Effect of Mass #Artesunate-Amodiaquine #Distribution on #Mortality of #Patients With #Ebola Virus Disease During West #African #Outbreak (Open Forum Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Open Forum Infect Dis. 2019 May 24;6(7):ofz250. doi: 10.1093/ofid/ofz250. eCollection 2019 Jul.

Effect of Mass Artesunate-Amodiaquine Distribution on Mortality of Patients With Ebola Virus Disease During West African Outbreak.

Garbern SC1, Yam D2, Aluisio AR1, Cho DK3, Kennedy SB4, Massaquoi M4, Sahr F5, Perera SM6, Levine AC1, Liu T2.

Author information: 1 Department of Emergency Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island. 2 Department of Biostatistics, Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island. 3 Brown University, Providence, Rhode Island. 4 Ministry of Health, Monrovia, Liberia. 5 Sierra Leone Ministry of Defense, Freetown, Sierra Leone. 6 International Medical Corps, Washington, DC.

 

Abstract

BACKGROUND:

Experiments in vitro have shown that the drug amodiaquine may inhibit Ebola virus activity. During the Ebola virus disease (EVD) epidemic in West Africa in 2014-2016, 2 mass drug administrations (MDAs) of artesunate-amodiaquine (ASAQ) were implemented to decrease the burden of malaria. The objective of this study was to assess the effect of the ASAQ MDAs on the mortality of patients with EVD.

METHODS:

A retrospective cohort design was used to analyze mortality data for patients with EVD admitted to 5 Ebola treatment units in Liberia and Sierra Leone. Patients admitted to the ETUs during the time period of ASAQ’s therapeutic effect from areas where the MDA was implemented were matched to controls not exposed to ASAQ, using a range of covariates, including malaria co-infection status, and a logistic regression analysis was performed. The primary outcome was Ebola treatment unit mortality.

RESULTS:

A total of 424 patients with EVD had sufficient data for analysis. Overall, the mortality of EVD patients was 57.5%. A total of 22 EVD patients were exposed to ASAQ during the MDAs and were found to have decreased risk of death compared with those not exposed in a matched analysis, but this did not reach statistical significance (relative risk, 0.63; 95% confidence interval, 0.37-1.07; P = .086).

CONCLUSIONS:

There was a non-statistically significantly decreased risk of mortality in EVD patients exposed to ASAQ during the 2 MDAs as compared with EVD patients not exposed to ASAQ. Further prospective trials are needed to determine the direct effect of ASAQ on EVD mortality.

KEYWORDS: Ebola virus disease; amodiaquine; epidemic; mass drug administration; mortality

PMID: 31281856 PMCID: PMC6602760 DOI: 10.1093/ofid/ofz250

Keywords: Ebola; Malaria; West Africa; Artesunate; Amodiquinine.

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Comparison of #artesunate–mefloquine and #artemether–lumefantrine fixed-dose combinations for #treatment of uncomplicated P. falciparum #malaria in #children younger than 5 yrs in sub-Saharan #Africa: … (Lancet ID., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Articles

Comparison of artesunate–mefloquine and artemether–lumefantrine fixed-dose combinations for treatment of uncomplicated Plasmodium falciparum malaria in children younger than 5 years in sub-Saharan Africa: a randomised, multicentre, phase 4 trial

Sodiomon B Sirima, MD, Bernhards Ogutu, MD, John P A Lusingu, MD, Ali Mtoro, MD, Zakayo Mrango, MD, Alphonse Ouedraogo, MD, Jean Baptiste Yaro, MD, Kevin Omondi Onyango, MBChB, Samwel Gesase, MD, Ernest Mnkande, MD, James Samwel Ngocho, MD, Isabelle Ackermann, MSc, François Aubin, MD, Joelle Vanraes, PharmD, Nathalie Strub, MD, Gwenaelle Carn, MS

Published Online: 15 July 2016 / Open Access / DOI: http://dx.doi.org/10.1016/S1473-3099(16)30020-2 / Open access funded by Department of Health UK

User License:  Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)

© 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.

 

Summary

Background

WHO recommends combinations of an artemisinin derivative plus an antimalarial drug of longer half-life as treatment options for uncomplicated Plasmodium falciparum infection. In Africa, artemether–lumefantrine is the most widely used artemisinin-based combination therapy, whereas artesunate–mefloquine is used infrequently because of a perceived poor tolerance to mefloquine. WHO recommends reconsideration of the use of artesunate–mefloquine in Africa. We compared the efficacy and safety of fixed-dose artesunate–mefloquine with that of artemether–lumefantrine for treatment of children younger than 5 years with uncomplicated P falciparum malaria.

Methods

We did this multicentre, phase 4, open-label, non-inferiority trial in Burkina Faso, Kenya, and Tanzania. Children aged 6–59 months with uncomplicated malaria were randomly assigned (1:1), via a computer-generated randomisation list, to receive 3 days’ treatment with either one or two artesunate–mefloquine tablets (25 mg artesunate and 55 mg mefloquine) once a day or one or two artemether–lumefantrine tablets (20 mg artemether and 120 mg lumefantrine) twice a day. Parasitological assessments were done independently by two microscopists who were blinded to treatment allocation. The primary outcome was the PCR-corrected rate of adequate clinical and parasitological response (ACPR) at day 63 in the per-protocol population. Non-inferiority was shown if the lower limit of the 95% CI for the difference between groups was greater than −5%. Early vomiting was monitored and neuropsychiatric status assessed regularly during follow-up. This study is registered with ISRCTN, number ISRCTN17472707, and the Pan African Clinical Trials Registry, number PACTR201202000278282.

Findings

945 children were enrolled and randomised, 473 to artesunate–mefloquine and 472 to artemether–lumefantrine. The per-protocol population consisted of 407 children in each group. The PCR-corrected ACPR rate at day 63 was 90·9% (370 patients) in the artesunate–mefloquine group and 89·7% (365 patients) in the artemether–lumefantrine group (treatment difference 1·23%, 95% CI −2·84% to 5·29%). At 72 h after the start of treatment, no child had detectable parasitaemia and less than 6% had fever, with a similar number in each group (21 in the artesunate–mefloquine group vs 24 in the artemether–lumefantrine group). The safety profiles of artesunate–mefloquine and artemether–lumefantrine were similar, with low rates of early vomiting (71 [15·3%] of 463 patients in the artesunate–mefloquine group vs 79 [16·8%] of 471 patients in the artemether–lumefantrine group in any of the three dosing days), few neurological adverse events (ten [2·1%] of 468 vs five [1·1%] of 465), and no detectable psychiatric adverse events.

Interpretation

Artesunate–mefloquine is effective and safe, and an important treatment option, for children younger than 5 years with uncomplicated P falciparum malaria in Africa.

Funding

Agence Française de Développement, France; Department for International Development, UK; Dutch Ministry of Foreign Affairs, Netherlands; European and Developing Countries Clinical Trials Partnership; Fondation Arpe, Switzerland; Médecins Sans Frontières; Swiss Agency for Development and Cooperation, Switzerland.

Keywords: Research; Abstracts; Malaria; Artemisin.

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#Effect of #Artesunate–Amodiaquine on #Mortality Related to #Ebola #Virus #Disease (N Engl J Med., abstract)

[Source: The New England Journal of Medicine, full page: (LINK). Abstract, edited.]

Original Article

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

Etienne Gignoux, M.P.H., Andrew S. Azman, Ph.D., Martin de Smet, M.D., Philippe Azuma, M.D., Moses Massaquoi, M.D., Dorian Job, M.D., Amanda Tiffany, M.P.H., Roberta Petrucci, M.D., Esther Sterk, M.D., M.I.H., Julien Potet, M.D., Motoi Suzuki, M.D., Andreas Kurth, Ph.D., Angela Cannas, Ph.D., Anne Bocquin, M.Sc., Thomas Strecker, Ph.D., Christopher Logue, Ph.D., Thomas Pottage, B.Sc., Constanze Yue, Ph.D., Jean-Clement Cabrol, M.D., Micaela Serafini, M.D., M.P.H., and Iza Ciglenecki, M.D.

N Engl J Med 2016; 374:23-32 / January 7, 2016 / DOI: 10.1056/NEJMoa1504605

 

Abstract

Background

Malaria treatment is recommended for patients with suspected Ebola virus disease (EVD) in West Africa, whether systeomatically or based on confirmed malaria diagnosis. At the Ebola treatment center in Foya, Lofa County, Liberia, the supply of artemether–lumefantrine, a first-line antimalarial combination drug, ran out for a 12-day period in August 2014. During this time, patients received the combination drug artesunate–amodiaquine; amodiaquine is a compound with anti–Ebola virus activity in vitro. No other obvious change in the care of patients occurred during this period.

Methods

We fit unadjusted and adjusted regression models to standardized patient-level data to estimate the risk ratio for death among patients with confirmed EVD who were prescribed artesunate–amodiaquine (artesunate–amodiaquine group), as compared with those who were prescribed artemether–lumefantrine (artemether–lumefantrine group) and those who were not prescribed any antimalarial drug (no-antimalarial group).

Results

Between June 5 and October 24, 2014, a total of 382 patients with confirmed EVD were admitted to the Ebola treatment center in Foya. At admission, 194 patients were prescribed artemether–lumefantrine and 71 were prescribed artesunate–amodiaquine. The characteristics of the patients in the artesunate–amodiaquine group were similar to those in the artemether–lumefantrine group and those in the no-antimalarial group. A total of 125 of the 194 patients in the artemether–lumefantrine group (64.4%) died, as compared with 36 of the 71 patients in the artesunate–amodiaquine group (50.7%). In adjusted analyses, the artesunate–amodiaquine group had a 31% lower risk of death than the artemether–lumefantrine group (risk ratio, 0.69; 95% confidence interval, 0.54 to 0.89), with a stronger effect observed among patients without malaria.

Conclusions

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.

Keywords: Research; Abstracts; Ebola; Liberia; Artesunate; Amodiaquine.

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