olds) phase 3 trials. Fifty percent plaque reduction neutralization test (PRNT50) titers are a potential surrogate for immunobridging VE to adults. METHODS: Using PRNT50 calibration datasets, we applied immunobridging approaches using baseline and/or M13 PRNT50 titers to estimate VE against VCD-DENV-AnyM0→M25 and against hospitalized VCD (HVCD)-DENV-AnyM0→M72 in hypothetical 18-45-y-old and 46-50-y-old CYD14 and CYD15 cohorts. RESULTS: Baseline and M13 geometric mean PRNT50 titers were greater in 18-45-y-olds and in 46-50-y-olds vs 9-16-y-olds for most comparisons. Estimated VE (95% CIs against VCD-DENV-AnyM0→M25 ranged from 75.3% to 90.9% (52.5% to 100%) for 18-45-y-olds and 74.8% to 92.0% (53.4% to 100%) for 46-50-y-olds. Estimated VE (95% CIs) against HVCD-DENV-AnyM0→M72 ranged from 58.8% to 78.1% (40.9 to 98.9%) for 18-45-y-olds and 57.2% to 78.4% (40.5 to 97.6%) for 46-50-y-olds. Corresponding predictions among baseline-seropositive individuals yielded comparable or higher VE estimates. CONCLUSIONS: VE M0→M25 against DENV-Any and VE against HVCD-DENV-AnyM0→M72 are both expected to be higher in 18-45 and 46-50-y-olds vs CYD14 and CYD15 9-16-y-olds.

Immune Response Persistence and Safety of a Booster Dose of the Tetravalent Dengue Vaccine in Adolescents and Adults Who Previously Completed the 3-dose Schedule 4-5 Years Earlier in Latin America: A Randomized Placebo-controlled Trial.

BACKGROUND: We previously described an increased immune response 28 days after a booster dose of the live, attenuated, tetravalent dengue vaccine (CYD-TDV) in healthy adolescents and adults in Latin America (CYD64, NCT02623725). This follow-up study evaluated immune response persistence and safety of a CYD-TDV booster dose up to Month (M) 24 post-booster. METHODS: This study included 250 participants who previously received 3 primary doses of CYD-TDV in the CYD13 (NCT00993447) and CYD30 (NCT01187433) studies, and who were randomized 4-5 years later to receive a CYD-TDV booster or placebo (3:1). Dengue neutralizing antibodies against the parental dengue virus strains were assessed using the plaque reduction neutralization test (PRNT50) at M6, M12, and M24 post-booster. Post-booster memory B-cell responses were assessed in a subset of participants using the FluoroSpot assay up to M12 post-booster. RESULTS: In the CYD-TDV group (n = 187), dengue neutralizing antibody geometric mean titers (GMTs) declined from the peak at day 28 through to M24 for all serotypes. GMTs at M24 were similar to those at pre-booster among baseline dengue seropositives. A similar trend was observed for baseline dengue seronegatives, albeit at a lower magnitude. Previous vaccination-induced detectable B-cell memory responses in seropositives and seronegatives that decreased to pre-booster levels at M12 post-booster. The CYD-TDV booster dose was well-tolerated. CONCLUSIONS: In baseline dengue seropositives, following a CYD-TDV booster dose administered 4-5 years after primary immunization, dengue neutralizing antibody GMTs and B-cell memory responses peaked in the short-term before gradually decreasing over time. A CYD-TDV booster dose could improve protection against dengue during outbreak periods.

Dengue Vaccine Booster in Healthy Adolescents and Adults in Latin America: Evaluation 4-5 Years After a Primary 3-Dose Schedule.

BACKGROUND: The tetravalent dengue vaccine (CYD-TDV, Dengvaxia, Sanofi Pasteur) demonstrated efficacy in 2 previous phase III trials conducted in endemic countries. Neutralizing antibodies (NAbs) elicited by 3 doses of this vaccine have been associated with efficacy. Long-term follow-up data has shown that NAb immune responses tend to wane over time, after the third dose. This study compared the immune response elicited by a booster (4th) dose of CYD-TDV with the immune responses from the same participants obtained post-dose 3 of the primary series administered 4-5 years earlier. METHODS: This multicenter, observer-blind, randomized, placebo-controlled, phase II noninferiority trial was conducted in healthy adolescents and adults in dengue endemic countries of Latin America (Colombia, Honduras, Brazil, Mexico and Puerto Rico). All participants had been immunized with 3 doses of CYD-TDV in phase II studies conducted 4-5 years earlier. NAb levels against each dengue virus serotype 28 days postbooster or placebo injection were reported. RESULTS: A total of 187 participants received CYD-TDV and 64 received placebo. Prospectively defined noninferiority criteria for dengue NAbs after the booster dose compared with postdose 3 were met for all 4 serotypes. Prospectively defined superiority criteria were met for 3 of the 4 serotypes. CONCLUSIONS: Antidengue NAb levels can be boosted to levels at least as high as, or higher than those observed after completion of the primary 3-dose series, with an additional dose of CYD-TDV 4-5 years after the standard 3-dose vaccination schedule.

Hábitos alimenticios, nocivos y rendimiento académico en estudiantes universitarios en tiempos de Covid-19

Resumen Los hábitos alimenticios influyen drásticamente en el rendimiento académico universitario, teniendo consecuencias a corto, mediano y largo plazo. Objetivo. Identificar los hábitos alimenticios nocivos y rendimiento académico en estudiantes universitarios en tiempos de Covid-19 en Ecuador-Azogues. Metodología . Estudio descriptivo transversal, población de estudio 623 estudiantes universitarios de la carrera de Medicina, se les aplicó una encuesta, el análisis estadístico se lo realizó mediante SPSS V20. Resultados. El 64,7% corresponden al sexo femenino, 58,3% proceden de la provincia del Cañar, el 82,7 son católicos y el 10,1% presentan bajo rendimiento, de los cuales el 28,6% presentaron sobrepeso y la probabilidad de que estos estudiantes tengan bajo rendimiento fue del 63%. Se demostró también que el 82,5% de estudiantes consumen comida chatarra, existiendo 3 veces (RP 3,12; IC95% 1,88-5,26) más probabilidad de que éstos estudiantes tengan bajo rendimiento, el sexo masculino también presentó 1,6 veces (IC95% 1,04-2,65) más probabilidad de tener bajo rendimiento en comparación con el sexo femenino, mientras que los estudiantes que proceden de las distintas provincias tienen 1,6 veces (RP 1,63; IC95% 1,03-2,63) más probabilidad de tener rendimiento deficiente. Un 85,7% de estudiantes consume alcohol y al menos el 25,4% ha consumido drogas existiendo 2 veces (PR 2; IC95% 1,19-3,44) más probabilidad de que estos estudiantes bajen su rendimiento. Conclusiones. Se determinó que el bajo rendimiento académico está relacionado no solo por el sexo sino también, por la procedencia, la malnutrición, consumo de comida chatarra y uso de drogas incrementando la proporción de estudiantes con bajo rendimiento.

Abstract Eating habits drastically influence university academic performance, having short, medium and long term consequences. Objective. To identify harmful eating habits and academic performance in university students in times of Covid-19 in Ecuador-Azogues. Methodology . Descriptive cross-sectional study, study population 623 university students of the Medicine career, a survey was applied to them, the statistical analysis was carried out using SPSS V20. Results . 64.7% were female, 58.3% were from the province of Cañar, 82.7% were Catholic and 10.1% were underachievers, of which 28.6% were overweight and the probability of these students being underachievers was 63%. It was also shown that 82.5% of students consume junk food, with 3 times (PR 3.12; 95%CI 1.88-5.26) more probability that these students have low performance, the male sex also presented 1.6 times (95%CI 1.04-2.65) more probability of having low performance compared to the female sex, while students coming from the different provinces have 1.6 times (PR 1.63; 95%CI 1.03-2.63) more probability of having poor performance. A 85.7% of students consume alcohol and at least 25.4% have consumed drugs existing 2 times (PR 2; 95%CI 1.19-3.44) more likely that these students have lower performance. Conclusions . It was determined that low academic performance is related not only by gender but also by origin, malnutrition, consumption of junk food and drug use, increasing the proportion of students with low performance.

Resumo Os hábitos alimentares influenciam drasticamente o desempenho acadêmico universitário, tendo conseqüências a curto, médio e longo prazo. Objetivo. Identificar hábitos alimentares prejudiciais e desempenho acadêmico em estudantes universitários durante o período Covid-19 no Equador-Azogues. Metodologia. Estudo descritivo transversal, população estudada 623 estudantes universitários de Medicina, uma pesquisa foi aplicada a eles, a análise estatística foi realizada utilizando o SPSS V20. Resultados. 64,7% eram do sexo feminino, 58,3% eram da província de Cañar, 82,7% eram católicos e 10,1% eram alunos com baixo aproveitamento, dos quais 28,6% tinham excesso de peso, e a probabilidade de esses alunos serem alunos com baixo aproveitamento era de 63%. Também foi demonstrado que 82,5% dos estudantes consomem comida de plástico, com 3 vezes (PR 3,12; 95%CI 1,88-5,26) mais propensos a serem sub-atingidos, os estudantes do sexo masculino também foram 1,6 vezes (95%CI 1,04-2,65) mais propensos a serem sub-atingidos em comparação com os estudantes do sexo feminino, enquanto os estudantes das diferentes províncias foram 1,6 vezes (PR 1,63; 95%CI 1,03-2,63) mais propensos a serem sub-atingidos. 85,7% dos estudantes usam álcool e pelo menos 25,4% usaram drogas sendo 2 vezes (PR 2; 95%CI 1,19-3,44) mais propensos a ter um desempenho mais fraco. Conclusões. Constatou-se que o baixo desempenho acadêmico estava relacionado não apenas por gênero, mas também, por formação, desnutrição, consumo de junk food e uso de drogas, aumentando a proporção de estudantes com baixo desempenho