Genital Warts in Women Vaccinated against HPV in Childhood: A Systematic Review.

Human papillomavirus (HPV) is the most prevalent sexually transmitted infection among young women. Notably, more than ten years after the introduction of HPV vaccination programs in Europe, it is essential to review the real-world evidence of the incidence of anogenital warts (GWs) among women vaccinated during childhood. In this systematic review, three databases were searched for studies published between January 2008 and September 2023. Nine cohort studies were included. A total of 890,320 HPV-vaccinated women and 1,922,033 unvaccinated women were evaluated. All the studies but one investigated the 4vHPV vaccine. The incidence rate of GWs in vaccinated women ranged from 0.0 to 1650 per 100,000 person-years. The highest incidence rates were found in women vaccinated with one dose at the age of 17-19 years old and in fully vaccinated women only after 19 years of age. Similar incidence values were reported among unvaccinated women. The incidence of GWs was lower when the age at first dose was 9-11 years old. This systematic review reveals that the incidence of GWs among HPV-vaccinated women is related to the age of vaccination and the number of vaccine doses received. In the post-vaccination era, epidemiological surveillance of the incidence of GWs and their genotypes is crucial.

Does repeated exposure to hydrogen peroxide induce Candida auris resistance?

BACKGROUND: To minimize environmental colonization by microorganisms that may persist and thrive in healthcare settings, thus reducing healthcare-associated infections (HAIs), new insights over already known biocides are certainly of relevance. Although the efficacy of hydrogen peroxide (H2O2) against the emergent yeast Candida auris is moderately documented, concerns over the potential induction of resistance after repeated exposure do persist. The main objective of the present study was to evaluate the hypothetical induction of Candida auris resistance following 30 days of consecutive exposure to lethal and sublethal concentrations of H2O2. Furthermore, the authors aimed to elucidate about the rank of efficacy of H2O2 against C. auris comparing to other Candida species and whether different strains of C. auris may display different susceptibilities to H2O2. METHODS: During the induction of resistance assays, both type strains and clinical isolates of Candida auris, Candida albicans and Candida parapsilosis were exposed repeatedly to defined concentrations of H2O2, for 30 days. RESULTS: After that period, no significant differences were found when comparing the minimal inhibitory concentration values of H2O2 in case of the induced strains versus each respective positive control. Moreover, H2O2 displayed similar effectiveness against all the tested Candida species and no differences were demonstrated among the distinct strains of C. auris. CONCLUSIONS: The adoption of H2O2 solutions in routine protocols in order to promote disinfection standards against Candida auris, improving patient safety and reducing healthcare costs, is certainly welcomed.

Impact of Human Papillomavirus Vaccination on Male Disease: A Systematic Review.

Human papillomavirus (HPV)-related diseases are highly prevalent in men worldwide, comprising external anogenital condyloma, anal intraepithelial neoplasia (AIN), penile intraepithelial neoplasia (PIN), and anogenital and oropharyngeal cancers. There is exceptionally low vaccine coverage in the male population. Only 4% of men were fully vaccinated, worldwide, as of 2019. The aim of this review is to assess the impact of HPV vaccination on male disease. Three databases (MEDLINE, Web of Science, Scopus) and Clinical Trials.gov were searched. We included thirteen studies, eight randomized controlled trials (RCTs), and five cohorts, comprising a total of 14,239 participants. Regarding anal disease, seven studies reported HPV vaccine efficacy ranging from 91.1% to 93.1% against AIN1, and ranging from 89.6% to 91.7% against AIN2|3 and anal cancer. Five studies showed an efficacy against genital condyloma of 89.9% in HPV-naïve males, varying between 66.7% and 67.2% in intention-to-treat populations. Studies reporting no efficacy have included older participants. These results support vaccination of young men previously infected, beyond HPV-naïve males. The evidence quality was moderate to low for most outcomes, namely genital diseases. RCTs are needed to assess the efficacy of HPV vaccination on male oropharyngeal cancer.

Mpox Person-to-Person Transmission-Where Have We Got So Far? A Systematic Review.

The recent multi-country outbreak of Mpox (Monkeypox disease) constituted a public health emergency. Although animal-to-human transmission is known to be the primary way of transmission, an increasing number of cases transmitted by person-to-person contact have been reported. During the recent Mpox outbreak sexual or intimate contact has been considered the most important way of transmission. However, other routes of transmission must not be ignored. The knowledge of how the Monkeypox Virus (MPXV) spreads is crucial to implement adequate measures to contain the spread of the disease. Therefore, this systematic review aimed to collect scientific data published concerning other implicated sources of infection beyond sexual interaction, such as the involvement of respiratory particles, contact with contaminated surfaces and skin-to-skin contact. The current study was performed using the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Publications analyzing contacts of Mpox index cases and their outcome after contact were included. A total of 7319 person-to-person contacts were surveyed and 273 of them became positive cases. Positive secondary transmission of MPXV was verified after contact with people cohabiting in the same household, with family members, with healthcare workers, or within healthcare facilities, and sexual contact or contact with contaminated surfaces. Using the same cup, sharing the same dishes, and sleeping in the same room or bed were also positively associated with transmission. Five studies showed no evidence of transmission despite contact with surfaces, skin-to-skin contact, or through airway particles within healthcare facilities where containment measures were taken. These records support the case for person-to-person transmission and suggest that other types of contact beyond sexual contact pose a significant risk of acquiring the infection. Further investigation is crucial to elucidate MPXV transmission dynamics, and to implement adequate measures to contain the spread of the infection.

Microbiota of Urine, Glans and Prostate Biopsies in Patients with Prostate Cancer Reveals a Dysbiosis in the Genitourinary System.

Prostate cancer (PCa) is the most common malignant neoplasm with the highest worldwide incidence in men aged 50 years and older. Emerging evidence suggests that the microbial dysbiosis may promote chronic inflammation linked to the development of PCa. Therefore, this study aims to compare the microbiota composition and diversity in urine, glans swabs, and prostate biopsies between men with PCa and non-PCa men. Microbial communities profiling was assessed through 16S rRNA sequencing. The results indicated that α-diversity (number and abundance of genera) was lower in prostate and glans, and higher in urine from patients with PCa, compared to non-PCa patients. The different genera of the bacterial community found in urine was significantly different in PCa patients compared to non-PCa patients, but they did not differ in glans and prostate. Moreover, comparing the bacterial communities present in the three different samples, urine and glans show a similar genus composition. Linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed significantly higher levels of the genera Streptococcus, Prevotella, Peptoniphilus, Negativicoccus, Actinomyces, Propionimicrobium, and Facklamia in urine of PCa patients, whereas Methylobacterium/Methylorubrum, Faecalibacterium, and Blautia were more abundant in the non-PCa patients. In glans, the genus Stenotrophomonas was enriched in PCa subjects, while Peptococcus was more abundant in non-PCa subjects. In prostate, Alishewanella, Paracoccus, Klebsiella, and Rothia were the overrepresented genera in the PCa group, while Actinomyces, Parabacteroides, Muribaculaceae sp., and Prevotella were overrepresented in the non-PCa group. These findings provide a strong background for the development of potential biomarkers with clinical interest.

Reducing Blood Loss in a Burn Care Unit: A Review of Its Key Determinants.

Patients with a major burn injury differ considerably from the typical critical ill and trauma population. Very often, burn patients suffer from anemia throughout their hospital stay. This is caused both by combination of persistent blood loss with decreased erythropoiesis. Therefore, burn patients do have major transfusion requirements. However, transfusion is not devoid of risks or costs. We hereby review the best surgical techniques and medical approaches, aiming to reduce blood loss in a burn patient and optimize red cell production, so that we can reduce the need of RBC transfusion. The implementation of a combination of surgical techniques aiming to reduce blood loss and medical care approaches to prevent anemia, rather than single attitudes, should be adopted in burn care. There is an urgent need for clear guidelines that can easily be accepted, applied, and spread across different burn units to methodically implement measures to reduce blood loss and transfusion needs, and ultimately improve burn patients' outcome and the health care financial status.

Microbiome in Male Genital Mucosa (Prepuce, Glans, and Coronal Sulcus): A Systematic Review.

The human body represents a complex and diverse reservoir of microorganisms. Although the human microbiome remains poorly characterized and understood, it should not be underestimated, since recent studies have highlighted its importance in health. This is especially evident when considering microbiota in the male reproductive system, responsible for men's fertility and sexual behavior. Therefore, the aim of this systematic review is to provide an overview of the microbial communities of the healthy male genital mucosa and its role in disease. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was limited to the English language and studies published until August 2022 that included culture-independent techniques for microbiome characterization in male genital mucosa. Ten articles were included. The bacterial composition of the male genital mucosa consists of several genera including Prevotella, Finegoldia, Peptoniphilus, Staphylococcus, Corynebacterium, and Anaerococcus, suggesting that the male genital microbiome composition shows similarities with the adjacent anatomical sites and is related with sexual intercourse. Moreover, male circumcision appears to influence the penile microbiome. Despite the lack of knowledge on the male genital mucosa microbiome in disease, it was reported that Staphylococcus warneri and Prevotella bivia were associated with balanoposthitis, whereas Enterobacteriaceae, Prevotella, and Fusobacterium were more abundant in male genital lichen sclerosus. The limited data and paucity of prospective controlled studies highlight the need for additional studies and established criteria for sampling methods and the microbiome assay procedure. Such a consensus would foster the knowledge about the composition of the genital microbiome of healthy males and its role in disease.

FKS1 mutation associated with decreased echinocandin susceptibility of Aspergillus fumigatus following anidulafungin exposure.

Invasive aspergillosis (IA) is a potentially lethal infection that affects mostly immunocompromised patients caused by Aspergillus fumigatus. Echinocandins are a second-line therapy against IA, used as a salvage therapy as well as for empirical or prophylactic therapy. Although they cause lysis of growing hyphal tips, they are considered fungistatic against molds. In vivo echinocandins resistance is uncommon; however, its wide clinical use could shortly lead to the emergence of A. fumigatus resistance. The aims of the present work was to assess the development of reduced echinocandins susceptibility phenotype by a A. fumigatus strain and to unveil the molecular mechanism underlying such phenotype. We induced in vitro cross-resistance to echinocandins following exposure of A. fumigatus to anidulafungin. Stability of the resistant phenotype was confirmed after removal of anidulafungin pressure. The FKS1 gene was partially sequenced and a E671Q mutation was found. A computational approach suggests that it can play an important role in echinocandin resistance. Given the emerging importance of this mechanism for clinical resistance in pathogenic fungi, it would be prudent to be alert to the potential evolution of this resistant mechanism in Aspergillus spp infecting patients under echinocandins therapeutics.

Mechanisms of Acquired In Vivo and In Vitro Resistance to Voriconazole by Candida krusei following Exposure to Suboptimal Drug Concentration.

Five Candida krusei isolates (susceptible and resistant) recovered from the urine of a kidney transplant patient treated with voriconazole (VRC) 200 mg twice daily for 20 days were studied. Eight unrelated clinical isolates of C. krusei were exposed in vitro to VRC 0.001 µg/ml for 30 days. Development of VRC transient resistance occurred in vivo, and induction of permanent resistance occurred in vitro Mostly, ABC1 and ERG11 genes were overexpressed, and a homozygous T418C mutation in the ERG11 gene was found.

Epidemiology and susceptibility profile to classic antifungals and over-the-counter products of Malassezia clinical isolates from a Portuguese University Hospital: a prospective study.

PURPOSE: Clinical epidemiological data about the distinct Malassezia species remain scarce. The recurrence of Malassezia-related skin diseases, despite long-term use of antifungals, raises concern about the hypothetical emergence of antifungal resistance. We aimed to assess the distribution of Malassezia species among patients from a University Hospital with pityriasis versicolor, seborrheic dermatitis and healthy volunteers, and to evaluate the susceptibility profile to classic antifungals and over-the-counter compounds, searching for clinical associations. METHODOLOGY: The enrollment of volunteers was conducted at the Dermatology Department of a University Hospital over a 3 year period. Malassezia culture isolates were identified to the species-level by sequencing. The drug susceptibility profile was assessed according to a broth microdilution assay, as recommended by the Clinical Laboratory Standards Institute. RESULTS: A total of 86 Malassezia isolates were recovered from 182 volunteers. Malassezia sympodialis was the most frequent isolated species. We found high MIC values and a wide MIC range in the case of tested azoles, and very low terbinafine MIC values against most isolates. Previous topical corticosteroid therapy was associated with a significant increase of MIC values of fluconazole and of terbinafine. CONCLUSION: Conversely to other European studies, M. sympodialis was the most common isolated species, which might be related to geographic reasons. The impact of previous topical corticotherapy upon the antifungal susceptibility profile was hereby demonstrated. In vitro susceptibility test results suggest that terbinafine might be a valid alternative for Malassezia-related skin diseases nonresponsive to azoles.

Malassezia infections with systemic involvement: Figures and facts.

Malassezia are lipophilic and commensal yeasts capable of inducing skin disease among susceptible hosts. However, severely immunocompromised patients and preterm infants admitted to intensive care units are particularly at risk of developing Malassezia systemic infections. Patients often have central venous catheters which are usually the portal of entry for colonization and infection. In addition to the clinically non-specific findings, a delay in the laboratorial diagnosis may occur as there is often the need to add lipid supplementation to culture in order to support these organisms' growth. Herein, we report three unrelated cases of Malassezia bloodstream infection at a university hospital during a 2-year period, followed by a discussion of the clinical results and comparison with the most recently available published data on epidemiology and risk factors, pathogenesis, diagnosis, susceptibility profile and treatment.

Anogenital warts in pediatric population.

The approach to children with anogenital warts in the context of sexual abuse is a challenge in clinical practice. This study aims to review the current knowledge of anogenital warts in children, the forms of transmission, and the association with sexual abuse and to propose a cross-sectional approach involving all medical specialties. A systematic review of the literature was conducted in Portuguese and English from January 2000 to June 2016 using the ISI Web of Knowledge and PubMed databases. Children aged 12 years or younger were included. The ethical and legal aspects were consulted in the Declaration and Convention on the Rights of Children and in the World Health Organization. Non-sexual and sexual transmission events of human papillomavirus in children have been well documented. The possibility of sexual transmission appears to be greater in children older than 4 years. In the case of anogenital warts in children younger than 4 years of age, the possibility of non-sexual transmission should be strongly considered in the absence of another sexually transmitted infection, clinical indicators, or history of sexual abuse. The importance of human papillomavirus genotyping in the evaluation of sexual abuse is controversial. A detailed medical history and physical examination of both the child and caregivers are critical during the course of the investigation. The likelihood of an association between human papillomavirus infection and sexual abuse increases directly with age. A multidisciplinary clinical approach improves the ability to identify sexual abuse in children with anogenital warts.

Anogenital warts in pediatric population

Abstract: The approach to children with anogenital warts in the context of sexual abuse is a challenge in clinical practice. This study aims to review the current knowledge of anogenital warts in children, the forms of transmission, and the association with sexual abuse and to propose a cross-sectional approach involving all medical specialties. A systematic review of the literature was conducted in Portuguese and English from January 2000 to June 2016 using the ISI Web of Knowledge and PubMed databases. Children aged 12 years or younger were included. The ethical and legal aspects were consulted in the Declaration and Convention on the Rights of Children and in the World Health Organization. Non-sexual and sexual transmission events of human papillomavirus in children have been well documented. The possibility of sexual transmission appears to be greater in children older than 4 years. In the case of anogenital warts in children younger than 4 years of age, the possibility of non-sexual transmission should be strongly considered in the absence of another sexually transmitted infection, clinical indicators, or history of sexual abuse. The importance of human papillomavirus genotyping in the evaluation of sexual abuse is controversial. A detailed medical history and physical examination of both the child and caregivers are critical during the course of the investigation. The likelihood of an association between human papillomavirus infection and sexual abuse increases directly with age. A multidisciplinary clinical approach improves the ability to identify sexual abuse in children with anogenital warts.

Genesis of Azole Antifungal Resistance from Agriculture to Clinical Settings.

Azole fungal resistance is becoming a major public health problem in medicine in recent years. However, it was known in agriculture since several decades; the extensive use of these compounds results in contamination of air, plants, and soil. The increasing frequency of life-threatening fungal infections and the increase of prophylactical use of azoles in high-risk patients, taken together with the evolutionary biology evidence that drug selection pressure is an important factor for the emergence and spread of drug resistance, can result in a dramatic scenario. This study reviews the azole use in agricultural and medical contexts and discusses the hypothetical link between its extensive use and the emergence of azole resistance among human fungal pathogens.

New Insights Regarding Yeast Survival following Exposure to Liposomal Amphotericin B.

In vitro resistance to amphotericin B is an extremely rare event among pathogenic yeasts. However, in vivo response is sometimes reduced, resulting in an unfavorable outcome. Such adverse outcomes might be related to subfungicidal plasma concentrations. We aimed to clarify the mechanisms of liposomal amphotericin B (AMB-L; AmBisome)-induced lesions and the mechanisms responsible for yeast cell recovery following exposure at plasma concentrations. The physiological statuses developing following exposure to AMB-L at simulated plasma concentrations (20 to 0.1 mg/liter) and at a constant concentration (3 mg/liter) were assessed in a 24-h time course assay. Time-kill experiments also were carried out under the same AMB-L treatment conditions. Our results suggest that yeast cells develop compensatory responses related to membrane polarization, metabolic activity, and reactive oxygen species (ROS) production after exposure to high plasma concentrations (20 to 5 mg/liter) during the first 6 h; in the remaining 18 h, when exposed to lower concentrations, cells reveal almost full recovery with no evidence of fungicidal activity. In contrast, whenever cells are exposed to a constant concentration above the MIC, despite initially exhibiting compensatory stress responses, soon afterwards they exhibit membrane depolarization, a decrease of metabolic activity, increasing ROS production, and lastly, programmed cell death and necrosis, resulting in succumbing to AMB-L fungicidal effects. This study may represent a step forward in the support of AMB-L use for clinical treatment of invasive fungal infections, since it demonstrates the importance of maintaining levels of AMB-L above the MIC in plasma and tissues to ensure it produces its fungicidal effects.

Associated injuries in pediatric patients with facial fractures in Portugal: Analysis of 1416 patients.

BACKGROUND: The authors performed a retrospective study to clarify the occurrence, causes, severity and predictors of concomitant injuries in pediatric patients with facial fractures in Portugal. METHODS: The clinical records of children and adolescents (0-18 years) with facial fractures treated by the Department of Plastic, Reconstructive, and Aesthetic Surgery and of Maxillofacial Surgery of São João Hospital, in Porto, Portugal, over a period of 20 years (1993-2012) were reviewed. RESULTS: A total of 1416 patients with facial fractures were included in this study. Concomitant injuries were observed in 1015 (71.7%) patients. No significant associations were found between sex and concomitant injury. Head and neck injuries other than facial fractures occurred in 962 patients (67.7%), lower limb injuries in 122 (8.6%), upper limb injuries in 115 (8.1%), thoracic injuries in 89 (6.3%) and abdominal injuries in 47 (3.3%). Concomitant injuries occurred more frequently after motor vehicle accidents (car accident, motorcycle accident and car-pedestrian accident) compared with other etiologies (p < 0.001). CONCLUSION: The incidence of these facial fractures and their concomitant injuries is very high in Portugal. It is necessary to continue with the implementation of control measures and educational programs for the population, so that the number and severity of accidents causing fractures and their associated injuries continue to decrease.

Evaluation of Giardia duodenalis viability after metronidazole treatment by flow cytometry

Giardia duodenalis (syn. lamblia; syn. intestinalis) susceptibility testing is not routinely performed because the classical culture methods are very time-consuming and laborious. We developed a novel flow cytometry (FC) assay to evaluate the susceptibility of G. duodenalis trophozoites to metronidazole (MTZ). Different concentrations of MTZ were added to cultures of trophozoites (10 5 /mL) and the cultures were incubated for different periods. The 50% inhibitory concentration was calculated and propidium iodide (PI) was used to quantify the number of dead cells. After treatment, PI-positive trophozoites increased with increasing drug concentration and exposure time. An excellent correlation was found between FC and the classical method. A novel, accurate and reliable method is now available to evaluate G. duodenalis viability. .

Evaluation of Giardia duodenalis viability after metronidazole treatment by flow cytometry.

Giardia duodenalis (syn. lamblia; syn. intestinalis) susceptibility testing is not routinely performed because the classical culture methods are very time-consuming and laborious. We developed a novel flow cytometry (FC) assay to evaluate the susceptibility of G. duodenalis trophozoites to metronidazole (MTZ). Different concentrations of MTZ were added to cultures of trophozoites (10 5 /mL) and the cultures were incubated for different periods. The 50% inhibitory concentration was calculated and propidium iodide (PI) was used to quantify the number of dead cells. After treatment, PI-positive trophozoites increased with increasing drug concentration and exposure time. An excellent correlation was found between FC and the classical method. A novel, accurate and reliable method is now available to evaluate G. duodenalis viability.

In vivo and in vitro acquisition of resistance to voriconazole by Candida krusei.

Candida krusei is an important agent of opportunistic infections that often displays resistance to several antifungals. We describe here the in vivo acquisition of resistance to voriconazole (VRC) by C. krusei isolates recovered from a leukemia patient during a long period of VRC therapy. In order to mimic the in vivo development of VRC resistance, a susceptible C. krusei isolate was exposed daily to 1 µg/ml of VRC in vitro. Interestingly, after 5 days of exposure to VRC, a MIC of 4 µg/ml was achieved; this value remained constant after 25 additional days of treatment with VRC and also after 30 consecutive days of incubation in VRC-free medium. Our objective was to determine the associated molecular resistance mechanisms, such as expression of efflux pump genes and ERG11 gene mutations, among the resistant strains. Synergistic effects between the efflux blocker tacrolimus (FK506) and VRC were found in all of the resistant strains. Moreover, ABC1 gene expression increased over time in both the in vivo- and in vitro-induced resistant strains, in contrast to the ABC2 and ERG11 genes, whose expression was invariably lower and constant. ERG11 gene sequencing showed two different types of mutations, i.e., heterozygosity at T1389T/C, corresponding to synonymous mutations, in C. krusei strains and a missense mutation at position T418C, resulting in a change from Tyr to His, among resistant C. krusei clinical isolates. This study highlights the relevance of ATP-dependent efflux pump (namely, Abc1p) activity in VRC resistance and describes new mutations in the ERG11 gene among resistant C. krusei clinical isolates.

Specific detection of Pneumocystis jirovecii in clinical samples by flow cytometry.

Pneumocystis jirovecii is an opportunistic pathogen responsible for severe pneumonia in immunocompromised patients. Flow cytometry (FC) is a method widely used in different areas of clinical diagnosis like hematology and immunology. Recently it has started to be used in microbiology with a great potential for diagnosis of emergent microorganisms in clinical samples, especially when present in low numbers. The detection of Pneumocystis jirovecii in respiratory samples can be performed by FC, using specific monoclonal antibodies. Considering clinical diagnosis as a reference method, we previously showed FC to be 100% sensitive and specific when compared to immunofluorescence. Being an automated method, it is faster and less subject to human error than microscopic evaluation.