Candidiasis Research Articles

Is the T2MR Candida Panel a suitable alternative to the SeptiFast for the rapid diagnosis of candidemia in routine clinical practice?

ObjectivesThe diagnosis of invasive Candida infection remains challenging because of tests with slow turnaround times or mediocre performance. T2magnetic resonance imaging is a new diagnostic tool. We investigated the diagnostic accuracy of the T2Candida panel (T2) in comparison with blood culture (BC) and the SeptiFast (SF) for the detection of five different Candida species among high-risk intensive care unit patients with suspected candidemia. MethodsWe analysed blood samples collected from patients with suspected candidemia (177 samples from 138 patients) from August 2018 to April 2020. Blood samples were collected and analysed concurrently by BC, SF, and T2Candida. Subsequently, based on clinical and microbiological findings, patient samples were assigned to specific risk categories (proven, probable, and no candidemia). ResultsTwenty-two samples from 17 patients were classified as proven candidemia, and 15 samples from 14 patients were classified as probable candidemia. A sensitivity of 68.2% (95% CI, 45–86%) was observed for the BC and the SF, and a sensitivity of 63.6% (95% CI, 41–83%) was observed for the T2 when only cases with proven candidemia were evaluated. For proven and probable candidemia, the sensitivity was 40.5% (95% CI, 23–58%) for BC, 81.1% (95% CI, 65–92%) for SF, and 73.0% (95% CI, 56–86%) for T2. DiscussionThe diagnostic performance of SF and T2 was similar. For samples with proven/probable candidemia, SF and T2 had a higher sensitivity compared to BC. Used in conjunction with other diagnostic methods, T2 can replace the no longer available SF for the diagnosis of candidemia, enabling the timely initiation of targeted antifungal therapy.

Common Oral Manifestations in a Denture Wearer Patients with Suspected Diabetes Mellitus

Background. Acute pseudomembranous candidiasis or often called oral thrush is a disease in the oral cavity caused by the overgrowth of Candida albicans. Angular cheilitis is an inflammatory lesion on the corners of the mouth. The purpose of this case report is to document the oral manifestations in patients with suspected diabetes mellitus. Case Report. A 57-year-old woman came with complaints of a burning sensation throughout the mouth and lips and presented a white spot on her tongue with soreness in the past year. The patient has diabetes mellitus and regularly takes medication. Despite this, the patient still has experienced classical signs of diabetes mellitus which are polyphagia, polydipsia, and polyuria. Intraorally the burning sensations were related to the full denture continuous wearness and were diagnosed as acute pseudomembranous candidiasis and angular cheilitis. The treatment given to this patient was symptomatic therapy in the form of Aloclair Plus mouthwash, causative therapy in the form of Nystatin oral suspension and referral to an internist to further examine the condition of diabetes mellitus, and supportive therapy in the form of lanolin and vaseline. Treatment ends with the provision of communication, instruction, and education.

Determination of amphotericin B antifungal susceptibility in Candida strains using an inverted microscope.

Invasive Candida infections have recently shown a significant increase in prevalence and are associated with high mortality rates. Initiating early antifungal treatment in patients with candidemia is vital. The aim of our study was to compare the antifungal susceptibility results of a new method called Flat Plate Method modified from reference "Clinical and Laboratory Standards Institute (CLSI) microdilution method by us with Sensitititre Yeast One colorimetric method and the reference CLSI method. We tested 100 Candida isolates from blood cultures. We followed the CLSI M27-A3 (reference method for broth dilution antifungal susceptibility testing of yeasts; third edition) guidelines for testing in vitro susceptibility to amphotericin B. In the Flat Plate method, 96-well plates were used for evaluation with an inverted microscope. Minimum inhibitory concentration (MIC) values in the SYO method were measured following the manufacturer's instructions. The MIC values obtained by all three methods were considered compatible if they were within ± 2 dilution limits. The SYO method detected C. albicans and C. glabrata with 100% essential agreement, whereas there was 96.29% essential agreement in the case of C. parapsilosis. In the Flat Plate method, the essential agreement with amphotericin B was 91.42%, for C. albicans isolates and 89.47%.for C. glabrata strains. When determining early antifungal susceptibility using the Flat Plate method, the results are obtained quickly, with high accuracy, and without incurring additional costs. However, there is a need for comprehensive studies comparing different antifungals.

A Quality Improvement Initiative To Reduce Invasive Candidiasis In Extremely Low Birth Weight Neonates

Objective: To evaluate the impact of a quality improvement (QI) initiative, which included a Fluconazole prophylaxis protocol and provider education on neonatal Candidiasis. Study Design: Retrospective longitudinal study. Place and Duration of Study: Neonatal Intensive Care Unit (NICU), Aga Khan University, Karachi Pakistan, from Apr 2015 to Dec 2019. Methodology: All extremely low birth weight neonates (ELBW) neonates admitted to the NICU between April 2015 and March 2017 were included in the pre-implementation phase. All ELBW neonates admitted between April 2017 and December 2019 were included in the post-implementation phase. Data were collected from medical records. The primary outcome was the frequency of Invasive Candidiasis (IC) before and after the QI initiative. Results: Altogether, 272 neonates were included in the study, with 115 neonates in the Pre-Implementation Group and 157 neonates in the Post-Implementation Group. The frequency of IC was 6(5.2%) in the pre-implementation and 1(0.6%) in the post-implementation period, (p=0.044). Candida parapsilosis 2(40%) and Candida glabrata 2(40%) were the organisms most commonly isolated from blood cultures. All organisms were sensitive to Fluconazole in both the pre-and post-implementation cohorts. There was no difference in mortality (54(50.5%) vs. 69(44.2%), p=0.32) or length of stay (19.6±13.3 vs. 23.4±18.4 days,p=0.061) before and after Fluconazole prophylaxis. Conclusion: The frequency of invasive Candidiasis in ELBW neonates was successfully reduced by introducing a Fluconazole prophylaxis protocol in the NICU as a QI initiative. A team-based approach and provider education ensured high compliance.

Transdermal administration of farnesol-ethosomes enhances the treatment of cutaneous candidiasis induced by Candida albicans in mice.

Cutaneous candidiasis attributed to Candida infection is a prevalent condition that impacts individuals of all age groups. As a type of microbial community, biofilms confer benefits to host infections and mitigate the clinical effects of antifungal treatments. In C. albicans, the yeast-to-hypha transition and biofilm formation are effectively suppressed by farnesol through its modulation of multiple signaling pathway. However, the characteristics of farnesol such as hydrophobicity, volatility, degradability, and instability in various conditions can impose limitations on its effectiveness. Nanotechnology holds the potential to enhance the efficiency and utilization of this molecule. Treatment of farnesol-ethosomes by transdermal administration demonstrated a very remarkable therapeutic effect against C. albicans in infection model of cutaneous candidiasis in mice. Many patients suffering fungal skin infection will benefit from this study.

Probing RNA structural landscapes across Candida yeast genomes.

Understanding the intricate roles of RNA molecules in virulence and host-pathogen interactions can provide valuable insights into combatting infections and improving human health. Although much progress has been achieved in understanding transcriptional regulation during host-pathogen interactions in diverse species, more is needed to know about the structure of pathogen RNAs. This is particularly true for fungal pathogens, including pathogenic yeasts of the Candida genus, which are the leading cause of hospital-acquired fungal infections. Our work addresses the gap between RNA structure and their biology by employing genome-wide structure probing to comprehensively explore the structural landscape of mRNAs and long non-coding RNAs (lncRNAs) in the four major Candida pathogens. Specifically focusing on mRNA, we observe a robust correlation between sequence conservation and structural characteristics in orthologous transcripts, significantly when sequence identity exceeds 50%, highlighting structural feature conservation among closely related species. We investigate the impact of single nucleotide polymorphisms (SNPs) on mRNA secondary structure. SNPs within 5' untranslated regions (UTRs) tend to occur in less structured positions, suggesting structural constraints influencing transcript regulation. Furthermore, we compare the structural properties of coding regions and UTRs, noting that coding regions are generally more structured than UTRs, consistent with similar trends in other species. Additionally, we provide the first experimental characterization of lncRNA structures in Candida species. Most lncRNAs form independent subdomains, similar to human lncRNAs. Notably, we identify hairpin-like structures in lncRNAs, a feature known to be functionally significant. Comparing hairpin prevalence between lncRNAs and protein-coding genes, we find enrichment in lncRNAs across Candida species, humans, and Arabidopsis thaliana, suggesting a conserved role for these structures. In summary, our study offers valuable insights into the interplay between RNA sequence, structure, and function in Candida pathogens, with implications for gene expression regulation and potential therapeutic strategies against Candida infections.

Oral Candida carriage and resistance against common antifungal agents in hematopoietic stem cell transplantation recipients

PurposeAllogeneic hematopoietic stem cell transplant (HSCT) recipients receiving long-term and high-dose immunosuppressive medications suffer commonly from oral candida infections. This prospective cohort study examined oral fungal carriage in HSCT recipients and screened the susceptibility against commonly used antifungal agents. An increasing oral occurrence of Candida spp. and the development of resistance against clinically administered fluconazole were hypothesized.MethodsTwo hundred HSCT recipients were included and followed up for 2 years post-HSCT. Oral microbiological specimens were analyzed with matrix-assisted laser desorption/ionization-time of flight mass spectrometry assays (MALDI-TOF). The colorimetric method was applied for the susceptibility testing by commercially available Sensititre YeastOne (SYO®, TREK Diagnostics Systems, Thermo-Fisher, UK).ResultsThe prevalence of oral Candida spp. carriage increased statistically significantly after a year post-HSCT being 30, 26, 35, 44, and 47%, pre-HSCT, 3, 6, 12, and 24 months post-HSCT, respectively. Altogether, 169 clinical oral Candida strains were isolated. Fourteen Candida spp. were identified, and C. albicans was predominant in 74% of the isolates pre-HSCT with a descending prevalence down to 44% 2 years post-HSCT. An increasing relative proportion of non-albicans species post-HSCT was evident. No development of resistance of C. albicans against fluconazole was found. Instead, a shift from C. albicans towards non-albicans species, especially C. dubliensis, C. glabrata, and relatively seldom found C. krusei, was observed.ConclusionOral Candida carriage increases after HSCT. Instead of the expected development of resistance of C. albicans against fluconazole, the relative proportion of non-albicans strains with innate resistance against azole-group antifungals increased.

Manganese(II), copper(II) and silver(I) complexes containing 1,10-phenanthroline/1,10-phenanthroline-5,6-dione against Candida species.

Background: New chemotherapeutics are urgently required to treat Candida infections caused by drug-resistant strains. Methods: The effects of 16 1,10-phenanthroline (phen)/1,10-phenanthroline-5,6-dione/dicarboxylate complexed with Mn(II), Cu(II) and Ag(I) were evaluated against ten different Candida species. Results: Proliferation of Candida albicans, Candida dubliniensis, Candida famata, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis and Candida tropicalis was inhibited by three of six Cu(II) (MICs 1.52-21.55μM), three of three Ag(I) (MICs 0.11-12.74μM) and seven of seven Mn(II) (MICs 0.40-38.06μM) complexes. Among these [Mn2(oda)(phen)4(H2O)2][Mn2(oda)(phen)4(oda)2].4H2O, where oda=octanedioic acid, exhibited effective growth inhibition (MICs 0.4-3.25μM), favorable activity indexes, low toxicity against Vero cells and good/excellent selectivity indexes (46.88-375). Conclusion: [Mn2(oda)(phen)4(H2O)2][Mn2(oda)(phen)4(oda)2].4H2O represents a promising chemotherapeutic option for emerging, medically relevant and drug-resistant Candida species.

Invasive candida infection as the cause of seizure in a patient with systemic lupus erythematosus: a report of unusual case

Background: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a complication of SLE involving the nervous and psychiatric systems with clinical manifestations including seizures, strokes, myelopathy, neuritis, meningitis, and psychosis. Seizures in NPSLE might be caused by intracranial infection, with bacteria as the most common pathogens. This study reported a rare case of seizure in a SLE patient due to invasive Candida infection. Case Presentation: A 26-year-old female presented in the emergency department of Dr. Soetomo Hospital Surabaya, Indonesia with seizure, which she has experienced in the last 2 days prior to hospital admission. She experienced a convulsion that lasted 5-10 minutes followed by loss of consciousness. The patient also complained of severe headaches two days before hospital admission. She was diagnosed with SLE in November 2022 and was currently taking methylprednisolone. Physical examination showed Glasgow Coma Scale (GCS) of E3V4M5, fever, dyspnea, and rough rhonchi on the right lung. Chest X-ray indicated pneumonia, while brain computed tomography (CT) suggested subacute to chronic thromboembolism. The patient was diagnosed with NPSLE due to intracranial infection, and hospital-acquired pneumonia (HAP), and was given Levofloxacin. On the 3rd day, a reddish lesion with central healing was found on the cheeks, and the patient had dyspnea, suggesting fungi infection. Methylprednisolone was stopped while fluconazole and urine cultures were initiated. Urine culture suggested Fluconazole-sensitive Candida and consultation with a dermato-venerologist confirmed Candida, thus, Fluconazole was continued along with dexamethasone, and Levofloxacin. The patient showed clinical improvement and was discharged after 12 days. Conclusion: Seizure is one of the most common manifestations of NPSLE, due to intracranial infection. Although rare, we cannot rule out the possibility of fungal infection in NPSLE patients with intracranial infection. Early diagnosis and prompt treatment are critical for better prognosis, as shown in this patient.

Mechanistic insight into the membrane disrupting properties of thymol in Candida species

Candida infection is a major problem in immunocompromised patients and has become a significant public health concern in recent years due to high toxicity, multidrug resistance and unfavourable side effects of conventional antifungal drugs. This study aims to investigate the antifungal efficacy of thymol, a natural monoterpenoid, on the membrane integrity of Candida albicans, Candida glabrata and Candida tropicalis. Minimum inhibitory concentrations (MICs) of thymol were 32 µg/ml, 63 µg/ml, and 125 µg/ml for C. albicans, C. tropicalis and C. glabrata, respectively. The minimum fungicidal concentrations (MFC) were 64 µg/ml, 110 µg/ml and 240 µg/ml, respectively. At MIC, thymol treated cells showed complete suppression of cell growth (growth kinetics, disc diffusion), altered morphology (scanning electron microscopy), leakage of intracellular macromolecules (absorption at 260 nm), significant reduction in ergosterol levels and inhibition of plasma membrane H+-ATPase (Pma1) activity. The disruption of the fungal membranes by thymol was further confirmed by propidium iodide uptake using flow cytometry and confocal microscopy. In silico studies with membrane-bound proteins (lanosterol 14-α demethylase (LDM) and Pma1), showed good binding affinity of −6.3 kcal/mol and −6.7 kcal/mol, respectively, and formed hydrogen bonds with crucial amino acid residues at the active site of target proteins. With low MIC values, negligible host toxicity, desirable ADME properties, thymol has immense potential as a potent antifungal drug that can be used for developing mechanism-based drugs as it has specific binding affinity for specific target proteins. Studies using animal models are required for further validation.

Antifungal Activity of Selected Indigenous Medicinal Plants in Sri Lanka Against Candida Infections

Candida infections have been recorded as an emerging health concern among immune- compromised patients, infants and pregnant women in Asia, Africa and Europe. Skin diseases, genital infections, candidiasis and candidemia caused by overgrowth of symbiotic Candida species in the human body are treated by antifungal drugs. The common drugs viz., fluconazole, flucytosine, amphotericin B, nystatin, etc. are responsible for more side effects in the human body while Candida species are indicating a resistance towards them. Therefore, the continuous discovery of antifungal compounds against Candida infections is an essential process. Thus, the current study focused on the determination of the antifungal activity of water extracts of selected indigenous medicinal plants in Sri Lanka towards Candida infections. Three common indigenous medicinal plants; Cyperus rotundus (roots, tubers, leaves and flowers), Acalipha indica (roots, stem, leaves and flowers) and Aloe barbadensis Miller (gel and leaves) were collected and their water extracts (10 g/25 mL) were screened for the antifungal activity against two common Candida species; Candida glabrata and Candida parapsilosis using disk diffusion method. Briefly, the pathogenic bacterial lawns were prepared by spreading equalized solutions of C. glabrata and C. parapsilosis on Muller Hinton Agar supplemented with 2% glucose. Sterile paper disks soaked with 30 µL of water extracts of each plant part were placed on pathogen lawns. Sterile distilled water was used as the negative control. The plates were incubated at 37° C overnight and observed for clear zone formation. According to the results, the water extract of C. rotundus tubers indicated an inhibitory action by giving clear inhibition zones against both tested Candida species. All other water extracts of medicinal plants indicated negative inhibitory actions against tested Candida species. The results revealed that C. rotundus tubers consist of antifungal activity against C. glabrata and C. parapsilosis. Hence, C. rotundus tubers can be used as an effective treatment for infections caused by the tested Candida species.
 
 Keywords: Antifungal activity, Candida infections, Indigenous medicinal plants, Cyperusrotundus, Water extracts

CG-MS, Radical Scavenging, Acetylcholinesterase Inhibition, Antifungal and Molecular Docking Studies of Essential Oil from the Leaves of Tapirira guianensis Aubl

The species Tapirira guianensis Aubl is used in folk medicine to treat leprosy, diarrhea, and syphilis. The present study aims to evaluate the chemical composition and the antioxidant, anticholinesterase, and antifungal potential of the essential oil from T. guianensis leaves. The plant material was collected at Arco Estadual do Cocó, with prior authorization from the Municipal Environment Department. The essential oil was extracted through the hydrodistillation process with a Clevenger-type apparatus, and the constituents were evaluated through Gas Chromatography coupled to Mass Spectrometry (GC-MS). The antioxidant potential was assessed through free radicals: DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS+ (2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)) in a 96-well plate. Antifungal activity was evaluated using the Clinical Laboratory Standards Institute - M38-A protocol (CLSI, 2018). Gas chromatography coupled with mass spectrometry revealed the presence of constituents such as eugenol (59.00%), α-copaene (0.40%), β-caryophyllene (29.91%), α-humulene in T. guianensis. The essential oil demonstrated very promising antioxidant and anticholinesterase potential in In vitro studies. Molecular docking regarding acetylcholinesterase enzyme inhibition revealed that α-copaene has superior action compared to the drug physostigmine. The results of molecular docking for Candida albicans showed that α-copaene and α-humulene interacted in the same binding region as the PepA inhibitor against SAP5. This indicates their action is similar to the aspartic protease inhibitor, in addition to the possibility of a synergistic effect with the drug fluconazole. This is the first study of the biological potential of the essential oil from T. guianensis leaves, thus revealing its high potential for future studies in the scientific community. Therefore, we can infer that the essential oil of T. guianensis is a source of antioxidant, anticholinesterase, and antifungal constituents, with promising therapeutic potential in the management of Alzheimer's disease and Candida infections.

Powder diet exacerbates oropharyngeal candidiasis in a mouse model.

This study reports on the influence of a powder diet in a mouse model of oropharyngeal candidiasis (OPC), a significant health concern caused primarily by Candida albicans. Despite identical nutritional composition, we found that a powdered diet significantly increased Candida burdens and oral lesions, and aggravated weight loss compared to a standard pelleted diet. High fungal burdens and severe oral lesions were accomplished within 48 hours after infection with only one dose of cortisone. Moreover, mice on a powder diet recovered a week after infection. Using a powder diet, we thus modified the cortisone OPC murine model in a way that simplifies the infection process, enhances reproducibility, and facilitates studies investigating both pathogenesis and recovery processes. Our findings also underscore the pivotal role of the physical form of the diet in the progression and severity of oral Candida infection in this model. Future research should investigate this relationship further to broaden our understanding of the underlying mechanisms, potentially leading to novel prevention strategies and improved disease management.IMPORTANCEOropharyngeal candidiasis (OPC) is a multifactorial disease and a significant health concern. We found that the physical form of the diet plays a critical role in the severity and progression of OPC. We developed a modified cortisone OPC murine model that facilitates studies investigating pathogenesis and recovery processes.

(266) Miconazole Vaginal Cream-Induced Acquired Neuroproliferative Vestibulodynia

Abstract Introduction The endodermal vestibule lies between the ectodermal vulva and the mesodermal vagina. Unlike the vulvar skin, the vestibular epithelium is thin, non-keratinized, and its submucosal immune cells are more susceptible to activation. Topical pharmaceutical agents that are applied to the genitals for various medical indications are likely to contact the vestibular epithelium. For example, miconazole vaginal cream (MVC) is approved for treatment of vaginal yeast infections and the irritation associated with the yeast infection. Active and inactive ingredients in MVC include miconazole nitrate, benzoic acid, cetyl alcohol, isopropyl myristate, polysorbate 60, potassium hydroxide, propylene glycol, purified water and stearyl alcohol. We have observed cases where individuals, previously without vestibular pain, have applied MVC to their genitals and immediately experienced excruciating burning that resulted in persistent unrelenting severe pain throughout the vestibule, which is a symptom of acquired neuroproliferative vestibulodynia (ANPV). Objective Our objective is to report cases of patients who used MVC and were diagnosed with ANPV in order to provide awareness of this condition. Methods We performed a retrospective chart review of persons with vulvas presenting to a single sexual medicine clinic between 6/2019-6/2023 who were clinically suspected to have ANPV after experiencing an allergic reaction following use of MVC. Patients were included who failed conservative treatments for provoked vestibular pain, underwent vestibulectomy and were histopathlogically diagnosed with ANPV (>8 CD117 stained immunopositive cells per high-power field (HPF), consistent with mast cells, and excess PGP117 stained immunopositive cells, consistent with nerves). Demographic data, prior diagnoses and treatments, and results from validated questionnaires were collected. Results Our patient cohort included 7 individuals who met the criteria for MVC-induced ANPV. Mean age at time of MVC-induced vestibular pain was 23 (range 18-29) years. Mean age of presentation to our sexual medicine facility was 28 (range 22-33) years. Mean years of delay in diagnosis of MVC-induced ANPV was 5 (range 1-12) years. 71% and 29% were previously diagnosed and unsuccessfully managed as hormone-mediated vestibulodynia and interstitial cystitis, respectively. The mean pain score and overall score for the Female Sexual Function Index (FSFI) was 1.2/6 (range 0-3.2/6) and 11.7/36 (range 4.2-18.1/36), respectively. All total FSFI scores were <26 and indicative of sexual dysfunction. The mean Female Sexual Distress Scale-Revised score was 32.2/52 (21-39/52), consistent with significant distress. Conclusions Our cohort of patients with MVC-induced ANPV experienced several years of misdiagnoses, unsuccessful treatments, and significant pain and distress. It is hypothesized that MVC induces ANPV in genetically susceptible individuals possibly due to activation of the innate submucosal immune cells from an allergic reaction to active or inactive ingredients in the MVC. This allergic reaction results in accumulation of mast cells in the subepithelial stroma that release cytokines and growth factors leading to proliferation of nerves with subsequent symptoms of allodynia and hyperalgesia. Avoidance of topical medications and use of systemic antifungal strategies in individuals with yeast infections may be advisable. Disclosure No.

Lymphadenitis and meningoencephalitis resulting from Cryptococcus neoformans infection in HIV patients

Background: Lymphadenopathy can occur at any stage of HIV infection, with multiple aetiologies including reactive, infectious and malignant. An accurate and timely diagnosis has obvious implications for treatment. Case Description: We report cryptococcal lymphadenitis as the presenting manifestation of HIV infection. Clinical symptoms observed in the patient included headaches, fever, non-productive cough, nausea, vomiting, white patches on the tongue, nodules in the right and left jaw area, a weight loss of 10 kilograms within a month, and a decrease in consciousness in the middle of treatment. The diagnosis was eventually confirmed with a lymph node fine needle aspiration biopsy. Fine needle aspiration biopsy (FNAB) indicated chronic granulomatous inflammation with a fungal (yeast) infection, suggestive of Cryptococcus. Conclusion: Cryptococcosis is a major invasive fungal infection capable of causing widespread disease outbreaks in immunocompromised hosts, and even in seemingly immunocompetent individuals. Cryptococcal infection should be a diagnostic consideration for lymphadenopathy in every patient, regardless of known HIV infection.

Anti-Candida Antibodies of Patients with Invasive Candidiasis Inhibit Growth, Alter Cell Wall Structure, and Kill Candida albicans In Vitro

Invasive candidiasis (IC), caused by Candida yeasts, particularly Candida albicans, poses a significant threat with high mortality rates. Diagnosis is challenging due to Candida's common presence in human microbiota. To address this, our research group developed an immunofluorescence assay detecting Candida albicans Germ Tube Antibodies (CAGTA) in IC patients. CAGTA, indicative of invasive processes, is associated with a lower mortality rate in ICU patients. Based on this premise, this study aims to provide results regarding the lack of knowledge about the potential activity of CAGTA against invasive infections in humans caused by the fungus Candida albicans. Therefore, in order to characterize the activity of CAGTA produced by patients with IC, we used sera from 29 patients with IC caused by either C. albicans or non-albicans Candida species. Whole serum IgG antibodies were fractionated into anti-blastospores, CAGTA-enriched, and purified CAGTA and the assessments included XTT colorimetric assays for metabolic activity, CFU counts for viability, and microscopy for growth, viability, and morphological analysis. The CAGTA-enriched IgG fraction significantly reduced the metabolic activity and viability of C. albicans compared to anti-blastospores. Purified CAGTA altered germ tube cell wall surfaces, as revealed by electron microscopy, and exhibited fungicidal properties by DiBAC fluorescent staining. In conclusion, antibodies in response to invasive candidiasis have antifungal activity against Candida albicans, influencing metabolic activity, viability, and cell wall structure, leading to cell death. These findings suggest the potential utility of CAGTA as diagnostic markers and support the possibility of developing immunization protocols against Candida infections.

Spectrum and management of rare Candida/yeast infections in Kuwait in the Middle East.

Invasive fungal infections (IFIs) are associated with high mortality rates and mostly affect patients with compromised immunity. The incidence of IFIs is increasing worldwide with the expanding population of susceptible patients. Candida and other yeast infections represent a major component of IFIs. Rare Candida/yeast infections have also increased in recent years and pose considerable diagnostic and management challenges as they are not easily recognized by routine phenotypic characteristic-based diagnostic methods and/or by the automated yeast identification systems. Rare Candida/yeasts also exhibit reduced susceptibility to antifungal drugs making proper management of invasive infections challenging. Here, we review the diagnosis and management of 60 cases of rare Candida/yeast IFIs described so far in Kuwait, an Arabian Gulf country in the Middle East. Interestingly, majority (34 of 60, 56.7%) of these rare Candida/yeast invasive infections occurred among neonates or premature, very-low-birth-weight neonates, usually following prior bacteremia episodes. The clinical details, treatment given, and outcome were available for 28 of 34 neonates. The crude mortality rate among these neonates was 32.2% as 19 of 28 (67.8%) survived the infection and were discharged in healthy condition, likely due to accurate diagnosis and frequent use of combination therapy. Physicians treating patients with extended stay under intensive care, on mechanical ventilation, receiving broad spectrum antibiotics and with gastrointestinal surgery/complications should proactively investigate IFIs. Timely diagnosis and early antifungal treatment are essential to decrease mortality. Understanding the epidemiology and spectrum of rare Candida/yeast invasive infections in different geographical regions, their susceptibility profiles and management will help to devise novel diagnostic and treatment approaches and formulate guidelines for improved patient outcome.

Estimation of Phagocytic activity by normal human peripheral blood mononuclear cells on various oral isolates of Candida species – An in-vitro study

Polymorphonuclear neutrophils (PMN) and mononuclear phagocytes represent an important first line and effector function in control of Candida infections. The aim of the study is to determine the in-vitro phagocytic activity of human peripheral blood mononuclear cells against oral isolates of Candida species and its antifungal susceptibility. The study also evaluates the degree of respiratory burst activity of PBMCs. Phagocytic and lytic indices by PBMCs were determined for Candida spp. The respiratory burst activity was evaluated by nitroblue tetrazolium test. Antifungal disc diffusion susceptibility testing was performed. A total of 100 Candida were isolated belonging to the species C.albicans, C. tropicalis, C.krusei and C.auris. Phagocytic and lytic indices of C.albicans was significant when compared to standard strain of C.albicans. For C.tropicalis and C.krusei phagocytic index was significant while lytic index was not significant when compared to standard strain. The inter species comparison of both the indices was not significant for the clinical isolates of Candida. A significant reduction in phagocytic activity was observed for clinical isolates of Candida spp. but lytic activity was variable when compared to the standard strain of C.albicans.

Vaginal candida infection is associated with host molecular signatures of neutrophil activation in the adjacent ectocervical mucosa in Kenyan sex workers

AbstractProblemOvergrowth of candida species in the human vaginal mucosa causes inflammation, which could render the mucosal barrier more susceptible to HIV infection. Here, we investigated whether this condition also affects the ectocervical mucosa, a potential site of HIV entry, in women at high risk of HIV infection.Method of studyRetrospective medical data and ectocervical tissue samples were obtained from a cohort of Kenyan sex workers. Among 108 women, seven had signs of vaginal candida infection by wet smear microscopy and/or the presence of characteristic discharge. Women lacking these two criteria served as controls. Host transcriptomic profiling and quantitative in situ image analysis of epithelial barrier markers and CD4+ cell distribution were performed.ResultsThe candida group had 162 differentially expressed genes out of 15 435 genes as compared with the control group. Among these 162 genes, 147 were upregulated and 15 were downregulated. Gene expression pathway analysis indicated associations with an upregulated inflammatory response, defined primarily by markers of neutrophil activation. Transcription factor analysis revealed upregulation of pathways related to RELA/REL/NFKB1, JUN and STAT1 in the candida group. In situ image analysis of ectocervical tissue samples showed no differences between groups in terms of epithelial height, expression of epithelial junction proteins (E‐cadherin, claudin‐1, zonula occludens 1, and desmoglein‐1), or epithelial CD4+ cell distribution.ConclusionsVaginal candida infection was associated with inflammation and neutrophil infiltration, but not with severe epithelial disruption or CD4+ cell infiltration, in the ectocervical mucosa.

A Case of Proliferative and Necrotizing Otitis Externa in a Scottish Fold Shorthair Cat

In this case report, the aim was to contribute to understanding PNOE's clinical presentation, histopathological features, and successful treatment approaches, emphasizing the significance of accurate diagnosis and appropriate management in affected felines. Proliferative necrotic otitis externa (PNOE) is a very rare skin disease of unknown etiology affecting the vertical ear canal and the concave surface of the auricle, which may be accompanied by secondary yeast or bacterial infections. In this case 8-month-old Scottish fold shorthair cat has fragile, papillomatous growths and caseous purulent exudate in the ear canal was presented. The differential diagnosis of this condition includes otoacariasis, plasma cell pododermatitis, papillomavirus and chronic bacterial or yeast otitis externa. Despite antimicrobial and antiparasitic based previous treatments, the lesions persisted. Histopathological examination revealed acanthotic epidermis, necrotic keratinocytes, and inflammatory cell infiltrates. Treatment involved methylprednisolone injection, topical pomades, and systemic antibiotics. The cat showed improvement after initial treatment week, with regression of lesions and cessation of ear discharge. Follow-up visits demonstrated continued improvement, and after two months, minimal sequelae remained. In conclusion, despite the unknown etiology of PNOE, the disease is quite responsive to immunosuppressive therapy, which is beneficial for both diagnosis and treatment.