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In March 2014, an outbreak of Ebola virus disease associated with a high fatality rate was identified in Guinea, with evidence of ongoing person-to-person transmission. In this update to the preliminary report, the virus is found to be a new strain related to Zaire ebolavirus . Outbreaks caused by viruses of the genera ebolavirus and marburgvirus represent a major public health issue in sub-Saharan Africa. Ebola virus disease is associated with a case fatality rate of 30 to 90%, depending on the virus species. Specific conditions in hospitals and communities in Africa facilitate the spread of the disease from human to human. Three ebolavirus species have caused large outbreaks in sub-Saharan Africa: EBOV, Sudan ebolavirus, and the recently described Bundibugyo ebolavirus . 1 , 2 Epidemics have occurred in the Democratic Republic of Congo, Sudan, Gabon, Republic of Congo, and Uganda. Reston ebolavirus circulates in the Philippines. It . . .

Lassa virus (LASV) outbreaks in West Africa pose a significant public health threat. We investigated the infection phenotype and transmission (horizontal and vertical) of LASV strain Ba366 in its natural host, Mastomys natalensis . Here we analyze viral RNA levels in body fluids, virus titers in organs and antibody presence in blood. In adults and 2-week-old animals, LASV causes transient infections with subsequent seroconversion. However, mice younger than two weeks exhibit persistent infections lasting up to 16 months despite antibody presence. LASV can be detected in various body fluids, organs, and cell types, primarily in lung, kidney, and gonadal epithelial cells. Despite the systemic virus presence, no pathological alterations in organs are observed. Infected animals efficiently transmit the virus throughout their lives. Our findings underscore the crucial role of persistently infected individuals, particularly infected females and their progeny, in LASV dissemination within the host population. Mastomys natalensis , a mouse found closely to rural human dwellings in Sub-Saharan Africa, is a major reservoir for Lassa Virus (LASV). Here, the authors show that LASV causes transient infections in adult M. natalensis , but persistent infections in young animals despite antibodies. LASV is found in various organs without causing pathology and infected animals efficiently transmit the virus.

Mice lacking the type I interferon receptor (IFNAR-/- mice) reproduce relevant aspects of Crimean-Congo hemorrhagic fever (CCHF) in humans, including liver damage. We aimed at characterizing the liver pathology in CCHF virus-infected IFNAR-/- mice by immunohistochemistry and employed the model to evaluate the antiviral efficacy of ribavirin, arbidol, and T-705 against CCHF virus. CCHF virus-infected IFNAR-/- mice died 2-6 days post infection with elevated aminotransferase levels and high virus titers in blood and organs. Main pathological alteration was acute hepatitis with extensive bridging necrosis, reactive hepatocyte proliferation, and mild to moderate inflammatory response with monocyte/macrophage activation. Virus-infected and apoptotic hepatocytes clustered in the necrotic areas. Ribavirin, arbidol, and T-705 suppressed virus replication in vitro by ≥3 log units (IC50 0.6-2.8 µg/ml; IC90 1.2-4.7 µg/ml). Ribavirin [100 mg/(kg×d)] did not increase the survival rate of IFNAR-/- mice, but prolonged the time to death (p<0.001) and reduced the aminotransferase levels and the virus titers. Arbidol [150 mg/(kg×d)] had no efficacy in vivo. Animals treated with T-705 at 1 h [15, 30, and 300 mg/(kg×d)] or up to 2 days [300 mg/(kg×d)] post infection survived, showed no signs of disease, and had no virus in blood and organs. Co-administration of ribavirin and T-705 yielded beneficial rather than adverse effects. Activated hepatic macrophages and monocyte-derived cells may play a role in the proinflammatory cytokine response in CCHF. Clustering of infected hepatocytes in necrotic areas without marked inflammation suggests viral cytopathic effects. T-705 is highly potent against CCHF virus in vitro and in vivo. Its in vivo efficacy exceeds that of the current standard drug for treatment of CCHF, ribavirin.

Background: Lassa virus (LASV) can cause severe acute systemic infection in humans. No approved antiviral drugs or vaccines are currently available. Antibody-based therapeutics are considered a promising treatment strategy in the management of LASV disease. Methods: We used chimeric Ifnar−/− C57BL/6 (Ifnar−/− Bl6) mice, a lethal LASV mouse model, to evaluate the protective efficacy of polyclonal antibodies purified from sera of rabbits hyperimmunized with virus-like particles displaying native-like LASV glycoprotein GP spikes. Results: Polyclonal anti-LASV GP antibodies provided 100% protection against lethal LASV infection in a pre- and post-exposure treatment setting and prevented LASV disease. Treatment also significantly lowered viremia level and virus load in organs. When treatment was initiated at the onset of symptoms, the hyperimmune antibodies provided partial protection and increased the survival rate by 80%. Conclusions: Our findings support the consideration of animal-derived hyperimmune antibodies targeting GP as an effective treatment option for highly pathogenic LASV.

Lassa fever is a viral hemorrhagic fever treated with supportive care and the broad-spectrum antiviral drug ribavirin. The pathophysiology, especially the role of hyperinflammation, of this disease is unknown. We report successful remission of complicated Lassa fever in 2 patients in Nigeria who received the antiinflammatory agent dexamethasone and standard ribavirin.

Downstream analysis of virus-infected cell samples, such as reverse transcription polymerase chain reaction (RT PCR) or mass spectrometry, often needs to be performed at lower biosafety levels than their actual cultivation, and thus the samples require inactivation before they can be transferred. Common inactivation methods involve chemical crosslinking with formaldehyde or denaturing samples with strong detergents, such as sodium dodecyl sulfate. However, these protocols destroy the protein quaternary structure and prevent the analysis of protein complexes, albeit through different chemical mechanisms. This often leads to studies being performed in over-expression or surrogate model systems. To address this problem, we generated a protocol that achieves the inactivation of infected cells through ultraviolet (UV) irradiation. UV irradiation damages viral genomes and crosslinks nucleic acids to proteins but leaves the overall structure of protein complexes mostly intact. Protein analysis can then be performed from intact cells without biosafety containment. While UV treatment protocols have been established to inactivate viral solutions, a protocol was missing to inactivate crude infected cell lysates, which heavily absorb light. In this work, we develop and validate a UV inactivation protocol for SARS-CoV-2, HSV-1, and HCMV-infected cells. A fluence of 10,000 mJ/cm 2 with intermittent mixing was sufficient to completely inactivate infected cells, as demonstrated by the absence of viral replication even after three sequential passages of cells inoculated with the treated material. The herein described protocol should serve as a reference for inactivating cells infected with these or similar viruses and allow for the analysis of protein quaternary structure from bona fide infected cells.

Electroencephalography (EEG) has been used for almost a century in well-equipped medical centers to facilitate the diagnosis of epilepsy and other brain disorders. Lassa fever (LF) and other emerging viral infections (EVI) are known to cause neurological complications, including meningitis, seizures, and encephalopathy, though to date it remains unclear whether these are secondary to metabolic disturbances caused by the disease or by direct involvement of the central nervous system (CNS). To better characterize how Lassa virus (LASV) affects the CNS, we established an EEG diagnostic unit in the LF isolation ward at Irrua Specialist Teaching Hospital in Edo State, Nigeria. Here, we report on the specific difficulties to successful implementation of EEG in this highly challenging setting. Technical artefacts due to electrical interferences and interrupted power supply, artefacts deriving from a partly improvised EEG setup within a high consequence pathogen isolation ward, and environmental factors, such as heat in the endemic West African setting are among the main difficulties encountered when setting up this diagnostic facility. It takes experienced neurophysiologists to distinguish such artefacts from actual EEG abnormalities as many of them are not commonly encountered to this extent in well-equipped EEG laboratories and can easily be confused with pathologies. The EEG recording process is further complicated by biosafety considerations and the necessity of wearing extensive personal protective equipment. Nevertheless, with the help of experienced neurophysiologists, it is possible to correctly set up the facility and interpret recordings. Taking the above into consideration, EEG is valuable in identifying CNS involvement in emerging infections, particularly regarding assessment of encephalitis, differential diagnosis of impaired consciousness and treatment adjustment in patients with symptomatic seizures. Although highly challenging under these circumstances, EEG can be an important, noninvasive diagnostic tool for neurological complications in EVI where other more advanced imaging modalities are not available.

There is limited epidemiological evidence on Lassa fever in pregnant women with acute gaps on prevalence, infection incidence, and risk factors. Such evidence would facilitate the design of therapeutic and vaccine trials and the design of control programs. Our study sought to address some of these gaps by estimating the seroprevalence and seroconversion risk of Lassa fever in pregnant women. We conducted a prospective hospital-based cohort between February and December 2019 in Edo State, Southern Nigeria, enrolling pregnant women at antenatal clinic and following them up at delivery. Samples were evaluated for IgG antibodies against Lassa virus. The study demonstrates a seroprevalence of Lassa IgG antibodies of 49.6% and a seroconversion risk of 20.8%. Seropositivity was strongly correlated with rodent exposure around homes with an attributable risk proportion of 35%. Seroreversion was also seen with a seroreversion risk of 13.4%. Our study suggests that 50% of pregnant women were at risk of Lassa infection and that 35.0% of infections might be preventable by avoiding rodent exposure and conditions which facilitate infestation and the risk of human-rodent contact. While the evidence on rodent exposure is subjective and further studies are needed to provide a better understanding of the avenues of human-rodent interaction; public health measures to decrease the risk of rodent infestation and the risk of spill over events may be beneficial. With an estimated seroconversion risk of 20.8%, our study suggests an appreciable risk of contracting Lassa fever during pregnancy and while most of these seroconversions may not be new infections, given the high risk of adverse outcomes in pregnancy, it supports the need for preventative and therapeutic options against Lassa fever in pregnancy. The occurrence of seroreversion in our study suggests that the prevalence obtained in this, and other cohorts may be an underestimate of the actual proportion of women of childbearing age who present at pregnancy with prior LASV exposure. Additionally, the occurrence of both seroconversion and seroreversion in this cohort suggests that these parameters would need to be considered for the development of Lassa vaccine efficacy, effectiveness, and utility models.

The aim of this study was to evaluate the use of a capture enzyme-linked immunosorbent assay (ELISA) for the detection of LASV-reactive IgG antibodies in Mastomys rodents. The assay was used for laboratory-bred Mastomys rodents, as well as for animals caught in the wild in various regions of West Africa. The ELISA reached an accuracy of 97.1% in samples of known exposure, and a comparison to an immunofluorescence assay (IFA) revealed a very strong agreement between the ELISA and IFA results (Cohen’s kappa of 0.81). The agreement is valid in Nigeria, and in Guinea and Sierra Leone where the lineages II and IV are circulating, respectively. Altogether, these results indicate that this capture ELISA is suitable for LASV IgG serostatus determination in Mastomys rodents as an alternative to IFA. This assay will be a strong, accurate, and semi-quantitative alternative for rodent seroprevalence studies that does not depend on biosafety level 4 infrastructures, providing great benefits for ecology and epidemiology studies of Lassa fever, a disease listed on the Research and Development Blueprint of the WHO.

Lassa fever (LASF) is a highly severe viral syndrome endemic to West African countries. Despite the annual high morbidity and mortality caused by LASF, very little is known about the pathophysiology of the disease. Basic research on LASF has been precluded due to the lack of relevant small animal models that reproduce the human disease. Immunocompetent laboratory mice are resistant to infection with Lassa virus (LASV) and, to date, only immunodeficient mice, or mice expressing human HLA, have shown some degree of susceptibility to experimental infection. Here, transplantation of wild-type bone marrow cells into irradiated type I interferon receptor knockout mice (IFNAR-/-) was used to generate chimeric mice that reproduced important features of severe LASF in humans. This included high lethality, liver damage, vascular leakage and systemic virus dissemination. In addition, this model indicated that T cell-mediated immunopathology was an important component of LASF pathogenesis that was directly correlated with vascular leakage. Our strategy allows easy generation of a suitable small animal model to test new vaccines and antivirals and to dissect the basic components of LASF pathophysiology.