IntroductionReports of high rates of primary microcephaly and Guillain–Barré syndrome associated with Zika virus infection in French Polynesia and Brazil have raised concerns that the virus circulating in these regions is a rapidly developing neuropathic, teratogenic, emerging infectious public health threat. There are no licensed medical countermeasures (vaccines, therapies or preventive drugs) available for Zika virus infection and disease. The Pan American Health Organization (PAHO) predicts that Zika virus will continue to spread and eventually reach all countries and territories in the Americas with endemic Aedes mosquitoes. This paper reviews the status of the Zika virus outbreak, including medical countermeasure options, with a focus on how the epidemiology, insect vectors, neuropathology, virology and immunology inform options and strategies available for medical countermeasure development and deployment.MethodsMultiple information sources were employed to support the review. These included publically available literature, patents, official communications, English and Lusophone lay press. Online surveys were distributed to physicians in the US, Mexico and Argentina and responses analyzed. Computational epitope analysis as well as infectious disease outbreak modeling and forecasting were implemented. Field observations in Brazil were compiled and interviews conducted with public health officials.

The ongoing Zika virus epidemic in the Americas and the observed association with both fetal abnormalities (primary microcephaly) and adult autoimmune pathology (Guillain–Barré syndrome) has brought attention to this neglected pathogen. While initial case studies generated significant interest in the Zika virus outbreak, larger prospective epidemiology and basic virology studies examining the mechanisms of Zika viral infection and associated pathophysiology are only now starting to be published. In this review, we analyze Zika fetal neuropathogenesis from a comparative pathology perspective, using the historic metaphor of “TORCH” viral pathogenesis to provide context. By drawing parallels to other viral infections of the fetus, we identify common themes and mechanisms that may illuminate the observed pathology. The existing data on the susceptibility of various cells to both Zika and other flavivirus infections are summarized. Finally, we highlight relevant aspects of the known molecular mechanisms of flavivirus replication.

Chikungunya virus (CHIKV), a mosquito-borne alphavirus of the family Togaviridae, has recently emerged in the Americas from lineages from two continents: Asia and Africa. Historically, CHIKV circulated as at least four lineages worldwide with both enzootic and epidemic transmission cycles. To understand the recent patterns of emergence and the current status of the CHIKV spread, updated analyses of the viral genetic data and metadata are needed. Here, we performed phylogenetic and comparative genomics screens of CHIKV genomes, taking advantage of the public availability of many recently sequenced isolates. Based on these new data and analyses, we derive a revised phylogeny from nucleotide sequences in coding regions. Using this phylogeny, we uncover the presence of several distinct lineages in Africa that were previously considered a single one. In parallel, we performed thermodynamic modeling of CHIKV untranslated regions (UTRs), which revealed evolutionarily conserved structured and unstructured RNA elements in the 3’UTR. We provide evidence for duplication events in recently emerged American isolates of the Asian CHIKV lineage and propose the existence of a flexible 3’UTR architecture among different CHIKV lineages.

IntroductionGiardiasis is an intestinal infection that affects more than two hundred million people annually worldwide; it is caused by the flagellated protozoan Giardia duodenalis. In tropical countries and in low or middle-income settings, like Brazil, its prevalence can be high. There is currently no systematic review on the presence of G. duodenalis in patients, animals or water sources in Brazil.MethodsThis systematic review was performed according to recommendations established by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). As databases for our searches, we have used PubMed, Embase, Scopus and the Brazilian database SciELO using the keywords Giardia* and Brazil.ResultsThis systematic review identified research studies related to G. duodenalis in water, giardiasis in animals, prevalence of giardiasis across Brazilian regions, genotyping of strains isolated in humans, and giardiasis in indigenous populations. We also propose a network of G. duodenalis transmission in Brazil based on genotypes analyses.ConclusionThis is the first time within the last twenty years that a review is being published on the occurrence of G. duodenalis in Brazil, addressing relevant issues such as prevalence, molecular epidemiology and analytical methods for parasite detection.

Zika virus (ZIKV) belongs to a class of neurotropic viruses that have the ability to cause congenital infection, which can result in microcephaly or fetal demise. Recently, the RNA-binding protein Musashi-1 (Msi1), which mediates the maintenance and self-renewal of stem cells and acts as a translational regulator, has been associated with promoting ZIKV replication, neurotropism, and pathology. Msi1 predominantly binds to single-stranded motifs in the 3′ untranslated region (UTR) of RNA that contain a UAG trinucleotide in their core. We systematically analyzed the properties of Musashi binding elements (MBEs) in the 3′UTR of flaviviruses with a thermodynamic model for RNA folding. Our results indicate that MBEs in ZIKV 3′UTRs occur predominantly in unpaired, single-stranded structural context, thus corroborating experimental observations by a biophysical model of RNA structure formation. Statistical analysis and comparison with related viruses show that ZIKV MBEs are maximally accessible among mosquito-borne flaviviruses. Our study addresses the broader question of whether other emerging arboviruses can cause similar neurotropic effects through the same mechanism in the developing fetus by establishing a link between the biophysical properties of viral RNA and teratogenicity. Moreover, our thermodynamic model can explain recent experimental findings and predict the Msi1-related neurotropic potential of other viruses.