Page 931 - Basic _ Clinical Pharmacology ( PDFDrive )

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Antiprotozoal Drugs

Philip J. Rosenthal, MD

C ASE STUD Y

A 5-year-old American girl presents with a 1-week history of and diagnosed with a viral syndrome. Examination reveals
intermittent chills, fever, and sweats. She had returned home a lethargic child, with a temperature of 39.8°C (103.6°F) and
2 weeks earlier after leaving the USA for the first time to spend splenomegaly. She has no skin rash or lymphadenopathy. Ini-
3 weeks with her grandparents in Nigeria. She received all tial laboratory studies are remarkable for hematocrit 29.8%,
3
standard childhood immunizations, but no additional treat- platelets 45,000/mm , creatinine 2.5 mg/dL (220 μmol/L), and
ment before travel, since her parents have returned to their mildly elevated bilirubin and transaminases. A blood smear
native Nigeria frequently without medical consequences. shows ring forms of Plasmodium falciparum at 1.5% parasit-
Three days ago, the child was seen in an outpatient clinic emia. What treatment should be started?

■ MALARIA infection of many erythrocytes and serious disease. Sexual stage
gametocytes also develop in erythrocytes before being taken up by
Malaria is the most important parasitic disease of humans and mosquitoes, where they develop into infective sporozoites.
causes hundreds of millions of illnesses per year. Four species In P falciparum and P malariae infection, only one cycle of liver
of plasmodium typically cause human malaria: Plasmodium cell invasion and multiplication occurs, and liver infection ceases
falciparum, P vivax, P malariae, and P ovale. A fifth species, spontaneously in less than 4 weeks. Thus, treatment that elimi-
P knowlesi, is primarily a pathogen of monkeys but has recently nates erythrocytic parasites will cure these infections. In P vivax
been recognized to cause illness, including severe disease, in and P ovale infections, a dormant hepatic stage, the hypnozoite, is
humans in Asia. Although all of the latter species may cause not eradicated by most drugs, and relapses can occur after therapy
significant illness, P falciparum is responsible for the majority of directed against erythrocytic parasites. Eradication of both erythro-
serious complications and deaths. Drug resistance is an important cytic and hepatic parasites is required to cure these infections.
therapeutic problem, most notably with P falciparum.

DRUG CLASSIFICATION
PARASITE LIFE CYCLE
Several classes of antimalarial drugs are available (Table 52–1 and
An anopheline mosquito inoculates plasmodium sporozoites to Figure 52–2). Drugs that eliminate developing or dormant liver
initiate human infection (Figure 52–1). Circulating sporozoites forms are called tissue schizonticides; those that act on erythro-
rapidly invade liver cells, and exoerythrocytic stage tissue schizonts cytic parasites are blood schizonticides; and those that kill sexual
mature in the liver. Merozoites are subsequently released from stages and prevent transmission to mosquitoes are gametocides.
the liver and invade erythrocytes. Only erythrocytic parasites No single available agent can reliably effect a radical cure, ie,
cause clinical illness. Repeated cycles of infection can lead to the eliminate both hepatic and erythrocytic stages. Few available

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