peripheral smear for confirmation and in order to determine both the species (possibly more
than one) and the level of parasitemia. Nonmicroscopic immunochromatographic tests such as
the Binax Now
1
Malaria Test assay are rapid and simple to perform. However, they may not
detect low parasitemias (<100 parasites/ml), and require microscopic confirmation (24).
Parasite density is clinically significant, as a quantitative relationship exists between the level
of falciparum parasitemia and mortality (<25,000 parasites/ml¼0.2% mortality; 25,000–
100,000 parasites/ml¼1.1% mortality; 100,000–500,000 parasites/ml¼14.8% mortality and
500,000 parasites/ml¼72% mortality) (25). As a frame of reference for the reader, 100,000
parasites/ml¼1% parasitemia.
The successful outcome of the patient with malaria relies upon prompt recognition and
initiation of effective therapy with a blood schizonticide to rapidly reduce parasitemia (26). For
those patients withP. falciparummalaria acquired in Central America, Haiti, the Dominican
Republic, and parts of the Middle East, oral or intravenous chloroquine may be sufficient.
However, monotherapy should only be used in areas where treatment efficacy has been
recently demonstrated and not for severe malaria (15,27). Severe malaria is a medical
emergency manifestated by prostration, impaired consciousness/coma, respiratory distress
(acidotic breathing), convulsions, circulatory collapse, pulmonary edema, acute respiratory
distress syndrome, abnormal bleeding, jaundice, severe anemia, acute renal failure, DIC,
acidosis, hemoglobinuria, and/or parasitemia>5% (28). Parenteral therapy is recommended
due to erratic absorption through the GI tract (29). Currently available treatments include
cinchona alkaloids [quinine dihydrochloride (IV/IM) or quinidine gluconate (IV only)] or
artemisinin derivatives [artesunate (IV) or artemether (IM)] (26,28).
Quinidine Gluconate
The only drug licensed in the United States for IV antimalarial therapy is quinidine gluconate,
which is typically used in combination with a second blood schizonticide (doxycycline,
tetracycline, or clindamycin) for radical cure (30). Unless the patient has received more than
40 mg/kg of quinine in the preceding 48 hours or has received mefloquine within the
preceding 12 hours, a loading dose of quinidine is used to rapidly attain effective drug levels
(31). Because quinidine use is associated with QRS widening and QTc prolongation, cardiac
monitoring is advisable. Hypotension and hypoglycemia are also associated with quinidine
use. A transition to oral therapy can be considered once the parasite density is<1% and the
patient can tolerate oral medications (quinidine course¼seven days if infection was acquired
in southeast Asia, three days if infection was acquired in Africa or South America). The second
drug (doxycycline/tetracycline/clindamycin) should continue for a total of seven days.
Artemesinins
This class of drug is not yet approved by the US FDA. However, because of their ability to
rapidly reduce levels of parasitemia (artemesinins are active against all of the erythrocytic
stages of the malaria parasite, including gametocytes), tolerability, and limited resistance,
artemesins are recommended by the World Health Organization (WHO) as first-line therapy
for uncomplicated malaria (32). In the management of severe malaria, artesunate is easier and
safer to use than quinine (33). A Cochrane review of the literature comparing artesunate with
quinine for the treatment of severe malaria concluded that in adults, treatment with artesunate
was associated with reduced parasite clearance time and significantly reduced risk of death
(relative risk, 0.62) (34). With evidence accumulating that artesuante may be superior to
quinine, the CDC issued guidance for its use by clinicians within the United States under an
investigational new drug (IND) protocol. To qualify for the protocol, patients must have severe
malaria and one of the following conditions must apply: (1) artesunate is more available than
quinidine (if the drugs are equally available, consultation with the CDC will help decide which
drug to use); (2) the patient has experienced quinidine failure or intolerance; or (3) use of
quinidine is contraindicated. To increase the availability of artesunate, the CDC has stockpiled
the drug in depots throughout the country. For details of the protocol, approval for use, and a
supply of the investigational drug on a free and emergent basis, health care providers can
telephone the CDC Malaria Hotline at 770-488-7788, Monday to Friday, 8 a.m. to 4:30 p.m.,
eastern time. At other times, clinicians should telephone 770-488-7100 and ask to speak with a
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