Mefloquine sulfadoxine pyrimethamine (MSP) combination delays in vitro emergence of mefloquine resistance in multiple drug resistant Plasmodium falciparum.

Sulfadoxine-pyrimethamine-resistant and chloroquine resistant, but mefloquine sensitive (MIC 5 x 10(-9] isolates of Plasmodium falciparum were used to study the emergence of mefloquine resistance. The continuously cultured isolates which were exposed intermittantly to varying concentrations of mefloquine alone became insensitive to the drug at 1 x 10(-7) M after 12 months, whereas the culture line exposed to the combination of mefloquine, sulfadoxine and pyrimethamine became only slightly insensitive to mefloquine (MIC 2 x 10(-8]. Thus, the efficacy of mefloquine may be prolonged through use in combination with sulfadoxine-pyrimethamine.

Development of in vitro microtest for the assessment of Plasmodium vivax sensitivity to chloroquine.

An in vitro microtest to assess P. vivax sensitivity to chloroquine has been developed using a medium mixture which contained RPMI, Waymouth (GIBCO) and 15% (vol/vol) human serum group AB. The rate of success was highest in samples which were not washed by centrifugation before culturing in microtest plates predosed with varying concentrations of chloroquine. Evaluation of the effective concentration of chloroquine using a program for probit analysis of log dose/response test proved superior to simply using the percentage of schizont maturation.

Flunarizine and verapamil inhibit chloroquine-resistant Plasmodium falciparum growth in vitro.

Using pharmacological properties in relation to the biochemistry of P. falciparum, verapamil, flunarizine, and chlorpromazine which are calcium blockers were selected to test for their antimalarial activity against P. falciparum in vitro. Results revealed that the drugs inhibited parasite population growth in the following order of IC50: verapamil 1 X 10(-6) M, chlorpromazine 3.5 X 10(-6) M, and flunarizine 5 X 10(-6) M. These three calcium blockers have antimalarial effects on chloroquine resistant parasite (alone T9/94) but are less potent when compared with the efficacy of quinine or mefloquine in vitro.

In vitro sensitivity of Plasmodium falciparum to sulfadoxine and pyrimethamine.

An in vitro microtechnique of Rieckmann et al., (1978) modified by Yisunsri and Rieckmann (1980) using 3 media; Waymouth, Waymouth plus 10% human serum, and RPMI was assessed to determine the sensitivity of P. falciparum to sulfadoxine, pyrimethamine and its combination. The study confirmed the synergism between sulfadoxine and pyrimethamine. There was no interaction between media and drug tested. MIC1 and MIC2 of sulfadoxine in different media showed significant difference (p less than 0.001). No significant difference was observed in MIC1 and MIC2 of pyrimethamine in the three media used (p greater than 0.05). For sulfadoxine-pyrimethamine combination, MIC1 and MIC2 in Waymouth alone and plus 10% human serum showed no significance (p greater than 0.05) while in RPMI showed positive correlation (p less than 0.001). MIC1 might be more applicable for clinical evaluation than MIC2. At present Waymouth medium with 5% patient serum, is considered to be the most suitable for testing sensitivity of malarial parasites.

Mefloquine-pyrimethamine-sulfadoxine combination delays emergence of mefloquine resistant Plasmodium falciparum in continuous culture.

The efficacy of mefloquine against Plasmodium falciparum in continuous culture was studied. The development of mefloquine resistance in P. falciparum was significantly inhibited by a combination of mefloquine, pyrimethamine and sulfadoxine. By contrast, more resistant variants were selected in continuous culture without drug pressure or with pyrimethamine-sulfadoxine pressure. The most mefloquine resistant variants were selected by step-wise increases in mefloquine pressure.

Studies on susceptibility of Pila ampullacea, to the infection with the rat lungworm, Angiostrongylus cantonensis.

Experimental infections of Pila ampullacea with first stage larvae of Angiostrongylus cantonensis were carried out to determine susceptibility of this molluscan host in relation to dose level and snail host size. Snails were divided into 3 size groups and exposed to A. cantonensis first stage larval suspensions of varying concentrations. The results showed that overall, about 20% of larvae ingested by the snails developed into infective third stage larvae, but the percentage was inversely related to both the number of larvae to which snails were exposed and snail weight. The infective worms were concentrated in the foot muscle and mantle of the molluscan host.

Growth and localization of Angiostrongylus cantonensis in the molluscan host, Achatina fulica.

The development of the rat lung worm Angiostrongylus cantonensis within the giant African snail Achatina fulica is reported. In this host, ingested first stage larvae penetrate the intestinal wall into the hemocoel and migrate to the mantle where they undergo two molts and become third stage larvae within 24 days. The mantle, harboring 85% of the total number recovered is the major location of infective larvae. The kidney contains about 11% but few larvae are found in the remaining visceral organs. Host response consists of encapsulation; destruction by means of phagocytosis was not observed.