Effects of Amphotericin B-Conjugated Functionalized Carbon Nanoparticles in the Treatment of Cutaneous Leishmaniasis.

Leishmaniasis is a parasitic disease spread by the bite of an infected sandfly and caused by protozoan parasites of the genus Leishmania. Currently, there is no vaccine available for leishmaniasis in humans, and the existing chemotherapy methods face various clinical challenges. The majority of drugs are limited to a few toxic compounds, with some parasite strains developing resistance. Therefore, the discovery and development of a new anti-leishmanial compound is crucial. One promising strategy involves the use of nanoparticle delivery systems to accelerate the effectiveness of existing treatments. In this study, Amphotericin B (AmB) was incorporated into functionalized carbon nanotube (f-CNT) and evaluated for its efficacy against Leishmania major in vitro and in a BALB/c mice model. The increase in footpad thickness was measured, and real-time PCR was used to quantify the parasite load post-infection. Levels of nitric oxide and cytokines IL-4 and IFN-γ were also determined. We found that f-CNT-AmB significantly reduced the levels of promastigotes and amastigotes of the Leishmania parasite. The nanoparticle showed strong anti-leishmanial activity with an IC50 of 0.00494 ± 0.00095 mg/mL for promastigotes and EC50 of 0.00294 ± 0.00065 mg/mL for amastigotes at 72 h post-infection, without causing harm to mice macrophages. Treatment of infected BALB/c mice with f-CNT-AmB resulted in a significant decrease in cutaneous leishmania (CL) lesion size in the foot pad, as well as reduced Leishmania burden in both lymph nodes and spleen. The levels of nitric oxide and IFN-γ significantly increased in the f-CNT-AmB treated groups. Also, our results showed that the level of IL-4 significantly decreased after f-CNT-AmB treatment in comparison to other groups. In conclusion, our results demonstrate that AmB loaded into f-CNT is significantly more effective than AmB alone in inhibiting parasite propagation and promoting a shift towards a Th1 response.

Tropicoporus tropicalis: A Newly Recognised Pathogen in Eumycetoma and Refractory Mycoses in Humans.

Tropicoporus tropicalis (formerly Phellinus tropicalis) is a saprophytic basidiomycete that has been implicated in refractory mycoses in humans, particularly in patients with chronic granulomatous disease. Despite its clinical significance, T. tropicalis is an under-recognised cause of eumycetoma, with no prior reports available. We present a case of white grain eumycetoma with associated osteomyelitis of the left foot, caused by T. tropicalis, confirmed through 18S-ITS1-5.8S-ITS2-28S rRNA gene amplification and sequencing. The patient was treated with itraconazole 200 mg daily, leading to gradual improvement. A review of the literature on T. tropicalis infections in humans reveals its characteristic manifestations, which include osteomyelitis, soft tissue abscesses, pulmonary nodules and keratitis. These infections are locally destructive but have the potential to disseminate. Diagnosis is often delayed and relies on molecular techniques. Amphotericin B combined with an azole appears to be the most effective treatment, often necessitating concurrent surgical drainage. In conclusion, T. tropicalis is a newly recognised pathogen associated with eumycetoma and poses an increased risk of osteomyelitis. Molecular identification, such as sequencing the internal transcribed spacer (ITS) region from cultures or tissue specimens, is crucial for accurate identification of this pathogen.

Mucosal leishmaniasis of the lips and cheeks: a first concomitant presentation of visceral and mucosal leishmaniasis in a patient living with HIV/AIDS in Monastir, Tunisia.

BACKGROUND: Visceral Leishmaniasis (VL) is the most severe and fatal disease if left untreated. In people living with HIV/AIDS (PLHA), VL is considered an emerging opportunistic infection. The aim of this manuscript was to report a first case in Tunisia of a concomitant presentation of visceral and oral leishmaniasis in a patient LHA. A systematic review of the literature was performed according to PRISMA guidelines, as well. CASE PRESENTATION: The patient, a 43-year-old heterosexual man, treated for HIV/AIDS was referred for macrocheilitis of the upper and lower lips. A noticeable nodular and painless swelling extending to the cheeks' mucosa was noted. The patient's poor oral hygiene was evident due to the presence of multiple dental caries. Histological analysis of the biopsied lower lip sample revealed the presence of numerous Leishmania amastigotes. The diagnosis of VL was clinically confirmed by the presence of a mild splenomegaly and pancytopenia and biologically by the identification of the parasite using PCR Lei and the species L. infantum involved using RFLP-PCR and culture. The treatment consisted of an intravenous administration of liposomal Amphotericin B (Ambisome®, 40 mg/kg/weight) for a period of 6 weeks. A favorable outcome was noted after one year with the resolution of clinical symptoms and a negative Leishmania blood PCR test. After 2 years, the patient remained asymptomatic but showed a positive Leishmania blood PCR test. Dolutegravir® was introduced in the patient's ART regimen. CONCLUSIONS: To the best of our knowledge, this is the first case report in Tunisia of atypical VL diagnosed through an uncommon oral location in an HIV/AIDS co-infected patient . Since VL is a severe and potentially fatal disease, it is essential for dentists to perform a thorough clinical examination and adopt a multidisciplinary approach in order to ensure an early diagnosis and an effective treatment outcome.

Spinal subdural abscess following chronic meningitis - A rare manifestation of Mucormycosis.

A 57-year old man with uncontrolled diabetes presented with features suggestive of chronic meningitis. Cerebrospinal fluid (CSF) analysis revealed a polymorphonuclear pleocytosis with low glucose and high protein levels in the CSF. Bacterial and fungal cultures and tests for M. tuberculosis were negative. MRI spine showed leptomeningeal enhancement. On ruling out other causes, fungal meningitis was considered. The patient developed paraparesis in the hospital. MRI showed peripherally enhancing subdural lesion with dorsal cord involvement at the level of D4 and D5 vertebrae. On laminectomy and exploration, an intradural extramedullary abscess and a granuloma were noticed at T4--T5 spinal levels causing compression of the cord below. Histopathological examination of the lesions revealed acute on chronic inflammatory infiltrates interspersed by broad, aseptate, ribbon-like fungal elements highlighted by PAS stain, diagnostic of mucormycosis. Intravenous amphotericin B and oral posaconazole were administered for more than 8 weeks. On follow-up, he had complete neurological recovery without sequelae.

Safety of different amphotericin B formulations among AIDS patients with invasive fungal disease: a retrospective observational study.

We conducted a retrospective, observational study among acquired immune deficiency syndrome (AIDS) patients with cryptococcal meningitis or talaromycosis to assess AmB formulations-related adverse events (AEs). Total 205 eligible patients were enrolled. Of them, 139 received AmB therapy, 51 received liposomal AmB (L-AmB) therapy, and 15 received AmB cholesteryl sulfate complex (ABCD) therapy. The incidences of total AEs between the AmB, L-AmB and ABCD group had no significant differences. The ABCD group had significantly higher incidences of hepatotoxicity and hematological toxicity than the AmB and L-AmB groups. The incidence of grade 3-4 hematological toxicity in the ABCD group was significantly higher than that in the AmB and L-AmB groups. Multinomial logistic regression models showed that compared with AmB, ABCD had a higher risk for the occurrence of grade 3-4 hematological toxicity (aOR = 43.924, 95%CI 6.296-306.418; p < 0.001). We demonstrated that ABCD was more prone to hepatotoxicity and hematological toxicity than AmB and L-AmB among AIDS patients, which is worth noting.

Visceral leishmaniasis complicated with hemophagocytic lymphohistiocytosis and resistant to amphotericin B: a case report.

INTRODUCTION: Hemophagocytic lymphohistiocytosis characterized by hemophagocytosis leading to uncontrolled inflammation; the most common etiology in secondary cases of hemophagocytic lymphohistiocytosis is viral infections, especially Epstein-Barr virus. Visceral leishmaniasis is a vectorborne protozoal disease caused by Leishmania donovani complex. It is common in tropical and subtropical regions, with 50,000-90,000 new cases annually. CASE PRESENTATION: A 15-month-old Arab female was admitted to our hospital with 15 days of fever and decreased weight. On clinical examination, she had a markedly enlarged liver and spleen that were palpable 4 cm and 6 cm below the costal margin, respectively. The peripheral blood smear showed hypochromic microcytic anemia, poikilocytosis, reactive lymphocytosis, and mild thrombocytopenia. Bone marrow aspiration did not show malignancy or any other pathological findings. The patient was put on antibiotic therapy without improvement. Repeated bone marrow aspiration showed erythrophagocytosis; intracellular small round organisms looked like the amastigote form of Leishmania (Donovan bodies) with no evidence of malignancies. Her lab values showed ferritin greater than 500 ug/L, pancytopenia, and hypertriglyceridemia. The patient was diagnosed with hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis. CONCLUSION: Hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis is an extensively rare phenomenon in the medical literature that causes challenges in diagnosis and management. Steroids should be used wisely to not cover the symptoms of infections or malignancy, and amphotericin B resistance should be kept in mind in unresponsive Leishmania cases.

Rapid Vision Loss After Root Canal Treatment Due to Invasive Fungal Sinusitis.

We present a novel case of acute invasive fungal rhinosinusitis (AIFRS) following a maxillary molar root canal in a 69-year-old diabetic female, who subsequently developed unilateral vision loss. The patient reported a 1-week history of progressive left facial pain, trismus, and numbness following the procedure. Initial evaluation was unremarkable, but her condition rapidly deteriorated, culminating in complete vision loss in the left eye. Imaging studies revealed opacification of the left-sided sinuses and a rim-enhancing collection in the left pterygopalatine fossa. Surgical debridement confirmed mucormycosis. The therapeutic approach included systemic and retrobulbar amphotericin B administration, along with multiple sinonasal debridements. The patient's poorly controlled diabetes mellitus significantly contributed to the rapid progression of the infection. Retrobulbar amphotericin B injections were effective in managing orbital involvement, thus avoiding the need for exenteration. Early diagnosis and aggressive treatment are paramount in improving outcomes for patients with AIFRS.

[Clinical efficacy and safety of liposomal amphotericin B in the salvage treatment of invasive fungal disease in patients with hematological diseases].

Objective: To investigate the efficacy and safety of liposomal amphotericin B (L-AmB) for the salvage treatment of invasive fungal disease (IFD) in patients with hematological diseases. Methods: Data were retrospectively collected from 80 patients with hematological issues treated with L-AmB between June 2023 and December 2023 after failure of previous antifungal therapy. Baseline patient information, clinical efficacy, and factors affecting the efficacy of L-AmB were analyzed by logistic regression. Moreover, adverse effects associated with L-AmB were evaluated. Results: Among the 80 patients, 9 (11.2%) had proven IFD, 43 (53.8%) had probable IFD, and 28 (35.0%) had possible IFD. The efficacy rate of L-AmB salvage therapy for IFD was 77.5%, with a median daily dose of 3 (range: 1-5) mg·kg(-1)·d(-1) and a median dosing course of 14 (range: 8-25) days. Multivariate logistic regression analysis showed that the disease remission status (OR=4.337, 95% CI 1.167-16.122, P=0.029) and duration of medication (OR=1.127, 95% CI 1.029-1.234, P=0.010) were independent factors affecting the efficacy of L-AmB. The incidence of infusion reactions associated with L-AmB, including fever and chills, was 5.0%. The incidence of hypokalemia was 28.8% (predominantly grades 1-2), and the incidence of nephrotoxicity was 11.3% (predominantly grades 1-2) . Conclusion: L-AmB is safe and effective in the treatment of patients with IFD who are intolerant to or who have experienced no effect of previous antifungal therapy, with a low rate of adverse reactions.

Successful treatment of mixed pulmonary Aspergillus and Mucor infection using intrabronchial amphotericin B infusion: a case report and literature review.

BACKGROUND: Reports of pulmonary aspergillosis and mucormycosis co-infections are rare; thus, limited guidance is available on early diagnosis and treatment. We present a case of mixed pulmonary Aspergillus and Mucor infection and review the literature regarding this co-infection. The diagnosis and treatment methods are summarized to improve clinicians' understanding of the disease and to facilitate early diagnosis and treatment. CASE PRESENTATION: A 60-year-old male farmer with poorly controlled diabetes mellitus was admitted to hospital with a fever of unknown origin that had been present for 15 days and pulmonary aspergillosis complicated by Mucor spp. INFECTION: Because multiple lobes were involved, the infection worsened despite surgical resection and antifungal therapy. Finally, we treated this patient with a bronchoscopic infusion of amphotericin B. After four courses of bronchoscopic amphotericin B infusion, we observed rapid clinical improvement and subsequent resolution of pulmonary infiltrates. CONCLUSION: Our case highlights the use of bronchoscopy in the successful clinical treatment of invasive fungal diseases of the lung.

Targeted orbital intervention in the management of sino-orbital mucormycosis cases.

INTRODUCTION: Many countries from South-East Asia reported an epidemic of sino-orbital mucormycosis (SOM), otherwise a rare disease, during the coronavirus disease 2019 pandemic. SOM, a potentially fatal disease, is typically treated with orbital exenteration and systemic antifungals after metabolic stabilization. There is no clear evidence of survival benefit of exenteration in the literature, and thus, there have been attempts at globe conserving treatments like orbital infusion after limited debridement and intraorbital injections with Amphotericin B (IOAB). METHODS: We conducted a prospective comparative interventional study at a tertiary eye care hospital to evaluate treatment outcomes with the use of adjunctive IOAB in cases of SOM with mild to moderate orbital disease. RESULTS: Thirty-six patients of SOM with mild to moderate orbital disease were recruited in the study. In the intervention group, 23/26 (885%) eyes had stable orbital disease at the end of treatment (4-6 weeks). No deterioration in visual acuity was noted as a result of treatment. In 8/26 (30.77%) patients, inflammation was noted as a side effect of IOAB requiring temporary discontinuation of injections. The mean follow-up for cases was 14.2 months (range 12-15 months). 1/23 (4.35%) patients had relapse of orbital disease at 3 months. Twenty-one patients are alive on last follow-up. Of the patients who refused treatment (controls), 2/9 (22.22%) patients relapsed. One of these patients with relapse underwent exenteration, while the other was managed with IOAB. At a follow-up of 14 months (range 12-15 months), eight patients are alive. On evaluating the ocular parameters in salvaged eyes, improvement in extraocular movements was noted in 75-80% cases. The degree of proptosis and resistance to retropulsion did not change significantly. CONCLUSION: In the current study, an improvement in the globe salvage rates was noted in cases of SOM with mild to moderate orbital disease treated with adjunctive IOAB as compared to controls at a mean follow-up of 14 months, although it did not achieve statistical significance. The study supports the inclusion of IOAB in routine management of mild to moderate orbital disease.

Genotyping of oral Candida albicans and Candida tropicalis strains in patients with orofacial clefts undergoing surgical rehabilitation by MALDI-TOF MS: Case-series study.

Patients with orofacial clefts are more likely to develop oral fungal diseases due to anatomo-physiological changes and surgical rehabilitation treatment. This case-series study evaluated the genetic diversity and dynamics of oral colonization and spread of C. albicans and C. tropicalis in four patients with orofacial clefts, from the time of hospital admission, perioperative and outpatient follow-up, with specialized physician. Candida biotypes previously identified by CHROMagar Candida and PCR methods were studied by MALDI-TOF MS assays and clustering analyses. Possible correlations with pathogenicity characteristics were observed, including production of hydrolytic exoenzymes and the antifungal sensitivity profiles. Amphotericin B-sensitive and fluconazole-resistant (low frequency) C. tropicalis and C. albicans, including clinically compatible MIC of nystatin, were found in the oral cavity of these patients. Clusters of isolates revealed phenomena of (i) elimination in the operative phase, (ii) maintenance or (iii) acquisition of oral C. tropicalis in the perioperative period and specialized outpatient and medical follow-up. For C. albicans, these phenomena included (i) elimination in the operative phase, (ii) acquisition in the operative phase and propagation from the hospital environment, and (iii) maintenance during hospitalization and operative phase. Amphotericin B and nystatin were shown to be effective in cases of clinical treatment and/or prophylaxis, especially considering the pre-existence of fluconazole-resistant strains. This study confirmed the phenomena of septic maintenance, septic neocolonization and septic elimination involving the opportunistic pathogens. MALDI-TOF MS associated with clustering analysis may assist the monitoring of clinical isolates or groups of epidemiologically important microbial strains in the hospital setting.

Treatments for pathogen infection rescued 2 patients with renal artery rupture after kidney transplantation: A case report.

RATIONALE: Renal artery rupture due to allograft infection, especially by fungi, is a serious clinical complication that can occur after kidney transplantation, and may lead to graft loss and death. PATIENT CONCERNS: Two kidney recipients from China who developed renal artery rupture at our hospital on 5 days (47-year-old female) and 45 days (39-year-old male) after surgery. DIAGNOSES: The male had immunoglobulin A nephropathy as a primary disease, and experienced a postoperative attack of vascular rejection and mixed infection by Mucor and bacteria. The female had chronic glomerulonephritis as a primary disease, and experienced renal artery rupture near the anastomosis site with infection by fungi and other pathogens. INTERVENTIONS: The male received resection of the implanted kidney and antibiotic therapy with intravenous vancomycin (0.5 g, 2 days) and amphotericin B (530 mg in 33 days). The female received replacing the segment of renal arterial and internal iliac artery by saphenous vein, as well as antibiotic therapy with amphotericin B (320 mg in 8 days). OUTCOMES: The male was recovered and received a second transplantation, while the female was discharged on postoperative day 19. LESSONS: In both patients, prompt surgery and aggressive treatment with an antifungal drug (amphotericin B) and antidrugs led to successful rescue.

Integration of genomic and pharmacokinetic data to predict clinical outcomes in HIV-associated cryptococcal meningitis.

Cryptococcal meningitis causes an estimated 112,000 global deaths per annum. Genomic and phenotypic features of the infecting strain of Cryptococcus spp. have been associated with outcomes from cryptococcal meningitis. Additionally, population-level pharmacokinetic variability is well documented in these patient cohorts. The relative contribution of these factors to clinical outcomes is unknown. Based in Malawi, we conducted a sub-study of the phase 3 Ambition-CM trial (ISRCTN72509687), collecting plasma and cerebrospinal fluid at serial time points during the first 14 days of antifungal therapy. We explored the relative contribution of pathogen genotype, drug resistance phenotype, and pharmacokinetics on clinical outcomes including lumbar opening pressure, pharmacodynamic effect, and mortality. We report remarkable genomic homogeneity among infecting strains of Cryptococcus spp., within and between patients. There was no evidence of acquisition of antifungal resistance in our isolates. Genotypic features of the infecting strain were not consistently associated with adverse or favorable clinical outcomes. However, baseline fungal burden and early fungicidal activity (EFA) were associated with mortality. The strongest predictor of EFA was the level of exposure to amphotericin B. Our analysis suggests the most effective means of improving clinical outcomes from HIV-associated cryptococcal meningitis is to optimize exposure to potent antifungal therapy. IMPORTANCE: HIV-associated cryptococcal meningitis is associated with a high burden of mortality. Research into the different strain types causing this disease has yielded inconsistent findings in terms of which strains are associated with worse clinical outcomes. Our study suggests that the exposure of patients to potent anti-cryptococcal drugs has a more significant impact on clinical outcomes than the strain type of the infecting organism. Future research should focus on optimizing drug exposure, particularly in the context of novel anticryptococcal drugs coming into clinical use.

Fusarium Keratitis: A Systematic Review (1969 to 2023).

BACKGROUND: Mycotic keratitis (MK) represents a corneal infection, with Fusarium species identified as the leading cause. Fusarium is a genus of filamentous fungi commonly found in soil and plants. While many Fusarium species are harmless, some can cause serious infections in humans and animals, particularly Fusarium keratitis, that can lead to severe ocular infections, prevalent cause of monocular blindness in tropical and subtropical regions of the world. Due to its incidence and importance in ophthalmology, we conducted a systematic analysis of clinical cases to increase our understanding of Fusarium keratitis by gathering clinical and demographic data. METHODS: To conduct an analysis of Fusarium keratitis, we looked through the literature from the databases PubMed, Embase, Lilacs, and Google Scholar and found 99 papers that, between March 1969 and September 2023, corresponded to 163 cases of Fusarium keratitis. RESULTS: Our analysis revealed the Fusarium solani species complex as the predominant isolate, with females disproportionately affected by Fusarium keratitis. Notably, contact lens usage emerged as a significant risk factor, implicated in nearly half of cases. Diagnosis primarily relied on culture, while treatment predominantly involved topical natamycin, amphotericin B, and/or voriconazole. Surprisingly, our findings demonstrated a prevalence of cases originating from the United States, suggesting potential underreporting and underestimation of this mycosis in tropical regions. This shows the imperative for heightened vigilance, particularly in underdeveloped regions with substantial agricultural activity, where Fusarium infections may be more prevalent than currently reported. CONCLUSION: Our study sheds light on the clinical complexities of Fusarium keratitis and emphasizes the need for further research and surveillance to effectively tackle this vision-threatening condition. Furthermore, a timely identification and early initiation of antifungal treatment appear to be as important as the choice of initial treatment itself.

Leishmania donovani infection mimicking ulcerative colitis in an immuno-competent patient.

We share a case of a 54-year-old Caucasian immune-competent male with a suspected long latent visceral leishmaniasis presenting primarily with parasitic colitis, splenomegaly, and pancytopenia. Due to histopathologically and endoscopically mimicking ulcerative colitis, the patient was initially treated for UC, until the parasites were identified and eradicated with liposomal Amphotericin B.

The nexus between Leishmania & HIV: Debilitating host immunity and Hastening Comorbid disease burden.

The scintillating association between Leishmania and HIV has contributed exceptionally towards expansion of Visceral Leishmaniasis (VL) with Acquired Immunodeficiency Syndrome (AIDS). The co-infection poses a grievous threat to elimination of VL and containment of Human Immunodeficiency Virus (HIV). When coinfected, Leishmania and HIV complement each other's proliferation and survival by inducing immunesenescence, T cell fatigue and exhaustion. Antigen presentation is lost, co-stimulatory molecules are diminished whereas co-inhibitory molecules such as CTLA-4, TIGIT, LAG-3 etc. are upregulated to ensure a Th2-baised immune environment. As a consequence, Leishmania-HIV coinfection causes poor outcomes, inflates the spread of Leishmania parasites, enhances the severity of side-effects to drugs, as well as escalate the probability of treatment failure and mortality. What makes control extremely strenuous is that there are frequent episodes of VL relapse with no prognostic markers, no standard immunophenotype(s) and appearance of atypical clinical symptoms. Thus, a standard therapeutic regimen has been difficult to develop and treatment is majorly dependent upon a combination of liposomal Amphotericin B and Miltefosine, a therapy that is expensive and capable of causing drastic side-effects in recipients. As World Health Organization is committed to eliminate both VL and HIV in due course of future, the existing therapeutic interventions require advancements to grapple and overcome this hazardous co-infection. In this context, an overview of HIV-VL co-infection, immunopathology of HIV and Leishmania co-inhabitance, available therapeutic options and their limitations in the treatment of co-infection are discussed in-depth.

Cost-effectiveness study of therapeutic approaches for mucosal leishmaniasis.

This study aimed to estimate the cost-effectiveness of four therapeutic approaches available for mucosal leishmaniasis in Brazil: miltefosine, meglumine antimoniate, combined with and without pentoxifylline, and liposomal amphotericin B. The perspective adopted was that of the Brazilian Unified National Health System (SUS). The outcome of interest was "cured patient", which was analyzed using a decision tree model. Estimates of direct costs and effectiveness were obtained from the scientific literature. Meglumine antimoniate alone was the base comparator strategy; liposomal amphotericin B showed an incremental cost-effectiveness ratio (ICER) of USD 7,409.13 per cured patient, and the combination of meglumine antimoniate with pentoxifylline presented an ICER of USD 85.13. Miltefosine was absolutely dominated, with higher cost and similar effectiveness when compared to meglumine antimoniate. Sensitivity analyses, varying the cost by ±25%, did not change the results. However, when the cost of miltefosine was estimated at less than USD 171.23, this strategy was dominant over meglumine antimoniate alone. The results confirm that treatment with liposomal amphotericin B remains the option with the highest ICER among the approaches analyzed. Miltefosine may be cost-effective based on the variation in the acquisition price, which deserves attention because it is the only available oral option. The non-accounting of other aspects prevent the use of these results immediately to support decision-making, but they point out the need to negotiate the prices of drugs available for mucosal leishmaniasis and indicates the need of encouraging technology transfer or other actions aimed at expanding the performance of the Brazilian national industrial complex.

Risk Factors of COVID-19 associated mucormycosis in Iranian patients: a multicenter study.

BACKGROUND: To evaluate the demographic, clinical, and prognostic characteristics of patients diagnosed with COVID-19-associated mucormycosis (CAM) in Iranian patients. METHODS: This prospective observational study was conducted in 8 tertiary referral ophthalmology centers in different provinces of Iran during the fifth wave of the COVID-19 pandemic. All patients were subjected to complete history taking and comprehensive ophthalmological examination and underwent standard accepted treatment strategy based on the disease stage. RESULTS: Two hundred seventy-four CAM patients (most were males (150, 54.7%)) with a mean age of 56.8 ± 12.44 years were enrolled. Patients with a history of cigarette smoking (Adjusted Odds Ratio (AOR) = 4.36), Intensive Care Unit admission (ICU) (AOR = 16.26), higher stage of CAM (AOR = 2.72), and receiving endoscopic debridement and transcutaneous retrobulbar amphotericin B (AOR = 3.30) had higher odds of mortality. History of taking systemic corticosteroids during COVID-19 was significantly associated with reduced odds of mortality (AOR = 0.16). Generalized Estimating Equations analysis showed that the visual acuity of deceased patients (LogMAR: 3.71, 95% CI: 3.04-4.38) was worse than that of patients who were discharged from the hospital (LogMAR: 2.42, 95% CI: 2.16-2.68) (P < 0.001). CONCLUSIONS: This study highlights significant risk factors for mortality in patients with CAM, such as cigarette smoking, ICU admission, advanced CAM stages, receiving transcutaneous retrobulbar amphotericin B and worser visual acuity. Conversely, a history of systemic corticosteroid use during COVID-19 was linked to reduced mortality. These findings underscore the critical need for early identification and targeted interventions for high-risk CAM patients to improve clinical outcomes.

The impact of immune recovery and treatment duration on disseminated histoplasmosis consolidation therapy in AIDS patients.

INTRODUCTION: The present study investigated the impact of immune recovery and the duration of antifungal adherence in the consolidation phase of disseminated histoplasmosis (DH) in acquired immune deficiency syndrome (AIDS) patients living in a hyperendemic area in northeastern Brazil. MATERIAL AND METHODS: Sixty-nine patients with DH/AIDS, admitted to the São José Hospital between 2010 and 2015, who continued histoplasmosis consolidation therapy at the outpatient clinic were studied. The follow-up duration was at least 24 months. RESULTS: Sixty-eight patients used itraconazole 200-400 mg/day or amphotericin B deoxycholate weekly during the consolidation phase, and six patients relapsed during follow-up. The overall median duration of consolidation antifungal use was 250 days [IQR 101 - 372]. Antifungal withdrawal by medical decision occurred in 41 patients (70.7 %) after a median of 293 days [IQR 128 - 372] of use; 16 patients discontinued by their own decision, with a median of 106 days [IQR 37 - 244] of therapy; three patients had no information available, and nine continued on AF therapy. The median CD4+ T-cell count in the group without relapse was 248 cells/µL [IQR 115-355] within 6 months after admission; conversely, in the relapse group, the median cell count remained below 100 cells/µL. Irregular adherence to highly active antiretroviral therapy (HAART) was the leading risk factor associated with relapse and death (p< 0.01). DISCUSSION: The regular use of HAART, combined with immune recovery, proved to be highly effective in preventing relapses in DH/AIDS patients, suggesting that long-term antifungal therapy may not be necessary.

Disseminated Histoplasma captulatum infection in a patient with HIV.

Histoplasmosis capsulatum is a dimorphic fungus, recognised for its endemic presence in multiple global regions. It may cause severe opportunistic disseminated infection in immunocompromised individuals. This is a case report of a 33-year-old man from Thailand who was admitted at a Danish hospital with fever, weight loss, cough, nosebleeds, and newly diagnosed HIV. The clinical condition rapidly deteriorated with lung and kidney failure. The patient was diagnosed with H. capsulatum fungaemia first detected on blood smear. He was treated with intravenous amphotericin B followed by oral itraconazole as well as antiretroviral therapy.