In vitro drug response of Plasmodium falciparum in the Philippines: increased resistance to amodiaquine.

A long term study was carried out at San Lazaro Hospital, Manila, Philippines, monitoring the in vitro response of Plasmodium falciparum to chloroquine, amodiaquine, mefloquine, and quinine. The in vitro effective dose giving 50% inhibition of schizogony was: 0.68 X 10(-6) M/liter blood for chloroquine; 0.18 X 10(-6) for amodiaquine; 0.2 X 10(-6) for mefloquine; and 1.12 X 10(-6) for quinine. The percent of isolates determined to be resistant in vitro was 85.2% for chloroquine, and 1.2% for both mefloquine and quinine. These figures were relatively unchanged over the course of 3 years studied. The in vitro resistance rate to amodiaquine increased from 5.1% in 1982 to 22.2% in 1984.

Chloroquine resistant Plasmodium falciparum: effect of rabbit serum and incubation time on the in vitro (microtechnique) prediction of in vivo resistance.

A study of chloroquine resistance of 54 isolates of Plasmodium falciparum is reported. Sixty-four percent of the isolates tested produced schizonts in vitro (micro-technique), whereas the remaining 36 percent did not. The accuracy of the in vitro test to predict in vivo resistance was increased when the primary parasite isolates were cultured in the presence of rabbit serum and when the cultures were allowed to incubate for more than 48 hours. Thirteen isolates of P. falciparum that showed in vitro resistance were confirmed in vivo resistant. Eleven of these cases were identified as R-I and two as R-II. Only one case of in vivo resistance (R-II) was observed among the 19 isolates that failed to produce schizonts in vitro.

Chloroquine and quinine resistant Plasmodium falciparum on the island of Mindoro, Philippines, 1982.

A field study was conducted on the island of Mindoro, Republic of the Philippines in which over 800 persons were screened for malaria and approximately 8% were found positive. The in vitro microtechnique was used to test for sensitivity to chloroquine, amodiaquine, mefloquine and quinine in 20 slide-confirmed P. falciparum cases. Sixteen of these cases were also followed for in vivo chloroquine sensitivity. Four cases showed in vitro resistance to chloroquine; 2 also showed resistance to quinine. All showed in vitro sensitivity to mefloquine and amodiaquine. The results of in vivo test were consistent with either a sensitive (S) or R-1, resistant response to chloroquine. Taken together, the in vitro and in vivo chloroquine tests indicate 4 cases of chloroquine resistance at the R1 level.

Cerebral malaria at San Lazaro Hospital, Manila, Philippines.

Forty cases of cerebral Plasmodium falciparum malaria seen at San Lazaro Hospital, Manila, Philippines from 1979-1981 were reviewed. These cases represented 7% of all Plasmodium falciparum cases seen during this period. All of the patients had fever and headache, 73% confusion, 70% chills, 68% jaundice or abdominal pain, 60% sweats. Findings more frequent in the fatal compared to the non-fatal cases were: the presence of schizonts in the peripheral smear, oliguria, coma, convulsions, urinary incontinence, jaundice, pulmonary symptoms and vomiting. Fatal cases were less likely to be clinically diagnosed as malaria and more likely to be diagnosed as hepatitis than malaria. The treatment and management of these cases is discussed.