Yellow fever mimicking dengue and leptospirosis in Nariño, Colombia, 2024/2025

Yellow fever (YF) remains a reemerging public health concern in South America, with 486 cases and 209 deaths (43%) across seven countries, up to May 27, 2026 [1], with recent outbreaks affecting multiple departments of Colombia [2]. In June 2024/February 2025, a focal outbreak was identified in the municipality of Ipiales, Nariño department, at the Andean–Amazon interface, near the Ecuadorian border, involving rural and indigenous communities exposed to sylvatic transmission cycles (Fig. 1). Notably, although Ipiales is widely recognized as a high-altitude Andean municipality (>2000 m above sea level), the affected area in Sucumbíos lies in a low-altitude Andean–Amazon transitional zone with ecological characteristics more consistent with Amazonian environments, which favor sylvatic transmission and may lead to under-recognition of yellow fever risk. Within this context, we conducted a retrospective review of YF cases in Nariño, highlighting diagnostic challenges and illustrating the clinical spectrum ranging from mild disease to fatal outcomes [3].

Fig. 1.

Yellow fever in Nariño, Colombia, 2024/2025. Origin of both cases.

In June 2024/February 2025, a total of 18 suspected cases were investigated in Nariño, of which 2 were positive (11%). Both positive patients were young males from rural areas of the corregimiento of Sucumbíos (Ipiales municipality) (Brisas del Gavilan and Santa Rosa towns), with occupational and environmental exposure to forested settings (Fig. 1). No YF cases have occurred in other municipalities of the Nariño department during the 2024-2026 outbreak in Colombia. Colombia's 2024-2026 outbreak had cumulated 200 cases and 89 deaths (44.5%) in 11 (out 32) departments, up to June 19, 2026 (www.ins.gov.co). Epidemiological investigations confirmed sylvatic transmission and identified the corregimiento of Sucumbíos as an active focus of YF circulation. Both cases occurred in socioeconomically vulnerable populations, including indigenous communities, consistent with the demographic profile observed in the outbreak.

Case 1 was a 20-year-old male who presented after 7–8 days of febrile illness with headache, persistent vomiting, epigastric abdominal pain, and jaundice (Table 1). Laboratory evaluation showed leukopenia, thrombocytopenia, hyperbilirubinemia, and elevated transaminases. Abdominal ultrasound revealed gallbladder wall edema suggestive of acalculous cholecystitis, a finding typically associated with dengue [4]. The initial clinical impression was dengue with warning signs, and leptospirosis was also considered. Serological tests were positive for dengue IgM (weak/positive) and Leptospira IgM, supporting alternative diagnoses. The patient developed hematemesis and rapidly deteriorated, dying within 24 hours of admission. RT-PCR performed at the national reference laboratory (National Institute of Health, Bogota) confirmed YF infection. RT-PCRs for dengue, chikungunya, and Zika were negative.

Table 1.

Main demographic, clinical, laboratory, and epidemiological features of yellow fever cases in Nariño, Colombia, 2024/2025.

Feature	Case 1 (Fatal)	Case 2 (Survived)
Location of exposure/report	Resguardo Santa Rosa (Cofán), Corregimiento Sucumbíos, Ipiales (Nariño)	Vereda Gavilanes, Corregimiento Sucumbíos, Ipiales (Nariño)
Age (years)	20	18
Sex	Male	Male
Residence	Rural	Rural
Occupation	Agricultural worker	Agricultural worker
Ethnicity	Indigenous (Cofán)	Not specified
Socioeconomic status	Low (public health insurance: subsidized regime)	Low (public health insurance: subsidized regime)
YF vaccination history	Not vaccinated	Not vaccinated
Exposure history	Forest-related activities (sylvatic risk)	Forest-related activities (sylvatic risk)
Days from symptom onset to admission	∼7–8 days	5 days
Initial clinical presentation	Fever, headache, vomiting, epigastric pain, jaundice, arthralgia, myalgia	Fever, headache, retro-orbital pain, vomiting, abdominal pain, arthralgia, myalgia
Key laboratory findings	Leukopenia, thrombocytopenia, hyperbilirubinemia, and elevated transaminases	Leukopenia, thrombocytopenia, elevated transaminases (AST 680 U/L, ALT 878 U/L)
Imaging findings	Gallbladder wall edema (acalculous cholecystitis-like)	Normal abdominal ultrasound
Initial clinical diagnosis	Dengue with warning signs; leptospirosis suspected	Dengue with warning signs
Serology	Dengue IgM weak/positive; Leptospira IgM positive	Not contributory/not reported
YF suspicion	Delayed	Early (sentinel case)
Complications	Hematemesis, rapid deterioration	None (no shock or organ failure)
Clinical course	Fulminant progression, hepatic Failure	Gradual improvement
Outcome	Death (<24 h after admission)	Full recovery
Laboratory confirmation	RT-PCR positive for YFV, RT-PCR negative for DENV, RT-PCR negative for CHIKV, RT-PCR negative for ZIKV	RT-PCR positive for YF
Notable feature	Acalculous cholecystitis-like presentation mimicking dengue	Dengue-like moderate illness with a favorable outcome

YF, yellow fever; YFV, yellow fever virus; RT-PCR, reverse transcription polymerase chain reaction; DENV, dengue virus; CHIKV, chikungunya virus; ZIKV, Zika virus; AST, aspartate aminotransferase; ALT, alanine aminotransferase; IgM, immunoglobulin M; ICU, intensive care unit.

Case 2 was an 18-year-old male farmer who presented on day five of illness with fever, headache, retro-orbital pain, vomiting, and abdominal pain (Table 1). Laboratory findings included leukopenia, thrombocytopenia, and elevated transaminases (AST 680 U/L, ALT 878 U/L), without evidence of jaundice, coagulopathy, or renal dysfunction. Abdominal ultrasound was normal. He was initially diagnosed with dengue with warning signs; however, given epidemiological risk factors, YF was suspected early, and surveillance protocols were activated. The patient received supportive treatment with intravenous fluids and symptomatic management, resulting in progressive clinical improvement and full recovery. RT-PCR performed at the national reference laboratory (National Institute of Health, Bogota) confirmed YF infection.

These two cases illustrate several clinically relevant points. First, YF may closely mimic dengue across its clinical spectrum, from moderate illness to fatal disease [5]. Both patients presented with classical dengue-like features, including fever, thrombocytopenia, leukopenia, abdominal pain, and vomiting. In Case 1, hepatobiliary imaging findings further supported a dengue diagnosis, suggesting that acalculous cholecystitis-like presentations may occur in YF and contribute to misdiagnosis. To our knowledge, acalculous cholecystitis has not been previously reported as a manifestation of yellow fever in the available literature, as occurred in patients with abdominal manifestations of dengue [4].

Second, serological cross-reactivity and concurrent positive results for other endemic infections may obscure the diagnosis [5]. In Case 1, positive dengue and Leptospira IgM results likely delayed suspicion of YF, underscoring the limitations of serological assays in endemic settings and the need for molecular confirmation.

Third, these cases demonstrate marked variability in clinical progression. While Case 2 had a favorable outcome with supportive care, Case 1 progressed rapidly to fatal hemorrhagic disease despite only moderate abnormalities at initial evaluation. This highlights the potential for abrupt deterioration in YF before the full classical laboratory profile is established.

Finally, these cases emphasize the importance of integrating clinical findings with epidemiological context and rapid public health response [2,3,5]. Both occurred within a defined outbreak focus in southern Colombia, where field investigations confirmed ongoing sylvatic transmission and the presence of competent vectors, including Aedes albopictus and Sabethes spp (Fig. 1). In response to these cases, coordinated interventions were implemented by local and national health authorities, including targeted vaccination campaigns, with at least 130 YF vaccine doses administered during field activities and additional prior immunization efforts in the affected communities. Active case finding through community-based surveillance (Búsqueda Activa Comunitaria, BAC) involved the systematic evaluation of households and individuals in the affected areas, with no further cases identified. Additional measures included strengthening of local surveillance networks, training of healthcare personnel, and community education on early symptom recognition and prevention. Vector control strategies were also implemented, including larval surveys, breeding-site interventions, entomological monitoring, and the installation of insecticide-treated mosquito nets in high-risk communities. These coordinated actions highlight the importance of rapid, integrated outbreak response to contain transmission and prevent further cases in rural and indigenous populations [2].

In endemic and outbreak settings, YF should be considered in any patient with acute febrile illness and gastrointestinal or hepatic involvement, even when clinical, laboratory, or imaging findings suggest dengue or leptospirosis, especially during ongoing YF epidemics in South American countries [3,5]. Early suspicion, prompt laboratory confirmation, and appropriate supportive care are critical to improving outcomes.

In conclusion, these two RT-PCR–confirmed cases from Nariño illustrate the diagnostic challenges and broad clinical spectrum of YF in Colombia, reinforcing its ability to mimic other endemic infections and the importance of early recognition in outbreak contexts. These findings underscore the critical role of integrated clinical, laboratory, and public health approaches in the early detection and control of yellow fever outbreaks in endemic regions.

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Ethics approval

We confirm that the manuscript has been read and approved by all named authors and that no other persons have satisfied the criteria for authorship but are not listed. We further confirm that all have approved the order of authors listed in the manuscript. The material is original and has not been previously published elsewhere. As the data were retrospective, additional ethical approval was not required.

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Data is available upon reasonable request.

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Declaration of generative AI and AI-assisted technologies in the manuscript

We confirmed that no generative artificial intelligence (AI) or AI-assisted technologies were used in the writing process.

Funding

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CRediT authorship contribution statement

Ivan Camilo Sanchez-Rojas: Data curation, Investigation, Supervision, Writing – original draft, Writing – review & editing. Catherin Lorena Solarte-Jimenez: Investigation, Resources, Validation, Writing – original draft, Writing – review & editing. Nery Astrid Pabón-Cadena: Methodology, Validation, Writing – original draft, Writing – review & editing. Andres Rodriguez-Cardona: Investigation, Supervision, Writing – original draft, Writing – review & editing. Derlis Caicedo-Triana: Resources, Visualization, Writing – original draft, Writing – review & editing. Lina Cristina Bravo-Muñoz: Investigation, Supervision, Visualization, Writing – original draft, Writing – review & editing. Darío S. López-Delgado: Investigation, Software, Supervision, Writing – original draft, Writing – review & editing. Marco A. Solarte-Portilla: Data curation, Investigation, Writing – original draft, Writing – review & editing. Jorge Luis Bonilla-Aldana: Formal analysis, Software, Validation, Writing – original draft, Writing – review & editing. D. Katterine Bonilla-Aldana: Conceptualization, Formal analysis, Software, Writing – original draft, Writing – review & editing. Alfonso J. Rodriguez-Morales: Conceptualization, Formal analysis, Methodology, Software, Supervision, Visualization, Writing – original draft, Writing – review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Abbreviations

ALT

alanine aminotransferase

AST

aspartate aminotransferase

BAC

Búsqueda Activa Comunitaria (active community case finding)

CHIKV

chikungunya virus

DENV

dengue virus

IgM

immunoglobulin M

RT-PCR

reverse transcription polymerase chain reaction

YF

yellow fever

YFV

yellow fever virus

ZIKV

Zika virus