Acta Leidensia最新文献

The evidence for male/female differences in prevalence, density of infection and clinical disease due to onchocerciasis is reviewed and related to what is known about differential exposure of females to infective vectors. Sex differentials are most marked in savanna areas of high transmission, and in these areas, worm burdens are lower from early childhood in females--as are ocular lesions. In forest areas, sex differences are less marked and ocular lesions are similar in men and women. Sex differences are most evident under conditions of high transmission and it is suggested that females are more resistant to infection than males. There is little substantive evidence that onchocerciasis is less frequent in females on the basis of exposure but controlled exposure and immunological studies, analysed by age and sex, are needed to confirm this. Little is known about onchocerciasis in pregnancy but increased resistance could influence the risk of transmission of infection from mother to child in highly endemic areas. Onchocerciasis in pregnancy is also likely to affect immune response to tetanus toxoid vaccination in mothers and birthweight of children. The disease therefore represents an important public health problem for women and their offspring.

The construction and antibody screening of Taenia solium cDNA libraries, generated in the Escherichia coli bacteriophage lambda gt11, with the identification of clones putatively expressing antigen B, T. solium-specific and other antigens is described. Lysogens were produced from a number of selected clones and beta-galactosidase fusion peptides ranging in Mr of approximately 135,000-150,000 were demonstrated. These proteins were shown by immunoblotting to be reactive with a pool of sera from cysticercotic patients originally used in the cDNA library screening. We report a method whereby Taenia (T. saginata and T. pisiformis) eggs can be detected with high sensitivity in a specific DNA dot-blot hybridisation assay using total parasite DNA as probe. We show also that intra-specific DNA variability occurs in T. solium isolates obtained from different geographical areas and discuss the potential significance of this heterogeneity.

A brief review is given of the transmission dynamics of the ovine cysticercoses Taenia hydatigena and T. ovis. The importance of the basic reproductive rate (Ro) and the parasite, host and socio-ecological factors determining the epidemiological steady states of Taeniidae are described. The transmission dynamics of these ovine cysticercoses have been used as models to assist in identifying the biological and epidemiological research needed for developing strategies for the control of porcine cysticercosis caused by T. solium.

The toxicity data on praziquantel, effective against trematodes and cestodes, on the schistosomicides hycanthone, metrifonate, niridazole, and oxamniquine, and on albendazole, effective against cestodes and nematodes, are discussed. Praziquantel's efficacy in neurocysticercosis treatment has been well established. Recently, therapy of brain cysticercosis with albendazole was reported as well. For hycanthone, metrifonate, niridazole, and oxamniquine a mutagenic potential was demonstrated, at least in bacterial systems. Hycanthone and niridazole affect reproductive functions and are carcinogenic in animals. As not many safety data on albendazole have been published, it is possible only to deduce a teratogenic risk and--in rare cases--a hepatotoxic potential. Its capacity to induce cytochrome P-448 needs further elucidation, because the activation of drugs and chemicals by this monooxygenase isozyme may produce toxic or even carcinogenic metabolites. Likewise, it needs to be established, how possible effects on the intracellular tubulin system, which are known to occur with related benzimidazoles, affect the safety profile of this drug. From the toxicological point of view, praziquantel is the most promising drug, because it lacks systemic toxicity after repeated administration of daily doses of up to 1000 or 180 mg/kg to rats and dogs, respectively, and after lifetime bioassays with rats and Syrian hamsters. It does not affect reproduction, and is devoid of any mutagenic or carcinogenic potential.

Taenia solium and Taenia saginata are of such close taxonomic relationship that each can be regarded as a model for the other. In these particular species the only available hosts are either humans or large domesticated animals. This has imposed severe safety and/or economic restrictions on the extent of the experimental work which could be attempted. Furthermore, there is a limit to the relevance of work with less closely related species such as Taenia ovis, Taenia taeniaeformis and Taenia pisiformis with their differing host species, larval forms and locations within the intermediate host tissue. However, the application of both monoclonal antibody based and modern molecular biological techniques to the T. solium and T. saginata systems does much to overcome or circumvent some of the problems. Thus advances made in the analysis, diagnosis or immuno-prophylaxis of one of these species are at least potentially both of direct and immediate or indirect benefit to the work on the other species.

Field trials and control programmes demonstrate that ovine echinococcosis (Echinococcus granulosus) and the cysticercoses (Taenia hydatigena and T. ovis) have different stabilities and may not respond in the same way to control. The first-named, which is usually in the endemic state, is readily transformed by a dog-dosing programme to extinction status. In contrast, the cysticercoses, usually in the hyperendemic state, may only be transformed to the endemic state. The consequence of this includes an increase in the larval population by superinfection due to a loss of immunity following this change in epidemiological status. These field trials and control programmes have been used as models for porcine cysticercosis caused by T. solium. It is concluded that future research should model the life cycle of this parasite mathematically and determine the most cost-effective control strategies. The impact of these on human prevalence can then be addressed by pilot field trials.

Taeniasis and cysticercosis caused by Taenia solium, the pork tapeworm, are widespread infections of Latin America, Africa, and Asia. The disease in humans (neurocysticercosis), caused by the cystic larval stages which develop in the central nervous system, is often disabling and sometimes fatal. T. solium infections are endemic in rural and urban areas in some countries that have limited resources to introduce and sustain control programs. To give T. solium control high national priority, the effect of the diseases on health and social care budgets must be accurately measured. Surveys are needed to establish prevalence and geographical distribution of the diseases, to obtain basic epidemiologic data, to learn about transmission, to provide baseline data for the establishment of control measures, and to monitor control measures. Continuing surveys can provide information on changes in prevalence brought about by specific control measures or by changes in the standard of living, education, animal husbandry, and meat processing. Data are not yet available for any endemic-cysticercosis area, and this has hindered efforts to control the disease. There are technical limitations of currently-available methods for diagnosing both taeniasis and cysticercosis in humans in and lower animal hosts. This paper reviews the status and limitations of diagnostic methods and emphasizes the need for further research.

The in vitro exoerythrocytic (EE) of Plasmodium berghei was compared in primary rat and mouse hepatocytes and the human hepatoma cell line HepG2. All of the cell-types supported the full maturation of EE stages, but the HepG2 cells were much more susceptible to infection than the primary rodent hepatocytes and were also the most efficient host cells. Following refinement of culture techniques, the development of EE forms which is now observed in HepG2 cells closely reflects that occurring in vivo with respect to the morphology and size of parasites and their rate of maturation. Furthermore, high densities of parasites are reproducibly achieved. A detailed description is presented of exoerythrocytic development in HepG2 cells. The application of these cultures to chemosensitivity studies is discussed and the relative advantages of employing cell lines or primary hepatocytes as host cells in such a system are considered.