Fatal Dengue Acquired in Florida

TO THE EDITOR:

The global burden of dengue, a mosquito-borne viral acute febrile illness common throughout the tropics, is worsening.^1,2 Approximately 5% of patients have progression to severe dengue, including plasma leakage, shock, and hemorrhage, but they may also present with acute cholecystitis.^1,3

In 2019, a total of 413 dengue cases were probably imported to Florida, including 14 cases of severe dengue (3.4%), resulting in 18 locally acquired cases, predominantly in the Miami area (Figs. S1 and S2 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). Most persons with travel-associated cases reported recent travel to Cuba and were infected with dengue virus (DENV) serotype 2 (DENV-2).

In August 2019, a woman in her 30s living in Miami presented with 7 days of fever, flank pain, and hypotension (Fig. 1). She reported having returned from Honduras 5 weeks earlier. Imaging showed acute cholecystitis (Fig. S3), and laparoscopic cholecystectomy was performed. Hemorrhage and multiorgan failure developed, and the patient died. Serologic testing of specimens that were collected on hospital days 4, 10, and 25 showed seroconversion on anti-DENV IgM enzyme-linked immunosorbent assay. Postmortem molecular testing of the same specimens detected DENV-2 with decreasing levels of viral RNA over time (Fig. S4). Phylogenetic analysis revealed the closest relationship to virus detected in travelers who had recently returned from Cuba (Fig. S5), findings that strongly suggested that infection occurred after importation from Cuba and subsequent circulation in the Miami area.

Figure 1. Timeline and Laboratory Values for a Patient with Dengue and Acute Cholecystitis, Florida, 2019.

In Panels B and C, laboratory values were not available for the day before hospital admission (day –1); the dashed lines indicate the inferred trend between the values measured on day –2 and day 0. CVVHD denotes continuous venovenous hemodialysis, and DENV-2 dengue virus serotype 2.

As dengue continues to expand outside the tropics, more frequent importation and local transmission of DENV in the United States is expected.² In evidence of this, most dengue cases that were detected in Florida during 2019 were imported from Cuba, and the locally acquired cases reported here included the first fatal case. Similarly, detection of Zika virus (which is transmitted by the same mosquito species as DENV) among returning travelers identified an unreported outbreak in Cuba during 2017.⁴

Timely diagnosis of this patient’s condition was complicated by a lack of available dengue rapid diagnostic tests, because none are yet cleared by the Food and Drug Administration for use in the United States. Had a rapid test been performed, surgery might have been avoided.³ Detection of DENV RNA in serum samples that were collected 3 weeks apart was unexpected, because detection more than 10 days after illness onset is known to occur only in patients with hematologic cancers or stem-cell transplantation; however, another patient with dengue who died after cholecystectomy had viral RNA detected 11 days after illness onset.⁵

Ensuring appropriate management of patient care, including close clinical monitoring and judicious use of intravenous fluids, can reduce dengue case-fatality rates.¹ Clinicians should suspect dengue and order molecular testing for patients with acute febrile illness and relevant epidemiologic exposure, because knowledge of this infection may alter clinical care.