Volume 01 · Issue 01 · 2019

Biological threats, whether naturally occurring, accidental, or deliberate in origin, can result in disasters that are regional, national, or even global in scope if not properly contained. Many global communities, international programs, and governmental organizations have been established to mitigate these risks and challenges. In China, for example, the government has systematically implemented long-term plans including a complete country-wide architecture for biosafety management. It includes the establishment of a series of improved biosafety laws/regulations/standards and of a large number of high-level biosafety laboratories. All countries should encourage preparedness and improve surveillance systems to predict, identify, and respond to the next public health crisis. More grants and funds should be established for research into biosafety and biosecurity. Most importantly, international collaborations, partnerships, and communications should be enhanced. The journal Biosafety and Health aims to provide a global communications platform on biosafety related to human and animal health.

Infectious disease research, like any scientific enterprise, is dependent on technology, subject matter experts, hard work …and engaged leadership. The pace of progress in research and development of vaccines, drugs, diagnostics or foundational knowledge is always more rapid when laboratory organizational cultures are collaborative and communication is open. Relationships of trust between individual scientists and with their leaders in an organization further fuel productivity. Laboratory safety is sometimes seen as just another administrative function, but that is far from the case. A focus on safety in an infectious disease laboratory not only protects the staff and the community around the lab; it also contributes to a healthy and vibrant organizational culture and even enhances productivity.

The development of monoclonal antibodies to treat disease caused by filoviruses, particularly Ebola virus, has risen steeply in recent years thanks to several key studies demonstrating their remarkable therapeutic potential. The increased drive to develop new and better monoclonal antibodies has necessarily seen an increase in animal model efficacy testing, which is critical to the pre-clinical development of any novel countermeasure. Primary and secondary efficacy testing against filoviruses typically makes use of one or more rodent models (mice, guinea pigs, and occasionally hamsters) or the more recently described ferret model, although the exact choice of model depends on the specific filovirus being evaluated. Indeed, no single small animal model exists for all filoviruses, and the use of any given model must consider the nature of that model as well as the nature of the therapeutic and the experimental objectives. Confirmatory evaluation, on the other hand, is performed in nonhuman primates (rhesus or cynomolgus macaques) regardless of the filovirus. In light of the number of different animal models that are currently used in monoclonal antibody efficacy testing, we sought to better understand how these efficacy tests are being performed by numerous different laboratories around the world. To this end, we review the animal models that are being used for antibody efficacy testing against filoviruses, and we highlight the challenge doses and routes of infection that are used. We also describe the various antibody treatment regimens, including antibody dose, route, and schedule of administration, that are used in these model systems. We do not identify any single best model or treatment regimen, and we do not advocate for field-wide protocol standardization. Instead, we hope to provide a comprehensive resource that will facilitate and enhance the continued pre-clinical development of novel monoclonal antibody therapeutics.

The onsite next generation sequencing (NGS) of Ebola virus (EBOV) genomes during the 2013–2016 Ebola epidemic in Western Africa provides an opportunity to trace the origin, transmission, and evolution of this virus. Herein, we have diagnosed a cohort of EBOV patients in Sierra Leone in 2015, during the late phase of the outbreak. The surviving EBOV patients had a recovery process characterized by decreasing viremia, fever, and biochemical parameters. EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection, including the previously described short stretches of 13 serial T>C mutations. Remarkably, within individual patients, samples collected during the early phase of infection possessed Ts at these nucleotide sites, whereas they were replaced by Cs in samples collected in the later phase, suggesting that these short stretches of T>C mutations could emerge independently. In addition, up to a total of 35 nucleotide sites spanning the EBOV genome were mutated coincidently. Our study showed the dynamic intra-host adaptation of EBOV during patient recovery and gave more insight into the complex EBOV-host interactions.

The surveillance and prevention of pathogenic microbiological contamination are the most important tasks of biosafety management in the lab. There is an urgent need to establish an effective and unbiased method to evaluate and monitor such contamination. This study aims to investigate the utility of next generation sequencing (NGS) method to detect possible contamination in the microbiology laboratory. Environmental samples were taken at multiple sites at the lab including the inner site of centrifuge rotor, the bench used for molecular biological tests, the benches of biosafety cabinets used for viral culture, clinical sample pre-treatment and nucleic acids extraction, by scrubbing the sites using sterile flocked swabs. The extracted total nucleic acids were used to construct the libraries for deep sequencing according to the protocol of Ion Torrent platform. At least 1G raw data was obtained for each sample. The reads of viruses and bacteria accounted for 0.01 ± 0.02%, and 77.76 ± 12.53% of total reads respectively. The viral sequences were likely to be derived from gene amplification products, the nucleic acids contaminated in fetal bovine serum. Reads from environmental microorganisms were also identified. Our results suggested that NGS method was capable of monitoring the nucleic acids contaminations from different sources in the lab, demonstrating its promising utility in monitoring and assessing the risk of potential laboratory contamination. The risk of contamination from reagents, remnant DNA and environment should be considered in data analysis and results interpretation.

Hand, foot and mouth disease (HFMD) was reported in May 2, 2008 to be the 38th legally notifiable disease in China's National Notifiable Disease Reporting and Surveillance System. In order to solve the infection, an extensive three-level HFMD surveillance laboratory network was established. In this study, the framework of that network is assessed and the incidence of HFMD in China from 2008 to 2017 is reported using a descriptive epidemiologic method. During these 10 years, a series of techniques have been widely applied in all the network laboratories. Using information and material obtained from the network, a virus bank and database containing 18,238 viruses were established. Nationally, 18,184,834 HFMD cases, including 152,436 severe cases and 3633 fatal cases, were reported in mainland of China. The average annual incidence in the population was 133.99/100,000 people, with a maximum incidence of 205.06/100,000 people in 2014. The incidence and mortality rates of HFMD were the highest in children aged 1–2 years. The numbers of reported cases fluctuated, with a high incidence observed every 2 years. An overall increase in the number of reported cases was also observed throughout the study period. Despite this, the incidence of severe cases and the mortality rate have been decreasing. High-risk regions are located in southern, eastern, and central China. Two peaks of HFMD infection cases were observed annually except for Northeast China. Different proportions of enterovirus serotypes were observed during the studied years. The predominant enterovirus varies from year to year, but the disease severity is always closely related to the specific serotype. EV-A71 is the dominant serotype associated with severe and fatal cases, with constituent ratios of 70.03% and 92.23%, respectively. The studied highly sensitive and efficient surveillance network provides information that is critical for prevention and control of the disease. It is extremely necessary and important to continuously conduct extensive virological surveillance for HFMD.

Mutations of influenza virus associated with adaptation occurring during passage in embryonated chicken eggs could result in antigenic change or reduced vaccine effectiveness. In this study, we investigated the mutations of influenza A(H1N1)pdm09 egg isolates from the Chinese National Influenza Surveillance Network between 2009 and 2016. Thirteen mutations were identified in the hemagglutinin (HA) protein from viruses passaged in eggs, in comparing to those in cells. After scanning public database, four mutations, D127E, L191I, D222G/N and Q223R in HA1, which may alter the receptor-binding specificity, were observed frequently. Although the A(H1N1) pdm09 virus has evolved in human for nearly ten years, most egg-cultured viruses acquired one or more further mutations. Using the egg isolates for influenza surveillance requires extra caution because of these selected mutations, and their impacts on antigenicity and receptor-binding property need further evaluation. Currently, most of the influenza vaccines are produced using egg isolates, particularly in China. Thus, there is an urge to promote the establishment of an alternative influenza vaccine production platform.

Concerns have been raised about both the disinfection and the reusability of respiratory protective equipment following a disinfection process. Currently, there is little data available on the effects of disinfection and decontamination on positive pressure respiratory protective hoods (PPRPH). In this study, we evaluated the effect of vaporized hydrogen peroxide (VHP) on the disinfection of PPRPH to determine applicability of this method for disinfection of protective equipment, especially protective equipment with an electric supply system.

A hydrogen peroxide-based fumigation sterilization cabinet was developed particularly for disinfection of protective equipment, and the disinfection experiments were conducted using four PPRPHs hung in the fumigation chamber. The pathogenic microorganism Geobacillus stearothermophilus ATCC 7953 was used as a biological indicator in this study and the relationship between air flow (the amount of VHP) and disinfection was investigated. Both function and the material physical properties of the PPRPH were assessed following the disinfection procedure. No surviving Geobacillus stearothermophilus ATCC 7953, both inside and outside of these disinfected PPRPHs, could be observed after a 60 min treatment with an air flow of 10.5–12.3 m³/h. Both function and material physical properties of these PPRPHs met the working requirements after disinfection.

This study indicates that air flow in the fumigation chamber directly influences the concentration of VHP. The protective equipment fumigation sterilization cabinet developed in this paper achieves the complete sterilization of the PPRPHs when the air flow is at 10.5–12.3 m³/h, and provides a potential solution for the disinfection of various kind of protective equipment.