Sentinel Enhanced Dengue Surveillance System (SEDSS) Sites to Evaluate the Epidemiology and Prevention of Dengue and other Acute Febrile Illnesses in Puerto Rico

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Sentinel Enhanced Dengue Surveillance System (SEDSS) Sites to Evaluate the Epidemiology and Prevention of Dengue and other Acute Febrile Illnesses in Puerto Rico: Dengue is an acute febrile illness caused by infection with any of the four dengue viruses (DENV), which are transmitted by selected species of Aedes mosquitoes. Dengue is a major public health problem in the tropics and subtropics, with an estimated 2.5-4 billion people living in areas at risk of infection (40-60% of the world’s population). With an estimated 390 million DENV infections and 100 million cases annually, dengue ranks as the most frequent mosquito-borne viral disease in the world.
In the United States, dengue is endemic in the Caribbean (Puerto Rico, Virgin Islands) and US-Affiliated Pacific Islands. In Puerto Rico, dengue occurs throughout the year but incidence increases dramatically during the warm, wet period of the year, which is from June to October. This island has the largest US population with endemic dengue and has seen a continued increase in disease severity and number of cases since dengue first became reportable to the Puerto Rico Department of Health (PRDH) in 1915. In the United States, dengue became a nationally notifiable disease to the Centers for Disease Control and Prevention (CDC) on January 1, 2010.
There is no long-lasting, cross protective immunity between the four DENV-types and individuals can be infected several times over their lifetime as they are exposed to different circulating DENV-types. Whereas DENV infection is most often asymptomatic, persons with a symptomatic infection (dengue) most often present with an acute febrile illness (AFI) and no signs or symptoms reliably differentiate dengue from other AFI early in the course of the illness. Previous DENV infection, whether asymptomatic or symptomatic, may predispose a person to more severe disease with subsequent infections.
Dengue has been difficult to prevent or control because there are no tools for the effective primary prevention of DENV transmission by vector mosquitoes or prevention of dengue through immunization. Worldwide, the reported incidence of dengue and its geographic distribution have increased several-fold over the past two decades, which is best observed in the region of the Americas, including Puerto Rico. During the mid-1950’s to 1960’s, the Aedes aegypti mosquito was nearly eradicated from the Americas through a DDT insecticide-based program. However, once this effort ended these mosquitoes aggressively regained and extended their geographic distribution. Community-based vector control programs to reduce mosquito breeding sites, which are often combined with indoor residual insecticide spraying have only been partially effective in reducing mosquito density and have not prevented or controlled dengue outbreaks. In addition, when evaluated, Aedes mosquitoes have become increasingly resistant to insecticides.
In the past 5 - 8 years a number of new tools that could potentially achieve primary prevention of dengue have been developed and are undergoing evaluation. For vector control, these include development of new insecticides to overcome resistance, growth inhibitors to interrupt metamorphosis, devices that attract, trap and kill ovipositing female mosquitoes, among others. Most of these novel tools have been shown in proof of concept studies to achieve reductions in vector density and several are now being evaluated in large-scale trials. However, none of the new vector control tools have been evaluated for their ability to prevent the actual disease.
Vaccines are the other potential primary prevention tool and there has been substantial progress in dengue vaccine development and evaluation during the past 10 years. Presently, there are three vaccines in Phase 1 (safety) clinical trials, two in Phase 2 (immunogenicity) trials and one 1 is completing a Phase 3 efficacy trial. All of these vaccine candidates are designed to protect against dengue caused by each of the four viruses.
Because of this lack of effective tools for the primary prevention of dengue, efforts have been directed at secondary prevention of the poor clinical outcomes (i.e., death, excess morbidity) among patients with dengue. Studies in Thailand and Vietnam have shown a reduction in the case fatality rate among persons with severe forms of dengue (e.g., dengue hemorrhagic fever, dengue shock syndrome), with improved approaches to clinical case management, including early recognition of plasma leakage and severe dengue, improved patient monitoring and appropriate fluid resuscitation. These finding have been incorporated in recommendations for clinical case management made by the WHO in 2009.
Due to the present lack of tools for primary prevention of dengue and DENV transmission, prevention efforts and research are focused on development of disease surveillance systems to evaluate the effectiveness of primary and secondary dengue prevention methods and strategies, including the eventual introduction of dengue vaccines and or new vector control methods. In 2012, the CDC began to establish a number of acute febrile illness surveillance sites in Puerto Rico for this purpose. These sites serve as platforms in which to study dengue and other acute febrile illnesses on the differential diagnosis of dengue. This cooperative agreement seeks to continue to support these population-based surveillance study sites that capture outpatients presenting with acute febrile illnesses to determine their etiology, basic epidemiology, outcomes and severity, and risk factors for severity outcomes. These sites also provide the opportunity to conduct research on dengue diagnostics to aid case management by improving case recognition and early treatment.
The purpose of this FOA is to build on the knowledge and accomplishments of the previous program that established the Sentinel Enhanced Dengue Surveillance System (SEDSS) sites to provide new information on dengue and other acute febrile illnesses (AFI) in Puerto Rico, which is located in the subtropics and where dengue epidemiology is similar to dengue endemic areas worldwide. The program will conduct research on dengue, diagnostic methods to differentiate the etiology of AFIs, and evaluate the effectiveness of tools for the primary and secondary prevention of dengue.