Single-cell transcriptomics reveals colonic immune perturbations during amyloid-ß driven Alzheimer's disease in mice.

The "gut-brain axis" is emerging as an important target in Alzheimer's disease (AD). However, immunological mechanisms underlying this axis remain poorly understood. Using single-cell RNA sequencing of the colon immune compartment in the 5XFAD amyloid-ß (Aß) mouse model, we uncovered AD-associated changes in ribosomal activity, oxidative stress, and BCR/plasma cell activity. Strikingly, levels of colon CXCR4 + antibody secreting cells (ASCs) were significantly reduced. This corresponded with accumulating CXCR4 + B cells and gut-specific IgA + cells in the brain and dura mater, respectively. Consistently, a chemokine ligand for CXCR4, CXCL12, was expressed at higher levels in 5XFAD glial cells and in in silico analyzed human brain studies, supporting altered neuroimmune trafficking. An inulin prebiotic fiber diet attenuated AD markers including Aß plaques and overall frailty. These changes corresponded to an expansion of gut IgA + cells and rescued peripheral T regs levels. Our study points to a key glia-gut axis and potential targets against AD. Study Highlights: AD is associated with altered immune parameters in the gut of 5XFAD mice. 5 XFAD colon has reduced ASCs, including CXCR4 + cells with a migratory gene signature. 5XFAD brain gliosis includes increased CXCL12 expression. CXCR4 + B cells and gut-specific IgA + ASCs accumulate in the 5XFAD brain and/or dura mater. Inulin diet attenuates AD disease parameters while boosting IgA + cell and T reg levels.

Species distribution and antifungal susceptibility profiles of clinical and environmental Fusarium isolates from Mexico: A multicenter study.

Fusarium spp. has emerged as an opportunistic etiological agent with clinical manifestations varying from localized infections to deep-seated systemic disease. It is also a phytopathogen of economic impact. There are few reports on the species diversity of this genus, and no comprehensive studies on the epidemiology nor the antifungal susceptibility of Fusarium in Mexico. The present multicentric study aims to shed light on the species distribution and antifungal susceptibility patterns of 116 strains of Fusarium isolated from clinical and environmental samples. Isolates were identified by standard phenotypic characteristics and by sequencing of the ITS (internal transcribed spacer), TEF1 (translation elongation factor 1-α), RPB2 (RNA polymerase II core subunit), and/or CAM1 (calmodulin) regions. Susceptibility tests were carried out against 15 antifungals of clinical and agricultural use. Regarding Fusarium distribution, we identified 27 species belonging to eight different species complexes. The most frequently isolated species for both clinical and environmental samples were F. falciforme (34%), F. oxysporum sensu stricto (12%), F. keratoplasticum (8%), and F. solani sensu stricto (8%). All Fusarium isolates showed minimum inhibitory concentrations (MICs) equal to or above the maximum concentration evaluated for fluconazole, 5-fluocytosine, caspofungin, micafungin, and anidulafungin. All isolates had a MIC of ≤16 µg/mL for voriconazole, with a mode of 4 µg/mL. F. verticillioides appeared to be the most susceptible to all antifungals tested.

Comparison of Omicron breakthrough infection versus monovalent SARS-CoV-2 intramuscular booster reveals differences in mucosal and systemic humoral immunity.

Our understanding of the quality of cellular and humoral immunity conferred by COVID-19 vaccination alone versus vaccination plus SARS-CoV-2 breakthrough (BT) infection remains incomplete. While the current (2023) SARS-CoV-2 immune landscape of Canadians is complex, in late 2021 most Canadians had either just received a third dose of COVID-19 vaccine, or had received their two-dose primary series and then experienced an Omicron BT. Herein we took advantage of this coincident timing to contrast cellular and humoral immunity conferred by three doses of vaccine versus two doses plus BT. Our results show thatBT infection induces cell-mediated immune responses to variants comparable to an intramuscular vaccine booster dose. In contrast, BT subjects had higher salivary immunoglobulin (Ig)G and IgA levels against the Omicron spike and enhanced reactivity to the ancestral spike for the IgA isotype, which also reacted with SARS-CoV-1. Serumneutralizing antibody levels against the ancestral strain and the variants were also higher after BT infection. Our results support the need for the development of intranasal vaccines that could emulate the enhanced mucosal and humoral immunity induced by Omicron BT without exposing individuals to the risks associated with SARS-CoV-2 infection.

Identification of Intestinal Lamina Propria Plasma Cells by Surface Transmembrane Activator and CAML Interactor Expression.

Plasma cells secrete an abundance of Abs and are a crucial component of our immune system. The intestinal lamina propria harbors the largest population of plasma cells, most of which produce IgA. These Abs can bind to beneficial gut bacteria to reinforce intestinal homeostasis and provide protection against enteric pathogens. Plasma cells downregulate many cell-surface proteins commonly used to identify B cells. In mice, expression of the surface marker CD138 has been widely used to identify plasma cells in lymph nodes, bone marrow, and spleen. Intestinal plasma cells require liberation via extensive tissue processing involving treatment with collagenase. We report that detection of CD138 surface expression is reduced following collagenase treatment. Using a mouse in which yellow fluorescent protein expression is controlled by the plasma cell requisite transcription factor Blimp-1, we show that surface detection of transmembrane activator and CAML interactor captures a significant proportion of Ab-secreting plasma cells in the intestinal lamina propria and gut-draining mesenteric lymph nodes. Additionally, we describe a flow cytometry panel based on the detection of surface markers to identify murine B cell subsets in the intestinal lamina propria and, as a proof of concept, combine it with a cutting-edge fate-tracking system to characterize the fate of germinal center B cells activated in early life. By identifying plasma cells and other key intestinal B subsets in a manner compatible with several downstream applications, including sorting and culturing and in vitro manipulations, this efficient and powerful approach can enhance studies of mucosal immunity.

Global and cell type-specific immunological hallmarks of severe dengue progression identified via a systems immunology approach.

Severe dengue (SD) is a major cause of morbidity and mortality. To define dengue virus (DENV) target cells and immunological hallmarks of SD progression in children's blood, we integrated two single-cell approaches capturing cellular and viral elements: virus-inclusive single-cell RNA sequencing (viscRNA-Seq 2) and targeted proteomics with secretome analysis and functional assays. Beyond myeloid cells, in natural infection, B cells harbor replicating DENV capable of infecting permissive cells. Alterations in cell type abundance, gene and protein expression and secretion as well as cell-cell communications point towards increased immune cell migration and inflammation in SD progressors. Concurrently, antigen-presenting cells from SD progressors demonstrate intact uptake yet impaired interferon response and antigen processing and presentation signatures, which are partly modulated by DENV. Increased activation, regulation and exhaustion of effector responses and expansion of HLA-DR-expressing adaptive-like NK cells also characterize SD progressors. These findings reveal DENV target cells in human blood and provide insight into SD pathogenesis beyond antibody-mediated enhancement.

The Role of Helicobacter pylori and Small Intestinal Bacterial Overgrowth in Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disorder whose etiology remains largely unexplained. Several studies have aimed to describe a causative effect in the interactions between the gastrointestinal tract and the brain, for both PD pathogenesis and disease course. However, the results have been controversial. Helicobacter pylori and small intestinal bacterial overgrowth (SIBO) are theorized to be agents capable of triggering chronic proinflammatory changes with a possible neurotoxic effect, as well as a cause of erratic L-dopa response in PD patients. This review evaluates the individual and possibly synergistic influence of H. pylori and SIBO on PD, to provide an opportunity to consider prospective therapeutic approaches.

Co-Infection between Dengue Virus and SARS-CoV-2 in Cali, Colombia.

The co-occurrence of COVID-19 with endemic diseases is a public health concern that may affect patient prognosis and outcomes. The objective of this study was to describe the clinical characteristics of patients with dengue virus (DENV) and SARS-CoV-2 co-infections and compare their outcomes against those of COVID-19 patients without dengue. A cross-sectional study was conducted in patients with SARS-CoV-2 infection who attended a single center in Cali, Colombia, from March 2020 to March 2021. All patients who were tested by both real-time polymerase chain reaction for SARS-CoV-2 and IgM/NS1 for DENV were included. Dengue was diagnosed as having either an IgM- or an NS1- positive test. A total of 90 patients were included (72 with COVID-19 only and 18 with co-infection). Patients with co-infection had more dyspnea (61.1% versus 22.2%; P = 0.003) as well as higher oxygen desaturation (53.3% versus 13.4%; P = 0.002) and neutrophil-to-lymphocyte ratio (5.59 versus 3.84; P = 0.038) than patients with COVID-19 alone. The proportion of patients classified with moderate to severe COVID-19 was higher in the co-infection group (88.3% versus 47.8%; P = 0.002). Also, co-infection was associated with an increased need for mechanical ventilation (P = 0.06), intensive care unit (ICU) initial management (P = 0.02), and ICU admission during hospitalization (P = 0.04) compared with COVID-19 only. The ICU mortality rate was 66.6% in patients with co-infection versus 29.4% in patients infected with only SARS-CoV-2 (P < 0.05). The possibility of DENV and SARS-CoV2 co-infection occurred in the convergence of both epidemic waves. Co-infection was associated with worse clinical outcomes and higher mortality in ICU-admitted patients than in patients with the COVID-19 only.

Severe strongyloidiasis: a systematic review and meta-analysis of 339 cases.

Strongyloidiasis is a parasitosis representing a significant public health problem in tropical countries. It is often asymptomatic in immunocompetent individuals but its mortality rate increases to approximately 87% in severe forms of the disease. We conducted a systematic review, including case reports and case series, of Strongyloides hyperinfection and dissemination from 1998 to 2020 searching PubMed, EBSCO and SciELO. Cases that met the inclusion criteria of the Preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist were analysed. Statistical analysis was performed using Fisher's exact test and Student's t-test and a Bonferroni correction for all the significant values. A total of 339 cases were included in this review. The mortality rate was 44.83%. The presence of infectious complications, septic shock and a lack of treatment were risk factors for a fatal outcome. Eosinophilia and ivermectin treatment were associated with an improved outcome.

Cutaneous tuberculosis as a manifestation of Pott's Disease: A diagnostic challenge in patients with Non-HIV immunosuppression.

Tuberculosis (TB) is one of the most important public health issues in developing countries. The World Health Organization estimates that approximately 20%-40% of the world's population is infected. Pulmonary forms account for the majority of cases; however, it can manifest as extrapulmonary disease in 8.4%-13.7% of cases. Of these extrapulmonary forms of TB, only 1%-2% may have skin manifestations. Cutaneous tuberculosis (CTB) is relatively uncommon and is not a well-defined disease, which complicates diagnosis. We present two patients with Pott's disease that manifested as CTB, one with tuberculous gumma and the other with scrofuloderma. Both patients with non-HIV immunosuppression. The diagnosis of CTB was made by detecting Mycobacterium tuberculosis in skin samples by real-time polymerase chain reaction (Xpert MTB/RIF test) and Ziehl-Neelsen staining. The histologic findings described in these two forms of TB may vary or be absent in immunosuppressed patients, making diagnosis difficult.

Magnitude and kinetics of the human immune cell response associated with severe dengue progression by single-cell proteomics.

Approximately 5 million dengue virus-infected patients progress to a potentially life-threatening severe dengue (SD) infection annually. To identify the immune features and temporal dynamics underlying SD progression, we performed deep immune profiling by mass cytometry of PBMCs collected longitudinally from SD progressors (SDp) and uncomplicated dengue (D) patients. While D is characterized by early activation of innate immune responses, in SDp there is rapid expansion and activation of IgG-secreting plasma cells and memory and regulatory T cells. Concurrently, SDp, particularly children, demonstrate increased proinflammatory NK cells, inadequate expansion of CD16+ monocytes, and high expression of the FcγR CD64 on myeloid cells, yet a signature of diminished antigen presentation. Syndrome-specific determinants include suppressed dendritic cell abundance in shock/hemorrhage versus enriched plasma cell expansion in organ impairment. This study reveals uncoordinated immune responses in SDp and provides insights into SD pathogenesis in humans with potential implications for prediction and treatment.

Recent Antifungal Pipeline Developments against Candida auris: A Systematic Review.

The alarming spread and impact of multidrug-resistant Candida auris infections alongside the limited therapeutic options have prompted the development of new antifungals. These promising agents are currently in different stages of development, offering novel dosing regimens and mechanisms of action. A systematic search in MEDLINE, EMBASE, Web of Science, and Scopus up to 27 June 2022 was conducted to find relevant articles reporting data of in vitro activity and in vivo efficacy of investigational antifungals against C. auris. These included new additions to existing antifungal classes (rezafungin and opelconazole), first-in-class drugs such as ibrexafungerp, manogepix/fosmanogepix, olorofim and tetrazoles (quilseconazole, oteseconazole and VT-1598), as well as other innovative agents like ATI-2307, MGCD290 and VL-2397. From 592 articles retrieved in the primary search, 27 met the eligibility criteria. The most studied agent was manogepix/fosmanogepix (overall MIC90: 0.03 mg/L), followed by ibrexafungerp (overall MIC90: 1 mg/L) and rezafungin (overall MIC mode: 0.25 mg/L), while VT-1598 and ATI-2307 were the least explored drugs against C. auris. All these compounds demonstrated significant improvements in survival and reduction in tissue fungal burden on neutropenic animal models of candidemia due to C. auris. Continual efforts towards the discovery of new treatments against this multidrug-resistant fungus are essential.

Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection.

Although SARS-CoV-2 infects the upper respiratory tract, we know little about the amount, type, and kinetics of antibodies (Ab) generated in the oral cavity in response to COVID-19 vaccination. We collected serum and saliva samples from participants receiving two doses of mRNA COVID-19 vaccines and measured the level of anti-SARS-CoV-2 Ab. We detected anti-Spike and anti-Receptor Binding Domain (RBD) IgG and IgA, as well as anti-Spike/RBD associated secretory component in the saliva of most participants after dose 1. Administration of a second dose of mRNA boosted the IgG but not the IgA response, with only 30% of participants remaining positive for IgA at this timepoint. At 6 months post-dose 2, these participants exhibited diminished anti-Spike/RBD IgG levels, although secretory component-associated anti-Spike Ab were more stable. Examining two prospective cohorts we found that participants who experienced breakthrough infections with SARS-CoV-2 variants had lower levels of vaccine-induced serum anti-Spike/RBD IgA at 2-4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups. These data suggest that COVID-19 vaccines that elicit a durable IgA response may have utility in preventing infection. Our study finds that a local secretory component-associated IgA response is induced by COVID-19 mRNA vaccination that persists in some, but not all participants. The serum and saliva IgA response modestly correlate at 2-4 weeks post-dose 2. Of note, levels of anti-Spike serum IgA (but not IgG) at this timepoint are lower in participants who subsequently become infected with SARS-CoV-2. As new surges of SARS-CoV-2 variants arise, developing COVID-19 booster shots that provoke high levels of IgA has the potential to reduce person-to-person transmission.

An 8-gene machine learning model improves clinical prediction of severe dengue progression.

BACKGROUND: Each year 3-6 million people develop life-threatening severe dengue (SD). Clinical warning signs for SD manifest late in the disease course and are nonspecific, leading to missed cases and excess hospital burden. Better SD prognostics are urgently needed. METHODS: We integrated 11 public datasets profiling the blood transcriptome of 365 dengue patients of all ages and from seven countries, encompassing biological, clinical, and technical heterogeneity. We performed an iterative multi-cohort analysis to identify differentially expressed genes (DEGs) between non-severe patients and SD progressors. Using only these DEGs, we trained an XGBoost machine learning model on public data to predict progression to SD. All model parameters were "locked" prior to validation in an independent, prospectively enrolled cohort of 377 dengue patients in Colombia. We measured expression of the DEGs in whole blood samples collected upon presentation, prior to SD progression. We then compared the accuracy of the locked XGBoost model and clinical warning signs in predicting SD. RESULTS: We identified eight SD-associated DEGs in the public datasets and built an 8-gene XGBoost model that accurately predicted SD progression in the independent validation cohort with 86.4% (95% CI 68.2-100) sensitivity and 79.7% (95% CI 75.5-83.9) specificity. Given the 5.8% proportion of SD cases in this cohort, the 8-gene model had a positive and negative predictive value (PPV and NPV) of 20.9% (95% CI 16.7-25.6) and 99.0% (95% CI 97.7-100.0), respectively. Compared to clinical warning signs at presentation, which had 77.3% (95% CI 58.3-94.1) sensitivity and 39.7% (95% CI 34.7-44.9) specificity, the 8-gene model led to an 80% reduction in the number needed to predict (NNP) from 25.4 to 5.0. Importantly, the 8-gene model accurately predicted subsequent SD in the first three days post-fever onset and up to three days prior to SD progression. CONCLUSIONS: The 8-gene XGBoost model, trained on heterogeneous public datasets, accurately predicted progression to SD in a large, independent, prospective cohort, including during the early febrile stage when SD prediction remains clinically difficult. The model has potential to be translated to a point-of-care prognostic assay to reduce dengue morbidity and mortality without overwhelming limited healthcare resources.

Immunoglobulin A nephropathy is characterized by anticommensal humoral immune responses.

IgA nephropathy (IgAN) is a leading cause of kidney failure, yet little is known about the immunopathogenesis of this disease. IgAN is characterized by deposition of IgA in the kidney glomeruli, but the source and stimulus for IgA production are not known. Clinical and experimental data suggest a role for aberrant immune responses to mucosal microbiota in IgAN, and in some countries with high disease prevalence, tonsillectomy is regarded as standard-of-care therapy. To evaluate the relationship between microbiota and mucosal immune responses, we characterized the tonsil microbiota in patients with IgAN versus nonrelated household-matched control group participants and identified increased carriage of the genus Neisseria and elevated Neisseria-targeted serum IgA in IgAN patients. We reverse-translated these findings in experimental IgAN driven by BAFF overexpression in BAFF-transgenic mice rendered susceptible to Neisseria infection by introduction of a humanized CEACAM-1 transgene (B × hC-Tg). Colonization of B × hC-Tg mice with Neisseria yielded augmented levels of systemic Neisseria-specific IgA. Using a custom ELISPOT assay, we discovered anti-Neisseria-specific IgA-secreting cells within the kidneys of these mice. These findings suggest a role for cytokine-driven aberrant mucosal immune responses to oropharyngeal pathobionts, such as Neisseria, in the immunopathogenesis of IgAN. Furthermore, in the presence of excess BAFF, pathobiont-specific IgA can be produced in situ within the kidney.

Challenges of dengue and coronavirus disease 2019 coinfection: two case reports.

BACKGROUND: Dengue fever and coronavirus disease 2019 have now begun to overlap within tropical and subtropical regions. This is due to the high prevalence of dengue fever in these regions and the current severe acute respiratory syndrome coronavirus 2 pandemic situation. The similarity of symptoms between the two diseases can confuse diagnoses, but coinfection can also occur. CASE PRESENTATION: We present two cases of patients with dengue and severe acute respiratory syndrome coronavirus 2 coinfection. The first case is that of a 24-year-old Hispanic woman with acute fever, odynophagia, and diarrhea, without respiratory symptoms and with positive molecular tests for both dengue and severe acute respiratory syndrome coronavirus 2. The second case is that of a 59-year-old Hispanic male patient with fever and respiratory symptoms of 2 weeks duration, negative molecular tests, and positive serological tests for both viruses. The clinical and epidemiological characteristics of both viral infections can help elucidate diagnoses and prognoses. CONCLUSIONS: Severe dengue infection is common in young adults, while coronavirus disease 2019 is generally asymptomatic. In older people, the severity of dengue fever will depend on their comorbidities or the infectious serotype, but coronavirus disease 2019 is consistently more severe in this group. The accurate diagnosis of both infections can better guide clinical management, as well as public health actions in transmission control, now especially important during the coronavirus disease 2019 pandemic.

CCR6 Expression on B Cells Is Not Required for Clinical or Pathological Presentation of MOG Protein-Induced Experimental Autoimmune Encephalomyelitis despite an Altered Germinal Center Response.

B cells have been implicated in the pathogenesis of multiple sclerosis, but the mechanisms that guide B cell activation in the periphery and subsequent migration to the CNS remain incompletely understood. We previously showed that systemic inflammation induces an accumulation of B cells in the spleen in a CCR6/CCL20-dependent manner. In this study, we evaluated the role of CCR6/CCL20 in the context of myelin oligodendrocyte glycoprotein (MOG) protein-induced (B cell-dependent) experimental autoimmune encephalomyelitis (EAE). We found that CCR6 is upregulated on murine B cells that migrate into the CNS during neuroinflammation. In addition, human B cells that migrate across CNS endothelium in vitro were found to be CCR6+, and we detected CCL20 production by activated CNS-derived human endothelial cells as well as a systemic increase in CCL20 protein during EAE. Although mice that lack CCR6 expression specifically on B cells exhibited an altered germinal center reaction in response to MOG protein immunization, CCR6-deficient B cells did not exhibit any competitive disadvantage in their migration to the CNS during EAE, and the clinical and pathological presentation of EAE induced by MOG protein was unaffected. These data, to our knowledge, provide new information on the role of B cell-intrinsic CCR6 expression in a B cell-dependent model of neuroinflammation.

Fatal Brucellosis Infection in a Liver Transplant Patient: A Case Report and Review of the Literature.

Brucellosis is the most common zoonosis, particularly in developing countries. The true incidence of human brucellosis is unknown. The WHO points out that 500,000 cases of brucellosis are reported each year from around the world. In Colombia, there is currently no regular surveillance of the event in humans and its prevalence is low due a low clinical suspicion. We report a case of a 66-year-old man, an urban merchant, who had received a liver transplant 11 years ago. The patient presented to the emergency department for two months of fatigue, severe myalgia, paresis of the extremities, loss of muscle strength, and progressive deterioration of functional class. In the emergency room, he became disoriented and was transferred to the intensive-care unit. He had a white blood cell count of 18990/uL and creatine phosphokinase 10302 U/L. Routine blood cultures were positive for Brucella melitensis. The patient reported consumption of unpasteurized bovine milk. He was treated with doxycycline and ciprofloxacin. Despite antibiotic management, after one month of hospitalization and in the context of septic shock with multiorgan failure, the patient died. Brucellosis is an unsuspected and underdiagnosed disease. It can occur in people with or without risk factors. Although the mortality is low, immunocompromised patients can develop fatal infections. A presumptive diagnosis can be established through the correlation of patient history and classic laboratory findings, which include transaminitis, anemia, and leukopenia with relative lymphocytosis; however, other findings can help us to guide the diagnosis, such as rhabdomyolysis, which appears as a complication in different infections; however, it had not been described before in brucellosis. A partnership between clinical suspicion laboratory diagnostic tests and improved disease surveillance systems is necessary to fight the disease.

Differentiating Dengue from COVID-19: Comparison of Cases in Colombia.

The differentiation between dengue and COVID-19 diagnoses is a challenge in tropical regions because of the similarity of symptoms and limited access to specific diagnostic tests for each disease. The objective of this study was to describe the initial symptoms and laboratory test values of patients who presented to the emergency department with dengue or COVID-19. A cross-sectional study was performed in a single center in Cali, Colombia. The inclusion criteria were patients with a diagnosis of dengue or COVID-19 who were older than 14 years of age. All patients experienced fever or other symptoms for fewer than 10 days. Linear regression was performed to evaluate the differences in the neutrophil-lymphocyte ratio (NLR) between patients diagnosed with COVID-19 and dengue, and was adjusted for sex and age group (≤ 31 and > 31 years). The sample size was calculated to test the hypothesis that the median NLR in COVID-19 patients is higher than that in dengue patients. A P value < 0.05 was considered statistically significant for all analyses. A total of 93 patients were included: 70 with dengue and 23 with COVID-19. Dengue patients were younger than COVID-19 patients. There were significant differences between dengue and COVID-19 patients regarding platelet count (P < 0.01), neutrophil count (P < 0.01), NLR (P < 0.01), and abnormal alanine transaminase (ALT) (P = 0.03). The NLR was significantly higher in COVID-19 patients than in dengue patients (P < 0.01). In conclusion, during the first week of symptoms, absolute neutrophil count, NLR, and platelet count could help guide the initial differential approach between dengue and COVID-19. These findings could be useful in geographical areas with a lack of resources.

Transmission of malaria from donors to solid organ transplant recipients: A case report and literature review.

Malaria is a febrile and potentially fatal infection. It is typically transmitted to humans through the bite of Anopheles mosquitoes and less frequently can be contracted through blood transfusions, sharing contaminated needles and syringes, mother-to-child transmission, or after solid organ transplantation. Posttransplant malaria has rarely been reported in the literature, even in endemic areas. We report the cases of three solid organ recipients in which Plasmodium vivax infection was documented during postsurgical evaluation 30 days after transplant surgery. The diagnosis of donor-derived malaria was confirmed in all patients by demonstrating Plasmodium in a peripheral blood smear and by polymerase chain reaction (PCR). All recipients had symptoms. The liver transplant recipient had myalgia, arthralgia, and thrombocytopenia; the kidney transplant recipient developed acute renal failure; and the heart transplant recipient had fever, cephalalgia, and tonic-clonic seizures. Pre-transplant screening of donors and recipients from endemic regions may not be sufficient to safely rule out persistent malaria. In Colombia, according to legislation, no mandatory testing is required for the diagnosis of malaria in organ donors in nonendemic areas. Therefore, donor screening by questionnaire is the only tool for preventing transplant-borne malaria. The migratory trend from Venezuela to Colombia has increased the number of imported cases of malaria, and the infection may be present in endemic and nonendemic regions. Although donor evaluation is not standardized in current guidelines, we suggest that donors be tested for malaria with a peripheral blood smear, detection of specific IgG antibodies against Plasmodium, and techniques such as PCR, if possible.

Physiological characterization and molecular identification of some rare yeast species causing onychomycosis.

INTRODUCTION: Onychomycosis are infections with a variety of etiological agents. Although dermatophytes are responsible for most infections, yeasts are gaining importance as agents of these pathologies. The use of antifungals has increased the incidence of what had been considered rare or novel pathogens. We reidentify three rare yeasts from a culture collection of onychomycosis agents by matrix-assisted laser desorption/ionization time of flight/mass spectrometry (MALDI-TOF/MS) and sequencing the internal transcribed spacer (ITS) regions or the intergenic spacer (IGS) 1 region of ribosomal DNA (rDNA), and present their enzymatic and antifungal susceptibility profiles. MATERIAL AND METHODS: We performed a phenotypical characterization and molecular identification of five yeast isolates. We tested the urease, gelatinase, DNase, phospholipase, protease, and esterase activities, as well as the hemolytic activity. We evaluated the antifungal susceptibility to amphotericin B, fluconazole, anidulafungin and caspofungin. RESULTS: Phenotypic methods could not identify the isolates. MALDI-TOF/MS was able to properly identify Candida duobushameulonii. The five isolates were successfully identified by sequence analysis as Candida duobushaemulonii, Meyerozyma caribbica and Cutaneotrichosporon dermatis. Candida duobushameulonii showed hemolytic, phospholipase, and protease activities. Meyerozyma caribbica was positive for gelatinase and protease activities. All antifungals exhibited minimum inhibitory concentrations (MICs) ≤2µg/mL against both species. The three isolates of Cutaneotrichosporon dermatis showed urease, DNase, and esterase activities, and resistance to echinocandins (MICs ≥8µg/mL), while amphotericin B and fluconazole exhibited low MICs against these isolates (0.50-2µg/mL). DISCUSSION: Sequencing of the ITS or IGS1 regions of rDNA remains the best method for identifying cryptic species over other commercially available systems. More reports are needed to define the enzymatic and antifungal profiles for these species. This is the first report of Meyerozyma caribbica and Cutaneotrichosporon dermatis as etiological agents of onychomycosis.