Snapshot A 32-year-old man presents to urgent care after returning from a trip to sub-Saharan Africa, where he did a safari tour and suffered from many bug bites. He reports feeling intermittently feverish since then and having a persistent headache. On physical exam, he has left upper quadrant tenderness and splenomegaly. Laboratory evaluation reveals anemia. Due to high index of suspicion for malaria, a peripheral blood smear is conducted, which shows trophozoite ring forms within the red blood cells, suggestive of malaria. He is started on atovaquone/proguanil. 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-Protozoal 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