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W Eling

Publications and source records attributed to W Eling.

51 records · Page 3Linked to original sources

Topographical distribution of the cerebral lesions in mice infected with Plasmodium berghei.

In the mouse P. berghei malaria model systematic studies were carried out on the relationship between the type and the topographical distribution of the brain lesion in cerebral malaria. As previously stated for pernicious P. falciparum malaria in man, petechial haemorrhage was not the sole morphologic lesion. In addition to severe brain oedema, microthrombosis, sludging of mononuclear cells, arteriolar spasms, scattered disturbances of the microcirculation, and the occasional proliferation of gliocytes were the prevailing morphologic changes. Pronounced perivascular oedema with compression of capillaries and ischaemic demyelinisation were particular frequent in the nucleus caudatus putamen, while the adjacent regions (radiatio corporis callosi, claustrum, hippocampus, and fimbria hippocampi) were the sites of predilection of petechial haemorrhage. Arteriolar spasms were particularly frequent in branches of the posterior choroidal artery. The proliferation of gliocytes was practically restricted to the tubercula olfactoria and to the subependymal zone of the lateral wall of the lateral ventricle. The present results indicate a neurovascular component in the pathogenesis of cerebral malaria. The preponderance of a special histopathological lesion in a certain cerebral region may be the result of a particular sensitivity of cells of these areas to noxious events (pathoclisis), for instance hypoxia, and/or exaggeration of autoregulatory phenomena that exist between the cerebral parenchyma and the supplying vasculature.

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Fading of malaria immunity in mice.

Fading of immunity in Swiss and C3H/StZ mice was progressive, and related to both, the interval elapsed since the last challenge infection and survival of parasites. In both mouse strains the proportion of mice that remained immune to challenge decreased with increasing fading periods. Moreover, a shift from delayed mortality to a normal course of infection as seen in non-immune controls was observed in C3H/StZ mice. Early parameters of fading were increasing peak parasitaemias after challenge in an increasing proportion of mice, and lethal infections instead of transient parasitaemias. Fading was also reflected by changes in the host cells preferentially infected early after reinfection: with increasing fading periods host cell preference shifted from predominantly polychromatophilic erythrocytes to mixed infections and finally to predominantly oxyphilic cells, especially in Swiss mice. The results of isodiagnosis indicated a positive correlation between persistence of parasites and immunity; whereas the absence of parasites was related to various phases of a fading immune response.

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Survival of parasites in mice immunized against Plasmodium berghei.

The rodent malaria parasite Plasmodium berghei may survive im immunized Swiss and C3H/StZ mice for a considerable period of time. Despite considerable differences in the observed survival time in animals of a given strain, a general, strain specific pattern is observed. Parasites generally survive longer in Swiss than in C3H/StZ mice. In some of the Swiss mice parasites survived throughout the experimental period, whereas in the others restricted survival was observed, possibly reflecting genetic disparity. Since booster infections did not affect the survival pattern, the effectiveness of elimination is not determined by "antigen" dependent, gradual differences in quality of the hosts' immune response. Repeated biotechnical manipulation of the animals may influence experimental results.

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Active immunization against the malaria parasite Plasmodium berghei in mice. The immunizing inoculum.

In the immunization procedure of Swiss and C3H/StZ mice against P. berghei the inoculum plays an important role. Only viable parasites are able to induce immunity when multiple inoculations (10(5) P.E. per mouse) or a single inoculation (1-4 X 10(7) P.E. per mouse) are administered. The inoculated parasitized erythrocytes should enter the vascular system. The subcutaneous route is inappropriate, since subsequent immune reactions are notably absent. In combination with a given suppressive regimen successful immunization depends on an optimum number of viable P.E. in the inoculum. All conditions that affect the proportion of viable parasites in the inoculum (route, storage, medium, temperature, donor) should be recognized and controlled. The actual immunizing capacity of the inoculum also depends on the magnitude and time of initiation of sulfathiazole treatment after inoculation. Suppressive treatment (300 mg/L) starting 2 days after inoculation was found optimal in order to render the procedure less sensitive to small differences in the number of P.E. inoculated. Conditions which lead to antimalarial immunity are apparently strain-specific.

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Ficoll fractionation for the separation of parasitized erythrocytes from malaria infected blood.

Separation and concentration of parasitized erythrocytes from infected blood was achieved by centrifugation of a sample placed in a layer on top of a cushion of a Ficoll solution with a critical density. Pure suspensions of parasitized erythrocytes were obtained from Plasmodium berghei infected rodent blood, whereas results with P. vivax infected monkey (Aotus trivirgatus) blood were partially successful. Titration experiments revealed that the parasitized erythrocytes obtained by Ficoll fractionation were infective.

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Active immunization against Plasmodium berghei malaria in mice, using different preparations of plasmodial antigen and different pathways of administration.

With regard to the effectiveness of the antigens in inducing clinical immunity against malaria parasites, the minimum amount of living antigen developed in mice during controlled low parasitaemia with Plasmodium berghei has been estimated and compared with the amount of non-living antigen obtained by various methods of freeing parasites from their erythrocyte hosts.Whereas about 100 mg of living antigen per kg of body-weight are sufficient to induce a degree of hyperimmunity, 1240 mg/kg of a freshly prepared crude antigen are necessary to enable the mice to survive a challenge infection while 3500 mg-7000 mg/kg of a vaccine prepared from freshly isolated plasmodia are necessary to produce a degree of immunity comparable with hyperimmunity. It appears, therefore, that every manipulation of the parasitized erythrocyte or the isolated plasmodium outside the host organism, as well as a storage time in excess of 36 hours, causes a reduction in antigenicity, up to a factor of 10(-2). However, this decrease in antigenicity is disproportionate compared with the reduced rate of infectivity of stored, parasitized erythrocytes and isolated parasites. After an incubation period of 18 hours, the ID(100) increases from 2 x 10 to 5 x 10(7) parasites. Therefore, the differences between the essential amount of living plasmodia and non-living antigen may be due to other, hitherto unknown, factors and not exclusively to degradation of the most important antigen.The saponin method of freeing parasites from their erythrocyte hosts was found to yield the purest antigen. Preparations of parasites obtained by treating parasitized erythrocytes with anti-erythrocyte serum or with formalin were highly contaminated with remnants of the host cells and showed no better antigenic qualities than the parasites isolated by means of saponin.Since the decrease of antigenicity associated with harvesting and isolation procedures is constant, vaccination with a fractionated antigen pool should be possible.

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Measurement by membrane feeding of reduction in Plasmodium falciparum transmission induced by endemic sera.

The standard laboratory test for reduction in malaria transmission is based on the measurement of oocyst numbers in mosquitoes fed on blood meals containing test and control sera. Interpretation of the results, however, is often hampered by the large variation in numbers of infected mosquitoes and oocysts. The objective of this study was to compare 3 measures for the assessment of transmission reduction (so-called R values) and to define the experimental criteria that allow interpretation of the results. To determine variability in R values of control sera, a replicate experiment was performed with 10 non-endemic sera of Dutch blood donors. Furthermore, 2 measures for calculation of transmission reduction were compared in a triplicate experiment using Plasmodium falciparum, Anopheles gambiae and malaria endemic sera. Calculations using the geometric mean of Williams are currently used to identify blocking and non-blocking sera. However, calculations using log-transformed data could distinguish more gradual levels of transmission reduction activity by endemic sera--i.e. blocking, reducing and non-blocking activity. Grading of transmission reduction activity is important for epidemiological studies on transmission immunity and for validation of future transmission-blocking vaccines.

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Susceptibility of Anopheles quadriannulatus Theobald (Diptera: Culicidae) to Plasmodium falciparum.

Anopheles quadriannulatus, the cattle-feeding member of the An. gambiae complex, was fed human blood which contained cultured gametocytes of Plasmodium falciparum, using a membrane feeding system. After 7 days, 33-80% of the mosquitoes that took a blood meal contained developing oocysts. In 7 out of 12 females sporozoites were found in the salivary glands 14 days after the infectious blood meal. Control groups of An. gambiae s.s. and An. stephensi became readily infected with > 90% developing oocysts. All of the An. gambiae dissected 14 days after the infectious blood meal had sporozoites in their salivary glands. The results demonstrate that An. quadriannulatus is susceptible to infections with P. falciparum.

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