Immunoproteomics based identification of thioredoxin reductase GliT and novel <Emphasis Type="Italic">Aspergillus fumigatus</Emphasis> antigens for serologic diagnosis of invasive aspergillosis

Background  

There has been a rising incidence of invasive aspergillosis (IA) in critically ill patients, even in the absence of an apparent predisposing immunodeficiency. The diagnosis of IA is difficult because clinical signs are not sensitive and specific, and serum galactomannan has relatively low sensitivity in this group of patients. Therefore, more prompt and accurate disease markers for early diagnosis are needed. To establish disease markers demands a thorough knowledge of fungal antigens which may be detected in the serum or other body fluids of patients. Herein we report novel immunodominant antigens identified from extracellular proteins of Aspergillus fumigatus.     

T2 magnetic resonance for the diagnosis of deep-seated invasive candidiasis in a liver recipient without candidemia

Background

T2 magnetic resonance imaging (T2MR) is a new method for the diagnosis of invasive candidiasis, although most studies have analyzed its role in patients with candidemia or not infection.

The continuous changes in the aetiology and epidemiology of invasive candidiasis: from familiar <Emphasis Type="Italic">Candida albicans</Emphasis> to multiresistant <Emphasis Type="Italic">Candida auris</Emphasis>

Recent changes in the aetiology and epidemiology of invasive candidiasis have serious implications for current and future diagnosis, treatment and prognosis. The aim of the current review was to discuss the epidemiology of invasive candidiasis, the distribution of Candida species in different regions of the world, the medical concerns of the changing aetiology and the emergence of antifungal resistance. Overall burden of invasive candidiasis remains high, especially in vulnerable persons, such as the elderly, immunosuppressed or debilitated patients. Moreover, there is a progressive shift in the aetiology of invasive candidiasis from Candida albicans to other species of Candida, probably related to the increased use of azole drugs with a clear trend towards increased antifungal resistance. Finally, the emergence and rise of multiresistant species, such as Candida auris or Candida glabrata, is a major threat making necessary invasive candidiasis worldwide surveillances. These changes have serious implications for the diagnosis, treatment and prognosis of invasive candidiasis. Updated knowledge of the current local epidemiology of invasive candidiasis is critical for the clinical management.     

A first step in understanding an invasive weed through its genes: an EST analysis of invasive <Emphasis Type="Italic">Centaurea maculosa</Emphasis>

Background  

The economic and biological implications of plant invasion are overwhelming; however, the processes by which plants become successful invaders are not well understood. Limited genetic resources are available for most invasive and weedy species, making it difficult to study molecular and genetic aspects that may be associated with invasion.     

Detection of excretory <Emphasis Type="Italic">Entamoeba histolytica</Emphasis> DNA in the urine,and detection of <Emphasis Type="Italic">E. histolytica</Emphasis> DNA and lectin antigen in the liver abscess pus for the diagnosis of amoebic liver abscess

Background  

Amoebic liver abscess (ALA) and pyogenic liver abscesses (PLA) appear identical by ultrasound and other imaging techniques. Collection of blood or liver abscess pus for diagnosis of liver abscesses is an invasive procedure, and the procedure requires technical expertise and disposable syringes. Collection of urine is a noninvasive procedure. Therefore, there has been much interest shown towards the use of urine as an alternative clinical specimen for the diagnosis of some parasitic infections. Here, we report for the first time the detection of E. histolytica DNA excreted in the urine for diagnosis of the cases of ALA.     

Use of 65-kDa mannoprotein gene primers for real-time identification of Candida albicans

Invasive candidiasis is associated with high morbidity and mortality, especially in immunocompromised patients. Early diagnosis is often difficult because most clinical signs and symptoms are nonspecific and blood cultures are often negative or become positive too late. Consequently, effective treatment is often delayed. Therefore, there has been an increased interest in the development of molecular-based technology in the diagnosis of invasive candidiasis. In this review, we compare molecular diagnostic tests currently adopted and those under evaluation. We highlight the advantages and the limitations of these methods for the diagnosis of invasive candidiasis. We also describe recent methods based on real time with primers of a gene coding for a 65-kDa mannoprotein of Candida albicans.     

A model of blood flow in the mesenteric arterial system

Background  

There are some early clinical indicators of cardiac ischemia, most notably a change in a person's electrocardiogram. Less well understood, but potentially just as dangerous, is ischemia that develops in the gastrointestinal system. Such ischemia is difficult to diagnose without angiography (an invasive and time-consuming procedure) mainly due to the highly unspecific nature of the disease.     

Species distribution and <Emphasis Type="Italic">in vitro</Emphasis> antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis

Background  

In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis.     

Predicting invasion in mammographically detected microcalcifcation: a preliminary report

Background  

With the increased use of mammography for breast cancer screening, the diagnosis of ductal carcinoma in situ (DCIS) too has increased. This study was carried out to identify clinical and radiological factors that may predict the presence of invasive disease within mammographically detected microcalcifcation.     

Candidiasis of the Central Nervous System in Neonates and Children With Primary Immunodeficiencies

Purpose of review

Candida infections of the central nervous system (CNS) are a life-threatening complication of invasive infections that most often affect vulnerable groups of patients, including neonates and children with primary immunodeficiency disorders (PID). Here, we review the currently known risk factors for CNS candidiasis, focusing predominantly on the PID caused by biallelic mutations in CARD9.

Recent findings

How the CNS is protected itself against fungal invasion is poorly understood. CARD9 promotes neutrophil recruitment and function, and is the only molecule shown to be critical for protection against CNS candidiasis in humans thus far.

Summary

Fundamental insights into the pathogenesis of CNS candidiasis gained from studying rare CARD9-deficient patients has significant implications for other patients at risk for this disease, such as CARD9-sufficient neonates. These findings will be important for the development of adjunctive immune-based therapies, which are urgently needed to tackle the global burden of invasive fungal diseases.

     

Invasive Fungal Infection in Primary Immunodeficiencies Other Than Chronic Granulomatous Disease

Purpose of review

We aimed to review invasive fungal infections complicating primary immunodeficiencies (PID).

Recent findings

Several PID predisposing to fungal infections were recently deciphered. CARD9 deficiency selectively predisposes to fungal infections including candidiasis, aspergillosis, deep dermatophytosis, and phaeohyphomycosis, with frequent central nervous system location, especially after Candida infection. Patients with heterozygous STAT1 gain-of-function mutations are mostly predisposed to chronic mucocutaneous candidiasis but may also display, even though less frequently, invasive fungal infections. Aspergillosis complicating STAT3 deficiency is also a major concern in patients with lung cavities. Antifungal prophylaxis is recommended in this first group of patients. Previously well-reported PID are known to predispose to fungal infections, such as genetic defects impairing the IL-12/IFN-γ axis can predispose to cryptococcosis, and dimorphic fungal infections.

Summary

Patients developing invasive fungal infections including candidiasis, aspergillosis, cryptococcosis, phaeohyphomycosis, pneumocystosis, or disseminated infections caused by dimorphic fungi, without known underlying risk factors, should be explored immunogenetically in order to diagnose primary immunodeficiencies, even in the absence of previous other infectious episodes.

     

Manifestaciones mucocutáneas y su relación con el recuento de linfocitos T CD4 en pacientes infectados con el virus de inmunodeficiencia humana hospitalizados en Medellín,Colombia

Introduction.

About 80-95% of patients infected with the human immunodeficiency virus (HIV) develop skin manifestations, which are markers of the patients’ immune status. Objective. To describe the dermatologic manifestations and the clinical and sociodemographic factors of hospitalized patients diagnosed with HIV and their correlation with CD4 T-lymphocyte count.

Materials and methods.

We conducted an observational, cross-sectional, and retrospective study of the medical records of 227 adult patients with HIV diagnosis evaluated by dermatology in a hospital in Medellín, Colombia.

Results.

We included 227 patient records with 433 dermatologic manifestations, 64.4% of them infectious. The most frequent manifestations were oral candidiasis, condylomata acuminata, and drug reactions. Moreover, a statistically significant relationship was found between disseminated herpes zoster virus and secondary syphilis with a CD4 count between 200-499 cells/mm³ (p=0.04 and 0.028, respectively). There was also a statistically significant relationship between oral candidiasis and a CD4 count of less than 100 cells/ mm³ (p=0.008).

Conclusions.

The relationship between disseminated herpes zoster with CD4 between 200-499 cells/mm³ suggests that, despite having high CD4 counts, severe forms of the disease may occur due to possible T-cell dysfunction and depletion of the immune system. Additionally, the relationship between oral candidiasis and CD4 less than 100 cells/mm³ indicates the potential role of oral candidiasis as an essential marker of weakened immune status in HIV patients.     

Untargeted Antifungal Treatment Strategies for Invasive Candidiasis in Non-neutropenic Critically Ill Patients: Current Evidence and Insights

Purpose of Review

The purpose of this study was to provide an overview and insights on important new concepts on untargeted antifungal treatment strategies, namely prophylaxis pre-emptive and empiric treatments for the management of invasive candidiasis (IC) in non-neutropenic critically ill patients.

Recent Findings

Recently, clinical practice guidelines provided recommendation for the management of IC. However, results from recent trials and systematic reviews questioned the effect of untargeted antifungal treatment strategies, especially in terms of survival benefits in non-neutropenic patients, even with septic shock.

Summary

Widespread use of untargeted antifungal treatment strategies seems not to be justified anymore. Future research should evaluate comprehensive diagnostic-therapeutic approaches, including the implementation of de-escalation. In the meanwhile, clinicians should take into account all available sources of information including clinical evaluation, risk factor assessment, scores, and surrogate biomarkers to tailor antifungal treatment before definitive microbiological diagnosis.

     

LOSITAN: A workbench to detect molecular adaptation based on a <Emphasis Type="Italic">F</Emphasis><Subscript><Emphasis Type="Italic">st</Emphasis></Subscript>-outlier method

Background  

Testing for selection is becoming one of the most important steps in the analysis of multilocus population genetics data sets. Existing applications are difficult to use, leaving many non-trivial, error-prone tasks to the user.     

Expression of recombinant <Emphasis Type="Italic">Clostridium difficile</Emphasis> toxin A and B in <Emphasis Type="Italic">Bacillus megaterium</Emphasis>

Background  

Major Clostridium difficile virulence factors are the exotoxins TcdA and TcdB. Due to the large size and poor stability of the proteins, the active recombinant TcdA and TcdB have been difficult to produce.     

Visual recovery after perinatal stroke evidenced by functional and diffusion MRI: case report

Background  

After perinatal brain injury, clinico-anatomic correlations of functional deficits and brain plasticity remain difficult to evaluate clinically in the young infant. Thus, new non-invasive methods capable of early functional diagnosis are needed in young infants.     

Emergence of Resistance to Fluconazole in <Emphasis Type="Italic">Candida albicans</Emphasis> Isolated From Vaginal Discharge

Purpose of Review

To provide information about the emergence of fluconazole resistance in Candida albicans isolated from vaginal discharge, in a global context, and to update the in vitro susceptibility profile of this species from Argentina.

Recent Findings

Vulvovaginal candidiasis is the second most common vaginal infection after vaginal bacteriosis. C. albicans remains the prevalent etiological yeast species, and despite antifungal treatment, the rate of recurrence remains high, which may be associated to antifungal resistance.

Summary

Data here presented were obtained from the study of C. albicans strains isolated from patients with clinical signs of vulvovaginal candidiasis from 1996 to 2017. Data obtained could represent the susceptibility profile of C. albicans strains circulating in Argentina and could be of potential usefulness to monitor and guide therapy, and also suggests the need for greater surveillance programs to detect fluconazole resistance over time.

     

<Emphasis Type="Italic">Anaplasma phagocytophilum</Emphasis> infection in a domestic cat in Finland: Case report

Background  

Anaplasmosis is a vectorborne disease caused by the gram-negative bacterium Anaplasma phagocytophilum. This species displays positive tropism to granulocytes and can cause illness in several mammalian species, including cats, dogs, and humans. It is considered as an emerging disease in Europe. The clinical signs are nonspecific and include fever, lethargy, and inappetence. The most typical hematologic abnormality is thrombocytopenia. A tentative diagnosis can be made by detecting intracytoplasmic morulae inside neutrophils. The diagnosis is confirmed by PCR and serology in paired serum samples. A sample for PCR analysis should be taken before treatment. Anaplasmosis is treated with doxycycline.