Rationale:

• Most travelers who acquire malaria develop symptoms within 3 months of exposure.
• Symptoms of malaria can be nonspecific and may include sensations of fever, chills, sweats, nausea, vomiting, lassitude, headaches, and body aches. Fever may be synchronous, recurring every 48 to 72 hours, or it may be asynchronous. Patients can be relatively asymptomatic during afebrile periods.

Evidence:

• Of 681 patients with imported malaria with onset of illness in 2002 and for whom clinical presentation and parasite species were known, clinical illness began within 1 month of arrival in the U.S. in 385 of 482 (80%) patients with P. falciparum and in 57 of 155 (37%) patients with P. vivax (22).
• In a few cases, onset of clinical illness may be delayed. In a case-control study involving 258 immigrants (197 controls and 61 cases) returning to France, the median time of diagnosis of malaria among cases was 5 months (interquartile range, 3 to 9 months) (41).
• The specificity of diagnosis from clinical signs and symptoms (even in endemic areas where malaria is common) can be only 20% to 60% compared with microscopy (42; 43; 44) and varies widely depending on geographic area.
• The most common presenting symptoms of 123 U.S. travelers who died of malaria between 1963 and 2001 were as follows: fever (77%), chills (46%), mental status changes (20%), myalgia (19%), fatigue or malaise (18%), diarrhea (16%), weakness (16%), vomiting (16%), headache (16%), and nausea (16%) (45).
• A series of 160 German nationals or residents with imported malaria presented to a travel clinic with the following symptoms: fever (100%), headache (100%), weakness (94%), profuse night sweats (91%), insomnia (69%), arthralgias (59%), myalgias (56%), diarrhea (13%), and abdominal cramps (8%) (46).
• A series of 612 Europeans with imported P. vivax malaria complained of fever (96%), headache (51%), fatigue (33%), and musculoskeletal symptoms (30%). The median time to symptom onset was 86 days and 31 days in patients with and without chemoprophylaxis, respectively (47).
• Symptoms of P. falciparum malaria occurred within 2 months in 96% of 1425 Israeli and American travelers. Few (<15%) were found to have taken effective blood-stage prophylaxis. In contrast, symptoms of P. vivax and P. ovale malaria occurred later than 2 months in 64% of 1569 Israeli and American travelers, of whom the majority (>60%) had taken effective blood-stage prophylaxis (48).
• A case-control study (46 cases, 557 controls) of UK travelers returning from The Gambia identified duration of stay to be a strong independent risk factor for acquiring malaria (OR, 2.05 per extra week [CI, 1.42 to 2.95]) (49).

Comments:

• The life cycle of malaria parasites is illustrated on the CDC's Laboratory Identification of Parasites of Public Health Concern Web site.
• Although malaria can present many months or years after exposure due to the emergence of latent hypnozoites of P. vivax or P. ovale from the liver, such relapses are almost nonexistent more than 5 years after exposure.
• Recrudescence of P. malariae infection from low-level persistent blood stages has been reported decades after initial exposure (50; 51; 52).
• All four Plasmodium species that infect humans have been transmitted in blood transfusions in the U.S. These blood donations are typically from asymptomatic persons from endemic areas with low-level parasitemia (53).
• Malaria has also been acquired via solid organ transplantation (54).
• Congenital transmission of malaria is rare but does occur. In one case, a mother with a history of multiple P. vivax relapses suffered acute relapse several days prior to delivery. The neonate presented at 3 weeks of age with inadequate feeding and somnolence, thrombocytopenia, and a blood film positive for P. vivax (22).
• On occasion, malaria may occur in persons who have never visited a malarious area. For example, a person may be bitten by a local Anopheline mosquito that has acquired infection from an immigrant or visitor from a malaria endemic country, or by an infected mosquito transported into a nonmalarious region (“airport malaria”).