Malaria

Background

• Malaria is a systemic infection of erythrocytes by plasmodia protozoa.
• While over 100 protozoal species of the genus Plasmodium have been identified, only 5 species are known to infect humans:
  • Plasmodium falciparum (most common)
  • Plasmodium vivax
  • Plasmodium malariae
  • Plasmodium ovale
  • Plasmodium knowlesi
• Transmission to humans is primarily through the bite of an infected female Anopheles mosquito, with less common routes of transmission including congenital transmission and blood transfusion.
• There were approximately 212 million cases worldwide in 2015, however estimates of malaria incidence tend to be low due to underreporting and lack of adequate surveillance.

Evaluation

• Suspect malaria in patients with signs and symptoms of malaria (such as, fever, chills, headache, and anorexia) and recent travel to, or residence in, malaria-endemic areas.
• Diagnosing malaria begins with parasitologic testing in any patient with suspected malaria before starting treatment, if possible; specimen collection and testing options include:
  • peripheral blood smear
  • rapid antigen detection tests (RDTs)
  • polymerase chain reaction
• Initial workup should also include blood glucose, hematocrit or hemoglobin, renal function, and routine chemistry panel.
• Severity of illness must be established to determine the therapeutic approach.
  • Uncomplicated malaria is defined as the presence of malaria symptoms and positive microscopy or rapid diagnostic test and no features of severe malaria.
  • Severe malaria is defined as the presence of malaria symptoms and positive microscopy or rapid diagnostic test and ≥ 1 clinical or laboratory indicator.
    • Clinical indicators:
      • deep coma suggestive of cerebral malaria (Glasgow Coma Score < 11 in adults or Blantyre Coma Score < 3 in children)
      • prostration or generalized weakness with inability to walk or sit up unassisted
      • ≥ 2 seizures within 24 hours
      • pulmonary edema
      • acute respiratory distress syndrome
      • shock
      • significant bleeding including recurrent or prolonged bleeding from gums, nose, or venipuncture sites; hematemesis; or melena
    • Laboratory indicator:
      • severe malarial anemia (parasite count > 10,000/mcL plus hematocrit ≤ 15% or hemoglobin ≤ 5 g/dL in children < 12 years old or hematocrit < 20% or hemoglobin < 7 g/dL in adults)
      • renal failure (plasma or serum creatinine > 265 mcmol/L [3 mg/dL] or blood urea > 20 mmol/L)
      • hypoglycemia (blood or plasma glucose < 2.2 mmol/L [< 40 mg/dL])
      • hyperparasitemia (P. falciparum parasitemia > 10%)
      • acidosis (base deficit of > 8 mEq/L or, if not available, plasma bicarbonate < 15 mmol/L [15 mEq/L] or venous plasma lactate ≥ 5 mmol/L)
      • hyperbilirubinemia/jaundice (plasma or serum bilirubin > 50 mcmol/L [3 mg/dL] plus parasite count > 100,000/mcL).

Management

• Treatment based solely on clinical suspicion should only be considered when parasitologic diagnosis is not possible.
• Antimalarial drug resistance has been documented in P. falciparum, P. vivax, and P. malariae, and the distribution of resistant infection is an important consideration when determining the treatment.
• Treatment of adults and children with uncomplicated malaria:
  • P. falciparum malaria (except pregnant patients in first trimester) consists of 3-day treatment with artemisinin combination therapy (ACT) using any of the following:
    • artemether/lumefantrine
    • artesunate/amodiaquine
    • artesunate/mefloquine
    • dihydroartemisinin/piperaquine
    • artesunate plus sulfadoxine/pyrimethamine
  • Treatment of P. falciparum malaria in special risk patients:
    • treat patients in first trimester of pregnancy with 7 days of quinine plus clindamycin
    • treat infants weighing < 5 kg with an ACT at same mg/kg target dose as children weighing 5 kg
    • patients coinfected with HIV should avoid artesunate plus sulfadoxine/pyrimethamine if they are receiving co-trimoxazole (sulfamethoxazole/trimethoprim), and artesunate plus amodiaquine if they are also receiving efavirenz or zidovudine
    • nonimmune travelers returning to nonendemic settings should be treated with an ACT
    • patients with uncomplicated hyperparasitemia require close monitoring and treatment with an ACT
  • Treatment of P. vivax, P. ovale, P. malariae, or P. knowlesi malaria:
    • treat patient as for uncomplicated P. falciparum infection if malaria species is not known
    • in areas of chloroquine-susceptible infections, treat all patients with an ACT (except pregnant patients in first trimester) or chloroquine
    • in areas of chloroquine resistance, treat all patients with an ACT (except pregnant patients in first trimester who use quinine)
    • primaquine should be given to patients with P. vivax or P. ovale infection to prevent relapse except patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, pregnant patients, infants < 6 months old, and patients breastfeeding infants < 6 months old, or older children with possible G6PD deficiency
• Treatment of severe malaria:
  • severe malaria should be considered a medical emergency
  • give all patients with severe malaria IV or intramuscular artesunate for ≥ 24 hours; once patient can tolerate oral medication give oral ACT (add single dose of primaquine in areas of low transmission)
  • give artemether in preference to quinine if artesunate is not available
  • in cases where facilities are not equipped to manage a patient with severe malaria, prereferral treatment with single-dose intramuscular artesunate, artemether, or quinine should be given and patient should be immediately referred to appropriate facility for further treatment
• Due to variations in drug availability, treatment options for adults and children in the United States:
  • with uncomplicated P. falciparum chloroquine-resistant malaria or malaria with unknown resistance include any of the following
    • atovaquone/proguanil
    • artemether/lumefantrine
    • quinine sulfate plus 1 of doxycycline, tetracycline, or clindamycin
    • mefloquine
  • with uncomplicated chloroquine-sensitive P. falciparum, P. malariae, P. knowlesi, P. vivax, or P. ovale malaria, include either
    • chloroquine phosphate (plus primaquine phosphate for P. vivax or P. ovale)
    • hydroxychloroquine (plus primaquine phosphate for P. vivax or P. ovale)
  • with uncomplicated chloroquine-resistant P. vivax include any of the following
    • quinine sulfate plus either doxycycline or tetracycline plus primaquine phosphate
    • atovaquone/proguanil plus primaquine phosphate
    • mefloquine plus primaquine phosphate
  • with severe malaria, give IV artesunate followed by artemether/lumefantrine, atovaquone/proguanil, doxycycline, clindamycin (if pregnant), or mefloquine (if other options not available)
  • for pregnant patients with
    • chloroquine-sensitive uncomplicated malaria, give either chloroquine phosphate or hydroxychloroquine
    • chloroquine-resistant uncomplicated malaria, give either mefloquine alone or quinine sulfate plus clindamycin
• Preventive measures include mosquito avoidance and chemoprophylaxis.