Last reviewed: 30 Sep 2020
Last updated: 14 Aug 2020
09 Apr 2019

Intravenous artesunate now first-line treatment for severe malaria in the US

The Centers for Disease Control and Prevention (CDC) has announced that intravenous artesunate is now the first-line treatment for severe malaria infection in the US. The change in treatment protocol is due to intravenous quinidine, the only intravenous antimalarial drug currently approved in the US, being discontinued by the manufacturer. The CDC has highlighted that:

  • Intravenous artesunate is not currently approved by the Food and Drug Administration, and it is not commercially available in the US. From 1 April 2019, clinicians will need to call the CDC’s malaria hotline to obtain the drug via an expanded-use investigational new drug (IND) protocol. In cases where there is a delay in receiving the drug, the CDC recommends treating patients with an oral antimalarial (via nasogastric tube or after administration of an antiemetic) while waiting for the drug to arrive.

  • Intravenous artesunate is the first-line treatment currently recommended by the World Health Organization for the treatment of severe malaria, and has been for some years. Clinical studies have shown that it is safe and well tolerated, and can be used in infants and children, in the second and third trimesters of pregnancy, and during lactation. The benefits outweigh the risks of treatment in the first trimester of pregnancy.

There are approximately 300 cases of severe malaria diagnosed in the US each year, with most cases reported in people who have traveled from countries where malaria is endemic.

See Management: approach

See Management: treatment algorithm

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History and exam

Other diagnostic factors

  • headache
  • weakness
  • myalgia
  • arthralgia
  • anorexia
  • diarrhea
  • seizures
  • nausea and vomiting
  • abdominal pain
  • pallor
  • hepatosplenomegaly
  • jaundice
  • altered level of consciousness
  • hypotension
  • anuria/oliguria
  • influenza-like respiratory symptoms

Risk factors

  • travel to endemic area
  • inadequate or absent chemoprophylaxis
  • insecticide-treated bed net not used in endemic area
  • settled migrants returning from travel to endemic area of origin
  • low host immunity (for severe disease)
  • pregnancy (for severe disease)
  • age <5 years (for severe disease)
  • immunocompromise (for severe disease)
  • older age (for severe disease)
  • iron administration (children)

Diagnostic investigations

1st investigations to order

  • Giemsa-stained thick and thin blood smears
  • rapid diagnostic tests (RDTs)
  • CBC
  • clotting profile
  • serum electrolytes, BUN and creatinine
  • serum LFTs
  • serum blood glucose
  • urinalysis
  • arterial blood gas
More 1st investigations to order

Investigations to consider

  • polymerase chain reaction (PCR) blood for malaria
  • chest x-ray
  • blood culture
  • urine culture
  • sputum culture
  • lumbar puncture
  • HIV test
  • PCR nasopharyngeal swabs for influenza
  • CT head
More investigations to consider

Emerging tests

  • loop-mediated isothermal amplification
More emerging tests

Treatment algorithm


Consultant in Tropical and Travel Medicine

Hospitals for Tropical Diseases

Senior Lecturer

London School of Hygiene and Tropical Medicine




RB is on the advisory board of Sigma Tau and on the Public Health England advisory committee for malaria prevention. His employer has received research payments from Sigma Tau. RB is an author of a number of references cited in this topic.

Dr Ron Behrens would like to gratefully acknowledge Mariyam Mirfenderesky, Dr Signe Maj Sorensen, Dr Joanna Allen, Dr Simon Warren, and Dr Behzad Nadjm, previous contributors to this topic.


MM, SMS, JA, and SW declare that they have no competing interests. BN is an author of a reference cited in this topic.

Peer reviewersVIEW ALL


Head of the Travel Clinic

Consultant of Tropical and Travel Medicine

University Hospital

Project leader

Swiss Tropical and Public Health Institute




BG has received a research grant from Novartis Pharma to assess the impact of the introduction of artemether-lumefantrine (Novartis) as first-line treatment for uncomplicated malaria on mortality of children under 5 years old in 2 districts in Tanzania and travel grants from Novartis Pharma to present the results of the study above. BG is an author of a reference cited in this topic.

Associate Professor

Malaria Research Institute and Department of Molecular Microbiology and Immunology

Johns Hopkins Bloomberg School of Public Health




DS has received royalties from antigen provision for a diagnostic test to Inverness. DS with Johns Hopkins University has patents on diagnostic tests that do not require blood.


Institute of Specific Prophylaxis and Tropical Medicine

Medical University of Vienna




WHW declares that he has no competing interests.

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