Workshop 2F: Chemotherapy-experimental and clinical

1018

R. C. A. THOMPSON

(c) Othertechniques The important problem of in vitro evaluation of drug sensitivity of Plasmodium falciparum was discussed by A. Sabchareon et al. WORKSHOP 2E: LUMEN-DWELLING HELMINTHS

K. YOSHIMURA*and H. J. S. DAWKXNst * Department of Parasitology, Akita University School of Medicine, Hondo, Akita, Japan t Regional Veterinary Laboratory, Department of Agriculture and Rural Affairs, Benalla, Victoria, Australia Only two posters and two oral and poster presentations were reviewed in this session due to late withdrawals. The first oral presentation by A. Kobayashi, K. Katakura and A. Hamada was entitled "Fate of Ascaris Eggs applied to the Soil under Natural Conditions". Ascaris suum eggs were placed in two locations and at two depths within the soil at monthly intervals for 1 year. At the end of the experimental period, the eggs were assessed for their viability. There was a clear relationship between egg degeneration and exposure to strong sunlight. Thus eggs not shaded or close to the soil surface degenerated very quickly. Ascaris e~gs in deeper soil or in shaded regions survived with the percentage viable after 12 months being between 54 and 99%. The implications of this study and the importance of similar studies prior to embarking on large and extensive epidemiological or transmission studies are obvious. Without a sound understanding of the basic parasitology elaborate studies have no basis for interpretation. Basic research is all too readily dismissed for more expensive and sophisticated research. The second presentation was entitled "Large Trichuris Eggs in Aboriginal Communities in Queensland" by A.J. Stewart and P. Prociv. Trichuris trichiuria eggs in the faeces of Aboriginals were observed to be of two different sizes. These eggs were present simultaneously in the uterus of single female Trichuris worms. The large eggs have been reported over a long period, however, since the commencement of a mebendazole treatment programme the large eggs have increased in incidence. It was suggested, as one possible scenario, that the large eggs were more resistant to mebendazole and their increased incidence was a measure of their selection by the treatment programme. If this should prove to be the situation, then the extensive treatment programme of trichuriasis will require modifying if it is to be effective. Irrespective of the outcome, this study further represented the need for small studies to be carried out prior to embarking on long costly programmes. Without such information all large scale projects have to be considered ill-advised and their success will depend on serendipitous events rather than informed decisions. The poster entitled "Light and Electron Microscopical Examination of the Location of Strongyloides stercoralis in the jejunum of the immunosuppressed dog" by D. I. Grove et al., represented a long overdue

description of the precise location of S. stercoralis adults. Understanding of the location of parasites is paramount to being able to correctly interpret the host response and its effect on the parasite. The second poster "Taiwan Taenia may be Considered as a New Species of Taenia" by P. C. Fan et al., concerned a small epidemiological investigation with a question on the taxonomy of the species. It is significant that this disease entity has been described for the past 70 years but is only now receiving some of the attention due to it. All the papers and posters in this session exemplified the need to continue basic parasitological research. It is only through basic parasitological investigations that the new technologies and sophisticated studies will have the solid grounding on which to base an interpretation of the results and arrive at the correct implications of the research. WORKSHOP 2F: CHEMOTHERAPY-EXPERIMENTAL AND CLINICAL

W. E. GUTTERIDGE* and D. I. GROVEt * Biochemical Microbiology, Wellcome Research Laboratories, Beckenham, Kent, U.K. t Department of Medicine, University of Western Australia, Nedlands, Western Australia In the area of anti-protozoal chemotherapy, further experimental work on D F M O has shown that whereas the drug is quite effective in controlling Trypanosoma gambiense infections, it is only suppressive against T. brucei and T. rhodesiense (abstract number 750). An adherence inhibition assay for Giardia sp. was described which was claimed to be more sensitive than growth inhibition assays (166). However, such growth inhibition assays, utilizing 3H-thymidine incorporation, have been used to demonstrate the variable sensitivity of laboratory stocks of Giardia. This may provide an explanation for treatment failures experienced with 5-nitroimidazoles (512). A clinical study with such drugs found that a single dose of ornidazole or tinidazole is usually effective in giardiasis; in amoebiasis, ornidazole seemed as effective but less toxic than metronidazole (46). CibaGeigy's new 5-nitroimidazole, Cibemid, which is shortly to be registered in India, was also reported to be active in giardiasis in a single dose (516); 3 days of treatment was required for the therapy of amoebic liver abscess (517). Presentations on existing antimalarial drugs indicated that the mutagenic effects of NTG and EMS could lead to chloroquine resistance in Plasmodiurn berghei infections (725), described the ultrastructural effects of chloroquine and mefloquine (119) and reported on the effects of pyrimethamine and proguanil upon the liver stages of Plasmodium cynomolgi (326). The need for new antimalarial drugs was emphasized yet again by a report of decreased sensitivity to chloroquine and quinine of some Plasmodium falciparum isolates from Senegal (91); plants could well serve as the source of such compounds (95).

Post Congress Scientific Report In anti-platyhelmintic chemotherapy, the in vitro effects of oxyclozanide on Gigantocotyle explanatum was described (14). Other reports indicated the efficacy of cyclosporin A and its non-immunosuppressive analogues (85) and arteannuin mixture (404) in experimental models of schistosomiasis. Preparations of isolated chick oesophagus were used as a model to study the effects of oxamniquine on neuromuscular systems (10). A clinical study indicated that despite rapid and extensive hepatic metabolism leading to relatively low levels of drug in the systematic circulation, praziquantel was dramatically effective in the treatment of cerebral schistosomiasis caused by Schistosoma ]aponicum (701). The effect of in vivo treatment with amides on the metabolism and the ultrastructure of alveolar cysts of Echinococcus multilocularis was reported (581). A study of the effects of drugs on protoscoleces of E. granulosus in vitro indicated that thiabendazole and liydroquinone did not affect parasite viability at the highest concentrations achievable in human therapy, whereas mebendazole was partially effective under such conditions (417). A clinical study reported on the efficacy of albendazole against clonorchiasis, metagonimiasis and tapeworm infections (543). However, the effects of such benzimidazoles in hydatidosis is often highly variable. This had led to a search for parasite-specific receptors which might be exploited in drug targetting: the D-amino acid transport system may fulfil this role (35). The treatment of human neurocysticercosis with albendazole was reported (206). In anti-nematode chemotherapy, over 30 years clinical experience of treating intestinal helminthiasis was reviewed (12). Topical formulations of levamisole appear to prevent infection by hookworm larvae both experimentally and in humans (304). A dual hookworm assay in the hamster offered the advantage of 'studying the activity of anthelmintics on two species simultaneously and also serving as a model for mixed hookworm infestations (530). A new experimental model for drug testing against Strongyloides ratti has been developed to take account of new observations on the life cycle of the organism (455). Work on similar systems has revealed that the known parasiticidal effects of cyclosporin A and its derivatives include intestinal nematodes (584). Two closely related 2-tertiary butyl benxthiazole derivatives were reported to have broad spectrum anthelmintic activity, including Schistosoma, Onchocerca and gastro-intestinal nematodes (632). Antifilarial and anti-schistosome activity was also described for CibaGeigy compound 6140 and its metabolite 13231 (631). A study on the action of ivermectin on the development of Onchocerca volvulus in Simulium damnosum revealed an intense, rapid and extended reduction in transmission (524). A Phase III study of ivermectin in Togo confirmed the potency of this compound in the treatment of onchocerciasis (588).

1019

WORKSHOP 2G: MALARIA AND OTHER SPOROZOEA

R. E. SINDEN*and C. KIDSONt * Department of Pure & Applied Biology, Imperial College of Science and Technology, Ascot, Berkshire, U.K. t Queensland Institute of Medical Research, Brisbane, Queensland, Australia All presentations related to malaria, and covered a wide range of topics from ultrastructure and epidemiology to drug treatment studies. Papers by V.M. Sehgal and J. F. Trape et al. examined the acquisition and maintenance of Plasmodium falciparum infections in children. In the coastal regions of Madang, Papua New Guinea (P.N.G.) Sehgal reported 31% of women (both prima- and multi-gravida) were P. falciparum positive just prior to delivery with 915% having infected placenta or chord blood; 4% of cases resulted in congenital malaria. The parasite prevalence ensuing in the children was 3% at 4 weeks; 7% at 4-8 weeks, 4% at 8-12 weeks, 18% at 12-16 weeks and rose steadily for a further 18 weeks. At 36 weeks 91% of children had received Amodiaquine (usually domestic administration), but quinine treatment by physicians paralleled malaria infection more closely, i.e. 11% at 36 weeks. The study of Trape et al. reported on the impact of urbanization on malaria in Brazzaville. Surrounding rural areas showed 79-94% of children infected, each receiving 200-1000 infected mosquito bites/year. Within town, prevalence rates varied widely from district to district 81-9% and 1-100 infected bites/year. The mortality rates were surprisingly similar 0.43 per 103 (0-4 years) and 0.08 per 103 (5-9 years) in both urban and rural communities. This low mortality was attributed to widespread use of anti-malarials. The emphasis on community mass prophylaxis was pursued in the study of W. Pribadi et al. where, in Indonesia, the introduction of simple learning techniques in the administration of chloroquine for key villagers, resulted in a 50-80% reduction in parasite or spleen rates in children and the adult population. Infant parasite rates were however less affected (from the original 30% to only 25%). Extensive and detailed studies on the efficiency of transmission of P. falciparum and P. vivax in Madang Province, P.N.G. by T.R. Burkot et al. showed sporozoite rates of 0-1% for P. vivax and 0.17-2.3% for P. falciparum. A strong positive correlation was found between parasite prevalence and entomological inoculation rates, with P.falciparum being transmitted roughly 2 × more efficiently than P. vivax. This efficiency was believed to be related to the higher sporozoite load in P.falciparum (mean 4000) vs. P. vivax infected mosquitoes (mean 400). All members of the Anaopheles punctatus groups exhibited similar sporozoite burdens. The very low estimates of mean sporozoite burden in P. vivax infected mosquitoes as revealed by the elegant and powerful E L I Z A method suggest a careful analysis of the onset