The emergence of resistance to artemisinins and the renewed efforts to eradicate malaria demand the urgent development of new drugs. In this endeavour, the evaluation of efficacy in animal models is often a go/no go decision assay in drug discovery. This important role relies on the capability of animal models to assess the disposition, toxicology and efficacy of drugs in a single test. Although the relative merits of each efficacy model of malaria as human surrogate have been extensively discussed, there are no critical analyses on the use of such models in current drug discovery. In this article, we intend to analyse how efficacy models are used to discover new antimalarial drugs. Our analysis indicates that testing drug efficacy is often the last assay in each discovery stage and the experimental designs utilized are not optimized to expedite decision-making and inform clinical development. In light of this analysis, we propose new ways to accelerate drug discovery using efficacy models.

In 1950 the author published a paper entitled ‘The Mites (Acarina) parasitic on Mammals, Birds and Reptiles’ in which it was stated that the subject of feather mites (Analgesidae) was too big to be included in that work, and though they were parasitic throughout their life upon the host or in the quills of the feathers they should be made the subject of a separate paper.

The study of malaria in the laboratory relies on either the in vitro culture of human parasites, or the use of non-human malaria parasites in laboratory animals. In this review, we address the use of non-human primate malaria parasite species (NHPMPs) in laboratory research. We describe the features of the most commonly used NHPMPs, review their contribution to our understanding of malaria to date, and discuss their potential contribution to future studies.

The inflammatory responses to lymphatic filariae and to Onchocerca volvulus are reviewed with particular attention to (1) evolutionary biology; (2) inflammatory host spectrum; (3) non-specific components; (4) immunoregulation; (5) immune evasion versus immunomodulation; (6) chronic tissue damage and scarring and (7) disease models. Basic principles of pathogenesis are emphasized, comparisons drawn with schistosome infection, and critical items of missing information are highlighted.

An ultrastructural study has been performed on radiation-attenuated parasites fixed in situ during their extended stay in the lungs. At day 7 post-infection all parasites were located within blood vessels. In contrast to normally migrating parasites, at days 13 and 21 post-infection the majority of radiation-attenuated parasites were lying free within alveoli. As far as could be seen, radiation-attenuated parasites had undergone the normal develop mental changes associated with the lung stage of migration. These included elongation of the body and loss of mid-body spines and the fibrous layer beneath the tegument. No ultrastructural evidence was found to suggest why schistosomula failed to migrate further and instead burst into alveoli. No parasites observed on day 7 post-infection were associated with a host inflammatory reaction. At day 13, inflammation was noticeable but could have been a response as much to pulmonary tissue damage as to the presence of parasites. At day 21 post-infection some parasites were internally disrupted but were not associated with host inflammatory reactions and had intact tegumental surfaces – all facts consistent with death by autophagy. One parasite was observed at day 21 with an adherent neutrophil infiltrate and extensive tegumental damage. The relevance of persisting lung-stage parasites to the induction of resistance to challenge is discussed.

An account is given of the technique and interpretation of a test which can be used for the detection of anthelmintics active against threadworm (Enterobius) in man and a number of the helminth infections in herbivorous animals.

It can also be used for the qualitative comparison of active compounds.

It has been used to investigate some of the fundamental practices in the use of anthelmintics—the results of which are to be published elsewhere.

The cytotoxicity of normal rat spleen cells to antibody-coated Trypanosoma cruzi epimastigotes has been studied by assaying the release of [3H]-labelled macromolecules from the parasites. The release of thymidine (DNA) is slower than the release of uridine (RNA), suggesting that the nucleus is broken down more slowly than the cytoplasmic membrane. Less than 50% of the leucine (protein) is released when the parasites are lysed, whereas uridine (RNA) is almost totally released. In practical terms these results show that the release of incorporated radioisotope-labelled uridine can be used as a sensitive assay for cytotoxicity of T. cruzi. Cytotoxicity by normal rat spleen cells is antibody dependent and proportional to the logarithm of effector cell number. The lag phase and the rate of RNA release is not altered by centrifuging the parasites and effector cells to enhance contacts between them.

Toxoplasma gondii has a unique enzyme, a NTPase, which has a wide specificity toward NTP. In the present study, we produced a monoclonal antibody (IgG1, 6C6) against the enzyme which could recognize NTPase isozymes among several strains of T. gondii. Three avirulent strains of T. gondii, ME49, Beverley and Nakayama, were found to have 1 NTPase (63kDa, pI 6·0), while a virulent strain RH and an avirulent strain Fukaya had 2 isozymes (63kDa) with different pIs (pIs 6·0 and 6·5 for the former, and pIs 6·2 and 6·4 for the latter, respectively), suggesting that this monoclonal antibody recognizes a common epitope of NTPase among T. gondii strains. Furthermore, 6C6 could inhibit NTPase activity in the presence of dithiothreitol in a dose-dependent manner, and immuno-EM study of NTPase revealed that this molecule is located on the surface membrane of T. gondii tachyzoites. When Vero cells were co-cultured with tachyzoites pre-treated with 6C6, the number of infected cells significantly decreased, suggesting that 6C6 inhibits invasion of the parasites to host cells. These data suggest that the molecule recognized by 6C6 might be considered a potential candidate antigen for vaccines against T. gondii tachyzoites.

The genus Apelma was erected by Kieffer (1919) for the inclusion of two European species, of which he had males only. The characters upon which he laid stress, and by which he separated the genus from Forcipomyia, were the length of the claws and the absence of an empodium. Nothing is known of the early stages of these two species. Subsequently, Ingram and Macfie (1923) described an African species from three males reared by Bacot from larvae in the leaf axils of Dracaena sp. The early stages of this species were not preserved.

Samples of largemouth bass were collected from Par Pond located on the Energy Research and Development Administration's Savannah River Plant in Aiken, South Carolina, from June 1972 to May 1973 inclusive. The sampling stations reflected water temperatures which were both normal and greater than 10°C above normal for the area. The acanthocephalan Neoechinorhynchus cylindratus was the dominant species found in the bass sampled. Incidences of infection for this parasite were generally greater than 95% regardless of location. A pronounced seasonal cycling pattern in the intensity of infection was noted in both thermal regions. Significant differences, however, in the mean density of N. cylindratus per host in fish taken from the heated area as compared with unheated areas were noted.

Turnover in the acanthocephalan population was measured by following the percentage of individuals less than 2 mm long. Fall proved to be the most intense parasite recruitment season, followed by maturation of the parasite and subsequent loss from the fish host.

The principal factors responsible for the seasonal incidence and intensity patterns are considered to be changes in the fish feeding behaviour and annual temperature regimes.

A description is given of some features of the embryonic development, the structure of the oncomiracidium and the postlarval development of R. emarginata, a hexabothriid parasite on the gills of Raia clavata.

There are three phases in the larval development of the haptor of Rajonchocotyle: an oncomiracidial or marginal hook stage, a hamulus stage and a sucker stage. Neither the embryo nor the oncomiracidium ever possesses more than five pairs of marginal hooks and marginal hooks I (the posterior-most pair) are considered to be missing. The marginal hooks develop within distinct binucleate oncoblasts. During the early stages of post-oncomiracidial growth the secondary attachment organs of the haptor are formed and it is only after the completion of the development of the haptor that the reproductive organs begin to appear. Firstly, a pair of hamuli is acquired, followed by four pairs of suckers, which form in posterior-anterior succession at the site of marginal hooks III-VI. The first pair of suckers remains unarmed while the other three pairs acquire hooked sclerites and become the main functional attachment organs of the adult. As the first pair of suckers appears the posterior part of the haptor lengthens to form a caudal appendage. Hexabothriids are considered to show closer affinity to the 8-suckered chimaericolids and diclidophorids than to the 6-suckered polysto-matids, the unarmed suckers representing a simplification, by loss of the sclerite and reduction in sucker size, of an originally armed sucker.

I would like to express my thanks to Dr J. Llewellyn for his interest and for much helpful discussion.

Thanks are also due to the Director and Staff of the Marine Biological Association at Plymouth, in particular Mr J. E. Green for material and assistance, and to Dr A.j Brinkmann, of the Department of Zoology, University of Bergen, for supplying specimens of Squalonchocotyle borealis.

The aim of this study was to use larval, parasitic female and egg antigens from Strongyloides venezuelensis to detect parasite-specific IgG and immune complexes in human serum samples by enzyme-linked immunosorbent assay (ELISA). In total, 95 serum samples were analysed, consisting of 30 patients harbouring S. stercoralis larvae, 30 healthy subjects and 35 patients with other parasites. Sensitivity, specificity and diagnostic efficiency were calculated. A significant statistical difference was found in the detection of immune complexes and antibodies in patients harbouring S. stercoralis larvae from larval and eggs antigens, with higher positivity using larval antigen. The larval antigen showed the highest values for sensitivity, specificity and diagnostic efficiency in ELISA from detection of immune complexes. For the first time we used IgG anti-larvae, IgG anti-parasitic females or IgG anti-eggs for immune complex detection. We concluded that the association of antibody and immune complex detection could be used in the diagnosis of human strongyloidiasis.

The understanding of the patterns and processes underlying the structure of parasite communities has progressed significantly in the last years; however, much of the evidence available to date on parasite community comes from unconfirmed studies. In this study the ectoparasite communities of 2 related rockfishes, Sebastes capensis and Helicolenus lengerichi, from the southern Chilean coast (ca. 40 °S) were examined to determine whether their specific compositions are similar, structured in non-random ways, and repeatable among years. From 2001 to 2004, 189 specimens of S. capensis and 101 of H. lengerichi were examined, 10 and 9 parasite species were recorded in S. capensis and H. lengerichi, respectively. Component ectoparasite communities of these hosts were taxonomically similar (60%), but the abundances and prevalences of their parasites differed significantly among years and between hosts. The most prevalent species were Lepeophtheirus chilensis, and Microcotyle sp. for S. capensis, and Microcotyle sp., Juanetia continentalis, and Interniloculus chilensis for H. lengerichi. Infracommunities of S. capensis showed higher species richness and parasite numbers than those of H. lengerichi. The similarity among infracommunities (measured as parasite abundance) varied significantly among years both within and between hosts. Despite this, temporal nestedness patterns were observed in infracommunities of these hosts, suggesting that their ectoparasite communities are structured and might be predictable in time, at least in the southern Chilean coast where they share the same habitat.

In the year 1881, G. Haller published a description of the sensory organ of ticks which has since borne his name; he was apparently so much impressed by its remarkable similarity in structure to the auditory organs of many Crustacea, that he assumed it to be an organ of hearing, and even went so far as to describe the presence of otoliths within one of the cavities of the organ. Since that time, other zoologists appear to have given little attention to this structure, the majority of those who have had occasion to mention it, contenting themselves with a brief resumé of Haller's observations and a reference to his paper.

[This paper deals with the biology of Pseudolynchia maura Bigot, the pupa and pupation period, sex ratio, offspring per female and longevity when bred under laboratory conditions by feeding on pigeons (the host in nature), chickens, mourning dove, man (hosts more or less unsuitable). Effects of the bite are described.—Ed.]

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.

A model is presented which describes the aggregation of female Onchocerca volvulus in nodules and their distribution in the human population. The basic model is based on a single parameter, the formation probability q, which represents the probability with which incoming larvae form a new nodule. This parameter describes parasite behaviour which cannot easily be recognized in available data without modelling. The estimate for the average formation probability of μq = 0.39 suggests an attraction of the invading infective larvae to already existing nodules or resident worms with probability 0.61. No significant difference in μq was found between the forest and savanna parasite strains. The model can be used inversely to estimate the worm burden of persons from palpation data. The observed variance in the number of nodules per person requires the assumption of a variance-increasing mechanism which was implemented by heterogeneity within the host population (extended model with 2 parameters). Possible reasons for this heterogeneity are presented and its implications concerning the reproductive biology of the parasite are discussed.

The native rat lungworm (Angiostrongylus mackerrasae) and the invasive rat lungworm (Angiostrongylus cantonensis) occur in eastern Australia. The species identity of A. mackerrasae remained unquestioned until relatively recently, when compilation of mtDNA data indicated that A. mackerrasae sensu Aghazadeh et al. (2015b) clusters within A. cantonensis based on their mitochondrial genomes (mtDNA). To re-evaluate the species identity of A. mackerrasae, we sought material that would be morphologically conspecific with A. mackerrasae. We combined morphological and molecular approaches to confirm or refute the specific status of A. mackerrasae. Nematodes conspecific with A. mackerrasae from Rattus fuscipes and Rattus rattus were collected in Queensland, Australia. Morphologically identified A. mackerrasae voucher specimens were characterized using amplification of cox1 followed by the generation of reference complete mtDNA. The morphologically distinct A. cantonensis, A. mackerrasae and A. malaysiensis are genetically distinguishable forming a monophyletic mtDNA lineage. We conclude that A. mackerrasae sensu Aghazadeh et al. (2015b) is a misidentified specimen of A. cantonensis. The availability of the mtDNA genome of A. mackerrasae enables its unequivocal genetic identification and differentiation from other Angiostrongylus species.

The morphology of the duodenal mucosal surface of chickens infected with Eimeria acervulina has been studied on days 5, 6, 8 and 11 post-infection and compared with that of the normal duodenal mucosa using the scanning electron microscope. The normal duodenum possessed tall, spatulate villi with horizontally-arranged surface clefts upon which a regular pattern of hexagonal absorptive cells and goblet cell mouths was superimposed.

A maximum degree of villous atrophy was shown on day 5 post-infection, the villi being thickened and flattened with frequent adhesions and fusions between them. The general effects of the disease together with the physical presence of intracellular parasites caused considerable changes in size and shape of the cell apices. By day 8 the mucosa was clearly recovering, with a normal pattern of somewhat thickened and truncated villi beginning to re-appear and by day 11 post-infection the mucosa had regained an outwardly normal morphological pattern. The mucosal changes are discussed in relation to similar changes which occur in diseases of the alimentary tract of other animals, including man.

In the course of work designed to measure the extent to which methionine absorbed in one region of a tapeworm became distributed throughout the strobila, it was observed that, whereas, in saline, Hymenolepis diminuta lost previously absorbed methionine slowly, in the intestine of a rat the methionine was lost very rapidly. The fact that two worms containing initially the same amount of free methionine should, after a short period in different environments, contain utterly different quantities of methionine indicated that the quantity of a free amino acid present at any time is not simply dependent on the amount previously absorbed less the amount metabolized.

This observation has a bearing on several aspects of tapeworm physiology. Do tapeworms normally absorb amino acids from the intestine during periods of high concentration and release them when the concentration falls? If they do, the presence of tapeworms in the intestine could be beneficial to the host by extending the period over which an amino acid is available to the host, an important point as a mammal is unable to store amino acids for more than a few hours (Gitler, 1964). A knowledge of the environmental conditions which influence the level of free amino acids in a tapeworm, and thereby its ability to synthesize proteins, is obviously also of critical importance to workers attempting to grow worms in vitro.