Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: The ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmissio

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Sustainability Agenda for the Pantanal Wetland: Perspectives on a Collaborative Interface for Science, Policy, and Decision-Making.

Building bridges between environmental and political agendas is essential nowadays in face of the increasing human pressure on natural environments, including wetlands. Wetlands provide critical ecosystem services for humanity and can generate a considerable direct or indirect income to the local communities. To meet many of the sustainable development goals, we need to move our trajectory from the current environmental destructive development to a wiser wetland use. The current article contain a proposed agenda for the Pantanal aiming the improvement of public policy for conservation in the Pantanal, one of the largest, most diverse, and continuous inland wetland in the world. We suggest and discuss a list of 11 essential interfaces between science, policy, and development in region linked to the proposed agenda. We believe that a functional science network can booster the collaborative capability to generate creative ideas and solutions to address the big challenges faced by the Pantanal wetland

Establishment and cryptic transmission of Zika virus in Brazil and the Americas

Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil1. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 20162) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 20162). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease3. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus

Cutaneous Infection by Different Alternaria Species in a Liver Transplant Recipient

Fungal invasive infections are rare in general population but are an emergent cause of infection in the immunocompromized population, especially in the solid organ transplant recipients. Herein the authors report a clinical case of a liver transplanted patient suffering a cutaneous co-existent infection with A. alternata as well as A. infectoria. To our knowledge this is the first case of cutaneous concomitant infection due to those two species reported not only in Portugal but also worldwide. The patient was treated with surgical excision of the lesions and oral itraconazol without relapse

Molecular diagnosis of invasive aspergillosis in a child with clinical suspicion of mucormycosis

Purpose: Invasive aspergillosis is difficult to manage in immunocompromised patients. We present a clinical case of a 13-year-old boy from Cabo Verde who was transferred to the Hematology Unit of a Central Hospital in Lisbon, Portugal, and diagnosed with aplastic anemia. Weeks after hospital admission, in June 2016, he presented febrile neutropenia with negative blood cultures. In August, the patient showed a necrotic lesion of the left wing of the nose. A CT scan of the sinuses showed densification and thickening of the soft tissues of the nasal pyramid, protruding into the nose. A rapid and accurate diagnosis was required since the patient was going to be subjected to bone marrow transplantation. Methods: A biopsy of the nose tissue was performed in the hospital (August 2016) and sent to the Mycology Reference Laboratory of the Portuguese NIH. Tissue fragments were sliced in small fragments and inoculated in Sabouraud dextrose agar and brain heart infusion. Samples were incubated at 30º and 35ºC. In parallel to culture, DNA was extracted from the tissue using the High Pure PCR Template Preparation Kit (Roche Diagnostics Corp., Indianapolis, IN, USA), according to the manufacturer’s instructions. A panfungal PCR reaction was performed in order to detect any fungal DNA present in the tissue sample. For that purpose, the universal fungal primers ITS1 and ITS2 were used. Positive PCR products are then sequenced by Sanger method. A specific PCR directed to Aspergillus was performed using the AsperGenius® multiplex real-time PCR assay (PathoNostics, Maastricht, The Netherlands), following the manufacturer's instructions. The detection of mutations in the Cyp51A gene for A. fumigatus conferring azole resistance was also performed. Results: A positive panfungal PCR was obtained and PCR products were sent to sequencing. Due to the urgency of the case, a real time PCR directed to Aspergillus was also performed directly from the DNA extracted from the biopsy. A positive signal was obtained for Aspergillus fumigatus and no mutations in Cyp51A gene were detected. Sequencing results revealed 100% homology with A. fumigatus sensu stricto. Results were immediately reported to the physician and posaconazole was administered with regression of the lesion. After 30 days, the cultures of the tissue remained negative. In September 2016, nodular lesions appeared in the patients’ lower limbs and voriconazole therapy was then initiated. A complete regression was observed. Multiresistant Klebsiella pneumoniae and Enterobacter asburiae were further isolated from a perianal ulcer and in October 2016 the patient revealed positive bloodcultures of multiresistant Klebsiella pneumoniae. Facing difficulties in the infection control, a multidisciplinary team decided to perform allogeneic bone marrow transplantation, with complete hematological and infections recovery. Conclusion: An early diagnosis and prompt initiation of appropriate antifungal therapy are imperative and essential for a favorable clinical outcome. In this case, the necrotic lesions of the nose and patient’s risk factors conducted to the clinical suspicion of mucormycosis. The molecular approach performed led to the rapid identification of Aspergillus fumigatus and therefore to the adequate antifungal therapy of the patient.N/