Snapshot A 25-year-old medical student is about to embark on an international rotation in Ethiopia. Given that malaria is endemic in that area, she presents to the travel clinic for required vaccination as well as chemoprophylaxis of malaria. Upon further investigating on the CDC website, she discovers that malarial strains in Ethiopia are resistant to chloroquine. As she is already on doxycycline for the treatment of acne, her travel clinic physician informs her that there is no need for additional chemoprophylaxis. Introduction Drugs chloroquine hydroxychloroquine quinidine quinine artemether/lumefantrine atovaquone/proguanil artesunate mefloquine primaquine doxycycline Clinical use malaria treatment prophylaxis P. falciparum and, increasingly, P. vivax may be resistant to chloroquine, hydroxychloroquine, and mefloquine Anti-Malarial Medications Drug Mechanism of Action Adverse Effects Indications Chloroquine Blocks heme polymerase, which causes heme accumulation Heme is toxic to plasmodia Retinopathy Pruritus Gastrointestinal upset Myopathy All plasmodial species: however, there is increasing resistance to P. falciparum and, recently, P. vivax Hydroxychloroquine Unknown, but impairs neutrophils and chemotaxis and may interfere with lysosomal degradation of hemoglobin Retinopathy Bleaching of hair Gastrointestinal upset All plasmodial species: however, there is increasing resistance to P. falciparum Quinidine A class IA antiarrhythmic drug Diarrhea QTc prolongation Palpitations Life-threatening/severe malaria due to P. falciparum: drug is discontinued in the US Quinine Disrupts plasmodial DNA transcription and replication Hemolytic anemia in G6PD deficiency Gastrointestinal upset Flushing Chloroquine-resistant P. falciparum and P. vivax Artemether/lumefantrine Inhibits nucleic acid and protein synthesis Gastrointestinal upset Headache QTc prolongation Chloroquine-resistant P. falciparum and P. vivax Atovaquone/proguanil Unknown, may interfere with cell membrane permeability and cause paralysis in the helminth Gastrointestinal upset Dizziness P. falciparum Babesia (used with azithromycin) Chemoprophylaxis Artesunate Inhibits arachidonic acid metabolism, making the helminth more susceptible to the host's innate immune system Hemolytic crisis in patients with G6PD deficiency: test for G6PD deficiency prior to starting First-line for life-threatening malaria due to P. falciparum Mefloquine Inhibits oogenesis and spermatogenesis Central nervous system toxicity: dizziness, hallucinations, altered mental status Gastrointestinal upset P. falciparum Also has increasing resistance Primaquine Interferes with electron transport chain in plasmodial mitochonrdia Gastrointestinal upset Hemolytic crisis in patients with G6PD deficiency: test for G6PD deficiency prior to starting Adjuvant for P. vivax/ovale to eradicate hypnozoites Chemoprophylaxis Doxycycline Inhibits 30S ribosomal subunit Gastrointestinal upset Esophagitis Photosensitivity Chemoprophylaxis Adjuvant therapy with chloroquine, quinine, or primaquine