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At least 523 records · Page 29Linked to original sources
PubMed2004

Calcium-mediated protein secretion potentiates motility in Toxoplasma gondii.

Apicomplexans such as Toxoplasma gondii actively invade host cells using a unique parasite-dependent mechanism termed gliding motility. Calcium-mediated protein secretion by the parasite has been implicated in this process, but the precise role of calcium signaling in motility remains unclear. Here we used calmidazolium as a tool to stimulate intracellular calcium fluxes and found that this drug led to enhanced motility by T. gondii. Treatment with calmidazolium increased the duration of gliding and resulted in trails that were twice as long as those formed by control parasites. Calmidazolium also increased microneme secretion by T. gondii, and studies with a deletion mutant of the accessory protein m2AP specifically implicated that adhesin MIC2 was important for gliding. The effects of calmidazolium on gliding and secretion were due to increased release of calcium from intracellular stores and calcium influx from the extracellular milieu. In addition, we demonstrate that calmidazolium-stimulated increases in intracellular calcium were highly dynamic, and that rapid fluxes in calcium levels were associated with parasite motility. Our studies suggest that oscillations in intracellular calcium levels may regulate microneme secretion and control gliding motility in T. gondii.

Animals↗
PubMed1988

Rapid reinfection by Giardia lamblia after treatment in a hyperendemic Third World community.

In a peri-urban shanty town in Lima, Peru, that was hyperendemic for Giardia lamblia, 44 children aged between 0.9 months and 10 years were effectively treated for Giardia lamblia with tinidazole. Stools were examined weekly in the 6 months after treatment to determine the rate of reinfection, and after reinfection stools continued to be examined. 98% of the children became reinfected with Giardia lamblia within 6 months, and after reinfection stool excretion of the parasite lasted a mean (SD) of 3.2 (3.3) months. The children's mean stool pH and their mean stool fat index was unaffected by Giardia lamblia reinfection. Treatment of all symptomless Giardia lamblia infections in a developing country hyperendemic for the disease is of questionable value because of rapid reinfection.

Animals↗
PubMed1998

Onchocerciasis.

Explore the source record for details and available documents.

Humans↗
PubMed1997

Eradicating guinea worm without wells: unrealized hopes of the Water Decade.

At the start of the United Nations International Drinking Water Supply and Sanitation Decade in the 1980s, guinea worm disease was targeted as the major indicator of the success of the Decade's efforts to promote safe water. By the late 1980s, most of the guinea worm endemic countries in Africa and South Asia had established guinea worm eradication programmes that included water supply as one of their main technical strategies. By surveying the water supply situation in Ifeloju Local Government Area (LGA) in Oyo State, Nigeria, in June 1996, as a case study, it was possible to determine the role that water supply has played in the eradication effort. Although two major agencies, the former Directorate for Food, Roads and Rural Infrastructure and UNICEF, provided hand dug and bore-hole wells respectively in many parts of the LGA, coverage of the smaller farm hamlets has been minor compared to efforts in the larger towns. This is ironic because the farm hamlets served as a reservoir for the disease in the 1980s, such that when the piped water system in the towns broke down, guinea worm was easily reintroduced into the towns. The survey of 188 ever-endemic hamlets with an estimated population of 23,556 found that 74.3% of the people still drink only pond water. Another 11.3% have wells that have become dysfunctional. Only 14.4% of this rural population has access' to functioning wells. Guinea worm was eliminated from 107 of the hamlets mainly by the use of cloth filters and chemical treatment of ponds. While this proves that it is possible to eradicate guinea worm, it fails to leave behind the legacy of reliable, safe water supplies that was the hope of the Water Decade.

Animals↗
PubMed1993

Schistosomiasis prevalence after administration of praziquantel to school children in Melela village, Morogoro region, Tanzania.

A study of the prevalence of schistosomiasis was carried out in 253 school children in Melela, Tanzania, one year after a single dose of praziquantel, 40 mg/kg body weight. The cure rate was 90.4%. However the new incidence estimate was 21.2% in children who were initially negative. The use of reagent strips in urine tests for the detection of urinary schistosomiasis was also evaluated. The presence of blood in the urine was highly sensitive (> 96%) and specific (87%). The sensitivity of proteinuria was less, but it was highly specific (94%). This study shows that chemotherapy will have to be combined with other measures to achieve lasting benefits and raises the question as to how often the population should be treated. It also confirms the value of urine test strips as an indirect diagnostic test for urinary schistosomiasis in an endemic area. Further follow-up is necessary to make useful predictions concerning incidence and reinfection rates in the community. This will also help in deciding how often chemotherapy should be given to the population.

Adolescent↗
PubMed1992

Isolation of Trypanosoma cruzi from blood by histopaque and continuous percoll gradient centrifugations.

Separation of the blood forms of trypanosomes from the blood of infected animals is difficult, especially in the case of Trypanosoma cruzi Y strain. Two procedures to isolate the Y strain blood forms of T. cruzi using polyvinyl pyrrolidone-coated silica (percoll) and histopaque are reported in this study. The recovery rates of parasites were 16 +/- 5 and 68 +/- 16%, respectively. The parasites isolated by these methods presented normal motility and morphology and were infective to albino mice with prepatent periods, parasitemia curves, and polymorphism patterns during the infection that were similar to those of control parasites. In addition, the preservation of surface antigens was confirmed by immunocytochemical studies.

Animals↗
PubMed2002

Vaccination of monkeys with recombinant Plasmodium falciparum apical membrane antigen 1 confers protection against blood-stage malaria.

A major challenge facing malaria vaccine development programs is identifying efficacious combinations of antigens. To date, merozoite surface protein 1 (MSP1) is regarded as the leading asexual vaccine candidate. Apical membrane antigen 1 (AMA1) has been identified as another leading candidate for an asexual malaria vaccine, but without any direct in vivo evidence that a recombinant form of Plasmodium falciparum AMA1 would have efficacy. We evaluated the efficacy of a form of P. falciparum AMA1, produced in Pichia pastoris, by vaccinating Aotus vociferans monkeys and then challenging them with P. falciparum parasites. Significant protection from this otherwise lethal challenge with P. falciparum was observed. Five of six animals had delayed patency; two of these remained subpatent for the course of the infection, and two controlled parasite growth at <0.75% of red blood cells parasitized. The protection induced by AMA1 was superior to that obtained with a form of MSP1 used in the same trial. The protection induced by a combination vaccine of AMA1 and MSP1 was not superior to the protection obtained with AMA1 alone, although the immunity generated appeared to operate against both vaccine components.

Animals↗
PubMed2001

The prevalence and transmission to exotic equids (Equus quagga antiquorum, Equus przewalskii, Equus africanus) of intestinal nematodes in contaminated pasture in two wild animal parks.

Wild equids maintained in large enclosures may suffer from helminth diseases because common hygiene practices have only limited effects on parasite populations. Weekly monitoring of helminth prevalences and pasture infestation was performed for 1 yr in several extensive maintenance systems of two wildlife parks with similar climates to determine when veterinary intervention to control parasites would be useful. We also sought evidence of natural immunogenic reactions among herds of Chapman zebras (Equus quagga antiquorum), Przewalski's horses (Equus przewalskii) and dwarf donkeys (Equus asinus africanus). Fecal and vegetation samples and cultures for third-stage larvae revealed permanent egg shedding in the three species and pasture infestation during the warm, moist periods (July-September) in all enclosures. Stable social structure and low equid population density may be sufficient to make prophylaxis unnecessary in adults, whereas biotic and abiotic environmental factors such as crowding, animal transfers, social integration of subadults, and weaning stress may facilitate temporary severe infections of individuals. Biweekly helminth monitoring is a useful diagnostic tool for extensive management of exotic equids.

Animal Husbandry↗
PubMed1997

Therapeutic and protective efficacy of doramectin injectable against gastrointestinal nematodes in cattle in New Zealand: a comparison with moxidectin and ivermectin pour-on formulations.

Two similar studies were conducted in New Zealand to compare the therapeutic and persistent activity of doramectin injectable, moxidectin pour-on, ivermectin pour-on and oxfendazole oral drench when administered to nematode-infected cattle which were then grazed on common pastures. On day 0 (treatment day), 40 cattle were weighed, faecal sampled and allocated on the basis of day--3 faecal egg counts (FEC) to four treatment groups. Cattle were then treated with either doramectin by subcutaneous (s.c.) injection, moxidectin and ivermectin by topical application, or oxfendazole orally using label-recommended dosages. Oxfendazole treatment served primarily as a control to monitor reinfection without persistent activity. Faecal samples for nematode egg counts and coprocultures for larval differentiation were collected six times between day 0 and day 56 and all cattle were reweighed on day 56. Doramectin reduced pretreatment FEC by 99.1% in the first study and by 100% in the second study when assessed at 14 days posttreatment. Corresponding reductions for moxidectin were 80.8% and 85.2%, for ivermectin 86.0% and 80% and oxfendazole 78.3% and 100%, respectively. Posttreatment rise in FEC indicated that reinfection of moxidectin-treated animals occurred at the same time as oxfendazole controls in both trials. Posttreatment rise in FEC with ivermectin pour-on was similar to moxidectin and oxfendazole in one study, but in the other study ivermectin pour-on delayed the rise by 14-21 days. The rise in FEC for doramectin was delayed for 14-21 days in one study and at least 21 days in the other. The better parasite control provided by doramectin resulted in greater weight gains for cattle over the 56-day period as compared to moxidectin pour-on, ivermectin pour-on and oxfendazole in both trials. Gains of doramectin treated cattle were significantly (p < 0.05) greater than those of ivermectin and moxidectin groups in one trial and the oxfendazole group only in the other.

Administration, Oral↗
PubMed2025

RNG2 tethers the conoid to the apical polar ring in Toxoplasma gondii to enable parasite motility and invasion.

The conoid is a dynamic, tubulin-based structure conserved across the Apicomplexa that undergoes extrusion during egress, gliding motility, and invasion in Toxoplasma gondii. This organelle traverses the apical polar ring (APR) in response to calcium waves and plays a critical role in controlling parasite motility. While the actomyosin-dependent extrusion of the conoid is beginning to be elucidated, the mechanism by which it remains apically anchored to the APR is still unclear. RNG2, a protein localized to both the conoid and the APR, has emerged as a strong candidate for mediating this connection. Biochemical analysis revealed that RNG2 is an unstable protein, undergoing extensive proteolytic cleavage both in the parasite and in heterologous expression systems. Its biochemical properties, with the presence of large coiled-coil domains, likely facilitate the formation of concatenated assemblies, enabling RNG2 to serve as a dynamic and resilient bridge between the conoid and the APR. Using a combination of iterative ultrastructure expansion microscopy and immunoelectron microscopy, we confirmed the localization of RNG2 to the 22 tethering elements bridging the APR and the conoid. Conditional depletion of RNG2 led to the striking detachment of the intact conoid organelle from the APR, supporting an essential role for RNG2 as a tether. Cryo-electron tomography of conoid-less parasites revealed that, in the absence of RNG2, the apical vesicle remains anchored to the plasma membrane, while the rhoptries follow the detached conoid. Although RNG2 depletion only mildly reduces microneme secretion, the parasites are immotile and exhibit impaired rhoptry discharge, highlighting the critical role of proper conoid anchorage in motility and host cell invasion. Comprehensive mutagenesis of RNG2 identified distinct regions responsible for binding to the conoid and the APR, and demonstrated that the full-length, intact protein is essential for bridging these two structures and for its functional activity. Altogether, RNG2 emerges as a pivotal protein that ensures conoid functionality and coordination in Coccidia.

Toxoplasma↗
PubMed1978

Methods to improve the health of cattle in the tropics: conclusions and economic appraisal.

The results of the immune responses of immunised and chemoprophylactically treated calves to tick-borne (Boophilus microplus) challenge indicate that the system of immunisation was effective in protecting cattle against Anaplasma marginale, Babesia argentina (bovis), and B. bigemina. However, chemoprophylaxis was effective only against Babesia spp. but not against A. marginale. Both methods showed a substantial advantage over no control system when using native cattle breeds in a zone endemic for bovine anaplasmosis and babesiosis. Based on the net economic gain per calf starting the experiment, sizeable differences were noted at 308 days between the calves in the immunised group, chemoprophylaxis group, tick and gastrointestinal parasite control group and the experiment control group.

Anaplasmosis↗
PubMed1998

Differentiation, regulation, and death of T helper cell subsets during infection with Leishmania major.

The development and regulation of specific types of immune responses are dependent on understanding the biology of T helper cell (Th cells) subsets. We primarily use murine infections with the intracellular protozoan parasite, Leishmania major, as our model to investigate Th1/2 cell biology, where following infection, some inbred strains of mice develop a Th1 response and heal, but others develop a Th2 response and fail to control parasite replication. We focus on three major questions: 1. What factors are involved in Th cell development? 2. How can we switch an established immune response from one type to another? 3. How are immune responses downregulated once the parasites are eliminated? We demonstrated that interleukin (IL)12 promotes Th1 cell development and that IL12 is an effective adjuvant for cell-mediated immunity. We are now defining factors regulating the expression of the IL12 receptor and the importance of CD28-B7 interactions for the development of vaccine-induced immunity. We also found that IL12, in combination with chemotherapy, abrogates a Th2 response. These results have implications for treatment of infectious diseases, autoimmunity, and allergy. Currently, we are studying how such switching occurs. Finally, we found that TNFRp55-/- mice are unable to heal leishmanial lesions in spite of eliminating the parasites. This result suggests that the tumor necrosis factor receptor (TNFR) p55 plays a critical, and previously unrecognized, role in downregulating pathogen-induced inflammatory responses. Our current hypothesis is that the TNFRp55 is required for induction of cell death in these lesions, and that in its absence, lymphocytes accumulate at the site of inflammation.

Animals↗
PubMed2004

Disease dynamics: all caused by males?

Some host individuals tend to acquire parasites at a much faster rate than do others--a consequence of heterogeneities in susceptibility and/or exposure. This is termed 'overdispersion' and, as for many other statistical phenomena, the degree of overdispersion often conforms to a 20/80 rule, where 20% of the host population is responsible for approximately 80% of the parasite transmission. But which are the hosts driving so much of the dynamics of an infectious disease? If host individuals at the tail of the frequency distribution can be identified by some common label, controlling parasitic diseases would be much easier. In two recent papers, Perkins et al. and Ferrari et al. have shown that male hosts are much more important than female hosts in the transmission of parasites.

Journal Article↗
PubMed1993

Use of reseeded pastures as an aid in the control of gastrointestinal nematodes.

The degree of nematode infectivity of a previously contaminated pasture which was reseeded after harvesting of a soya bean crop was determined by use of four tracer lambs and four tracer calves. The eight tracers were put to graze for 14 days and housed for another 14 days before being slaughtered, when faeces and the intestinal tracts were examined for worm eggs and parasites. With the exception of one animal, which was found to be harbouring 20 Cooperia punctata, the tracers had no adult or immature nematodes. The implications of the use of such pastures are discussed in relation to their possible role in parasite control and anthelmintic resistance in Brazil.

Animals↗
PubMed2004

Speckle interferometry applied to pharmacodynamic studies: evaluation of parasite motility.

The work reported here describes the application of the optical technique known as dynamic speckle interferometry to evaluate the motility of nematode parasites exposed to different anthelmintic drugs. This technique, a well proven tool for assessing the time evolution of different phenomena, is here successfully used to quantify parasite motility in pharmacodynamic assays. The characterization of the pharmacological properties of anthelmintic drugs is critical to optimize their use in parasite control. Besides, the evaluation of nematode motility is a relevant indicator of the pharmacodynamic effect of anthelmintic drugs. The application of this approach to study the motility of Haemonchus contortus (used as a model of nematode parasites) larvae exposed to different drugs is presented, showing its usefulness.

Animals↗
PubMed2004

Distinct roles for lymphotoxin-alpha and tumor necrosis factor in the control of Leishmania donovani infection.

Tumor necrosis factor (TNF) is critical for the control of visceral leishmaniasis caused by Leishmania donovani. However, the role of the related cytokine lymphotoxin (LT) alpha in this infection is unknown. Here we report that C57BL/6 mice deficient in TNF (B6.TNF(-/-)) or LT alpha (B6.LT alpha(-/-)) have increased susceptibility to hepatic L. donovani infection. Furthermore, the outcome of infection in bone marrow chimeric mice is dependent on donor hematopoietic cells, indicating that developmental defects in lymphoid organs were not responsible for increased susceptibility to L. donovani. Although both LT alpha and TNF regulated the migration of leukocytes into the sinusoidal area of the infected liver, their roles were distinct. LT alpha was essential for migration of leukocytes from periportal areas, an event consistent with LT alpha-dependent up-regulation of VCAM-1 on liver sinusoid lining cells, whereas TNF was essential for leukocyte recruitment to the liver. During visceral leishmaniasis, both cytokines were produced by radio-resistant cells and by CD4(+) T cells. LT alpha and TNF production by the former was required for granuloma assembly, while production of these cytokines by CD4(+) T cells was necessary to control parasite growth. The production of inducible nitric oxide synthase was also found to be deficient in TNF- and LT alpha-deficient infected mice. These results demonstrate that both LT alpha and TNF are required for control of L. donovani infection in noncompensatory ways.

Animals↗