1. MALARIA Seema Jain, MS4 6/9/16

2. BIOLOGY Female Anopheles mosquito is infected with malaria parasites. The mosquito acts as a vector, carrying disease from human to human. Mosquito bites human, injecting sporozoites, which grow and multiply in the liver and then the RBCs. Successive parasites grow in RBCs, destroying them and releasing daughter cells that continue the cycle

3. INCIDENCE IN US  Eliminated in US in early 1950s  Tennessee Valley Authority created to help develop region surrounding TN river – mosquito breeding sites eliminated by controlling water levels and using insecticide.  Locally transmitted mosquito borne malaria can occur (63 outbreaks in past 60 years) – local mosquitoes bite persons carrying malaria parasites and then transmit malaria to local residents.  97 cases in past 60 years of transfusion-transmitted malaria  Approximately 1500-2000 cases of malaria are reported every year in the US, almost all in recent travelers.  First and second generation immigrants from malaria-endemic countries returning home tend not to use appropriate malaria preventive measures and are thus more likely to become infected.

4. PATHOPHYSIOLOGY Clinical symptoms are caused by the blood stage parasites. These parasites lead to accumulation of toxins like hemozoin pigment, which enter the bloodstream when the infected cells are lysed and merozoites are released. These toxins stimulate cytokines and other immunological factors to cause fever, rigors, etc. P. falciparum-infected RBCs can adhere to the vascular endothelium, causing sequestration of infected RBCs. When this occurs in the brain, it can lead to cerebral malaria.

5. PRESENTATION Incubation period varies from 7-30 days. P. vivax and P. ovale can produce dormant liver stage parasites, which can reactivate and cause disease months later. Most commonly presents with nonspecific flu-like symptoms. Fever, chills, sweats, headache, body aches, malaise, n/v Classically, but less frequently observed, attacks of chills -> fever/HA -> sweats, occur every 2-3 days. Physical exam Fevers, tachypnea, perspiration, HSM, jaundice

6. COMPLICATIONS Severe Malaria - Organ failure Cerebral – AMS, seizures. can cause lasting deficits. P. falciparum Hemolytic anemia ARDS DIC Shock AKI Metabolic acidosis, hypoglycemia Repeated infections – nephrotic syndrome, severe anemia P. vivax – splenic rupture Pregnancy LBW, prematurity, IUFD and SAB

7. EVALUATION AND DIAGNOSIS Gold standard diagnosis is microscopy Specimen is spread as thick or thin smear, stained with Giemsa, and examined with 100X oil immersion objective. Thick smear helps establish diagnosis by detecting parasites Thin smear helps determine malaria species and parasitemia Supportive labs CBC - Anemia, thrombocytopenia Chemistries – Hypoglycemia, AKI, Acidosis LFTs - Hyperbili, elevated AST and ALT FDA approved first rapid diagnostic test for use in US. in 2007 PCR is of limited utility in acutely ill patients as results are not available fast enough

8. TREATMENT AND PROPHYLAXIS Treatment depends on species, area of infection, and status of drug-resistance, in addition to clinical status of patient Most drugs used attack the blood stage parasites – choloroquine, Malarone, quinidine, doxycycline-quinine, clindamycin-quinine Primaquine is used for the dormant liver stage (hypnozoite) to prevent relapse. Must exclude G6PD deficiency  https://www.cdc.gov/malaria/travelers/country_table/a.html https://www.cdc.gov/malaria/travelers/country_table/a.html