Educating for health: the integrated project's IEC program.
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Schistosomiasis and the molecular biology of the male-female interaction of S. mansoni.
Parasitic helminths of the genus Schistosoma are the causative agents of schistosomiasis, an infectious disease affecting humans and animals. For humans, it is one of the most prevalent parasitemias in the world, second behind malaria. Estimates of the World Health Organisation (WHO) indicate that more than 200 million people live in endemic areas (WHO, Fact Sheet No 115). With respect to animals, a number of 530 million cattle is estimated to live in endemic territories of Africa and Asia. In the last two decades ambitious efforts have been made to develop an effective vaccine against schistosomes, but without resounding success. In addition, there is a pressing need to develop new anthelmintics due to the potential emerging resistance against the commonly used drug praziquantel. Therefore, the understanding of essential physiological or developmental processes of schistosome biology and attempts to intervene in these processes may open new ways to control the parasite. Towards this end, one possibility is to study the unusual biology of schistosomes. These digenean parasites differ from other parasitic flukes by living in the blood vessels. Furthermore, schistosomatids are the only bisexual family of the class trematoda. A nearly unique phenomenon in nature is that a continuous pairing-contact is essential for the development of the reproductive organs of the female, an aspect for the possible design of novel control strategies.
Animals↗
Apical membrane antigen 1 is a cross-reactive antigen between Neospora caninum and Toxoplasma gondii, and the anti-NcAMA1 antibody inhibits host cell invasion by both parasites.
The cross-reactive antigens of Neospora caninum and Toxoplasma gondii are important in the exploration to determine the common mechanisms of parasite-host interaction. In this study, a gene encoding N. caninum apical membrane antigen 1 (NcAMA1) was identified by immunoscreening of a N. caninum tachyzoite cDNA expression library with antisera from mice immunized with recombinant T. gondii apical membrane antigen 1 (TgAMA1). NcAMA1 was encoded by an open reading frame of 1695 bp, which encoded a protein of 564 amino acids. The single-copy NcAMA1 gene was interrupted by seven introns. NcAMA1 showed 73.6% amino acid identity to TgAMA1. Mouse polyclonal antibodies raised against the recombinant NcAMA1 (rNcAMA1) recognized a 69-kDa native parasite protein by Western blotting. Immunofluorescence analysis showed that NcAMA1 was localized to the apical end of tachyzoites. Two-dimensional electrophoresis and Western blotting indicated that an approximately 57-kDa cleavage product was released into the excretory/secretory products of N. caninum. Preincubation of free tachyzoites with anti-rNcAMA1 IgG antibodies inhibited the invasion into host cells by N. caninum and T. gondii. These results indicated that AMA1 is a cross-reactive antigen between N. caninum and T. gondii and a potential common vaccine candidate to control two parasites.
Amino Acid Sequence↗
Comparison of oral artesunate and quinine plus tetracycline in acute uncomplicated falciparum malaria.
In Thailand Plasmodium falciparum malaria is highly resistant to available antimalarials. Investigations on the efficacy of existing antimalarials and of alternative drugs are urgently needed. Artesunate has been shown to be effective against falciparum malaria, but is associated with a high recrudescence rate. We have carried out a comparative clinical trial of the standard regimen of quinine + tetracycline versus oral artesunate at a 700-mg total dose given over 5 days to patients with acute uncomplicated falciparum malaria. The 64 male patients who took part in the study were randomized to receive either quinine-tetracycline (33 patients) or oral artesunate (31 patients). All the patients were admitted to the Bangkok Hospital for Tropical Diseases for 28 days. Oral artesunate had faster parasite and fever clearance times than the combination quinine-tetracycline, but the cure rate was not significantly different for the two regimens. However, the occurrence of adverse effects, such as tinnitus, was significantly higher in the quinine-tetracycline group. Surprisingly nausea and dizziness were rather common with artesunate. The possibility of neurological adverse effects for artesunate should also be borne in mind. Oral artesunate (700 mg given over 5 days) is effective and better tolerated than the combination quinine-tetracycline. The cure rate we obtained is higher than that reported in previous studies with 600 mg of oral artesunate given over 5 days. Oral artesunate can be considered as an alternative drug for multiple-drug-resistant falciparum malaria; however, adverse effects, particularly neurotoxicity, should be closely monitored before its widespread use can be recommended.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Genetic control of immune responses to parasites: selection for responsiveness and non-responsiveness to Trichuris muris in random-bred mice.
Populations of Schofield strain, random-bred mice were shown to have a bimodal variation in ability to bring about immune expulsion of the nematode Trichuris muris. This variation was genetically determined and independent of the size of infection experienced. The proportion of mice unable to achieve worm expulsion (non-responders) was relatively constant in various populations of the strain but was increased by selective breeding from mice of known status. Crosses made between non-responder and responder mice produced progeny that were almost all (92%) of responder phenotype, showing that the ability to achieve worm expulsion was inherited as a dominant characteristic. It is suggested that the genetic control involves a small number of genes; the possible immunological mechanisms by which control is mediated are briefly discussed.
Animals↗
In vitro and in vivo activities of three acridine thioethers against Leishmania donovani.
The lack of definitive chemotherapeutic agents to fight against visceral leishmaniasis has lead to the testing of numerous compounds. In the present work, we carry out an in-depth study of the activity against Leishmania donovani of three acridine derivatives both in vitro and in vivo. These compounds have proven to be highly effective at medium and high concentrations of 10 microg/ml, against both flagellate and nonflagellate forms of the parasite, which, though obtained in vitro, closely resemble natural intracellular amastigotes. The in vivo assays showed a significant reduction in the percentage of parasitation versus control, for all the compounds tested. In addition, we have studied the possible mechanism by which these acridine derivatives act: they displayed a greater inhibitory effect against macromolecule synthesis in treated flagellates, yet alterations are also caused in the production of end metabolites and in the activity of different enzymes. The data obtained indicate that the acridine derivatives had several targets, one of them is the synthesis of nucleic acids and proteins, while the second one might be interaction with the carbohydrate and energy-production processes in the parasite. This conclusion is consistent with our observations concerning the ultrastructural changes induced in the parasite by these compounds principally at the mitochondrial level.
Acetates↗
The impact of traditional management on seasonal internal parasite burdens and productivity of indigenous Tswana goats in southern Botswana.
Data collected monthly over a period of two years were live weight, packed cell volume (PCV), nematode faecal egg counts (FECs) and coccidial oocyst counts from faecal analyses for 100 mixed age (3-7 years) indigenous Tswana does. The aims of this experiment were to determine seasonal FECs and coccidial oocysts in these goats and quantify the relationships of these burdens to liveweight and PCV. FECs significantly (P < 0.05) varied with season, with the warmer seasons viz spring, summer and autumn having higher log (x + 1) parasite burdens than the cooler winter, while seasonal trends for coccidial oocysts were not obvious. PCV was also significantly (P < 0.05) lower in the warmer seasons than winter. FECs and coccidial oocysts in all seasons were less than the mean log (x + 1) of 3.3 inferred to reduce production in small stock. Correlation coefficients were strongly negative: -0.95 for FECs and liveweight and -0.84 for FECS and PCV, indicating that these worms had a negative impact on productivity. A further study should be conducted to quantify the effects of controlling these parasites during the warm seasons on productivity.
Animals↗
Kinetics of an experimental inflammatory reaction induced by Leishmania major during the implantation of paraffin tablets in mice.
In leishmaniasis, macrophages play important but potentially divergent roles. They act as the host cell in which the parasite may reside and replicate, and, at the same time, they act as an effector cell with the potential to eliminate the parasite. In this work, we experimentally induced an inflammatory model that provokes a continued recruitment of the monocytes to the site of inflammation. This model was carried out by means of implanting paraffin tablets under the skin of Balb/c or C57BL/6 mice. Mice were then infected with Leishmania major to determine how the monocyte inflammatory response to paraffin could influence the course of infection with L. major. Mice were sacrificed 15, 21, 30, and 45 days after infection, and skin and inflammatory capsule were collected for histopathology. At 15 days and 21 days, the lesions induced by L. major in combination with paraffin contained markedly increased numbers of parasites relative to lesions in parallel control animals infected with L. major (without paraffin). Both Balb/c and C57BL/6 mice exhibited high parasite numbers in their lesions. The intense parasite burden observed following paraffin implantation would suggest that the monocytes-macrophages that are recruited to the lesion are acting more as a host cell permitting parasite growth than as an effector cell capable of eliminating L. major. At later times, the two strains of mice stratified according to their genetic susceptibility/resistance profiles. Susceptible Balb/c mice continue to have large parasite burdens, whereas the resistant C56BL/6 mice begin to control parasite numbers. This later observation indicates that the genetic difference between susceptible and resistant strains is not due to differences in monocyte recruitment and cannot be reversed through the altering of monocyte inflammation.
Animals↗
Immunity of ivermectin treated cattle to challenge from helminth parasites in the following season.
Two groups of yearling cattle which had been treated with ivermectin either three and eight, or three, eight and 13 weeks after turn out to trichostrongyle contaminated pasture in their first grazing season were exposed in the following season to natural challenge with helminth parasites. To assess their immunity to this challenge each group shared a pasture with parasite naive first season calves. No anthelmintic treatments were administered at any time during the year. Throughout the grazing period the yearlings showed normal respiratory rates, negative faecal lungworm larval counts, and, relative to the calves, low faecal trichostrongyle egg counts. All the first season calves developed patent lungworm infections and on one occasion the mean respiratory rates of each group of calves were significantly greater than those of the yearling cattle. At the end of the grazing period, from early May until late September or October 1986, the cattle were removed from pasture and together with parasite naive controls challenged with either 10 or 22 third stage larvae of Dictyocaulus viviparus/kg bodyweight and necropsied between 18 and 23 days later. Although the experimental challenge resulted in relatively heavy lungworm infection of the naive controls, none of the yearlings and only three of the 11 calves which had been at pasture were found to be infected. However, large numbers of arrested fourth stage larvae of Ostertagia ostertagi were present in all the naturally infected yearlings and calves.
Animals↗
Evaluation of the integrated projects in Tanzania and Zambia, March 12-19, 1988.
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Africa↗
Pentoxifylline as an ancillary treatment for severe falciparum malaria in Thailand.
Pentoxifylline, an inhibitor of tumor necrosis factor, has been evaluated as an antimalarial agent in combination with artesunate in 45 patients with severe falciparum malaria. Patients were admitted to the intensive care unit at the Hospital for Tropical Diseases in Bangkok, Thailand, and randomly assigned to treatment for 72 hr with a combination of intravenously administered artesunate and 1) placebo, 2) low-dose pentoxifylline (0.83 mg/kg/hr), or 3) high-dose pentoxifylline (1.67 mg/kg/hr). All 45 patients had one or more manifestations of severe malaria such as cerebral malaria (n = 18), renal failure requiring hemodialysis (n = 9), azotemia (n = 8), jaundice (n = 25), or hyperparasitemia (n = 30). The overall severity was comparable in the three groups. Clinical outcome was assessed with respect to the parasite clearance time and the fever clearance time in all patients. In addition, a number of subsidiary outcome variables were examined in specific subgroups, including the recovery time from coma for patients with cerebral malaria, the duration of intubation in patients with respiratory distress, the number of hemodialysis treatments needed for patients with acute renal failure, and the number of units of blood administered to patients requiring transfusion. Concentrations of tumor necrosis factor were reduced in all three groups at 48 hr after treatment. No significant differences among the three treatment groups were found for any of the outcome variables examined. We conclude that the addition of pentoxifylline to artesunate therapy for severe malaria produced no evident clinical benefit.
Adolescent↗
Reproductive performance of farmed red deer (Cervus elaphus) in New Zealand. IV. Biological markers as risk factors for yearling and adult hind conception.
A 2-year observational study of 15 red deer (Cervus elephus) farms was carried out in New Zealand from March 1992. In each year of study, approximately 1650 hinds were individually monitored for reproductive success. During farm visits in March 1992 and 1993, five yearling and five adult hinds per farm were randomly selected and blood sampled to define their haematological, biochemical and blood mineral profile. Faecal samples were taken for parasite egg and larvae count. Biological markers potentially affecting the probability of conception before May 1 or of conception that year were investigated separately using multivariable logistic regression analysis. Adult hinds with low serum phosphorus concentrations were more likely to conceive before May 1. Lower conception rates were observed in yearling hinds when blood glutathione peroxidase, serum vitamin B12, and serum albumin concentrations were low, and when faecal lungworm larval counts were high. While these associations have yet to be proven as causal, data suggests that monitoring and maintaining adequate blood elements, and controlling internal parasites in yearling hinds, may assist farmers to achieve optimum reproductive performance in farmed red deer herds.
Animals↗
Prevalence of intestinal parasitosis within three population groups in La Plata, Argentina.
The prevalence of intestinal parasites was studied as a function of socioeconomic conditions within La Plata, Argentina. Age, sex, and environmental factors were considered. Thus, from each of three areas within the city - the first a 'marginal' zone, the second a lower-income suburb, the third a middle-income urban district - 100,101, and 91 children up to 14 years old, respectively, were examined for intestinal parasites. Giardia lamblia was the most frequent species found. The respective prevalences of intestinal parasites overall (73, 54.4, and 35.1%), of polyparasitism (61.6, 27.2, and 12.5%), and of helminthic infection (32, 10.9, and 0.0%) were the highest within the population group having significantly inferior sanitary and environmental conditions. A positive statistical association between the prevalence of intestinal parasitosis and age was observed in all three of the neighborhoods. We also noted a correspondence between the frequency of such infections and school attendance in the two suburban districts. Management practices in accordance with the specific characteristics of an urban environmental and sociocultural ecosystem are thus important for the control of intestinal-parasite infection within municipal populations.
Adolescent↗
Genetic control of immune responses to parasites: immunity to Trichuris muris in inbred and random-bred strains of mice.
A comparison has been made of the responses of random-bred CFLP and inbred NIH mice to infection with Trichuris muris. Random-bred mice showed greater variation in worm burdens and less uniformity in worm expulsion. Irradiation prior to infection reduced variation, but did not increase the mean level of infection above that shown by the most susceptible unirradiated mice. In NIH mice, however, irradiation raised the level of infection in all mice. The factors responsible for variation between CFLP mice and for the level of infection in NIH mice came into play after the fifth day of infection and were inactivated by cortisone acetate. It is suggested that these factors are immunologically mediated and under direct genetic control. Uniformity of infection and expulsion in NIH mice is therefore seen as a consequence of genetic uniformity; variability in CFLP mice as a consequence of genetic variation. The time of worm expulsion was found to differ markedly between inbred strains of mice. Hybrid progeny showed the expulsion time characteristic of the parental strain with the most rapid expulsion; greater resistance was therefore inherited as a dominant characteristic. The genetic control of immunity to T. muris is discussed in the context of the antibody- and cell-mediated components of the expulsion process.
Animals↗
The efficacy of Michel's dose and move system on gastrointestinal nematode infections in diary calves.
The efficacy of a move to aftermath in July combined with moxidectin or fenbendazole treatment for the control of parasitic gastroenteritis (PGE) in calves was evaluated in three field experiments in the Netherlands. In all five treated groups high gastrointestinal nematode infections and PGE were prevented by a dose and move in July. Cooperia infections increased to moderate levels in two groups treated with moxidectin and one group treated with fenbendazole. In both other groups and also for Ostertagia in these three groups, low to extremely low infections were acquired. In the first experiment high primary infections, resulting in high faecal egg counts and a moderate increase of blood pepsinogen values occurred before the dose and move. Nevertheless, these primary infections were not high enough to result in PGE. In both other experiments primary infection levels were low and faecal egg counts increased to 100-650 eggs/g faeces at the end of the grazing season. The blood pepsinogen values of non-treated control groups demonstrated that it took more than a month after their move to aftermath before substantial reinfection occurred on the new pasture. In the first and the last experiment only, high Ostertagia and Cooperia infections developed in the control group at the end of the grazing season, though it did not result in clinical PGE. The experiments demonstrate all theoretical risks of the dose and move system: (1) PGE early in the grazing season as a result of high overwintered pasture infectivity. (2) PGE just before the move as a result of an early midsummer increase in pasture infectivity. (3) PGE around housing as a result of insufficient suppression of pasture infectivity late in the grazing season. (4) Underexposure to nematode infections due to a high suppression of nematode infections. Nevertheless, it can be concluded that under normal conditions the dose and move system remains to be a valuable and easily applicable system for the control of PGE.
Animal Husbandry↗
Interaction of natural killer cells with Trypanosoma cruzi-infected fibroblasts.
The protozoan parasite Trypanosoma cruzi circulates in the blood as trypomastigotes and invades a variety of cells to multiply intracellularly as amastigotes. The acute phase triggers an immune response that restricts the proliferation of the parasite. However, parasites are able to persist in different tissues causing the pathology of Chagas' disease. Natural killer (NK) cells play an important role in innate resistance to a variety of pathogens. In the present study we demonstrate that NK cells trigger trypanocidal mechanisms in infected L929 cells that are critically dependent on inducible nitric oxide (NO) synthase (iNOS) induction which is, to a major degree, triggered by interferon (IFN)-gamma provided by NK cells. This work provides a more detailed analysis of how NK cells as a part of the innate immune system participate in the control of parasites that reside intracellularly in fibroblast-like L929 cells.
Animals↗