[Intrahospital Protocol for the Management of COVID-19 Disease in Adults]. / Protocolo Intra-Hospitalar para Abordagem da Doença COVID-19 no Adulto.

The COVID-19 pandemic is currently responsible for over 526 million infections and over 6.3 million deaths. As a new disease, the number of papers on the subject is extensive, motivating considerable heterogeneity in its approach. Despite some medicines having sound evidence of benefit, new interventions and strategies continue to be proposed, and some still lack scientific evidence, which hinders a uniform and consensual approach. This article aims to standardize healthcare to adult patients with moderate-to-critical COVID-19, from the emergency department to hospitalization, either in a general ward or in level 2 or level 3 intensive care units, based on the best and most updated scientific evidence available. This protocol presents recommendations for the stratification of adult patients with COVID-19 disease, adequate workup at admission and during hospitalization, inpatient treatment criteria, general treatment measures, pharmacological treatment, management of complications such as organizing pneumonia and bacterial superinfection, thromboprophylaxis, special considerations on pregnancy and breastfeeding and possible future therapies.

A pandemia de COVID-19 é, atualmente, responsável por mais de 526 milhões de infeções e mais de 6,3 milhões de mortes. Como nova doença, é extenso o número de publicações sobre o tema, motivando uma considerável heterogeneidade na sua abordagem. Apesar de existirem terapêuticas com benefício comprovado, continuam a ser propostas novas intervenções e estratégias, algumas das quais carecendo ainda de suporte científico, dificultando assim uma abordagem uniforme e consensual. Este documento tem como objetivo uniformizar, baseando-se na melhor e mais atualizada evidência científica disponível, a prestação de cuidados aos doentes adultos com COVID-19 moderada a crítica, desde o serviço de urgência até à hospitalização, quer em enfermarias gerais, quer em enfermarias de cuidados intensivos de nível 2 e 3. Este protocolo apresenta recomendações para a estratificação da doença COVID-19, critérios de hospitalização, meios complementares de diagnóstico adequados à admissão e durante a hospitalização, medidas terapêuticas gerais e terapêutica farmacológica dirigida, gestão de complicações como pneumonia organizativa e sobreinfeção bacteriana, tromboprofilaxia, considerações especiais na gravidez e amamentação, e possíveis opções terapêuticas futuras.

Dual beta-lactam treatment: Pros and cons.

The battle against microscopic pathogens has always baffled the scientific community. Nowadays, multidrug-resistant microorganisms lead to high in-hospital mortality, increased hospital stays, and high health-related costs. Treating infections due to these high-resistance pathogens with a low number of antibiotic molecules creates the need for new strategies. Although some already think of a "postantibiotic era" with bacteriophages as the main futuristic weapon in antibacterial armament, others rethink the usage of the already existent drugs. Dual beta-lactam therapy has been used for quite some time as an empirical therapy for some severe infections such as endocarditis or meningitis. However, studies regarding the use of a beta-lactam combination stopped being made a long time ago, and it seems the scientific community has no interest in evaluating this as a treatment option. Could this strategy be applied to treat infections due to multidrug-resistant bacteria? Could this be the answer while waiting for the "postantibiotic era"? What kind of pathogens could we fight using dual beta-lactams? What are the downsides of this strategy? These are some of the questions the authors try to answer in this review. In addition, we try to convince our peers to turn once more into researching beta-lactam combinations and exploring its potential benefits.

[Venomous Animals in the Portuguese Territory: Clinical Management of Bites and Stings]. / Animais Venenosos em Território Português: Abordagem Clínica de Picadas e Mordeduras.

There are many native species of animals with the potential to cause severe disease in Portugal. Of the four clinically relevant snake species, the vipers (Vipera latastei and Vipera seoanei) are the most concerning. They can cause severe disease and require in-hospital management, monitoring and specific treatment, including the administration of anti-snake venom serum. The Malpolon monspessulanus and Macroprotodon brevis snakes cause mostly localized clinical manifestations, which do not require specific treatment. Only a minority of the spider species in Portugal possess chelicerae (mouthparts of the Chelicerata, shaped as either articulated fangs or pincers, which may contain venom or be connected to the venom glands and are used for predation or capture of food) long enough to perforate the human skin. Nevertheless, Latrodectus tredecimguttatus and Loxosceles rufescens spider bites may require specialized treatment in a hospital setting, as well as careful active symptom surveillance. Diversely, the treatment for Scolopendra cingulata and Scolopendra oraniensis centipedes' bites is merely symptomatic. The only existing scorpion species in Portugal is the Buthus ibericus; its sting typically causes local symptoms with intense pain, and its treatment consists essentially of analgesia. The insects of the Hymenoptera order, such as bees and wasps, have the ability to inject venom into the skin. Most people present only with local or regional inflammatory response, and symptomatic treatment is usually effective. Even so, individuals with hypersensitivity to bee venom may develop anaphylaxis. Several marine species in the Portuguese coast are venomous to humans, including weeverfish (Trachinidae family), stingrays (Dasyatis pastinaca, Taeniura grabata, Myliobatis aquila), red scorpion fish (Scorpaena scrofa), cnidaria (Pelagia noctiluca, Chrysaora hysoscella, Physalia physalis) and bearded fireworm (Hermodice carunculata); treatment is symptomatic. Contact with the larvae or bristles (chitinous structures with locomotor or tactile functions) of Thaumetopoea pityocampa (pine processionary) can cause cutaneous, ocular and, rarely, respiratory reactions; its management is also symptomatic.

Em território português, existem várias espécies autóctones de animais capazes de provocar envenenamento e doença clinicamente significativa, com potencial de gravidade. Das quatro espécies de serpentes com relevância clínica, as víboras (Vipera latastei e Vipera seoanei) são as mais preocupantes; podem causar doença grave e necessitam de abordagem hospitalar, monitorização e tratamento específico, incluindo soro antiveneno. As serpentes Malpolon monspessulanus e Macroprotodon brevis causam maioritariamente manifestações clínicas locais, sem tratamento específico. Apenas uma minoria das espécies de aranha presentes em Portugal possui quelíceras (apêndices bucais dos Chelicerata, em forma de tenaz ou gancho, que podem conter veneno ou encontrar-se ligados às glândulas venenosas, usados para predação ou captura de alimentos) suficientemente compridas para perfurar a pele humana, mas as picadas de Latrodectus tredecimguttatus e Loxosceles rufescens podem implicar tratamento diferenciado em ambiente hospitalar, com necessidade de vigilância ativa. O tratamento da picada das centopeias Scolopendra cingulata e Scolopendra oraniensis é sintomático. A única espécie de escorpião presente em território nacional, Buthus ibericus, causa geralmente sintomas locais com dor intensa; o tratamento habitualmente baseia-se apenas na administração de analgesia. Os insetos da ordem Hymenoptera, como as abelhas e vespas, possuem capacidade de libertar veneno através de picadas; a maior parte dos indivíduos apresenta apenas reações inflamatórias locais ou regionais, para as quais a aplicação de medidas sintomáticas é suficiente, mas indivíduos que apresentem hipersensibilidade ao veneno podem desenvolver reações anafiláticas. Na costa portuguesa e em águas pouco profundas, encontram-se várias espécies marinhas venenosas para os humanos, como Echiichthys vipera (peixe-aranha comum), Dasyatis pastinaca, Taeniura grabata e Myliobatis aquila (ratões), Scorpaena scrofa (rascasso-vermelho), Pelagia noctiluca, Chrysaora hysoscella e Physalia physalis (cnidários) e Hermodice carunculata (verme-do-fogo), cujas picadas necessitam apenas de tratamento sintomático. O contacto com as larvas ou cerdas (estruturas quitinosas com funções locomotoras ou tácteis) de Thaumetopoea pityocampa (lagarta-do-pinheiro) pode provocar reações cutâneas, oculares e, raramente, respiratórias; a sua abordagem também é sintomática.

Microtus arvalis and Arvicola scherman: Key Players in the Echinococcus multilocularis Life Cycle.

A broad range of rodent species are described as potential intermediate hosts for Echinococcus multilocularis, a wide-spread zoonotic cestode causing alveolar echinococcosis. However, little is known about the relative contribution of these species for parasite reproduction and the maintenance of its life cycle. In a comparative study in a high endemic region in Zurich, Switzerland, we investigated prevalence rates and fertility of E. multilocularis in the most abundant vole species as well as the predation rate of foxes on these species. To ensure that the fox families had access to different vole species and that these voles were exposed to the same environmental contamination with parasite eggs, we selected eight study plots where at least two rodent species co-occurred. The parasite prevalence in Microtus arvalis [11.0%, confidence intervals (CI) 8.9-13.4] was significantly higher than in Arvicola scherman (5.3%, 3.9-7.1) and Myodes glareolus (3.9%, 2.0-6.7). None of the, only 29 individuals of, Microtus agrestis was infected (0%, 0.0-9.8) and the species was excluded for further analyses. Logistic regression models for the prevalences revealed significant differences between nearby study plots and higher infection rates for females, heavier individuals, and individuals trapped during spring, when the prevalence in M. arvalis peaked up to 65% (CI 50-79) in one plot. Furthermore, we detected significantly higher percentages of fertile infections in M. arvalis and M. glareolus than in A. scherman (OR 11.2 and 6.4, respectively) and a significantly higher protoscolex number in M. glareolus (median 100,000) than in M. arvalis (13,500) and A. scherman (4,290). The most abundant fox prey remains were of the genera Microtus (12.3%, CI 8.4-17.2) and Arvicola (11.5%, 7.7-16.3), whereas Myodes was never recorded as prey (0.0-1.3%). We conclude that M. arvalis and to a lesser extent A. scherman can be regarded as key intermediate hosts in Western and Central European high-endemic regions whereas M. glareolus and M. agrestis play a marginal role. We, therefore, postulate that distribution models of these species could contribute to predict parasite occurrence on a more detailed spatial scale than models of the distribution of foxes which have a very broad and uniform distribution.

Stability of the southern European border of Echinococcus multilocularis in the Alps: evidence that Microtus arvalis is a limiting factor.

SUMMARY The known range of the zoonotic fox tapeworm Echinococcus multilocularis has expanded since the 1990s, and today this parasite is recorded in higher abundances throughout large parts of Europe. This phenomenon is mostly attributed to the increasing European fox populations and their invasion of urban habitats. However, these factors alone are insufficient to explain the heterogeneous distribution of the parasite in Europe. Here, we analysed the spatial interrelationship of E. multilocularis with the known distribution of seven vole species in Ticino, southern Switzerland. Among 404 necropsied foxes (1990-2006) and 79 fox faecal samples (2010-2012), E. multilocularis was consistently found in the north of the investigated area. No expansion of this endemic focus was recorded during the 22 years of the study period. This stable endemic focus is coincident with the known distribution of the vole species Microtus arvalis but not, or only partly, with the distribution of the other autochthonous vole species. Our results give evidence that this vole species plays a crucial role in the maintenance of the parasite's life cycle and that its absence could be a limiting factor for the spread of E. multilocularis in this region.

Chlamydiaceae and Chlamydia-like organisms in free-living small mammals in Europe and Afghanistan.

Few data are available on the occurrence of chlamydial infections in wild small mammals. We investigated the significance of free-living small mammals as reservoirs or transmission hosts for microorganisms of the phylum/class Chlamydiae. We obtained 3,664 tissue samples from 911 animals in Switzerland, Germany, Austria, the Czech Republic, and Afghanistan. Samples included internal organs (n = 3,652) and feces (n = 12) from 679 rodents (order Rodentia) and 232 insectivores (order Soricomorpha) and were tested by three TaqMan® real-time PCRs specific for members of the family Chlamydiaceae and selected Chlamydia-like organisms such as Parachlamydia spp. and Waddlia spp. Only one of 911 (0.11%) animals exhibited a questionable positive result by Chlamydiaceae-specific real-time PCR. Five of 911 animals were positive by specific real-time PCR for Parachlamydia spp. but could not be confirmed by quantitative PCR targeting the Parachlamydia acanthamoebae secY gene (secY qPCR). One of 746 animals (0.13%) was positive by real-time PCR for Waddlia chondrophila. This result was confirmed by Waddlia secY qPCR. This is the first detection of Chlamydia-like organisms in small wildlife in Switzerland. Considering previous negative results for Chlamydiaceae in wild ruminant species from Switzerland, these data suggest that wild small mammals are unlikely to be important carriers or transport hosts for Chamydiaceae and Chlamydia-like organisms.

Taeniid species of the Iberian wolf (Canis lupus signatus) in Portugal with special focus on Echinococcus spp.

Taeniid species represent relevant pathogens in human and animals, circulating between carnivorous definitive hosts and a variety of mammalian intermediate hosts. In Portugal, however, little is known about their occurrence and life cycles, especially in wild hosts. An epidemiological survey was conducted to clarify the role of the Iberian wolf as a definitive host for taeniid species, including Echinococcus spp. Wolf fecal samples (n = 68) were collected from two regions in Northern Portugal. Taeniid eggs were isolated through a sieving-flotation technique, and species identification was performed using multiplex-PCR followed by sequencing of the amplicons. Taenia hydatigena (in 11.8% of the samples), Taenia serialis (5.9%), Taenia pisiformis (2.9%), Taenia polyacantha (1.5%) and Echinococcus intermedius (Echinococcus granulosus 'pig strain', G7) (1.5%) were detected. This is the first study to characterize the taeniid species infecting the Portuguese Iberian wolf, with the first records of T. polyacantha and E. intermedius in this species in the Iberian Peninsula. Iberian wolves can be regarded as relevant hosts for the maintenance of the wild and synanthropic cycles of taeniids in Portugal.