Malaria

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Basics

Description

  • Infection with Plasmodium species protozoa, transmitted to humans by Anopheles spp. mosquitoes
  • Most morbidity and mortality is caused by Plasmodium falciparum.
  • Nonimmune individuals are most susceptible to rapid progression to severe disease.
  • System(s) affected: cardiovascular, hematologic, renal, respiratory, cerebral, lymphatic, immunologic, hepatic

Epidemiology

  • Cases imported to the United States: 68% P. falciparum; 12% Plasmodium vivax; 3% Plasmodium malariae; 5% Plasmodium ovale; 1% mixed; 11% unknown
  • Occurs worldwide in tropical latitudes: P. falciparum, P. malariae, P. vivax, and P. ovale; Plasmodium knowlesi in parts of Southeast Asia
  • Malaria is responsible for 1–3 million deaths/year (primarily children in sub-Saharan Africa)
  • 300–500 million cases annually across the globe.
  • Most prevalent in rural tropics (altitude below 1000 m)

Incidence
  • Most U.S. cases (>99%) are imported.
  • There are ~30 million travelers to tropical areas each year. 10,000–30,000 travelers from the U.S. and Europe contract malaria annually
  • ~2,000 cases and 5 deaths per year in the U.S.
Prevalence
  • Predominant age: all ages
  • Predominant sex: male = female

Etiology and Pathophysiology

  • Plasmodia are transmitted via saliva from infected Anopheles mosquito during a blood meal. Circulating plasmodia enter red blood cells (RBC), digest RBC proteins, and alter the RBC membrane, causing hemolysis, increased splenic clearance, and anemia.
  • RBC lysis stimulates release of cytokines and tumor necrosis factor (TNF-α), causing fever and systemic symptoms.
  • P. falciparum alters RBC viscosity, causing obstruction and end-organ ischemia.

Genetics
Unknown, but inherited conditions may affect disease severity and susceptibility (glucose-6-phosphate dehydrogenase [G6PD] deficiency, sickle cell disease or trait, Duffy-negative blood group, and hereditary elliptocytosis).

Risk Factors

  • Travel to or migration from endemic areas
  • Rarely, blood transfusion, mother-to-fetus transmission, and local autochthonous transmission

General Prevention

  • Mosquito avoidance: Use insect repellent, wear clothing to cover exposed skin, use mosquito nets treated with insecticides such as permethrin, and avoid outdoor activity from dusk to dawn (when feeding activity of Anopheles mosquito is the greatest).
  • Malarial chemoprophylaxis in endemic areas
    • Atovaquone/proguanil: Begin 1 to 2 days before arrival and continue for 1 week after leaving area. Adults, 1 adult tablet daily; children 5 to 8 kg, 1/2 pediatric tablet daily; children 9 to 10 kg, 3/4 pediatric tablet daily; children >10 to 20 kg, 1 pediatric tablet daily; children >20 to 30 kg, 2 pediatric tablets daily; children >30 to 40 kg, 3 pediatric tablets daily; children >40 kg, 1 adult tablet daily
      • Caution: don’t use in pregnant women and infants <5 kg.
    • Chloroquine: Begin 1 to 2 weeks before arrival and continue for 4 weeks after leaving area. Adults, 500 mg salt (300-mg base) weekly; children, 8.3 mg/kg salt (5-mg base/kg) weekly up to 500 mg salt.
      • Caution: chloroquine-resistant areas, can make psoriasis worse.
    • Doxycycline: Begin 1 to 2 days before arrival and continue for 4 weeks after leaving area. Adults, 100 mg daily; children >8 years old, 2 mg/kg up to 100 mg daily
      • Caution: don’t use in pregnant women and children ≤ 8 years old.
    • Hydroxychloroquine sulfate: Begin 1 to 2 weeks before arrival and continue for 4 weeks after leaving area. Adults, 400 mg salt (310 mg base) weekly; children, 6.5 mg/kg salt (5 mg base/kg) weekly up to 400 mg salt.
      • Caution: chloroquine-resistant areas, can make psoriasis worse.
    • Mefloquine: Begin at least 2 weeks before arrival and continue for 4 weeks after leaving area. Adults, 250 mg (1 tablet) weekly; children ≤9 kg, 5 mg/kg weekly; children >9 to 19 kg, 1/4 tablet weekly; children >19 to 30 kg, 1/2 tablet weekly; children >30 to 45 kg, 3/4 tablet weekly; children >45 kg as adult dosing
      • Caution: mefloquine-resistant areas; don’t use if history of psychiatric disorders.
    • Primaquine: Begin 1 to 2 days before arrival and continue for 1 week after leaving area; adults, 30 mg/day; children, 0.5 mg/kg/day up to adult dose
      • For use only in areas predominantly endemic for P. vivax
      • Caution: Exclude G6PD deficiency prior to first use, do not use in pregnant women or breastfeeding women unless infant has been tested for G6PD deficiency.
    • Tafenoquine: Take daily 3 days before arrival, weekly during travel, and 1 week after leaving area; adults 200 mg per dose
      • Caution: Exclude G6PD deficiency prior to first use; don’t use if history of psychiatric disorders; don’t use in children; do not use in pregnant or breastfeeding women.

Commonly Associated Conditions

  • Bacterial coinfections sometimes occur.
  • Sickle cell trait confers an element of protection against malaria due to changes in the RBC cytoskeleton.

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Basics

Description

  • Infection with Plasmodium species protozoa, transmitted to humans by Anopheles spp. mosquitoes
  • Most morbidity and mortality is caused by Plasmodium falciparum.
  • Nonimmune individuals are most susceptible to rapid progression to severe disease.
  • System(s) affected: cardiovascular, hematologic, renal, respiratory, cerebral, lymphatic, immunologic, hepatic

Epidemiology

  • Cases imported to the United States: 68% P. falciparum; 12% Plasmodium vivax; 3% Plasmodium malariae; 5% Plasmodium ovale; 1% mixed; 11% unknown
  • Occurs worldwide in tropical latitudes: P. falciparum, P. malariae, P. vivax, and P. ovale; Plasmodium knowlesi in parts of Southeast Asia
  • Malaria is responsible for 1–3 million deaths/year (primarily children in sub-Saharan Africa)
  • 300–500 million cases annually across the globe.
  • Most prevalent in rural tropics (altitude below 1000 m)

Incidence
  • Most U.S. cases (>99%) are imported.
  • There are ~30 million travelers to tropical areas each year. 10,000–30,000 travelers from the U.S. and Europe contract malaria annually
  • ~2,000 cases and 5 deaths per year in the U.S.
Prevalence
  • Predominant age: all ages
  • Predominant sex: male = female

Etiology and Pathophysiology

  • Plasmodia are transmitted via saliva from infected Anopheles mosquito during a blood meal. Circulating plasmodia enter red blood cells (RBC), digest RBC proteins, and alter the RBC membrane, causing hemolysis, increased splenic clearance, and anemia.
  • RBC lysis stimulates release of cytokines and tumor necrosis factor (TNF-α), causing fever and systemic symptoms.
  • P. falciparum alters RBC viscosity, causing obstruction and end-organ ischemia.

Genetics
Unknown, but inherited conditions may affect disease severity and susceptibility (glucose-6-phosphate dehydrogenase [G6PD] deficiency, sickle cell disease or trait, Duffy-negative blood group, and hereditary elliptocytosis).

Risk Factors

  • Travel to or migration from endemic areas
  • Rarely, blood transfusion, mother-to-fetus transmission, and local autochthonous transmission

General Prevention

  • Mosquito avoidance: Use insect repellent, wear clothing to cover exposed skin, use mosquito nets treated with insecticides such as permethrin, and avoid outdoor activity from dusk to dawn (when feeding activity of Anopheles mosquito is the greatest).
  • Malarial chemoprophylaxis in endemic areas
    • Atovaquone/proguanil: Begin 1 to 2 days before arrival and continue for 1 week after leaving area. Adults, 1 adult tablet daily; children 5 to 8 kg, 1/2 pediatric tablet daily; children 9 to 10 kg, 3/4 pediatric tablet daily; children >10 to 20 kg, 1 pediatric tablet daily; children >20 to 30 kg, 2 pediatric tablets daily; children >30 to 40 kg, 3 pediatric tablets daily; children >40 kg, 1 adult tablet daily
      • Caution: don’t use in pregnant women and infants <5 kg.
    • Chloroquine: Begin 1 to 2 weeks before arrival and continue for 4 weeks after leaving area. Adults, 500 mg salt (300-mg base) weekly; children, 8.3 mg/kg salt (5-mg base/kg) weekly up to 500 mg salt.
      • Caution: chloroquine-resistant areas, can make psoriasis worse.
    • Doxycycline: Begin 1 to 2 days before arrival and continue for 4 weeks after leaving area. Adults, 100 mg daily; children >8 years old, 2 mg/kg up to 100 mg daily
      • Caution: don’t use in pregnant women and children ≤ 8 years old.
    • Hydroxychloroquine sulfate: Begin 1 to 2 weeks before arrival and continue for 4 weeks after leaving area. Adults, 400 mg salt (310 mg base) weekly; children, 6.5 mg/kg salt (5 mg base/kg) weekly up to 400 mg salt.
      • Caution: chloroquine-resistant areas, can make psoriasis worse.
    • Mefloquine: Begin at least 2 weeks before arrival and continue for 4 weeks after leaving area. Adults, 250 mg (1 tablet) weekly; children ≤9 kg, 5 mg/kg weekly; children >9 to 19 kg, 1/4 tablet weekly; children >19 to 30 kg, 1/2 tablet weekly; children >30 to 45 kg, 3/4 tablet weekly; children >45 kg as adult dosing
      • Caution: mefloquine-resistant areas; don’t use if history of psychiatric disorders.
    • Primaquine: Begin 1 to 2 days before arrival and continue for 1 week after leaving area; adults, 30 mg/day; children, 0.5 mg/kg/day up to adult dose
      • For use only in areas predominantly endemic for P. vivax
      • Caution: Exclude G6PD deficiency prior to first use, do not use in pregnant women or breastfeeding women unless infant has been tested for G6PD deficiency.
    • Tafenoquine: Take daily 3 days before arrival, weekly during travel, and 1 week after leaving area; adults 200 mg per dose
      • Caution: Exclude G6PD deficiency prior to first use; don’t use if history of psychiatric disorders; don’t use in children; do not use in pregnant or breastfeeding women.

Commonly Associated Conditions

  • Bacterial coinfections sometimes occur.
  • Sickle cell trait confers an element of protection against malaria due to changes in the RBC cytoskeleton.

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