Hematology and Clinical Chemistry Reference Ranges for Laboratory-Bred Natal Multimammate Mice (Mastomys natalensis)

Laboratory-controlled physiological data for the multimammate rat (Mastomys natalensis) are scarce, despite this species being a known reservoir and vector for zoonotic viruses, including the highly pathogenic Lassa virus, as well as other arenaviruses and many species of bacteria. For this reason, M. natalensis is an important rodent for the study of host-virus interactions within laboratory settings. Herein, we provide basic blood parameters for age- and sex-distributed animals in regards to blood counts, cell phenotypes and serum chemistry of a specific-pathogen-monitored M.natalensis breeding colony, to facilitate scientific insight into this important and widespread rodent species.Peer Reviewe

Persistent Zika virus infection in porcine conceptuses is associated with elevated in utero cortisol levels

Persistent Zika virus infection in porcine conceptuses is associated with elevated <i>in utero</i> cortisol level

Neonatal pigs are susceptible to experimental Zika virus infection

Emerging Microbes & Infections (2017) 6, e6; doi:10.1038/emi.2016.133; published online 15 February 201

The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset

With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs

Human Polyclonal Antibodies Produced from Transchromosomal Bovine Provides Prophylactic and Therapeutic Protections Against Zika Virus Infection in STAT2 KO Syrian Hamsters

Zika virus (ZIKV) infection can cause severe congenital diseases, such as microcephaly, ocular defects and arthrogryposis in fetuses, and Guillain–Barré syndrome in adults. Efficacious therapeutic treatments for infected patients, as well as prophylactic treatments to prevent new infections are needed for combating ZIKV infection. Here, we report that ZIKV-specific human polyclonal antibodies (SAB-155), elicited in transchromosomal bovine (TcB), provide significant protection from infection by ZIKV in STAT2 knockout (KO) golden Syrian hamsters both prophylactically and therapeutically. These antibodies also prevent testicular lesions in this hamster model. Our data indicate that antibody-mediated immunotherapy is effective in treating ZIKV infection. Because suitable quantities of highly potent human polyclonal antibodies can be quickly produced from the TcB system against ZIKV and have demonstrated therapeutic efficacy in a small animal model, they have the potential as an effective countermeasure against ZIKV infection

Characterization of a Novel STAT 2 Knock Out Hamster Model of Crimean Congo Hemorrhagic Fever Virus Pathogenesis

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen causing a febrile illness in humans, which can progress to hemorrhagic manifestations, multi-organ failure, and death. Current mouse models of CCHFV infection reliably succumb to virus challenge but vary in their ability to reflect signs of disease similar to humans. In this study, we established a signal transducer and activator of transcription 2 (STAT2) knockout hamster model to expand the repertoire of animal models of CCHFV pathogenesis that can be used for therapeutic development. These hamsters demonstrated a systemic and lethal disease in response to infection. Hallmarks of human disease were observed including petechial rash, blood coagulation dysfunction, and various biochemistry and blood cell count abnormalities. Furthermore, we also demonstrated the utility of this model for anti-CCHFV therapeutic evaluation. The STAT2 knock-out hamster model of CCHFV infection may provide some further insights into clinical disease, viral pathogenesis, and pave the way for testing of potential drug and vaccine candidates

Detection of Lassa Virus, Mali

To determine whether Lassa virus was circulating in southern Mali, we tested samples from small mammals from 3 villages, including Soromba, where in 2009 a British citizen probably contracted a lethal Lassa virus infection. We report the isolation and genetic characterization of Lassa virus from an area previously unknown for Lassa fever

Use of Favipiravir to Treat Lassa Virus Infection in Macaques

Lassa virus, the cause of Lassa fever in humans, is endemic to West Africa. Treatment of Lassa fever is primarily supportive, although ribavirin has shown limited efficacy if administered early during infection. We tested favipiravir in Lassa virus–viremic macaques and found that 300 mg/kg daily for 2 weeks successfully treated infection

Environmental-mechanistic modelling of the impact of global change on human zoonotic disease emergence: A case study of Lassa fever

1. Human infectious diseases are a significant threat to global human health and economies (e.g., Ebola, SARs), with the majority of infectious diseases having an animal source (zoonotic). Despite their importance, the lack of a quantitative predictive framework hampers our understanding of how spill-overs of zoonotic infectious diseases into the human population will be impacted by global environmental stressors. 2. Here, we create an environmental-mechanistic model for understanding the impact of global change on the probability of zoonotic disease reservoir host-human spill-over events. As a case study, we focus on Lassa fever virus (LAS). We firstly quantify the spatial determinants of LAS outbreaks, including the phylogeographic distribution of its reservoir host Natal multimammate rat (Mastomys natalensis) (LAS host). Secondly, we use these determinants to inform our environmental-mechanistic model to estimate present day LAS spill-over events and the predicted impact of climate change, human population growth, and land use by 2070. 3. We find phylogeographic evidence to suggest that LAS is confined to only one clade of LAS host (Western clade Mastomys natalensis), and that the probability of its occurrence was a major determinant of the spatial variation in LAS historical outbreaks (69.8%), along with human population density (20.4%). Our estimates for present day LAS spill-over events from our environmental-mechanistic model were consistent with observed patterns, and we predict an increase in events per year by 2070 from 195,125 to 406,725 within the LAS endemic western African region. Of the component drivers, climate change and human population growth are predicted to have the largest effects by increasing landscape suitability for the host and human-host contact rates, while land use change has only a weak impact on the number of future events. 4. LAS spill-over events did not respond uniformly to global environmental stressors, and we suggest that understanding the impact of global change on zoonotic infectious disease emergence requires an understanding of how reservoir host species respond to environmental change. Our environmental-mechanistic modelling methodology provides a novel generalizable framework to understand the impact of global change on the spill-over of zoonotic diseases

Pathogenesis and Host Response in Syrian Hamsters following Intranasal Infection with Andes Virus

Hantavirus pulmonary syndrome (HPS), also referred to as hantavirus cardiopulmonary syndrome (HCPS), is a rare but frequently fatal disease caused by New World hantaviruses. In humans HPS is associated with severe pulmonary edema and cardiogenic shock; however, the pathogenesis of this disease remains unclear largely due to a lack of suitable animal models for the study of disease progression. In this study we monitored clinical, virological, pathophysiological parameters and host immunological responses to decipher pathological factors and events in the lethal Syrian hamster model of HPS following intranasal inoculation of Andes virus. Transcriptional profiling of the host gene responses demonstrated a suppression of innate immune responses in most organs analyzed during the early stage of infection, except for in the lung which had low level activation of several pro-inflammatory genes. During this phase Andes virus established a systemic infection in hamsters, with viral antigen readily detectable in the endothelium of the majority of tissues analyzed by 7–8 days post-inoculation. Despite wide-spread infection, histological analysis confirmed pathological abnormalities were almost exclusively found in the lungs. Immediately preceding clinical signs of disease, intense activation of pro-inflammatory and Th1/Th2 responses were observed in the lungs as well as the heart, but not in peripheral organs, suggesting that localized immune-modulations by infection is paramount to pathogenesis. Throughout the course of infection a strong suppression of regulatory T-cell responses was noted and is hypothesized to be the basis of the aberrant immune activations. The unique and comprehensive monitoring of host immune responses to hantavirus infection increases our understanding of the immuno-pathogenesis of HPS and will facilitate the development of treatment strategies targeting deleterious host immunological responses