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The development and validation of an age-structured model for the evaluation of disease control strategies for intestinal helminths.

Epidemiological modelling can be a useful tool for the evaluation of parasite control strategies. An age-structured epidemiological model of intestinal helminth dynamics is developed. This model includes the explicit representation of changing worm distributions between hosts as a result of treatment, and estimates the morbidity due to heavy infections. The model is used to evaluate the effectiveness of different programmes of age-targeted community chemotherapy in reducing the amount of morbidity due to helminth infection. The magnitude of age-related heterogeneities is found to be very important in determining the results of age-targeted treatment programmes. The model was verified using field data from control programmes for Ascaris lumbricoides and Trichuris trichiura, and was found to provide accurate predictions of prevalence and mean intensities of infection during and following different control regimes.

Adult↗

Survey of intestinal parasites in pigs from intensive farms in Guangdong Province, People's Republic of China.

The prevalence of intestinal parasites was investigated in intensive pig farms in Guangdong Province, China between July 2000 and July 2002. Faecal samples from 3636 pigs (both sexes and five age groups) from 38 representative intensive pig farms employing different parasite control strategies were examined for the presence of helminth ova and protozoan oocysts, cysts and/or trophozoites using standard techniques. Of the 3636 pigs sampled, 209 (5.7%) were infected with Trichuris suis, 189 (5.2%) with Ascaris, 91 (2.5%) with Oesophagostomum spp., 905 (24.9%) with coccidia (Eimeria spp. and/or Isospora suis) and 1716 (47.2%) with Balantidium coli. These infected pigs were mainly from farms without a strategic anti-parasite treatment regime. Concurrent infection of multiple parasites was common, and T. suis was the most common nematode infecting breeding, young and mature pigs. The results of the present investigation provide relevant 'base-line' data for assessing the effectiveness of control strategies against intestinal parasitism in intensively raised pigs in Guangdong Province, China.

Animals↗

Overberg Research Projects: III. A preventive worm control programme for sheep in the Rûens, in the winter rainfall region of South Africa.

The mass gains and internal parasite burdens of a flock of untreated ewes and lambs were compared with those of a similar flock of treated ewes and lambs. These data, combined with climatic data, were used to compile a nematode parasite control programme for sheep in the Rûens, a sub-region of the winter rainfall area of South Africa. Teladorsagia were the most numerous parasites in the ewes and later in the season, also in the lambs. From July onwards, the development of Teladorsagia was inhibited regardless of previous exposure to worms, the number of worms present or the age of the host. Initially, Nematodirus dominated in the lambs and its development was not inhibited. Low numbers of Nematodirus, mainly inhibited, were found in the ewes. Both parasites were rife in winter but disappeared from the pasture during spring, while Trichostronglus rugatus, the dominant species of Trichostronglus, infested the lambs in spring and persisted in them throughout summer. Anthelmintic treatments had no significant effect on the live mass gains of ewes and suckling lambs while they were on lush, but heavily infested lucerne pastures for 5.5 months, but after a further 6 months on safe wheat stubble pastures, the overall mean live mass gain of the treated lambs was a significant 4.7 kg more than that of the untreated lambs. The integrated, preventive worm control programme recommended consists of pre-winter, pre-spring and pre-summer treatments with broad spectrum anthelmintics, but transfer to safe pastures after each treatment is essential.

Animals↗

The calyx fluid of Microplitis rufiventris parasitoid and growth of its host Spodoptera littoralis larvae.

The morphology of the female reproductive system of pupal and adult stages of Microplitis rufiventris and the ultrastructure of the ovaries are described and illustrated. Two morphologically distinct types of particles of nuclear origin, i.e., polydnavirus (PDV) and a virus-like filamentous particle (VLFP) were detected in the ovarian calyx fluid of the female wasp. It is likely that these particles are injected into the host during oviposition. PDV initiated replication in the calyx of mid-aged pupae and in pharate adults and were present throughout adult life. VLFP were only seen in the calyx fluid of newly emerged adults, and therefore observed after the PDV. Feulgen and methyl-green pyronin staining revealed the presence of DNA in both types of particles. The effects of injection of Spodoptera littoralis larvae with a combination of parasitoid viruses and venom of M. rufiventris females (CxFV) were investigated and the results were compared with two control groups, i.e., larvae injected with Pringle's saline (PS) and naturally parasitized larvae. CxFV-larvae showed significant declines (P<0.05) in food consumption, weight of ejected faeces and weight gain when compared with PS-larvae. However, naturally parasitized larvae (parasitoid egg+CxFV+ovarian protein) displayed a high significance score (P<0.01) in comparison with those of PS-larvae. The approximate digestibility (AD) values of S. littoralis larvae were positively affected as early as day 2 post-treatment by either injection of CxFV or parasitization. However, a reduction in AD was observed in both PS- and CxFV-larvae on day 3-7 in comparison with naturally parasitized larvae. Other indices of food utilization were unchanged in CxFV-larvae when compared to saline treated or parasitized controls.

Animals↗

The interplay between environmental and host factors during an outbreak of visceral leishmaniasis in eastern Sudan.

Parasitic diseases, including human visceral leishmaniasis, are multifactorial. Factors that are expected to play an important role in the parasite-human interaction are exposure, parasite "virulence" and host resistance factors. In populations exposed to Leishmania donovani most subjects do not allow the parasites to establish themselves or remain asymptomatic. Some individuals, however, fail to control parasite expansion and dissemination and develop a visceral disease. We report here the results of a longitudinal survey whose aims were to identify risk factors underlying visceral leishmaniasis (VL) susceptibility during an outbreak that occurred in a Sudanese village between 1995 and 1999. Most of the 660 subjects (90%) living in the central district were exposed to Leishmania and 20.9% (n = 138), mostly teenagers, developed VL. VL cases increased markedly in adults late in the outbreak, suggesting some changes in adult resistance status or in Leishmania "virulence" during the epidemic. Age and ethnic origin of the patients were the most important critical risk factors to account for the distribution of the VL cases that were recorded during the whole epidemic. This and the high frequency of VL in certain families suggest that host genetic factors played an important role in shaping the outbreak in this village. However, environmental factors (the presence of cows and neems in the households) that increase/decrease exposure to the parasite had significant effects on the distribution of VL cases in the village in the first phase of the outbreak.

Adult↗

Protective role of IgE in immunocompromised rat toxoplasmosis.

In contrast to euthymic adult Fischer rats, immunocompromised Nu/Nu animals develop a lethal infection when inoculated with the RH strain of the protozoan Toxoplasma gondii. However, a significant period of survival is obtained when Nu/Nu rats are passively transferred with sera from 28-day infected Fischer +/+ (euthymic) animals. Specific IgE are involved since IgE-depleted sera are unable to afford such a protection. Only excreted/secreted Ag or living tachyzoites are able to induce a significant protective IgE response in intact animals. In addition, platelets or, to a lesser extent, eosinophil-rich populations from Toxoplasma infected or excreted-secreted Ag-immunized euthymic animals bear surface IgE and are cytotoxic for the parasite in vitro. Also, adoptive transfer of immune platelets confers a significant degree of protection to Toxoplasma-infected Nu/Nu animals. Our results clearly show the key role of Ag present in both living parasites and excreted-secreted Ag to induce, in this model, a protective IgE response. In addition, as in other parasitic infections, platelets and probably eosinophils are the effector cells involved in controlling parasitic dissemination during Toxoplasma infection in immunocompromised rats.

Animals↗

Expression and regulation of mitochondrial uncoupling protein 1 from brown adipose tissue in Leishmania major promastigotes.

Rat uncoupling protein 1 (UCP1) was successfully translated in transfected Leishmania major promastigotes. Immune electron microscopy revealed that the protein was exclusively in the mitochondria. UCP1 expression was about 350,000 copies per promastigote, accounting for 4.7% of the total mitochondrial protein. In intact parasites, expression of UCP1 induced a slight increase in respiratory rate and a modest decrease in mitochondrial membrane potential (delta psi(m)). In contrast, in digitonin-permeabilized parasites, a significantly lower value both in delta psi(m) (57 +/- 10 vs 153 +/- 12 mV) and respiratory control ratio (0.99 vs 1.54) were observed for UCP1 versus control parasites, although when UCP1 activity was inhibited by bovine serum albumin (BSA) and GDP, control values were restored. Therefore, a fully functional UCP1 was present and only partially inhibited in vivo by endogenous purine nucleotides. However, neither ATP levels, growth rate nor mitochondrial protein import differed significantly between both types of parasites. Expression of the pore-like mutant UCP1 delta 9 was deleterious to the organism. Consequently, Leishmania was capable of expressing and importing into mitochondria proteins from higher eukaryotes lacking an N-terminal targeting pre-sequence as UCP1. As described previously, parasite metabolism had only a limited tolerance to mitochondrial disfunction. Transfection of Leishmania with foreign proteins which play an important regulatory role in metabolism is a useful tool to study both parasite metabolism in general, and alternative pathways involved in maintaining internal homeostasis.

Adipose Tissue, Brown↗

A critical look at the importance, prevalence and control of toxocariasis and the possibilities of immunological control.

The visceral infection of humans with Toxocara canis is particularly prevalent in children and may cause a variety of symptoms that commonly persist for 6-24 months. The ocular infection usually causes permanent loss of visual acuity. Human infection is acquired by ingestion of embryonated T. canis eggs with contaminated dirt. Review of recent reports indicates that patent T. canis infection is widely prevalent in the general population of dogs all over the world (3-81%) and results in a substantial contamination of the ground (0.3-87%). The results of sensitive and specific serological tests suggest that about 7% of the clinically healthy human population of the United States, about 5% of that of Canada, and about 4% of that in Great Britain is infected with the parasite. Control of transmission of the parasite to man is often attempted by eliminating the infection in dogs, reducing the population of dogs and the environmental contamination with their feces, and educating the public about the zoonotic potential of toxocariasis. The evidence reviewed indicates that these methods are only marginally effective. Because T. canis relies on congenital and lactogenic transmission to persist in nature, only a procedure that effects the sustained killing of the reservoir larvae in the tissues of the bitch, or of newly-acquired parasites, is expected to be successful. Research with mice, rabbits and dogs demonstrated that prior infections of the host induce the development of protective immunity to reinfections. This procedure, however, leaves remnant populations of larvae from the immunizing infections that are resistant to anthelmintics and to the effect of prior irradiation. Hyperimmunization with partially-purified extracts of T. canis larvae induced 37% resistance to a challenge in mice when the extract was administered alone, and 76% resistance when administered with lipopolysaccharide adjuvant. Production of complete resistance, however, will probably require the prior control of the immunosuppression induced by the parasite. T. canis infections inhibit the production of homologous protective immunity and antibody responses to heterologous antigens, probably by interfering with the activity of helper T-cells, competing with protective antigens, and suppressing antibody synthesis. The evidence indicates, however, that an anti-T. canis vaccine to eliminate the parasite in dogs is feasible.

Animals↗

Immune response induced by New World Leishmania species in C57BL/6 mice.

In the present study, C57BL/6 mice were inoculated with metacyclic Leishmania amazonensis or L. braziliensis promastigotes. While these animals were capable of controlling the infection by L. braziliensis, they developed chronic lesions with elevated numbers of parasites when infected by L. amazonensis. The differences in parasite control were associated with a decreased production of IFN-gamma and TNF by lymph node cells from L. amazonensis-infected mice. Furthermore, these animals presented decreased spleen cell proliferation and activation of germinal centers. In addition, we compared the ability of these parasites to hydrolyze extracellular ATP and AMP. While the ATPase activity of both parasite species was similar, L. amazonensis promastigotes presented higher AMP hydrolytic activity. This increased activity may lead to an increased production of adenosine, which has been shown to present anti-inflammatory activity and may thus be involved in the establishment of the immunosuppression observed in mice infected by L. amazonensis.

Adenosine Monophosphate↗

Selective killing of Leishmania amastigotes expressing a thymidine kinase suicide gene.

The thymidine kinase gene of Herpes simplex type-1 virus was transfected into several Leishmania species to create drug-sensitive mutants. Expression of the thymidine kinase gene is not by itself harmful to Leishmania cells but it is capable of phosphorylating ganciclovir, a nucleoside analog, into a highly toxic product. In addition to the generation of Leishmania promastigotes highly sensitive to ganciclovir, the thymidine kinase gene was expressed similarly by amastigotes engulfed either by murine or by human macrophages. Leishmania major amastigotes expressing thymidine kinase were eliminated by 85% when treated with ganciclovir. Selective killing of parasites expressing suicide genes at their infective stage could suggest novel strategies for controlling parasitic infections.

Animals↗

Role of T lymphocytes in the resistance and immunopathology of experimental Chagas' disease. I. Histopathological studies.

The results reported here show that Trypanosoma cruzi can parasitize almost all tissues of mice; however, the T-dependent immune response controls parasite invasion, leading undesirable immunopathological effects. Inflammatory infiltrate was rare in heart or skeletal muscle and other organs of Nu/Nu, but was abundant in tissues of Nu/+ mice. Cellular inflammatory lesions could be induced in Nude mice by the transfer of lymph node cells from Nu/+ animals infected with T. cruzi.

Adrenal Glands↗

Research needs on internal parasites of horses.

The importance of the horse industry to the economy of the United States and the impact of parasitic infections on the industry are well documented. However, contemporary research activity on internal parasites of horses has not kept pace with growth of the horse population. Parasitic infections are a major facet of enteritis and colic in horses. Parasites are also associated with poor growth and development, respiratory tract disease, dermatitis, and CNS lesions. Babesia infections remain a threat to horses imported from some regions of the world. Most research activity has dealt with the development of new antiparasitic drugs. Efforts must be made to integrate these studies with observations on the bionomics of parasites in different regions and under different management conditions into more effective and less costly integrated parasite control programs. Increased research activity concerning the pathogenesis and immune response to equine parasitic infections is also necessary. A better understanding of these factors will lead to improved diagnostic, treatment, and preventative measures. Specific research objectives designed to produce short-term and long-term benefits are suggested.

Animals↗

Management and control of nematode parasites of small ruminants in the face of total anthelmintic failure.

Total failure of modern broad spectrum anthelmintics to control nematode parasites of sheep and goats is a reality, of rapidly increasing dimension, on many farms in the tropical / subtropical regions of the world. This is primarily associated with the highly pathogenic, blood sucking parasite, Haemonchus contortus, and where it now cannot be controlled by chemotherapy, annual mortalities exceeding 20% of the flock can be expected. Thus sheep and goat enterprises become totally unsustainable, unless major changes in management are effected. These must include a change away from reliance on suppressive anthelmintic treatment and to include several non-chemotherapeutic management options. In situations where livestock numbers need to be preserved and there is no opportunity to increase the grazing area available, then zero grazing with cut-and-carry herbage from uncontaminated pasturelands is the only option. In other circumstances stocking rates need to be substantially reduced, so that short-term rotational grazing can be effectively practiced. This strategy is improved if it is combined with the biological control of the free-living stages of the parasites, using the microfungus Duddingtonia flagrans. Monitoring the parasitological status of the animals by faecal sampling sentinel sub-flocks for nematode faecal egg counts, or the use of the FAMACHA procedure, are also valuable tools. Improving overall nutrition of the flock is an important adjunct to control. As a long-term priority, attempts to change the genotype of the flocks to those breeds that have been shown to possess natural resistance to H. contortus are worthwhile.

Journal Article↗

Apoptosis in the malaria protozoan, Plasmodium berghei: a possible mechanism for limiting intensity of infection in the mosquito.

Death by apoptosis regulates cell numbers in metazoan tissues and it is mediated by activation of caspases and results in characteristic morphological and biochemical changes. We report here that the malaria protozoan, Plasmodium berghei, exhibits features typical of metazoan apoptotic cells including condensation of chromatin, fragmentation of the nuclear DNA and movement of phosphatidylserine from the inner to the outer lamellae of the cell membrane. In addition, proteins with caspase-like activity were identified in the cytoplasm of the ookinete suggesting that the cellular mechanism of cell death may be similar to that of multicellular eukaryotes. Our data show that more than 50% of the mosquito midgut stages of the parasite die naturally by apoptosis before gut invasion. Cell death was prevented by a caspase inhibitor, treatment resulting in a doubling of parasite intensity. All these features also occur in vitro. Cell suicide thus plays a major and hitherto unrecognised role in controlling parasite populations and could be a novel target for malaria control strategies.

Animals↗

[Drug resistance makes new control measures of stomach parasites in small ruminants necessary].

Control of parasitic gastroenteritis in small ruminants is threatened by the worldwide growing problem of anthelmintic resistance. Therefore, alternative approaches for worm control are imperative. Of utmost importance is to slow down selection pressure for anthelmintic resistance by using alternative control measures combined with minimal anthelmintic usage. New control options for the Netherlands are discussed.

Animals↗

Transmission dynamics of lymphatic filariasis: vector-specific density dependence in the development of Wuchereria bancrofti infective larvae in mosquitoes.

The principles of meta-analysis developed in a previous study were extended to investigate the process of Wuchereria bancrofti (Cobbold) (Filarioidea: Onchocercidae) infection in mosquito (Diptera: Culicidae) hosts, focusing specifically on the functional forms and strength of density dependence in the development of ingested microfilariae (mf) to infective (third instar) larvae (L3). Mathematical models describing observed mf-L3 functional responses for each of the major three parasite-transmitting vector genera, Aedes, Culex and Anopheles mosquitoes, were fitted to paired mf-L3 data collated from all available studies in the published literature. Model parameters were estimated and compared by deriving and applying a data synthetic framework, based on applying a non-linear weighted regression model for fitting mathematical models to multistudy data. The results confirm previous findings of the existence of significant between-genera differences in the mf-L3 development relationship, particularly with regard to the occurrence of limitation in Culex mosquitoes and facilitation in Aedes and Anopheles mosquitoes. New and unexpected findings regarding L3 development from ingested mf were discovered as follows: (1) for Culex, overcompensation in L3 development at higher intensities of mf (or a peaked mf-L3 functional response) was detected; (2) for Aedes mosquitoes, facilitation (with an apparent asymptotic constraint on L3 development at high mf densities) was shown to be the major process governing L3 development, and (3) for Anopheles, a stronger facilitation type of response with no apparent saturation in L3 development appears to govern L3 output from ingested mf. These results yield major new insights regarding filarial vector infection dynamics and their potential impacts on parasite control, and demonstrate the efficacy of employing a data synthetic approach to reveal and estimate parasitic infection processes in host populations.

Aedes↗

Parasites, animal production and sustainable development.

Ecologically sustainable development is aimed at reducing environmental degradation while enabling economic development with equity between the developed and developing worlds and between generations. Parasite control in livestock can both contribute to, and take advantage of, sustainable agriculture. This will tend towards less intensive, lower input, diversified crop and animal production with less risk of parasite-induced losses and greater opportunities for integrated control including the exploitation of grazing management. Chemotherapy will continue to play a part but the most serious problem is resistance in the target species. Except for a few isolated issues, currently used parasiticides are relatively minor contaminants of the food supply or the environment. Nevertheless, the compounds of the future will need to be narrow-spectrum, non-persistent and rapidly degraded, with convenience in the hands of the user reduced in importance. Environmentally friendly alternatives to chemotherapy, including genetic resistance of hosts, vaccines, and biological control, show considerable promise and must be pursued. Sustainable systems pose optimisation problems and more attention must be given to systems research, models and products to aid decisions. If governments are serious about sustainable development, greater support will be needed for longer-term patient, multi-disciplinary research.

Agriculture↗

Microorganisms in the development of subunit vaccines against parasites.

Because of the increasing problems of resistance to chemicals and chemical residues, preventative vaccination has increasing appeal as a way to control parasite infestations in humans and in animals. Such vaccines are now feasible through the application of genetic engineering technology to allow production of parasite protective antigens in microorganisms in commercially viable quantities at an acceptable cost. This concept is illustrated by describing research toward subunit vaccines against human malaria (P. falciparum) and against the tropical cattle tick (B. microplus). Although the concept is straightforward, difficulties include the identification of a protective antigen, refolding of the initial microbial product to achieve the native conformation, and its formulation to produce a vaccine eliciting an adequate and appropriate immune response.

Animals↗