G lobally, over 2.5 billion people are estimated to be at risk of dengue virus (DENV) infection with an estimated 96 million symptomatic cases of dengue occurring annually (1). Despite ongoing research efforts, there are no sustainable vector control approaches or effective antiviral drugs to prevent or treat dengue, and vaccines have only recently been licensed by few countries and with suboptimal efficacy (2, 3, 4, 5). However, improvements in patient clinical management has been shown to reduce mortality among patients with severe dengue from 5% to Ͻ0.5% (6-9).Delayed dengue case identification often occurs in areas with limited diagnostics or surveillance resources, especially where dengue outbreaks are episodic or have been under-recognized (e.g., Africa and Oceania) (10, 11). These factors decrease health care provider awareness to include dengue in the differential diagnosis with other acute febrile illnesses (AFIs) such as malaria, leptospirosis, and influenza (12). Lastly, minimal or no laboratory infrastructure to conduct standard dengue diagnostic assays or perform them in a timely manner limits their utility for case management (13).Laboratory diagnosis of dengue can be achieved with a single serum specimen obtained during the febrile phase of the illness by testing for DENV analytes (e.g., nucleic acid, nonstructural protein 1 [NS1], and anti-DENV IgM) (14). DENV viremia occurs for up to 7 days after the onset of fever, and anti-DENV IgM begins to appear around 3 days after fever onset (15, 16). Although detection of DENV nucleic acid by real-time reverse transcriptase PCR (rRT-PCR) is the most sensitive and specific means to detect DENV viremia (17), immunoassays to detect DENV NS1 antigen provide acceptable levels of detection sensitivity and specificity (18,19). Immunoassays with good sensitivities and specificities to detect anti-DENV IgM are also widely available (20). However, both of these diagnostic approaches are instrument dependent and require facilities capable of performing complex diagnostic tests.The availability of dengue rapid diagnostic tests (RDTs) has the potential to change the current situation in resource-limited areas and improve dengue clinical management. We evaluated an RDT that detected both DENV NS1 antigen and anti-DENV IgM for its ability to provide accurate information for detecting dengue from outbreaks as the main cause of febrile illness in areas without ongoing laboratory testing. In all settings, a suspected dengue case was defined as a person with an AFI presenting for medical care. Serum specimens were collected from all suspected dengue cases upon initial presentation along with patient demographics, days post onset of illness (DPO), and specimen collection date (Table 1). Second convalescent specimens were not collected for patients, and only specimens collected upon patient presentation to hospital or clinic were used in this study. MATERIALS AND METHODS Study design. The Centers for Disease Control and PreventionDiagnostic testing. The RDT used during each ...
Dengue is a potentially fatal acute febrile illness caused by four mosquito-transmitted dengue viruses (DENV-1–4). Although dengue outbreaks regularly occur in many regions of the Pacific, little is known about dengue in the Republic of the Marshall Islands (RMI). To better understand dengue in RMI, we investigated an explosive outbreak that began in October 2011. Suspected cases were reported to the Ministry of Health, serum specimens were tested with a dengue rapid diagnostic test (RDT), and confirmatory testing was performed using RT-PCR and IgM ELISA. Laboratory-positive cases were defined by detection of DENV nonstructural protein 1 by RDT, DENV nucleic acid by RT-PCR, or anti-DENV IgM antibody by RDT or ELISA. Secondary infection was defined by detection of anti-DENV IgG antibody by ELISA in a laboratory-positive acute specimen. During the four months of the outbreak, 1,603 suspected dengue cases (3% of the RMI population) were reported. Of 867 (54%) laboratory-positive cases, 209 (24%) had dengue with warning signs, six (0.7%) had severe dengue, and none died. Dengue incidence was highest in residents of Majuro and individuals aged 10–29 years, and ∼95% of dengue cases were experiencing secondary infection. Only DENV-4 was detected by RT-PCR, which phylogenetic analysis demonstrated was most closely related to a virus previously identified in Southeast Asia. Cases of vertical DENV transmission, and DENV/Salmonella Typhi and DENV/Mycobacterium leprae co-infection were identified. Entomological surveys implicated water storage containers and discarded tires as the most important development sites for Aedes aegypti and Ae. albopictus, respectively. Although this is the first documented dengue outbreak in RMI, the age groups of cases and high prevalence of secondary infection demonstrate prior DENV circulation. Dengue surveillance should continue to be strengthened in RMI and throughout the Pacific to identify and rapidly respond to future outbreaks.
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