---
title: "Fatal Coinfection: Dengue Virus and Avian Orthoavulavirus 1 Detected in Traveler from Saudi Arabia"
id: "cdc-emerging-infectious-diseases-journal-1-fatal-infection-with-dengue-virus-and-avian-orthoavulavirus-1-in-traveler"
canonical_url: "https://medichelpline.com/clinical-feed/cdc-emerging-infectious-diseases-journal-1-fatal-infection-with-dengue-virus-and-avian-orthoavulavirus-1-in-traveler"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "CDC Emerging Infectious Diseases Journal"
source_url: "https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article"
published_at: "2026-09-11T04:00:00.000Z"
evidence_level: "Agency Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Fatal Coinfection: Dengue Virus and Avian Orthoavulavirus 1 Detected in Traveler from Saudi Arabia
## Provenance & Clinical Metadata
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- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** CDC Emerging Infectious Diseases Journal
- **Source URL:** [Original Journal Publication](https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article)
- **Published At:** 2026-09-11T04:00:00.000Z
- **Evidence Rating:** Agency Feed
## Executive GIST (TL;DR)
- A previously healthy 26-year-old man returned from Mecca, Saudi Arabia, and within 4 days developed fever, myalgia, headache, abdominal pain, and diarrhea; he sought care in Paris and was admitted to ICU with fever, hypotension, oliguria, conjunctival hemorrhage, and hematuria. - Despite fluid resuscitation and broad antimicrobial therapy, the patient progressed rapidly to multiple organ dysfunction, fulminant hepatitis, disseminated intravascular coagulation, acute kidney failure, refractory shock, and death 36 hours after hospital admission. - Routine PCR and serology for many pathogens (malaria, SARS-CoV-2, influenza, cytomegalovirus, Ebola, Zika, chikungunya; HIV; hepatitis A, B, C, E) were negative on premortem samples; initial blood tests for dengue virus were also negative by PCR and serology. - Postmortem testing detected low-level **dengue virus** RNA in urine (pan-dengue Ct 39; DENV-1–specific Ct 40) with robust fluorescence curves, and serum tested positive for **NS1 antigen** (positivity ratio 2.5), supporting recent DENV infection. - Metagenomic next-generation sequencing (mNGS) on plasma and liver biopsy unexpectedly revealed extremely high levels of **avian orthoavulavirus 1 (AOAV-1)** reads (191,718 and 244,781 reads per million, respectively); complete AOAV-1 coding sequences were obtained. - AOAV-1 was confirmed by specific real-time PCR with low Ct values in liver (Ct 17.23), plasma (Ct 15.74), urine (Ct 18.23), sputum (Ct 18.5), and cerebrospinal fluid (Ct 35.9), indicating disseminated infection. - Phylogenetic analysis classified the isolate as AOAV-1 clade II, genotype VI, subgenotype VI.2.1.2 — a pigeon-adapted lineage historically termed pigeon paramyxovirus type 1 — with a velogenic fusion protein cleavage site motif (RRRKRF), consistent with systemic tissue tropism. - Plasma cytokine profiling demonstrated extremely high levels of type I interferons (IFN-α and IFN-β >10^4 pg/mL) and markedly elevated IFN-γ, CXCL10, CXCL11, IL-6, and TNF-α, indicative of a hyperinflammatory response. - Authors could not definitively ascribe the fatal syndrome to one virus; however, the very high AOAV-1 loads across tissues and fluids suggest a major pathogenic role for **AOAV-1** in this disseminated, fatal infection. - The case highlights an unexpected human infection with a velogenic avian virus and concurrent evidence of **dengue** infection, emphasizing the value of mNGS for pathogen discovery in severe acute illness and the difficulty of attributing causality in coinfections.
## Clinical Analysis & Structured Key Points
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[EID Journal](https://wwwnc.cdc.gov/eid/) 2. [Volume 32](https://wwwnc.cdc.gov/eid/early-release) 3. [Early Release](https://wwwnc.cdc.gov/eid/early-release#issue-1346) 4. [Main Article](https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article) * [Facebook](https://www.facebook.com/sharer/sharer.php?u=%2Feid%2Farticle%2F32%2F10%2F26-0736_article "Share to Facebook") * [Twitter](http://twitter.com/share?url=%2Feid%2Farticle%2F32%2F10%2F26-0736_article&text= "Share to Twitter") * [LinkedIn](https://www.linkedin.com/shareArticle?url=%2Feid%2Farticle%2F32%2F10%2F26-0736_article&title= "Share to LinkedIn") * [Syndicate](https://tools.cdc.gov/medialibrary/index.aspx#/sharecontent//eid/article/32/10/26-0736_article "Embed this Page") [ Emerging Infectious Disease journal ISSN: 1080-6059 ](https://wwwnc.cdc.gov/eid/) _Disclaimer: Early release articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released._ #### Volume 32, Number 10—October 2026 ##### _Dispatch_ ### Fatal Infection with Dengue Virus and Avian Orthoavulavirus 1 in Traveler Returning from Saudi Arabia to France, 2025 On This Page [The Study](https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article) * * * [Conclusions](https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article) * * * [Suggested Citation](https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article) Figures [Figure 1](https://wwwnc.cdc.gov/eid/article/32/10/26-0736-f1) * * * [Figure 2](https://wwwnc.cdc.gov/eid/article/32/10/26-0736-f2) * * * [Figure 3](https://wwwnc.cdc.gov/eid/article/32/10/26-0736-f3) Downloads [RIS [TXT - 2 KB] ](https://wwwnc.cdc.gov/eid/article/32/10/26-0736.ris) Article Metrics [Metric Details](https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article) Maud Salmona, Salomé Schlupmann, Morgane Mailhe, Dorothée Chopin, Quentin Richier, Karine Lacombe, Lila Bouadma, Jean-Francois Timsit, Vincent Bondet, Quentin Le Hingrat, Jérôme Le Goff, Jamie Sugrue, Darragh Duffy, Olivier Schwartz, Michael White, Valérie Paradis, Franck Verdonk, François-Xavier Lescure, and Marie Jaspard[![Comments to Author](https://wwwnc.cdc.gov/eid/content/images/icon/email.gif)](https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article#comment) Author affiliation: Author affiliations: Hôpital Saint-Louis, Paris, France (M. Salmona, J. Le Goff); Hôpital Saint-Antoine, Paris (S. Schlupmann, D. Chopin, Q. Richier, K. Lacombe, M. Jaspard); Hôpital Bichat Claude-Bernard, Paris (M. Mailhe, F.-X. Lescure); Sorbonne Universite, Paris (Q. Richier, K. Lacombe, F. Verdonk); Assistance Publique—Hopitaux de Paris, Paris (L. Bouadma, J.-F. Timsit, Q. Le Hingrat, V. Paradis, F.-X. Lescure); IAME, INSERM, Université Paris Cité, Paris (L. Bouadma, J.-F. Timsit, F.-X. Lescure); Université Paris Diderot, Paris (J.-F. Timsit, F.-X. Lescure); Institut Pasteur, Paris (V. Bondet, J. Sugrue, D. Duffy, O. Schwartz, M. White) [Suggested citation for this article](https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article#suggestedcitation) ### Abstract A previously healthy 26-year-old man died of hemorrhagic fever with fulminant hepatitis and shock 36 hours after returning to France from Mecca, Saudi Arabia. Postmortem analyses detected low-level dengue virus RNA and positive NS1 antigen along with unexpected extremely high-titer disseminated velogenic avian orthoavulavirus 1 infection with elevated systemic cytokine responses. A previously healthy 26-year-old man sought care in Paris, France, immediately after returning from Mecca, Saudi Arabia, in January 2025. He was experiencing fever, myalgia, headache, abdominal pain, and diarrhea that began 4 days earlier. He reported no specific exposure during his trip, including no contact with animals, contaminated food or water, or insect bites. He had no history of immunosuppression or repeated infection. No family members traveling with him experienced similar symptoms. We report the patient’s clinical course and laboratory findings. ### The Study At admission to the intensive care unit in Saint-Antoine hospital (Paris, France), the patient had fever (40°C), tachypnoea (45 breaths/min, SpO2 95% on room air), poor tissue perfusion, and oliguria. Results of cardiopulmonary, abdominal, and neurologic examination were unremarkable. Conjunctival hemorrhage and hematuria were present at hospital admission. Despite early fluid resuscitation and empirical antimicrobial treatment, his condition rapidly deteriorated. He experienced multiple organ dysfunction syndrome including hypotension, purpuric livedo, anuria, and acute kidney failure (creatinine 600 μmol/L), elevated level of lactate (4.4 mmol/L), major hepatic dysfunction (alanine aminotransferase and aspartate aminotransferase levels were >100 times the upper limit of normal and factor V was at 51%), thrombocythemia (29 × 109/L), decreased hematocrit (39%), decreased prothrombin time (52%), and disseminated intravascular coagulation. Inflammatory markers were elevated (C-reactive protein 320 mg/L; procalcitonine 136 µg/L). We could not perform bacterial analysis because the patient was isolated for initial suspicion of highly infectious pathogens. Body computed tomography results were unremarkable. We applied resuscitation measures and escalated antimicrobial therapy. Etiologic assessment included PCR testing for malaria, SARS-CoV-2, influenza, cytomegalovirus, Ebola virus, Zika virus, chikungunya virus, and serology for HIV and for hepatitis A, B, C, and E; all results were negative. At that time, the patient’s blood tested negative by PCR and IgM and IgG serology for dengue virus (DENV). The patient’s condition continued to deteriorate; he experienced refractory shock, fulminant hepatitis, and disseminated intravascular coagulation. He died 36 hours after hospital admission. Figure 1 ![Liver biopsy images from study of a fatal infection with dengue virus and avian orthoavulavirus 1 in traveler from Saudi Arabia, 2025. A\) Sirius red stain showing normal architecture without any fibrosis. Solid arrow indicates centrilobular vein; dashed arrow indicates portal tract. Original magnification ×100. B\) Hematoxylin and eosin stain showing extensive parenchymal necrosis; all hepatocytes of the lobule are necrotic. Lobules contain few inflammatory cells. Solid arrow indicates centrilobular vein. Original magnification ×200.](https://wwwnc.cdc.gov/eid/images/26-0736-F1-tn.jpg) [Figure 1](https://wwwnc.cdc.gov/eid/article/32/10/26-0736-f1 "Figure 1"). Liver biopsy images from study of a fatal infection with dengue virus and avian orthoavulavirus 1 in traveler from Saudi Arabia, 2025. A) Sirius red stain showing normal architecture without... Postmortem laboratory results revealed a low dengue viral load in urine with quantitative reverse transcription PCR results at a cycle threshold (Ct) of 39 from a pan-dengue duo test and Ct of 40 from a dengue-1–specific test; both had a robust fluorescence curve. Serum was positive for nonstructural 1 glycoprotein antigen (positivity ratio 2.5) by VIDAS Dengue NS1 (bioMérieux, [External Link](https://www.biomerieux.com)). Postmortem liver biopsy demonstrated normal architecture and extensive parenchymal necrosis without any viral inclusions ([Figure 1](https://wwwnc.cdc.gov/eid/article/32/10/26-0736-f1)). Figure 2 ![Maximum-likelihood phylogenetic tree of APMV-1 from study of a fatal infection with dengue virus and avian orthoavulavirus 1 in traveler from Saudi Arabia, 2025. The tree was inferred from 120 complete APMV-1 clade II genomes retrieved from GenBank. Black stars indicate sequences obtained from the patient’s liver biopsy and plasma samples, which cluster within subgenotype VI.2.1.2 \(inset\). Scale bar indicates nucleotide substitutions per site. APMV-1, avian paramyxovirus type-1.](https://wwwnc.cdc.gov/eid/images/26-0736-F2-tn.jpg) [Figure 2](https://wwwnc.cdc.gov/eid/article/32/10/26-0736-f2 "Figure 2"). Maximum-likelihood phylogenetic tree of APMV-1 from study of a fatal infection with dengue virus and avian orthoavulavirus 1 in traveler from Saudi Arabia, 2025. The tree was inferred from 120... We further analyzed plasma and liver biopsy samples using metagenomic shotgun next-generation sequencing (mNGS). mNGS detected avian orthoavulavirus 1 (AOAV-1), the virus historically associated with Newcastle disease, at extremely high levels; 191,718 reads per million in liver tissue, and 244,781 reads per million in plasma. We obtained complete coverage of all AOAV-1 coding sequences (GenBank accession no. PX575854). Phylogenetic analysis classified the strain as AOAV-1 clade II, genotype VI, subgenotype VI.2.1.2 ([Figure 2](https://wwwnc.cdc.gov/eid/article/32/10/26-0736-f2)), a pigeon-adapted lineage historically termed pigeon paramyxovirus type 1, with a velogenic fusion protein cleavage site motif (RRRKRF) ([_1_](https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article#r1 "1")). Velogenic strains are highly virulent AOAV-1 variants defined by a polybasic fusion-protein cleavage site, which enables ubiquitous protease activation and systemic multiorgan tissue tropism, in contrast to low-virulence strains, which carry a monobasic cleavage site and remain confined to the respiratory and enteric tract ([_1_](https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article#r1 "1")). Figure 3 ![Cytokine concentrations from study of a fatal infection with dengue virus and avian orthoavulavirus 1 in traveler from Saudi Arabia, 2025. A\) IFN-α. B\) IFN-γ. C\) IFN-induced CXCL10. D\) IFN-induced CXCL11. E\) Pro-inflammatory IL-6. F\) Pro-inflammatory TNF-α. We measured concentrations in blood samples from the study patient compared with those from healthy donors. Boxes indicate 95% CI; horizontal bars within boxes indicate median; whiskers indicate ranges; dots indicate individual patient samples. We measured concentrations for interferon-α using single molecule array digital-ELISA using an in-house Simoa bead-based assay on the HD-X platform \(Quanterix, https://www.quanterix.com\) and multiplexed Luminex assay \(R&D Systems, Inc., https://www.rndsystems.com\) for other cytokines. We determined p values by Mann-Whitney test. CXCL, C-X-C motif chemokine ligand; IFN, interferon; IL, interleukin; TNF, tumor necrosis factor-α. ](https://wwwnc.cdc.gov/eid/images/26-0736-F3-tn.jpg) [Figure 3](https://wwwnc.cdc.gov/eid/article/32/10/26-0736-f3 "Figure 3"). Cytokine concentrations from study of a fatal infection with dengue virus and avian orthoavulavirus 1 in traveler from Saudi Arabia, 2025. A) IFN-α. B) IFN-γ. C) IFN-induced CXCL10. D) IFN-induced... We confirmed AOAV-1 infection by specific real-time PCR detection on postmortem liver biopsy (Ct 17.23) and plasma (Ct 15.74) samples, as well as on premortem urine (Ct 18.23), cerebrospinal fluid (Ct 35.9), and sputum (Ct 18.5) specimens, confirming a disseminated infection. In addition, analysis of the plasma type I interferon (IFN) response by single molecule array digital-ELISA using an in-house Simoa bead-based assay on the HD-X platform (Quanterix, [External Link](https://www.quanterix.com)) showed extremely high levels of IFN-α (>104 pg/mL) ([Figure 3](https://wwwnc.cdc.gov/eid/article/32/10/26-0736-f3), panel A) and IFN-β (>104 pg/mL, data not shown), as well as extremely high levels of IFN-γ, C-X-C motif chemokine ligand 10 and 11, interleukin 6, and tumor necrosis factor-α measured by Luminex (R&D Systems, Inc., [External Link](https://www.rndsystems.com)) ([Figure 3](https://wwwnc.cdc.gov/eid/article/32/10/26-0736-f3), panels B–F). [Top](https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article) ### Conclusions We describe a fulminant febrile illness associated with 2 unusual virologic findings: low-level evidence of DENV infection and high-titer disseminated AOAV-1. We could not establish the relative contribution of each virus to the fatal syndrome with certainty. However, the high AOAV-1 loads detected in plasma and multiple tissues and body fluids provide strong evidence of disseminated infection and a major role for AOAV-1 in the clinical manifestation of the infection. Severe forms of dengue occur in ≈5% of cases ([_2_](https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article#r2 "2")). Because this patient had no history of dengue infection and no detected DENV IgG, his illness was consistent with primary dengue fever, which although typically milder than subsequent infections, can also lead to severe disease ([_2_](https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article#r2 "2")). Initial blood PCR and serology were negative for DENV, as was the mNGS performed in the liver biopsy. We diagnosed dengue on the basis of DENV-1–specific and pan-dengue PCR assay on urine and the detection of NS1 antigen in blood. AOAV-1 infection was detected after patient’s death and was completely unexpected. The AOAV-1 strain genotype VI.2 is a lineage maintained primarily in a pigeon/columbiform reservoir ([_3_](https://wwwnc.cdc.gov/eid/article/32/10/26-0736_article#r3 "3")–[ _5_](https://wwwnc.cdc.
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