Host immune responses in dermatophytes infection.

Dermatophytosis is a skin infection caused by keratinophilic, filamentous fungi. These are highly prevalent, common mycoses, affecting approximately 20% of the population. These fungi invade the stratum corneum, and other keratinised tissues, like nails and hair, where they grow by secreting enzymes and degrading keratin to obtain nutrients. Clinical presentation is variable and may depend on many factors, such as the infection site, the host's immunity and the dermatophyte's virulence. Generally, patients with acute superficial dermatophytosis mount cell-mediated immune responses. However, those suffering from chronic or recurrent infections are unable to develop this response, for reasons yet unknown. Several reports have described severe and occasionally life-threatening invasive diseases (deep dermatophytosis) associated with genetic mutations in the innate immunity-associated molecule CARD9, displaying the need to better understand its immune response. These dermatoses have substantial clinical consequences, producing chronic and difficult to treat skin lesions. They also lead to a decline in the patient's quality of life and impact their self-esteem. This review summarises findings on the immune response against dermatophytes.

Recovery of Renal Function in a Kidney Transplant Patient After Receiving Hemodialysis for 4 Months.

Renal transplant is the preferred choice of treatment for end-stage renal diseases. To avoid rejection, increasingly potent immunosuppressants are administered to recipients of kidney transplants. Complications, when there is excess immunosuppression, include possible lethal infections, which reduce allograft survival and compromise patient survival. When there is insufficient immunosuppression, rejections could impair allograft outcomes. Moreover, recurrent primary diseases could also threaten allograft outcomes. Here, we report a case of a patient who underwent ABO-incompatible and living-related renal transplant in which the patient experienced 7 acute kidney injury episodes, including recurrent malignant hypertension, rejection, and infections. After the patient underwent 4 months of hemodialysis (with serum creatinine level of 17 mg/dL), which was later terminated, no adverse effects were found for 1 year (serum creatinine level of 3.7 mg/dL). Therefore, renal function recovery may be longer in patients with renovascular diseases with hypertension. For recipients undergoing hemodialysis with allograft failure, we suggest that the treatment should be not completely withdrawn of immunosuppressants so that acute kidney injuries are minimized. Even after prolonged hemodialysis (eg, for 4 months), recipients may still be able to recover renal function.

[Combined application of NPWT-therapy and reamberin infusion in treatment of lower limb trophic ulcer (clinical case)]. / Sochetannoe primenenie NPWT-terapii i infuzii reamberina v lechenii troficheskoi iazvy nizhnei konechnosti (klinicheskoe nabliudenie).

A clinical case of successful combined use of NPWT-therapy and Reamberin infusion in the treatment of a non-healing (over 5 months) trophic ulcer of the lower limb in an elderly patient is presented. It was manifested that introduction of antioxidant/antihypoxant drug reamberin on the background of NPWT-therapy in patient with slow healing wounds has a positive effect on metabolic processes, resulting in more active and rapid cleansing of wound surface from opportunistic microflora by the 5th day of therapy. Absence of adverse effects to drug application allows to recommend its inclusion in the complex treatment scheme in patients with this pathology.

Variations in the Clinical Course of Patients with Herpes Simplex Virus Esophagitis Based on Immunocompetence and Presence of Underlying Esophageal Disease.

BACKGROUND AND AIMS: Herpes simplex esophagitis (HSE) is the second most common cause of infectious esophagitis and occurs in both immunocompetent and immunocompromised patients. The aim of this study was to reappraise the clinical course of HSE in different patient populations based on degree of immunocompetence and the presence or absence of underlying esophageal disease. METHODS: Patients with histopathologically confirmed HSE identified from the Mayo Clinic pathology database from 2006 to 2016 were included in this study. Relevant demographic, clinical, and endoscopic data were retrospectively reviewed and compared between two cohorts: (a) immunocompromised and immunocompetent patients and (b) patients with and without underlying esophageal disorders. RESULTS: Forty-six patients were included in the study. The most common presenting symptoms were odynophagia (34.8%) and dysphagia (30.4%). Thirty-three (71.7%) patients were immunocompromised, and these patients who experienced longer duration of symptoms (25.5 ± 23.4 days vs. 7.0 ± 5.5 days, p = 0.04) were more likely to require an extension of treatment course (38.1% vs. 8.3%, p = 0.05) compared to their immunocompetent counterparts. Seventeen (37%) patients had underlying esophageal disease, and these patients were more likely to have concomitant esophageal candidiasis (41.2% vs. 10.3%, respectively; p = 0.01). CONCLUSION: Herpes simplex virus causes esophagitis in both immunocompetent and immunocompromised patients. While the disease course appears to be self-limited for all patient populations, clinical and endoscopic differences in the disease presentation and clinical course based on immune status and the presence or absence of underlying esophageal disease exist.

Impact of colonizing organism in the respiratory tract on the incidence, duration, and time between subsequent hospitalizations among patients with cystic fibrosis.

BACKGROUND: This study aimed to examine the association between colonizing respiratory tract organism and frequency, duration, and time between subsequent hospitalizations among hospitalized patients with cystic fibrosis (CF). METHODS: This retrospective cohort study of 312 CF patients from 2 New York City hospitals (2006-2016) examined the effects of colonization with Pseudomonas aeruginosa, methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant S aureus (MRSA), co-colonization on incidence of hospitalization, time to next hospitalization, and total length of stay (LOS). RESULTS: Annual rate of subsequent hospitalizations was highest in patients with P aeruginosa: adjusted incidence rate ratios (aIRRs) were 2.75 (95% confidence interval [CI], 1.72-4.41) for P aeruginosa versus MSSA, 2.57 (95% CI, 1.52-4.31) for co-colonization versus MSSA, and 1.77 (95% CI, 1.04-3.01) for P aeruginosa versus MRSA. Time to readmission was shortest for P aeruginosa: aIRRs were 1.75 (95% CI, 1.05-2.94) for MRSA versus P aeruginosa, 1.64 (95% CI, 1.03-2.59) for MSSA versus P aeruginosa, and 1.61 (95% CI, 1.04-2.47) for co-colonization versus P aeruginosa. LOS was longest for P aeruginosa: aIRRs were 3.41 (95% CI, 2.19-5.32) for P aeruginosa versus MSSA, 1.66 (95% CI, 1.01-2.75) for co-colonization versus MSSA, 2.50 (95% CI, 1.58-3.93) for P aeruginosa versus MRSA, and 2.05 (95% CI, 1.32-3.18) for P aeruginosa versus co-colonization. CONCLUSIONS: CF patients with P aeruginosa alone experienced more hospitalizations, longer LOS, and shorter time to readmission versus patients with S aureus or both organisms.

The DH31/CGRP enteroendocrine peptide triggers intestinal contractions favoring the elimination of opportunistic bacteria.

The digestive tract is the first organ affected by the ingestion of foodborne bacteria. While commensal bacteria become resident, opportunistic or virulent bacteria are eliminated from the gut by the local innate immune system. Here we characterize a new mechanism of defense, independent of the immune system, in Drosophila melanogaster. We observed strong contractions of longitudinal visceral muscle fibers for the first 2 hours following bacterial ingestion. We showed that these visceral muscle contractions are induced by immune reactive oxygen species (ROS) that accumulate in the lumen and depend on the ROS-sensing TRPA1 receptor. We then demonstrate that both ROS and TRPA1 are required in a subset of anterior enteroendocrine cells for the release of the DH31 neuropeptide which activates its receptor in the neighboring visceral muscles. The resulting contractions of the visceral muscles favors quick expulsion of the bacteria, limiting their presence in the gut. Our results unveil a precocious mechanism of defense against ingested opportunistic bacteria, whether they are Gram-positive like Bacillus thuringiensis or Gram-negative like Erwinia carotovora carotovora. Finally, we found that the human homolog of DH31, CGRP, has a conserved function in Drosophila.

Aspergillus precipitating antibody in patients with Mycobacterium avium complex lung disease: A cross-sectional study.

RATIONALE: Little is known about the role of Aspergillus precipitating antibody (APAb) in patients with Mycobacterium avium complex lung disease (MAC-LD). OBJECTIVES: We investigated the clinical characteristics of patients with MAC-LD positive for APAb. METHODS: We conducted a cross-sectional study targeting patients with MAC-LD. APAb was checked in all participants. Clinical variables included laboratory data, pulmonary function, high-resolution computed tomography findings, and health-related quality of life. RESULTS: We analyzed 109 consecutive patients. Their median age was 68 years, and the median duration of MAC-LD was 4.8 years. Twenty (18.3%) patients tested positive for APAb. APAb-positive patients had significantly longer duration of MAC-LD (9.4 vs. 4.0 years, P = 0.017), more severe bronchiectasis evaluated by modified Reiff score (6.5 vs. 4, P = 0.0049), and lower forced expiratory volume in 1 s (%FEV1) (75.1% vs. 86.2%, P = 0.013) than APAb-negative patients. Analysis of covariance adjusted for background factors and underlying pulmonary disease revealed that %FEV1 was also significantly lower in patients with APAb (P = 0.045). Ten patients were newly diagnosed with chronic pulmonary aspergillosis (N = 5) or allergic bronchopulmonary aspergillosis (N = 5). CONCLUSIONS: APAb is associated with lower pulmonary function, and observed especially in patients with longer duration of MAC-LD and severe bronchiectasis, even in the absence of cavitary lesions.

Clinical characteristics and outcomes of patients with chronic disseminated candidiasis who need adjuvant corticosteroid therapy.

We performed a retrospective study involving 21 patients with chronic disseminate candidiasis (CDC) and 38 patients with candidemia. Neutropenia of >2 weeks' duration was more common in those with CDC (71%) than in those with candidemia (26%, P < .001), and the azole-resistant rate in patients with CDC (5%) was lower than that in those with candidemia (29%, P = .03). Of the 21 patients with CDC, five (24%) needed adjuvant corticosteroid therapy due to persistent debilitating fever (median, 19 days). Rapid defervescence (median, 5 days) occurred after adjuvant corticosteroid therapy. However, there were no significant differences in 90-day mortality between CDC patients with and without corticosteroid therapy. Further prospective data are needed to define the role of steroids in this setting.

Host-Pathogen Interactions and Chronic Lung Allograft Dysfunction.

Lung transplantation is now considered to be a therapeutic option for patients with advanced-stage lung diseases. Unfortunately, due to post-transplant complications, both infectious and noninfectious, it is only a treatment and not a cure. Infections (e.g., bacterial, viral, and fungal) in the immunosuppressed lung transplant recipient are a common cause of mortality post transplant. Infections have more recently been explored as factors contributing to the risk of chronic lung allograft dysfunction (CLAD). Each major class of infection-(1) bacterial (Staphylococcus aureus and Pseudomonas aeruginosa); (2) viral (cytomegalovirus and community-acquired respiratory viruses); and (3) fungal (Aspergillus)-has been associated with the development of CLAD. Mechanistically, the microbe seems to be interacting with the allograft cells, stimulating the induction of chemokines, which recruit recipient leukocytes to the graft. The recipient leukocyte interactions with the microbe further up-regulate chemokines, amplifying the influx of allograft-infiltrating mononuclear cells. These events can promote recipient leukocytes to interact with the allograft, triggering an alloresponse and graft dysfunction. Overall, interactions between the microbe-allograft-host immune system alters chemokine production, which, in part, plays a role in the pathobiology of CLAD and mortality due to CLAD.

Fatal disseminated Rasamsonia infection in cystic fibrosis post-lung transplantation.

BACKGROUND: Disseminated fungal infections are a known serious complication in individuals with cystic fibrosis (CF) following orthotopic lung transplantation. Aspergillus fumigatus and Scedosporium species are among the more common causes of invasive fungal infection in this population. However, it is also important for clinicians to be aware of other emerging fungal species which may require markedly different antifungal therapies. CASE SUMMARY: We describe the first laboratory-documented case of a fatal disseminated fungal infection caused by Rasamsonia aegroticola in a 21-year-old female CF patient status post-bilateral lung transplantation, which was only identified post-mortem. Molecular analysis revealed the presence of the identical Rasamsonia strains in the patient's respiratory cultures preceding transplantation. DISCUSSION: We propose that the patient's disseminated fungal disease and death occurred as a result of recrudescence of Rasamsonia infection from her native respiratory system in the setting of profound immunosuppression post-operatively. Since Rasamsonia species have been increasingly recovered from the respiratory tract of CF patients, we further review the literature on these fungi and discuss their association with invasive fungal infections in the CF lung transplant host. CONCLUSION: Our report suggests Rasamsonia species may be important fungal pathogens that may have fatal consequences in immunosuppressed CF patients after solid organ transplantation.

Development of a simple screening tool for opportunistic COPD case finding in primary care in Latin America: The PUMA study.

BACKGROUND AND OBJECTIVE: Opportunistic chronic obstructive pulmonary disease (COPD) case finding approaches for high-risk individuals with or without symptoms is a feasible option for disease identification. PUMA is an opportunistic case finding study conducted in primary care setting of Argentina, Colombia, Venezuela and Uruguay. The objectives were to measure COPD prevalence in an at-risk population visiting primary care for any reason, to assess the yield of this opportunistic approach and the accuracy of a score developed to detect COPD. METHODS: Subjects attending routine primary care visits, ≥40 years of age, current or former smokers or exposed to biomass smoke, completed a questionnaire and performed spirometry. COPD was defined as post-bronchodilator (post-BD) forced expiratory volume in 1 s (FEV1 )/forced vital capacity (FVC) < 0.70 and the lower limit of normal of FEV1 /FVC. RESULTS: A total of 1743 subjects completed the interview; 1540 performed acceptable spirometry. COPD prevalence was 20.1% (n = 309; ranging from 11.0% in Venezuela to 29.6% in Argentina) when defined using post-BD FEV1 /FVC < 0.70, and 14.7% (n = 226; ranging from 8.3% in Venezuela to 21.8% in Colombia) using the lower limit of normal. Logistic regression analysis for both definitions showed that the risk of COPD was significantly higher for persons >50 years, heavy smokers (>30 pack-years), with dyspnoea, and having prior spirometry. A simple score and a weighted score constructed using the following predictive factors: gender, age, pack-years smoking, dyspnoea, sputum, cough and spirometry, had a mean accuracy for detecting COPD (post-BD FEV1 /FVC < 0.70) of 76% and 79% for the simple and weighted scores, respectively. CONCLUSION: This simple seven-item score is an accurate screening tool to select subjects for spirometry in primary care.

A Randomized Trial of Daily Prednisone versus Pulsed Dexamethasone in Treatment-Naïve Adult Patients with Immune Thrombocytopenia: EIS 2002 Study.

Oral prednisone is considered the standard first-line therapy of adult immune thrombocytopenia, but its long-term efficacy is limited. We performed a prospective, randomized, multicenter trial comparing daily prednisone (1-2 mg/kg/day for 2-4 weeks with subsequent dose reduction) with six 3-week cycles of pulsed dexamethasone (0.6 mg/kg/day, days 1-4). The primary endpoint was remission duration. Of 26 patients enrolled, 22 were evaluable for response. Nine were treated with prednisone and 13 with dexamethasone. The median follow-up was 46 months. The initial response rate (PLT ≥50 × 109/l) was 100% in both groups. Long-term remissions were significantly more frequent with pulsed dexamethasone than with daily prednisone (12 months posttreatment: 77 vs. 22%; p = 0.027). The side effects were similar, but patients on dexamethasone suffered significantly more often from insomnia, while patients on prednisone tended to have more infectious complications. Although the cumulative cortisol equivalent dose was comparable during the first 4 weeks of therapy, it was significantly higher in the dexamethasone arm than in the prednisone arm during the ensuing treatment period. We conclude that repeated cycles of pulsed dexamethasone are a good alternative to daily prednisone as a first-line treatment of immune thrombocytopenia. The duration and intensity of glucocorticoid therapy are important determinants of treatment outcome.

[Visceral leishmaniasis concurrent with splenic marginal zone B-cell lymphoma].

Splenic marginal zone B-cell lymphoma (SMZBCL) is a rare non-Hodgkin B-cell lymphoma that presents with morphologically mature lymphoid cells corresponding in their immunological characteristics to secondary follicular marginal zone lymphocytes. It is clinically characterized by splenomegaly, moderate lymphocytosis, usually focal bone marrow lesion, sometimes moderate of monoclonal immunoglobulin in the serum (generally IgM or IgG) and/or urea, and a relatively benign course. Leishmaniasis is a transmissible natural focal infectious endemic disease that has a great diversity of clinical manifestations. The authors describe Russia's first case of SMZBCL concurrent with visceral leishmaniasis in a 52-year-old female patient admitted to a hematology hospital with weakness, splenomegaly, and lymphadenopathy. The simultaneous detection of lymphoma and leishmaniasis in the same biopsy specimen is extremely rare. Visceral leishmaniasis should be borne in mind as an opportunistic infection in patients with malignancies, particularly in immunocompromised persons who live or have stayed in the endemic areas.

Deletion of the entire interferon-γ receptor 1 gene causing complete deficiency in three related patients.

PURPOSE: Complete interferon-γ receptor 1 (IFN-γR1) deficiency is a primary immunodeficiency causing predisposition to severe infection due to intracellular pathogens. Only 36 cases have been reported worldwide. The purpose of this article is to describe a large novel deletion found in 3 related cases, which resulted in the complete removal of the IFNGR1 gene. METHODS: Whole blood from three patients was stimulated with lipopolysaccharide (LPS) and IFN-γ to determine production of tumor necrosis factor (TNF), interleukin-12 p40 (IL-12p40) and IL-10. Expression of IFN-γR1 on the cell membrane of patients' monocytes was assessed using flow cytometry. IFNGR1 transcript was analyzed in RNA and the gene and adjacent regions were analyzed in DNA. Finally, IL22RA2 transcript levels were analyzed in whole blood cells and dendritic cells. RESULTS: There was no expression of the IFN-γR1 on the monocytes. Consistent with this finding, there was no IFN-γ response in the whole blood assay as measured by effect on LPS-induced IL-12p40, TNF and IL-10 production. A 119.227 nt homozygous deletion on chromosome 6q23.3 was identified, removing the IFNGR1 gene completely and ending 117 nt upstream of the transcription start of the IL22RA2 gene. Transcript levels of IL22RA2 were similar in patient and control. CONCLUSIONS: We identified the first large genomic deletion of IFNGR1 causing complete IFN-γR1 deficiency. Despite the deletion ending very close to the IL22RA2 gene, it does not appear to affect IL22RA2 transcription and, therefore, may not have any additional clinical consequence.

Clinical Analysis of Pulmonary Nocardiosis in Patients With Autoimmune Disease.

Nocardiosis is an opportunistic infection that most commonly involves the lung; however, only a few case reports of autoimmune disease complicated by pulmonary nocardiosis exist in the literature. We conducted a retrospective analysis of 24 cases of both autoimmune disease and pulmonary nocardiosis at the Peking Union Medical College Hospital between 1990 and 2012. Fifty-two cases were hospitalized with nocardiosis, 24 of whom had at least 1 autoimmune disease before the diagnosis of pulmonary nocardiosis. The cohort patients consisted of 5 men and 19 women, with a mean age of 44.2 years. All were negative for human immunodeficiency virus. All but 1 patient had received immunosuppressants, including corticosteroids, cyclophosphamide, azathioprine, methotrexate, or hydroxychloroquine. Fever (87.5%), cough (83.3%), and sputum (79.2%) were the most common clinical manifestations. Ten cases were accompanied by subcutaneous nodules and/or cutaneous abscesses, and 4 had brain abscess. Half of them were lymphocytopenic. Thirteen of the 16 cases who underwent lymphocyte subtype analysis had decreased CD4+ T-cell counts. Nineteen cases had decreased serum albumin levels. Nocardia was isolated from sputum (13/24), bronchoalveolar lavage fluid (4/6), lung tissue (5/6), pleural effusions (3/5), skin or cutaneous pus (7/10), and brain tissue (1/1). The most common imaging findings were air-space opacities (83.3%), followed by nodules (62.5%), cavitations (45.8%), and masses (37.5%). Five were administered co-trimoxazole only, and the others were treated with 2 or more antibiotics. All 5 cases with skin abscesses and 2 of the 4 cases with brain abscesses were treated by surgical incision and drainage. None underwent thoracic surgery. Corticosteroid dosages were decreased in all cases, and cytotoxic agents were discontinued in some cases. Twenty-two cases recovered, and 2 died. Pulmonary nocardiosis associated with an underlying autoimmune disease showed a female predominance and presentation at younger age. Immunosuppressant therapy, lymphocytopenia, particularly low CD4+ T-lymphocyte counts, and low serum albumin levels may be disease susceptibility factors. Air-space opacities and nodules were the most common chest imaging features, and disseminated nocardiosis with lung and skin involvement was more common among them. Early diagnosis and anti-nocardial antibiotics with modulation of the basic immunosuppressive therapy were important for them.

Characteristics and Outcome of Streptococcus pneumoniae Endocarditis in the XXI Century: A Systematic Review of 111 Cases (2000-2013).

Streptococcus pneumoniae is an infrequent cause of severe infectious endocarditis (IE). The aim of our study was to describe the epidemiology, clinical and microbiological characteristics, and outcome of a series of cases of S. pneumoniae IE diagnosed in Spain and in a series of cases published since 2000 in the medical literature. We prospectively collected all cases of IE diagnosed in a multicenter cohort of patients from 27 Spanish hospitals (n = 2539). We also performed a systematic review of the literature since 2000 and retrieved all cases with complete clinical data using a pre-established protocol. Predictors of mortality were identified using a logistic regression model. We collected 111 cases of pneumococcal IE: 24 patients from the Spanish cohort and 87 cases from the literature review. Median age was 51 years, and 23 patients (20.7%) were under 15 years. Men accounted for 64% of patients, and infection was community-acquired in 96.4% of cases. The most important underlying conditions were liver disease (27.9%) and immunosuppression (10.8%). A predisposing heart condition was present in only 18 patients (16.2%). Pneumococcal IE affected a native valve in 93.7% of patients. Left-sided endocarditis predominated (aortic valve 53.2% and mitral valve 40.5%). The microbiological diagnosis was obtained from blood cultures in 84.7% of cases. In the Spanish cohort, nonsusceptibility to penicillin was detected in 4.2%. The most common clinical manifestations included fever (71.2%), a new heart murmur (55%), pneumonia (45.9%), meningitis (40.5%), and Austrian syndrome (26.1%). Cardiac surgery was performed in 47.7% of patients. The in-hospital mortality rate was 20.7%. The multivariate analysis revealed the independent risk factors for mortality to be meningitis (OR, 4.3; 95% CI, 1.4-12.9; P < 0.01). Valve surgery was protective (OR, 0.1; 95% CI, 0.04-0.4; P < 0.01). Streptococcus pneumoniae IE is a community-acquired disease that mainly affects native aortic valves. Half of the cases in the present study had concomitant pneumonia, and a considerable number developed meningitis. Mortality was high, mainly in patients with central nervous system (CNS) involvement. Surgery was protective.

TB meets COPD: An emerging global co-morbidity in human lung disease.

Chronic obstructive pulmonary disease (COPD) is emerging as the third largest cause of human mortality worldwide after heart disease and stroke. There is growing evidence of a co-morbidity between COPD and tuberculosis (TB), the leading cause of death globally due to respiratory infection. Thus, the increase in the burden of COPD over the coming decades, as predicted by the World Health Organisation, is of concern with respect to the control of TB. A better understanding of the interactions between these two diseases is essential for the design of complementary preventive and control strategies. In this review, some of the known risk factors that are common to both diseases are discussed. Furthermore, we examine how impairment of the innate immune system, and corticosteroid therapy, in COPD patients may increase the risk of TB manifestation. Conversely, we review how TB lung pathology may heighten susceptibility to subsequent development of COPD, even after completion of effective TB treatment. Growing evidence appears to point towards a bi-directional relationship between these two lung diseases where each may act as an independent risk factor for the other. This has important implications for the respective long-term management of TB and COPD.