Assessment of benefits and risks associated with dengue vaccination at the individual and population levels: a dynamic modeling approach.

BACKGROUND: A case-cohort study, using a novel assay and data from three dengue vaccine efficacy trials, highlighted differences in vaccination outcomes according to baseline serostatus. Based on these results, we explored, with a model, the benefits and risks associated with vaccination. RESEARCH DESIGN AND METHODS: Parameters of a previously developed transmission model were estimated with subject-level data from a case-cohort study. The model was used to assess vaccination outcomes for a range of transmission settings over 5-30 years, with or without indirect protection. MAIN OUTCOME MEASURES: Symptomatic dengue cases, dengue hospitalizations, and severe dengue cases. RESULTS: The model is consistent with previous results indicating a transitory period at increased risk for dengue-seronegative vaccine recipients (setting-dependent duration) and long-term benefits for dengue-seropositive recipients. At the population level, benefits to seropositive individuals over 10 years outweighed the risk to those seronegative in moderate to high transmission settings (≥50% seropositivity at age 9), especially in high transmission settings (no excess hospitalizations in dengue-seronegative for ≥80% seropositivity at age 9). Results were more favorable when longer time horizons or indirect protection were considered. CONCLUSIONS: Results indicate a public health benefit associated with dengue vaccination especially in high-transmission settings, even with the initial excess risks to dengue-seronegative patients which diminish over time.

Tetravalent Dengue Vaccine Reduces Symptomatic and Asymptomatic Dengue Virus Infections in Healthy Children and Adolescents Aged 2-16 Years in Asia and Latin America.

BACKGROUND: Asymptomatic dengue virus-infected individuals are thought to play a major role in dengue virus transmission. The efficacy of the recently approved quadrivalent CYD-TDV dengue vaccine against asymptomatic dengue virus infection has not been previously assessed. METHODS: We pooled data for 3 736 individuals who received either CYD-TDV or placebo at 0, 6, and 12 months in the immunogenicity subsets of 2 phase 3 trials (clinical trials registration NCT01373281 and NCT01374516). We defined a seroconversion algorithm (ie, a ≥4-fold increase in the neutralizing antibody titer and a titer of ≥40 from month 13 to month 25) as a surrogate marker of asymptomatic infection in the vaccine and placebo groups. RESULTS: The algorithm detected seroconversion in 94% of individuals with a diagnosis of virologically confirmed dengue between months 13 and 25, validating its discriminatory power. Among those without virologically confirmed dengue (n = 3 669), 219 of 2 485 in the vaccine group and 157 of 1 184 in the placebo group seroconverted between months 13 and 25, giving a vaccine efficacy of 33.5% (95% confidence interval [CI], 17.9%-46.1%) against asymptomatic infection. Vaccine efficacy was marginally higher in subjects aged 9-16 years (38.6%; 95% CI, 22.1%-51.5%). The annual incidence of asymptomatic dengue virus infection in this age group was 14.8%, which was 4.4 times higher than the incidence for symptomatic dengue (3.4%). CONCLUSIONS: The observed vaccine efficacy against asymptomatic dengue virus infections is expected to translate into reduced dengue virus transmission if sufficient individuals are vaccinated in dengue-endemic areas.

Chronic Lung Allograft Dysfunction: A Systematic Review of Mechanisms.

Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. Chronic lung allograft dysfunction manifests as bronchiolitis obliterans syndrome or the recently described restrictive allograft syndrome. Although numerous risk factors have been identified so far, the physiopathological mechanisms of CLAD remain poorly understood. We investigate here the immune mechanisms involved in the development of CLAD after lung transplantation. We explore the innate or adaptive immune reactions induced by the allograft itself or by the environment and how they lead to allograft dysfunction. Because current literature suggests bronchiolitis obliterans syndrome and restrictive allograft syndrome as 2 distinct entities, we focus on the specific factors behind one or the other syndromes. Chronic lung allograft dysfunction is a multifactorial disease that remains irreversible and unpredictable so far. We thus finally discuss the potential of systems-biology approach to predict its occurrence and to better understand its underlying mechanisms.

Comparative transcriptomic analysis between an artificially induced SIRS in healthy individuals and spontaneous sepsis.

Sepsis is defined as a syndrome combining a systemic inflammatory response with a documented infection. It may progress to more serious cases such as septic shock following the failure of one or more organs and the emergence of hemodynamic defects. Assuming that the emergence of serious septic syndromes may be partially explained by the early loss of regulation of the inflammatory response, we decided to compare, in a transcriptomic perspective, the biological mechanisms expressed during an induced systemic inflammatory response with those expressed during severe septic syndromes. By using open-access transcriptomic databases, we first studied the kinetics of an induced inflammatory response. The use of functional analysis helped us identify discriminating biological mechanisms, such as the mTOR signaling pathway, between the pathological cases of sepsis and non-pathological (i.e., the artificially induced SIRS) cases.