The reemergence of dengue virus serotype 3 (DENV-3) in Brazil after 17 years could help worsen fresh outbreaks of the disease there since the population is not immunized against this serotype, and serotypes 1 and 2 (DENV-1 and DENV-2) continue to circulate.
The warning features in an article written by researchers at the São José do Rio Preto Medical School (FAMERP) in São Paulo state, and published in the Journal of Clinical Virology.
"The last significant DENV-3 epidemic in Brazil, and more specifically in São José do Rio Preto, occurred more than 15 years ago [in 2007]. DENV-1 and DENV-2 are continuously circulating in Brazil. If DENV-3 establishes itself again and the situation persists [with these serotypes co-circulating], severe forms of dengue epidemic could result. This is precisely the situation we're experiencing right now in São José do Rio Preto," Maurício Lacerda Nogueira , a professor at FAMERP and last author of the article, told Agência FAPESP.
For 20 years, Nogueira and colleagues have conducted a Thematic Project that is supported by FAPESP and includes genomic and epidemiological surveillance of dengue and other diseases caused by insect-born viruses (arboviruses) in São José do Rio Preto, where dengue has been endemic for several decades, with a succession of outbreaks caused by different serotypes.
"The annual average temperature in São José do Rio Preto is about 25 °C , and rainfall averages about 2,000 millimeters per year. This warm wet weather creates ideal conditions for the mosquitos that transmit arboviruses to breed and makes the city a suitable place for genomic and epidemiological monitoring of arboviruses, including dengue. We've been doing this for a long time, so we're able to make reliable epidemiological inferences," Lacerda said.
The researchers have documented a rise in cases of the disease caused by DENV-3 in the city since late 2023 via active surveillance of arboviruses in patients with dengue-like symptoms treated at Hospital de Base and UPAs (public clinics specializing in medium-complexity cases).
Thirty-one blood samples collected between November 2023 and November 2024 tested positive for DENV-3. The most common symptoms were muscle pain, headache, and fever.
"In 2023-24, we had a dengue epidemic in São José do Rio Preto, caused mainly by DENV-1 and -2. In mid-2024, DENV-1 almost disappeared, and DENV-2 became the main agent. The number of DENV-3 cases then began to rise, and it's now the main agent in the city," Lacerda said.
Studies conducted by other groups show that the last outbreak of dengue in Brazil, in 2021, was caused by DENV-1, and that sequential infection by DENV-3 is associated with increased severity during epidemics.
"However, we didn't observe increased severity in the patients who participated in our study," Lacerda said.
Need for active surveillance
The researchers also sequenced the genomes and analyzed the phylogenies of the viral isolates collected from the blood samples donated by patients with acute fever. The results of the analysis showed that the DENV-3 strain in question belonged to the same lineage as the one identified in Florida (USA) and the Caribbean, and differed from the strains of DENV-3 that circulated in Brazil in the 2000s.
These findings suggest that the outbreak of DENV-3 in Florida and the Caribbean in 2022-24 probably contributed to the introduction of the virus to Brazil and its spread throughout the country, according to the researchers.
"This demonstrates the extent to which molecular and genomic surveillance of circulating DENV strains is crucial to public health preparedness efforts and the response to the surge in cases of the disease," Lacerda said.
Dengue transmission is widespread across tropical and subtropical regions worldwide. However, at-risk areas have expanded in past decades, owing mainly to climate change and an increased range of Aedes aegypti, the mosquito that transmits the virus, the article notes.
Brazil is the most affected country in the Americas and has long been hyperendemic for all dengue virus serotypes. In recent years, DENV-1 and -2 have been the most common serotypes in circulation. Although DENV-3 was detected during the period discussed in the article, the number of cases was very small. In fact, fewer than 100 cases were reported nationwide between 2010 and 2022. However, the number of cases reported increased in 2023, reaching 106, and jumped to 1,008 in 2024.
"We've been studying dengue in Brazil since 2010, and the epidemiological pattern is similar to that observed for SARS-CoV-2 during the COVID-19 pandemic. When a different serotype emerges, it escapes the population's established immunity, and an epidemic occurs shortly afterward. We're seeing this now with DENV-3," Lacerda said.
About FAPESP
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the state of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration.
