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We describe the results of a prospective observational study of the clinical natural history of human monkeypox (mpox) virus (MPXV) infections at the remote L'Hopital General de Reference de Kole (Kole hospital), the rainforest of the Congo River basin of the Democratic Republic of the Congo (DRC) from March 2007 until August 2011. The research was conducted jointly by the Institute National de Recherche Biomedical (INRB) and the US Army Medical Research Institute of Infectious Diseases (USAMRIID). The Kole hospital was one of the two previous WHO Mpox study sites (1981–1986). The hospital is staffed by a Spanish Order of Catholic Nuns from La Congregation Des Seours Missionnaires Du Christ Jesus including two Spanish physicians, who were members of the Order as well, were part of the WHO study on human mpox. Of 244 patients admitted with a clinical diagnosis of MPXV infection, 216 were positive in both the Pan-Orthopox and MPXV specific PCR. The cardinal observations of these 216 patients are summarized in this report. There were three deaths (3/216) among these hospitalized patients; fetal death occurred in 3 of 4 patients who were pregnant at admission, with the placenta of one fetus demonstrating prominent MPXV infection of the chorionic villi. The most common complaints were rash (96.8%), malaise (85.2%), sore throat (78.2%), and lymphadenopathy/adenopathy (57.4%). The most common physical exam findings were mpox rash (99.5%) and lymphadenopathy (98.6%). The single patient without the classic mpox rash had been previously vaccinated against smallpox. Age group of less than 5 years had the highest lesion count. Primary household cases tended to have higher lesion counts than secondary or later same household cases. Of the 216 patients, 200 were tested for IgM & IgG antibodies (Abs) to Orthopoxviruses. All 200 patients had anti-orthopoxvirus IgG Abs; whereas 189/200 were positive for IgM. Patients with hypoalbuminemia had a high risk of severe disease. Patients with fatal disease had higher maximum geometric mean values than survivors for the following variables, respectively: viral DNA in blood (DNAemia); maximum lesion count; day of admission mean AST and ALT. Author summary: This is a prospective observational study of human mpox disease, an emerging infectious disease that has traditionally occurred in Central and West Africa. There are certain differential characteristics when compared to other pox diseases. We describe the presenting symptoms and signs of human mpox disease, laboratory findings and make recommendations for the medical treatment of patients with mpox disease. The classic MPX rash was seen in 99.5% of patients. Unlike other pox diseases, enlarged lymph nodes were observed in 98.6% of patients. The pathologic findings of MPXV infected placenta and fetus are presented as well. [ABSTRACT FROM AUTHOR]

Marburg virus (MARV) causes a severe hemorrhagic fever disease in primates with mortality rates in humans of up to 90%. MARV has been identified as a category A bioterrorism agent by the Centers for Disease Control and Prevention (CDC) and priority pathogen A by the National Institute of Allergy and Infectious Diseases (NIAID), needing urgent research and development of countermeasures because of the high public health risk it poses. The recent cases of MARV in West Africa underscore the substantial outbreak potential of this virus. The potential for cross-border spread, as had occurred during the 2014–2016 Ebola virus outbreak, illustrates the critical need for MARV vaccines. To support regulatory approval of the chimpanzee adenovirus 3 (ChAd3)–MARV vaccine that has completed phase 1 trials, we showed that the nonreplicating ChAd3 vector, which has a demonstrated safety profile in humans, protected against a uniformly lethal challenge with MARV/Ang. Protective immunity was achieved within 7 days of vaccination and was maintained through 1 year after vaccination. Antigen-specific antibodies were an immune correlate of protection in the acute challenge model, and their concentration was predictive of protection. These results demonstrate that a single-shot ChAd3-MARV vaccine generated a protective immune response that was both rapid and durable with an immune correlate of protection that will support advanced clinical development. Fighting filoviruses: Fighting filovirusesMarburg Virus (MARV) outbreaks remain a major global health concern, and an effective vaccine is urgently needed. Here, Hunegnaw et al. report that a single-shot chimpanzee adenovirus-vectored vaccine expressing the MARV glycoprotein, ChAd3-MARV, confers protection in non-human primates. Animals were protected as soon as one week after vaccination and protection lasted up to a year after vaccination, with antigen-specific antibodies serving as a predictor of protection. Together, these results support clinical use of ChAd3-MARV. -CM [ABSTRACT FROM AUTHOR]

Lassa virus (LASV) is a significant human pathogen that is endemic to several countries in West Africa. Infection with LASV leads to the development of hemorrhagic fever in a significant number of cases, and it is estimated that thousands die each year from the disease. Little is known about the complex immune mechanisms governing the response to LASV or the genetic determinants of susceptibility and resistance to infection. In the study presented here, we have used a whole-genome, microarray-based approach to determine the temporal host response in the peripheral blood mononuclear cells (PBMCs) of non-human primates (NHP) following aerosol exposure to LASV. Sequential sampling over the entire disease course showed that there are strong transcriptional changes of the immune response to LASV exposure, including the early induction of interferon-responsive genes and Toll-like receptor signaling pathways. However, this increase in early innate responses was coupled with a lack of pro-inflammatory cytokine response in LASV exposed NHPs. There was a distinct lack of cytokines such as IL1β and IL23α, while immunosuppressive cytokines such as IL27 and IL6 were upregulated. Comparison of IRF/STAT1-stimulated gene expression with the viral load in LASV exposed NHPs suggests that mRNA expression significantly precedes viremia, and thus might be used for early diagnostics of the disease. Our results provide a transcriptomic survey of the circulating immune response to hemorrhagic LASV exposure and provide a foundation for biomarker identification to allow clinical diagnosis of LASV infection through analysis of the host response. Author Summary: Lassa virus (LASV), a member of the Arenaviridae family, is a viral hemorrhagic fever causing virus endemic to several countries in West Africa with a history of sporadic importation into the United States. It has been characterized as a Category A agent, and despite the significant public health issues posed by LASV and the potential biodefense risks, little is known about the immune response to the virus. In the study presented here, we have taken an unbiased genomics approach to map the temporal host response in the peripheral blood mononuclear cells (PBMCs) of non-human primates (NHP) exposed to LASV. Gene expression patterns over the entire disease course showed that there are strong transcriptional changes of the immune response to LASV exposure, including the upregulation of Toll-like receptor signaling pathways and innate antiviral transcription factors. However, there was a lack of pro-inflammatory cytokine response in LASV exposed NHPs similar to what is seen in human disease. Our data suggests that LASV induces negative regulation of immunological events, leading to an inefficient adaptive immune response as observed in LASV-infected human patients. Our results provide a picture of the host's circulating immune response to hemorrhagic LASV exposure and demonstrate that gene expression patterns correlate with specific stages of disease progression. [ABSTRACT FROM AUTHOR]