Relationship Between Viremia and Specific Organ Damage in Ebola Patients: A Cohort Study

Lanini, Simone; Portella, Gina; Vairo, Francesco; Kobinger, Gary P.; Artigas, Antonio; Langer, Martin; Kabia, Soccoh; Brogiato, Giorgio; Amone, Jackson; Castilletti, Concetta; Miccio, Rossella; Capobianchi, Maria Rosaria; Strada, Gino; Zumla, Alimuddin; Di, Antonino; Ippolito, Giuseppe; Biava, Mirella; Cannas, Angela; Chiappini, Roberta; Coen, Sabrina; Colavita, Francesca; Grassi, Germana; Lapa, Daniele; Mazzarelli, Antonio; Meschi, Silvia; Minosse, Claudia; Quartu, Serena; Valli, Maria Beatrice; Venditti, Carolina; Vulcano, Antonella; Zaccaro, Paola; Ahmad, Umar; Checcarelli, Elisabetta; Guanti, Michela Delli; Giovanella, Elena; Gottardello, Davide; Guastalegname, Maurizio; Jocic, Milos; Monti, Giorgio; Parsons, Clare; Rossi, Nicola De; Salvati, Giampiero; Scaccabarozzi, Giovanna; Sisillo, Erminio; Tagliabue, Paola; Turella, Marta; Valdatta, Caterina

doi:10.1093/cid/cix704

Cited by 14 publications

(16 citation statements)

References 30 publications

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“…Similar elevations were seen in our data. A study of APTT values in Sierra Leonean patients reported elevation in all cases (mean = 68.4 s), but greater elevation in fatal cases (mean = 84.9 s) compared to survivors (mean = 49.6 s) [25] leading to the hypothesis that coagulation parameters “may have value as a potential prognostic indicator of disease severity” in patients with EVD [23]. Our data indicated a similar prognostic possibility.…”

Section: Discussionsupporting

confidence: 66%

Haemostatic Changes in Five Patients Infected with Ebola Virus

Smither

O’Brien

Eastaugh

et al. 2019

Viruses

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Knowledge on haemostatic changes in humans infected with Ebola virus is limited due to safety concerns and access to patient samples. Ethical approval was obtained to collect plasma samples from patients in Sierra Leone infected with Ebola virus over time and samples were analysed for clotting time, fibrinogen, and D-dimer levels. Plasma from healthy volunteers was also collected by two methods to determine effect of centrifugation on test results as blood collected in Sierra Leone was not centrifuged. Collecting plasma without centrifugation only affected D-dimer values. Patients with Ebola virus disease had higher PT and APTT and D-dimer values than healthy humans with plasma collected in the same manner. Fibrinogen levels in patients with Ebola virus disease were normal or lower than values measured in healthy people. Clotting times and D-dimer levels were elevated during infection with Ebola virus but return to normal over time in patients that survived and therefore could be considered prognostic. Informative data can be obtained from plasma collected without centrifugation which could improve patient monitoring in hazardous environments.

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Section: Discussionsupporting

confidence: 66%

Haemostatic Changes in Five Patients Infected with Ebola Virus

Smither

O’Brien

Eastaugh

et al. 2019

Viruses

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“…Indeed, our choice to consider past exposure to Ebola virus as an explanatory variable for current malaria parasite infection in our analysis was arbitrary, and additional analyses confirmed that reversing the positions of the 2 pathogens in the model did not qualitatively change the observed association pattern (Appendix Table 6, Figures 5, 6). Furthermore, a biological mechanism of interaction between the 2 pathogens with the potential to cause the association found here (such as persistent inflammatory processes in EVD survivors [10,27,28] or damage to specific tissues targeted by both pathogens [29,30]) remains to be elucidated. We do, however, point out that the mechanism is not likely to be general or the result of immunosuppression (e.g., because of AIDS) because neither of the 2 common filarial infections included as co-factors (L. loa and M. perstans) were risk factors for infection with Plasmodium parasites (Figure 3) and Ebola virus exposure (Appendix Figure 5).…”

Section: Discussionmentioning

confidence: 98%

Exposure to Ebola Virus and Risk for Infection with Malaria Parasites, Rural Gabon

Abbate¹,

Becquart²,

Leroy³

et al. 2020

Emerg. Infect. Dis.

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M ajor outbreaks of infections with Ebola virus, such as the 2014-2016 West Africa epidemic and the ongoing 2018-2019 outbreak in eastern Democratic Republic of the Congo, pose several obvious and immediate threats to public health. Less obvious, but as concerning for public health, is the possibility that Ebola virus might also interact with common cocirculating infectious agents at both the population and within-host (individual) levels. Indeed, much attention has been paid to the relationship between malaria and Ebola virus disease (EVD), primarily because of the clinical resemblance between the 2 diseases (1) and the high frequency of Plasmodium spp. co-infection among patients undergoing treatment for confirmed EVD (2). At the individual level, several retrospective epidemiology studies of patients undergoing treatment for confirmed EVD have attempted to determine whether concurrent malaria affects patient outcomes. In Sierra Leone (3) and at 1 Ebola treatment center in Liberia (4), mortality risk was much higher among Ebola patients who were coinfected with Plasmodium parasites than among patients who were not co-infected, and a study in Guinea found that adverse outcomes were higher among EVD patients with higher P. falciparum parasite loads than among those with lower levels of parasitemia (5). A similar study of patients at several Ebola treatment centers in Liberia reported the opposite relationship, that the probability of survival for EVD patients was positively associated with both presence and level of Plasmodium spp. parasitemia (6). Together, these results point to a strong potential for biological interactions between Plasmodium parasites and Ebola virus that may influence the severity of EVD. At the population level, interruption of normal public health services and disease control measuresincluding patient avoidance of healthcare facilitiesduring an EVD epidemic has been projected to cause increases in untreated cases and deaths from malaria, in addition to several otherwise preventable or treatable diseases (7-9). Yet whether biological interactions at the within-host level, such as inflammatory processes leading to prolonged post-Ebola syndrome symptoms common in acute EVD survivors (10), may also lead to a change in malaria transmission dynamics by influencing susceptibility remains unknown. Knowledge of the extent of possible interactions between infection with Plasmodium parasites and Ebola virus is especially helpful because geographic regions where prevalence of antibodies against Ebola

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“…Different factors, like delay in admission, organ failure, comorbidities, complications, factors not changed by the availability of intensive care, contribute to the mortality in patients with “low” Ebola viral load (LVL < 7.5). Patients with very high viral load (LVL > 8.5) may have a very limited benefit from intensive care support without effective antiviral treatment, because of the rapid progression of EVD to fatal multiple organ failure [ 28 ]. Only exceptionally it was possible to buy enough time for the immune system to clear the virus and reverse organ failure.…”

Section: Discussionmentioning

confidence: 99%

Intensive care support and clinical outcomes of patients with Ebola virus disease (EVD) in West Africa

Langer

Portella²,

Finazzi

et al. 2018

Intensive Care Med

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PurposeWe investigate the impact on outcome of different levels of supportive treatment in Ebola virus disease (EVD). The NGO EMERGENCY delivered care sequentially at two Ebola Treatment Centres (ETC) in Sierra Leone: first at Lakka (fluids, symptomatic, antibiotic, antimalaria treatment, and hospital level medical care), and thereafter in Goderich, adding organ support in the only African ETC with an equipped and staffed intensive care unit (ETC-ICU).MethodsThe primary outcome in this retrospective cohort study was in-ETC mortality. Secondarily, we used multivariable logistic regression to investigate the independent impact of the IC on mortality by comparing patients in two ETCs, adjusting for potential confounders, including the viral load (base-10 logarithm in copies/ml) (LVL), modelled as a piecewise linear function. Mortality was plotted versus LVL. Confidence bands were constructed by a bootstrap technique. The number of hospital-free days within 28 was computed to assess the burden of EVD.ResultsData from 229 EVD patients were analysed (123 in Lakka, 106 in Goderich). Crude analysis showed a non-statistically significant difference in mortality (57.7% in Lakka vs 50.0% in Goderich; p = 0.19). Age and LVL were associated with mortality. Adjusted mortality was lower at the Goderich ICU-ETC (p = 0.055). This difference was observed with 80% confidence for patients with LVL between 7.5 and 8.5 copies/ml. Hospital-free days (of 28 days) were greater (7.7 vs 5.5; p = 0.03) for patients treated in the ICU-ETC.ConclusionsProvision of critical care to patients with EVD is feasible in resource-limited settings and was associated with improved survival and less time in hospital.Electronic supplementary materialThe online version of this article (10.1007/s00134-018-5308-4) contains supplementary material, which is available to authorized users.

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Relationship Between Viremia and Specific Organ Damage in Ebola Patients: A Cohort Study

Cited by 14 publications

References 30 publications

Haemostatic Changes in Five Patients Infected with Ebola Virus

Haemostatic Changes in Five Patients Infected with Ebola Virus

Exposure to Ebola Virus and Risk for Infection with Malaria Parasites, Rural Gabon

Intensive care support and clinical outcomes of patients with Ebola virus disease (EVD) in West Africa

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