We have attempted to provide a rational basis for improving the protocols for chemotherapy of malaria. We model the regression of parasitaemia by Plasmodium falciparum, its subsequent elimination from the body, or recrudescence, for populations of cells treated with chloroquine. Our model assumes that the drug forms a complex with some receptor in the parasite and that parasites possessing this complex die at a defined rate. We take into account that chloroquine is eliminated exponentially from the body. We show how the parameters of the model can be derived from observations in the field. The model correctly predicts the effects of drug dose, degree of initial parasitaemia, rate of parasite multiplication and degree of drug resistance to chloroquine chemotherapy. The level of parasitaemia will reduce to a minimum at sufficiently high concentrations of chloroquine, but only if the parasitaemia is reduced to below that of 1 parasite per infected person will a cure of malaria be obtained. Otherwise, recrudescence will, sooner or later, occur. We show that, even for drug-resistant malaria, if 2 doses of chloroquine are given to a patient with an interval of some 10 days between them, parasites can be eliminated from the body without toxic levels of chloroquine being reached.

Sera from donors exposed to malaria were tested for their ability to block the transmission of isolates from Cameroonian Plasmodium falciparum gametocyte carriers. Sera were selected from amongst Cameroonian and Gambian donors who had positive antibody reactivity against the surface of activated gametes and against epitopes of Pfs 48/45 (a potential transmission-blocking vaccine candidate antigen). Aliquots of washed blood from gametocyte carriers were resuspended in test and control sera and fed to An. gambiae mosquitoes via a membrane feeder. Comparisons of the prevalence and intensity of infections in dissected mosquitoes showed variations in the ability of sera to block the transmission of the different isolates. Sera were identified that had little or no blocking effect on the transmission of isolates unless the isolate was poorly infectious. Some sera completely blocked the transmission of some isolates whilst having little or no effect on others. The observed variation in transmission-modulating activity may have implications for the development of a transmission-blocking vaccine.

In laboratory experiments, the swimming behaviour of the ectoparasite Argulus foliaceus and its infection rates on juvenile perch (Perca fluviatilis) and roach (Rutilus rutilus) were examined. The highest infection rate and a preference for perch juveniles were obtained in darkness, the lowest infection rate and a lack of preference in the light, when aquaria with glass walls (high reflectivity) were used. In the light, when aquaria were lined with black plastic (low reflectivity) an intermediate level of infection for perch and the highest for roach was recorded. Under such conditions roach were significantly more heavily infected than perch; an attack rate 4 times greater was recorded for brighter (more reflective) roach juveniles than for perch. Within the aquaria with a low reflective interior parasites swam 4·4 times slower and were observed predominantly in the central area, while in the highly reflective aquaria fast swimming A. foliaceus were recorded mainly near the walls. The primary role of visual stimuli for the host search behaviour of A. foliaceus in the light is suggested. Parasites can effectively use such stimuli only in the low reflective surroundings. Highly reflective glass aquarium walls produce numerous secondary local light sources, which cause fast, erratic parasite movements and prevent the efficient location of potential hosts.

We investigated the influence of infection by the trematode Curtuteria australis on the burrowing behaviour of its intermediate host, the bivalve Austrovenus stutchburyi. Laboratory experiments and field observations revealed that cockles, unable to bury completely or even partially under the sediment, have a reduced foot length compared with buried individuals. The ability to bury proved to be highly repeatable in field experiments: cockles found at the surface and transplanted to an experimental area did not bury themselves, and cockles found buried stayed buried when relocated. All metacercariae of C. australis were found strictly in the foot and for each of 3 samples collected in different sites, there was a negative and significant relationship between the relative length of the foot and the parasite load. A predation test conducted under natural conditions indicated that cockles with the stunted foot and the altered behaviour are significantly more susceptible to predation by aquatic birds than other cockles. Given that the definitive host of C. australis is an oystercatcher, we first discuss our results in the context of transmission strategy. Comparisons with other studies on more or less related trematode species parasitic in bivalves and evolving under similar constraints for their transmission, shed light on the origin of this adaptation in C. australis.

Light and electron microscopy were used to study the ultrastructure of the cement apparatus, namely cement glands and cement ducts of mature specimens of the acanthocephalan parasite Pomphorhynchus laevis Müller, 1776, recovered from the digestive tracts of fish Leuciscus cephalus Risso, 1826. In addition, the cement glands of immature P. laevis found within the body cavity of the fish Alburnus alburnus alborella De Filippi, 1844 were examined. In a mature male of P. laevis the 6 cement glands are rounded to oval in shape and each of them has an outer cytoplasmic layer containing nuclei and surrounding a space for storage of the cement material within the gland. The nuclei have an irregular outline and the cytoplasm of the cells contains round, membrane-bound secretory granules approximately 1 μm in diameter. Nuclei surrounded by secretory granules were present inside the gland lumen. Within the gland ducts of mature males, granules were present within the wall thickness and, inside the luminal area, mitochondria were encountered. In contrast, within the cement glands of immature P. laevis there were no secretory granules and the chromatin of the nuclei appeared condensed. The nature of the secretory product of the cement glands was investigated with histological and electrophoretic methods. A protein with molecular weight of 23 kDa was recorded as a major component of cement.

The effects of dietary protein and zinc restrictions on Heligmosomoides polygyrus were compared following primary and challenge infection in female BALB/c mice fed either control (24%), marginal (7%) or low (3%) protein combined with either high or low zinc (60 or 3 mg Zn/kg diet). Dietary protein restriction (3%) resulted in significantly lower body weight gain. As well, blood urea nitrogen (BUN) significantly decreased with decreasing dietary protein level. However, neither plasma albumin concentration nor relative thymus or spleen weights were reduced. Marginal zinc deficiency was confirmed by significantly lower tibia and liver zinc concentration, but food intake, body weight gain, relative thymus and spleen weights, and alkaline phosphatase activity were not altered. On day 29 post-primary infection, worm burdens were significantly higher in mice fed either marginal or low protein and in mice fed a low zinc diet, while parasite egg output was significantly higher in mice fed both low protein and low zinc diets. Immune status was compromised in mice fed low protein (significantly lower serum IgG1 and lower eosinophilia), and in mice fed low zinc diet (significantly lower eosinophilia). Early in the infection, IgE titres were elevated in mice fed low protein or low zinc, but IgE titres declined to levels lower than the control diet groups after 14–21 days. On day 29 post-challenge infection, worm burdens and parasite egg output were significantly higher in mice fed low protein, whereas the other groups had expelled almost all parasites. Dietary restriction had no effect on serum IgE. Significantly reduced serum IgG1 titres and eosinophilia in mice fed 3% protein supported the view that low dietary protein but not low zinc increased host susceptibility to H. polygyrus by compromising host immune function following reinfection in immunized mice.

The kinetics of serum antibody response against infection with Echinococcus multilocularis eggs was evaluated in AKR mice. The animals were infected by oral inoculation with 300 parasite eggs, and necropsied at 1, 2, 4, 6, 9, 12 and 16 weeks post-infection (p.i.), respectively. The parasite formed the laminated layer at 4 weeks p.i., the brood capsule with a massive proliferation of germinal cells at 9 weeks p.i. and protoscoleces at 16 weeks p.i. Serum antibody responses of the mice to antigen preparations from metacestodes of different stages and protoscoleces were evaluated by ELISA, immunoblotting and immunohistochemistry. In ELISA, the antibody responses began to increase at 4 weeks and became more apparent at 9 weeks p.i. and thereafter. Immunoblots using sera collected at 16 weeks p.i. showed some common bands among the 3 different antigen preparations. In addition to this, the germinal cells and brood capsules of mature metacestodes were stained strongly in an immunohistochemical study. From above, it is suggested that some antigen molecules are expressed in the parasite through these stages and stimulated host antibody responses.

Electrophysiological and pharmacological techniques were used to study glutamatergic signalling in the parasitic nematode, Ascaris suum. Glutamate or kainate injections into whole worms produced a paralysed quasi-static posture similar to the waveform in behaving worms. The DE2 motorneuron class is a primary target. Several glutamatergic substances produced pronounced conductance increases and depolarization in DE2; domoate and kainate were the most potent agonists tested. Glutamate responses and spontaneous excitatory post-synaptic potentials in DE2 were reversibly blocked in sodium-free saline. DE2 sensitivity to exogenous glutamate was sustained during block of synaptic transmission suggesting that glutamatergic receptors are located on DE2 neurons. The glutamate-induced response was localized to the DE2 dendrite, coincident with the synapses responsible for spontaneous potentials in DE2. Steady-state potentials reached during glutamate superfusion were similar to the reversal potentials for both the spontaneous post-synaptic potentials and glutamate, also suggesting that these potentials may be glutamatergic. Non-N-methyl-D-aspartate receptor antagonists partially blocked spontaneous DE2 excitatory potentials and responses elicited by exogenous glutamate and kainate. This glutamatergic pathway may play a role in nematode locomotory behaviour and account for the paralysing anthelmintic action of excitatory amino acid analogues like kainate and domoate.

Electrophysiological and pharmacological experiments suggest the presence of an electrogenic glutamate transporter in the motornervous system of the parasitic nematode Ascaris suum. This putative transporter occurs in hypodermis (a tissue in some respects analogous to glia) and in DE2 motorneurons, a dorsal excitatory motorneuron class which receives excitatory glutamatergic post-synaptic potentials. Glutamate application to hypodermis produced non-conductance mediated depolarizations that were smaller in amplitude and slower in rate of rise than DE2 responses where a glutamate-activated conductance occurs. The hypodermal response is sodium dependent and calcium independent. Excitatory amino acid ionotropic receptor agonists (kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid and N-methyl-D-aspartate) were ineffective in eliciting hypodermal responses. The ionotropic receptor antagonist, 6,7-dinitroquinoline-2,3-dione, had no effect on hypodermal glutamate responses. The L- and D-forms of glutamate, aspartate and homocysteate produced hypodermal and DE2 depolarizations consistent with the pharmacological profile for glutamate transporters in other systems. Glutamate transport inhibitors (L-trans-pyrrolidine-2,4-dicarboxylate and beta-hydroxyaspartate) elicited electrogenic depolarizations in hypodermis and DE2. These results suggest that the hypodermal glutamate response has an electrogenic transporter component, while the DE2 response has 2 components, one conductance-mediated and the other due to an electrogenic transporter.