The Ongoing Ebola Epidemic in the Democratic Republic of Congo, 2018–2019

O, Ilunga Kalenga; Moeti, Matshidiso; Sparrow, Annie; Vk, Nguyen; Lucey, Daniel R.; Ta, Ghebreyesus

doi:10.1056/nejmsr1904253

Cited by 148 publications

(128 citation statements)

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“…Ebola virus (EBOV) is among the world's most lethal pathogens, with an estimated case fatality rate of 66% in the recent epidemic in the Democratic Republic of the Congo (Ilunga Kalenga et al, 2019;World Health Organization, 2019) and 40% in the 2013-2016 epidemic in West Africa (Lo et al, 2017) . EBOV infection in humans causes Ebola virus disease (EVD), characterized by fever, malaise, muscle aches, and gastrointestinal distress, rapidly progressing to coagulopathy, shock, and multi-organ failure (Malvy et al, 2019) .…”

Section: Introductionmentioning

confidence: 99%

Single-cell profiling of Ebola virus infectionin vivoreveals viral and host transcriptional dynamics

Kotliar

Lin

Logue

et al. 2020

Preprint

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Ebola virus (EBOV) causes epidemics with high case fatality rates, yet remains understudied due to the challenge of experimentation in high-containment and outbreak settings. To better understand EBOV infection in vivo , we used single-cell transcriptomics and CyTOF-based single-cell protein quantification to characterize peripheral immune cell activity during EBOV infection in rhesus monkeys. We obtained 100,000 transcriptomes and 15,000,000 protein profiles, providing insight into pathogenesis. We find that immature, proliferative monocyte-lineage cells with reduced antigen presentation capacity replace conventional circulating monocyte subsets within days of infection, while lymphocytes upregulate apoptosis genes and decline in abundance. By quantifying viral RNA abundance in individual cells, we identify molecular determinants of tropism and examine temporal dynamics in viral and host gene expression. Within infected cells, we observe that EBOV down-regulates STAT1 mRNA and interferon signaling, and up-regulates putative pro-viral genes (e.g., DYNLL1 and HSPA5 ), nominating cellular pathways the virus manipulates for its replication. Overall, this study sheds light on EBOV tropism, replication dynamics, and elicited immune response, and provides a framework for characterizing interactions between hosts and emerging viruses in a maximum containment setting. over-activation of innate and adaptive immunity underlies much of EVD pathology, rather than solely virus-mediated cytotoxicity (Geisbert et al., 2003a(Geisbert et al., , 2003b .

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Section: Introductionmentioning

confidence: 99%

Single-cell profiling of Ebola virus infectionin vivoreveals viral and host transcriptional dynamics

Kotliar

Lin

Logue

et al. 2020

Preprint

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“…Despite the lack of proper drugs that effectively mitigate sepsis, the mortality of sepsis has gradually reduced thanks to consolidated efforts of clinicians, such as the Surviving Sepsis Campaign Guidelines, which was recently updated in 2018 1 . However, we are still in desperate need of developing a new strategy to fight against infectious outbreaks worldwide whenever infectious diseases, such as severe acute respiratory syndrome (SARS) 10 , Ebola 11 , middle east respiratory syndrome (MERS) 12 , surfaced and threatened the world. In the past five years, we experienced multiple severe outbreaks of Ebola (2014-2016 in West Africa), MERS (2015 in the Republic of Korea), and the recent coronavirus outbreak (COVID-19 in Wuhan, China).…”

Section: Introductionmentioning

confidence: 99%

Multiscale Biofluidic and Nanobiotechnology Approaches for Treating Sepsis in Extracorporeal Circuits

Kang

2020

BioChip J

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Infectious diseases and their pandemics periodically attract public interests due to difficulty in treating the patients and the consequent high mortality. Sepsis caused by an imbalanced systemic inflammatory response to infection often leads to organ failure and death. The current therapeutic intervention mainly includes "the sepsis bundles," antibiotics (antibacterial, antiviral, and antifungal), intravenous fluids for resuscitation, and surgery, which have significantly improved the clinical outcomes in past decades; however, the patients with fulminant sepsis are still in desperate need of alternative therapeutic approaches. One of the potential supportive therapies, extracorporeal blood treatment, has emerged and been developed for improving the current therapeutic efficacy. Here, I overview how the treatment of infectious diseases has been assisted with the extracorporeal adjuvant therapy and the potential utility of various nanobiotechnology and microfluidic approaches for developing new auxiliary therapeutic methods.

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“…The outbreak in Western Africa in 2014-2016 killed over 11,000 and caused over $53bn in economic damage (13). The current ongoing outbreak in the Democratic Republic of the Congo, in which well over 2200 people have died to date at the time of writing, and where the current case fatality is ∼67% (14)), emphasizes this need for new drugs while there is still no FDA approved drug for this disease. Several small molecule drugs such as favipiravir (15, 16) and most recently remdesivir (17) have been tested against EBOV in patients, although it is unclear whether any of them demonstrate efficacy (18, 19).…”

Section: Introductionmentioning

confidence: 99%

Pyronaridine Tetraphosphate Efficacy Against Ebola Virus Infection in Guinea Pig

Lane

Massey²,

Comer³

et al. 2020

Preprint

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31The recent outbreaks of the Ebola virus (EBOV) in Africa have brought global visibility to 32 the shortage of available therapeutic options to treat patients infected with this or closely 33 related viruses. We have recently computationally identified three molecules which have 34 all demonstrated statistically significant efficacy in the mouse model of infection with 35 mouse adapted Ebola virus (ma-EBOV). One of these molecules is the antimalarial 36 pyronaridine tetraphosphate (IC 50 range of 0.82-1.30 µM against three strains of EBOV 37 and IC 50 range of 1.01-2.72 µM against two strains of Marburg virus (MARV)) which is 38 an approved drug in the European Union and used in combination with artesunate. To 39 date, no small molecule drugs have shown statistically significant efficacy in the guinea 40 pig model of EBOV infection. Pharmacokinetics and range-finding studies in guinea pigs 41 directed us to a single 300mg/kg or 600mg/kg oral dose of pyronaridine 1hr after 42 infection. Pyronaridine resulted in statistically significant survival of 40% at 300mg/kg 43 and protected from a lethal challenge with EBOV. In comparison, oral favipiravir (300 44 mg/kg dosed once a day) had 43.5 % survival. The in vitro metabolism and metabolite 45 identification of pyronaridine and another of our EBOV active molecules, tilorone, which 46 suggests significant species differences which may account for the efficacy or lack 47 thereof, respectively in guinea pig. In summary, our studies with pyronaridine 48 demonstrates its utility for repurposing as an antiviral against EBOV and MARV, 49 providing justification for future testing in non-human primates. 50 51 52 4 Importance 53There is currently no antiviral small molecule drug approved for treating Ebola Virus 54 infection. We have previously used machine learning models to identify new uses for 55 approved drugs and demonstrated their activity against the Ebola virus in vitro and in 56 vivo. We now describe the pharmacokinetic properties of the antimalarial pyronaridine in 57 the guinea pig. In addition, we show that this drug is effective against multiple strains of 58 EBOV and MARV in vitro and in the guinea pig model of Ebola virus infection. These 59 combined efforts indicate the need to further test this molecule in larger animal efficacy 60 studies prior to clinical use in humans. These findings also may be useful for 61 repurposing this drug for use against other viruses in future. 62 63

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The Ongoing Ebola Epidemic in the Democratic Republic of Congo, 2018–2019

Cited by 148 publications

References 5 publications

Single-cell profiling of Ebola virus infectionin vivoreveals viral and host transcriptional dynamics

Single-cell profiling of Ebola virus infectionin vivoreveals viral and host transcriptional dynamics

Multiscale Biofluidic and Nanobiotechnology Approaches for Treating Sepsis in Extracorporeal Circuits

Pyronaridine Tetraphosphate Efficacy Against Ebola Virus Infection in Guinea Pig

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