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W Harnett

Publications and source records attributed to W Harnett.

67 records · Page 4Linked to original sources
PubMed1989

Evaluation of the potential of excretions-secretions (E-S) of Litomosoides carinii to substitute for human filarial E-S.

The antigenic cross-reactivity of the excretions-secretions (E-S) of Litomosoides carinii was investigated. Immunoprecipitation using pooled sera from a number of human filarial infections in combination with sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed variations in the cross-reactivity of individual molecules. Some were specific to L. carinii, the major examples in this category being two E-S components of 140 and 160 kDa released by day 40- to 42-day-old female worms. Another, a high-molecular-weight product of 26- to 28-day E-S, was broadly cross-reactive. A third group appeared to exhibit reactivity to antibody to some but not all human filarial parasites. The most striking examples of this were two distinct 14-kDa products that bound solely to antibodies in an onchocerciasis serum pool. These results are discussed in relation to the use of cross-reacting molecules in investigating the immunisation potential, defining the function, and evaluating the diagnostic utility of human filarial E-S.

Animals↗
PubMed1989

Origin, kinetics of circulation and fate in vivo of the major excretory-secretory product of Acanthocheilonema viteae.

The excretions-secretions (E-S) of Acanthocheilonema viteae consist mainly of one product, molecular weight 62kDa. This molecule is synthesized during the vertebrate phase of the parasite life-cycle and is first detectable in the E-S of L4 parasites. It is cross-reactive with E-S of human filarial parasites as a consequence of possessing a phosphorylcholine (PC) moiety. The 62 kDa molecule has been employed as a model for the study of the origin and fate of filarial E-S. Immunohistological analysis has shown the molecule to be located predominantly in the parasite gut. Transplantation of adult female [35S] methionine pulsed worms into uninfected jirds resulted in the radio-labelled secreted 62 kDa antigen being detected in the bloodstream within 4 h by SDS-PAGE/immunoprecipitation analysis. The systemic half-life of the molecule as estimated by clearance of injected, purified 125I-labelled material was measured in naive and infected jird hosts. It was reduced from 2-7 h in naive animals to less than 30 min in 4-10 week infected rodents, a finding which correlated with clearance of antigen by antibody in the infected group. In animals infected for longer time periods the serum half-life returned to the values observed in naive jirds. The idea that this change in half-life may reflect differences in the nature of 62 kDa antigen containing circulating immune complexes as infection progresses is discussed. The 125I-labelled antigen is predominantly removed from the circulation via the liver and ultimately excreted in the urine in a non-antigenic form. This work provides the first description of the origin, kinetics of circulation and fate of a defined filarial E-S product and may aid in determining the function and assessing the diagnostic utility of PC-bearing E-S components.

Animals↗
PubMed1988

The anthelmintic action of praziquantel.

Although fairly expensive (around US$4.00 per single dose) praziquantel is now the most favoured drug against all forms of schistosomiasis, and against many other helminth infections. It is now marketed by four companies: E. Merck and Bayer (F.R.G.), Ames-Myers (USA), and Shin-Poon Pharmaceuticals (S. Korea). Administration of praziquantel typically causes paralysis of susceptible worms, or damage to their tegument, making them more vulnerable to host enzymes or antibody-dependent immune effector mechanisms. Other effects may also be involved. Here, Bill Harnett reviews the range of anthelmintic effects displayed by this remarkable drug.

Journal Article↗
PubMed1987

Onchocerca antigens in protection, diagnosis and pathology.

Characterization of the immune response to Onchocerca volvulus is important for the diagnosis, control and understanding of the disease it causes. The antibody response to surface, secreted and somatic antigens of the worm has therefore been examined at an individual immunoglobulin (Ig) class level, by using a panel of different human sera. Onchocerca-specific antigens tend to be of low molecular mass and preferentially recognized by IgG4 and IgE. There is considerable cross-reaction between O. volvulus and O. gibsoni, so that the latter may be an alternative source of material for use in diagnosis. A surface-enriched fraction of low molecular mass appears to be a most promising diagnostic tool. Amongst somatic antigens, two were uniquely recognized by IgG3 antibodies in sera from sowda patients, thereby providing a molecular correlate for a recognized pathological condition. Improved diagnosis is needed for detecting infection in both humans and the vector. Our target for detection in humans is a continuously released, nonimmunogenic product, which is ideally stage and parasite specific. The excretions of adult worms do contain components not recognized by antibodies in infected serum, but we cannot rule out that these are of host, rather than parasite origin. Excretions of Litomosoides carinii contain both host and parasite molecules and, in addition, stage-specific and sex-specific components. Unfortunately, however, the rate of production of excretions varies during the life of L. carinii. This finding may be relevant to the detection of Onchocerca excretions if they are produced at a similarly uneven rate. Finally, for detecting infective larvae in the vectors, we are currently screening a genomic library of O. volvulus for an appropriate probe. To date, one DNA sequence has been cloned that shows promising specificity.

Animals↗
PubMed1987

Nematode antigens in protection, diagnosis and pathology.

A thorough study of parasite antigens is a prerequisite for control programmes based on protection by vaccination, accurate serodiagnosis and perhaps immune modulation to diminish pathological sequelae. Stage specific surface secreted and somatic antigens may be of particular value in proceeding towards these goals. The design of vaccines is most appropriately focused on surface antigens. With respect to pathology, certain antigens must stimulate humoral and, or cellular immune responses which are responsible for the undesirable immunopathologic consequences of the disease. The ultimate objective, therefore, is identification of those particular antigens followed by appropriate down regulation of the immune system in order to delete such potentially harmful immunological reactions. The relevant illustration presented in this context is an interesting correlation between one particular clinical condition of onchocerciasis ("sowda") and the serological response, defined both in terms of the parasite antigen and an immunoglobulin class restricted antibody response. Current parasitological methods of diagnosis consistently underestimate parasite prevalence. Failure to detect low level patent infections incurs the risk of having a reservoir capable of perpetuating infections. There is, then, an urgent requirement for accurate serodiagnosis, to be used in association with, and for the evaluation of, drug treatment and vector elimination in parasite control programmes. Given the high sensitivity of current immunoassay technology, the only bar to establishing the necessary immunological tests is the choice of suitably specific antibody-antigen systems. Once these are identified, a combination of recombinant nucleic acid biochemistry and hybridoma technology should provide the necessary reagents for inexpensive, robust and specific diagnostic tests. In addition, it may not be many years before the ubiquitous RIA and ELISA technology gives way to the newly developing biosensor systems. Finally, given the sensitivity and specificity of today's nucleic acid hybridization techniques, we may soon expect to see specific identification of infective larvae in their vectors of this, a cloned DNA probe specific for Onchocerca volvulus, and with potential for the detection of infective larvae in blackflies is described.

Animals↗
PubMed1987

Variation in class-specific humoral immune responses of different mouse strains to microfilariae of Dipetalonema viteae.

The class-specific antibody responses of 3 strains of mice (C57/Bl10, BALB/C and CBA/N) known to vary in their ability to control the microfilaraemia which follows the subcutaneous transplantation of adult female Dipetalonema viteae has been investigated. The 3 mouse strains showed significant variation (a) in total levels of immunoglobulins and (b) in ability to recognize individual radio-isotope-labelled antigens as measured by coprecipitation. Within each mouse strain it was noted that antigens could vary with respect to the nature of the isotype of the antibody response which they elicited. Furthermore, by comparing results obtained from class-specific coprecipitation with surface ELISA it was found that a similar variation between responses to individual epitopes was also likely. No differences were observed in the humoral response of the 3 mouse strains which could explain the known resistance of the C57/Bl10 strain; reasons for this are discussed.

Animals↗
PubMed1986

Schistosoma mansoni: exposure in vitro of adult male surface antigens.

Incubation of adult male Schistosoma mansoni for 24 hr in medium containing newborn calf serum or normal human plasma resulted in an increase in the amount of parasite antigen exposed at the worm surface. No effect was observed on the amount of host antigen which was present. The increase in the exposure of parasite antigens takes place progressively over 24 hr and is partially dependent on the presence of lipoproteins in the culture medium. The possibility is discussed that the increase is due to environmentally induced changes in surface membrane lipid composition.

Animals↗
PubMed1986

Quantitative and qualitative changes in production of excretions/secretions by Litomosoides carinii during development in the jird (Meriones unguiculatus).

Excretions and secretions (E-S) were collected from a series of developmental stages of Litomosoides carinii maintained in vitro. Measurement of the protein content of E-S obtained from each stage indicates that the rate of production of E-S varies enormously during development of the worm. E-S was iodinated using both Iodogen and the Bolton and Hunter Reagent and was also biosynthetically labelled by incubating worms in the presence of [35S]methionine and [3H]leucine. Attempts to biosynthetically label E-S of mature worms and microfilariae with [3H]glucose were unsuccessful. Examination of radio-isotope labelled E-S by SDS-PAGE revealed that some components were sex specific and that the differences in total E-S production during development were due to the existence of both stage-specific components and components whose rate of release varied during parasite maturation. Antigenic characterization of E-S, carried out by immunoprecipitation in combination with SDS-PAGE, indicated that E-S consists of immunogenic components, a molecule which is probably a non-immunogenic parasite product, and host albumin. The implications of these findings for the construction of diagnostic tests to detect products of human filarial parasites are discussed.

Animals↗
PubMed1985

The use of aldehydes to show a relationship between host and parasite antigens at the surface of adult male Schistosoma mansoni.

An indirect radiolabelled antibody method has been developed to measure the effects of aldehydes on the amount of antigen detectable at the surface of adult male Schistosoma mansoni. Incubation of schistosomes in formaldehyde (0.01-10% wt/vol.) or glutaraldehyde (0.01-0.1% wt/vol.) was found to result in increased exposure of parasite antigens with a concomitant decrease in the amount of surface located host RBC antigens. Those concentrations of formaldehyde or glutaraldehyde which were most effective in removing or displacing host antigens were also most able to expose parasite antigens. These findings are consistent with the hypothesis that host antigens mask parasite antigens at the surface of the adult schistosome.

Animals↗
PubMed1982

The effects of retinol (vitamin A alcohol) and various non-ionic detergents on he surfaces of schistosomula and adult Schistosoma mansoni.

It was found that retinol at concentrations of 0.2-1.0 mg . ml-1 caused significant 51Cr release from schistosomula, while adult worms appeared unaffected. Retinol was shown, by spectrofluorimetry and fluorescence microscopy, to be absorbed into the membrane systems of both schistosomulum and adult worm, particularly when the parasites were incubated in retinol dissolved in non-ionic detergents (Tweens 20, 40 and 80). The retinol within the adult membrane could be induced to cause detectable 51Cr and 125I wheat germ agglutinin release if the adult was treated with retinol in combination with Tween 20. The effect of the combination of Tween 20 and retinol, was synergistic for the release of both isotopes. Their synergism was also observed when haemolysis of human erythrocytes was measured. Thus it is possible to greatly enhance the effect on the schistosome and the erythrocyte membrane of one membrane-active compound by presenting it in combination with another. This may have implications in chemotherapy when membrane active drugs are employed.

Animals↗
PubMed1981

The use of membrane-active compounds to examine the structure of the surface membrane of Schistosoma mansoni.

The effects of a variety of lipophilic compounds on the young stage (schistosomulum) and adult Schistosoma mansoni have been studied by measuring the release of 51Cr and 125I-labelled wheat-germ agglutinin from labelled parasites. The compounds could be classified into three groups, one of which described reagents which affected only the schistosomulum. It is concluded that during development, changes occur in the organization of the lipid phase of the parasite membrane.

Amphotericin B↗
PubMedDate not supplied

Onchocerca ochengi transmission dynamics and the correlation of O. ochengi microfilaria density in cattle with the transmission potential.

The intensity of natural transmission of Onchocerca ochengi and Onchocerco volvulus by anthropo-boophilic Simulium damnosum s.l. was studied longitudinally in two cattle watering sites of a cattle ranch within a predominantly cattle populated area of the Guinea savanna of Cameroon and related to cattle O. ochengi skin microfilaria abundance. During the 12 months study period, a total of 4696 flies was individually dissected to examine the monthly transmission potential (MTP) of O. ochengi and O. volvulus. The estimated Simulium damnosum s.l. annual biting rates (ABR) on human baits were 47529 flies at the bank of the Vina "du sud" river. The ABR at the lake, which was situated at about 2 km upland from the perennial river, was 8579. The monthly parous rate was highly correlated with monthly biting rate. The annual transmission potentials (ATP) of O. ochengi were calculated to be 7732 and 1669 at the riverbank and the lake, respectively. Transmission occurred mainly in the dry season, peaking in the months of January to mid-March when dermal microfilaria density in the animals was also the highest. The O. ochengi microfilaria uptake by the fly vectors was host microfilaria density-dependent. The MTP of O. ochengi was positively correlated with dermal microfilaria density. The mean number of microfilariae per fly taken up during a blood meal was high during the dry season as was the mean number of infective larvae per fly but declined significantly with the onset of the early rains. A similar seasonality of transmission was also observed for O. volvulus that was concurrently transmitted by the same vector flies, but its ATP was comparatively much lower: 1332 infective larvae per man per year at the riverbank and 107 around the lake. The population dynamics of cattle microfilariae therefore plays an important role in the regulation of O. ochengi transmission.

Animals↗