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This case study describes a feasibility assessment of a novel isolation care tent used in health facilities in Uganda during the 2022 Sudan ebolavirus outbreak. The Isolation System for Treatment and Agile Response to High-Risk Infections Model 1B (ISTARI 1B) is a single-occupancy, portable, negative-pressure isolation tent designed for the safe delivery of standard care to patients with a communicable disease, including Ebola disease (Sudan). At the request of the Uganda Ministry of Health, the Makerere University Infectious Diseases Institute and University of Nebraska Medical Center partnered to evaluate 7 health facilities across 4 districts in Uganda for infrastructure, case management, and infection prevention and control (IPC) capacity relevant to isolation care and ISTARI 1B use. A 3-day workshop was held with IPC leaders to provide familiarization and hands-on experience with the ISTARI 1B, delineate appropriate use scenarios in Ugandan healthcare settings, contextualize ISTARI 1B use in case management and IPC workflows, develop a framework for site assessment and implementation readiness, and consider ongoing monitoring, assessment, and intervention tools. Workshop participants performed a comprehensive site assessment and mock deployment of the ISTARI 1B. In this case study, we describe lessons learned from health facility assessments and workshop outcomes and offer recommendations to support successful ISTARI 1B implementation. Use scenarios and implementation strategies were identified across facility levels, including tools for site assessment, training, risk communication, and ongoing quality and safety monitoring. [ABSTRACT FROM AUTHOR]

[Display omitted] Although two vaccines for Zaire ebolavirus (EBOV) have been licensed and deployed successfully to combat recurring outbreaks of Ebolavirus Disease in West Africa, there are no vaccines for two other highly pathogenic members of the Filoviridae , Sudan ebolavirus (SUDV) and Marburg marburgvirus (MARV). The results described herein document the immunogenicity and protective efficacy in cynomolgus macaques of a single-vial, thermostabilized (lyophilized) monovalent (SUDV) and bivalent (SUDV & MARV) protein vaccines consisting of recombinant glycoproteins (GP) formulated with a clinical-grade oil-in-water nanoemulsion adjuvant (CoVaccine HT™). Lyophilized formulations of the vaccines were reconstituted with Water for Injection and used to immunize groups of cynomolgus macaques before challenge with a lethal dose of a human SUDV or MARV isolate. Sera collected after each of the three immunizations showed near maximal GP-binding IgG concentrations starting as early as the second dose. Most importantly, the vaccine candidates (monovalent or bivalent) provided 100% protection against severe and lethal filovirus disease after either SUDV or MARV infection. Although mild, subclinical infection was observed in a few macaques, all vaccinated animals remained healthy and survived the filovirus challenge. These results demonstrate the value that thermostabilized protein vaccines could provide for addressing an important gap in preparedness for future filovirus outbreaks. [ABSTRACT FROM AUTHOR]

Background: Ebola virus disease (Ebola) is highly pathogenic, transmissible, and often deadly, with debilitating consequences. Superspreading within a cluster is also possible. In this study, we aim to document Ebola basic reproduction number (R0): the average number of new cases associated with an Ebola case in a completely susceptible population. Methods: We undertook a systematic review and meta-analysis. We searched PubMed, EMBASE, and Web of Science for studies published between 1976 and February 27, 2023. We also manually searched the reference lists of the reviewed studies to identify additional studies. We included studies that reported R0 during Ebola outbreaks in Africa. We excluded studies that reported only the effective reproduction number (Rt). Abstracting data from included studies was performed using a pilot-tested standard form. Two investigators reviewed the studies, extracted the data, and assessed quality. The pooled R0 was determined by a random-effects meta-analysis. R0 was stratified by country. We also estimated the theoretically required immunization coverage to reach herd-immunity using the formula of (1-1/R0) × 100 %. Results: The search yielded 2042 studies. We included 53 studies from six African countries in the systematic review providing 97 Ebola mean R0 estimates. 27 (with 46 data points) studies were included in the meta-analysis. The overall pooled mean Ebola R0 was 1.95 (95 % CI 1.74–2.15), with high heterogeneity (I2 = 99.99 %; τ2 = 0.38; and p

Due to its high mortality rate and continued re-emergence, Ebolavirus disease (EVD) continues to pose a serious threat to global health. A group of viruses within the genus Ebolavirus causes this severe hemorrhagic disease in humans: Ebola virus (EBOV; species Zaire ebolavirus), Sudan virus (SUDV; species Sudan ebolavirus), Bundibugyo virus, and Taï Forest virus. EBOV and SUDV are associated with the highest case fatality rates. While the host response to EBOV has been comprehensively examined, limited data exists for SUDV infection. For medical countermeasure testing, well-characterized SUDV nonhuman primate (NHP) models are thus needed. Here, we describe a natural history study in which rhesus (N = 11) and cynomolgus macaques (N = 14) were intramuscularly exposed to a 1000 plaque-forming unit dose of SUDV (Gulu variant). Time-course analyses of various hematological, pathological, serological, coagulation, and transcriptomic findings are reported. SUDV infection was uniformly lethal in cynomolgus macaques (100% mortality), whereas a single rhesus macaque subject (91% mortality) survived to the study endpoint (median time-to-death of ∼8.0 and ∼8.5 days in cynomolgus and rhesus macaques, respectively). Infected macaques exhibited hallmark features of human EVD. The early stage was typified by viremia, granulocytosis, lymphopenia, albuminemia, thrombocytopenia, and decreased expression of HLA-class transcripts. At mid-to-late disease, animals developed fever and petechial rashes, and expressed high levels of pro-inflammatory mediators, pro-thrombotic factors, and markers indicative of liver and kidney injury. End-stage disease was characterized by shock and multi-organ failure. In summary, macaques recapitulate human SUDV disease, supporting these models for use in the development of vaccines and therapeutics.

This review describes key aspects of the development of the rVSVΔG-ZEBOV-GP Ebola vaccine and key activities which are continuing to further expand our knowledge of the product. Extensive partnerships and innovative approaches were used to address the various challenges encountered during this process. The rVSVΔG-ZEBOV-GP Ebola vaccine was initially approved by the European Medicines Agency and prequalified by the World Health Organization in November 2019. It was approved by the United States Food and Drug Administration in December 2019 and approved in five African countries within 90 days of prequalification. The development resulted in the first stockpile of a registered Ebola vaccine that is available to support outbreak response. This also provides insights into how the example of rVSVΔG-ZEBOV-GP can inform the development of vaccines for Sudan ebolavirus, Marburg virus, and other emerging epidemic diseases in terms of the types of approaches and data needed to support product registration, availability, and the use of a filovirus vaccine. [ABSTRACT FROM AUTHOR]

Sudan ebolavirus (SUDV) is one of four members of the Ebolavirus genus known to cause Ebola Virus Disease (EVD) in humans, which is characterized by hemorrhagic fever and a high case fatality rate. While licensed therapeutics and vaccines are available in limited number to treat infections of Zaire ebolavirus, there are currently no effective licensed vaccines or therapeutics for SUDV. A well-characterized animal model of this disease is needed for the further development and testing of vaccines and therapeutics. In this study, twelve cynomolgus macaques (Macaca fascicularis) were challenged intramuscularly with 1000 PFUs of SUDV and were followed under continuous telemetric surveillance. Clinical observations, body weights, temperature, viremia, hematology, clinical chemistry, and coagulation were analyzed at timepoints throughout the study. Death from SUDV disease occurred between five and ten days after challenge at the point that each animal met the criteria for euthanasia. All animals were observed to exhibit clinical signs and lesions similar to those observed in human cases which included: viremia, fever, dehydration, reduced physical activity, macular skin rash, systemic inflammation, coagulopathy, lymphoid depletion, renal tubular necrosis, hepatocellular degeneration and necrosis. The results from this study will facilitate the future preclinical development and evaluation of vaccines and therapeutics for SUDV. [ABSTRACT FROM AUTHOR]

The 2014–2016 Ebola virus epidemic in West Africa triggered extensive investments from public and private partners in an attempt to slow the spread of disease and bring the outbreak under control. This significantly accelerated the pace of development of countermeasures against Zaire ebolavirus that enabled vaccines to be a part of an effective response to the most recent 2018–2019 outbreak in the Democratic Republic of the Congo. However, there remain urgent and unmet needs for medical countermeasures against other members of the Filoviridae family that cause viral hemorrhagic fevers. To improve the national and global preparedness posture for viral hemorrhagic fevers, a renewed emphasis is being placed on developing vaccines for filoviruses other than Zaire ebolavirus. Here we discuss lessons learned from the West Africa epidemic and how those lessons apply to the development of vaccine candidates for other filoviruses, specifically Sudan ebolavirus and Marburg virus. This commentary will highlight some of the key product development gaps to address in preparation for future disease outbreaks caused by these viruses.

This review describes key aspects of the development of the rVSVΔG-ZEBOV-GP Ebola vaccine and key activities which are continuing to further expand our knowledge of the product. Extensive partnerships and innovative approaches were used to address the various challenges encountered during this process. The rVSVΔG-ZEBOV-GP Ebola vaccine was initially approved by the European Medicines Agency and prequalified by the World Health Organization in November 2019. It was approved by the United States Food and Drug Administration in December 2019 and approved in five African countries within 90 days of prequalification. The development resulted in the first stockpile of a registered Ebola vaccine that is available to support outbreak response. This also provides insights into how the example of rVSVΔG-ZEBOV-GP can inform the development of vaccines for Sudan ebolavirus, Marburg virus, and other emerging epidemic diseases in terms of the types of approaches and data needed to support product registration, availability, and the use of a filovirus vaccine.

Sudan ebolavirus (SUDV) is one of four members of the Ebolavirus genus known to cause Ebola Virus Disease (EVD) in humans, which is characterized by hemorrhagic fever and a high case fatality rate. While licensed therapeutics and vaccines are available in limited number to treat infections of Zaire ebolavirus, there are currently no effective licensed vaccines or therapeutics for SUDV. A well-characterized animal model of this disease is needed for the further development and testing of vaccines and therapeutics. In this study, twelve cynomolgus macaques (Macaca fascicularis) were challenged intramuscularly with 1000 PFUs of SUDV and were followed under continuous telemetric surveillance. Clinical observations, body weights, temperature, viremia, hematology, clinical chemistry, and coagulation were analyzed at timepoints throughout the study. Death from SUDV disease occurred between five and ten days after challenge at the point that each animal met the criteria for euthanasia. All animals were observed to exhibit clinical signs and lesions similar to those observed in human cases which included: viremia, fever, dehydration, reduced physical activity, macular skin rash, systemic inflammation, coagulopathy, lymphoid depletion, renal tubular necrosis, hepatocellular degeneration and necrosis. The results from this study will facilitate the future preclinical development and evaluation of vaccines and therapeutics for SUDV.

Ebola virus disease (Ebola) is highly pathogenic, transmissible, and often deadly, with debilitating consequences. Superspreading within a cluster is also possible. In this study, we aim to document Ebola basic reproduction number (R 0): the average number of new cases associated with an Ebola case in a completely susceptible population. We undertook a systematic review and meta-analysis. We searched PubMed, EMBASE, and Web of Science for studies published between 1976 and February 27, 2023. We also manually searched the reference lists of the reviewed studies to identify additional studies. We included studies that reported R 0 during Ebola outbreaks in Africa. We excluded studies that reported only the effective reproduction number (R t). Abstracting data from included studies was performed using a pilot-tested standard form. Two investigators reviewed the studies, extracted the data, and assessed quality. The pooled R 0 was determined by a random-effects meta-analysis. R 0 was stratified by country. We also estimated the theoretically required immunization coverage to reach herd-immunity using the formula of (1-1/R 0) × 100 %. The search yielded 2042 studies. We included 53 studies from six African countries in the systematic review providing 97 Ebola mean R 0 estimates. 27 (with 46 data points) studies were included in the meta-analysis. The overall pooled mean Ebola R 0 was 1.95 (95 % CI 1.74–2.15), with high heterogeneity (I2 = 99.99 %; τ2 = 0.38; and p < 0.001) and evidence of small-study effects (Egger's statistics: Z = 4.67; p < 0.001). Mean Ebola R 0 values ranged from 1.2 to 10.0 in Nigeria, 1.1 to 7 in Guinea, 1.14 to 8.33 in Sierra Leone, 1.13 to 5 in Liberia, 1.2 to 5.2 in DR Congo, 1.34 to 2.7 in Uganda, and from 1.40 to 2.55 for all West African countries combined. Pooled mean Ebola R 0 was 9.38 (95 % CI 4.16–14.59) in Nigeria, 3.31 (95 % CI 2.30–4.32) in DR Congo, 2.0 (95 % CI 1.25–2.76) in Uganda, 1.83 (95 % CI 1.61–2.05) in Liberia, 1.73 (95 % CI 1.47–2.0) in Sierra Leonne, and 1.44 (95 % CI 1.29–1.60) in Guinea. In theory, 50 % of the population needs to be vaccinated to achieve herd immunity, assuming that Ebola vaccine would be 100 % effective. Ebola R 0 varies widely across countries. Ebola has a much wider R 0 range than is often claimed (1.3–2.0). It is possible for an Ebola index case to infect more than two susceptible individuals. [ABSTRACT FROM AUTHOR]

Background: Ebola virus disease (Ebola) is highly pathogenic, transmissible, and often deadly, with debilitating consequences. Superspreading within a cluster is also possible. In this study, we aim to document Ebola basic reproduction number (R 0 ): the average number of new cases associated with an Ebola case in a completely susceptible population., Methods: We undertook a systematic review and meta-analysis. We searched PubMed, EMBASE, and Web of Science for studies published between 1976 and February 27, 2023. We also manually searched the reference lists of the reviewed studies to identify additional studies. We included studies that reported R 0 during Ebola outbreaks in Africa. We excluded studies that reported only the effective reproduction number (R t ). Abstracting data from included studies was performed using a pilot-tested standard form. Two investigators reviewed the studies, extracted the data, and assessed quality. The pooled R 0 was determined by a random-effects meta-analysis. R 0 was stratified by country. We also estimated the theoretically required immunization coverage to reach herd-immunity using the formula of (1-1/R 0 ) × 100 %., Results: The search yielded 2042 studies. We included 53 studies from six African countries in the systematic review providing 97 Ebola mean R 0 estimates. 27 (with 46 data points) studies were included in the meta-analysis. The overall pooled mean Ebola R 0 was 1.95 (95 % CI 1.74-2.15), with high heterogeneity (I 2  = 99.99 %; τ 2  = 0.38; and p < 0.001) and evidence of small-study effects (Egger's statistics: Z = 4.67; p < 0.001). Mean Ebola R 0 values ranged from 1.2 to 10.0 in Nigeria, 1.1 to 7 in Guinea, 1.14 to 8.33 in Sierra Leone, 1.13 to 5 in Liberia, 1.2 to 5.2 in DR Congo, 1.34 to 2.7 in Uganda, and from 1.40 to 2.55 for all West African countries combined. Pooled mean Ebola R 0 was 9.38 (95 % CI 4.16-14.59) in Nigeria, 3.31 (95 % CI 2.30-4.32) in DR Congo, 2.0 (95 % CI 1.25-2.76) in Uganda, 1.83 (95 % CI 1.61-2.05) in Liberia, 1.73 (95 % CI 1.47-2.0) in Sierra Leonne, and 1.44 (95 % CI 1.29-1.60) in Guinea. In theory, 50 % of the population needs to be vaccinated to achieve herd immunity, assuming that Ebola vaccine would be 100 % effective., Conclusions: Ebola R 0 varies widely across countries. Ebola has a much wider R 0 range than is often claimed (1.3-2.0). It is possible for an Ebola index case to infect more than two susceptible individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We had previously shown that three anti–Marburg virus nanobodies (VHH or single-domain antibody [sdAb]) targeted a cryptotope within an alpha-helical assembly at the nucleoprotein (NP) C-terminus that was conserved through half a century of viral evolution. Here, we wished to determine whether an anti–Ebola virus sdAb, that was cross-reactive within the Ebolavirus genus, recognized a similar structural feature upstream of the ebolavirus NP C-terminus. In addition, we sought to determine whether the specificities of a less cross-reactive anti– Zaire ebolavirus sdAb and a totally specific anti– Sudan ebolavirus sdAb were the result of exclusion from this region. Binding and X-ray crystallographic studies revealed that the primary determinant of cross-reactivity did indeed appear to be a preference for the helical feature. Specificity, in the case of the Zaire ebolavirus– specific sdAb, arose from the footprint shifting away from the helices to engage more variable residues. While both sdAbs used CDRs, they also had atypical side-on approaches, with framework 2 helping to accommodate parts of the epitope in sizeable paratope gullies. The Sudan ebolavirus –specific sdAb was more remarkable and appeared to bind two C-terminal domains simultaneously via nonoverlapping epitopes—"paratope duality." One mode involved paratope gullying, whereas the other involved only CDRs, with CDR3 restructuring to wedge in between opposing walls of an interdomain crevice. The varied routes used by sdAbs to engage antigens discovered here deepen our appreciation of the small scaffold's architectural versatility and also reveal lucrative opportunities within the ebolavirus NP C-termini that might be leveraged for diagnostics and novel therapeutic targeting. Image 1 • Differential specificities of anti–Ebola virus nucleoprotein nanobodies are explained. • Frameworks enable atypical "side-on" binding of antigens by nanobodies. • Atypical paratopes are recontoured to accommodate nonconcave epitopes. • Typical and atypical nanobody approaches are not necessarily mutually exclusive. • Paratope duality allows the simultaneous engagement of two nonoverlapping epitopes. [ABSTRACT FROM AUTHOR]

Ebola hemorrhagic fever is a viral disease from Ebolavirus genus and lethal to primates, including humans. The case fatality rate is 30%-90%. Until now, no vaccines nor drugs that could effectively combat Ebola hemorrhagic fever. Sudan ebolavirus (SEBOV) is the second deadliest species after Zaire ebolavirus, with a fatality rate of 50-70%. In Ebola life cycle, glycoprotein (GP) is crucial for mediating Ebolavirus entry into the host cell. Thus, molecules that could inhibit GP activity has a potential to become an ideal therapeutic compound of Ebola hemorrhagic fever. Flavonoid compounds are potential because of its antiviral properties. In this research, the in silico method was utilized to investigate the potency of flavonoid compounds as an inhibitor of SEBOV GP through molecular docking and computational ADMET test. Moreover, the oral bioavailability and toxicity prediction of the flavonoid compounds were performed as well to get the best flavonoid compounds. In this research, about 1358 flavonoid compounds and 3D structure of SEBOV GP were retrieved from ChEBI database and RCSB PDB, respectively. Moreover, MOE 2014.09 software was used as the primary software. Furthermore, the Osiris DataWarrior and SwissADME were used as the software for conducting computational ADMET test. In the end, cyanidin-3-(p-coumaroyl)-rutinoside-5-glucoside, myricitrin V, and 7-O-(6-feruoylglucosy) were selected as the potential inhibitor of SEBOV GP because they have the best binding affinity and low toxicity risk. [ABSTRACT FROM AUTHOR]

Ebolaviruses have a surface glycoprotein (GP1,2) that is required for virus attachment and entry into cells. Mutations affecting GP1,2 functions can alter virus growth properties. We generated a recombinant vesicular stomatitis virus encoding Ebola virus Makona variant GP1,2 (rVSV-MAK-GP) and observed emergence of a T544I mutation in the Makona GP1,2 gene during tissue culture passage in certain cell lines. The T544I mutation emerged within two passages when VSV-MAK-GP was grown on Vero E6, Vero, and BS-C-1 cells but not when it was passaged on Huh7 and HepG2 cells. The mutation led to a marked increase in virus growth kinetics and conferred a robust growth advantage over wild-type rVSV-MAK-GP on Vero E6 cells. Analysis of complete viral genomes collected from patients in western Africa indicated that this mutation was not found in Ebola virus clinical samples. However, we observed the emergence of T544I during serial passage of various Ebola Makona isolates on Vero E6 cells. Three independent isolates showed emergence of T544I from undetectable levels in nonpassaged virus or virus passaged once to frequencies of greater than 60% within a single passage, consistent with it being a tissue culture adaptation. Intriguingly, T544I is not found in any Sudan, Bundibugyo, or Tai Forest ebolavirus sequences. Furthermore, T544I did not emerge when we serially passaged recombinant VSV encoding GP1,2 from these ebolaviruses. This report provides experimental evidence that the spontaneous mutation T544I is a tissue culture adaptation in certain cell lines and that it may be unique for the species Zaire ebolavirus. [ABSTRACT FROM AUTHOR]

Two large outbreaks of Ebola hemorrhagic fever occurred in Uganda in 2000 and 2007. In May 2011, we identified a single case of Sudan Ebola virus disease in Luwero District. The establishment of a permanent in-country laboratory and cooperation between international public health entities facilitated rapid outbreak response and control activities.

Filoviruses represent a significant public health threat worldwide. West Africa recently experienced the largest-scale and most complex filovirus outbreak yet known, which underlines the need for a predictive understanding of the geographic distribution and potential for transmission to humans of these viruses. Here, we used ecological niche modeling techniques to understand the relationship between known filovirus occurrences and environmental characteristics. Our study derived a picture of the potential transmission geography of Ebola virus species and Marburg, paired with views of the spatial uncertainty associated with model-to-model variation in our predictions. We found that filovirus species have diverged ecologically, but only three species are sufficiently well known that models could be developed with significant predictive power. We quantified uncertainty in predictions, assessed potential for outbreaks outside of known transmission areas, and highlighted the Ethiopian Highlands and scattered areas across East Africa as additional potentially unrecognized transmission areas. [ABSTRACT FROM AUTHOR]

TheEbolavirusgenus includes five member species, all of which pose a threat to global public health. These viruses cause fatal hemorrhagic fever in humans and nonhuman primates, and are considered category A pathogens due to the risk of their use as a bioweapon. The potential for an outbreak, either as a result of a natural emergence, deliberate release, or imported case underscores the need for protective vaccines. Recent progress in advancing vaccines for use against the strain ofZaire ebolavirus(EBOV) responsible for the West African Ebola outbreak offers reasons for optimism against EBOV, and demonstrates that protection against otherEbolavirusspecies is achievable. [ABSTRACT FROM PUBLISHER]

E bola virus disease (EVD) is a rare but highly contagious and lethal disease that occurs predominantly in African countries, with a case-fatality rate of 30-90%. The causative viral pathogens of EVD are within the genus Ebolavirus in the family Filoviridae . The primary route of human-to-human transmission is through direct contact with blood, bodily fluids and secretions from infected individuals. Direct contact with virally contaminated objects and sexual transmission have also been reported. Management of EVD is aggressive supportive care with possibly new therapeutic options. On 20 September 2022, an EVD outbreak was declared in Uganda, caused by Sudan ebolavirus . As of 7 November 2022, a total of 136 confirmed cases, 53 confirmed deaths have been reported, including 18 cases with seven deaths among healthcare workers. In the Democratic Republic of Congo (DRC), an EVD outbreak was also declared on 22 August 2022 (which ended on 27 September 2022); with only one case, a middle-aged woman. At the time when most countries in the world have been occupied with the coronavirus disease 2019 (COVID-19) pandemic and the recent human monkeypox outbreak, these two outbreaks of EVD have the potential to significantly add to the burden on global health. Authorities need to augment their multi-faceted response, including stringent contact tracing and border control, to avoid the catastrophe of the 2014-2016 EVD epidemic., Competing Interests: All the authors declare that there are no conflicts of interest., (© 2022 The Author(s).)

Due to its high mortality rate and continued re-emergence, Ebolavirus disease (EVD) continues to pose a serious threat to global health. A group of viruses within the genus Ebolavirus causes this severe hemorrhagic disease in humans: Ebola virus (EBOV; species Zaire ebolavirus ), Sudan virus (SUDV; species Sudan ebolavirus ), Bundibugyo virus, and Taï Forest virus. EBOV and SUDV are associated with the highest case fatality rates. While the host response to EBOV has been comprehensively examined, limited data exists for SUDV infection. For medical countermeasure testing, well-characterized SUDV nonhuman primate (NHP) models are thus needed. Here, we describe a natural history study in which rhesus ( N  = 11) and cynomolgus macaques ( N  = 14) were intramuscularly exposed to a 1000 plaque-forming unit dose of SUDV (Gulu variant). Time-course analyses of various hematological, pathological, serological, coagulation, and transcriptomic findings are reported. SUDV infection was uniformly lethal in cynomolgus macaques (100% mortality), whereas a single rhesus macaque subject (91% mortality) survived to the study endpoint (median time-to-death of ∼8.0 and ∼8.5 days in cynomolgus and rhesus macaques, respectively). Infected macaques exhibited hallmark features of human EVD. The early stage was typified by viremia, granulocytosis, lymphopenia, albuminemia, thrombocytopenia, and decreased expression of HLA-class transcripts. At mid-to-late disease, animals developed fever and petechial rashes, and expressed high levels of pro-inflammatory mediators, pro-thrombotic factors, and markers indicative of liver and kidney injury. End-stage disease was characterized by shock and multi-organ failure. In summary, macaques recapitulate human SUDV disease, supporting these models for use in the development of vaccines and therapeutics.