Malaria

Mosquito-borne parasitic infection caused by Plasmodium species, transmitted by female Anopheles mosquitoes. Major global cause of morbidity/mortality, especially sub-Saharan Africa.

Species:

• P. falciparum: most lethal, responsible for majority of severe disease/deaths, no dormant liver stage, high parasitemia potential

• P. vivax and P. ovale: relapsing (dormant hypnozoites in liver can reactivate months-years later), generally milder acute illness

• P. malariae: chronic, low-grade parasitemia, can persist for decades, associated with nephrotic syndrome

• P. knowlesi: zoonotic (Southeast Asia), can cause severe disease, rapid replication cycle (24-hour)

• Incubation: typically 7-30 days (falciparum shorter, vivax/ovale can be much longer with relapses)

• Classic paroxysm (less reliably periodic in early/mixed infection): cold stage (rigors) → hot stage (high fever, headache, vomiting) → sweating stage (defervescence) cycle timing reflects species (48h tertian for vivax/ovale/falciparum, 72h quartan for malariae)

• Non-specific symptoms predominate initially: fever, headache, myalgia, malaise, nausea/vomiting, diarrhea; mimics many febrile illnesses, high index of suspicion needed in travelers/endemic exposure

• Examination: may be unremarkable early; splenomegaly, mild hepatomegaly, pallor (hemolysis-related anemia) common with progression

• Severe malaria (WHO criteria, ANY of the following in falciparum infection; medical emergency):

• Impaired consciousness/coma (cerebral malaria)

• Seizures (multiple)

• Respiratory distress/acidotic breathing

• Circulatory collapse/shock

• Pulmonary edema/ARDS

• Abnormal bleeding/DIC

• Jaundice

• Hemoglobinuria ("blackwater fever")

• Severe anemia (Hb <7g/dL)

• Hypoglycemia

• Acute kidney injury (creatinine >265μmol/L)

• Hyperparasitemia (>10% parasitized RBCs, though threshold varies)

• Hyperlactatemia/acidosis

• Blood film microscopy (thick and thin films) ; gold standard: thick film for detection/parasitemia quantification, thin film for species identification and % parasitemia calculation; repeat if initial negative but clinical suspicion high (2-3 films over 24-48 hours before excluding)

• Rapid diagnostic tests (RDTs): detect parasite antigens (HRP-2 for falciparum, pLDH for pan-species); useful where microscopy unavailable, faster but cannot quantify parasitemia or reliably distinguish species/monitor treatment response

• PCR: highest sensitivity, used for species confirmation, low-density infections, research/reference settings

• Additional labs for severity assessment: FBC (anemia, thrombocytopenia common), glucose (hypoglycemia risk, especially in severe disease/on quinine), U&E/creatinine (AKI), LFTs (jaundice), lactate (severity marker), coagulation profile if bleeding, blood cultures (rule out concurrent bacteremia, particularly in severe malaria where co-infection is recognized, especially in children)

Differentials: typhoid fever, dengue, other viral hemorrhagic fevers, sepsis/bacteremia, viral hepatitis, leptospirosis, rickettsial disease; malaria must be actively excluded in any febrile returned traveler from endemic area regardless of other apparent diagnosis.

Uncomplicated malaria:

• P. falciparum (or mixed/unidentified species, or chloroquine-resistant areas): artemisinin-based combination therapy (ACT); first-line globally

• Artemether-lumefantrine: 6-dose regimen over 3 days (weight-based dosing)

• Alternatives: artesunate-amodiaquine, dihydroartemisinin-piperaquine

• P. vivax/ovale (chloroquine-sensitive): chloroquine 25mg/kg total dose over 3 days (where chloroquine-sensitive; ACT if resistant, e.g., parts of Southeast Asia/Oceania)

• Radical cure: primaquine 0.25-0.5mg/kg/day for 14 days (or tafenoquine single dose) to eradicate hypnozoites and prevent relapse; MUST screen for G6PD deficiency first (hemolysis risk in deficient patients); contraindicated in pregnancy (use chloroquine prophylaxis for suppression until postpartum, then radical cure)

• P. malariae/knowlesi: chloroquine (malariae); ACT typically for knowlesi given severity potential

Severe malaria (medical emergency, admit/ICU):

• IV artesunate; first-line, superior to quinine (reduced mortality in both adults and children per major trials): 2.4mg/kg IV at 0, 12, 24 hours, then once daily; switch to oral ACT once able to tolerate and clinically improving (complete minimum 24 hours parenteral treatment)

• Alternative if artesunate unavailable: IV quinine (loading dose 20mg/kg over 4 hours, then 10mg/kg 8-hourly) + doxycycline/clindamycin; requires cardiac monitoring (QT prolongation), glucose monitoring (hypoglycemia risk)

• Supportive management: correct hypoglycemia, manage seizures (benzodiazepines), careful fluid management (avoid over-resuscitation; pulmonary edema risk, especially adults), blood transfusion for severe anemia, renal replacement therapy for AKI if indicated, treat DIC/bleeding

• Exchange transfusion: historically considered for extreme hyperparasitemia, evidence weak, not routinely recommended now given artesunate efficacy

Pregnancy: falciparum malaria in pregnancy is high-risk (severe disease, miscarriage, stillbirth, low birth weight); ACT is used in all trimesters per current WHO guidance (artemether-lumefantrine preferred); IV artesunate for severe malaria in pregnancy.

Prevention:

• Vector control: insecticide-treated bed nets (ITNs), indoor residual spraying

• Chemoprophylaxis for travelers to endemic areas: choice depends on resistance patterns — atovaquone-proguanil, doxycycline, or mefloquine (contraindicated in psychiatric history/seizures); start before travel, continue during and after per drug-specific schedule

• Seasonal malaria chemoprevention (SMC) in high-transmission areas (children, sulfadoxine-pyrimethamine + amodiaquine monthly during high-transmission season)

• Malaria vaccines (RTS,S/AS01, R21/Matrix-M): recommended for children in moderate-high transmission settings as part of comprehensive prevention strategy, not standalone

Monitoring: repeat blood films to confirm parasite clearance (particularly in severe malaria or if not improving as expected), watch for delayed hemolysis post-artesunate (can occur 2-4 weeks post-treatment, especially after high parasitemia; advise follow-up FBC).