Lingering Dengue NS1 Antigen Complicates Diagnosis of Visceral Leishmaniasis Coinfection

A 23-year-old migrant worker from the Dang district of Nepal has become the centerpiece of an unusual clinical saga that stretched across three countries and exposed the diagnostic pitfalls of overlapping tropical infections. In a case report published in BMC Infectious Diseases, clinicians and researchers describe how persistent dengue NS1 antigenemia and undiagnosed visceral leishmaniasis intertwined in a single patient, prolonging his fever, misleading physicians in two nations, and ultimately requiring a rescue therapy after first-line treatment failed. The report, led by Bimal Sharma Chalise of Sukraraj Tropical and Infectious Disease Hospital in Kathmandu, underscores how coinfections can warp the apparent clinical picture of two diseases that are individually well understood.

The patient, who had been working in Malaysia, first fell ill with intermittent fever during his period of immigration there. Screening at that stage returned a positive result for dengue, a diagnosis that seemed unremarkable in a region where the dengue virus circulates intensely. Yet the fever refused to settle. Dengue is typically a self-limited, mosquitoborne viral illness in which the nonstructural protein 1, or NS1, antigen circulates in blood during the acute phase and clears within days to a couple of weeks as the immune response takes hold. In this patient, however, the fever persisted long enough that he was forced to return to Nepal, carrying with him a dengue label that would shape every subsequent clinical decision.

Back in South Asia, the diagnostic journey grew more tangled rather than less. During evaluation in India, clinicians confronting the patient’s prolonged febrile illness and laboratory abnormalities turned their suspicion toward a hematological malignancy, an understandable but ultimately erroneous interpretation. Visceral leishmaniasis, caused by the protozoan parasite Leishmania donovani and transmitted by phlebotomine sand flies, is famous for mimicking other conditions: it produces splenomegaly, hepatomegaly, pancytopenia, weight loss, and relentless fever, a constellation that can indeed resemble lymphoma or leukemia on superficial review. The misdirection meant that the true diagnosis remained unmade while the underlying parasitic infection continued its indolent destruction of the patient’s immune defenses.

It was only after a third discrete febrile episode that visceral leishmaniasis was finally identified. By that point, however, the case had acquired another layer of complexity: the dengue NS1 antigen was still detectable, a strikingly prolonged persistence for a protein that normally vanishes as acute infection resolves. The reporting team argues that the concomitant infections appear to have driven this prolonged persistence of dengue features and, in parallel, may have propelled a previously asymptomatic Leishmania infection into symptomatic, life-threatening visceral disease. The immunology of such an interaction is plausible if speculative: dengue and Leishmania both manipulate mononuclear phagocytes, and the profound cell-mediated immunosuppression of active visceral leishmaniasis could plausibly impair clearance of viral antigens, while the viral insult could tip a controlled parasitic infection toward clinical manifestness.

Treatment brought the next setback. The patient received liposomal amphotericin B, or LAMB, the recommended first-line therapy for visceral leishmaniasis in many endemic settings, prized for its potency against Leishmania parasites sequestered in the spleen, liver, and bone marrow. Six doses were administered, yet the patient demonstrated no adequate response. Relapse followed the initial course, an outcome that forced the clinical team to reconsider both the diagnosis and the therapeutic strategy. Drug failure in visceral leishmaniasis can arise from host immunosuppression, parasite resistance, inadequate drug exposure, or an incorrect initial diagnosis, and in a patient whose dengue serology remained abnormal, every one of those possibilities demanded attention.

The decisive moment in the odyssey arrived through careful serial testing. When repeat assays for dengue NS1 antigen, dengue-specific IgM, and dengue-specific IgG all finally returned negative results, the diagnostic fog began to lift. With the dengue infection definitively behind him and active visceral leishmaniasis confirmed as the driver of his ongoing febrile illness, the clinicians turned to miltefosine, an oral alkylphosphocholine originally developed as an anticancer agent and later repurposed as a leishmanicidal drug. The intervention proved highly effective: the patient’s visceral leishmaniasis resolved, closing a clinical narrative that had spanned Malaysia, India, and Nepal and involved misdiagnosis, failed therapy, and relapse along the way.

The case carries technical lessons that extend well beyond one patient. Rapid diagnostic tests for dengue, including NS1 antigen detection and IgM/IgG antibody assays, are cornerstones of febrile illness triage in low- and middle-income countries, but their performance assumes a typical immunocompetent, monoinfected host. When a second pathogen remodels the immune landscape, antigen clearance kinetics can change in ways that no single test anticipates. Conversely, the rK39 rapid diagnostic test for visceral leishmaniasis, which the authors highlight among their keywords, detects antibodies that may be absent early or inconsistent across the disease course. A febrile traveler or migrant whose work history spans multiple endemic regions therefore represents a diagnostic worst case for panel-based, single-pathogen thinking, and the authors argue that the case demonstrates a clear need for better diagnostic tools and management strategies specifically designed for coinfections.

Epidemiologically, the report sits at the intersection of two burdens of the same geography. Visceral leishmaniasis remains endemic in the lowland plains of Nepal, India, and Bangladesh, where elimination programs have driven incidence down but not to zero, and dengue has expanded dramatically across the same territories in recent decades, with Nepal experiencing increasingly large seasonal epidemics. Migrant workers such as this patient, who move between endemic countries for employment, occupy a distinctive risk niche: they may acquire one infection in one country, carry it across borders, and have it diagnosed or misdiagnosed in another, fragmenting the clinical record that any single physician depends upon. The three-country trajectory recorded in this report illustrates how health systems that do not share records can each hold a partial truth about the same patient.

The authors caution, appropriately, that a single case report cannot establish the mechanism by which dengue and Leishmania interacted in this individual, only that the association coincided with atypical antigen persistence, disease progression, and treatment failure. Still, the therapeutic implication is concrete: in patients with visceral leishmaniasis who fail liposomal amphotericin B, especially those with concurrent or recent viral infections, clinicians should consider rescue therapy with miltefosine and should pursue serial virological testing to clarify what is resolving and what is not. The patient’s consent, anonymization of identifying details, ethical approval from the Nepal Health Research Council, and adherence to the Declaration of Helsinki documented in the report reflect the care taken to convert one man’s prolonged illness into a lesson for the clinics of the tropical world.

Subject of Research: Leishmania-dengue virus coinfection with persistent NS1 antigenemia complicating visceral leishmaniasis diagnosis and treatment

Article Title: Persistent dengue NS1 antigen in a patient with visceral leishmaniasis: A diagnostic and therapeutic odyssey

Article References: Chalise, B. S., Shrestha, S., Sapkota, A. S., Bajracharya, M., Basaula, Y. N., Bras‑Goncalves, R., & Manandhar, K. D. (2026). Persistent dengue NS1 antigen in a patient with visceral leishmaniasis: A diagnostic and therapeutic odyssey. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14469-y

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14469-y

Keywords: visceral leishmaniasis, dengue virus, NS1 antigen, coinfection, miltefosine, liposomal amphotericin B, rK39 RDT, neglected tropical diseases, Nepal, migrant workers, case report, diagnostic challenges