Monitoring of Prognostic Laboratory Markers in Ebola Virus Disease

Janvier, Frédéric; Foissaud, Vincent; Cotté, Jean; Aletti, M.; Savini, Hélène; Cordier, Pierre Yves; Maugey, Nancy; Duron, Sandrine; Koulibaly, Fassou; Graníer, H.; Carmoi, T.; Sagui, Emmanuel

doi:10.1093/infdis/jiv546

Cited by 9 publications

(5 citation statements)

References 9 publications

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“…Our finding that, in lieu of viral load, laboratory values at 5 dpi could potentially predict survival duration is not entirely surprising given that Warren et al ( 28 ) published NHP data that showed the course of EBOV viral load is mirrored by the course of clinical chemistries in the setting of successful EVD treatment using the nucleotide prodrug GS-5734. Although it has been shown that AST levels can predict survival in EBOV-infected humans ( 5 , 10 , 11 ), we found that LDH may be a better predictor of survival time in NHP models using IM administered EBOV. In all 3 models in our study, LDH and viral load significantly increased at 5 dpi in EBOV Kikwit–infected rhesus and cynomolgus macaques and at 7 dpi in EBOV Makona–infected rhesus macaques.…”

Section: Discussioncontrasting

confidence: 84%

“…Herein, we summarize and compare the clinical features and laboratory values of 3 NHP lethal models of EVD and explore features associated with early manifestations of infection and improved survival. Similar to Janvier et al ( 11 ), who recommended the use of high AST levels in humans as a surrogate marker of EBOV viral load and, therefore, disease detection and survival, we explored whether NHP laboratory data would lend support to the use of clinical laboratory values as predictors of survival and surrogates for EBOV viral loads. Further analysis was conducted to determine if clinical laboratory values could be used for indication of infection with the goal of developing a standardized trigger for the initiation of treatment in the NHP model.…”

mentioning

confidence: 98%

“…Analysis of the most recent EBOV epidemic and previous outbreaks identified predictors associated with decreased survival: high quantitative viral load ( 3 – 7 ); low PCR cycle threshold ( 8 – 12 ); age (very young and very old) ( 5 , 6 , 10 , 13 – 16 ); male sex ( 12 , 17 ); country of residence ( 1 , 17 ); levels of D-dimer ( 18 ), aspartate aminotransferase (AST) ( 5 , 10 , 11 ), blood urea nitrogen (BUN) ( 5 ), and serum creatinine ( 5 , 10 ); and clinical symptoms of diarrhea, pain, myalgia, hemorrhage, and difficulty breathing ( 10 , 12 , 15 , 19 , 20 ). Of the various EVD animal models that have been developed, those using nonhuman primates (NHPs) appear to most closely reproduce the known features of lethal disease in humans.…”

mentioning

confidence: 99%

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Clinical Laboratory Values as Early Indicators of Ebola Virus Infection in Nonhuman Primates

Reisler¹,

Yu²,

D’Onofrio³

et al. 2017

Emerg. Infect. Dis.

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The Ebola virus (EBOV) outbreak in West Africa during 2013–2016 demonstrated the need to improve Ebola virus disease (EVD) diagnostics and standards of care. This retrospective study compared laboratory values and clinical features of 3 nonhuman primate models of lethal EVD to assess associations with improved survival time. In addition, the study identified laboratory values useful as predictors of survival, surrogates for EBOV viral loads, and triggers for initiation of therapeutic interventions in these nonhuman primate models. Furthermore, the data support that, in nonhuman primates, the Makona strain of EBOV may be less virulent than the Kikwit strain of EBOV. The applicability of these findings as potential diagnostic and management tools for EVD in humans warrants further investigation.

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Section: Discussioncontrasting

confidence: 84%

mentioning

confidence: 98%

mentioning

confidence: 99%

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Clinical Laboratory Values as Early Indicators of Ebola Virus Infection in Nonhuman Primates

Reisler¹,

Yu²,

D’Onofrio³

et al. 2017

Emerg. Infect. Dis.

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“…b Source: [10]; c Source: [11]; d Source: [12]; e Sources: [13][14][15]; f Source: [16] g Data for humans are from the following sources: [11,[17][18][19][20][21]. h Data for humans are from the following sources: [20,[22][23][24][25][26][27][28][29][30][31]. i Data for humans are from the following sources: [12,32].…”

Section: Rhesus Im/ebov Disease Compared To Human Evdmentioning

confidence: 99%

Characterization of Ebola Virus Disease (EVD) in Rhesus Monkeys for Development of EVD Therapeutics

Warren

Zumbrun

Weidner

et al. 2020

Viruses

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Recent Ebola virus (EBOV) outbreaks in West Africa and the Democratic Republic of the Congo have highlighted the urgent need for approval of medical countermeasures for treatment and prevention of EBOV disease (EVD). Until recently, when successes were achieved in characterizing the efficacy of multiple experimental EVD therapeutics in humans, the only feasible way to obtain data regarding potential clinical benefits of candidate therapeutics was by conducting well-controlled animal studies. Nonclinical studies are likely to continue to be important tools for screening and development of new candidates with improved pharmacological properties. Here, we describe a natural history study to characterize the time course and order of progression of the disease manifestations of EVD in rhesus monkeys. In 12 rhesus monkeys exposed by the intramuscular route to 1000 plaque-forming units of EBOV, multiple endpoints were monitored for 28 days following exposure. The disease progressed rapidly with mortality events occurring 7–10 days after exposure. Key disease manifestations observed consistently across the infected animals included, but were not limited to, viremia, fever, systemic inflammation, coagulopathy, lymphocytolysis, renal tubular necrosis with mineralization, and hepatocellular degeneration and necrosis.

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“…Ebola can result in significant hematological abnormalities [52,83]. It can also lead to liver failure followed by coagulopathy [60]. Thrombocytopenia, leukopenia, and anemia are all common and treatment should be based on the specific abnormality encountered.…”

Section: Treatmentmentioning

confidence: 99%