Intravenous Artesunate for the Treatment of Severe and Complicated Malaria in the United States: Clinical Use under an Investigational New Drug Protocol

Details

• Alternative Title:
  Ann Intern Med
• Personal Author:
  Twomey, Patrick S. ; Smith, Bryan L. ; McDermott, Cathy ; Marino, Anne ; McCarthy, William ; Kachur, S. Patrick ; Ransom, Janet ; Arguin, Paul M.
• Description:
  Background
  
  Quinidine gluconate, the only FDA-approved treatment for life-threatening malaria in the United States, has a problematic safety profile and is often unavailable in hospitals.
  
  Objective
  
  Assess the safety and clinical benefit of intravenous artesunate as a quinidine alternative
  
  Design
  
  Retrospective case series
  
  Setting
  
  United States hospitals
  
  Patients
  
  Patients with severe and complicated malaria received 4 doses of intravenous artesunate 2.4 mg/kg under a treatment protocol implemented by the Centers for Disease Control and Prevention (CDC). Protocol eligibility required the presence of microscopically confirmed malaria, the need for intravenous treatment, and an impediment to quinidine. From January 2007 through December 2010, 102 patients received artesunate. Age range was 1-72 years, with 90% adults and 61% males. At baseline, 35% had evidence of cerebral malaria and 17% had severe hepatic impairment.
  
  Measurements
  
  Clinical and laboratory data from each patient’s hospital records were abstracted retrospectively, including information from baseline through a maximum 7-day follow-up. The abstracted data were presented before a physician committee for the evaluation of safety and clinical benefit outcomes.
  
  Results
  
  Seven deaths occurred (mortality 6.9%), with the most frequent adverse events being anemia (65% of patients) and elevated hepatic enzymes (49%). All deaths and most adverse events were attributed to the severity of malaria. Patients’ symptoms generally improved or resolved within 3 days, and the median time to discharge from the Intensive Care Unit was 4 days, even for patients who had presented with severe liver disease or cerebral malaria. Over 100 concomitant medications were used, with no documented drug-drug interactions.
  
  Limitations
  
  Potential late-presenting safety issues might lie outside the 7-day follow-up period.
  
  Conclusions
  
  Artesunate was a safe and clinically beneficial alternative to quinidine.
  
  
• Subjects:
  Adolescent Adult Aged Antimalarials Artemisinins Article Child Child, Preschool Drugs, Investigational Drug Therapy, Combination Female Humans Infant Injections, Intravenous Malaria Male Medication Adherence Middle Aged Parasitemia Retrospective Studies Treatment Outcome Young Adult

  More +
• Source:
  Ann Intern Med. 163(7):498-506.
• Pubmed ID:
  26301474
• Pubmed Central ID:
  PMC4627466
• Document Type:
  Journal Article
• Funding:
  CC999999/Intramural CDC HHS/United States
• Place as Subject:
  United States
• Volume:
  163
• Issue:
  7
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:dba62f1342909384c480ede1bae58fed713c9132090176e6daf125f778033b33
• Download URL:
  https://stacks.cdc.gov/view/cdc/36341/cdc_36341_DS1.pdf
• File Type:
  [PDF - 397.77 KB ]