Malaria Organism-Specific Therapy
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Several antibody-based rapid diagnostic tests (RDTs) are available for diagnosing malaria, but they cover only four of the five species that cause human malaria (all except Plasmodium knowlesi). Symptomatic patients from areas where P knowlesi is present should be investigated as described below. All efforts should be made to confirm the diagnosis of malaria and to identify the species. Diagnosis is based on Giemsa-stained thick and thin peripheral blood smears.
Complications influence the choice of treatment. Complications of Plasmodium falciparum malaria include impaired consciousness, seizures, severe anemia, renal failure, pulmonary edema or acute respiratory distress syndrome (ARDS), refractory hypotension, and disseminated intravascular coagulation (DIC). Criteria for the diagnosis of severe malaria are provided by the World Health Organization (WHO) and should be used in the clinical management of the patient. [1, 2, 3, 4]
Conditions such as pregnancy also affect the choice of treatment. Resistance patterns at a regional level are currently less important, as the first choice for uncomplicated P falciparum malaria should always be artemisinin combination therapy. As chloroquine can be used for prophylaxis and for therapy in very limited circumstances, resistance patterns to this drug will also be covered.
Key points
If the patient meets the criteria for severe malaria and treatment must be initiated before the species is known, treat for P falciparum.
P falciparum should be presumed to be chloroquine-resistant, except in a few areas of Central America and the Middle East.
Primaquine should be given if Plasmodium vivax or Plasmodium ovale is suspected after checking for the presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Chloroquine-resistant P falciparum
Chloroquine-sensitive P falciparum
Mefloquine-resistant P falciparum
Chloroquine-resistant P vivax
The 2015 WHO malaria treatment guidelines [2] state that uncomplicated P falciparum malaria should always be treated with oral artemisinin combination therapy (ACT), as follows:
Not all of the above combinations are available in Europe or the United States. Available drugs include AL (United States) and AL or DHAP (Europe).
The 2016 British guidelines for the treatment of malaria [5] also signal the possibility to adopt other treatments (atovaquone plus proguanil or quinine sulphate) if artemisinin combination therapy is not available.
Dosages for uncomplicated P falciparum malaria are as follows: [5]
The 2015 WHO guidelines for the treatment of malaria [2] state that, if the species cannot be confirmed, the patient should be managed as if the infection is caused by P falciparum. This also applies to all patients who acquire malaria in regions with chloroquine-resistant infections.
In areas of chloroquine sensitivity, chloroquine should be used.
Co-infections (generally P falciparum and other species) should be actively ruled out in patients from areas where co-infections are known to occur. Treatment for P falciparum malaria is sufficient to eradicate both species. Primaquine should be added if P vivax or P ovale is present to avoid relapses caused by the permanence of hypnozoites in the liver.
Dosages for P malariae and P knowlesi malaria are as follows: [5]
Dosages for P vivax and P ovale malaria are as follows:
Prevention of P vivax malaria relapse
Tafenoquine, an 8-aminoquinoline derivative, is indicated for the radical cure (prevention of relapse) of P vivax malaria in patients aged 16 years or older who are receiving appropriate antimalarial therapy (eg, chloroquine) for acute P vivax infection.
A single 300-mg oral dose of tafenoquine is coadministered on the first or second day of the appropriate antimalarial therapy (eg, chloroquine) for acute P vivax malaria infection. Nearly 90% of patients were relapse-free at 6 months after treatment. [6]
According to the 2015 WHO guidelines for the treatment of malaria, complicated malaria should be treated first with intravenous artemether, followed by oral artemisinin combination therapy as soon as the patient is able to take oral medication (generally after at least 48 hours following intravenous therapy). If artemether is not available, quinine can be used as an alternative, followed by the oral phase of the therapeutic course.
Dosages are as follows: [2]
Malaria prophylaxis relies on mosquito avoidance measures (which include wearing long-sleeved shirts and long pants, using DEET-based repellents, and sleeping under bed nets) and chemoprophylaxis. Several drugs can be used for chemoprophylaxis, but indications may vary depending on the country of destination. Updated information is available on websites such as that of the Centers for Disease Control and Prevention. [7]
Atovaquone-proguanil
Chloroquine phosphate
Doxycycline
Mefloquine
Primaquine [2]
Tafenoquine [9]
Patients prescribed primaquine should be tested for G6PD deficiency.
Perez-Jorge E, Herchline T. Malaria. Medscape Reference. Available at http://emedicine.medscape.com/article/221134-overview.
[Guideline] World Health Organization (WHO). Guidelines for the Treatment of Malaria. 3rd Edition. World Health Organization, Geneva, Switzerland: WHO Press; 2015. [Full Text].
Sagara I, Piarroux R, Djimde A, Giorgi R, Kayentao K, Doumbo OK, et al. Delayed anemia assessment in patients treated with oral artemisinin derivatives for uncomplicated malaria: a pooled analysis of clinical trials data from Mali. Malar J. 2014 Sep 12. 13(1):358. [Medline].
Carvalho LJ, Moreira Ada S, Daniel-Ribeiro CT, Martins YC. Vascular dysfunction as a target for adjuvant therapy in cerebral malaria. Mem Inst Oswaldo Cruz. 2014 Aug. 109(5):577-88. [Medline]. [Full Text].
[Guideline] Lalloo DG, Shingadia D, Bell DJ, Beeching NJ, Whitty CJ, Chiodini PL, et al. UK malaria treatment guidelines 2016. J Infect. 2016 Feb 12. [Medline]. [Full Text].
Llanos-Cuentas A, Lacerda MV, Rueangweerayut R, Krudsood S, Gupta SK, Kochar SK, et al. Tafenoquine plus chloroquine for the treatment and relapse prevention of Plasmodium vivax malaria (DETECTIVE): a multicentre, double-blind, randomised, phase 2b dose-selection study. Lancet. 2014 Mar 22. 383 (9922):1049-58. [Medline].
Paul M. Arguin, Kathrine R. Tan. Malaria Information and Prophylaxis, by Country. CDC – Centers for Disease Control and Prevention. Available at http://www.cdc.gov/malaria/travelers/country_table/a.html. 2015 Nov 29; Accessed: 2016 Apr 29.
FDA Drug Safety Communication: FDA approves label changes for antimalarial drug mefloquine hydrochloride due to risk of serious psychiatric and nerve side effects. Available at http://www.fda.gov/Drugs/DrugSafety/ucm362227.htm#. Accessed: July 30, 2013.
Arakoda (tafenoquine) [package insert]. Washington DC: 60 Degrees Pharms, LLC. August, 2018. Available at [Full Text].
Paczkowski MM, Landman KL, Arguin PM. Update on cases of delayed hemolysis after parenteral artesunate therapy for malaria – United States, 2008 and 2013. MMWR Morb Mortal Wkly Rep. 2014 Aug 29. 63(34):753-5. [Medline].
Kathrine R. Tan, Paul M. Arguin, Stefanie F. Steele. Yellow Fever & Malaria Information, by Country. CDC – Centers for Disease Control and Prevention. Available at http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/yellow-fever-malaria-information-by-country. 2015 Jul 10; Accessed: 2016 Apr 29.
Enrico Brunetti, MD Associate Professor, Department of Infectious Diseases, Division of Infectious and Tropical Diseases, University of Pavia, Italy; Staff Physician, Department of Infectious Diseases, IRCCS S Matteo Hospital Foundation, Pavia, Italy
Enrico Brunetti, MD is a member of the following medical societies: American Society of Tropical Medicine and Hygiene, European Society of Clinical Microbiology and Infectious Diseases
Disclosure: Nothing to disclose.
Tommaso Manciulli Medical Student, University of Pavia, Italy; Medical Traineeship for Thesis, Assistance Publique Hospital of Marseille; Traineeship, Parasitology and Mycology Laboratory, La Timone Hospital, France
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Thomas E Herchline, MD Professor of Medicine, Wright State University, Boonshoft School of Medicine; Medical Consultant, Public Health, Dayton and Montgomery County (Ohio) Tuberculosis Clinic
Thomas E Herchline, MD is a member of the following medical societies: Alpha Omega Alpha, Infectious Diseases Society of America, Infectious Diseases Society of Ohio
Disclosure: Nothing to disclose.
Joseph U Becker, MD Fellow, Global Health and International Emergency Medicine, Stanford University School of Medicine
Joseph U Becker, MD is a member of the following medical societies: American College of Emergency Physicians, Phi Beta Kappa, Society for Academic Emergency Medicine, Emergency Medicine Residents’ Association
Disclosure: Nothing to disclose.
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