Effect of Artesunate–Amodiaquine on Mortality Related to Ebola Virus Disease

Abstract

Patients who were prescribed artesunate-amodiaquine had a lower risk of death from EVD than did patients who were prescribed artemether-lumefantrine. However, our analyses cannot exclude the possibility that artemether-lumefantrine is associated with an increased risk of death or that the use of artesunate-amodiaquine was associated with unmeasured patient characteristics that directly altered the risk of death.

Clinical, virological, and biological parameters associated with outcomes of Ebola virus infection in Macenta, Guinea

“…Plasmodium may bias the antiviral immune response, as this parasite is known to suppress adaptive immunity to heterologous antigens through the hemozoin-induced failure of dendritic cell functions (11). A role of the drug combination used at our ETC in the increased mortality is also a possibility, as suggested by a recent study showing a decrease in mortality in artesunate-amodiaquine-treated EVD patients compared with artesunate-lumefantrine-treated ones (12). Indeed, this treatment may be harmful because of the risk of prolongation of QT-interval and of fatal arrhythmias in patients presenting hypokalemia or hypomagnesemia.…”

Repurposed Therapeutic Agents Targeting the Ebola Virus: A Systematic Review

“…Of the 4 case studies, 2 studies52, 53 were judged to have poor reporting quality, 1 study 55 was judged to have fair reporting quality, and the last study 54 had good reporting quality. All the nonrandomized cohort studies51, 56, 57, 58, 59 were found to have a low risk of bias.…”

“…This resulted in 11 drug screening,23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 17 preclinical studies,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 and 9 clinical studies 51, 52, 53, 54, 55, 56, 57, 58, 59…”

“…All treated patients had medium to high viral loadBorobia et al 52 2015 SpainCase report on a single case of Ebola infection in Spain treated with a combination of convalescent plasma and favipiravir1 patientConvalescent plasma, favipiravir (loading dose of 50 mg/kg BID, maintenance dose of 25 mg/kg TID)11 d from Day 9NonePatient survivedNicholson-Roberts et al 53 2015 United Kingdom/Sierra LeoneCase report on management of a severe case of EVD with supportive care and convalescent whole blood1 male patientConvalescent whole blood (500 mL over 2 d)2 dNonePatient survivedFlorescu et al 54 2015 United StatesCase report on the management of a case of EVD with supportive care, convalescent plasma, and an experimental drug brincidofovir1 male patient200 mg brincidofovir PO on Day 6, followed by 100 mg doses on Day 9, 13, and 16. On Day 8, 3 U convalescent plasma were givenConvalescent plasma: 1 dNonePatient survivedMupapa et al 55 1999 Democratic Republic of CongoObservational study on 8 patients with confirmed EVD receiving treatment with convalescent blood transfusions8 female patientsConvalescent blood, variable quantityVariable durationNo direct control, overall case fatality rate of the Ebola epidemic in Kikwit2 out 9 patients died (12.5% Mortality compared with 80% overall case fatality rate)Gignoux et al 56 2016 Liberia/FranceRetrospective analysis of relative risk of mortality for treatment with 2 different antimalarial drugs, using adjusted and unadjusted regression models381 in total, divided into 4 groupsArtesunate-amodiaquine (dose according to age)3-d courseGroup receiving artemether-lumefantrine50.7% (36 out of 71) mortality rate for artesunate-amodiaquine group compared to 64.4% (125 out of 194) for the artemether-lumefantrine groupVan Griensven et al 57 2016 Guinea/BelgiumNonrandomized, comparative trial including 84 patients treated with up to 500 mL convalescent plasma with Unknown levels of neutralizing antibodies84 patients in treatment group 57% female2 U ABO-compatible convalescent plasma, 200ã 250 mL eachTransfusion on day of diagnosis or up to 2 d later418 patients in control group treated during previous 5 mo31% mortality in the treatment group and 38% for control (not significant). The difference was reduced after adjustment for age and cycle-threshold value (adjusted risk difference, −3 percentage points; 95% CI, −13 to 8).…”

Antiviral Agents Against Ebola Virus Infection: Repositioning Old Drugs and Finding Novel Small Molecules

“…Docking studies highlighted the FDA-approved antimalarials CQ and amodiaquine (Fig. 139 Other compounds with the pyrrolidinone scaffold were also reported. 21,138 However, as already mentioned, a few studies showed that CQ was not able to increase the survival rate either in animals or in EVD patients.…”