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At least 1,207 records · Page 67Linked to original sources
PubMed1983

Ivermectin: a potent new antiparasitic agent.

Ivermectin is the 22,23-dihydro derivative of avermectin B1, a macrocyclic lactone produced by an actinomycete, Streptomyces avermitilis. It is active at extremely low dosage against a wide variety of nematode and arthropod parasites, apparently by virtue of its action on the mediation of neurotransmission by gamma-aminobutyric acid. It is now in commercial use in various countries for the treatment and control of parasites in cattle, horses, and sheep, and is expected to become available for use in swine and dogs. Since studies with the drug in man are in a preliminary stage, it is not yet known whether ivermectin will be useful in human medicine.

Animals↗
PubMed1997

Giardia lamblia infections in B-cell-deficient transgenic mice.

In the present study, we infected B-cell (and antibody-)-deficient transgenic mice with the Giardia lamblia clone GS/M-83-H7. These animals were inhibited in intestinal anti-Giardia immunoglobulin A (IgA) production and could not resolve the parasite infection, and antigenic diversification within the respective parasite populations occurred in an unusually slow manner. These findings indicate an important immunological function of local IgA antibodies which promotes antigenic variation of the parasite and is involved in control of the parasite infection.

Animals↗
PubMed2001

Identification and role of thiols in Toxoplasma gondii egress.

The nucleoside triphosphate hydrolase of Toxoplasma gondii is a potent apyrase that is secreted into the parasitophorous vacuole where it appears to be essentially inactive in an oxidized form. Recent evidence shows that nucleoside triphosphate hydrolase can be activated by dithiothreitol in vivo. On reduction of the enzyme, there is a rapid depletion of host cell ATP. Previous results also demonstrate a dithiothreitol induced egress of parasites from the host cell with a concurrent Ca2+ flux, postulated to be a consequence of the release of ATP-dependent Ca2+ stores within the tubulovesicular network of the parasitophorous vacuole. Reduction of the nucleoside triphosphate hydrolase appears crucial for its activation; however, the exact mechanism of reduction/activation has not been determined. Using a variety of techniques, we show here that glutathione promoters activate a Ca2+ flux and decrease ATP levels in infected human fibroblasts. We further show the in vitro activation of nucleoside triphosphate hydrolase by endogenous reducing agents, one of which we postulate might be secreted into the PV by T. gondii. Our findings suggest that the reduction of the parasite nucleoside triphosphate hydrolase, and ultimately parasite egress, is under the control of the parasites themselves.

Acetylcysteine↗
PubMed1977

Glochidiosis of salmonid fishes. I. Comparative susceptibility to experimental infection with Margaritifera margaritifera (L.) (Pelecypoda: Margaritanidae).

This is the first report on the susceptibility of salmonid fishes to infection with the glochidia of the freshwater mussel Margaritifera margaritifera using known numbers of parasites under controlled conditions. The relative susceptibility of six species of salmonid fish, 20 to 80 mm in total length, to glochidiosis was determined by exposing fish individually to different numbers of parasites and plotting mortalities against these exposure levels at 70 days postexposure and also against the numbers of parasites recovered from fish 48 hr postinfection. The 70-day interpolated LE50 values (exposure concentrations of glochidia that killed 50% of the fish) for kokanee salmon (Oncorhynchus nerka kennerlyi), cutthroat trout (Salmo clarki), Atlantic salmon (S. salar), steelhead trout (S. gairdneri) and coho salmon (O. kisutch) were 17,500, 29,000, 35,000, 57,000, and 105,000, respectively. Chinook salmon (O. tshawytscha) was the most susceptible species. The LE50 values could not be estimated even at the lowest exposure levels because mortalities were too high. On the basis of the LE50 value, coho salmon was the most resistant species.

Animals↗
PubMed1987

Oxfendazole pulse release intraruminal devices and bovine parasitic bronchitis: comparison of two control strategies in a field experiment.

Lungworm-infected seeder calves were used on two 1.41 ha paddocks to ensure that groups of 11 susceptible trial calves would be exposed to heavy early season challenge with Dictyocaulus viviparus. This produced conditions for an artificially severe test of two control strategies. The first employed a front-loaded oxfendazole pulse release bolus, ie, an intraruminal device which released one therapeutic anthelmintic dose immediately and five subsequent pulses at approximately three-weekly intervals. These front-loaded boluses were given to five of 11 calves on one paddock as soon as parasitic bronchitis had become clinically obvious (34 days after turnout) while the remaining six calves were kept as untreated controls. Clinical signs quickly subsided in the treated animals and no further respiratory problems occurred despite continued exposure to reinfection. The other control strategy involved the administration at turnout of an oxfendazole pulse release device which released the first of five anthelmintic doses approximately three weeks after administration, to all 11 calves on the other paddock. This strategy was almost completely successful in preventing patent infections from establishing and reduced the infectivity of the pasture in August and September by 94.1 per cent as shown by tracer calf studies. The calves treated at turnout performed better than the calves treated with the front-loaded boluses for most of the season and had an average weight-gain advantage of 20.4 kg at housing (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Measurement of triclabendazole and its metabolites in liver flukes: method development and full validation.

The trematode parasite Fasciola hepatica is still the cause of considerable loss in livestock production all over the world. The knowledge of the pharmacological properties of the available flukicidal drugs is critical to control this parasite. Triclabendazole is an halogenated benzimidazole anthelmintic with potent flukicidal activity. A simple reversed-phase high-performance liquid chromatographic analytical method has been developed, validated and applied for the quantitative determination of the flukicidal drug triclabendazole and its sulpho- and hydroxy-metabolites in the liver fluke, F. hepatica. Triclabendazole, triclabendazole sulphoxide, triclabendazole sulphone, hydroxy-triclabendazole, hydroxy-triclabendazole sulphoxide and hydroxy-triclabendazole sulphone were measured simultaneously in this trematode parasite. Linearity, resolution, precision, accuracy, recovery, limits of detection and quantification of the method were determined. Drug extraction from the parasite's tissue homogenate was effectively performed using liquid extraction (acetonitrile), avoiding clean up by solid phase extraction, prior to analysis by reversed-phase high-performance liquid chromatography. The resolution of all the halogenated benzimidazole thiol molecules assayed was obtained on a C(18) reversed-phase (5 microm, 250 mm x 4.6 mm) column using acetonitrile and ammonium acetate as the mobile phase and ultraviolet detection at 300 nm. Regression analyses were linear over the concentration range examined (from 0.272 to 16.331 nmol/100 mg trematode protein) and the correlation coefficients of the calibration curves ranged between 0.996 and 1.000. The calculated limits of detection of the proposed method for the parent drug and its metabolites ranged between 0.007 and 0.079 nmol/100 mg trematode protein. The extraction efficiency for the different analytes from the parasite material was greater than 71%. The results obtained indicated that the developed chromatographic method was selective, accurate and easy to reproduce. The developed procedure was successfully applied to quantify triclabendazole/metabolites in F. hepatica incubated under ex vivo conditions, demonstrating to be efficient for the determination of the most extensively used flukicidal drug available for veterinary medicine, and its metabolites. The analytical method described here is an useful tool for the measurement of this flukicidal compound in different studies addresses to evaluate drug influx/eflux and metabolism in its main target parasite.

Animals↗
PubMed2004

CD28 is required for T cell activation and IFN-gamma production by CD4+ and CD8+ T cells in response to Trypanosoma cruzi infection.

In the present study we evaluated the mechanisms behind the implication of the costimulatory molecule CD28 for the immune response against the intracellular protozoan parasite Trypanosma cruzi. Our results reveal a critical role for CD28 in the activation of both CD4+ and CD8+ T cells and induction of the effector mechanisms that ultimately mediate the control of parasite growth and pathogenesis in infected mice. CD28-deficient (CD28-/-) mice are highly susceptible to T. cruzi infection, presenting higher parasitemia and tissue parasitism, but less inflammatory cell infiltrate in the heart than C57Bl/6 wild-type (WT) mice. All the infected WT mice survived acute infection, whereas 100% of CD28-/- mice succumbed to it. The increased susceptibility of the CD28-/- mice was associated with a dramatic decrease in the production of IFN-gamma by both CD4+ and CD8+ T cells resulting in a diminished capacity to produce nitric oxide (NO) and mediate parasite killing. T cell activation was also profoundly impaired in CD28-/- mice, which presented decreased lymphoproliferative response after the infection compared to WT mice. Together, these data represent the first evidence that CD28 is critical for efficient CD4+ T cell activation in response to T. cruzi infection in mice.

Animals↗
PubMed2006

Interleukin-27R (WSX-1/T-cell cytokine receptor) gene-deficient mice display enhanced resistance to leishmania donovani infection but develop severe liver immunopathology.

The interleukin-27 (IL-27)/T-cell cytokine receptor (TCCR) pathway plays an important role in development of protective immunity against cutaneous leishmaniasis caused by Leishmania major. In this study, we analyzed the role of IL-27/TCCR pathway in the host defense against visceral leishmaniasis (VL) by monitoring the course of L. donovani infection in TCCR-deficient C57BL/6 (TCCR-/-) mice. TCCR-/- mice mounted a robust inflammatory response, produced high levels of pro-inflammatory cytokines, and developed severe liver pathology after L. donovani infection that eventually resolved. Interestingly, L. donovani-infected TCCR-/- mice controlled the parasite growth in their organs significantly faster than similarly infected TCCR+/+ mice. Adoptive cell transfer and cell depletion studies revealed that CD4(+) T cells were involved in mediating liver immunopathology and controlling L. donovani growth in TCCR-/- mice. These results indicate that the IL-27/TCCR pathway is not essential for the induction of protective Th1 response during VL but is involved in mediating susceptibility to L. donovani. Additionally, the data demonstrate that although the IL-27/TCCR interaction limits the severity of liver inflammation during VL by controlling CD4(+) T-cell activity, it is not required for the resolution of hepatic immunopathology.

Adoptive Transfer↗
PubMed1997

Follow-up of Gambian children recruited to a pilot safety and immunogenicity study of the malaria vaccine SPf66.

A pilot safety and immunogenicity trial of the malaria vaccine SPf66 was undertaken in The Gambia in 1993. One hundred and fifty infants aged 6-11 months were immunized with either 0.5 mg or 1.0 mg of SPf66 produced either in Colombia or in the USA or with a control vaccine. Children who received SPf66 experienced more clinical attacks of malaria than did children in the control group during the first period of surveillance and the difference in incidence between children who had received high dose Colombian vaccine and the control children was statistically significant at the 5% level. During the 1995 malaria transmission season, 127 children from the original cohort of 150 were observed. During 18 weeks of intensive surveillance, the incidence of clinical malaria was again higher among children who had received SPf66 than among children who had received inactivated polio vaccine (6.23 vs 4.89 clinical attacks per 1000 days at risk), the effect being most marked among children who were in the high dose groups, but differences between groups were now no longer statistically significant.

Child↗
PubMed2004

A small-molecule approach to studying invasive mechanisms of Toxoplasma gondii.

Toxoplasma gondii is the most common protozoan parasite of humans. Infection with T. gondii can lead to life-threatening disease as a result of repeated cycles of host cell invasion, parasite replication, and host cell lysis. Relatively little is known about the invasive mechanisms of T. gondii and related parasites within the Phylum Apicomplexa (including Plasmodium spp., the causative agents of malaria), due to difficulties associated with studying genes essential to invasion in haploid obligate intracellular organisms. To circumvent this problem, we have developed a high-throughput microscope-based assay, which we have used to screen a collection of 12,160 structurally diverse small molecules for inhibitors of T. gondii invasion. A total of 24 noncytotoxic invasion inhibitors were identified. Secondary assays demonstrated that different inhibitors perturb different aspects of invasion, including gliding motility, secretion of host cell adhesins from apical organelles (the micronemes), and extension of a unique tubulin-based structure at the anterior of the parasite (the conoid). Unexpectedly, the screen also identified six small molecules that dramatically enhance invasion, gliding motility, and microneme secretion. The small molecules identified here reveal a previously unrecognized complexity in the control of parasite motility and microneme secretion, and they constitute a set of useful probes for dissecting the invasive mechanisms of T. gondii and related parasites. Small-molecule-based approaches provide a powerful means to address experimentally challenging problems in host-pathogen interaction, while simultaneously identifying new potential targets for drug development.

Animals↗
PubMed1999

Cost-effectiveness analysis of artesunate and quinine + tetracycline for the treatment of uncomplicated falciparum malaria in Chanthaburi, Thailand.

A randomized, controlled, malaria-clinic-based field trial was carried out to compare the cost-effectiveness of a 5-day 700-mg oral artesunate and a 7-day quinine + tetracycline regimen for the treatment of uncomplicated falciparum malaria in Thailand. Cost-effectiveness was determined from the providers' perspective and based on curative effectiveness. A total of 137 patients, aged 15-60 years, attending a malaria clinic were followed for 28 days, 60 of them received quinine + tetracycline and 77 received artesunate. Cure rates were assessed on day 5 (artesunate) and day 7 (quinine + tetracycline), using the intention-to-treat approach. Cost-effectiveness and sensitivity analyses were performed by varying the day 5/day 7 curative effectiveness and cost of artesunate. The cure rate with artesunate (100%) was significantly higher than with quinine + tetracycline (77.4%) (relative risk adjusted for sex (aRR) = 1.32, 95% confidence interval (CI) = 1.12-1.55; referent quinine + tetracycline). Artesunate was more cost-effective than quinine + tetracycline at the following costs: artesunate, < or = US$0.36 per 50-mg tablet; quinine, US$0.06 per 300-mg tablet; tetracycline, US$0.02 per 250-mg capsule; and services per case found, < or = US$11.49. Because of the higher cure rate and higher cost-effectiveness of the artesunate regimen compared with quinine + tetracycline, we recommend its use for the treatment of uncomplicated falciparum malaria in malaria clinics in Thailand.

Adolescent↗
PubMed1999

Response of falciparum malaria to different antimalarials in Myanmar.

The purpose of the study was to ascertain the therapeutic efficacy of different treatments for uncomplicated falciparum malaria in the hospitals in Sagaing, northern and eastern Shan, to facilitate updating the existing national antimalarial drug policy. The proposed 14-day trial for monitoring the efficacy of treatments of uncomplicated falciparum malaria is an efficient method for identifying treatment failure patterns at the intermediate level (township hospital) in the Union of Myanmar. Minimal clinical and parasitological data for days 0-14 were required to classify treatment failure and success. Clinical and parasitiological responses on day 3 and days 4-14 were used as clear examples of early and late treatment failure, respectively. Mefloquine is five times more likely to be effective than chloroquine and sulfadoxine pyrimethamine (S-P), whereas chloroquine and S-P treatments have nearly identical failure patterns. The alarming frequency of clinical and parasitological failure (failure rate > 50%) following chloroquine treatment was reported in Sagaing and following S-P treatment in Sagaing and eastern Shan.

Adolescent↗
PubMed1992

Assessment of sanitation conditions by qualitative sanitation measurement.

Survey of sanitation conditions by qualitative sanitation measurement were carried out in three districts, Chachoengsao Province, Thailand. The sanitation of each household was assessed in terms of positive stool examination and scores of seven main sanitary activities which were used to classify each household's sanitation as hygienic or non-hygienic. Stool collections were made from each household's housewife and examined for pathogenic bacteria and parasites. It was found that in the qualitative measurement of the household's sanitation as hygienic or non-hygienic, most sanitary activities were highly associated with the results of stool examination. From consideration of the sensitivity, specificity and kappa coefficient of significant sanitary activities as predictors and the result of stool examination was used as gold standard, it was apparent that a package of all main sanitary activities was the most appropriate measurement in the survey to assess sanitation conditions in the community.

Animals↗
PubMed1988

Efficacy of early season anthelmintic treatment against gastrointestinal nematodes.

The efficacy of levamisole and ivermectin in multiple-dose regimes for the control of parasitic gastroenteritis in first-season grazing calves was evaluated on a dairy cattle farm in Belgium. Thirty-nine female Holstein crossbred calves were randomly divided into three groups. Paddock 1 was used for the controls, paddock 2 for the levamisole group (dosed at 3, 6 and 9 weeks after the start of grazing) and paddock 3 for the ivermectin group (dosed at 3 and 8 weeks after turn-out). The treatments were evaluated on the basis of live weight, faecal egg output, and serum pepsinogen levels. The impact of the therapeutic dosing at timed intervals during the first months of the grazing season was remarkable; egg output in the levamisole and ivermectin groups between June and early October was substantially lower. The treatments seem to adequately control Ostertagia, because serum pepsinogen values were much lower from August onwards. Better weight gains were observed in both the treatment groups. The experiment also illustrated the advantage of early housing of calves.

Animals↗
PubMed1993

Natural killer cells participate in the early defense against Leishmania major infection in mice.

In this study the role of natural killer (NK) cells in the course of experimental Leishmania major infection was investigated. NK cells in genetically resistant C57BL/6 mice were depleted by in vivo administration of anti-asialo-GM1 or anti-NK1.1 antibodies. A marked exacerbation of the infection was found in the NK-depleted mice within the first two weeks of infection. Both the local tissue swelling and the number of parasites in the lesions were significantly higher than in normal animals. Lymph node cells taken from infected NK-depleted mice released less interferon-gamma (IFN-gamma) when cultured in vitro. As an alternate approach we have used poly I:C treatment in order to activate NK cell activity in vivo in BALB/c mice, which are genetically susceptible to L. major infection. Poly I:C treatment led to milder symptoms and to a significantly lower parasite burden in the early course of infection. Lymph node cells from infected and poly I:C-treated BALB/c mice released higher amount of IFN-gamma in vitro than cells from control mice. These data show that NK cells are active participants in the non-specific phase of anti-leishmanial activity in the control of parasite multiplication early in the course of L. major infection in mice.

Animals↗
PubMed1996

Development of immunity to lungworm in vaccinated calves treated with an ivermectin sustained release bolus or an oxfendazole pulse release bolus at turnout.

The ivermectin sustained release bolus (IVSRB), when used at turnout as recommended, will provide season-long control of parasitic bronchitis, thus obviating the need for use of a lungworm vaccine. However, some concerns have been expressed that calves treated with an IVSRB will receive so little exposure to Dictyocaulus viviparus that it will compromise their immunity in subsequent grazing seasons, which would be of particular importance in dairy herds. Although there is evidence that IVSRB-treated calves can develop immunity to D. viviparus when exposed to pasture infection, it was considered worthwhile to evaluate the compatibility of the IVSRB and lungworm vaccination to allow veterinary surgeons the option of using these products concurrently when they have particular concerns about the long term immune status of replacement dairy heifers. Thirty-two dairy replacement heifers were vaccinated with two doses of lungworm vaccine and, at turnout, half the calves received an IVSRB and the remainder an oxfendazole pulse release bolus (OPRB). At the end of the grazing season four replicate bolus treated pairs and four parasite-naive calves were challenged with 1000 D. viviparus infective larvae. At slaughter there was a 95% and 93% reduction in D. viviparus burdens in the IVSRB and OPRB treated calves respectively, compared with the unvaccinated, untreated controls. These results indicate that where it is considered necessary to use lungworm vaccination in addition to an IVSRB or an OPRB, the compatibility of these products with lungworm vaccine will allow development of a protective level of immunity to D. viviparus.

Animals↗