Malaria- always consider in patients with recent travel to endemic areas and fever!

Always consider malaria on the differential diagnosis list for the febrile traveler! Travelers to regions when malaria is prevalent are at increased risk, particularly if they have had no previous exposure to malaria parasites; these people are at risk of significantly severe disease if infected with Plasmodium falciparum!

NOTE: P. falciparum can be rapidly fatal; >90% of travelers that are affected are ill within 30 days of return!

Incubation: bite from an infected mosquitoà inoculated sporozoites head to the liver and invade hepatocytes (1-2 hours)à often asymptomatic for period (12-35 days, depending on the parasite species; i.e. P. falciparum incubation period is 12-14 days)à divide & form schizonts which contain merozoitesà asymptomatic until the erythrocytic stage of the parasite life cycleà release of merozoites into the bloodstreamà infect red blood cells (RBCs)à rupture à clinical manifestations

NOTE: longer incubation periods may arise in patients taking ineffective malaria prophylaxis medications or patients that are semi-immune

When to clinically suspect Malaria

• Febrile illness in a patient who has recently traveled to a region where malaria is endemic
• Symptoms: initially nonspecific (i.e. chills, malaise, fatigue, headache, nausea, vomiting, abdominal pain, arthralgias, myalgias, tachypnea, tachycardia, fever

Clinical Manifestations: Uncomplicated versus Complicated

·       Uncomplicated Malaria: can occur with any Plasmodium species (*note: Falciparum is the most virulent)

o   Physical Exam: palpable spleen may be present (with multiple exposures, it may shrink in size due to infarctions), jaundice

o   Investigations: parasitemia, anemia, thrombocytopenia, elevated liver enzymes, mild coagulopathy, elevated Cr/Urea

o   Diagnosis: thick & thin smear

·       Complicated Malaria: complicated or “severe” malaria often involves hyper-parasitemia (³100,000 parasites/microL of blood, or ³5-10% of parasitized RBCs; the WHO uses a cutoff of 5% in low transmission areas versus 10% in high transmission areas)

o   Clinical symptoms: predominantly due to the parasitized & non-parasitized RBCs adhering to blood vessels, leading to capillary leakage and infarction, culminating in organ dysfunction:

§  Alteration in mental status +/- seizures, hypotension (hemodynamic instability), respiratory complications (ARDS), metabolic acidosis, renal dysfunction (AKI, hemoglobinuria- aka “blackwater fever”), hepatic failure, severe anemia with intravascular hemolysis, alterations in glucose metabolism, coagulopathy +/- DIC

o   Physical Exam: pallor, jaundice, petechiae; HSM

o   Investigations: anemia, thrombocytopenia, may have coagulopathy, elevated liver enzymes, AKI (elevated Cr, urea), acidemia, hypoglycemia, parasitemia (5-10%); if a lumbar puncture is done with cerebral malaria expect slightly elevated CSF protein & cell count with a mean opening pressure of 16 cm of CSF

o   Prognosis: grave if evidence of complicated malaria, particularly if there are signs of cerebral malaria, which can progress to coma and death (mortality rate untreated-essentially fatal; mortality with treatment: 15-20%)

Treatment varies based on numerous factors (i.e. uncomplicated versus complicated, pregnant versus non-pregnant)

Severe falciparum malaria: Artesunate IV is first line

• Pregnant women: in the first trimester, use Quinine IV. In the 2^nd and 3^rd trimesters, Artesunate IV
•  Duration for severe malaria: for quinine/quinidine based therapy, treat for 7 days versus 3 days for artemisinin based therapy. After the acute stage of illness has been treated with IV therapy and the patient can swallow with minimal nausea/vomiting, complete a course of oral therapy

Uncomplicated malaria

• Chloroquine; consider atovaquone, quinine based regimes, etc
• May need to consider areas that are drug resistant!

NOTE: an infectious disease (ID) consult is often of benefit!

Resources: WHO

World Health Organization (WHO) Guidelines