To evaluate the efficacy of pyrimethamine on the blood stage (suppressive prophylaxis) and liver stage (causal prophylaxis) of Plasmodium falciparum in pregnant women, in vivo and in vitro field studies were conducted in Ilorin, Nigeria, from Jan 1 to June 30, 1988. For pregnant women with P falciparum infections who received 25 mg of pyrimethamine weekly for suppressive prophylaxis, 67% (59/88) of in vivo and 60% (6/10) of in vitro tests showed pyrimethamine resistance. A second group of parasitaemic and parasite-free pregnant women was enrolled to evaluate the efficacy of pyrimethamine as a primary tissue schizonticide; after receiving a curative dose of chloroquine (25 mg/kg), half the women were given 25 mg of pyrimethamine weekly and half received no prophylaxis. Parasitologic failure rates did not differ between the pyrimethamine-treated (8/34) and the control (11/37) groups during the 16-week follow-up. Thus, pyrimethamine is not effective for suppressive or causal prophylaxis in pregnant women in Ilorin.
PIP: New studies on the suppressive and curative effects of the anti-malarial drug pyrimethamine in pregnant women from Ilorin, Nigeria showed both ineffective prophylaxis and suppression, and parasite resistance. The drug has been used in pregnant women because of its effectiveness in suppression of asexual forms of malaria infections due to Plasmodium falciparum, its long half life and its safety. 1st a group of 88 pregnant women infected with only P falciparum received 25 mg pyrimethamine weekly for 4 weeks and parasites were counted on blood smears. 67% retained parasites by Day 7, and 60% by Day 14. All were treated with curative doses of chloroquine. A 2nd group of 71 pregnant women were first treated for malaria parasites with 2 doses of chloroquine, 25 mg/kg, in 300 mg tablets, followed by weekly pyrimethamine 25 mg for 10 weeks. All subjects and controls were given iron and folic acid supplements to take daily. 24% developed parasitemia during the 10 weeks of the study, compared to 30% of the controls. The mean intervals to development of parasitemia, and the geometric mean parasite density in blood did not differ significantly. In 6 of 10 in vitro tests of parasite resistance to pyrimethamine, parasite growth was uninhibited, compared to 22 of 23 tests for resistance to chloroquine. In vivo and in vitro tests correlated well for pyrimethamine resistance. The results also indicated that primigravidae, who are more likely to harbor malaria parasites, were also more likely to fail in parasite suppression with pyrimethamine treatment. Thus pyrimethamine is not expected to reduce incidence of premature and low birth weight infants due to malaria in this area.