Researchers collected skin, hair and nail specimens from patients attending private mycology clinics and governmental university hospitals in Ardabil, Fars, Golestan, Isfahan, Khuzestan, Mazandaran, Razavi Khorasan, Tehran and West Azerbaijan. Every included patient had fungal elements visible by direct KOH microscopy in at least one sample, and culture recovered dermatophytes from 1,568 of the 2,211 suspected cases, a yield of 70.9%.

The researchers combined a lineage-specific PCR with ITS rDNA sequencing, restriction analysis and haplotype comparisons. The specific PCR identified 1,191 isolates as T. mentagrophytes var. indotineae. Sequencing of 78 randomly selected PCR-positive isolates confirmed their placement within the lineage: 57 represented two sub-genotypes of ITS genotype VIII, while 20 belonged to a previously unrecognised genotype XXIX within the T. mentagrophytes var. indotineae lineage. The study used the variety designation in line with taxonomic databases and recent population-genetic studies.

Clinical forms involving the groin and trunk predominated. Tinea cruris accounted for 656 cultured infections, or 41.8% of the total, followed by tinea corporis with 376 cases, or 23.9%; mixed tinea cruris and tinea corporis accounted for 144 cases, or 9.2%, and generalised infection accounted for 128, or 8.2%. T. mentagrophytes var. indotineae was identified in 544 of 656 tinea cruris cases, 279 of 376 tinea corporis cases, 110 of 144 mixed cruris and corporis cases, and 112 of 128 generalised infections. It was also found in 17 of 29 nail infections and 17 of 45 cases of tinea capitis.

Patients with T. mentagrophytes var. indotineae infection had a mean age of 34.5 ± 13.6 years, a median of 35 and a range of 1–85. The group included 588 males and 603 females, with no statistically significant difference in sex distribution (p = 0.664). Species distribution was associated with age group, province, clinical form and involved body site, with all reported p-values below 0.001. The largest numbers of confirmed infections came from Khuzestan, with 607 cases, followed by Mazandaran with 130 and Ardabil and Fars with 115 each.

Among 73 confirmed cases with reliable patient histories, none had documented travel abroad. This absence of recorded international travel does not establish where infection was acquired, but it means travel alone cannot explain the lineage’s presence in the surveyed population. Retrospective analysis placed several Iranian isolates collected in 2011 and 2015 within genotype VIII, indicating that the lineage was already present before the earliest reports from the Indian subcontinent. The study also identified genotype XXIX, adding to previously reported local genetic diversity. Related lineages have been recovered from sheep in rural Iran, but a local animal reservoir remains an unconfirmed hypothesis, and the data do not resolve the lineage’s geographic origin or centre of diversity.

Partial sequencing of the squalene epoxidase gene, SQLE, in 410 T. mentagrophytes var. indotineae isolates detected mutations in 184 isolates, or 44.8%. The mutations comprised the F397L amino-acid substitution in 132 mutant isolates, representing 71.7%, and L393S in 52, representing 28.3%. Mutation proportions were highest in Khuzestan at 52.4% and Fars at 46%, and lowest in Golestan at 8.5%. Both substitutions have previously been associated with terbinafine resistance in isolates from Asia and Europe. The reported 44.8% frequency was higher than mutation rates of 17.8% in an Iranian survey from 2020 and 14.35% in one from 2024, although the present study sequenced only part of the SQLE gene and targeted mutations at positions 393 and 397, so other mutations may not have been detected.

No antifungal susceptibility testing was performed, and the study did not collect clinical outcome data demonstrating treatment failure. The findings therefore identify a substantial proportion of isolates carrying mutations associated with likely terbinafine resistance, but they do not directly establish phenotypic resistance or explain individual treatment outcomes. The hospital-based design and reliance on patients referred to specialised clinics also limit how directly the observed proportions can be applied to Iran’s general population.

Overall, the survey documents a major shift in the epidemiology of referred dermatophytosis in Iran: T. mentagrophytes var. indotineae was the leading identified cause across the sampled settings and was detected in skin, scalp and nail infections. The authors said the findings highlight the need for routine molecular identification, SQLE genotyping and stronger national surveillance, while broader genomic studies and integration of clinical outcome data are needed to clarify transmission, origin and therapeutic implications.

Subject of Research: Epidemiology and terbinafine-resistance-associated SQLE mutations in Iranian dermatophyte isolates

Article Title: Dermatophytosis in Iran: a sharp increase in cases caused by Trichophyton mentagrophytes var. indotineae

Article References: Takesh, A., Wennrich, A., Kolařík, M., Zarei-Mahmoudabadi, A., Kiasat, N., Pazyar, N., Rafiei, A., Abastabar, M., Haghani, I., Kharazi, M., Basiri, S., Jahanshiri, Z., Khodadadi, H., Mohammadi, R., Zarrinfar, H., Seifi, Z., Diba, K., Kamali Sarvestani, H., & Rezaei-Matehkolaei, A. (2026). Dermatophytosis in Iran: a sharp increase in cases caused by Trichophyton mentagrophytes var. indotineae. IMA Fungus, 17, Article e180817. https://doi.org/10.3897/imafungus.17.180817

Image Credits: AI Generated

DOI: 10.3897/imafungus.17.180817

Keywords: dermatophytosis, Trichophyton mentagrophytes, T. mentagrophytes var. indotineae, Iran, terbinafine resistance, SQLE mutations, tinea cruris, tinea corporis, molecular surveillance, fungal infection, sharp, increase

The study reviewed records from the Second Affiliated Hospital of Zhejiang University School of Medicine, where 428 adult COVID-19 inpatients with microbiological surveillance data were admitted between November 2022 and February 2023. A total of 333 patients, or 77.8%, developed at least one additional infection. An infection detected within 48 hours of hospitalization was classified as a co-infection, while one first detected after 48 hours was classified as a secondary infection. Pathogens were grouped into Gram-negative bacteria, Gram-positive bacteria and fungi, with resistant isolates identified separately.

Resistant Acinetobacter baumannii was the most frequently detected pathogen, appearing in 55.9% of patients with infection, followed by resistant Klebsiella pneumoniae in 38.4%, fungi in 33.0% and resistant Pseudomonas aeruginosa in 14.1%. The researchers categorized patients into four pathogen-detection trajectories: no infection, sensitive-bacterial infection, resistant-bacterial infection and fungal-involved infection. They also examined the shape and burden of daily pathogen detections, then tested associations with death, total hospital stay, intensive-care stay and duration of mechanical ventilation.

After adjustment for age, Sequential Organ Failure Assessment score, the ratio of arterial oxygen tension to inspired oxygen fraction, admission to intensive care and underlying comorbidities, all three infection trajectories remained associated with in-hospital death. Compared with the no-infection group, adjusted odds ratios were 2.87 for sensitive-bacterial infections, 3.15 for fungal-involved infections and 4.69 for resistant-bacterial infections, with all 95% confidence intervals excluding one. The secondary outcomes followed the same broad gradient: total hospital stay, intensive-care stay and mechanical-ventilation duration were shortest in patients without additional infection and longest in the resistant-bacterial and fungal-involved groups.

Several analytic approaches supported the association. Propensity-score matching produced an odds ratio of 2.05 for a high-risk infection group compared with the no-infection group, while inverse-probability-of-treatment weighting yielded an adjusted odds ratio of 4.13 for resistant-bacterial infections. In time-dependent competing-risk analyses, infection onset was also associated with a higher instantaneous hazard of death for sensitive-bacterial, resistant-bacterial and fungal trajectories. These methods strengthen the robustness of the observed relationship, but the single-center, retrospective design cannot establish that infections caused the excess mortality. Differences in illness severity, treatment exposure, surveillance practices or unmeasured confounding could contribute to the findings, and the results describe a specific hospitalized population rather than all patients with COVID-19.

Subject of Research: Associations between secondary pathogen infections, clinical trajectories and mortality in hospitalized COVID-19 patients

Article Title: Pathogen trajectory and prognosis of co-infection and secondary infection in hospitalized COVID-19 patients

Article References: Wang, X., Yu, J., Zhang, K., Bai, S., Pan, W., Yang, W., Shao, X., Shen, Z., Zhen, N., Cui, W., Cai, J., Zhang, S., & Zhang, G. (2026). Pathogen trajectory and prognosis of co-infection and secondary infection in hospitalized COVID-19 patients. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14260-z

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14260-z

Keywords: COVID-19, co-infection, secondary infection, hospital mortality, antimicrobial resistance, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, fungal infection, retrospective cohort, Pathogen, trajectory

Candida auris is a yeast species first identified in Japan in 2009 and has since spread to dozens of countries, earning a place on public health watchlists because of its unusual combination of traits. Unlike most Candida species, it persists on skin and hospital surfaces for weeks, resists routine disinfection, spreads between patients in intensive care units, and frequently shows reduced susceptibility to the antifungal drugs that clinicians rely on. Compounding the problem, the organism is notoriously difficult to identify in the laboratory: conventional biochemical methods often misidentify it as Candida haemulonii or other related species, which means accurate detection typically requires matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, known as MALDI-TOF MS, or molecular sequencing. Misidentification delays both appropriate treatment and the infection control measures needed to contain outbreaks.

The Palestinian study included 36 patients with laboratory-confirmed C. auris infection treated at the tertiary care hospital. The mean age of the cohort was 54 years, with a standard deviation of 19.9 years, and 69 percent of the patients were female. The overwhelming majority, 89 percent, required intensive care unit admission, and their median ICU stay was strikingly long at 32 days, with an interquartile range of 18 to 58 days. This prolonged critical care exposure reflects both the severity of the underlying illnesses that predispose patients to invasive fungal infection and the persistent, difficult-to-eradicate nature of C. auris itself, which can colonize patients for weeks and complicate every subsequent hospitalization.

The researchers documented the invasive medical devices that characterize this patient population and that serve as classic gateways for fungal entry. Central venous catheters were present in 81 percent of patients, urinary catheters in 75 percent, and mechanical ventilation in 72 percent. These figures align with the international understanding of C. auris as a pathogen that exploits breaches in natural barriers and indwelling hardware in critically ill patients. The anatomical distribution of infection mirrored this device burden: the urinary tract was involved in 56 percent of cases, the respiratory tract in 50 percent, the bloodstream in 33 percent, and wounds in 17 percent, with some patients harboring the organism at multiple sites simultaneously.

The clinical trajectory of these infections was severe. Septic shock, the life-threatening circulatory collapse that represents the most extreme manifestation of sepsis, developed in 89 percent of the cohort. This extraordinary rate underscores how C. auris infection tends to emerge in patients already fighting for their lives, often superimposed on bacterial infections, organ failure, and prolonged ventilatory support. Distinguishing the specific contribution of the fungus to a patient’s deterioration from that of their underlying condition remains one of the central diagnostic challenges in invasive candidiasis, and the high septic shock rate in this cohort illustrates the grim context in which these infections typically declare themselves.

Treatment patterns revealed notable prescribing choices that the authors flag as potential stewardship targets. Definitive antifungal therapy consisted of azoles in 50 percent of patients, amphotericin B in 44 percent, and echinocandins in only 14 percent. This distribution is significant because international treatment guidelines generally recommend echinocandins, such as anidulafungin, caspofungin, or micafungin, as first-line agents for invasive Candida infections, including C. auris, due to their favorable efficacy and safety profile. The comparatively low echinocandin use and the prominent reliance on azoles, a class to which many C. auris strains exhibit reduced susceptibility, raise questions about antifungal stewardship practices, drug availability, cost constraints, and local susceptibility patterns that the authors suggest warrant further investigation.

The central outcome of the study was stark: all-cause in-hospital mortality reached 50 percent. On univariate analysis using Fisher’s exact test, two factors emerged as more frequent among non-survivors. Respiratory tract isolation of C. auris carried a crude odds ratio of 8.2, with a 95 percent confidence interval of 1.4 to 47.3 and a p-value of 0.008, while septic shock was also significantly associated with death, with a p-value of 0.034. The wide confidence interval around the odds ratio reflects the small sample size and the inherent imprecision of estimates drawn from 36 patients. The authors are careful to emphasize that these are exploratory, hypothesis-generating findings and should not be interpreted as independent predictors or causal relationships, since univariate comparisons cannot disentangle confounding factors such as illness severity, mechanical ventilation, or concurrent bacteremia.

From a methodological standpoint, the study followed the Strengthening the Reporting of Observational Studies in Epidemiology, or STROBE, framework and received ethical approval from the An-Najah National University Institutional Review Board, with a waiver of informed consent granted because of the retrospective design and the use of de-identified data. Laboratory confirmation relied on the hospital’s microbiology diagnostics, and susceptibility considerations were framed in terms of minimum inhibitory concentrations as defined by the Clinical and Laboratory Standards Institute. The retrospective cohort design, while efficient for characterizing a rare and recently emerged pathogen, carries limitations including reliance on documentation quality, the absence of a comparison group, and the possibility that some C. auris isolates were colonization rather than true infection, a distinction that even experienced clinicians find difficult in this population.

The significance of this work extends beyond a single institution. C. auris has been reported across the Middle East and globally, but granular clinical data from many regional health systems remain sparse, and this cohort provides a rare quantitative window into how the pathogen behaves in a tertiary hospital serving the Palestinian population. The 50 percent mortality figure sits within, though at the higher end of, the range reported in international literature, where mortality for invasive C. auris infection often falls between 30 and 60 percent depending on the population and the proportion of bloodstream infections. The heavy representation of urinary and respiratory tract isolates in this cohort, rather than predominantly bloodstream infection, may reflect local diagnostic and sampling practices as well as the patient mix.

The authors conclude that prospective, multicenter studies are needed to confirm these observations, define risk factors with adequate statistical power, and inform evidence-based antifungal stewardship and infection control policies in the region. In the meantime, the study delivers a clear message for clinicians and hospital epidemiologists: C. auris is established in this healthcare setting, it strikes patients who are already among the most vulnerable, and survival depends on early laboratory detection, judicious device management, rapid escalation to appropriate antifungal therapy, and rigorous adherence to the contact precautions and environmental disinfection protocols that are the only proven tools for interrupting its transmission within hospitals. As this pathogen continues its global expansion, cohorts like this one from previously underrepresented settings will be essential for building the collective evidence base needed to confront it.

Subject of Research: Clinical characteristics and in-hospital mortality of Candida auris infection in a Palestinian tertiary hospital cohort

Article Title: Candida auris infection in a palestinian tertiary hospital: 36-patient retrospective cohort with high mortality

Article References: Abutaha, M., Hattab, S., dweik, H., Mlitat, A., Najjar, N., Ayesh, B., Taha, A. A., & Sabatin, A. (2026). Candida auris infection in a palestinian tertiary hospital: 36-patient retrospective cohort with high mortality. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14648-x

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14648-x

Keywords: Candida auris, fungal infection, antimicrobial resistance, in-hospital mortality, intensive care unit, septic shock, antifungal stewardship, Palestine, retrospective cohort, nosocomial infection, echinocandins, infection control

The patient was a 68-year-old man who had spent his career working outdoors with plants and soil. He lived in Florida, had no history of international travel, and was being treated with vedolizumab, a targeted biologic medication for Crohn’s disease that selectively blocks a gut-homing molecule on white blood cells. Unlike broad immunosuppressants, vedolizumab is considered relatively gut-specific, and the patient was, for practical purposes, fairly immunocompetent. He presented with a swelling on the dorsal aspect of his hand, a location entirely consistent with his occupational exposure to thorns, splinters, and plant debris.

Surgeons performed an excisional biopsy, and the pathology told an unusual story. Under the microscope, the lesion was a subcutaneous phaeohyphomycosis, an infection caused by pigmented, or dematiaceous, fungi that form dark-walled hyphae in tissue. Critically, the inflammatory reaction appeared to be nucleated by a fragment of plant matter, suggesting that a splinter or similar vegetative foreign body had carried the fungus beneath the skin and seeded the infection. This mechanism, known as inoculation through traumatic implantation, is the classic route by which environmental molds gain access to the subcutaneous tissues of gardeners, farmers, and foresters.

Identifying the organism required more than conventional microbiology. Broad-range polymerase chain reaction, a technique that amplifies conserved fungal genetic regions and compares the resulting sequence against reference databases, pinpointed the culprit as Gloniopsis leucaenae. The genus Gloniopsis belongs to the class Dothideomycetes, a large and diverse group of fungi that includes many plant pathogens. Before this case, G. leucaenae had been isolated in 2019 and reported exclusively from plant matter in Thailand. Its appearance in a human hand in Florida, in a patient who had never left the United States, was entirely unexpected.

The clinical course added another layer of complexity. The initial lesion was excised surgically, and no antifungal therapy was given, a reasonable approach when an infection is thought to be fully removed. Yet a second lesion subsequently arose at the site and had to be excised as well. On histology, fungal hyphae were again demonstrated, but this time both culture and PCR came back negative, a pattern that can occur when the fungal burden is low, when prior surgery has disrupted the organism, or when laboratory conditions fail to support growth. Faced with evidence of recurrence, the team initiated empiric treatment with itraconazole, an azole antifungal commonly used against pigmented molds because of its reliable activity against this group.

The case carries particular significance when set against the only other documented Gloniopsis infection in humans. A prior report involved a related species that caused disseminated disease in an immunocompromised host, spreading beyond the initial site and posing a serious systemic threat. The new report stands in contradistinction to that picture: G. leucaenae caused a localized infection in a relatively immunocompetent individual, apparently contained by surgical excision with antifungal coverage added for security. This contrast suggests that different Gloniopsis species, and different host immune states, can produce dramatically different disease spectra, ranging from a contained subcutaneous nodule to widespread disseminated infection.

For the authors, one of the most important lessons is geographic. A pathogen described on one continent caused an infection on another, in a patient with no identifiable travel history. How G. leucaenae reached Florida remains unknown, but the plausible explanations point to forces reshaping the microbial world. Global trade networks move plants, soil, timber, and agricultural products across oceans at unprecedented speed, and microscopic fungi hitchhike readily in these shipments. Climate change simultaneously alters temperature and rainfall patterns, expanding the ecological niches available to environmental molds and allowing them to establish populations far from where they were first catalogued. A fungus described from Thai plant material may now be living quietly in North American soil or vegetation, awaiting the right opportunity to inoculate a human host.

The report also underscores the diagnostic challenges posed by rare fungal infections. Phaeohyphomycosis itself is uncommon, and when it occurs, the causative agents span dozens of dematiaceous genera, including Alternaria, Exophiala, Bipolaris, and Curvularia. Traditional identification by morphology and culture is slow and often imprecise, and many environmental fungi fail to grow at all in the laboratory. Molecular methods such as broad-range PCR and sequencing have become indispensable, as they were here, where the organism would likely have remained nameless without genetic analysis. The authors argue that clinicians need to broaden the differential diagnosis for fungal infections, considering organisms that were previously regarded strictly as plant pathogens, particularly in patients with occupational or recreational exposure to vegetation.

There is also a pharmacological dimension worth noting. Vedolizumab, the biologic the patient was taking, is designed to minimize systemic immunosuppression by targeting the alpha-4-beta-7 integrin and limiting lymphocyte trafficking to the gut. Its safety profile is generally favorable with respect to opportunistic infections, which makes the appearance of an invasive fungal lesion in this patient noteworthy, even if the plant-matter inoculation likely explains the infection more directly than the medication does. The case raises open questions about whether gut-selective biologics alter skin-level fungal immunity in subtle ways, or whether the exposure burden of landscaping work simply overwhelmed local defenses. The report does not resolve this, but it flags the interaction between modern immunomodulatory therapies and environmental pathogens as an area deserving closer study.

Ultimately, the first human case of Gloniopsis leucaenae infection is less a story about one patient than about the changing map of fungal disease. Fungi are emerging as significant human pathogens at a growing pace, driven by international commerce, shifting climates, expanding immunosuppressed populations, and better molecular detection. Most Dothideomycetes will never harm a person, but the ones that occasionally do tend to arrive unannounced, hiding in a splinter of wood or a handful of soil. The Miami team’s careful integration of surgery, histopathology, and sequencing turned an anonymous hand swelling into a documented first, and their message to clinicians is clear: when a pigmented fungal infection appears, especially in someone who works with plants, the list of possible culprits is longer, and more global, than ever before.

Subject of Research: First human case of cutaneous phaeohyphomycosis caused by the plant-associated fungus Gloniopsis leucaenae

Article Title: Cutaneous phaeohyphomycosis with the recently described fungus Gloniopsis leucaenae: first case report

Article References: Sethia, S., Patel, M., Bakshi, R., Panthaki, Z. J., Villada, G. F., Salipante, S. J., & Gelman, M. A. (2026). Cutaneous phaeohyphomycosis with the recently described fungus Gloniopsis leucaenae: first case report. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14551-5

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14551-5

Keywords: Gloniopsis leucaenae, phaeohyphomycosis, fungal infection, Dothideomycetes, vedolizumab, broad-range PCR, itraconazole, plant pathogen, emerging infectious disease, case report, Florida, climate change

The patient was a 66-year-old man with hypertension and schizophrenia who had undergone bilateral burr-hole drainage at another hospital two years earlier to treat chronic subdural hematomas, collections of old blood that accumulate slowly between the dura mater and the brain surface, typically in older adults after minor head trauma. Burr-hole drainage is favored because it is minimally invasive and generally safe: surgeons drill a small opening in the skull, evacuate the liquid hematoma, and often leave a temporary drain. In this patient, drainage had been limited, the drain was removed after 48 hours, the wound healed well, and he was discharged without fever or any obvious complication. On the surface, the operation appeared to be a success.

Over the following two years, however, the man experienced recurrent, progressively worsening headaches, along with involuntary tongue protrusion and shaking of his limbs. His body temperature remained normal throughout, a detail that would later prove diagnostically misleading. Ten days before admission, he suffered a generalized tonic-clonic seizure that resolved spontaneously after roughly two minutes. Imaging performed on arrival revealed bilateral frontotemporoparietal hematomas of inhomogeneous density, including hyperdense areas and a significant mass effect on the brain. Those hyperdense regions suggested that the chronic hematomas had organized, meaning the liquid blood had transformed into a thick, fibrous, scar-like structure, a known but troublesome evolution of subdural collections.

Because organized hematomas cannot be drained through a burr hole, the surgical team concluded that conservative management or repeat drainage would fail to relieve the brain compression. After confirming that the patient had normal serum immunoglobulin levels and no immunosuppressive history, they performed a bilateral craniotomy to evacuate the hematomas. What they found in the operating room was unusual: the hematoma membrane had become abnormally thickened and organized, reaching approximately one centimeter at its thickest point, with a leathery, tough consistency. The cavity contained a small amount of yellowish fluid and abundant organized material with a distinctive sandy appearance. Recognizing that these findings deviated from a typical chronic subdural hematoma, the surgeons sent the membrane and its contents for pathological examination, a decision that would ultimately crack the case.

The patient was transferred to intensive care with a low-grade fever and lethargy, and empirical antibiotics were started. Five days after surgery, histopathological examination of the resected membrane revealed fibrous connective tissue with hyaline degeneration, hemosiderin deposition from old blood, and structures suggestive of fungal hyphae on hematoxylin and eosin staining. Specialized fungal stains, including Grocott’s methenamine silver and periodic acid-Schiff, could not be performed due to technical constraints at the treating institution, but the suspicious findings were enough to trigger a multidisciplinary team meeting. A lumbar puncture followed, revealing cerebrospinal fluid with a markedly elevated nucleated cell count dominated by polymorphonuclear cells, and a serum (1→3)-β-D-glucan test, which detects a cell wall component shared by many pathogenic fungi, came back positive. Empirical antifungal therapy with voriconazole was initiated, and a lumbar drain was placed for continuous cerebrospinal fluid drainage to limit fungal spread within the now widely opened subdural cavity.

Definitive identification came from the laboratory. Cerebrospinal fluid was inoculated onto Sabouraud dextrose agar and incubated at 35 degrees Celsius; after 48 hours, creamy-white, smooth, glistening colonies appeared, and Gram staining revealed ovoid budding yeast-like cells. Matrix-assisted laser desorption ionization-time of flight mass spectrometry, a technique that identifies microbes by the mass fingerprint of their proteins, identified the isolate as Candida parapsilosis with 99.9 percent confidence. Fungal spores were also visible on direct microscopic examination of the cerebrospinal fluid sediment. To rule out contamination and hematogenous spread, the team applied rigorous controls: sterile saline served as a negative control in all fungal cultures, three serial blood culture sets incubated for 14 days were all negative, and only isolates recovered from at least two independent specimens were accepted as true pathogens. Once the identification was confirmed, therapy was switched to targeted fluconazole at 400 milligrams daily.

The recovery was not smooth. The hospitalization was complicated by intestinal obstruction, pneumonia, and bacteremia, all managed successfully with supportive care and targeted antibiotics. A follow-up CT scan on postoperative day 40 showed near-complete absorption of the subdural fluid collection and good re-expansion of the brain. After completing eight weeks of antifungal therapy, the patient was discharged with only mild residual involuntary tongue protrusion, free of headaches and limb shaking. At three months after discharge, he remained asymptomatic, with no clinical or radiological evidence of recurrent infection.

The two-year latency period is the most scientifically provocative element of the case. The authors propose a multifactorial model to explain it. The most likely source is iatrogenic contamination during the original burr-hole drainage, since surgery is the most common route by which fungi enter the central nervous system, gaining access via the patient’s skin, the surgeon’s gloves, or contaminated instruments. Candida parapsilosis is a commensal of human skin with a well-characterized ability to form biofilms on plastic surfaces, which makes it a notorious cause of device-associated infections even when a drain is in place for only 48 hours. Biofilm fragments or colonized fungi can persist after device removal and serve as a reservoir for late-onset infection. The organized hematoma cavity itself may then function as an immune-privileged niche: relatively enclosed, hypoxic, iron-rich, and physically sequestered by a membrane up to a centimeter thick, it suppresses local immunity and shields the fungus from both host defenses and circulating antifungal drugs. This model neatly accounts for the patient’s two asymptomatic years, his persistently normal temperature, and his negative blood cultures.

The case also exposes a dangerous diagnostic blind spot. Chronic fungal infections of the central nervous system account for less than five percent of all central nervous system infections, but retrospective reviews of post-neurosurgical Candida infections report mortality rates exceeding 30 percent, with diagnostic delays being common. The insidious presentation here, progressive headache, a movement disorder, and a single seizure without fever, closely mimicked simple recurrence and organization of the original hematoma, and preoperative imaging could not distinguish a sterile organized hematoma from an infected one. The authors argue that atypical intraoperative findings, such as an abnormally thickened or leathery membrane, should prompt immediate submission of tissue for pathological and microbiological study. They also note that cerebrospinal fluid testing for (1→3)-β-D-glucan offers a rapid screening tool for preemptive diagnosis of iatrogenic fungal infections. Treatment, they emphasize, rarely succeeds with drugs alone: surgical resection of infected membranes and removal of contaminated material are essential, while fluconazole, which achieves cerebrospinal fluid concentrations of roughly 70 to 80 percent of serum levels, remains the drug of choice for fluconazole-susceptible C. parapsilosis. The team acknowledges the limitations inherent in a single case report: the exact route of infection could not be determined, antifungal susceptibility testing was not possible due to low specimen volume, and long-term follow-up will be needed to watch for late recurrence. Still, the message for surgeons and microbiologists alike is clear: when an old surgical site behaves strangely, the pathology laboratory may hold the answer that imaging cannot.

Subject of Research: A delayed intracranial Candida parapsilosis infection diagnosed two years after burr-hole drainage for chronic subdural hematoma

Article Title: Intracranial Candida parapsilosis infection occurring 2 years after burr-hole drainage for chronic subdural hematoma: a case report

Article References: Li, J., Lin, S., Liu, W., Li, P., & Luo, L. (2026). Intracranial Candida parapsilosis infection occurring 2 years after burr-hole drainage for chronic subdural hematoma: a case report. British Journal of Biomedical Science, 83, Article 16761. https://doi.org/10.3389/bjbs.2026.16761

Image Credits: AI Generated

DOI: 10.3389/bjbs.2026.16761

Keywords: Candida parapsilosis, chronic subdural hematoma, burr-hole drainage, fungal infection, neurosurgery, biofilm, cerebrospinal fluid, MALDI-TOF, voriconazole, fluconazole, case report, iatrogenic infection

The research, led by Richard Nyeko of Lira University and the University of Antwerp together with colleagues at the Uganda Cancer Institute, Mulago National Specialized Hospital, Mbarara Regional Referral Hospital and partner institutions in South Africa and Belgium, set out to quantify two of the most feared events in paediatric leukaemia care: induction failure and early death. Induction failure was defined as the inability to achieve microscopic remission after the first phase of chemotherapy, including deaths that occurred during induction itself. Early death was defined more starkly as death before, or within forty-two days of, starting induction therapy. That forty-two-day window is not arbitrary; it corresponds to the standard duration of the initial intensive chemotherapy block, the period when a child’s bone marrow is deliberately wiped out by cytotoxic drugs and when the risk of overwhelming infection and bleeding is at its peak.

Acute myeloid leukaemia is a cancer of the myeloid blood-forming cells, the lineage that normally produces neutrophils, monocytes, red cells and platelets. In AML, malignant precursors crowd out normal haematopoiesis, so children frequently arrive at hospital already neutropenic, anaemic and thrombocytopenic. Induction chemotherapy, typically built around an anthracycline such as daunorubicin or idarubicin combined with cytarabine, and in many contemporary protocols with etoposide, aims to clear the blasts from the marrow. The price of that clearance is profound myelosuppression: for several weeks the child has essentially no functional immune system. In centres in high-income countries, this window is managed with laminar-flow rooms or strict isolation, broad-spectrum antibiotics delivered at the first fever, empiric antifungal therapy, ready access to irradiated blood products, and intensive nutritional support. The Ugandan data describe what happens when several of those safeguards are missing or delayed.

Of the 159 children in the cohort, 87, or 54.7 percent, were male, and the median age at diagnosis was nine years. Nearly half the children, 62 of them or 39.0 percent, were malnourished when assessed using World Health Organization growth standards, including weight-for-height, body mass index-for-age and mid-upper-arm circumference z-scores. More than a third, 59 children or 37.1 percent, presented with a peripheral white blood cell count of at least 50,000 cells per microlitre, a marker of high tumour burden that carries its own risks, including leukostasis and tumour lysis. Only 149 of the children, 93.7 percent of the cohort, actually received induction chemotherapy, meaning that some children died or deteriorated before treatment could even begin, a phenomenon almost never seen in wealthy settings.

The headline numbers are sobering. Of the 149 children who received induction chemotherapy, 39, or 26.2 percent, experienced induction failure. Early death claimed 44 of the 159 children in the cohort, a rate of 27.7 percent. The causes of those deaths read like a catalogue of the complications that intensive care is designed to prevent: sepsis accounted for 35 percent of deaths, bleeding for 25 percent, organ failure for 15 percent, severe anaemia for 13 percent, and severe pneumonia with respiratory failure for 12 percent. In other words, the majority of children who died did so not because their leukaemia was chemoresistant, but because the treatment stripped away their defences while their bodies, already weakened by malnutrition and invasive infection, could not withstand the assault.

The statistical analysis, performed with logistic regression in IBM SPSS version 27, identified consistent risk factors. Induction failure was significantly associated with malnutrition, with presumed fungal infection, and with the absence of any assessment for central nervous system involvement at diagnosis. Early death was significantly associated with malnutrition, suspected fungal infection and pneumonia. The p-values for these associations ranged from 0.031 down to 0.005, and while the retrospective design means these are associations rather than proven causal relationships, the pattern is biologically coherent. Malnutrition impairs immune competence, wound healing and drug tolerance; invasive fungal infections flourish in profoundly neutropenic patients and are difficult to diagnose without advanced imaging and galactomannan or polymerase chain reaction testing; and pneumonia in a neutropenic child can progress to fatal respiratory failure within hours.

The finding that failure to assess central nervous system involvement at diagnosis was linked to induction failure deserves particular attention. In high-income protocols, lumbar puncture with cerebrospinal fluid examination is a standard part of the AML workup, because occult leukaemic involvement of the meninges can seed relapse and requires intrathecal therapy. In resource-limited settings, this assessment may be skipped because of staffing constraints, coagulation concerns in thrombocytopenic children, or the simple pressure of competing demands on a busy ward. The Ugandan results suggest that such omissions are not benign; they mark a subset of children whose disease is being understaged and, consequently, undertreated.

What emerges from this study is not a story of clinical failure by Ugandan oncologists but a demonstration of how structural inequity is written into survival statistics. The chemotherapy regimens used, built around cytarabine and anthracyclines, are internationally recognised. The difference lies in everything that surrounds the drugs: reliable supplies of broad-spectrum antibiotics and antifungals, the laboratory capacity to identify pathogens quickly, transfusion services that can deliver platelets on demand, dietitians and nutritional rehabilitation teams, and the human resources to monitor a neutropenic child around the clock. The authors found no funding associated with the work, and the study drew on records from three public institutions that serve much of Uganda’s paediatric oncology burden, giving the findings a representative weight that single-centre reports often lack.

The implications are concrete rather than abstract. If malnutrition is independently associated with both induction failure and early death, then nutritional assessment and aggressive early feeding support should be treated as core components of leukaemia therapy in low- and middle-income settings, not as an optional extra. If suspected fungal infection and pneumonia predict both outcomes, then empiric antifungal coverage, prompt fever evaluation and lower thresholds for starting antibiotics could save lives at modest cost. If missing CNS assessment marks children destined to fail induction, then a simple lumbar puncture protocol change, with platelet support where needed, is an achievable fix. The authors emphasise the need for improved supportive care and early management of complications, and their data show exactly where that investment should be directed.

Globally, childhood cancer survival has become one of the most inequitable metrics in medicine: overall survival in high-income countries now exceeds eighty percent for many paediatric malignancies, while in much of sub-Saharan Africa the majority of children with cancer still die. AML is among the hardest cases, because its treatment is so immunologically destructive that cure depends as much on intensive care as on chemotherapy itself. This Ugandan cohort, with its 27.7 percent early death rate and its clear linkage of mortality to malnutrition and infection, quantifies that dependency with unusual clarity. The forty-two days after a child with AML begins treatment are a physiological gauntlet; in Kampala and Mbarara as much as in any city, but with far fewer nets strung beneath the tightrope. The study’s message to the global paediatric oncology community is that exporting drug protocols is not enough, and that the next great gains in childhood cancer survival in Africa will come from the unglamorous infrastructure of supportive care.

Subject of Research: Induction failure and early death in paediatric acute myeloid leukaemia in Uganda

Article Title: Induction failure and early death in paediatric acute myeloid leukaemia in Uganda: a developing country experience

Article References: Nyeko, R., Kruger, M., Niyonzima, N., Atwiine, B., Kambugu, J. B., Verhulst, S., & van Heerden, J. (2026). Induction failure and early death in paediatric acute myeloid leukaemia in Uganda: a developing country experience. BMC Cancer. https://doi.org/10.1186/s12885-026-16989-x

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16989-x

Keywords: acute myeloid leukaemia, paediatric oncology, induction failure, early death, malnutrition, fungal infection, sepsis, pneumonia, supportive care, Uganda, low- and middle-income countries, chemotherapy

The research, published in BMC Nursing, was conducted at the Children’s Cancer Hospital Egypt (CCHE) 57357, one of the largest pediatric oncology centers in the Middle East. A team of nursing researchers led by Amira El-Sayed of October 6 University in Giza set out to answer a deceptively simple question: if you teach pediatric oncology nurses about mucormycosis in a systematic way, do their knowledge and their actual bedside practices improve? The answer, measured with rigorous before-and-after assessments, was a resounding yes, at least in the short term. The findings arrive at a moment when clinicians worldwide are paying renewed attention to fungal infections, which are increasingly recognized as a growing danger for patients whose immunity has been compromised by cancer therapy, transplantation, or other modern medical interventions.

Mucormycosis is caused by fungi in the order Mucorales, ubiquitous organisms that most healthy people encounter daily without consequence. In an immunocompromised host, however, these molds can germinate and invade blood vessels, causing tissue death, a process known as angioinvasion. The disease can manifest in the rhinocerebral form, attacking the sinuses and brain; the pulmonary form, destroying lung tissue; or the gastrointestinal and cutaneous forms, each carrying substantial mortality. Children with hematologic malignancies such as leukemia, and those undergoing hematopoietic stem cell transplantation, sit squarely in the highest-risk category. Neutropenia, the depletion of infection-fighting white blood cells induced by chemotherapy, removes the body’s primary cellular defense against these fungi. Because early diagnosis is difficult and treatment options are limited, prevention becomes paramount, and prevention in a hospital setting depends heavily on the vigilance of nursing staff.

Nurses occupy a uniquely influential position in infection prevention. They control the environment around the patient, from the cleanliness of surfaces and equipment to the handling of food, the management of personal protective equipment, and the early recognition of warning signs. Yet studies have repeatedly shown that knowledge about rare fungal infections among nursing staff can be patchy, particularly in resource-limited settings where formal training on emerging pathogens may be scarce. The Egyptian research team recognized this gap and designed a quasi-experimental study to test whether targeted education could close it. They enrolled 81 pediatric oncology nurses at CCHE 57357, measuring their baseline knowledge with a structured questionnaire and their actual infection-control behaviors with an observational checklist completed at the bedside.

The educational intervention itself consisted of three structured sessions covering the risk factors for mucormycosis, its pathophysiology, and the infection control measures that nurses can implement in daily practice. This content was not exotic. It included fundamentals such as environmental hygiene, appropriate use of personal protective equipment, meticulous hand hygiene, safe food handling for neutropenic patients, and surveillance for early signs of infection. But the study’s design ensured that the effect of this teaching could be quantified. Every participant completed the same knowledge assessment before and after the program, and trained observers evaluated the same set of practices using the same checklist at both time points, allowing direct comparison of scores across the intervention.

The results were striking. The mean knowledge score nearly doubled, rising from 5.82 plus or minus 0.91 before the program to 12.1 plus or minus 0.76 afterward, a difference that was statistically significant with a p-value below 0.001. The mean practice score, reflecting what observers actually saw nurses do rather than what they claimed to know, climbed from 3.86 plus or minus 1.13 to 7.58 plus or minus 1.02, also highly significant. In other words, the training did not merely fill heads with facts; it changed hands-on behavior at the bedside. Nurses who had completed the sessions were demonstrably more likely to perform the preventive measures that the checklist captured, from environmental controls to protective equipment use.

Equally interesting was the relationship between knowledge and practice. The researchers found a positive correlation between the two at both time points: before the intervention, the correlation coefficient was 0.348 with a p-value of 0.001, and after the intervention it was 0.382 with a p-value below 0.001. This suggests that what nurses know is linked to what they do, and that strengthening knowledge may be a viable pathway to strengthening practice. The correlation is moderate rather than perfect, which is a familiar pattern in health-services research; knowing the right thing does not always translate into doing it, particularly under the time pressures and staffing constraints of a busy oncology ward. But the consistency of the association before and after training reinforces the case for education as a lever for behavioral change.

The authors are careful, and rightly so, about the limits of what their study can claim. Because the design was a one-group pretest-posttest study without a control group, and because patient outcomes were not tracked, the findings cannot be interpreted as evidence that the training reduced actual mucormycosis infection rates. No children were followed to see whether their risk of fungal infection declined. The improvements measured were in nurse knowledge and observed practice, over a short-term horizon, and the study cannot rule out other explanations for the change, such as heightened attention from being observed or the general effect of participating in a research project. These are standard caveats for this study design, but they matter for anyone hoping to translate the results into policy.

Nevertheless, the study carries real weight for a field that urgently needs practical solutions. Invasive fungal infections in pediatric cancer patients are associated with prolonged hospitalizations, expensive antifungal therapy, and significant mortality, and the arsenal of preventive tools is limited. Environmental measures and vigilant nursing care are among the few interventions available on the front lines, and they cost far less than new drugs. If a three-session educational program can nearly double knowledge scores and substantially improve observed infection-control behavior among nurses caring for the most vulnerable children, that is an intervention worth replicating and testing more rigorously. The Egyptian team’s work provides a template: a structured curriculum, validated assessment tools, and an observational checklist that other institutions could adapt.

The broader lesson extends beyond mucormycosis. As fungal infections gain prominence in global health discussions, driven by rising numbers of immunocompromised patients and growing awareness of fungal threats, the healthcare workforce’s preparedness becomes a critical variable. This study demonstrates that targeted, relatively brief professional education can move the needle on both knowledge and practice in a specialized nursing population. The authors call for continuous professional development and targeted training to sustain and build on these gains, a reminder that a single educational burst is unlikely to be enough. For the nurses of CCHE 57357 and the children they care for, the message is clear: understanding the enemy is the first step in defending against it, and that understanding can be taught.

Subject of Research: Effect of a structured educational program on pediatric oncology nurses' knowledge and mucormycosis-prevention practices

Article Title: Changes in pediatric oncology nurses’ knowledge and observed mucormycosis-prevention practices following an educational programme: a one-group pretest-posttest study

Article References: El-Sayed, A., Alsharkawy, S., Hassan, E. A., Wahid, H., Ragab, N., & El-Hamid, H. A. (2026). Changes in pediatric oncology nurses’ knowledge and observed mucormycosis-prevention practices following an educational programme: a one-group pretest-posttest study. BMC Nursing, 25(1), Article 966. https://doi.org/10.1186/s12912-026-05382-5

Image Credits: AI Generated

DOI: 10.1186/s12912-026-05382-5

Keywords: mucormycosis, pediatric oncology, nursing education, infection control, fungal infection, chemotherapy, immunocompromised children, quasi-experimental study, Egypt, nurse training, knowledge and practice, BMC Nursing

The clinical puzzle began innocuously. Chest tightness and exertional dyspnea are nonspecific complaints, and the finding of diffuse pulmonary nodules on computed tomography opens a dauntingly broad differential diagnosis that spans sarcoidosis, tuberculosis, fungal infections, metastatic malignancy, and autoimmune vasculitis. Each possibility demands a different therapeutic pathway, and choosing wrongly can cost precious weeks. In the first round of testing, the clinicians performed bronchoscopy and collected bronchoalveolar lavage fluid, the saline washings that sample the cells and secretions lining the deep airways. Targeted next-generation sequencing, a technique that amplifies and sequences the DNA of a predefined panel of likely pathogens, detected Streptococcus pneumoniae, the bacterium best known as a cause of community-acquired pneumonia. On the face of it, the result seemed to offer a straightforward answer, and the patient was started on empirical antibacterial therapy directed against the pneumococcus.

The treatment failed. Follow-up chest imaging showed that the pulmonary lesions continued to progress despite the antibiotics, a red flag that the detected bacterium was more likely a bystander, a colonizer of the airways, or a reflection of the lavage fluid’s mixed microbial content than the true driver of disease. This distinction matters enormously in modern respiratory medicine. The human lung is not sterile in the way textbooks once assumed, and sequencing technologies are sensitive enough to detect trace amounts of DNA from organisms that play no pathogenic role. A positive molecular result, in other words, is a clue rather than a verdict, and the Hangzhou team treated it accordingly, escalating the workup rather than simply switching antibiotics in a blind rotation.

The decisive step came through transbronchial lung cryobiopsy, a technique in which a frozen probe is passed through a bronchoscope and briefly supercooled to adhere to lung tissue, allowing a larger and better-preserved specimen to be extracted than is possible with conventional forceps biopsy. Histopathological examination of the biopsy revealed granulomatous inflammation, the organized clusters of immune cells, including macrophages and multinucleated giant cells, that the body deploys when it cannot quickly eliminate a persistent irritant. Granulomas are the lung’s signature response to certain infectious agents, most famously Mycobacterium tuberculosis, but also to fungi, foreign material, and the idiopathic processes behind sarcoidosis. Yet here the special stains routinely used to visualize pathogens in tissue, including Periodic acid-Schiff staining for fungi and searches for mycobacterial DNA, came back negative, leaving the pathologists with an inflammatory pattern but no visible culprit.

Into this evidentiary gap stepped metagenomic next-generation sequencing, or mNGS, an unbiased approach that sequences all nucleic acid extracted from a clinical sample and then computationally maps the millions of resulting reads against databases of known genomes. Unlike targeted panels, mNGS makes no assumptions about which organisms might be present, which is precisely why it excels at detecting unexpected or fastidious pathogens. When the team applied mNGS to the patient’s bronchoalveolar lavage fluid, the analysis identified 88 sequencing reads assigned to Exophiala oligosperma, corresponding to a normalized abundance of 34 reads per ten million, a metric known as RPTM that helps distinguish genuine signal from background noise. The organism is a melanized fungus, its dark pigmentation derived from cell-wall melanin, and it belongs to a genus notorious for causing phaeohyphomycosis, a spectrum of infections that range from superficial skin colonization to deep, occasionally disseminated disease, particularly in immunocompromised hosts.

Pulmonary infection by Exophiala oligosperma is vanishingly rare, and the authors of the report describe their case as extremely uncommon in the medical literature. The fungus thrives in wet environments, having been isolated from shower drains, sink traps, and other biofilm-rich niches of the built environment, and human exposure is plausibly far more frequent than recognized disease. Why this particular patient developed granulomatous lung inflammation remains unresolved; the report does not establish an obvious immunodeficiency, and the interplay between host immunity and this opportunistic organism is an open question. What the case does establish is that when histology shows granulomas and special stains are negative, the pathogen may still be present in quantities too low for microscopy but detectable by the deep sequencing of lavage fluid.

Diagnosis in such cases is deliberately hedged. The authors classified the illness as probable pulmonary Exophiala oligosperma infection rather than proven infection, a distinction that reflects the standards of fungal disease diagnostics. Definite proof typically requires culture of the organism or demonstration of fungal elements invading tissue on histology, neither of which was achieved here. Instead, the diagnosis rested on the integration of four streams of evidence: the clinical presentation, the progressive nodular imaging findings, the granulomatous histopathology, and the molecular detection of the fungus in lavage fluid. This composite approach, the authors argue, is indispensable, because relying on histopathological sections alone frequently proves difficult and lacks adequate sensitivity. The caution embedded in the word probable is not academic timidity but an honest reflection of how molecular medicine is reshaping, and sometimes straining, traditional diagnostic categories.

The therapeutic response provided the final piece of corroborating evidence. The patient received nine weeks of antifungal therapy, and at the three-month follow-up after the drugs were discontinued, chest computed tomography demonstrated complete resolution of the pulmonary lesions. In infectious disease, the resolution of lesions after targeted therapy is itself a diagnostic test of sorts, a natural experiment in which removing the presumed cause removes the disease. A pneumococcal pneumonia would not have persisted through a course of appropriate antibiotics, and the failure of antibacterial treatment followed by the success of antifungal treatment brackets the causal role of the fungus with unusual clarity for a single case.

Beyond its clinical narrative, the report carries broader implications for the differential diagnosis of pulmonary granulomatous inflammation. Tuberculosis remains the dominant concern worldwide whenever granulomas appear in lung tissue, and the Hangzhou team appropriately excluded mycobacterial disease through dedicated testing, including assessment for Mycobacterium tuberculosis DNA. But as molecular diagnostics proliferate, clinicians are increasingly encountering fungi that were previously invisible to routine workflows. The Exophiala genus, and black yeasts generally, sit at the margins of most laboratories’ routine identification capabilities, and without mNGS this patient’s infection would almost certainly have gone unnamed, perhaps misclassified as sarcoidosis or another idiopathic granulomatous condition and treated with immunosuppression, a strategy that could have been actively harmful if a living pathogen were driving the inflammation.

The case also underscores a methodological lesson that is rippling through infectious disease practice: sequencing results must always be weighed against clinical context. The initial targeted panel’s detection of Streptococcus pneumoniae was technically accurate but clinically misleading, while the metagenomic detection of a rare fungus at modest read depth proved decisive only because it aligned with the histology, the imaging trajectory, and the treatment response. The authors, Xiaohong Wu, Fan Yang, Zhiyao Xu, and Wenjing Ruan, present their findings as valuable clinical evidence for the recognition and differential diagnosis of atypical fungal pulmonary diseases, and the phrase captures the report’s real contribution. For physicians confronting diffuse pulmonary nodules and granulomatous inflammation of uncertain cause, the message is that the answer may lie in organisms too rare, too slow-growing, or too fastidious for conventional detection, and that the combination of cryobiopsy histology and unbiased metagenomic sequencing of lavage fluid offers a route to diagnoses that were effectively unattainable a decade ago.

Subject of Research: Pulmonary granulomatous inflammation associated with the rare fungus Exophiala oligosperma, diagnosed using metagenomic next-generation sequencing

Article Title: Probable Exophiala oligosperma-associated pulmonary granulomatous inflammation: a case report

Article References: Wu, X., Yang, F., Xu, Z., & Ruan, W. (2026). Probable Exophiala oligosperma-associated pulmonary granulomatous inflammation: a case report. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14470-5

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14470-5

Keywords: Exophiala oligosperma, pulmonary granulomatous inflammation, metagenomic next-generation sequencing, bronchoalveolar lavage fluid, fungal infection, diffuse pulmonary nodules, transbronchial cryobiopsy, antifungal therapy, black yeast, BMC Infectious Diseases, case report, molecular diagnostics

The core principle of a chimeric antigen receptor is elegant: a synthetic receptor is built by fusing an antibody-derived recognition domain to the intracellular signaling machinery of the T-cell receptor. When the recognition domain binds its target antigen on a cell surface, the signaling domains activate the T cell, triggering killing of the target cell, proliferation and cytokine release. In cancer, this has produced dramatic remissions in patients with relapsed leukemias and lymphomas. In infection, the theoretical appeal is equally strong. Chronic pathogens such as HIV, hepatitis B virus, Epstein-Barr virus and cytomegalovirus establish reservoirs inside host cells that evade or exhaust the natural immune response, and conventional antimicrobial drugs often cannot reach or eliminate these sanctuaries. An engineered T cell, in principle, could seek out infected cells wherever they hide.

The review identifies three distinct recognition classes that have emerged in the field. The first targets pathogen surface structures, molecules displayed directly by the infectious agent itself. The second targets infected-cell surface antigens, host or viral proteins that appear on the membrane of a cell once it has been hijacked. The third and most sophisticated class targets pathogen-derived peptide-human leukocyte antigen complexes, in which fragments of microbial proteins are presented on the cell surface by HLA molecules, mimicking the way natural T cells recognize infection. Each class carries distinct trade-offs in specificity, coverage and safety, and the choice among them shapes everything downstream, from receptor affinity tuning to the risk of off-tumor, off-infection tissue damage.

HIV provides the most mature clinical evidence base. Because the virus infects and ultimately depletes the very CD4 T cells that a CAR approach would deploy, researchers have had to engineer HIV-specific CARs into cells resistant to infection, and early clinical studies have demonstrated that such products can persist long-term in patients. Encouragingly, trials have recorded reductions in reservoir-associated markers, suggesting that engineered cells can reach and engage the latent viral reservoir that antiretroviral therapy suppresses but never eradicates. The critical limitation, however, is equally clear: no study has yet achieved reproducible control of HIV without ongoing antiretroviral therapy. The engineered cells persist and function, but they have not yet delivered a functional cure, and the review is careful to frame current results as proof of biological feasibility rather than therapeutic victory.

The hepatitis viruses illustrate a different set of challenges. Studies of CAR-T cells directed against hepatitis B virus, including targets such as the hepatitis B surface antigen, have shown that engineered cells can recognize and eliminate infected hepatocytes. But the liver is an unforgiving arena. Eliminating infected hepatocytes en masse risks hepatic injury in organs already compromised by chronic inflammation and, in some patients, by hepatocellular carcinoma. Epstein-Barr virus and cytomegalovirus programs have produced evidence that infected cells can be recognized, but they have also exposed two recurring problems: antigen expression on infected cells is variable and often heterogeneous, meaning that cells with low or absent target levels escape killing, and infected cells can actively resist lysis through immune-evasion mechanisms honed over long co-evolution with their hosts.

Perhaps the most surprising frontier is fungal infection. The review describes preclinical CAR-T cells engineered to recognize fungal cell wall components, including β-glucan, hyphal antigens, glucuronoxylomannan, the capsular polysaccharide of Cryptococcus, and mannan. These constructs have shown activity against fungal pathogens in laboratory and animal models, opening a genuinely novel therapeutic category for invasive fungal disease, which carries high mortality in immunocompromised patients and is increasingly threatened by antifungal drug resistance. Bacterial targets, by contrast, remain largely untouched. Direct antibacterial CAR-T evidence is minimal, and the reason is fundamental rather than technical: bacterial clearance in the body depends heavily on phagocytes and the complement system, effector mechanisms that a cytotoxic T cell does not replicate. A CAR-T cell is optimized to kill host cells, not to engulf or opsonize extracellular bacteria.

Across all pathogens, the review catalogs a shared set of constraints that repeatedly blunt efficacy. Antigens may be dynamic, appearing and disappearing as infection cycles progress, or soluble, circulating in the blood and acting as decoys that exhaust engineered cells before they reach their targets. Tissue reservoirs, particularly in sanctuary sites with poor T-cell trafficking, remain hard to reach. The patient’s own T cells, the raw material for manufacturing, are often impaired by the very infection being treated, yielding products with poor fitness. Manufacturing delay is another critical variable: acute infections move on a timescale of days, while autologous cell production takes weeks, demanding either allogeneic off-the-shelf platforms or infections with a stable, chronic treatment window. Finally, organ-specific inflammation in infected tissues amplifies the risk of cytokine release syndrome and collateral damage.

The engineering response to these problems is already substantial. Multispecific receptors that recognize several antigens simultaneously can counter antigen escape. Transient or switchable receptor designs, in which CAR expression or activity can be controlled with an administered drug, offer a dose-control mechanism that oncology CAR-T lacks. Safety switches allow engineered cells to be eliminated if toxicity escalates. Local delivery, depositing cells directly into infected tissue such as the liver or the central nervous system, may bypass trafficking barriers. Checkpoint modulation, blocking inhibitory pathways such as PD-1 and PD-L1, can rescue exhausted products, while cytokine-armored designs engineer cells to secrete supportive factors like interleukins or interferon-γ that sustain their own function in hostile tissue. Longitudinal blood-based monitoring, tracking engineered cell persistence and reservoir markers over time, is proposed as the framework for measuring whether any of these interventions actually works.

The review’s most consequential contribution may be its prioritization framework. Rather than chasing every pathogen, the authors argue that development should concentrate on infections with stable target exposure, a treatment window compatible with cell delivery timelines, measurable microbiological endpoints that can demonstrate effect in trials, and a tolerable consequence of eliminating infected cells. That last criterion is the subtlest: in cancer, destroying the target cell is the goal, but in chronic hepatitis B, for example, every infected hepatocyte killed is liver tissue lost, so the therapeutic index depends on the liver’s capacity to regenerate and on how precisely the receptor discriminates infected from healthy cells. Clinical progress, the authors conclude, will depend on matching the engineered effector mechanism to pathogen biology, tissue location and host immune status, a discipline-specific calibration that no oncology playbook can provide.

What emerges from the analysis is a field at an inflection point. The biology has been proven in principle: engineered cells can persist in patients, traffic to infected tissues, engage viral reservoirs and reduce disease-associated markers. The engineering toolkit for safety, control and multi-target recognition is maturing rapidly, and preclinical fungal programs suggest the concept extends beyond viruses. Yet the distance between reservoir-marker reduction and therapy-free control remains wide, and the review is explicit that every proposed improvement, from switchable receptors to armored cytokines, requires infection-specific validation rather than extrapolation from cancer data. If that validation succeeds, the coming years could see cellular immunotherapy expand from the oncology ward into infectious disease units, offering a precision weapon against pathogens that have so far outlasted every drug aimed at them.

Subject of Research: CAR-T-cell immunotherapy for infectious diseases

Article Title: CAR-T-cell therapy for infectious diseases: from concept to clinic

Article References: Su, S., Zhou, M., Chen, L., Zhu, X., & Xiao, Y. (2026). CAR-T-cell therapy for infectious diseases: from concept to clinic. Journal of Translational Medicine. https://doi.org/10.1186/s12967-026-08906-4

Image Credits: AI Generated

DOI: 10.1186/s12967-026-08906-4

Keywords: CAR-T-cell therapy, infectious diseases, HIV, hepatitis B virus, Epstein-Barr virus, cytomegalovirus, fungal infection, antimicrobial immunity, cellular therapy, target antigens, chimeric antigen receptor, immunotherapy

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