Rationale:

• Although some recommendations exist for hospitalization of patients who present in nonendemic regions with uncomplicated malaria, it is difficult even for experienced physicians to predict who will progress to severe disease.
• Clinical deterioration may follow a sudden and dramatic course: parasitemias can suddenly increase to high levels or may synchronously develop into mature forms, leading to cerebrovascular sequestration and coma and/or seizures.
• Complications in adults (e.g., acute renal failure, acute lung injury, hepatic failure) can occur even when parasitemia is decreasing or while the patient appears to be improving in other ways.
• Successful treatment of patients with severe malaria requires frequent clinical monitoring and intensive nursing care and may demand sophisticated interventions.

Evidence:

• Pregnant women, children, and the elderly are at increased risk of morbidity and mortality and should be hospitalized regardless of their clinical state (82; 83; 84).
• A prospective, observational study at a London hospital compared the clinical presentation of “malaria-naïve” adults (born and residing in a nonendemic country, n=167) and “partially immune” adults (born and residing in a malaria-endemic country of Africa, n=93) and found no differences in time to presentation, median parasitemia at presentation, peak parasitemia, or time to parasite clearance. Although malaria-naïve patients had a significantly higher risk of parasitemia >5% (OR, 4.5 [CI, 1.5 to 13.2]), the proportion of patients who had parasitemia >2% or required parenteral therapy or intensive care was similar between the two groups (85).
• Patients who present without adverse signs may deteriorate over the next 24 hours despite prompt hospitalization and apparently adequate treatment, as highlighted by recent case reports (86).

Comments:

• Although some patients with nonsevere P. falciparum malaria can be treated successfully in an outpatient setting (87), patients with no immunity or partial immunity are at increased risk of severe disease and should be hospitalized (for at least 48 hours) to ensure adequate response to therapy regardless of how well they appear at presentation. Acute P. falciparum malaria in a nonimmune individual is highly dangerous and unpredictable.
• Management of severe malaria also requires appropriate care of the unconscious patient, prevention and rapid treatment of convulsions, treatment of hyperpyrexia, and early recognition and treatment of other complications of severe malaria, especially hypoglycemia, aspiration pneumonia, and gram-negative sepsis.
• Anecdotal evidence indicates that patients who previously acquired some immunity against P. falciparum can lose it during prolonged stays away from their home endemic areas and can experience symptomatic malaria episodes upon returning home. One review article refers to data (published in French and in book form) showing that West African immigrants to France are susceptible to clinical malaria when they return to their country after several years. The authors comment that although the case fatality rate was not measured, such patients rarely have cerebral malaria (88).
• Patients at high risk of severe P. falciparum malaria include those unable or unlikely to take oral medication.
• Patients with malarias other than P. falciparum (P. vivax, P. ovale, P. malariae) rarely require hospitalization.
• Rarely, acute P. vivax infection leads to splenic rupture, requiring surgery or conservative management (89; 90; 91).
• Chronic P. malariae infection can lead to nephrotic syndrome in young children living in endemic areas. This immune-complex-mediated glomerulopathy can progress relentlessly to renal failure and is generally unresponsive to steroids, other immunosuppressive drugs, or antimalarials (92).