Chapter 35: Chemotherapy of Malaria
A physician is planning to treat a 27-year-old woman with primaquine for a documented P. vivax infection. Prior to beginning treatment the physician must test the patient for
a. elevated serum amylase.
b. glucose-6-phosphate dehydrogenase deficiency.
d. elevated serum calcium.
e. vitamin B12 deficiency.
Answer is b. Primaquine may cause acute hemolysis and hemolytic anemia in humans with G6PD deficiency. More than 400 genetic variants of G6PD deficiency produce a variable response to oxidative stress. About 11% of African-Americans have a variant of G6PD deficiency; primaquine-induced hemolysis can be even more severe in white ethnic groups, including Sardinians, Sephardic Jews, Greeks, and Iranians as these populations have a G6PD variant in which 2 amino acid substitutions impair both enzyme stability and activity.
A 35-year-old man will be traveling to an area that is endemic for malaria. His physician starts him on an oral artemisinin derivative prior to his trip. This drug is likely to be ineffective as chemoprophylactic therapy because
a. it is effective against only the blood stages of P. falciparum.
b. its side effects are so severe that compliance is unlikely.
c. it is likely to have cross-resistance with chloroquine.
d. its active metabolite dihydroartemisinin has a short plasma t½.
e. its effectiveness after oral administration is poor.
Answer is d. Artemisinins have a relatively short plasma t½ that makes them unsuitable for prophylactic therapy.
A 42-year-old man is being treated with atovaquone-proguanil for uncomplicated P. falciparum malaria. This combination product is preferred to the use of atovaquone alone because
a. there is a reduced risk of resistance.
b. proguanil improves the absorption of atovaquone.
c. proguanil decreases the clearance of atovaquone.
d. proguanil decreases the side effects of atovaquone.
e. atovaquone improves the absorption of proguanil.
Answer is a. Resistance to atovaquone alone in P. falciparum develops easily and it is conferred by a nucleotide polymorphisms in the cytochrome b gene located in the parasite’s mitochondrial genome. These polymorphyisms appear to affect atovaquone binding. The addition of proguanil markedly reduces the frequency of appearance of atovaquone-resistance.