Dengue Virus

Dengue fever is caused by dengue viruses, which are members of the Flavivirus family. Dengue is transmitted to humans by bite of Aedes aegypti and Aedes albopictus mosquitos. Dengue is the most common arboviral disease globally. 

Aedes aegypti and Aedes albopictus mosquitos,are most prevalent in tropical and subtropical countries. Dengue transmission peaks during the warmer and wetter months. Aedes mosquitoes are sensitive to small changes in temperature and their range has been expanding as the planet warms due to climate change. Aedes has already spread to Mexico and Central America and is gradually spreading into large parts of southern Europe and the United States.

Dengue cases resurged globally after the COVID-19 pandemic. In 2023, more than 4.6 million cases and 4000 deaths were reported in the Americas region. As of June 24, 2024, more than 9.7 million dengue cases were reported in the Americas, which was twice as many as in all of 2023.

Dengue is already an increasing health threat in the US. The CDC reported 1890 travel-associated cases in 2023. Aedes aegypti and Aedes albopictus mosquitos are present throughout much of the southeastern United States and can spread dengue virus if they bite an infected person. Locally acquired dengue cases have been reported in Arizona, California, Florida, Hawaii, and Texas. 

The Dengue virus has four strains. A person cannot be reinfected with the same strain twice, but can be infected with one of the other three. Most dengue virus infections are asymptomatic, but 25% patients may develop either dengue fever or the more severe dengue hemorrhagic fever. The incubation period from infection to onset of symptoms is 3 to 10 days. Dengue fever is usually a self-limited acute illness that lasts for 2 to 7 days and includes high fever, headache, rash, myalgia, and arthralgia. Leukopenia is common. 

Approximately 5% of people with symptomatic dengue develop hemorrhagic fever. This is characterized by resolving fever, thrombocytopenia, bleeding and increased vascular permeability. The latter is characterized by hemoconcentration, hypoalbuminemia, ascites, or pleural effusion. Dengue hemorrhagic fever can result in circulatory instability or shock. 

IgM antibodies directed against dengue virus envelope protein typically develop during the first week of illness and may persist in serum for months or years after initial infection. Neutralizing IgG antibodies develop shortly after IgM antibodies and persist for multiple years. 

Patients with suspected dengue virus disease should be tested with a combination of a RT-PCR or a NS1 (nonstructural protein 1) antigen enzyme immunoassay and also with an IgM antibody test. The sensitivity of RT-PCR and NS1 antigen tests decrease after the first 7 days of symptoms. RT-PCR can detect all four serotypes of dengue virus. Dengue IgM antibody may cross-react with other flaviviruses such as West Nile, St. Louis encephalitis, Japanese encephalitis and yellow fever viruses.

Pregnant women with a clinically compatible illness and recent possible exposure to either dengue or Zika virus should have concurrent diagnostic testing for both infections. PCR and IgM antibody testing should be performed on a serum specimen. PCR for Zika virus should also be performed on a urine specimen. A positive PCR result typically provides evidence of recent infection. 

For serum specimens collected <7 days after onset of symptoms, the combination of a negative PCR result and a negative IgM antibody test suggests the patient did not have a recent flavivirus infection. However, in the absence of PCR testing, a negative acute IgM antibody by itself might be due to specimen collection prior to development of detectable antibodies and does not rule out infection. For specimens collected from 7 days to 12 weeks after onset of symptoms, a negative IgM antibody result to dengue virus rules out recent infection and other etiologies should be considered.

Plaque reduction neutralization tests (PRNTs) are quantitative assays that measure virus-specific neutralizing antibody titers for dengue and other flaviviruses. PRNTs can resolve false-positive antibody results caused by nonspecific reactivity. CDC uses a 90% cutoff value titer ≥10 in serum and ≥2 in cerebrospinal fluid to define positive specimens. Negative PRNT titers against dengue virus in a serum specimen collected >7 days after illness onset rule out infection.

If both dengue and Zika virus RT-PCRs are negative but either IgM antibody test is positive, confirmatory PRNTs should be performed against dengue, Zika, and other flaviviruses endemic to the region where exposure occurred. For indeterminate IgM antibody results, PRNT should be performed on the same specimen. 

References

Sharp TM, Fischer M, Muñoz-Jordán JL, et al. Dengue and Zika Virus Diagnostic Testing for Patients with a Clinically Compatible Illness and Risk for Infection with Both Viruses. MMWR Recomm Rep 2019;68(No. RR-1):1–10. DOI: http://dx.doi.org/10.15585/mmwr.rr6801a1external icon

CDC Health Alert Network, CDCHAN-00511, Increased Risk of Dengue Virus Infections in the United States, June 25, 2024. https://emergency.cdc.gov/han/2024/han00511.asp

Adams LE, Wong JM, Paz-Bailey G. Dengue. JAMA. 2024;332(24):2109–2110. doi:10.1001/jama.2024.21094