Safety and immunogenicity of a three-component blood-stage malaria vaccine in adults living in an endemic area of Papua New Guinea.

A Phase I safety and immunogenicity study with a three-component blood-stage malaria vaccine was conducted in adult male subjects living in an endemic area of Papua New Guinea. The preparations were recombinant proteins which corresponded to parts of the two merozoite surface proteins of Plasmodium falciparum (MSP1 and 2), and of the ring-infected erythrocyte surface antigen (RESA). The three proteins were emulsified with the adjuvant Montanide ISA720. Ten subjects were injected twice (four weeks apart) with the vaccine formulation and two with the adjuvant alone. Mild pain at the site of injection was reported by about half of the subjects but no systemic reaction related to the formulation occurred. There was a sharp rise in geometric mean stimulation index after the second dose compared to baseline for MSP1 and RESA, while the rise was small for MSP2. Geometric mean antibody titres increased for MSP1 during the study, whereas they hardly changed for MSP2 and RESA. The vaccine formulation was safe when used in an already immune population. The vaccine induced good cellular responses, especially for MSP1 and RESA. Boosting of humoral responses was weak, probably because of high baseline antibody levels.

Mefloquine in the Prophylaxis of P. Falciparum Malaria.

Background: The objectives of this study were (1) to compare the efficacy of Lariam (mefloquine) with that of Fansimef (mefloquine, sulfadoxine, and pyrimethamine), Fansidar (sulfadoxine and pyrimethamine), chloroquine, and placebo in suppressing asexual parasitemia in semi-immune persons living in an area endemic for Plasmodium falciparum malaria; and (2) to compare the tolerance of these drugs when taken over a prolonged period of time. Method: A randomized double-blind comparative placebo-controlled study was undertaken in the village of Biasso, 60 km from Abidjan in the southern part of the Ivory Coast, a region where P. falciparum malaria is endemic. Four hundred and ninety nine male volunteers (five parallel groups), who were inhabitants of Biasso, were involved. The main outcome measures concerned the incidence of malaria breakthroughs (acute malaria attacks) and the incidence of parasitemia. Results: Within this strictly defined epidemiologic context, prophylaxis, taken once weekly, proved to be fully protective (parasitic index: 0) in the Lariam, Fansidar, and Fansimef groups throughout the whole study period. Prophylaxis with chloroquine proved incompletely protective (parasitic index: 2.5) The most frequent side effects were pruritus (5.6%), diarrhea (1.2%) and headache (0.06%). No significant differences in the incidence of side effects in each group (chi-square test) was observed. All side effects were transient and judged to be mild by the investigators. Conclusions: Excellent efficacy was observed in the prophylaxis of P. falciparum malaria with Lariam, Fansidar, and Fansimef as compared to the partial protection provided by chloroquine. Safety and tolerance were comparable in all groups during the whole period of observation (5 months).

Mefloquine prophylaxis: an overview of spontaneous reports of severe psychiatric reactions and convulsions.

Since the time of its introduction in 1985, mefloquine (Lariam) has been used extensively for malaria prophylaxis. The international Drug Safety Department of the manufacturer gathered all spontaneous adverse drug reactions reported in association with this drug from all available sources and monitored the literature on a world-wide basis. The serious neurologic and psychiatric adverse events reported in association with Lariam prophylaxis from the time of introduction until May 1991 were reviewed. During this time, 59 serious neurologic and psychiatric adverse reactions were reported as follows: 26 convulsions, 12 depressions, 20 psychotic episodes, and one toxic encephalopathy; none were fatal. While spontaneous reporting systems are biased by under-reporting, they provide useful instruments for analysis of clinical risks factors. The neurologic and psychiatric adverse events reported in association with mefloquine prophylaxis were of the same types as those reported with other quinine derivative antimalarials. The precise mechanism of serious neurologic and psychiatric reactions is unknown. The only patient population identified at this time as having an increased risk of developing these serious reactions to mefloquine are persons with a history of seizures or manic-depressive illness. Mefloquine prophylaxis should not be prescribed to such patients.