Snapshot A 25-year-old female student presents to the ER with a three day history of fever and headache with shaking chills. She recently returned from a trip to Nigeria to see her grandparents. Her temperature is 102°F (38.9°C), pulse is 94/min, respirations are 18/min, and blood pressure is 125/70 mmHg. Patient appears pale on physical exam with mild scleral icterus. Complete blood count is notable for a hematocrit of 30%. Total bilirubin was 2.5 mg/dL with direct bilirubin being 0.3mg/dL. Results of a peripheral blood smear are as shown on the right. Introduction Classification protozoa Plasmodia spp. Pathogenesis Plasmodia spp. have 2 hosts and multiple distinct forms during its complex life cycle infection results in lysis and agglutination of RBCs rupture of RBCs correlates with fever spikes lysis occurs in a synchronized fashion (all RBCs lyse at the same time) 4 species of Plasmodium cause malaria P. falciparum most common and most deadly species occasionally causes death within 24 hours of symptom onset malignant tertian malaria irregular fever spikes (36-48 hours) cerebral malaria lysed RBCs occlude capillaries in brain no hypnozoite stage P. vivax and P. ovale benign tertian malaria 48 hour fever spikes "tertian" because you count day 1 and day 3, although fevers are actually 48 hours apart hypnozoite stage P. malariae quartan malaria 72 hour fever spikes recrudescence symptoms recur from low levels of organisms in RBCs no hypnozoite stage Transmission Anopheles mosquito Immunity HbS heterozygote (sickle cell trait) protection against P. falciparum absence of Duffy (Fy) on RBC protect against P. vivax most common in people of African descent Presentation Malaria cyclic fever at 48-72 hour intervals shaking chills soaking sweats anemia (hemolytic) splenomegaly typically after > 4 days of symptoms agitation hyperventilation bleeding history of exposure in malaria-endemic area patients are often asymptomatic between attacks Symptoms suggesting an alternate diagnosis include rash lymphadenopathy neck stiffness photophobia Complications cerebral malaria severe hemolytic anemia renal failure acute tubular necrosis noncardiogenic pulmonary edema Evaluation Blood smear Giemsa- or Wright-stained thick and thin blood films trophozoites and schizonts visualized within RBCs diagnosis of strain is essential to guide treatment Rapid antigenic tests Normocytic, normochromic anemia on CBC Differential Babesiosis Viral hemorrhagic fever Meningitis Typhoid fever Treatment Drugs chloroquine kills erythrocytic forms of all susceptible Plasmodia spp. P. vivax, ovale, and malariae are sensitive P. falciparum can be resistant retinopathy associated with long-term use pruritus in dark-skinned persons primaquine use for P. vivax/ovale to kill latent hypnozoites test for G6PD deficiency for chloroquine-resistant P. falciparum use mefloquine quinine (test for G6PD deficiency) artemether atavaquone-proguanil (Malarone) pyrimethamine/sulfadoxine pyrimethamine is a dihydrofolate reductase inhibitor also used in toxoplasmosis for severe infections use IV quinidine Prognosis, Prevention and Complications Prevention kill mosquitoes bed nets long-sleeved clothes DEET or other repellent chemical prophylaxis for travelers daily prophylaxis: atovaquone-proguanil, doxycycline, primaquine weekly prophylaxis : chloroquine, mefloquine can be used by pregnant travelers Complications occasionally fatal within 24 hrs may present as complications (see presentation) especially in pregnancy, children, and travellers from non-endemic areas