Ischemic stroke during dengue–Plasmodium vivax coinfection in a young woman: a case report

Abstract

Background

Malaria and dengue are tropical endemic infections that can cause severe vascular and neurologic complications. Coinfection with Plasmodium vivax and dengue virus is uncommon but increasingly reported in co-endemic areas, complicating diagnosis and suggesting possible pathogenic synergy. Although each pathogen has been linked to stroke, cerebrovascular events during coinfection are exceptionally rare.

Case presentation

We describe a 23-year-old Colombian woman, who recently returned from Chocó, and developed acute right-leg monoparesis after 7 days of fever. Exam: hypotension and jaundice. Labs confirmed P. vivax malaria (8200 parasites/μL) and acute dengue (NS1 antigen positive; IgM-positive/IgG-negative). MRI revealed an acute left ACA infarct. There are no traditional stroke risk factors. She received artesunate–primaquine, supportive dengue care, and aspirin after her thrombocytopenia resolved; her neurologic function improved with rehabilitation.

Conclusions

This case highlights the potential of P. vivax-dengue coinfection to cause ischemic stroke through synergistic endothelial injury. Early recognition, targeted treatment, and coinfection screening are essential in endemic areas, especially during vector expansion.

Highlights

• Ischemic stroke during dengue–Plasmodium vivax coinfection; exceptionally rare.   

• MRI revealed left ACA infarct with acute right-leg monoplegia.

• Endothelial–immunothrombotic synergy suspected as stroke mechanism.

• Artesunate–primaquine, dengue support, and aspirin lead to recovery.

• Recommend screening for coinfection in febrile patients with focal deficits.

    

Background

Malaria and dengue are endemic infectious diseases in tropical and subtropical regions, transmitted by mosquitoes of the Anopheles and Aedes aegypti genera, respectively. Both of these conditions represent major public health threats due to their high disease burden and potential to cause severe complications. While their clinical presentations are usually distinct in uncomplicated infections, severe disease—and especially coinfection—can produce substantial clinical overlap and multiorgan dysfunction, with prominent vascular and neurological involvement.

Coinfection with Plasmodium vivax and dengue virus has been sporadically reported in areas where both vectors coexist, particularly in Southeast Asia and South America [1, 2]. This condition poses a diagnostic and therapeutic challenge due to overlapping clinical symptoms and potential pathogenic synergy, which may increase the risk of rare adverse events such as ischemic stroke [3, 4].

Although isolated reports have documented stroke associated with either dengue or malaria individually [5, 6], its occurrence in the context of coinfection is exceedingly rare. The low incidence may be explained by the distinct geographical distribution of the vectors, limiting co-occurrence of the diseases. However, the recent dengue epidemics across the Americas—reaching record numbers in 2023 and 2024—have increased the likelihood of unusual clinical encounters, including coinfection and its severe vascular complications [7].

Herein, we report the case of a young woman who developed an acute ischemic stroke associated with dengue and Plasmodium vivax coinfection.

Case presentation

A 23-year-old woman with no relevant medical history, residing in Cali, Colombia, presented with a 7-day history of intermittent fever, malaise, myalgia, and arthralgia. She had returned five weeks earlier from the Chocó region, an endemic area for vector-borne diseases. Twenty-four hours before hospital admission, she experienced sudden onset monoparesis of the right lower limb.

Upon admission, she was febrile (38.5 °C), hypotensive (BP 82/48 mmHg; MAP 59 mmHg), with a heart rate of 98 bpm, respiratory rate of 19 bpm, and oxygen saturation of 93%. Physical examination revealed conjunctival jaundice and monoplegia of the right lower limb, with signs consistent with upper motor neuron involvement.

Initial laboratory tests showed lymphopenia, anemia, severe thrombocytopenia, hyperbilirubinemia, and elevated liver transaminases (Table 1). Thick blood smear was positive for Plasmodium vivax with a parasitemia of 8,200 parasites/μL. Dengue infection was confirmed using a combined rapid diagnostic test detecting NS1 antigen and total IgM/IgG antibodies, which showed NS1 antigen positivity with an IgM-positive and IgG-negative serologic profile, consistent with an acute dengue infection. Other coinfections, as well as metabolic, hematological, and immunological causes of stroke, were ruled out (Table 1).

Table 1.

Admission laboratory results

Variable (Unit)	Result	Reference range
Complete blood count
Leukocytes (mm3)	3,55	5,000–11,000
Neutrophils (mm3)	2,76	1,800–7,200
Lymphocytes (mm3)	520	1,500–4,000
Monocytes (mm3)	240	200–1,000
Eosinophils (mm3)	30	50–500
Basophils (mm3)	< 10	0–200
Hemoglobin (g/dL)	7.8	12.0–16.0 (female)
Hematocrit (%)	24.5	36–48 (female)
MCV (fL)	84.2	80–100
MCH (pg)	28.5	27–33
MCHC (g/dL)	33.8	32–36
Platelets (mm3)	34	150,000–450,000
Transferrin saturation (%)	15	15–50
Ferritin (ng/mL)	150	10–120
Haptoglobin (mg/dL)	15	30–200
Sickling test	Negative	No sickled cells
LDH (U/L)	331	120–250
Liver function tests
AST (U/L)	43.9	0–35
ALT (U/L)	41.4	0–35
Alkaline phosphatase (U/L)	153	44–147
Total bilirubin (mg/dL)	4.44	0.2–1.0
Direct bilirubin (mg/dL)	3.18	0.0–0.2
Indirect bilirubin (mg/dL)	1.26	0.2–0.8
Infectious serology
HIV antibodies	Nonreactive	Negative
HBsAg	Nonreactive	Negative
Anti-HCV	Nonreactive	Negative
HTLV I/II	Nonreactive	Negative
IgM Leptospira	Nonreactive	Negative
IgM/IgG Rickettsia sp.	Nonreactive	Negative
Syphilis (treponemal)	Nonreactive	Negative
Autoimmunity and thrombosis
ANA	Negative	< 1:80
ENA panel	Negative	Negative
ANCA	Negative	Negative
Complement C3 (mg/dL)	85	90–180
Complement C4 (mg/dL)	12	10–40
Lupus anticoagulant	Negative	Negative
Homocysteine (µmol/L)	10.2	< 15
Cardiometabolic profile
HbA1c (%)	5.71	< 5.7%
Fasting glucose (mg/dL)	92	70–99
Total cholesterol (mg/dL)	160	< 200
LDL cholesterol (mg/dL)	90	< 100
HDL cholesterol (mg/dL)	55	> 50
Triglycerides (mg/dL)	85	< 150
Transthoracic echocardiogram	Normal	Preserved function, no structural abnormalities

Brain MRI revealed an acute ischemic infarct in the territory of the left anterior cerebral artery (ACA) (Fig. 1), with no evidence of spinal cord involvement. In the absence of vascular risk factors or structural abnormalities, the cerebrovascular event was attributed to complications arising from dengue and P. vivax coinfection.

Fig. 1.

Multimodal MRI showing acute ischemic lesions in the anterior cerebral artery territory in a patient with Plasmodium vivax and dengue coinfection. A Diffusion-Weighted Imaging (DWI): Multiple punctate hyperintense lesions (arrows) indicating restricted water diffusion, consistent with acute ischemic infarcts. B Apparent Diffusion Coefficient (ADC) maps: Corresponding areas of hypointensity confirm true diffusion restriction and acute nature of the lesions. C Fluid-Attenuated Inversion Recovery (FLAIR): Subtle cortical and subcortical hyperintensities in the same regions, indicating cytotoxic edema associated with infarction

She was treated with intravenous artesunate for 3 days, followed by oral primaquine (15 mg/day for 14 days) after excluding G6PD deficiency. Supportive care included guided fluid resuscitation and platelet monitoring. Dengue management included close hepatic and hematological monitoring. Once platelet count exceeded 100,000/μL, aspirin 100 mg/day was initiated as secondary stroke prevention. The patient underwent intensive physical rehabilitation and achieved progressive neurological recovery, confirmed by follow-up imaging at 4 weeks.

Discussion

We report the case of a 23-year-old woman with coinfection by Plasmodium vivax and dengue virus who developed an acute ischemic stroke in the left anterior cerebral artery territory, presenting with focal motor deficit and severe systemic involvement. The rarity of this neurological complication, particularly in the context of viral coinfection, raises the possibility of an unrecognized pathogenic synergy.

To date, only three cases of ischemic stroke associated with P. vivax have been reported internationally, involving patients aged 16 to 52 years [6, 8, 9].

Although our patient falls within this age range, her clinical course was more atypical and aggressive, progressing from intermittent fever to shock, jaundice, and monoplegia within just seven days. This multisystemic evolution contrasts with prior cases, where fever was the predominant and often sole initial symptom, suggesting a more severe pathophysiological behavior in the setting of coinfection.

Neurologically, our patient exhibited right-sided monoplegia, differing from the hemiparesis or diplopia reported in earlier cases. MRI revealed multifocal ischemia, including severe stenosis of middle cerebral artery branches, unilateral frontal infarction, and multiple ischemic lesions in the left basal ganglia, with predominant involvement of the left ACA territory. Treatment with intravenous artesunate followed by primaquine, along with hemodynamic support and intensive rehabilitation, led to complete neurological recovery within four weeks—longer than previously reported durations (5–15 days) but with a favorable outcome.

Dengue virus has been significantly associated with both hemorrhagic and ischemic stroke, with a relative risk increase of 4.13 and 3.80 times, respectively [5]. This relationship is mediated by viral binding to platelet receptors such as DC-SIGN, CLEC-2, and FcγRII, triggering the release of proinflammatory mediators (IL-1β, CXCL8, CCL5, CXCL4) [10–12]. The resulting immune activation induces endothelial dysfunction, blood–brain barrier disruption, increased vascular permeability, and a prothrombotic state conducive to microvascular thrombosis and ischemic infarcts [13, 14].

Although historically considered less virulent than P. falciparum, P. vivax can also cause endothelial damage and vascular events. Its glycosylphosphatidylinositol (GPI) and histamine activate endothelial TLR-2 and TLR-4 receptors, stimulating the release of Weibel–Palade bodies (WPBs) containing Ang-2, ICAM-1, and E-selectin, which promote leukocyte adhesion and microthrombosis [8, 9]. In addition, reduced ADAMTS13 activity increases circulating levels of large von Willebrand factor (vWF) multimers, further enhancing thrombotic risk [13, 14]. In this context, coinfection with dengue and P. vivax may exert synergistic effects, intensifying endothelial dysfunction, cytokine storm, and microthrombosis—potentially explaining the unusual clinical presentation observed in our patient (Fig. 2). The interaction between both pathogens amplifies oxidative stress, capillary leak, and hypercoagulability, favoring rapidly progressive cerebral ischemia.

Fig. 2.

Proposed integrative pathophysiological model of ischemic stroke in Plasmodium vivax and dengue virus coinfection. Synergistic effects include glycocalyx degradation, immune-mediated endothelial activation, release of Weibel–Palade bodies, and formation of cerebral microthrombi leading to acute ischemia

In Colombia, where dengue, Zika, and chikungunya co-circulate, laboratory confirmation of dengue can be challenging because of serologic cross-reactivity. Current recommendations favor NS1 antigen detection or molecular testing during the acute phase, as isolated IgM positivity may yield false-positive results in up to 30% of cases in co-endemic settings [15]. In this patient, dengue infection was confirmed by a combined rapid test showing NS1 antigen positivity with an IgM-positive and IgG-negative profile, supporting an acute dengue infection.

This case underscores the importance of maintaining a high index of suspicion in young patients with recent exposure to multiple endemic regions. Our patient had traveled from a malaria-endemic area to a city experiencing an active dengue outbreak, facilitating the coinfection. It also highlights the need for strict neurological and hemodynamic monitoring in rapidly progressing symptoms and timely initiation of antiparasitic therapy. Furthermore, it encourages exploration of adjunctive therapies aimed at preserving endothelial integrity.

Finally, this case illustrates how global ecological changes and the increasing circulation of arboviruses and blood-borne parasites can lead to novel coinfection scenarios, whose pathogenic interactions remain poorly understood [1].

Conclusions

Coinfection with Plasmodium vivax and dengue virus, although rare, should be recognized as a potential cause of severe neurological complications in endemic regions. This case illustrates how synergistic interactions between both pathogens may intensify endothelial dysfunction—via glycocalyx degradation, immune overactivation, and cerebral microthrombosis—leading to ischemic stroke even in young, healthy individuals. These findings highlight the need for systematic coinfection screening in febrile patients with neurological or hemodynamic compromise, early targeted therapy, and consideration of endothelial-protective strategies, especially amid expanding vector distribution and ecological change.

List of Abbreviations

ACA

Anterior Cerebral Artery

ADAMTS13

A Disintegrin and Metalloprotease with Thrombospondin Type 1 Motif, Member 13

ALT

Alanine Aminotransferase

ANA

Antinuclear Antibody

ANCA

Antineutrophil Cytoplasmic Antibody

AST

Aspartate Aminotransferase

BP

Blood Pressure

CBC

Complete Blood Count

CLEC-2

C-type Lectin-like Receptor 2

CXCL

C-X-C Motif Chemokine Ligand

DC-SIGN

Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin

ECG

Electrocardiogram

ENA

Extractable Nuclear Antigen

FiO₂

Fraction of Inspired Oxygen

G6PD

Glucose-6-Phosphate Dehydrogenase

HbA1c

Glycated Hemoglobin

HDL

High-Density Lipoprotein

HIV

Human Immunodeficiency Virus

HTLV

Human T-lymphotropic Virus

ICAM-1

Intercellular Adhesion Molecule 1

IL

Interleukin

LDH

Lactate Dehydrogenase

LDL

Low-Density Lipoprotein

MAP

Mean Arterial Pressure

MCV

Mean Corpuscular Volume

MCH

Mean Corpuscular Hemoglobin

MCHC

Mean Corpuscular Hemoglobin Concentration

MRI

Magnetic Resonance Imaging

NS1

Nonstructural Protein 1 (of Dengue virus)

P. vivax

Plasmodium vivax

PEEP

Positive End-Expiratory Pressure

PIP

Peak Inspiratory Pressure

TLR

Toll-Like Receptor

vWF

Von Willebrand Factor

WPB

Weibel–Palade Body

XDR

Extensively Drug-Resistant

Author contributions

Conceptualization: HAN, JMC; Methodology: HAN, JSS, JMC, JIC, AG, EOP; Software: HAN, JSS, JMC, JIC, EOP; Validation: JIC; Investigation: HAN, JSS, JMC, JIC, AG, EOP; Resources: HAN, JSS, JMC; Data curation: JIC, EOP; Writing—original draft: HAN, JSS, JMC, AG; Writing—review and editing: JIC, EOP; Visualization: HAN, JIC; Supervision: JIC; Project administration: JIC; Funding acquisition: JIC. All authors have read and approved the final version of the manuscript.

Funding

None declared.

Data availability

All data generated or analyzed during this study are included in this published article. Additional information or anonymized data supporting the findings is available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

This case report was reviewed and approved by the Ethics Committee of Clínica DESA (Cali, Colombia). All procedures were conducted in accordance with institutional ethical standards and the principles of the Declaration of Helsinki. Written informed consent for participation, data collection, and use of clinical information was obtained from the patient prior to publication.

Consent for publication

Written informed consent for publication of clinical data and imaging was obtained from the patient. The report contains no identifiable personal information.

Competing interests

The authors declare no competing interests.