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K D Murrell

Publications and source records attributed to K D Murrell.

At least 73 records · Page 4Linked to original sources

Immunodiagnosis of nematode infections and prospects for vaccination, with special reference to Trichinella spiralis.

Within the phylum Nematoda are species not only responsible for several chronic, debilitating diseases of man, but also for significant economic losses resulting from parasitaemias of livestock. Parasitic zoonoses caused by nematodes, such as trichinosis, present a public health concern as well. In an effort to combat these diseases, much research has been directed towards the development of vaccines that will protect man and animals from selected parasitic infections. Concomitantly, sensitive, reproducible diagnostic assays are required to assess accurately the maturation of a putative protective immune response generated by prophylactic vaccine therapy. This review emphasises studies on the epidemiology and control of Trichinella spiralis in swine as a paradigm for the diagnosis of nematode infections in livestock, and the potential implementation of vaccines in control strategies.

Animals↗

Effects of microclimatic variables on the availability and movement of third-stage larvae of Ostertagia ostertagi on herbage.

Assessments were made of the influence of several microclimatic variables on the availability of third-stage larvae of Ostertagia ostertagi, on pasture herbage. Variables most closely related to recovery of larvae from the lower herbage samples were: maximum air, mat and dung temperatures. Recovery of larvae from the upper portion of the herbage was closely correlated with dung temperature, sampling-time air temperature and maximum air temperature. Bearing in mind that the moisture threshold was maintained throughout the trial the results of this study suggest that under field conditions, larval movement of third-stage O. ostertagi larvae on herbage is regulated primarily by temperature.

Animals↗

Trichinella spiralis in an agricultural ecosystem: transmission in the rat population.

Four hundred forty-three Norway rats (Rattus norvegicus) were examined to determine their role in the transmission and maintenance of Trichinella spiralis on a pig farm. Rats, classified by sex and weight, were examined for trichinellosis by peptic digestion of muscle samples. Over a 25-mo period, 188 (42.4%) rats were found to be infected with T. spiralis. The mean intensity of infection was 293.2 larvae per gram (LPG) of muscle; 65 (34.6%) infected rats had intensities of infection greater than 100 LPG. Even in the absence of a known source of infected meat (garbage containing meat scraps or dead animals), the rat population maintained the infection, probably through cannibalism. Population reduction was an effective method for reducing the prevalence of infection within the rat population. Therefore, to reduce the likelihood of transmission of T. spiralis between rats and swine, it is essential that rat populations in a farmyard environment be controlled.

Animals↗

The serological response of pigs experimentally infected with a species of Taenia from Taiwan.

An enzyme-linked immunosorbent assay (ELISA) for the detection of antibody in pigs infected with a possibly new species of Taenia isolated in Taiwan is described. The test antigen ThFAS was fractionated from the cyst fluid of a heterologous cestode Taenia hydatigena. In lightly infected pigs (less than or equal to 4 recovered cysts at necropsy 17 weeks post-inoculation), antibody was detected as early as 3 weeks post-inoculation. In more heavily infected pigs (6-72 recovered cysts at necropsy 32 weeks post-inoculation), antibody was still detectable at the time of necropsy. Cysticerci were found only in the livers of the infected pigs. This ELISA should be highly useful for detecting infection of pigs with this larval cestode in regions where the presence of Taenia solium is unlikely.

Animals↗

Comparative efficacy of antigen and antibody detection tests for human trichinellosis.

Sera collected from patients with suspected or confirmed exposure to Trichinella spiralis were tested for circulating parasite antigens and antiparasite antibodies. Using an immunoradiometric assay, excretory--secretory antigens from muscle-stage larvae of T. spiralis were detected in the sera of 47% of 62 patients with clinical trichinellosis and 13% of 39 patients without clinical signs but suspected of exposure to infected meat. In comparison, antibodies were detected using an indirect immunofluorescent test in the circulation of 100% of the 62 patients with clinical trichinellosis and 46% of the 39 patients with suspected exposure. The presence of antibodies specific to excretory-secretory products of T. spiralis muscle larvae was confirmed in the majority of the samples tested by a monoclonal antibody-based competitive inhibition assay. These results indicate that antibody detection is a more sensitive diagnostic method for human trichinellosis, but that antigen detection might be a useful confirmatory test because it is a direct demonstration of parasite products in the circulation.

Antibodies, Helminth↗

Comparison of egg excretion and serum pepsinogen levels as measures of nematode worm burdens in calves with limited pasture exposure.

Four- to 6-mo-old calves raised on clean pastures were allowed to graze for about 30 days on pastures naturally contaminated with Ostertagia ostertagi, Cooperia spp., Haemonchus placei, and Nematodirus helvetianus. The calves were then housed on concrete for 3 wk before slaughter. At necropsy the eggs per gram of feces (EPG) and the total worm burdens from the abomasum and small intestine were determined. Blood samples were also obtained for serum pepsinogen (PEP) assays. A total of 44 calves was sampled over 27 mo. Adult worm totals were distributed more normally after logarithmic transformation (LOGTOTAL), and EPG and PEP were distributed more normally after square root transformation (SQRT--EPG; SQRT--PEP). Correlation between LOGTOTAL and either SQRT--EPG or SQRT--PEP was about 0.7. These correlations were higher than those obtained with nontransformed data, suggesting that either EPG or PEP are easily measured variables that explain a significant amount of the variation observed in total worm burdens. Polynomial regression models of a cubic order using the SQRT--EPG accounted for 78% of the variation observed in the LOGTOTAL, whereas SQRT--PEP accounted for 58% of the variance. Within the range of worm burdens observed, these results indicate that EPG has value in estimating total worm burdens of naturally infected calves, and that pepsinogen levels are of less value for analysis of total worm burden in calves with a limited previous exposure to trichostrongyle nematodes.

Abomasum↗

Evidence for genetic control of nematode egg-shedding rates in calves.

Differences in nematode fecal egg counts from 167 purebred Angus calves born in 1986 and 133 born in 1987 that had been naturally exposed to infection on pasture were analyzed for sire effects. The calves were sired by 26 different bulls, all of which were related. Differences among fecal egg counts were attributable to sires (P less than 0.0002), to age of the calf (P less than 0.0007), to age of dam (P less than 0.05), and to collection year (P less than 0.0001). No variation in fecal egg count was attributable to calf sex (P greater than 0.23). After accounting for the effects of year, age of calf, and age of dam, heritability was estimated to be 29% (SE = 18%). It was concluded that a paternal contribution to the genome of each calf played an important role in determining average fecal egg output of the sire group. With heritability at 29%, selection against higher fecal egg counts or selection for lower fecal egg counts would be expected to produce measurable genetic change in a population.

Animals↗

Immunogenetic analysis of Trichinella spiralis infections in swine.

The immune responses of outbred swine, inoculated with several different low doses of Trichinella spiralis muscle larvae (ML), was followed over 5-6 weeks of primary infection, in order to determine an inoculation dose which could be used to identify genetic controls on the response to this helminth parasite. Reproducible infections were established when swine were inoculated with 100-300 ML. Humoral antibody responses to different larval stages were evident at 4 weeks using enzyme-linked immunosorbent assay (ELISA) of antibody-binding to excretory-secretory (ES) products of ML, and flow cytometric (FCM) analysis of antibody-binding to newborn larvae. T-cell blastogenesis to T. spiralis ML antigens was predominantly in the CD4+, class II restricted, T-cell subset. Having established an appropriate inoculation dose, swine leukocyte antigen (SLA) inbred miniature swine were then inoculated with this low dose of T. spiralis ML, to determine whether major histocompatibility complex (MHC) genes regulate swine immune responses to T. spiralis, as has been found in rodent models. Preliminary evidence indicated that swine of the SLA c/c haplotype may exhibit a lower burden of T. spiralis larvae in the tongue and diaphragm. This lower muscle burden correlated with the earlier development of a humoral antibody response in these genetically-defined swine.

Animals↗

Evaluation of excretory-secretory antigens for the serodiagnosis of swine trichinellosis.

Groups of hog sera from endemic and non-endemic areas for swine trichinellosis in Yugoslavia were tested by ELISA using excretory-secretory (ES) antigens collected from T. spiralis muscle larvae maintained in vitro for 24, 48 or 72 h. The 24-h ES had the highest level of specificity for T. spiralis infection. Antigen preparations recovered after 48 or 72 h yielded an increasing rate of false-positive reactions. Additional antigens occurred in the 48- and 72-h ES preparations as determined by gel electrophoresis and monoclonal antibody binding. The occurrence of false-negative reactions was directly correlated with T. spiralis worm burdens. Hogs with muscle larvae densities greater than 10 larvae per gram were all positive by ELISA. Among 17 hogs with less than 10 larvae per gram, only one hog was negative by ELISA with 24-h ES antigen; the false-negative rate was higher with 48- and 72-h ES. These results show that ES antigen produced during the first 24 h of in vitro cultivation is highly specific for the immunodiagnosis of swine trichinellosis.

Animals↗

Trichinella spiralis in an agricultural ecosystem. III. Epidemiological investigations of Trichinella spiralis in resident wild and feral animals.

As part of a larger epidemiological study examining the transmission of Trichinella spiralis in an agricultural ecosystem, resident wild and feral animals were trapped to determine the extent of their involvement in the natural, on-farm cycling of the parasite among swine. During a 21-mo-study, seven of 15 skunks (Mephitis mephitis), one of three opossums (Didelphis virginiana), two of two feral domestic cats and a raccoon (Procyon lotor) were found to be infected, while five shrews (Blarina brevicauda) and 18 deer mice (Peromyscus spp.) were uninfected. Most of the former hosts probably became infected by scavenging dead infected swine or rats (Rattus norvegicus). However, infections obtained through predation of living rats, particularly with regard to the cats, cannot be excluded. Our observations do not suggest that there was transmission of T. spiralis from the wild animals to swine. Therefore, transmission of T. spiralis appeared to occur only from the farm's swine and rats to the associated wild and feral animals.

Agriculture↗

Application of biotechnology methods to the study of cestodes.

The advent of biotechnology has invigorated research on the control of cestode diseases, especially cysticercosis infections in man and animals. The utilization of hybridoma technology to produce antigen-specific monoclonal antibodies has resulted in great strides towards obtaining pure antigens relevant for immunodiagnostic purposes and for research on vaccines. However, the isolation and identification of antigens is only the initial step in the development of such reagents. Production of antigens in quantities sufficient for research/development and commercialization is hampered by the scarcity of viable parasite material for extraction. Expectations are that this problem can be surmounted by application of recombinant DNA methods to produce cloned genes for antigen expression in cultured microorganisms or cells. Remarkable progress has been made recently in isolating and cloning genes from several important cestode species and antigens have been expressed in vitro with genes cloned from Taenia taeniaformis and T. hydatigena. Although these early efforts have not as yet resulted in practical antigen production, the prospects for doing so appear good. The complex epidemiology of cestode diseases is another research subject that has benefited from the successful application of the tools of biotechnology. For example, the greater precision in typing biological variants afforded by DNA analysis has led to important revisions of the understanding of hydatid disease. DNA probes are now available for Echinococcus spp, which are effective for typing isolates. These probes may also find use as reagents for distinguishing eggs of Echinococcus from other taeniid eggs, a serious difficulty for field investigations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Impact of biotechnology on trichinellosis control.

The century-old effort to rid Trichinella spiralis from the food supply has had variable success, and in some regions trichinellosis remains a serious public health concern. However, the research advanced during the past 5 years points toward greater success in developing practical and efficient control strategies. The application of monoclonal antibody and recombinant DNA technologies has permitted great improvement in diagnosis and production of diagnostic reagents. Further, the epidemiology of the disease has undergone considerable revision because of the power of DNA analytical technics which are unravelling the complex genetics of Trichinella spiralis. This improved understanding of the parasite's epidemiology is critical to the design of improved control strategies.

Animals↗

Trichinella spiralis: immunization of pigs with newborn larval antigens.

The potential of crude Trichinella spiralis newborn larval antigens for pig immunization was investigated. A preparation of whole newborn larvae killed by freezing and thawing, and combined with Freund's complete adjuvant, induced a high level of protection against challenge (78%), compared to a 40% resistance level in pigs immunized with excretory secretory antigens of muscle larvae. Sera from pigs immunized with newborn larvae contained antibodies which bound to the surface of the newborn larvae, as determined by immunofluorescence. In a second trial, the freeze thawed newborn larvae preparation was compared with a soluble and insoluble fraction prepared by sonication of whole newborn larvae. Pigs receiving whole newborn larvae or the insoluble fraction developed strong immunity to challenge (88.2 and 85.5%, respectively); the soluble fraction was ineffective. Immunization with all preparations induced antibody to newborn larval antigens, but not to adult or muscle larvae excretory secretory antigens. Polyacrylamide gel electrophoresis of the soluble and insoluble fractions indicated that sonication was ineffective in solubilizing the larger molecular weight components. These results demonstrate that newborn larval antigens are highly protective in pigs, but that their further development as a vaccine will require more efficient procedures for antigen solubilization and large-scale production.

Animals↗

Trichinella spiralis: genetic evidence for synanthropic subspecies in sylvatic hosts.

Isolates of the nematode genus Trichinella from sylvatic hosts differ in their potential to reproduce in domestic swine. The structure of the genomic DNA from 13 sylvatic isolates from North America and 5 pig isolates, 4 from North America and 1 from Asia, was examined and correlated with the infectivity of the isolate for domestic pigs. DNA restriction fragment length differences, identified by ethidium bromide staining and by hybridization with 32P-labeled ribosomal RNA, served as molecular markers to classify each isolate. All 5 pig isolates and 8 of 13 sylvatic isolates had a high infectivity and reproductive capacity in pigs. All isolates that were highly infectious for pigs regardless of host origin had similar DNA characteristics and were classified operationally as T. spiralis spiralis (pig) and those of the second group as T. spiralis ssp. A DNA clone of repetitive DNA from T. s. spiralis, pBP2, was selected from a library of genomic DNA in plasmid pUC8. When used as a probe, pBP2 hybridized only to the DNA of T. s. spiralis isolates, thus making it a useful diagnostic reagent to predict whether new isolates are highly infectious for pigs (i.e., T. s. spiralis). These results show that T. s. spiralis occurs in wild mammals and this should be considered a serious obstacle to efforts to eradicate trichinellosis from domestic swine.

Animals↗

Progress in the development of vaccines against parasitic diseases.

Vaccines for parasitic diseases have lagged behind the development of vaccines for important viral and bacterial diseases. Among the reasons for this is the extreme antigenic complexity of parasites and also the adaptive ability of parasites to co-exist with their host, often through modulation of the host's immune response. Advances in technology including in vitro cultivation, hybridoma and recombinant DNA methods have provided valuable tools for the study of parasite immunology and have resulted in major strides toward vaccines for several protozoan and helminth parasites.

Animals↗

Parasitic modulation of host immune mechanisms in schistosomiasis.

Antigen antibody complexes are suspected to play a role in the pathogenesis of some of the lesions that result from schistosomiasis. To examine the effect of immune complexes on the immune system of mice experimentally infected with Schistosoma mansoni, we measured antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-mediated serum hemolysis in normal and infected animals. ADCC activity in infected mice was depressed compared to control mice. However, preincubation of spleen cells for 24 h in medium followed by washing restored ADCC activity. This suggested that a soluble factor(s), presumably immune complexes, was bound to the Fc receptors with resultant block in ADCC activity and this was removed in vitro during the 24-hour preincubation. Furthermore, the complement activity of mouse serum was markedly depressed in mice infected for 3 or 6 weeks. Again, the presence of immune complexes could explain this depression since immune complexes bind complement. We attempted to confirm and extend these findings with an immunoperoxidase-staining technique using antibody to S. mansoni antigen. Most of the granuloma formations identified in portal tracts and intestinal mucosa were composed of macrophages and epithelial cells surrounding a central nidus of schistosome egg. In addition, schistosome antigen was seen diffusely bound to some of the lymphoid elements in the lamina propria and many of these cells appeared plasmacytoid. Furthermore, large amounts of schistosome antigen were sequestered in the medullary cords of the mesenteric lymph nodes and in the Billroth cords of the spleen. This suggests that the antigen is conveyed to the lymph nodes and the spleen through the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Trichinella spiralis in an agricultural ecosystem. II. Evidence for natural transmission of Trichinella spiralis spiralis from domestic swine to wildlife.

Epidemiological investigations of an outbreak of trichinellosis were carried out in a domestic swine herd and it was established that the parasite also occurred in rats, and in skunks, opossums, and raccoons. Because considerable uncertainty exists regarding the role of sylvatic trichinellosis as a reservoir for the synanthropic cycle, studies were conducted to determine the genetic nature of the various isolates from this ecosystem. Pig infectivity trials, isoenzyme analyses, and repetitive DNA sequence analyses were performed. The results showed that all isolates from the farm environs were genetically similar and that they are related to Trichinella spiralis isolated from domestic pigs. The implication of these findings, in contrast to studies on isolates from wildlife elsewhere, is that this parasite is transmitted from domestic swine to sylvatic hosts and that any control or eradication efforts must take into account the potential for reinfection of hogs from wild animals.

Animals↗

Trichinella spiralis in an agricultural ecosystem: transmission under natural and experimentally modified on-farm conditions.

A hog found infected with Trichinella spiralis at slaughter was traced to its farm of origin, where an epidemiological investigation found the infection prevalent in swine and rats. Garbage-feeding was not responsible for maintaining the high prevalence of infection on this farm, although it may have been responsible historically for the introduction of the infection. Poor husbandry, malnutrition, and intercurrent disease resulted in frequent death and the availability of porcine carcasses for cannibalism. Tissue samples from partly devoured carcasses contained T. spiralis larvae, implicating cannibalism as a major vehicle for the spread of T. spiralis in the herd. Rats also fed on these carcasses, and their rate of infection increased markedly during the first 5 mo of observation. Experimental investigation indicated that rats could also be important in maintaining a high prevalence of infection in swine. For the purpose of our investigation, the farm was depopulated of swine and restocked with parasite-free, sentinel pigs confined in 3 groups exposed to increasing degrees of contact with rats. Pigs exposed to large numbers of rats acquired infections rapidly, whereas pigs with strongly limited rat exposure failed to acquire infection during a 12-mo period. These results indicate that, when rats are available to swine and the prevalence of T. spiralis infection in the former is high, predation (or scavenging) on rats may be as effective as cannibalism in maintaining a high prevalence of porcine T. spiralis infection.

Animals↗