Candida auris Updates: Outbreak Evaluation through Molecular Assays and Antifungal Stewardship-A Narrative Review.

Candida auris was reported by the WHO as second to Cryptococcus neoformans, in the list of nineteen fungal priority pathogens, along with two species with a new nomenclature, Nakaseomyces glabrata (Candida glabrata) and Pichia kudriavzevii (Candida krusei). This novel classification was based on antifungal resistance, the number of deaths, evidence-based treatment, access to diagnostics, annual incidence, and complications and sequelae. We assessed which molecular assays have been used to diagnose Candida auris outbreaks in the last five years. Using "Candida auris; outbreak; molecular detection" as keywords, our search in PubMed revealed 32 results, from which we selected 23 original papers published in 2019-2024. The analyzed studies revealed that the detection methods were very different: from the VITEK® 2 System to MALDI TOF (Matrix-Assisted Laser Desorption Ionization-Time of Flight), NGS (Next-Generation Sequencing), WGS (Whole Genome Sequencing), and commercially available real-time PCR (Polymerase Chain Reaction) assays. Moreover, we identified studies that detected antifungal resistance genes (e.g., FKS for echinocandins and ERG11 for azoles). The analyzed outbreaks were from all continents, which confirms the capability of this yeast to spread between humans and to contaminate the environment. It is important that real-time PCR assays were developed for accurate and affordable detection by all laboratories, including the detection of antifungal resistance genes. This will allow the fast and efficient implementation of stewardship programs in hospitals.

The Optimal Management of Neisseria gonorrhoeae Infections.

Neisseria gonorrhoeae is one of the most frequent etiologic agents of STDs (sexually transmitted diseases). Untreated asymptomatic gonococcal infection in women can lead to spreading of the infection in the sexually active population and could lead to late consequences, such as sterility or ectopic pregnancies. One important issue about N. gonorrhoeae is its increasing resistance to antibiotics. This paper summarized the newest molecular antimicrobial resistance (AMR) detection assays for Neisseria gonorrhoeae connected with the latest therapeutic antimicrobials and gonococcal vaccine candidates. The assays used to detect AMR varied from the classical minimal inhibitory concentration (MIC) detection to whole-genome sequencing. New drugs against multi drug resistant (MDR) N. gonorrhoeae have been proposed and were evaluated in vivo and in vitro as being efficient in decreasing the N. gonorrhoeae burden. In addition, anti-N. gonorrhoeae vaccine candidates are being researched, which have been assessed by multiple techniques. With the efforts of many researchers who are studying the detection of antimicrobial resistance in this bacterium and identifying new drugs and new vaccine candidates against it, there is hope in reducing the gonorrhea burden worldwide.

Host mRNA Analysis of Periodontal Disease Patients Positive for Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Tannerella forsythia.

Periodontal disease is a frequent pathology worldwide, with a constantly increasing prevalence. For the optimal management of periodontal disease, there is a need to take advantage of actual technology to understand the bacterial etiology correlated with the pathogenic mechanisms, risk factors and treatment protocols. We analyzed the scientific literature published in the last 5 years regarding the recent applications of mRNA analysis in periodontal disease for the main known bacterial species considered to be the etiological agents: Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Tannerella forsythia. We identified new pathogenic mechanisms, therapeutic target genes and possible pathways to prevent periodontal disease. The mRNA analysis, as well as the important technological progress in recent years, supports its implementation in the routine management of periodontal disease patients.

Diagnostics of HNSCC Patients: An Analysis of Cell Lines and Patient-Derived Xenograft Models for Personalized Therapeutical Medicine.

Head and neck squamous cell carcinomas (HNSCC) are very frequent worldwide, and smoking and chronic alcohol use are recognized as the main risk factors. For oropharyngeal cancers, HPV 16 infection is known to be a risk factor as well. By employing next-generation sequencing, both HPV-positive and negative HNSCC patients were detected as positive for PI3K mutation, which was considered an optimal molecular target. We analyzed scientific literature published in the last 5 years regarding the newly available diagnostic platform for targeted therapy of HNSCC HPV+/-, using HNSCC-derived cell lines cultures and HNSCC pdx (patient-derived xenografts). The research results are promising and require optimal implementation in the management of HNSCC patients.

Merkel Cell Polyoma Virus and Cutaneous Human Papillomavirus Types in Skin Cancers: Optimal Detection Assays, Pathogenic Mechanisms, and Therapeutic Vaccination.

Oncogenic viruses are recognized to be involved in some cancers, based on very well-established criteria of carcinogenicity. For cervical cancer and liver cancer, the responsible viruses are well-known (e.g., HPV, HBV); in the case of skin cancer, there are still many studies which are trying to identify the possible viral etiologic agents as principal co-factors in the oncogenic process. We analysed scientific literature published in the last 5 years regarding mechanisms of carcinogenicity, methods of detection, available targeted therapy, and vaccination for Merkel cell polyomavirus, and beta human papillomavirus types, in relation to skin cancer. This review is targeted at presenting the recent findings which support the involvement of these viruses in the development of some types of skin cancers. In order to optimize the management of skin cancer, a health condition of very high importance, it would be ideal that the screening of skin cancer for these two analysed viruses (MCPyV and beta HPV types) to be implemented in each region's/country's cancer centres' molecular detection diagnostic platforms, with multiplex viral capability, optimal sensitivity, and specificity; clinically validated, and if possible, at acceptable costs. For confirmatory diagnosis of skin cancer, another method should be used, with a different principle, such as immunohistochemistry, with specific antibodies for each virus.

Update in pediatric primary brain tumors - from histology to genetically defined tumors.

In childhood and in adolescence, primary tumors of the central nervous system (CNS) are the second most common malignancy after leukemia. The most common entities are gliomas, craniopharyngiomas and embryonal tumors, including primitive neuroectodermal tumors of the CNS, such as medulloblastoma. Proper management of malignancies requires a histological diagnosis, especially in childhood, since diagnostic errors have a significant negative influence on the treatment and subsequently on the patient's care. Experimental research conducted in the last years regarding the genomic and epigenetic landscape of pediatric brain tumors has provided considerable help in understanding their pathogenesis. New mutations and new signaling pathways have been associated with pediatric neoplasia, according to recent studies. Current therapeutic protocols recommend triple therapy, consisting in the surgical resection of the tumor, radiotherapy and chemotherapy. However, the success of the therapy depends on the precociousness of establishing the diagnosis and initiating the treatment, age of the child, type of surgery (total∕partial), result of the histological examination, chemotherapy protocols and type of radiotherapy. Although immunotherapy and gene therapy continue to be a challenge, extensive studies are needed in order to confirm their promising role in the management of pediatric brain tumors.

Epidemiological aspects of hydatidosis in children, in some areas of north-eastern Romania.

UNLABELLED: Hydatid cyst is a major public health problem in the pediatric population, both in terms of its frequency and of its endemic character in certain regions. The aim of the study was to present the incidence of hydatidosis in children who were hospitalized in pediatric clinics specialized in surgery of the Emergency Hospital for Children "St. Maria" from lasi. MATERIAL AND METHODS: Prospective study conducted in the interval 2008-2012 in a series of 194 children patients from Moldova, Romania. RESULTS: The peak incidence of the hydatid disease is located around the age of 11-14 years (33%) in male patients (55%) from rural areas (79%) and families with low socioeconomic level. The hepatic localization of the hydatid cyst (50.51%) among children was more common than pulmonary localization (16.49%). Liver and lung localization was found in 22.16% of cases. CONCLUSIONS: Hydatidosis remains a major health problem requiring drastic measures to limit the spread and transmission of the parasite in humans, primarily by reducing the number of stray dogs.

[Pulmonary toxoplasmosis in immunosuppressed patient]. / Toxoplasmoza pulmonara la pacientul imunodeprimat.

Pulmonary toxoplasmosis occurs mainly in immunosuppressed patients and its diagnosis mainly relies upon biological confirmation of the parasite. We present the case of a 47 years patient in medullar aplasia after induction chemotherapy for acute lymphoblastic leukemia that developed pulmonary infiltrates of parasitic origin. The diagnosis of pulmonary toxoplasmosis was established after identification of the parasite in brochioloalveolar lavage fluid (BAL) and peripheral blood. Serological tests are of limited utility in immunosuppressed patients. We used classical methods for the diagnosis of parasitosis but they are being replaced by molecular methods. Polymerase Chain Reaction (PCR) allows a highly specific and sensitive diagnosis on any sample but it cannot be performed in any center.

Correlation between asthma and Toxocara canis infection.

UNLABELLED: The aim of the current study was to examine the relationship between asthma and toxocariasis. MATERIAL AND METHODS: We have studied 76 patients with asthma and 88 controls (without asthma) aged 5-16 years. An ELISA test based on the detection of anti-Toxocara canis (E/S antigen) serum immunoglobulin G (IgG) and E (IgE) was done in both groups. Ordinary allergens and E/S antigen of T. canis infections were used to evaluate cutaneous reactivity. RESULTS: Seroprevalence in asthma patients was 68.42% and in the controls 13.63%. This difference was significant. The percentage of asthmatic patients with two anti-Toxocara antibodies was 26.31%, and of 4.54% in controls. All asthma patients with anti-Toxocara IgE had cutaneous reactivity to Ag E/S. CONCLUSIONS: Asthma patients with anti-Toxocara IgE and IgG may have toxocariasis.

[Sensitization to ascaris lumbricoides and asthma severity in children]. / Influenta ascaridiozei asupra severitatii astmului bronsic la copil.

UNLABELLED: There is little information concerning asthma severity and sensitization to Ascaris lumbricoides in pediatric patients. MATERIAL AND METHODS: The relationship between sensitization to Ascaris lumbricoides and asthma severity in 219 patients with a high prevalence of parasitic exposure (IgE antibodies) was studied by using linear, multivariate and logistic regression. RESULTS: Sensitization to Ascaris lumbricoides was associated with positive skin tests for aeroallergens, increased total serum IgE, increased eosinophils, reductions in FEV1 and FEV1/FVC ratio, increased airway Methacholine, bronchodilator responsiveness, and hospitalizations for asthma in the past year. CONCLUSIONS: Sensitization to Ascaris lumbricoides is associated with increased severity of asthma among Romanian children. This association is mediated by a high degree of atopy among the asthma children sensitized to Ascaris lumbricoides and belonging to a population with a low prevalence of helminthiasis.

[Atopic diseases and intestinal helminth infections]. / Afectiunile atopice si infectia intestinala cu helminti.

UNLABELLED: The purpose of the current study was to examine the relationship between past and current intestinal helminth infections, and asthma, allergic rhino-conjunctivitis, and atopic dermatitis. MATERIAL AND METHOD: The study was performed on 84 patients aged 2-18 years with a mean of 9.31 +/- 3.75 years. Helminth infection was determined by stool examinations and questionnaire. Asthma was diagnosed by spirometry, atopic dermatitis and allergic rhino-conjunctivitis by skin prick testing. RESULTS: Stool examinations revealed infection with A. lumbricoides in 5.95% of cases and E. vermicularis in 4.76% of cases. 8 patients had positive tests for at least a helminth. The most frequent respiratory symptoms were caught, wheezing and dispneea. Spirometry showed anormal results in 4.76% of patients and skin tests were positive in 20.24% of cases. 11 patients were diagnosed with allergic rhinoconjunctivitis and 5 with atopic dermatitis. A history of infection with E. vermicularis was associated with increased risk of atopic dermatitis (OR 1.86), asthma (OR 2.11), and allergic rhinoconjunctivitis (OR 1.34), and a positive stool examination for A. lumbricoides was negatively associated with asthma (OR 2.60). CONCLUSIONS: Current A. lumbricoides infection protects against asthma while past infection with E. vermicularis are risk factors for allergic rhinoconjunctivitis, asthma and atopic dermatitis. Interactions depend on the type of helminth and time of infestation.

[Toxocariasis respiratory manifestations in cases hospitalized in the Paediatric Diseases Clinic of Iasi, between 2005-2008]. / Manifestari respiratorii la copiii cu toxocaroza spitalizati in perioada 2005-2008.

UNLABELLED: The authors present the results of retrospective epidemiological, clinical and laboratory diagnosis on toxocariasis cases hospitalized in the Pediatric Diseases Clinic of Iasi, between January 2005-June 2008. MATERIAL AND METHOD: The study included a number of 228 children. RESULTS: Respiratory manifestations were present in 184 children: 105 boys (46.05%) and 79 girls (34.64%), with a slight advance of the rural environment (44.29%). The age distribution highlighted a predominance of 1-5 years of age (65.76%). Respiratory manifestations were fever, coughing, wheezing, asthma, infections of respiratory pathways, pneumonia. The distribution of toxocariasis in children patients in Moldavia, Romania, highlighted a predominance in Iasi. The children with respiratory manifestations had hypereosinophilia associated with hyperleucocytosis. All the patients were serologically confirmed with toxocariasis. The children responded well to treatment with albendazole.

[Cutaneous manifestations on toxocariasis cases hospitalized in the Paediatric Diseases Clinic of Iasi, between 2005-2008]. / Manifestari cutanate la copiii cu toxocaroza spitalizati in perioada 2005-2008.

UNLABELLED: The authors present the results of retroprospective epidemiological, clinical and laboratory diagnosis on toxocariasis cases hospitalized in the Paediatric Diseases Clinic of Iasi, between January 2005- June 2008. MATERIAL AND METHOD: The study included a number of 228 children. RESULTS: Cutaneous manifestations were present in 65 children: 30 boys (46.15%) and 34 girls (52.30%), with a slight advance of the urban environment (53.84%). The age distribution highlighted a predominance of 1-6 age (66.15%). Cutaneous manifestations were pruritus, urticaria, atopic dermatitis, prurigo. The distribution of toxocariasis in children patients in Moldavia, Romania, highlighted a predominance in Iasi. The laboratory diagnosis of the children with cutaneous manifestations: hypereosinophilia was present on 87.69% of the children associated with hyperleucocytosis. All the patients were serologicaly confirmed with toxocariasis. The children responded well to treatment with albendazole.