Malaria
Epidemiology
Demographics
Prevalence Malaria Causes Approximately 500 Million Cases and 2 Million Deaths Annually Worldwide Geography Malaria is Common in Sub-Saharan Africa, Asia, Latin America, the Middle East, and Parts of Greece and Turkey Micro-Epidemics of Malaria in the United States : have been reported where infected immigrants from these regions are believed to be the reservoirMalaria is the Most Common infectious Disease Causing Severe Illness in International Travelers Returning to the United States Approximately 1000 Cases of Malaria are Diagnosed Annually in the United States Teleology
Beta Thalassemia Trait (see Thalassemias )Believed to Confer a Survival Advantage Against Malaria This Explains the Concentration of Beta Thalassemia Trait in Geographic Areas Affected by Malaria (Middle East, Mediteranean, Africa, etc) Etiology
Plasmodium Falciparum Physiology Infects Red Blood Cells of All Ages (Not Just Young Ones), Resulting in Higher Levels of Parasitemia Generates Electron-Dense Knob-Like Excrescences on RBC Surface, Mediating Cytoadherence and Microvascular Obstruction Clinical Fatal Illness Occurs Mainly with Plasmodium Falciparum Plasmodium Knowlesi Clinical Can Result in Rapidly Progressive Severe Illness/Death Plasmodium Malariae Clinical Less Likely to Result in Severe Clinical Manifestations Plasmodium Ovale Clinical Less Likely to Result in Severe Clinical Manifestations Treatment Requires Treatment of Hypnozoite (Dormant) Forms in the Liver, Which May Result in Relapsing Infection Plasmodium Vivax Clinical Less Likely to Result in Severe Clinical Manifestations Treatment Requires Treatment of Hypnozoite (Dormant) Forms in the Liver, Which May Result in Relapsing Infection Physiology
Routes of Transmission Bite from Female Anopheles Mosquito (see Mosquito Bite ): most bites occur between dusk and dawn, as mosquitoes are nocturnalContaminated Blood Product Maternal-Fetal Transmission Organ Transplant Course Parasite Invades the Red Blood Cell Diagnosis
General Comments Blood Smears Should Be Repeated Every 12-24 hrs for a Total of 3 Sets Since Non-Immune Patients May Be Symptomatic at Very Low Parasite Densities Which May be Undetectable by a Single Smear Three Sets of Smears at Intervals are Adequate to Rule Out Malaria Thin Smear (Standard Peripheral Blood Smear) Preparation of Thin Smear Performed with Monolayer of Red Blood Cells (with Red Blood Cells Just Touching Each Other, at Approximately 400 Red Blood Cells Per Field) Interpretation Examine Under Oil Immersion at 100x Magnification and Count 500-2000 Red Blood Cells to Determine the Percentage of Infected Cells (Containing Ring Forms, Gametocytes, etc) Thick Smear Preparation of Thick Smear Apply Drop of Blood, Allow to Dry -> Apply Drop of Blood, Allow to Dry -> Apply Drop of Blood, Allow to Dry -> Add Water to Lyse Red Blood Cells Interpretation Examine for the Presence of Organisms (Ring Forms, Gametocytes, etc) Although this Technique Concentrates Organisms (and Therefore, is More Sensitive), it May Be Difficult to Detect Organisms Due to the Presence of Cellular Debris Rapid Diagnostic Tests
Available in Dipstick/Cassette Format Findings Decreased Glucose Increased Opening Pressure : mean of 16 cm H2O in the setting of cerebral malariaSlight Pleocytosis : may be observedSlightly Elevated Total Protein : may be observedClinical Presentations
Clinical Classification
Uncomplicated Malaria : absence of below criteriaSevere Malaria : characterized by at least one of the following criteriaSevere Falciparum Malaria
Cardiovascular Manifestations
Dermatologic Manifestations
Endocrinologic Manifestations
Hypoglycemia (see Hypoglycemia ): may be severeMechanisms Decreased Hepatic Gluconeogenesis Depletion of Hepatic Glycogen Stores Increased Host Consumption of Glucose Quinine-Induced Hyperinsulinemia Gastrointestinal Manifestations
Acute Liver Failure (Fulminant Hepatic Failure) (see Acute Liver Failure )Epidemiology May Occur in the Setting of Plasmodium Falciparum Infection (More Commonly in Adults than in Children) Physiology Due to Cholestasis and Hepatocyte Injury Clinical Presents with Severe Hyperbilirubinemia Prognosis Hepatic Dysfunction with Acute Kidney Injury Portends a Poor Prognosis Hepatomegaly (see Hepatomegaly )Jaundice/Hyperbilirubinemia (see Hyperbilirubinemia )Hematologic Manifestations
Absence of Peripheral Eosinophilia Coagulopathy with/without Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation )Hemolytic Anemia (see Hemolytic Anemia )Mechanisms of Anemia Cytokine Suppression of Hematopoesis Hemolysis of Parasitized Red Blood Cells Recurrent Infection Shortened Red Blood Cell Survival Splenic Sequestration and Clearance of Red Blood Cells with Diminished Deformability Clinical Hematocrit <15% (with Parasitemia >5%) Splenomegaly (see Splenomegaly )Thrombocytopenia (see Thrombocytopenia )Neurologic Manifestations (Cerebral Malaria)
General Comments Focal Neurologic Findings are Uncommon Onset May Be Gradual or Abrupt (For Example, Following a Seizure) Altered Mental Status (see Altered Mental Status )Due to Adherence of Red Blood Cells (“Cytoadherence”) within the Microcirculation, Resulting in Ischemia and/or Micro-Infarcts Delirium/Encephalopathy (see Delirium )Obtundation/Coma (see Obtundation-Coma )Increased Intracranial Pressure/Cerebral Edema (see Increased Intracranial Pressure )Seizures (see Seizures )Due to Adherence of Red Blood Cells (“Cytoadherence”) within the Microcirculation, Resulting in Ischemia and/or Micro-Infarcts Extreme Weakness (see Weakness )Pulmonary Manifestations
Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome )Physiology Sequestration of Parasitized Red Blood Cells in the Lung Microvasculature and/or Capillary Leak Secondary Bacterial Pneumonia Renal Manifestations
Acute Kidney Injury (AKI) (see Acute Kidney Injury )Epidemiology Common in Adults with Severe Plasmodium Falciparum Malaria (However, it is Relatively Rare in Children) Hemoglobinuria (see Hemoglobinuria )Black/Brown/Red Urine Due to Hemolytic Anemia (see Hemolytic Anemia )“Blackwater Fever” (Rare) : black urine (due to large amounts of hemoglobin and malarial pigments in urine) occurring after repeated attacks of Plasmodium Falciparum malariaLactic Acidosis (see Lactic Acidosis )Mechanisms Decreased Hepatic/Renal Lactate Clearance Hypovolemia Increased Anaerobic Glycolysis (Due to Parasite Impairment of Micro-Circulatory Flow) Lactate Production by Parasite Prognosis : severe acidosis portends a poor prognosisHyponatremia (see Hyponatremia )Other Manifestations
Sepsis (see Sepsis )Epidemiology Salmonella Bacteremia Has Been Associated with Plasmodium Falciparum MalariaFever (see Fever ): >40 °CRigors (see Rigors )Malaria in Pregnancy (see Pregnancy )
Malaria in Children
Treatment
Prevention and Monitoring
Prevention of Exposure to Mosquito Bites Netting DEET Repellants Permethrins for Clothing Monitor for Febrile Illnesses Malaria Can Be Acquired Despite Protective Measures and Prophylaxis Pre-Exposure Prophylaxis
General Comments Begin Medication Before Departure and Continue Until a Certain Time After Leaving the Malaria Risk Area Chloroquine (see Chloroquine )Mefloquine (Lariam) (see Mefloquine )For Areas with Chloroquine Resistance (Mexico, Central America, Caribbean islands, North Africa, Portions of Middle East, China) Alternatives Antibiotics
General Comments Uncomplicated Malaria : can generally be treated with oral anti-malarialsSevere Malaria : generally require intravenous anti-malarialsArtemether + Lumefantrine (Coartem) Artemisinin Derivatives Artesunate (see Artesunate )Availability: available on compassionate use from the CDC (as is currently not licensed for use in the US) Administration: IV Atovaquone + Proguanil (Malarone) (see Atovaquone )Chloroquine (see Chloroquine ): active against parasite forms in the bloodClindamycin (see Clindamycin ): used in combination with quinineMefloquine (Lariam) (see Mefloquine )Primaquine (see Primaquine ): active against dormant parasite forms (hypnozoites) and effective to prevent relapsesQuinine Sulfate IV (see Quinine ): not available in USQuinidine Gluconate IV (see Quinidine )Tetracyclines (see Tetracyclines )Doxycycline (see Doxycycline ): used in combination with quinineTetracycline (see Tetracycline ): used in combination with quinineExchange Transfusion
History Indications Parasitemia >5% (High Level) or Clinical Signs of Poor Prognosis Efficacy An 8-10 Unit Exchange Decreases Level of Parasitemia to <1% Trial Data :Exchange Transfusion Has Not Been Demonstrated to Have Clinical Benefit in Randomized, Controlled Trials and is No Longer Recommended by the CDC References
Treatment of severe malaria in the United States with a continuous infusion of quinidine gluconate and exchange transfusion. N Engl J Med 1989; 321:65-70 Malaria: overview and update. Clin Infect Dis 1993; 16:449-458 The treatment of malaria. N Engl J Med 1996; 335:800-806 Malaria: the global resurgence of disease. Emerg Med Clin North Am 1997; 1:113-155
Property of Kenneth J. Serio, MD. Author is not responsible for errors in content, site is for information purposes only.
