One of the reasons for establishing the Peoples-uni Blog was to create a useful resource for our students, volunteers and readers. Ebola is dominating world news and on Wednesday (12th August 2014) the World Health Organisation announced that untested drugs can be used to treat patients infected with the virus.The WHO said it was ethical in light of the scale of the outbreak and high number of deaths - more than 1,000 people have died in West Africa. The statement was made after its medical experts met in Switzerland on Monday to discuss the issue. Today (15th August 2014), the New York Times has published an article (http://www.nytimes.com/2014/08/16/opinion/can-statins-help-treat-ebola.html?_r=0) by David Fedson and Steven Opal suggesting that cardiovascular prevention drugs could be used in the outbreak.In this blog posting we are sharing a summary of a debate on whether cardiovascular therapies (i.e. statins) could be of benefit in this instance. This paper outlines the arguments but reaches no firm conclusions and we are sharing this for information and discussion. The Ebola treatment debate: could conventional cardiovascular therapies be used in severe sepsis cases? In a recent article published in the New York Times, David Fedson, MD and retired professor of medicine and Steven Opal professor of medicine have suggested that in the absence of any licensed prophylaxis or treatment for Ebola Virus Disease (EVD) off-the-shelf, inexpensive and widely tolerated cardiovascular prevention drugs with immunomodulatory effects such as statins may help in the syndromic treatment of host response in patients with EVD exhibiting signs of sepsis. Fedson’s hypothesis is built on evidence pieced together from previous studies of biomarkers during the 2000-2001 EVD outbreak in Uganda (McElroy et al., 2014), animal studies of sepsis (Xu et al., 2010), pharmacological action of statins (Undas et al., 2013) and experimental studies of statins and sepsis in humans (Patel et al., 2012). Other authors (The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network, 2014) argue against this. What makes Fedson’s hypothesis and suggestion appealing is that EVD mortality is driven largely by host response (i.e. sepsis) as outlined in a review on Ebola Haemorrhagic Fever by Feldmann and Gesibert (2011). Fedson is not the only one who has argued for the use of already approved drugs (albeit for different indications) and low toxicity as adjuncts to conventional treatment in sepsis patients if there are sound data from preclinical and clinical research to support their use. Other drugs suggested as worth considering in cases of severe sepsis include chloroquine (Yasuda et al., 2008 and Yang et al., 2013) and doxycycline (Fink, 2012). Others may argue that before looking towards novel adjuvant treatment, obvious measures must be taken; these include increasing health care capacity via recruitment of volunteer health care professionals (particularly, intensivists) from non-affected settings, improved clinical facilities with basic cleaning supplies, availability and administration of intravenous fluids, proper isolation of patients, contact tracing, education of the public on early identification of EVD and advice on prevention and treatment, respiratory support and access to critical care facilities (perhaps through mobile critical care units). While Fedson’s hypothesis offers hope for EVD patients with sepsis, a key question for policy makers and clinicians alike, is whether it is ethically justifiable to recommend therapies for EVD that are not backed by evidence from trials that are specific to EVD. Bausch et al. (2007) in a commentary on filovirus, argue for a more flexible stance on untested therapies with potential benefit: “Despite the sense of urgency to intervene when faced with the devastating social and economic impacts of outbreaks of filovirus hemorrhagic fever in Africa, we cannot cut corners on safety. Nevertheless, given the overwhelming human suffering, we must explore ways of safely expediting promising products to field testing and compassionate use, as well as to monitor their effectiveness—that is, to do clinical research.” The World Health Organisation (WHO) has released a consensus statement on the ethical considerations for use of unregistered interventions for EVD (WHO, 2014) that, ‘it is ethical to offer unproven interventions with as yet unknown efficacy and adverse effects, as potential treatment or prevention’, provided there is transparency of care and informed consent is received. Some clinicians may wish to exert their clinical judgement and try Fedson’s suggestion of statins as adjunctive therapy with informed patient consent, in which case the question of appropriate dosing arises. Finally, in keeping with the WHO consensus statement (WHO, 2014), all clinicians dealing with EVD patients and especially those opting for unproven treatments, have ‘a moral obligation’ to keep and share detailed patient records including patient socio-demographic characteristics, pre-existing comorbidities, laboratory confirmation of diagnosis, illness onset dates, severity of illness at presentation (ideally using a recognised severity index), symptoms, treatment and patient outcomes. Such records would be invaluable for retrospective observational studies and will provide more substantial evidence on the potential applicability of adjuvant therapies for future EVD outbreaks.   References Bausch, D.G. et al. (2007). Outbreaks of Filovirus Haemorraghic Fever: Time to refocus on the patient. J Infect Dis. 196 (Supplement 2): S136-S141. Doi: 10.1086/520542Available at: http://jid.oxfordjournals.org/content/196/Supplement_2/S136.long [Accessed on 12.08.2014] Feldman, H. and Gesibert, T.W. (2011). Ebola haemorrhagic fever. Lancet. 377:849-62. Available at: http://www.sciencedirect.com/science/article/pii/S0140673610606678 [Accessed on: 12.08.2014] Fink, M. (2012). Matrix metalloproteinase-8 as a potential drug target for the therapy of sepsis. Critical Care Medicine. 40(2): 655-656. doi: 10.1097/CCM.0b013e31823b97d7 Available at: http://journals.lww.com/ccmjournal/Citation/2012/02000/Matrix_metalloproteinase_8_as_a_potential_drug.41.aspx [Accessed on: 12.08.2014] McElroy AK, Erickson BR, Flietstra TD, et al. (2014). Ebola hemorrhagic fever: novel biomarker correlates of clinical outcome. J Infect Dis. 210: 558-66.Available at: http://jid.oxfordjournals.org/content/210/4/558.long [Accessed on: 12.08.2014] Patel JM, Snaith C, Thickett DR, et al. (2012). Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial). Crit Care. 16: R231.Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672620/ [Accessed on: 12.08.2014] The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network (2014) Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome. N Engl J Med 2014; 370:2191-2200 Available at: http://www.nejm.org/doi/full/10.1056/NEJMoa1401520 [Accessed on 12.08.2014] Undas A, Brummel-Ziedins KE, Mann KG. (2013). Anticoagulant effects of statins and their clinical implications. Thromb Haemost. 111: 392-400. Available at: http://th.schattauer.de/en/contents/archive/issue/1844/manuscript/20547.html [Accessed on: 12.08.2014] Xu H, Ye X, Steinberg H, Liu SF (2010). Selective blockade of endothelial NF-kB pathway differentially affects systemic inflammation and multiple organ dysfunction and injury in septic mice. J Pathol. 220: 490-8. Available at: http://onlinelibrary.wiley.com/doi/10.1002/path.2666/abstract;jsessionid=6FA1D959006D85B5A51EB0B754FD225D.f03t02 [Accessed on: 12.08.2014] Yang, M. et al. (2013). Chloroquine inhibits HMGB1 inflammatory signalling and protects mice from lethal sepsis. Biochem Pharmacol. 86 (3): 410-8. doi: 10.1016/j.bcp.2013.05.013 Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713089/ [Accessed on: 12.08.2013] Yasuda, H. et al. (2008). Chloroquine and inhibition of Toll-like receptor 9 protects from sepsis-induced acute kidney injury. Am J Physiol Renal Physiol. 294: F1050-F1058. Doi: 10.1152/ajprenal.00461.2007 Available at: http://ajprenal.physiology.org/content/294/5/F1050 [Accessed on: 12.08.2014]WHO (2014). Ethical considerations for use of unregistered interventions for Ebola viral disease (EVD). Available at: http://who.int/mediacentre/news/statements/2014/ebola-ethical-review-summary/en/ [Accessed on: 12.08.2014][Related links: Other useful resources on EVD]WHO Factsheet on Ebola Virus Disease [http://www.who.int/mediacentre/factsheets/fs103/en] CDC webpage on Ebola virus disease which includes the latest updates on the outbreak [http://www.cdc.gov/vhf/ebola/]

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