Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma.

OBJECTIVE: The lysyl oxidase-like protein 2 (LOXL2) contributes to tumour progression and metastasis in different tumour entities, but its role in pancreatic ductal adenocarcinoma (PDAC) has not been evaluated in immunocompetent in vivo PDAC models. DESIGN: Towards this end, we used PDAC patient data sets, patient-derived xenograft in vivo and in vitro models, and four conditional genetically-engineered mouse models (GEMMS) to dissect the role of LOXL2 in PDAC. For GEMM-based studies, K-Ras +/LSL-G12D;Trp53 LSL-R172H;Pdx1-Cre mice (KPC) and the K-Ras +/LSL-G12D;Pdx1-Cre mice (KC) were crossed with Loxl2 allele floxed mice (Loxl2Exon2 fl/fl) or conditional Loxl2 overexpressing mice (R26Loxl2 KI/KI) to generate KPCL2KO or KCL2KO and KPCL2KI or KCL2KI mice, which were used to study overall survival; tumour incidence, burden and differentiation; metastases; epithelial to mesenchymal transition (EMT); stemness and extracellular collagen matrix (ECM) organisation. RESULTS: Using these PDAC mouse models, we show that while Loxl2 ablation had little effect on primary tumour development and growth, its loss significantly decreased metastasis and increased overall survival. We attribute this effect to non-cell autonomous factors, primarily ECM remodelling. Loxl2 overexpression, on the other hand, promoted primary and metastatic tumour growth and decreased overall survival, which could be linked to increased EMT and stemness. We also identified tumour-associated macrophage-secreted oncostatin M (OSM) as an inducer of LOXL2 expression, and show that targeting macrophages in vivo affects Osm and Loxl2 expression and collagen fibre alignment. CONCLUSION: Taken together, our findings establish novel pathophysiological roles and functions for LOXL2 in PDAC, which could be potentially exploited to treat metastatic disease.

Imported Strongyloides stercoralis infection and diabetes mellitus and other metabolic diseases: Is there any association?

OBJECTIVES: Strongyloidiasis is a nematode infection caused by Strongyloides stercoralis. Previous studies have addressed the possibility of the parasite to establish a complex relationship with the host that could affect the risk of developing diabetes mellitus or modify its presentation. This study aims to evaluate the potential impact of strongyloidiasis in diabetes mellitus and other metabolic diseases. METHODS: Case-control observational retrospective study that included 95 S. stercoralis-infected patients and 83 non-infected individuals. Epidemiological and clinical variables were retrieved from medical records, and a statistical analysis was carried out to explore any association between strongyloidiasis and diabetes mellitus and other metabolic diseases. RESULTS: Most of the patients were men (99, 55.60%) with a mean age of 42.53 ± SD 14 years. Twelve (6.70%) patients were diabetic; 30 (16.90%) presented arterial hypertension; 28 (15.70%) had dyslipidaemia; and 10 (5.60%) had thyroid pathology. When comparing patients with strongyloidiasis and uninfected patients, no differences were found regarding diabetes mellitus or other metabolic diseases. CONCLUSIONS: The results obtained in the present study do not confirm any type of association between strongyloidiasis and diabetes mellitus or other metabolic diseases.

Weil syndrome coincident with upper gastrointestinal bleeding.

A 48 year old male was referred to our center due to a gastrointestinal bleeding with melena secondary to a Forrest IIb gastric ulcer treated endoscopically. Physical examination revealed bilateral conjunctival suffusion, bradypsychia, and asterixis. Epidemiological history included a trip to Dominican Republic two weeks before, presenting later a flu-like syndrome. He had no history of NSAID use. Laboratory tests showed a normocytic anemia, leukocytosis with neutrophilia, acute renal failure, severe hyponatremia, a predominant direct hyperbilirubinemia, hyperamylasemia, and mild coagulopathy (Table 1). An abdominal ultrasound was performed, with no pathological findings, and a chest-abdominal computed tomography (CT), bilateral diffuse ground glass pulmonary opacities and pleural effusion, mild hepatomegaly, and peritoneal and gastrohepatic ligament lymphadenopathy, with no signs of acute pancreatitis. A second look upper endoscopy revealed a Forrest III gastric ulcer. Gastric biopsies results ruled out malignancy and Helicobacter pylori infection. Due to his recent travel history combined with his characteristic signs and symptoms a clinical diagnosis of leptospirosis was made and empirical antibiotic therapy with meropenem was started. The serology for Leptospira was positive (IgG 1/1600) and antibiotic therapy was de-escalated to ceftriaxone with clinical and analytical remission on day five of his hospital stay with complete radiological resolution at 6 months.

SOLTI-1904 ACROPOLI TRIAL: efficacy of spartalizumab monotherapy across tumor-types expressing high levels of PD1 mRNA.

Improved selection of cancer patients who are most likely to respond to immune checkpoint inhibitors remains an unmet clinical need. Recently, a positive correlation between levels of PD1 mRNA and clinical outcome in response to PD1 blockade across diverse tumor histologies has been confirmed in several datasets. ACROPOLI is a parallel cohort, non-randomized, phase II study that aims to evaluate the efficacy of the anti-PD1 immune checkpoint inhibitor spartalizumab as monotherapy in metastatic patients with solid tumors that express high levels of PD1 (cohort 1; n = 111). An additional cohort of 30 patients with tumors expressing low levels of PD1, where PD1/PD-L1 antibodies in monotherapy are standard treatment, will also be included (cohort 2). Primary end point is overall response rate in cohort 1. Trial registration number: NCT04802876 (ClinicalTrials.gov).

[Intensified epidemiological surveillance of arbovirosis: First case of native dengue fever in Catalonia (Spain), Northern Metropolitan Area of Barcelona, 2018-2019]. / Vigilancia epidemiológica intensificada de arbovirosis: primer caso de dengue autóctono en Cataluña (España), zona Metropolitana Norte de Barcelona, 2018-2019.

OBJECTIVE: To evaluate the results obtained by a surveillance network on arbovirosis composed by doctors and nurses located at hospitals and Primary Care trained in their identification, diagnostic confirmation and clinical management. LOCATION: North Metropolitan Area of Barcelona (1,400,000 inhabitants; Catalonia; Spain) during a calendar year. PARTICIPANTS: Seven Primary Care and 10 hospital physicians plus 4 Primary Care nurses. TYPE OF STUDY: A prospective observational study. MAIN MEASUREMENTS: Demographic, epidemiological (autochthonous/imported, suspect/probable/confirmed case) and healthcare variables (symptoms, serological profile, viral period) were defined. RESULTS: Of the 34 patients identified, 26 (76.5%) met study criteria. Among them, any arbovirosis was confirmed in 14 (53.8%): 13 dengue plus 1chikungunya fever. There were no cases of Zika fever. There was a history of travel to endemic areas 23 (88.4%), but not in 3cases (11.6%) in which the possibility of an indigenous transmission was considered; of them, a case of dengue was confirmed. The estimated incidence of arbovirosis was 0.4 (95%CI: 0.33-0.51) cases ×10,000hab/year which, when compared to the estimated incidence in the same geographical area during the period 2009-2013 (0.19cases ×10,000hab/year; 95%CI: 0.07-0.31), a significant increase was found (P=.044). Patients within viremia period at the time of their first medical visit were 11 (42.3%). CONCLUSIONS: An intensified epidemiological surveillance program defined at Primary Care and hospital levels is able to detect significantly more cases of imported and autochthonous arbovirosis. Possibly we are witnessing an increase in the incidence of imported arbovirosis and, thus, measures aimed at their identification and confirmation should be reinforced.

Hantavirus Pulmonary Syndrome in Traveler Returning from Nepal to Spain.

Most human hantavirus infections occur in Asia, but some cases have been described in Europe in travelers returning from Asia. We describe a case of hantavirus pulmonary syndrome in a previously healthy traveler occurring shortly after he returned to Spain from Nepal. Serologic tests suggested a Puumala virus-like infection.

Strongyloidiasis screening in migrants living in Spain: systematic review and meta-analysis.

OBJECTIVES: To provide information regarding the prevalence of strongyloidiasis among migrants coming from Strongyloides stercoralis-endemic areas who reside in Spain. METHODS: Systematic review of the literature and meta-analysis of studies showing prevalence of S. stercoralis infection among migrants from Latin America, Africa, Eastern Europe, Asia and Oceania who reside in Spain. We included articles published until 30 April 2019 without language restriction. The keywords used for the search included 'Strongyloides stercoralis', 'strongyloidiasis', 'Spain', 'screening' and 'migrants'. RESULTS: Twenty-four studies were included in the review and meta-analysis, comprising 12 386 screened people. Eleven studies (7020 patients) evaluated the presence of S. stercoralis infection only through investigation of larvae in faeces, showing an overall prevalence of 1% (95%CI 1-1%). Thirteen studies (5366 patients) used a serological test, showing an overall prevalence of 14% (95%CI 11-17%). Strongyloidiasis seroprevalence was 20% (95%CI 15-24%) among migrants from sub-Saharan Africa, 14% (95%CI 10-18%) among those from Latin America and 8% (95%CI 5-11%) among migrants from North Africa. CONCLUSIONS: Migrants coming from strongyloidiasis-endemic areas living in Spain had a high S. stercoralis infection prevalence, particularly those from sub-Saharan Africa and Latin America. This population should be screened using serology as the most sensitive test for S. stercoralis infection. This could be easily implemented at primary care level.

OBJECTIFS: Fournir des informations sur la prévalence de la strongyloïdose parmi les migrants résidant en Espagne et provenant de zones endémiques pour Strongyloides stercoralis. MÉTHODES: Revue systématique de la littérature et méta-analyse des études montrant la prévalence de l'infection à S. stercoralis parmi les migrants d'Amérique latine, d'Afrique, d'Europe de l'Est, d'Asie et d'Océanie qui résident en Espagne. Nous avons inclus des articles publiés jusqu'au 30 avril e 2019 sans restriction de langue. Les mots clés utilisés pour la recherche comprenaient "Strongyloides stercoralis", "strongyloïdose", "Espagne", "dépistage" et "migrants". RÉSULTATS: Vingt-quatre études ont été incluses dans la revue et la méta-analyse, comprenant 12.386 personnes dépistées. Onze études (7.020 patients) ont évalué la présence d'une infection à S. stercoralis uniquement en examinant les larves dans les selles, montrant une prévalence globale de 1% (IC95%: 1-1%). Treize études (5.366 patients) ont utilisé un test sérologique, montrant une prévalence globale de 14% (IC95%: 11-17%). La séroprévalence de la strongyloïdose était de 20% (IC95%: 15-24%) chez les migrants d'Afrique subsaharienne, 14% (IC95%: 10-18%) chez ceux d'Amérique latine et 8% (IC95%: 5-11%) chez ceux d'Afrique du Nord. CONCLUSIONS: Les migrants en provenance de zones d'endémie pour la strongyloïdose vivant en Espagne avaient une prévalence élevée d'infection à S. stercoralis, en particulier ceux d'Afrique subsaharienne et d'Amérique latine. Cette population devrait être dépistée en utilisant la sérologie comme le test le plus sensible pour l' infection à S. stercoralis. Cela pourrait être facilement mis en œuvre au niveau des soins primaires.

From latency to overt bone metastasis in breast cancer: potential for treatment and prevention.

Bone metastasis is present in a high percentage of breast cancer (BCa) patients with distant disease, especially in those with the estrogen receptor-positive (ER+ ) subtype. Most cells that escape primary tumors are unable to establish metastatic lesions, which suggests that target organ microenvironments are hostile for tumor cells. This implies that BCa cells must achieve a process of speciation to adapt to the new conditions imposed in the new organ. Bone has unique characteristics that can be exploited by cancer cells: it undergoes constant remodeling and comprises diverse environments (including osteogenic, perivascular, and hematopoietic stem cell niches). This allows colonizing cells to take advantage of numerous adhesion molecules, matrix proteins, and soluble factors that facilitate homing, survival, and, eventually, metastatic outgrowth. However, in most cases, metastatic lesions enter into a latency state that can last months, years, or even decades, before forming a clinically detectable macrometastasis. This dormant state challenges the effectiveness of adjuvant chemotherapy. Detecting which tumors are more prone to metastasize to bone and developing new specific therapies that target bone metastasis represent urgent clinical needs. Here, we review the biological mechanisms of BCa bone metastasis and provide the latest options of treatments and predictive markers that are currently in clinical use or are being tested in clinical assays. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Telemedicine experience between two hospitals from Angola and Spain.

OBJECTIVE: Telemedicine uses information and communication technologies to provide services in the field where the distance is a critical factor. The aim of the present study is to describe the experience of a synchronous telemedicine between two hospitals in Spain and Angola. METHODS: This is a retrospective observational study of all synchronous telemedicine sessions conducted between the Hospital Nossa Senhora da Paz in Angola and the Vall d'Hebron University Hospital in Spain from January 2011 to December 2014. RESULTS: Seventy-two cases were discussed in the telemedicine sessions. The average age of patients was 18.02 (SD 13.75) years and mostly women (54.38 percent). Reasons to discuss the cases were 46.47 percent doubts in the diagnosis and therapeutic management, 15.47 percent were purely formative cases, and only 8.45 percent treatment doubt. At the time of presentation, 29 percent of the patients were already diagnosed, 95 percent of whom with infectious disease diagnostic, and from the undiagnosed patients 36 percent presented a febrile syndrome. CONCLUSION: This study shows the viability of synchronous telemedicine between European and African countries without an excessively sophisticated technology.

Lysyl oxidase-like 2 represses Notch1 expression in the skin to promote squamous cell carcinoma progression.

Lysyl oxidase-like 2 (LOXL2) is involved in a wide range of physiological and pathological processes, including fibrosis and tumor progression, implicating intracellular and extracellular functions. To explore the specific in vivo role of LOXL2 in physiological and tumor contexts, we generated conditional gain- and loss-of-function mouse models. Germ-line deletion of Loxl2 promotes lethality in half of newborn mice mainly associated to congenital heart defects, while Loxl2 overexpression triggers male sterility due to epididymal dysfunction caused by epithelial disorganization, fibrosis and acute inflammation. Remarkably, when challenged to chemical skin carcinogenesis, Loxl2-overexpressing mice increased tumor burden and malignant progression, while Loxl2-deficient mice exhibit the opposite phenotypes. Loxl2 levels in premalignant tumors negatively correlate with expression of epidermal differentiation markers and components of the Notch1 pathway. We show that LOXL2 is a direct repressor of NOTCH1. Additionally, we identify an exclusive expression pattern between LOXL2 and members of the canonical NOTCH1 pathway in human HNSCC. Our data identify for the first time novel LOXL2 roles in tissue homeostasis and support it as a target for SCC therapy.

Evaluation of risk factors associated to detection of Blastocystis sp. in fecal samples in population from Barcelona, Spain: a case-control study.

Blastocystis sp. is the most common intestinal parasite isolated in humans. The aim of the study was to describe the risk factors associated to Blastocystis sp. detection. A case-control retrospective study was carried out at Vall d'Hebron University Hospital (Barcelona, Spain), which receives all fecal samples collected in Barcelona at primary care level. Eligible patients were patients older than 18 years in whom three consecutive stool samples were examined for parasitic diagnosis from January to December 2017. Positive patients for Blastocystis sp. were assigned as cases whereas negative patients were assigned as controls. Overall, 4174 patients were eligible for the study, from whom 724 (17.3%) had Blastocystis sp. detection. From these, 170 cases (Blastocystis sp. positive) and 170 controls (Blastocystis sp. negative) were randomly selected for inclusion. One hundred and twenty-six (37.1%) of them were immigrants, and 171 (50.3%) patients had traveled out of Spain the year before. The majority of individuals had jobs with no direct contact with other people (health personnel, teachers, and caregivers) (85.6%), and 29.4% were in usual contact with animals. Regarding clinical information, 68.2% of patients presented digestive symptoms, 3.5% presented an immunosuppressant condition, and 6.5% were infected by other intestinal parasites. Variables associated to Blastocystis sp. detection were being born in Africa, having traveled abroad, and working in direct contact with other people. Having other intestinal parasitic infections had a protective value. Our study provides new insights into the epidemiology of Blastocystis sp. in industrialized countries.

A case report of long treatment with Itraconazole in a patient with chronic Chagas disease.

BACKGROUND: Current available treatments (benznidazole and nifurtimox) for Chagas disease (CD) show limited efficacy in chronic phase and frequent undesirable effects. Ergosterol synthesis inhibitors (ESI) had been considered as promising drugs for CD treatment and despite its recent poor results in several clinical trials, different strategies have been proposed to optimize its role in this infection. CASE PRESENTATION: We present a case of chronic Chagas disease in patient diagnosed with HIV who received treatment for histoplasmosis with itraconazol during twelve months. Even though T. cruzi rt-PCR was persistently negative during treatment, when itraconazol was stopped she presented with a positive blood rt-PCR. CONCLUSION: Several studies using different ESI had been published for CD treatment. Either in vitro or in vivo assays demonstrated activity against T. cruzi of the different triazole derivatives so different clinical trials had been carried out to evaluate its efficacy and safety. Despite contradictory evidence in the animal model, longer treatments along with other treatment strategies previously proposed suggests that ESI failure rates in positive peripheral blood rt-PCR are higher than that obtained with the current treatments of choice.

Lysyl Oxidase-Like 2 Protects against Progressive and Aging Related Knee Joint Osteoarthritis in Mice.

BACKGROUND: The goal of this study was to determine if adenovirus-delivered LOXL2 protects against progressive knee osteoarthritis (OA), assess its specific mechanism of action; and determine if the overexpression of LOXL2 in transgenic mice can protect against the development of OA-related cartilage damage and joint disability. METHODS: Four-month-old Cho/+ male and female mice were intraperitoneally injected with either Adv-RFP-LOXL2 or an empty vector twice a month for four months. The proteoglycan levels and the expression of anabolic and catabolic genes were examined by immunostaining and qRT-PCR. The effect of LOXL2 expression on signaling was tested via the pro-inflammatory cytokine IL1ß in the cartilage cell line ATDC5. Finally; the OA by monosodium iodoacetate (MIA) injection was also induced in transgenic mice with systemic overexpression of LOXL2 and examined gene expression and joint function by treadmill tests and assessment of allodynia. RESULTS: The adenovirus treatment upregulated LOXL2; Sox9; Acan and Runx2 expression in both males and females. The Adv-RFP-LOXL2 injection; but not the empty vector injection increased proteoglycan staining and aggrecan expression but reduced MMP13 expression. LOXL2 attenuated IL-1ß-induced phospho-NF-κB/p65 and rescued chondrogenic lineage-related genes in ATDC5 cells; demonstrating one potential protective mechanism. LOXL2 attenuated phospho-NF-κB independent of its enzymatic activity. Finally; LOXL2-overexpressing transgenic mice were protected from MIA-induced OA-related functional changes; including the time and distance traveled on the treadmill and allodynia. CONCLUSION: Our study demonstrates that systemic LOXL2 adenovirus or LOXL2 genetic overexpression in mice can protect against OA. These findings demonstrate the potential for LOXL2 gene therapy for knee-OA clinical treatment in the future.

Zika virus dynamics in body fluids and risk of sexual transmission in a non-endemic area.

OBJECTIVE: To understand Zika virus (ZIKV) dynamics in fluids of infected individuals and the risk of sexual transmission. METHODS: Prospective study at two centres in Spain. Patients with probable or confirmed diagnosis of ZIKV infection were clinically followed up, and fluid samples were collected from saliva, serum, urine and semen or vaginal secretion following the study protocol. Non-traveller-sexual partners were offered to participate. RESULTS: From January 2016 to December 2016, we included a total of 11 traveller patients and six sexual contacts. Six patients were male, with a median age of 38 years (IQR 30-45). We performed 61 RT-PCR determinations, seven of which were positive. Positive results were retrieved from serum, urine, semen and vaginal tract. One of four women tested positive for ZIKV RNA in vaginal swabs collected during the first 45 days after symptoms onset. Clearance occurred between day 37 and day 69 after symptoms onset. One of five men tested positive for ZIKV RNA in semen collected during the first 45 days after symptoms onset. Clearance occurred between day 23 and 107 after symptoms onset. Six patients had sexual relations during the defined period. All tested patients were negative for ZIKV infection by serological testing. CONCLUSION: ZIKV shedding persistence in genital fluids occurs in a significant number of symptomatic patients after visiting an endemic area. We did not find any ZIKV seroconversion among the three male contacts who were investigated. Diagnostic algorithms may be updated to include genital tract fluid specimens in the diagnostic process.

Ultrasound findings and associated factors to morbidity in Schistosoma haematobium infection in a highly endemic setting.

OBJECTIVE: To evaluate the usefulness of the WHO classification of ultrasound pathological changes and to establish risk factors for morbidity in a highly endemic setting. METHODS: One hundred and fifty-seven ultrasounds were performed on school-aged children previously diagnosed with urinary schistosomiasis in Cubal, Angola. The findings were analysed according to the WHO guidelines. Factors for morbidity were studied. RESULTS: Mean age of the children was 8.7 (SD 3.2) years. Pathological changes were found in 85.3% (84.7% in the bladder, 34.4% the ureter and 6.3% kidney lesions). The global score according to the WHO classification was 5.74. Male gender [OR 2.61 (1.04-6.58); P 0.043] and older age [OR 2.96 (1.17-7.46); P 0.023] were associated with a higher risk of developing any kind of urinary abnormality. Proteinuria was present in 61.7% of the children. Macroscopic haematuria [OR 2.48 (1.11-5.58); P = 0.02)] and a high level of proteinuria > 300 mg/dl [OR 5.70 (2.17-14.94); P 300 mg/dl)] were associated with abnormalities of the upper urinary tract and showed good positive and negative predictive values for the detection of pathology in the upper urinary tract (65.5% and 71.1%, respectively). CONCLUSIONS: Severe urinary tract pathology was found in a high percentage of the children in our setting. Microhaematuria and proteinuria were good markers of morbidity, proteinuria being more precise for severe alterations of the upper urinary tract. We suggest initial and evolutive ultrasound in children diagnosed with schistosomiasis, and close monitoring including periodic controls. As schistosomiasis control efforts are currently focused on reducing morbidity, tests that detect the presence or degree of morbidity are essential for targeting treatment and tracking the progress of control campaigns.

Field and laboratory comparative evaluation of a LAMP assay for the diagnosis of urogenital schistosomiasis in Cubal, Central Angola.

OBJECTIVE: To evaluate the performance of Rapid-Heat LAMPellet assay in field conditions for diagnosis of urogenital schistosomiasis in an endemic area in Cubal, Angola, and to assess the reproducibility in a reference laboratory. METHODS: A total of 172 urine samples from school-age children were tested for microhaematuria, microscopic detection of Schistosoma haematobium eggs and LAMP for DNA detection. Urine samples were stored in a basic equipped laboratory. Field-LAMP tests were performed with and without prior DNA extraction from urine samples, and the results were read by turbidity and by colour change. When field procedures were finished, samples were sent to a reference laboratory to be reanalysed by LAMP. RESULTS: A total of 83 of 172 (48.3%) were positive for microhaematuria, 87/172 (50.6%) were microscopy-positive for S. haematobium eggs detection, and 127/172 (73.8%) showed LAMP-positive results for detecting S. haematobium using purified DNA and 109/172 (63.4%) without prior DNA extraction. MacNemar's test showed a statistical significant relation between LAMP results and microscopy-detected S. haematobium infections and microhaematuria (P < 0.001 in both cases), respectively. When samples of purified DNA were reanalysed in a reference laboratory in Spain using the same LAMP methodology, the overall reproducibility achieved 72.1%. CONCLUSIONS: The ease of use, simplicity and feasibility demonstrated by LAMP assay in field conditions together with the acceptable level of reproducibility achieved in a reference laboratory support the use of LAMP assay as an effective test for molecular diagnosis of urogenital schistosomiasis in endemic remote areas.

Randomized trial of posaconazole and benznidazole for chronic Chagas' disease.

BACKGROUND: Current therapeutic options for Chagas' disease are limited to benznidazole and nifurtimox, which have been associated with low cure rates in the chronic stage of the disease and which have considerable toxicity. Posaconazole has shown trypanocidal activity in murine models. METHODS: We performed a prospective, randomized clinical trial to assess the efficacy and safety of posaconazole as compared with the efficacy and safety of benznidazole in adults with chronic Trypanosoma cruzi infection. We randomly assigned patients to receive posaconazole at a dose of 400 mg twice daily (high-dose posaconazole), posaconazole at a dose of 100 mg twice daily (low-dose posaconazole), or benznidazole at a dose of 150 mg twice daily; all the study drugs were administered for 60 days. We assessed antiparasitic activity by testing for the presence of T. cruzi DNA, using real-time polymerase-chain-reaction (rt-PCR) assays, during the treatment period and 10 months after the end of treatment. Posaconazole absorption was assessed on day 14. RESULTS: The intention-to-treat population included 78 patients. During the treatment period, all the patients tested negative for T. cruzi DNA on rt-PCR assay beyond day 14, except for 2 patients in the low-dose posaconazole group who tested positive on day 60. During the follow-up period, in the intention-to-treat analysis, 92% of the patients receiving low-dose posaconazole and 81% receiving high-dose posaconazole, as compared with 38% receiving benznidazole, tested positive for T. cruzi DNA on rt-PCR assay (P<0.01 for the comparison of the benznidazole group with either posaconazole group); in the per-protocol analysis, 90% of the patients receiving low-dose posaconazole and 80% of those receiving high-dose posaconazole, as compared with 6% receiving benznidazole, tested positive on rt-PCR assay (P<0.001 for the comparison of the benznidazole group with either posaconazole group). In the benznidazole group, treatment was discontinued in 5 patients because of severe cutaneous reactions; in the posaconazole groups, 4 patients had aminotransferase levels that were more than 3 times the upper limit of the normal range, but there were no discontinuations of treatment. CONCLUSIONS: Posaconazole showed antitrypanosomal activity in patients with chronic Chagas' disease. However, significantly more patients in the posaconazole groups than in the benznidazole group had treatment failure during follow-up. (Funded by the Ministry of Health, Spain; CHAGASAZOL ClinicalTrials.gov number, NCT01162967.).

Red blood cell transfusion-transmitted acute hepatitis E in an immunocompetent subject in Europe: a case report.

BACKGROUND: Acute hepatitis E in industrialized countries is usually related to intake or manipulation of undercooked or raw meat. Cases of transfusion-transmitted hepatitis E have rarely been documented in immunosuppressed patients, mainly after receiving frozen plasma. STUDY DESIGN AND METHODS: A 61-year-old man was admitted to hospital for jaundice. His personal history included disseminated bacillus Calmette-Guerin infection treated with antituberculous drugs. He had received red blood cell (RBC) transfusion 2 months previously, during admission for mycotic aneurysm surgery. Since liver function tests worsened despite stopping antituberculous drugs, other causes of acute hepatitis were explored. RESULTS: Acute hepatitis E was diagnosed by the presence of both immunoglobulin M and hepatitis E virus (HEV) RNA. Traceback procedure for the 8 RBC units was carried out, and one of the eight archive plasma samples tested positive for HEV RNA, with an estimated viral load of 75,000 IU/mL. Phylogenetic analysis revealed the same HEV strain Genotype 3 in one of the transfused RBC products and in the patient's serum sample. CONCLUSION: Transfusion of RBCs with detectable HEV RNA is a risk factor for acute hepatitis E in immunocompetent patients in Europe.

Strongyloides stercoralis infection increases the likelihood to detect Trypanosoma cruzi DNA in peripheral blood in Chagas disease patients.

OBJECTIVES: In a previous study performed by our group, Strongyloides stercoralis infection in patients with Chagas disease was associated with higher proportion of Trypanosoma cruzi DNA detection in peripheral blood. The aim of the study was to confirm this association in a larger cohort of patients. METHODS: Cross-sectional study of all patients with Chagas disease diagnosed from 2005 to 2015 during blood donation at the Catalan Blood Bank. Demographic data and T. cruzi RT-PCR were collected. S. stercoralis infection diagnosis was based on a serological test. RESULTS: Two hundred and two blood donors were included. T. cruzi RT-PCR was positive in 72 (35.6%) patients, and S. stercoralis serology was positive in 22 (10.9%) patients. Patients with positive S. stercoralis serology had higher proportion of positive T. cruzi RT-PCR than those with negative serology (54.5% vs. 33.3%, P = 0.050), and the difference increased when taking a serological index cut-off of 2.5, which increases the specificity of the test to detect a confirmed strongyloidiasis (60% vs. 33%, P = 0.017). CONCLUSIONS: Patients with Chagas disease with positive S. stercoralis serology had higher proportion of positive T. cruzi RT-PCR in peripheral blood than those with negative serology, which reflects the potential immunomodulatory effects of S. stercoralis in T. cruzi co-infected patients.