Dengue severity by serotype and immune status in 19 years of pediatric clinical studies in Nicaragua.

Background: Dengue virus, a major global health threat, consists of four serotypes (DENV1-4) that cause a range of clinical manifestations from mild to severe and potentially fatal disease.

Methods: This study, based on 19 years of data from the Pediatric Dengue Cohort Study and Pediatric Dengue Hospital-based Study in Managua, Nicaragua, investigates the relationship of serotype and immune status with dengue severity. Dengue cases were confirmed by molecular, serological, and/or virological methods, and sudy participants 6 months to 17 years old were followed during their hospital stay or as ambulatory patients.

Dengue and Zika virus infections in children elicit cross-reactive protective and enhancing antibodies that persist long term.

Dengue virus serotypes 1 to 4 (DENV1–4) and Zika virus (ZIKV) are mosquito-borne flaviviruses that induce both virus-specific and broadly reactive antibodies. A first DENV infection is thought to induce antibodies that wane over 2 years to titers that can subsequently enhance severe dengue disease. Secondary DENV infection with a different serotype is thought to induce stable, cross-serotype protective antibodies.

Zika virus infection enhances future risk of severe dengue disease.

The Zika pandemic sparked intense interest in whether immune interactions among dengue virus serotypes 1 to 4 (DENV1 to -4) extend to the closely related Zika virus (ZIKV). We investigated prospective pediatric cohorts in Nicaragua that experienced sequential DENV1 to -3 (2004 to 2015), Zika (2016 to 2017), and DENV2 (2018 to 2020) epidemics. Risk of symptomatic DENV2 infection and severe disease was elevated by one prior ZIKV infection, one prior DENV infection, or one prior DENV infection followed by one ZIKV infection, compared with being flavivirus-naïve.

Dengue illness index-A tool to characterize the subjective dengue illness experience.

Dengue virus infections are a major cause of febrile illness that significantly affects individual and societal productivity and drives up health care costs principally in the developing world. Two dengue vaccine candidates are in advanced clinical efficacy trials in Latin America and Asia, and another has been licensed in more than fifteen countries but its uptake has been limited. Despite these advances, standardized metrics for comparability of protective efficacy between dengue vaccines remain poorly defined.

Development of standard clinical endpoints for use in dengue interventional trials.

Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness.

Evaluation of the traditional and revised WHO classifications of Dengue disease severity.

Dengue is a major public health problem worldwide and continues to increase in incidence. Dengue virus (DENV) infection leads to a range of outcomes, including subclinical infection, undifferentiated febrile illness, Dengue Fever (DF), life-threatening syndromes with fluid loss and hypotensive shock, or other severe manifestations such as bleeding and organ failure. The long-standing World Health Organization (WHO) dengue classification and management scheme was recently revised, replacing DF, Dengue Hemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS) with Dengue without Warning Signs, Dengue with Warning Signs (abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing hematocrit with decreasing platelets) and Severe Dengue (SD; dengue with severe plasma leakage, severe bleeding, or organ failure).

Unusual dengue virus 3 epidemic in Nicaragua, 2009.

The four dengue virus serotypes (DENV1-4) cause the most prevalent mosquito-borne viral disease affecting humans worldwide. In 2009, Nicaragua experienced the largest dengue epidemic in over a decade, marked by unusual clinical presentation, as observed in two prospective studies of pediatric dengue in Managua. From August 2009-January 2010, 212 dengue cases were confirmed among 396 study participants at the National Pediatric Reference Hospital.

Severe coinfections of dengue and pandemic influenza A H1N1 viruses.

Here we report on 4 hospitalized patients with dengue-influenza virus coinfections. All patients were RT-PCR positive for dengue virus and pandemic influenza A H1N1. Clinical findings at presentation ranged from influenza-like illness to severe dengue.