A combination of new screening assays for prioritization of transmission-blocking antimalarials reveals distinct dynamics of marketed and experimental drugs.

OBJECTIVES: The development of drugs to reduce malaria transmission is an important part of malaria eradication plans. We set out to develop and validate a combination of new screening assays for prioritization of transmission-blocking molecules. METHODS: We developed high-throughput assays for screening compounds against gametocytes, the parasite stages responsible for onward transmission to mosquitoes. An existing gametocyte parasitic lactate dehydrogenase (pLDH) assay was adapted for use in 384-well plates, and a novel homogeneous immunoassay to monitor the functional transition of female gametocytes into gametes was developed. A collection of 48 marketed and experimental antimalarials was screened and subsequently tested for impact on sporogony in Anopheles mosquitoes, to directly quantify the transmission-blocking properties of antimalarials in relation to their effects on gametocyte pLDH activity or gametogenesis. RESULTS AND CONCLUSIONS: The novel screening assays revealed distinct stage-specific kinetics and dynamics of drug effects. Peroxides showed the most potent transmission-blocking effects, with an intermediate speed of action and IC50 values that were 20-40-fold higher than the IC50s against the asexual stages causing clinical malaria. Finally, the novel synthetic peroxide OZ439 appeared to be a promising drug candidate as it exerted gametocytocidal and transmission-blocking effects at clinically relevant concentrations.

Biocompatibility of glass-encapsulated electronic chips (transponders) used for the identification of pigs.

The biocompatibility of electronic transponders encapsulated in two different types of glass was studied after they had been implanted subcutaneously into pigs for the purpose of identification. Rods of white crystal glass or green iron-containing glass were screened for superficial impurities by scanning electron microscopy and X-ray analysis, revealing a few crystalline and plaque impurities which were similar for both types of glass, and no differences in elemental composition. In vitro cytotoxicity tests using cell cultures of human dermal fibroblasts and haemolysis and clot formation tests in human blood after contact with the rods, showed that both types of glass were biocompatible. When implanted subcutaneously at the base of the ears of pigs for from three to 150 days, both types of transponder appeared to induce a similar connective tissue capsule, on average less than 0.2 mm in thickness, surrounding the rods. A classic foreign body reaction did not occur. It is concluded that the fibrous capsules were due to scar tissue formed around the glass rods as a result of the tissue being damaged when they were implanted. There were no significant differences between the reactions to the two types of glass. The subcutaneous implantation of glass-encapsulated transponders appears to be a good method for identifying pigs.