Blood kinetics of Ebola virus in survivors and nonsurvivors

Lanini, Simone; Portella, Gina; Vairo, Francesco; Kobinger, Gary P.; Pesenti, Antonio; Langer, Martin; Kabia, Soccoh; Brogiato, Giorgio; Amone, Jackson; Castilletti, Concetta; Miccio, Rossella; Zumla, Alimuddin; Capobianchi, Maria Rosaria; Di, Antonino; Strada, Gino; Ippolito, Giuseppe

doi:10.1172/jci83111

Cited by 89 publications

(78 citation statements)

References 22 publications

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“…A number of studies have correlated nonsurvival at 90% or more if the viral load exceeds 6 log copies per millilitre [210][211][212][213][214] in untreated patients. In a study of 84 patients infected with EBOV in West Africa, all patients with a viral load >7.71 log copies per millilitre of blood died, whereas all those with counts below this threshold survived 215 . Thus, for example, in the case of the TKM-130803 EBOV trial, the patients who survived would almost certainly have died without at least receiving supportive care in addition to TKM-130803, but whether treatment with TKM-130803 had any contribution was not possible to determine with confidence owing to the issues with the trial discussed earlier.…”

Section: Discussionmentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

111

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| The filoviruses -Ebola virus and Marburg virus -cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus. This Review briefly discusses these failures and what has been learned from these experiences, and summarizes the current status of post-exposure medical countermeasures in development, including antibodies, small interfering RNA and small molecules. We outline how our current knowledge could be applied to the identification of novel interventions and ways to use interventions more effectively. R E V I E W SNATURE REVIEWS | DRUG DISCOVERY VOLUME 17 | JUNE 2018 | 413 © 2 0 1 8 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . AstheniaMuscular weakness. MyalgiaMuscular pain. ArthralgiaJoint pain. LeukopeniaA condition of having a low number of circulating leukocytes, including neutrophils, eosinophils, basophils, lymphocytes and monocytes. LymphocytopeniaA condition of having a low number of circulating leukocytes, including natural killer cells, T cells and B cells. ThrombocytopeniaA condition of having a low number of circulating thrombocytes, also known as platelets.and Ebolavirus. The Marburgvirus genus contains a single species, Marburg marburgvirus, which contains two members, Marburg virus (MARV) and Ravn virus (RAVV). The Ebolavirus genus consists of five distinct species: Bundibugyo ebolavirus (BDBV), Reston ebolavirus (RESTV), Sudan ebolavirus (SUDV), Tai Forest ebolavirus (TAFV; previously termed 'Côte d'Ivoire ebolavirus' but more commonly known as 'Ivory Coast ebolavirus') and Zaire ebolavirus (EBOV). MARV, RAVV, BDBV, SUDV and EBOV are important human pathogens, with case fatality rates often up to 90% for MARV, RAVV and EBOV, and around 55% for SUDV 8,10 . On the basis of two small outbreaks in 2007 and 2012, BDBV seems to be the least pathogenic, with a case fatality rate of about 40-48% 11,12 . In 1994, TAFV was associated with a number of deaths in chimpanzees and a single symptomatic but non-lethal human infection in the Republic of Côte d'Ivoire 13,14 . RESTV is lethal for macaques but is not thought to cause disease in humans 15 . An outbreak of RESTV was reported in pigs in the Philippines in 2008; however, it remains uncertain whether the disease observed in the pigs was caused by RESTV or other agents reported to have co-infected the animals 16 . Clinical manifestationsClinical and laboratory signs of disease caused by filovirus infection are nonspecific and usually associated with an incubation period of 2-21 days (mean 4-10 days) 8,17 . Illness begins with an abrupt onset of fever, astheni...

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Section: Discussionmentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

111

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“…Measurement of viral load is an important parameter in Marburg virus disease and Ebola virus disease, because viral load correlates with severity of disease, survival, and infectivity. [9][10][11][12][13][14][15][16] Assessing the viral load, and thus the potential infectivity of a patient, can guide triage and admission placement to minimise risk of interperson trans mission. Viral load measurements are also important to better understand the clinical presentation and pathogenesis of fi lovirus disease, and to interpret the effi cacy of candidate therapies and vaccines in animal models and human beings.…”

Section: Importance Of Fi Lovirus Load Determinationmentioning

confidence: 99%

“…42 For instance, a 1-2 log 10 diff erence in Ebola virus viral load, which may be within the margin of error of RT-PCR testing within and between many laboratories and assays, might correlate with signifi cant diff erences in lethality. 10,[12][13][14] Standard curves, generated by assessing multiple samples with known quantities of fi loviral RNA, can be used to measure the variability of results and off er a better understanding of the meaning of results across laboratories and time points. However, standard curves have rarely been generated under outbreak conditions, probably because of the high numbers of samples processed and to obtain and provide results rapidly.…”

Section: Variability Of Fi Lovirus Load Determinationmentioning

confidence: 99%

Essentials of filoviral load quantification

Cnops

Griensven

Honko

et al. 2016

The Lancet Infectious Diseases

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Quantitative measurement of viral load is an important parameter in the management of fi lovirus disease outbreaks because viral load correlates with severity of disease, survival, and infectivity. During the ongoing Ebola virus disease outbreak in parts of Western Africa, most assays used in the detection of Ebola virus disease by more than 44 diagnostic laboratories yielded qualitative results. Regulatory hurdles involved in validating quantitative assays and the urgent need for a rapid Ebola virus disease diagnosis precluded development of validated quantitative assays during the outbreak. Because of sparse quantitative data obtained from these outbreaks, opportunities for study of correlations between patient outcome, changes in viral load during the course of an outbreak, disease course in asymptomatic individuals, and the potential for virus transmission between infected patients and contacts have been limited. We strongly urge the continued development of quantitative viral load assays to carefully evaluate these parameters in future outbreaks of fi lovirus disease.

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“…7 RNA copies/ml blood at the time of diagnosis (typically seen as C T values of Ͻ25) (4,12,(33)(34)(35)(36). Recent evidence from a longitudinal study of four EVD survivors suggests that C T values greater than ϳ35 in the setting of convalescence are not associated with infectious virus (37); however, a C T value of Յ40 is typically used as the cutoff to designate a positive sample (37).…”

Section: Real-time Rt-pcrmentioning

confidence: 99%

“…The reported durations of persistence of detectable RNA in the serum or plasma of EVD survivors appear to depend on the RT-PCR assay used, although differences in study populations between testing centers render comparisons between assays difficult. Field laboratories in the 2014-2015 epidemic (employing a variety of commercial and laboratory-developed assays) reported variable times to clearance of detectable RNA in their survivor populations, ranging from day 13 to 45 of illness (12,15,35) (Fig. 1).…”

Section: Real-time Rt-pcrmentioning

confidence: 99%

Diagnosis of Ebola Virus Disease: Past, Present, and Future

2016

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SUMMARYLaboratory diagnosis of Ebola virus disease plays a critical role in outbreak response efforts; however, establishing safe and expeditious testing strategies for this high-biosafety-level pathogen in resource-poor environments remains extremely challenging. Since the discovery of Ebola virus in 1976 via traditional viral culture techniques and electron microscopy, diagnostic methodologies have trended toward faster, more accurate molecular assays. Importantly, technological advances have been paired with increasing efforts to support decentralized diagnostic testing capacity that can be deployed at or near the point of patient care. The unprecedented scope of the 2014-2015 West Africa Ebola epidemic spurred tremendous innovation in this arena, and a variety of new diagnostic platforms that have the potential both to immediately improve ongoing surveillance efforts in West Africa and to transform future outbreak responses have reached the field. In this review, we describe the evolution of Ebola virus disease diagnostic testing and efforts to deploy field diagnostic laboratories in prior outbreaks. We then explore the diagnostic challenges pervading the 2014-2015 epidemic and provide a comprehensive examination of novel diagnostic tests that are likely to address some of these challenges moving forward.

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Blood kinetics of Ebola virus in survivors and nonsurvivors

Abstract: Italian Ministry of Health; Italian Ministry of Foreign Affairs; EMERGENCY's private donations; and Royal Engineers for DFID-UK.

Cited by 89 publications

References 22 publications

Post-exposure treatments for Ebola and Marburg virus infections

Post-exposure treatments for Ebola and Marburg virus infections

Essentials of filoviral load quantification

Diagnosis of Ebola Virus Disease: Past, Present, and Future

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