Introduction and Spread of Dengue Virus 3, Florida, USA, May 2022

engue virus (DENV) is not endemic in the conti-

nental United States (1); most cases occur among

travelers to DENV-endemic areas (2). In Florida, USA,

DENV infections are primarily reported among trav-

elers (https://ndc.services.cdc.gov/case-denitions/

dengue-virus-infections-2015); however, locally ac-

quired cases and limited outbreaks have been report-

ed in Monroe County in 2009–2010 (n = 88), Martin

County in 2013 (n = 24), and Monroe County in 2020

(n = 72) (3–5). During 2009–2021, an annual median of

83 (range 19–413) travel-associated DENV infections

and 7 (range 0–77) locally acquired cases were report-

ed in Florida; all DENV types (DENV-1−4) occurred

among both travel-associated and locally acquired

cases (6). Previous work demonstrated the DENV

vectors Aedes aegypti and A. albopictus mosquitoes are

present across Florida (7).

In early 2022, the Florida Department of Health

(FDOH) identied an increase in travel-associated

DENV infections, primarily among travelers return-

ing from Cuba. In July 2022, a DENV-3 outbreak was

reported in Cuba (8); DENV-3 case increases were

also documented in other countries in the Americas

(9,10). On July 18, Miami-Dade County health of-

cials issued a mosquito-borne illness advisory after

the rst locally acquired DENV infection in 2022 was

conrmed in a Florida resident (11). We document

the DENV-3 outbreak in Florida by describing the

epidemiologic features of reported cases, analyzing

DENV-3 genomic sequences, and reconstructing pos-

sible transmission trees.

The Study

FDOH routinely conducts active case-nding activi-

ties for DENV and conducts IgM and reverse tran-

scription PCR testing for conrmation and DENV

serotype identication. Suspected case-patients are

interviewed to identify risk factors, possible mos-

quito exposure locations, and additional suspected

cases (3). Ethics approval was not required because

this work was part of standard public health outbreak

surveillance and response.

During May 1, 2022–April 30, 2023 (52 weeks),

1,037 DENV infections were reported, 966 (93%)

were travel-associated and 71 (7%) locally acquired.

DENV-3 was the most frequently identied serotype

Introduction and Spread of

Dengue Virus 3, Florida, USA,

May 2022–April 2023

Forrest K. Jones,

Andrea M. Morrison,

Gilberto A. Santiago, Kristyna Rysava, Rebecca A. Zimler,

Lea A. Heberlein, Edgar Kopp, Florida Department of Health Bureau of Public Health Laboratory Team,

Katharine E. Saunders, Samantha Baudin, Edhelene Rico, Álvaro Mejía-Echeverri, Emma Taylor-Salmon,

Verity Hill, Mallery I. Breban, Chantal B.F. Vogels, Nathan D. Grubaugh, Lauren M. Paul, Scott F. Michael,

Michael A. Johansson, Laura E. Adams, Jorge Munoz-Jordan, Gabriela Paz-Bailey, Danielle R. Stanek

376 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 30, No. 2, February 2024

DISPATCHES

Author aliations: Centers for Disease Control and Prevention,

San Juan, Puerto Rico, USA (F.K. Jones, G.A. Santiago,

M.A. Johansson, L.E. Adams, J. Munoz-Jordan, G. Paz-Bailey,

K. Rysava); Centers for Disease Control and Prevention, Atlanta,

Georgia, USA (F.K. Jones, K.E. Saunders); Florida Department

of Health, Tallahassee, Florida, USA (A.M. Morrison, R.A. Zimler,

L.A. Heberlein, E. Kopp,

K.E. Saunders, S. Baudin, E. Rico,

Á. Mejía-Echeverri, D.R. Stanek); Yale School of Medicine,

New Haven, Connecticut, USA (E. Taylor-Salmon); Yale School of

Public Health, New Haven (E. Taylor-Salmon, V. Hill, M.I. Breban,

C.B.F. Vogels, N.D. Grubaugh); Florida Gulf Coast University,

Fort Myers, Florida, USA (L.M. Paul, S.F. Michael)

DOI: https://doi.org/10.3201/eid3002.231615

These authors shared rst authorship.

Team members are listed at the end of this article.

During May 2022–April 2023, dengue virus serotype 3

was identied among 601 travel-associated and 61 lo-

cally acquired dengue cases in Florida, USA. All 203

sequenced genomes belonged to the same genotype

III lineage and revealed potential transmission chains in

which most locally acquired cases occurred shortly after

introduction, with little sustained transmission.

Dengue Virus 3, Florida, USA, May 2022–April 2023

(64%, n = 662), followed by DENV-2 (10%, n = 104),

DENV-1 (7%, n = 68), and DENV-4 (5%, n = 57); in 146

(14%) cases, multiple serotypes or no serotype was

identied (Figure 1, panel A). Among DENV-3 cases,

601 (91%) were travel-associated and 61 (9%) were lo-

cally acquired cases (Figure 1, panel B). Most DENV-3

case-patients identied as White (n = 609; 92%) and

Hispanic or Latino (n = 642, 97%).

Among 601 travel-associated DENV-3 cases,

the median age was 52 (interquartile range 41–61)

years; 51% of patients were male and 49% female.

Most (98%, n = 589) case-patients with travel-associ-

ated DENV-3 had recently traveled from Cuba; they

were reported in 21/67 Florida counties (Figure 1,

panel C). Miami-Dade County had the most travel-

associated DENV-3 cases (71%, n = 428). Among 61

locally acquired DENV-3 cases, the median age was

54 (interquartile range 36–58) years; 67% of patients

were male and 33% female, and nearly all (93%, n =

57) were reported in Miami-Dade County. The 485

DENV-3 case-patients in Miami-Dade County were

identied in 60/82 postal (ZIP) codes.

We performed genomic characterization of

DENV-3 by sequencing the complete genomes of

203 cases at the Centers for Disease Control and Pre-

vention (San Juan, Puerto Rico, USA), Yale School

of Public Health (New Haven, CT, USA), and

FDOH (Appendix 1, https://wwwnc.cdc.gov/EID/

article/30/2/23-1615-App1.pdf) (12). Sequencing

was prioritized and successful for 34 locally acquired

cases, as well as case-patients with recent travel his-

tory to Cuba (n = 168) or Guyana (n = 1). To assess the

representativeness of DENV sequences, we evaluated

symptom onset dates and counties of residence for

cases selected for sequencing and all cases detected

(Appendix 1 Figure 1). We conducted maximum-

likelihood phylogenetic analysis to infer the genetic

relatedness of DENV-3 to contemporary circulation

globally. Global context was provided with a subsam-

ple of 146 publicly available genomes that represent

relevant genotypes.

The DENV-3 genomes identied in Florida are

classied as genotype III and cluster within the novel

American II lineage (9). We observed a close relation-

ship with DENV-3 genomes recently identied in

Arizona, Puerto Rico, and Brazil, indicating that the

lineage is spreading across the Americas (Figure 2).

However, the limited sampling of the new American

II lineage prevented us from inferring a potential time

of emergence in Florida. The short branch lengths and

similarity between locally acquired and travel-associ-

ated cases in the phylogenetic tree demonstrate low

genomic diversity during the sampling period, where

genomes from locally acquired cases cluster random-

ly with travel-associated cases. The tree topology sug-

gests frequent importation events occurred during

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 30, No. 2, February 2024 377

Figure 1. DENV serotype

distribution and DENV-3 case

distribution by week of symptom

onset, county of reporting, and

origin of travel, Florida, USA,

May 1, 2022–April 30, 2023.

A) Number of dengue cases

by each virus serotype. Cases

with an unknown dengue virus

type (asterisk) only had a

positive serologic test or multiple

serotypes identied. B) Epidemic

curve of reported cases of

DENV-3, showing 601 travel-

associated cases and 61 locally

acquired cases. C) Heat map

indicating number of DENV-3

cases by county and by travel

history. Other countries were

Bangladesh, Colombia, Guyana,

India, Jamaica, Mexico, Pakistan,

and Sri Lanka. The names of

counties reporting >3 DENV-3

cases are shown and sorted

by the total number of cases

reported. DENV, dengue virus;

DENV-3, DENV serotype 3.

DISPATCHES

the sampling period and indicate frequent movement

of DENV between Cuba and Florida without estab-

lishing sustained local transmission in Florida.

To model a possible transmission tree, we adapted

a graph-based model using genomic sequences and

symptom onset dates from 31 locally acquired and

144 travel-associated cases (Appendix 1) (13,14). To ac-

count for infections in transmission chains that went

undetected between reported cases, we included a sur-

veillance reporting probability (i.e., the probability an

infection was detected as a case) and performed sensi-

tivity analyses assuming different reporting probabili-

ties of 1%, 5%, 10%, and 15%. Assuming a 5% reporting

probability, we identied 22 travel-associated cases

(15%) with most compatible linkages leading to the 31

locally acquired cases (Appendix 1 Figure 2). Overall,

122 (85%) travel-associated cases had no likely link-

age to locally acquired cases, 17 (11%) were linked to 1

case, 2 (1%) were linked to 2 cases, 2 (1%) were linked

to 3 cases, and 1 (1%) was linked to 4 cases.

Conclusions

We documented an unprecedented number of travel-

associated and locally acquired DENV-3 cases in

Florida during May 2022–April 2023; circulation of

the DENV-3 genotype III was recently identied in

the Americas. Our investigation illustrates that local

transmission and spread in Florida was limited, de-

spite multiple introductions from outside the coun-

try. Sequencing and phylogenetic analysis revealed

that cases were from the same DENV-3 genotype III

lineage and were highly related to one another and to

cases identied in Puerto Rico, Arizona, and Brazil.

Assessment of possible linkages between sequenced

cases indicated that local transmission during this

outbreak was limited; most travel-associated cases

did not lead to further transmission.

DENV activity in Cuba and Florida are linked

given their proximity and the extensive travel be-

tween them. Our results are similar to ndings in

Florida in 2019 (5), where many DENV case-patients

reported recent travel to Cuba, leading to an in-

crease in locally acquired cases. An elevated number

of locally acquired DENV cases in Florida might be

expected after a high number of introductions, but

our analysis suggests that DENV introductions did

not result in sustained local transmission beyond

small-scale outbreaks. Factors potentially reducing

transmission include living conditions (e.g., use of

air conditioning and screens), rapid case notica-

tion that enabled vector interventions (e.g., spray-

ing insecticide, conducting surveillance, community

education, and removing standing water), or limited

availability of mosquito breeding sites (15).

The relatively low genetic diversity in this da-

taset limited our ability to estimate the timing of ini-

tial DENV-3 introductions and fully reconstruct local

spread. We did not use case locations to determine the

compatibility of transmission links. DENV case detec-

tion continued through 2023 in Florida; efforts to un-

derstand those transmission dynamics are ongoing.

In summary, we used epidemiologic surveil-

lance and genomic sequencing to identify a newly

emerging lineage of DENV-3 genotype III that

caused an unusually large number of travel-as-

sociated and locally acquired DENV infections in

378 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 30, No. 2, February 2024

Figure 2. Evolutionary analysis of dengue virus serotype 3 sampled in Florida, USA, May 1, 2022–April 30, 2023. Maximum-likelihood

phylogenetic tree was generated from a subset of 203 complete genomes from Florida (34 local cases, 168 cases in persons with recent

travel history to Cuba, and 1 traveler case from Guyana) and 146 complete genomes publicly available (1985–2022) from GenBank

representing genotype III, American lineage II. A subset of the sequences was used because of the low diversity in the population

sample, which was limiting the phylogenetic signal and hampering the statistical analyses that supported the tree accuracy and certainty

in major nodes. Sampling locations are coded by shape and color. Scale bar represents nucleotide substitutions per site.

Dengue Virus 3, Florida, USA, May 2022–April 2023

Florida, particularly in Miami-Dade County. Our

analysis suggests that locally acquired cases were

driven by large numbers of case-patients with recent

travel to Cuba and that DENV persistence in Florida

was limited. Close monitoring of DENV activity in-

ternationally, as well as increasing healthcare pro-

vider awareness about DENV identication and test-

ing, can strengthen preparedness and response to

future introductions in non–DENV-endemic areas.

Florida Department of Health Bureau of Public Health

Laboratory Team: Sylvia Bunch, Natalia Cano, Amanda

Davis, Yibo Dong, Rayah Jaber, Timothy Locksmith,

Charles Panzera, Brittany Rowlette, Sarah Schmedes,

Julieta Vergara.

Acknowledgments

We thank Joshua Wong for help with initial discussions

on analysis plans. We also gratefully acknowledge the

Arizona Department of Health Services and the Maricopa

County Department of Public Health for contributing

specimens for the phylogenetic analysis.

Code presented in this study is available at

https://github.com/fjones2222/denv-3-orida-2022/.

Research reported in this publication was supported by

the National Institute of Allergy and Infectious Diseases

of the National Institutes of Health under award number

DP2AI176740 (NDG), and by CTSA Grant Number UL1

TR001863 from the National Center for Advancing

Translational Science (NCATS), a component of the

National Institutes of Health (CBFV), and by the

National Institute of General Medical Sciences of the

National Institutes of Health under award number

R21GM142011 (SFM).

About the Author

Dr. Jones is an Epidemic Intelligence Service ofcer

stationed at the Centers for Disease Control and

Prevention Dengue Branch (Division of Vector-Borne

Diseases, National Center for Emerging and Zoonotic

Infectious Diseases) in San Juan, Puerto Rico.

His research interest is surveillance and modeling

of infectious diseases.

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Address for correspondence: Forrest Kirby Jones, Centers for

Disease Control and Prevention, 1324 Calle Cañada, San Juan,

00920, Puerto Rico, USA; email: [email protected]

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 30, No. 2, February 2024 379