The survival characteristics of free-living cercarial populations of Transversotrema patialensis were described and shown to be age-dependent. The maximum life-span was found to be 44 h with a 50% survival at 26 h. Activity and infectivity of the larvae were also characterized by age-dependence, and were demonstrated to be closely correlated with one another. For individual cercariae, both activity and infectivity had dropped to extremely low levels many hours before death occurred. An attempt was made to interrelate activity and infectivity, in a theoretical manner, with the availability of energy reserves.Conceptual understanding of the biological processes involved was aided by the formulation of simple mathematical models.

The bioactivity of an ethyl acetate extract of ginger (Zingiber officinale) towards Schistosoma mansoni adult pairs, both cultured in vitro and in vivo in laboratory mice, was investigated by monitoring worm mortality and fecundity. In vitro, a concentration of 200 mg l(-1) of extract killed almost all worms within 24 h. Male worms seemed more susceptible than female under these conditions. Cumulative egg output of surviving worm pairs in vitro was considerably reduced when exposed to the extract. For example, after 4 days of exposure to 50 mg l(-1), cumulative egg output was only 0.38 eggs per worm pair compared with 36.35 for untreated worms. In vivo efficacy of the extract was tested by oral and subcutaneous delivery of 150 mg kg(-1) followed by assessment of worm survival and fecundity. Neither delivery route produced any significant reduction in worm numbers compared with untreated controls. Worm fecundity was assessed in vivo by cumulative egg counts per liver at 55 days post infection with mice treated subcutaneously. Such infections showed egg levels in the liver of about 2000 eggs per worm pair in 55 days, in both treated and control mice, with no significant difference between the two groups. To ensure that density-dependent effects did not confound this analysis, a separate experiment demonstrated no such influence on egg output per worm pair, at intensities between 1 and 23 worms per mouse.

Schistosoma mansoni infection in mice has been fingerprinted using CE to study the capabilities of this technique as a diagnostic tool for this parasitic disease. Two modes of separation were used in generating the electrophoretic data, with each untreated urine sample the following methods were applied: (i) a fused-silica capillary, operating with an applied potential of 18 kV, in micellar EKC (MEKC) and (ii) a polyacrylamide-coated capillary, operating with an applied potential of -20 kV under zonal CZE conditions. By combining normal and reverse polarities in the data treatment we have extracted more information from the samples, which is a better approach for CE metabolomics. The traditional problems associated with variability in electrophoretic peak migration times for analytes were countered by using a dynamic programming algorithm for the electropherograms alignment. Principal component analyses of these aligned electropherograms and partial least square discriminant analysis (PLS-DA) data are shown to provide a valuable means of rapid and sample classification. This approach may become an important tool for the identification of biomarkers, diagnosis and disease surveillance.

No abstract

2,4-Disubstituted quinolines with additional substituents in positions 5-8 have been found to have anthelmintic properties. A number of 2,4-dimethoxy-6- or 8-arylquinolines have potent activity against the sheep nematode Haemonchus contortus, with LD99 values of the same order of magnitude as levamisole. These arylquinolines maintain their activity against levamisole-, ivermectin- and thiabendazole-resistant strains of H. contortus.

Phytochemical studies using a range of chromatographic and spectroscopic techniques coupled with in vitro bioassays against larval Schistosoma mansoni, L4 larvae of Ostertagia circumcincta, and adults and larvae of Caenorhabditis elegans have led to the isolation of an active anthelmintic compound in the Chinese medicinal plant Evodia rutaecarpa (Rutaceae) and its identification as atanine (3-dimethylallyl-4-methoxy-2-quinolone). Atanine has not previously been found to possess antiparasitic activity.

Franz cells (2-chambered, air/fluid phase static diffusion devices, previously used for the study of drugs across viable human skin) are utilized for the first time to investigate the process of infection of human skin by Schistosoma mansoni cercariae. Skin obtained from cosmetic surgery sources was used in the Franz cells to describe the temporal dynamics of the early interaction of cercariae with skin. At 38 degrees C, about 50% of cercariae applied in water to the epidermal surface of the skin were irreversibly attached within 1 min and after 5 min about 85%, were similarly irrecoverable. The technique also provides the means of following the early penetration path of cercariae by histological methods. Franz cell results on the dynamics of attachment/early penetration have been compared with those obtained using artificial skin equivalents and non-human mammalian skin models in the context of the physical and chemical differences between these systems and viable human skin. It is concluded that Franz cells provide a convenient system for directly investigating the early phases of S. mansoni cercariae interaction with human skin.

SummaryThe number of cercariae of Transversotrema patialense which attach to the fish host Brachydanio rerio, during a fixed exposure period, is shown to be directly proportional to cercarial density within an experimental infection arena. The distribution of successful infections/host is shown to change from a random pattern to an over-dispersed form as cercarial exposure density or duration of host exposure to infection increases. A stochastic simulation model is used to demonstrate that small differences in host susceptibility to infection, within a population of hosts, can generate patterns of dispersion in parasite numbers/host similar to those observed in the experimental studies. Differences in host behaviour, during the period of exposure to infection, are thought to generate variability in host susceptibility to cercarial infection.