Cryptococcosis by Cryptococcus gattii in immunocompetent goats in Spain and review of the literature

Cryptococcus neoformans  has been described for years as a species causing spontaneous mycosis in a great variety of animals. The new species C. gattii has been described as an agent of animal cryptococcosis mainly in Australia, but it has been found also in many parts of the world. The main group of animals suffering those natural infections are mammals, but also birds, reptiles and some invertebrates have suffered cryptococcosis. Usually the infections are sporadic and occasional, but some epidemic outbreaks have been reported affecting a high number of animals. In 1998 the isolation of C. gattii was reported by the first time in Europe in 5 epidemic outbreaks of cryptococcosis in goats grazing freely in west Spain grasslands. In all outbreaks, mycological studies were possible from samples obtained on necropsy of some animals dead during the epidemic. Animals belonged to various milking breeds and were grazing with variable status of health and husbandry. Goats affected by cryptococcosis showed similar respiratory symptoms, consisting in mucopurulent nasal discharge, cough, dyspnea and progressive cachexia, causing death in a period of 2 to 4 weeks. In three outbreaks many animals also showed ataxia, midriasis, blindness and progressive paralysis. Clinical prevalence varied from 2 to 12% in the different outbreaks. It is evident that in spite of the great amplitude of geographical distribution observed for C. gattii, this species has a limited presence, possibly restricted to determined habitats, as that of infection of goats flocks in Spain. Veterinarians must be concerned about Cryptococcosis in grazing animals. This finding introduced new elements connected to the epidemiology and ecology of Cryptococcus gattii

Complete inhibition of extranodal dissemination of lymphoma by edelfosine-loaded lipid nanoparticles

Lipid nanoparticles (LN) made of synthetic lipids Compritol® 888 ATO and Precirol® ATO 5 were developed, presenting an average size of 110.4 ± 2.1 nm and 103.1 ± 2.9 nm, for Compritol® and Precirol®, respectively, and encapsulation efficiency above 85 % for both type of lipids. These LN decrease the hemolytic toxicity of the drug by 90 %. Pharmacokinetic and biodistribution profiles of the drug were studied after intravenous and oral administration of edelfosine-containing LN, providing an increase in relative oral bioavailability of 1500 % after a single oral administration of drug-loaded LN, maintaining edelfosine plasma levels over 7 days in contrast to a single oral administration of edelfosine solution, which presents a relative oral bioavailability of 10 %. Moreover, edelfosine-loaded LN showed a high accumulation of the drug in lymph nodes and resulted in slower tumor growth than the free drug in a murine lymphoma xenograft model, as well as potent extranodal dissemination inhibition

Rapid and accurate identification and differentiation of Mycobacterium tuberculosis and non-tuberculous mycobacteria using PCR kits available in a high-burden setting

Infections caused by mycobacteria, including Mycobacterium tuberculosis complex (MTBC) and non-tuberculous mycobacteria (NTM), are a major public health issue worldwide. An accurate diagnosis of mycobacterial species is a challenge for surveillance and treatment, particularly in high-burden settings usually associated with low- and middle-income countries. In this study, we analyzed the clinical performance of two commercial PCR kits designed for the identification and differentiation of MTBC and NTM, available in a high-burden setting such as Ecuador. A total of 109 mycobacteria isolates were included in the study, 59 of which were previously characterized as M. tuberculosis and the other 59 as NTM. Both kits displayed great clinical performance for the identification of M. tuberculosis, with 100% sensitivity. On the other hand, for NTM, one of the kits displayed a good clinical performance with a sensitivity of 94.9% (CI 95%: 89–100%), while the second kit had a reduced sensitivity of 77.1% (CI 95%: 65–89%). In conclusion, one of the kits is a fast and reliable tool for the identification and discrimination of MTBC and NTM from clinical isolates

In Vitro and In Vivo Efficacy of Ether Lipid Edelfosine against Leishmania spp. and SbV-Resistant Parasites

Leishmaniasis represents a major international health problem, has a high morbidity and mortality rate, and is classified as an emerging and uncontrolled disease by the World Health Organization. The migration of population from endemic to nonendemic areas, and tourist activities in endemic regions are spreading the disease to new areas. Unfortunately, treatment of leishmaniasis is far from satisfactory, with only a few drugs available that show significant side-effects. Here, we show in vitro and in vivo evidence for the antileishmanial activity of the ether phospholipid edelfosine, being effective against a wide number of Leishmania spp. causing cutaneous, mucocutaneous and visceral leishmaniasis. Our experimental mouse and hamster models demonstrated not only a significant antileishmanial activity of edelfosine oral administration against different wild-type Leishmania spp., but also against parasites resistant to pentavalent antimonials, which constitute the first line of treatment worldwide. In addition, edelfosine exerted a higher antileishmanial activity and a lower proneness to generate drug resistance than miltefosine, the first drug against leishmaniasis that can be administered orally. These data, together with our previous findings, showing an anti-inflammatory action and a very low toxicity profile, suggest that edelfosine is a promising orally administered drug for leishmaniasis, thus warranting clinical evaluation

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

Brote zoonótico de tiña causado por una cepa disgónica de Microsporum canis de gatos callejeros

[EN]: [Background]: Cats are frequent carriers of Microsporum canis and veterinary students are at high risk of exposure and acquisition of the organism a la infección. [Objectives]: An outbreak of zoonotic ringworm carried by a litter of stray cats is described. Four veterinary students, four dogs, and six cats living in five separate locations were affected. All had direct or indirect contact with the infected kitten litter. We tried to identify the causal dermatophyte. [Methods]: Conventional and mycological culture methods were used. [Results]: Microscopic features of scrapings and hairs treated with 20% KOH strongly suggested a M. canis etiology, and a diagnosis of ringworm was empirically supported by successful treatment of humans and animals. Nevertheless, cultures failed to show the expected morphology. [Conclusions]: Culture features of our strain are compared with those described by other authors for dysgonic M. canis strains. Epidemiological features are also discussed.[ES]: [Antecedentes]: Los gatos son frecuentemente portadores de Microsporum canis. Los estudiantes de veterinaria están especialmente expuestos a la infección. [Objetivos]: Se describe un brote de tiña zoonótica difundido por una camada de gatos callejeros. Cuatro estudiantes de veterinaria, cuatro perros y seis gatos de cinco localizaciones diferentes se vieron afectados. Todos tuvieron contacto directo o indirecto con la camada de gatitos infectados. Se intenta identificar el dermatofito causal. [Métodos]: Se utilizan los procedimientos micológicos morfológicos y de cultivo convencionales. [Resultados]: Los hallazgos microscópicos en pelo y raspados cutáneos aclarados en KOH al 20% sugirieron fuertemente una etiología por M. canis, y el diagnóstico de tiña fue apoyado empíricamente por el éxito en el tratamiento de humanos y animales. Sin embargo, los cultivos no mostraron la morfología esperada. [Conclusiones]: Los caracteres del cultivo de nuestra cepa son comparados con los descritos por otros autores en cepas disgónicas de M. canis. Las características epidemiológicas son discutidas también.Peer Reviewe