Mucormycosis is caused by environmental molds belonging to the order Mucorales, most notoriously the genus Rhizopus, whose spores float freely in soil, decaying organic matter, and damp air. In most people, inhaled spores are simply engulfed and destroyed by neutrophils and macrophages, the innate immune cells that patrol the airways. But when those defenses falter, as in diabetes, cancer, or organ transplantation, the spores germinate into broad, ribbon-like fungal hyphae that invade blood vessels with terrifying speed. This angioinvasion triggers thrombosis and tissue death, driving a fulminant infection that kills 40 to 50 percent of affected patients even with treatment. Diabetes remains the most common predisposing factor, associated with an overall mortality of roughly 46 percent, and more than half of all mucormycosis cases in large reviews occur in people with overt immunosuppression.

The Iranian patient’s initial symptoms were strikingly atypical, which is precisely why the diagnosis proved so treacherous. He complained of severe right-sided epigastric pain and excessive watering of the right eye, with no nasal congestion, no fever, and no neurological signs. His doctor prescribed topical ketorolac eye drops for presumed conjunctivitis. Instead of improving, he deteriorated: marked redness around the eye progressed to bruising-like ecchymosis and swelling, prompting admission to Prophet Azam Hospital at Kerman University of Medical Sciences. The authors of the report suggest that the abdominal pain may have reflected inadvertent ingestion of fungal spores, since gastrointestinal acquisition of Mucorales is well documented and greenhouse workers handle contaminated material constantly, though it may equally have been an incidental finding that contributed to the dangerous delay.

On admission, the man was alert, oriented, and afebrile, with intact vision and no cranial nerve deficits, findings that could easily have reassured clinicians. But computed tomography and magnetic resonance imaging of his sinuses and orbits told a more alarming story: right-sided proptosis, meaning the eye was being pushed forward, together with significant edema and infiltration of both the intraconal and extraconal fat spaces inside the orbit. T2-weighted MRI sequences showed the bright signal characteristic of acute inflammatory change, though without definite evidence of intracranial extension or cavernous sinus thrombosis. Such imaging findings are non-specific and can appear in severe bacterial cellulitis, but the combination of rapid deterioration, extensive orbital involvement, and the patient’s occupational history in a high-risk environment raised immediate suspicion of invasive fungal disease and guided the urgent biopsy that followed.

The laboratory work-up was equally revealing for what it did not find. The patient’s white blood cell count was mildly elevated at 12.6 × 10³ per microliter with 95 percent neutrophils, C-reactive protein stood at 37 mg/L, and his erythrocyte sedimentation rate was 21 mm/h, all consistent with a robust systemic inflammatory response. Yet targeted immunological testing, including HbA1c of 5.3 percent, negative HIV serology, and normal immunoglobulin G, A, and M levels, confirmed that he was genuinely immunocompetent. His fasting glucose of 110 mg/dL represented only an impaired fasting glucose, a subtle metabolic derangement. The authors note that even mild hyperglycemia can upregulate endothelial receptors such as GRP78, enhancing fungal adhesion and angioinvasion, and emerging evidence suggests that transient or subclinical dysglycemia can predispose otherwise healthy individuals to opportunistic mycoses.

Definitive diagnosis came from the mycology laboratory. During drainage of the eye discharge, necrotic tissue and purulent secretions were sampled and examined under potassium hydroxide preparation, hematoxylin and eosin staining, and Giemsa staining. All three revealed the pathognomonic signature of Mucorales: broad, aseptate, ribbon-like hyphae branching at wide angles. Culture on Sabouraud dextrose agar produced luxuriant, fluffy, grayish-white to brown colonies within seven days at 30 degrees Celsius, and lactophenol cotton blue microscopy of the isolate, showing sporangiophores with rhizoids at their base and a columella, identified the culprit as a Rhizopus species. Repeat sampling from the skull base again yielded positive results. Critically, treatment was initiated on the basis of microscopy alone, because fungal culture sensitivity is only 30 to 50 percent and its slow turnaround makes it useless for guiding urgent therapy.

What followed was an aggressive multimodal assault on the infection. Surgeons performed an urgent orbital exenteration, the radical removal of the entire contents of the eye socket, after intraoperative inspection revealed extensive necrotic tissue that had to be excised to prevent extension to the skull base, a complication carrying a mortality above 80 percent. Simultaneously, the patient received intravenous liposomal amphotericin B at 5.0 to 10 mg/kg per day, continued for a total of three weeks. The combined medical-surgical approach was well tolerated and produced a favorable clinical response. He was discharged in stable condition upon completing the antifungal course, and final culture results corroborated the diagnosis seven days after discharge. At follow-up three months later, he remained asymptomatic with no signs of recurrence, though he has been counseled on occupational safety measures should he return to greenhouse work.

The case fits a growing pattern in which occupational and environmental exposure, rather than host immunosuppression, precipitates invasive disease. A cohort study of cucumber greenhouse workers documented substantial exposure to airborne fungi, including Mucorales species, using next-generation sequencing alongside biomarkers of systemic inflammation, lending biological plausibility to the exposure route even though invasive disease was not observed in that cohort. Comparable risk has been described after natural disasters, including a case of rhino-orbital mucormycosis in an immunocompetent adult following prolonged mold exposure during post-hurricane cleanup, and rural living or contact with organic matter has been implicated in pediatric orbital mucormycosis without underlying immunodeficiency. The authors argue that a sufficiently high inoculum of spores can simply overwhelm innate defenses, particularly phagocytosis by neutrophils and macrophages, which are typically effective against Mucorales.

A literature search across PubMed, Scopus, and Web of Science covering January 2000 to October 2025, summarized by the authors, shows how consistently diagnostic delay haunts immunocompetent patients. A 67-year-old woman who developed headache, diplopia, and vision loss after post-hurricane mold cleanup recovered fully after multiple debridements and amphotericin B. A 12-year-old girl with a nasal foreign body and Rhizopus oryzae infection survived after surgery and antifungal therapy, as did a 22-year-old man with a minor skin lesion who required exenteration. But a 59-year-old woman with no identified risk factors died of multiple organ failure, diagnosed only at post-mortem, and a 32-year-old man died after treatment non-compliance, a reminder that even favorable biology depends on adherence to therapy. Across these reports, the absence of classic risk factors and the non-specific nature of early symptoms repeatedly misled clinicians.

For physicians on the front lines, the message is stark: progressive orbital infections deserve consideration of mucormycosis even in patients with no diabetes, no malignancy, and no immunosuppressive drugs, particularly when their work or environment involves soil, decaying vegetation, or mold-laden air. Interestingly, angioinvasion in immunocompetent hosts may follow a somewhat less fulminant course than in diabetic patients, offering a window for recovery if clinicians act quickly. High clinical suspicion, prompt histopathological diagnosis using KOH preparations and tissue staining, and aggressive combined surgical and antifungal treatment remain the pillars of survival, with combined approaches yielding roughly 60 percent survival in rhino-orbital-cerebral disease compared with more than 90 percent mortality in disseminated infection. As greenhouse agriculture expands worldwide, this single case suggests that the boundary between harmless environmental mold and life-threatening invasion may be thinner than the immune status of the host alone would suggest.

Subject of Research: Rhino-orbital mucormycosis in an immunocompetent adult linked to occupational greenhouse mold exposure

Article Title: Rhino‐Orbital Mucormycosis in an Immunocompetent Adult: A Case Report Emphasizing Diagnostic and Therapeutic Challenges

Article References: Mousavi, S. M., Mousavi, S. A. A., Faryabi, O., Sharifi, I., Kamyab, H., & Shirazi, Z. (2026). Rhino‐Orbital Mucormycosis in an Immunocompetent Adult: A Case Report Emphasizing Diagnostic and Therapeutic Challenges. Clinical Case Reports, 14(10), Article e73683. https://doi.org/10.1002/ccr3.73683

Image Credits: AI Generated

DOI: 10.1002/ccr3.73683

Keywords: mucormycosis, Rhizopus, orbital exenteration, immunocompetent patient, greenhouse workers, occupational exposure, liposomal amphotericin B, fungal infection, angioinvasion, diagnostic delay, Mucorales, Iran

The team, led by Olena Zubach of Danylo Halytsky Lviv National Medical University together with colleagues at the Lviv Oblast Clinical Hospital of Infectious Diseases and the Lviv Oblast Center for Diseases Control and Prevention, performed a lumbar puncture and recovered cerebrospinal fluid for analysis. The fluid showed moderate lymphocytic pleocytosis, an elevated count of lymphocytes that serves as a cellular fingerprint of viral central nervous system infection. Serological testing then delivered the first answer. The patient’s serum contained diagnostic levels of both IgM and IgG antibodies against tick-borne encephalitis virus, the flavivirus transmitted by Ixodes ticks across much of Europe and Asia, while her cerebrospinal fluid carried IgG antibodies against the same virus. Combined with her epidemiological history, which included travel to an endemic region and a documented tick bite, the diagnosis of tick-borne encephalitis was firmly established.

But the cerebrospinal fluid held a second surprise. Polymerase chain reaction testing detected DNA from human herpesvirus 7, a betaherpesvirus better known as a ubiquitous, usually silent passenger in the human population. The detection of HHV-7 DNA in the central nervous system of an immunocompetent patient already fighting tick-borne encephalitis raised an immediate and difficult question: was the herpesvirus an innocent bystander, a latent virus passively present in the sample, or was it actively replicating and contributing to the neurological damage? The authors of the report, published in Virology Journal, framed their case precisely around this interpretive dilemma, and their literature review situates it within a growing but still incomplete body of evidence on viral co-infections of the brain.

Human herpesvirus 7 was first isolated in 1990 and is closely related to human herpesvirus 6, the other member of the Roseolovirus genus. Like its relative, HHV-7 infects the vast majority of people early in life, typically causing a mild febrile illness or the childhood rash known as roseola, after which it establishes lifelong latency in T lymphocytes and other tissues. In healthy carriers, the virus usually remains dormant, controlled by cellular immunity. Reactivation is a well-recognized complication in transplant recipients and other immunosuppressed patients, in whom HHV-7 has been implicated in febrile syndromes, encephalitis, and graft complications. Detection of the virus in the cerebrospinal fluid of an immunocompetent adult, however, is genuinely uncommon, and determining whether such detection reflects true productive infection rather than latent viral DNA is a persistent technical challenge in clinical virology.

This challenge stems from the biology of herpesviruses themselves. Latent HHV-7 genomes can persist in cells that traffic through the central nervous system, and PCR amplification alone cannot always distinguish between low-level latent DNA and the replicating viral genomes that would indicate an active infection. Quantitative viral load measurements, detection of viral mRNA transcripts, and demonstration of intrathecal antibody synthesis are among the tools virologists use to strengthen the case for active replication, but each has limitations. In the Ukrainian case, the detection of HHV-7 DNA in the cerebrospinal fluid was unexpected precisely because the patient’s immune status gave no obvious reason for herpesvirus reactivation, and the clinical picture was already well explained by tick-borne encephalitis. The co-occurrence forced the clinicians to consider whether the two viruses might be interacting in ways that shaped the severity or course of the disease.

Viral co-infections of the central nervous system are an area of intensifying research interest, and the mechanisms by which one virus can modify the pathogenesis of another are varied and, in many cases, still hypothetical. Direct interference is one possibility: one virus may upregulate or suppress cellular pathways that the second virus depends on. Immune-mediated effects are another. A primary viral infection can transiently perturb the antiviral response, altering interferon signaling, T cell function, or cytokine profiles in ways that permit a second, normally controlled agent to reactivate from latency. Tick-borne encephalitis virus itself is known to affect immune cells, and herpesviruses such as HHV-7 reside within CD4-positive T lymphocytes, creating a plausible cellular environment in which acute flaviviral infection and herpesvirus reactivation could intersect. The authors emphasize that the infectious process resulting from the combined influence of neurotropic viruses may differ in important ways from infection with either agent alone, complicating both diagnosis and the interpretation of disease severity.

The literature review accompanying the case report surveys what is known about HHV-7 as a cause of meningoencephalitis. Reports of HHV-7-associated encephalitis cluster heavily among immunocompromised populations, particularly hematopoietic stem cell transplant recipients, in whom the virus has been detected in cerebrospinal fluid during episodes of neurological deterioration. In immunocompetent patients, documented cases are rare and often rest on single-center detections without definitive proof of causality. This evidentiary gap mirrors a broader problem in clinical virology: the widespread use of sensitive multiplex PCR panels on cerebrospinal fluid increasingly uncovers viral sequences whose clinical significance is uncertain. A positive PCR result for a latent herpesvirus in a patient with another clear diagnosis, such as tick-borne encephalitis, exemplifies the interpretive tightrope that clinicians must walk between over-attributing disease to an incidental finding and missing a genuine co-pathogen.

In the present case, the practical outcome was favorable. The patient received prescribed therapy, her condition improved steadily, and she was discharged on the twenty-third day of her hospital stay. The report does not claim that anti-herpesvirus treatment was decisive, nor does it attribute any specific portion of her neurological illness to HHV-7; instead, it uses the case to illustrate how diagnostic reasoning must accommodate the possibility of coexisting viral processes. For clinicians working in tick-borne encephalitis endemic zones, the case is a reminder that a confirmed flaviviral diagnosis does not automatically explain every feature of a patient’s course, and that molecular testing of cerebrospinal fluid can reveal additional agents whose contribution requires careful weighing.

Beyond its immediate clinical message, the case carries implications for surveillance and research. Tick-borne encephalitis is expanding its geographic footprint in Europe, with rising case numbers and newly affected regions reported in recent years, and Ukraine sits within the endemic belt where awareness of the disease is critical for early diagnosis and supportive care. As molecular diagnostics become more widely deployed, detecting additional viruses in the cerebrospinal fluid of TBE patients will likely become more common, and the field will need systematic studies, with quantitative viral loads, longitudinal sampling, and matched controls, to determine when such findings represent reactivation, co-infection, or noise. The Lviv team’s report, grounded in a single well-documented patient and an honest acknowledgment of interpretive complexity, contributes to exactly that foundation. It also underscores a broader truth of modern virology: the human body is a layered ecosystem of persistent viruses, and acute infections can disturb that equilibrium in ways medicine is only beginning to map.

For now, the case stands as both a clinical observation and a caution. A febrile immunocompetent woman with meningoencephalitis, a tick bite, and serology pointing squarely at tick-borne encephalitis virus turned out to carry the DNA of a second neurotropic virus in her spinal fluid. Her recovery suggests that the combined infection was survivable with appropriate care, but the virological questions her case raises, about viral interference, latency, and the true pathogenic potential of HHV-7 in the healthy brain, remain open. The authors’ literature review makes clear that answering them will require more than isolated case reports; it will require the kind of structured, comparative research that turns surprising laboratory findings into actionable clinical knowledge.

Subject of Research: Co-infection of tick-borne encephalitis virus and human herpesvirus 7 in a patient with meningoencephalitis

Article Title: Tick-borne encephalitis co-occurring with human herpesvirus 7 replication: a case report and literature review

Article References: Zubach, O., Prykuda, N., Zadorozhnyi, A., Fedorenko, S., Zbarashchuk, L., Romaniuk, U., & Zinchuk, A. (2026). Tick-borne encephalitis co-occurring with human herpesvirus 7 replication: a case report and literature review. Virology Journal. https://doi.org/10.1186/s12985-026-03313-z

Image Credits: AI Generated

DOI: 10.1186/s12985-026-03313-z

Keywords: tick-borne encephalitis, human herpesvirus 7, meningoencephalitis, viral co-infection, cerebrospinal fluid, PCR diagnostics, flavivirus, herpesvirus latency, immunocompetent patient, case report, neurotropic viruses, Ukraine