Description

• Malaria is a febrile illness caused by the Plasmodium species of protozoan parasites, transmitted by the Anopheles mosquito vector.
• Five Plasmodium strains infect humans: Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, and Plasmodium knowlesi. P. falciparum and P. vivax cause the majority of disease.
• Classic symptoms include stages of chills, followed by high fevers, and then sweating. However, this classic symptom pattern is less likely to be seen in children. Children may manifest initially with only fever as a complaint.

Epidemiology

• High-risk areas of endemic malaria include Africa, parts of Central and South America, Oceania, and tropical regions of Asia.
• P. falciparum is the major species in sub-Saharan Africa. Both P. falciparum and P. vivax are found in India, Southeast Asia, Oceania, and Central and South America, and P. vivax is present in some areas of Africa. P. ovale is usually found in West Africa.
• P. falciparum causes more deaths in children <5 years of age than any other organism.
• The World Health Organization (WHO) reports that 70% of malaria deaths occur in children <5 years of age. Pregnant women are also at high risk.
• Mortality has decreased by 35% from 2010 to 2015 for children <5 years old.

Risk Factors

General Prevention

• Personal protective measures against mosquito bites are extremely important.
  • Remain in well-screened areas.
  • Wear protective clothing, including pants and long-sleeved shirts.
  • Use insect repellents containing N,N-Diethyl-meta-toluamide (DEET).
  • Use insecticide-treated bed nets.
• Chemoprophylaxis is strongly advised for travelers to endemic areas.
  • In areas with chloroquine-sensitive parasites only, chloroquine may be used (5 mg/kg base [8.3 mg/kg salt] once a week—max 300 mg base/500 mg salt).
  • In chloroquine-resistant areas, effective options are atovaquone-proguanil (Malarone^®), mefloquine, or doxycycline.
    • Malarone^® can be used in all areas but is contraindicated in severe renal impairment and pregnancy, or mothers breastfeeding infants <5 kg.
      • Dosing: 5 to 8 kg: 1/2 pediatric tab daily; 8 to 10 kg: 3/4 pediatric tab daily; 10 to 20 kg: 1 pediatric tab (62.5/25) daily; 20 to 30 kg: 2 pediatric tabs daily; 30 to 40 kg: 3 pediatric tabs daily; ≥40 kg: 1 adult tab (250/100) daily
  • Mefloquine resistance is present in parts of Asia. Contraindications to mefloquine include seizure disorder, major psychiatric illness, or cardiac disease. It is safe in pregnancy and for young infants.
    • Dosing: ≤9 kg: 4.6 mg/kg weekly; 9 to 19 kg: 1/4 tablet weekly; 19 to 30 kg: 1/2 tab weekly; 30 to 45 kg: 3/4 tab weekly; >45 kg: 1 tab weekly
  • Doxycycline is contraindicated if <8 years of age and in pregnancy; dosing: 2.2 mg/kg daily (max 100 mg/day)
• Chloroquine and mefloquine are started 1 and 2 weeks respectively before travel, continued during the period of exposure and for 4 weeks after leaving the endemic region. Malarone is started 2 days prior to travel and continued 1 week after return. Doxycycline is started 2 days before travel and continued for 4 weeks after return.

Etiology

• Infection is typically transmitted by the bite of the female Anopheles mosquito, but it can also be transmitted through contaminated blood transfusions or acquired congenitally.
• The majority of human disease is caused by P. falciparum and P. vivax.
  • P. vivax and P. ovale can cause relapsing disease because of the persistent hepatic (hypnozoite) stage of the infection.
  • Asymptomatic carriage for years may occur with P. malariae.
  • P. knowlesi is a primate parasite that can cause severe disease in humans. To date, it has occurred in humans only in Southeast Asia.

Commonly Associated Conditions

• Severe malaria is most commonly caused by P. falciparum; however, severe cases caused by P. vivax have been reported.
• Severe malaria is defined as parasitemia >5%, shock, acidosis, severe anemia or signs of CNS or other end-organ involvement such as renal failure, pulmonary edema, respiratory distress (acidotic/irregular breathing), impaired consciousness, seizures, hemoglobinuria, disseminated intravascular coagulation (DIC), or hypoglycemia.
• Cerebral malaria is a serious consequence of malaria infection, defined as coma in conjunction with P. falciparum parasitemia.
  • Occurs most often in children age 1 to 6 years in Africa but often occurs in adolescents and adults in Southeast Asia
• Severe anemia is common and can be severe, especially with P. falciparum. This is due to high parasitemia, hemolysis, sequestration and bone marrow suppression.
• Respiratory distress has high mortality, particularly if combined with impaired consciousness.
• Blackwater fever is a complication associated with falciparum malaria. It occurs due to massive hemolysis with resulting hemoglobinuria and acute renal failure.
• Pulmonary edema, renal failure, distributive shock, and progression to coma or death can occur.
• Acute kidney injury is common in children with severe malaria but rarely requires dialysis.
• Hyperreactive malarial splenomegaly is seen with chronic exposure to malaria in endemic areas. High levels of malaria IgM are present, and massive hepatosplenomegaly is seen.
• Splenic rupture may occur due to splenomegaly.
• P. malariae can cause nephrotic syndrome.