A Comprehensive Analysis of Renal and Endothelium Dysfunction Markers Fourteen Years after Hemorrhagic Fever with Renal Syndrome Contraction.

While the pathology of acute hemorrhagic fever with renal syndrome (HFRS) has been widely researched, details on the chronic HFRS sequelae remain mainly unexplored. In this study, we analyzed the clinical and laboratory characteristics of 30 convalescent HFRS patients 14 years after the disease contraction, mainly emphasizing several endothelial dysfunction parameters. Convalescent HFRS patients exhibited significantly higher serum levels of erythrocyte sedimentation rate, von Willebrand factor, uric acid, C-reactive protein and immunoglobulin A when compared to healthy individuals.

Strategies for Vaccine Prioritization and Mass Dispensing.

We propose a system that helps decision makers during a pandemic find, in real time, the mass vaccination strategies that best utilize limited medical resources to achieve fast containments and population protection. Our general-purpose framework integrates into a single computational platform a multi-purpose compartmental disease propagation model, a human behavior network, a resource logistics model, and a stochastic queueing model for vaccination operations. We apply the modeling framework to the current COVID-19 pandemic and derive an optimal trigger for switching from a prioritized vaccination strategy to a non-prioritized strategy so as to minimize the overall attack rate and mortality rate.

The Origin of COVID-19 and Why It Matters.

The COVID-19 pandemic is among the deadliest infectious diseases to have emerged in recent history. As with all past pandemics, the specific mechanism of its emergence in humans remains unknown. Nevertheless, a large body of virologic, epidemiologic, veterinary, and ecologic data establishes that the new virus, SARS-CoV-2, evolved directly or indirectly from a β-coronavirus in the sarbecovirus (SARS-like virus) group that naturally infect bats and pangolins in Asia and Southeast Asia.

An Infectious cDNA Clone of SARS-CoV-2.

The ongoing pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underscores the urgency to develop experimental systems for studying this virus and identifying countermeasures. We report a reverse genetic system for SARS-CoV-2. Seven complimentary DNA (cDNA) fragments spanning the SARS-CoV-2 genome were assembled into a full-genome cDNA.

Wild Rats, Laboratory Rats, Pet Rats: Global Seoul Hantavirus Disease Revisited.

Recent reports from Europe and the USA described Seoul orthohantavirus infection in pet rats and their breeders/owners, suggesting the potential emergence of a "new" public health problem. Wild and laboratory rat-induced Seoul infections have, however, been described since the early eighties, due to the omnipresence of the rodent reservoir, the brown rat . Recent studies showed no fundamental differences between the pathogenicity and phylogeny of pet rat-induced Seoul orthohantaviruses and their formerly described wild or laboratory rat counterparts.

Clinical Characteristics of Ratborne Seoul Hantavirus Disease.

Although Seoul orthohantavirus is the only globally spread hantavirus pathogen, few confirmed human infections with this virus have been reported in Western countries, suggesting lower medical awareness of the milder, transient, and often chameleon-like symptoms of this zoonosis. We describe lesser known clinical and laboratory characteristics to help improve underreporting of this virus.

Confronting the threat of bioterrorism: realities, challenges, and defensive strategies.

Global terrorism is a rapidly growing threat to world security, and increases the risk of bioterrorism. In this Review, we discuss the potential threat of bioterrorism, agents that could be exploited, and recent developments in technologies and policy for detecting and controlling epidemics that have been initiated intentionally. The local and international response to infectious disease epidemics, such as the severe acute respiratory syndrome and west African Ebola virus epidemic, revealed serious shortcomings which bioterrorists might exploit when intentionally initiating an epidemic.

Meeting report: Tenth International Conference on Hantaviruses.

The 10th International Conference on Hantaviruses, organized by the International Society on Hantaviruses, was held from May 31-June 3, 2016 at Colorado State University, Fort Collins, CO, USA. These conferences have been held every three years since 1980. The current report summarizes research presented on all aspects of hantavirology: ecology and epidemiology, virus replication, phylogeny, pathogenesis, immune response, clinical studies, vaccines and therapeutics.

Building Infectious Disease Research Programs to Promote Security and Enhance Collaborations with Countries of the Former Soviet Union.

Addressing the threat of infectious diseases, whether natural, the results of a laboratory accident, or a deliberate act of bioterrorism, requires no corner of the world be ignored. The mobility of infectious agents and their rapid adaptability, whether to climate change or socioeconomic drivers or both, demand the science employed to understand these processes be advanced and tailored to a country or a region, but with a global vision. In many parts of the world, largely because of economic struggles, scientific capacity has not kept pace with the need to accomplish this goal and has left these regions and hence the world vulnerable to infectious disease outbreaks.

Commentary: How useful is 'burden of disease' to set public health priorities for infectious diseases?

For many infectious diseases, a low burden of disease does not equate to reduced potential public health importance. Many zoonotic infectious diseases have the potential for human-to-human transmission with potentially devastating consequences as currently seen with Ebola. Policymakers should not be lulled into thinking that the best use of resources is to allocate them only to the most obvious current problems.

Adapting high-throughput screening methods and assays for biocontainment laboratories.

High-throughput screening (HTS) has been integrated into the drug discovery process, and multiple assay formats have been widely used in many different disease areas but with limited focus on infectious agents. In recent years, there has been an increase in the number of HTS campaigns using infectious wild-type pathogens rather than surrogates or biochemical pathogen-derived targets. Concurrently, enhanced emerging pathogen surveillance and increased human mobility have resulted in an increase in the emergence and dissemination of infectious human pathogens with serious public health, economic, and social implications at global levels.

Transmission of Ebola viruses: what we know and what we do not know.

Available evidence demonstrates that direct patient contact and contact with infectious body fluids are the primary modes for Ebola virus transmission, but this is based on a limited number of studies. Key areas requiring further study include (i) the role of aerosol transmission (either via large droplets or small particles in the vicinity of source patients), (ii) the role of environmental contamination and fomite transmission, (iii) the degree to which minimally or mildly ill persons transmit infection, (iv) how long clinically relevant infectiousness persists, (v) the role that "superspreading events" may play in driving transmission dynamics, (vi) whether strain differences or repeated serial passage in outbreak settings can impact virus transmission, and (vii) what role sylvatic or domestic animals could play in outbreak propagation, particularly during major epidemics such as the 2013-2015 West Africa situation. In this review, we address what we know and what we do not know about Ebola virus transmission.

A BSL-4 high-throughput screen identifies sulfonamide inhibitors of Nipah virus.

Nipah virus is a biosafety level 4 (BSL-4) pathogen that causes severe respiratory illness and encephalitis in humans. To identify novel small molecules that target Nipah virus replication as potential therapeutics, Southern Research Institute and Galveston National Laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within BSL-4 biocontainment. Using this platform, we screened a 10,080-compound library using a cell-based, high-throughput screen for compounds that inhibited the virus-induced cytopathic effect.

Comparative Burkholderia pseudomallei natural history virulence studies using an aerosol murine model of infection.

Melioidosis is an endemic disease caused by the bacterium Burkholderia pseudomallei. Concerns exist regarding B. pseudomallei use as a potential bio-threat agent causing persistent infections and typically manifesting as severe pneumonia capable of causing fatal bacteremia.

Potential impact of a 2-person security rule on BioSafety Level 4 laboratory workers.

Directors of all major BioSafety Level 4 (BSL-4) laboratories in the United States met in 2008 to review the current status of biocontainment laboratory operations and to discuss the potential impact of a proposed 2-person security rule on maximum-containment laboratory operations. Special attention was paid to the value and risks that would result from a requirement that 2 persons be physically present in the laboratory at all times. A consensus emerged indicating that a video monitoring system represents a more efficient, economical standard; provides greater assurance that pathogens are properly manipulated; and offers an increased margin of employee safety and institutional security.

Genome sequence diversity and clues to the evolution of variola (smallpox) virus.

Comparative genomics of 45 epidemiologically varied variola virus isolates from the past 30 years of the smallpox era indicate low sequence diversity, suggesting that there is probably little difference in the isolates' functional gene content. Phylogenetic clustering inferred three clades coincident with their geographical origin and case-fatality rate; the latter implicated putative proteins that mediate viral virulence differences. Analysis of the viral linear DNA genome suggests that its evolution involved direct descent and DNA end-region recombination events.

The host response to smallpox: analysis of the gene expression program in peripheral blood cells in a nonhuman primate model.

Smallpox has played an unparalleled role in human history and remains a significant potential threat to public health. Despite the historical significance of this disease, we know little about the underlying pathophysiology or the virulence mechanisms of the causative agent, variola virus. To improve our understanding of variola pathogenesis and variola-host interactions, we examined the molecular and cellular features of hemorrhagic smallpox in cynomolgus macaques.

Exploring the potential of variola virus infection of cynomolgus macaques as a model for human smallpox.

Smallpox virus (variola) poses a significant threat as an agent of bioterrorism. To mitigate this risk, antiviral drugs and an improved vaccine are urgently needed. Satisfactory demonstration of protective efficacy against authentic variola will require development of an animal model in which variola produces a disease course with features consistent with human smallpox.

A novel coronavirus associated with severe acute respiratory syndrome.

Background: A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiologic agent of this outbreak.

Methods: We received clinical specimens from patients in seven countries and tested them, using virus-isolation techniques, electron-microscopical and histologic studies, and molecular and serologic assays, in an attempt to identify a wide range of potential pathogens.