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PubMed1984

Cooperation between developing countries and the pharmaceutical industry in the control of parasitic diseases: a proposal for a practical approach.

In this paper a pragmatic approach to the cooperation between developing countries and the pharmaceutical industry is proposed. This approach is based upon a division of tasks between the partners involved, thus maximizing the output through optimal use of each partner's capabilities. In the model proposed here, the pharmaceutical industry remains responsible for continued therapeutic research and development. These efforts are rewarded by the industry's transfers of active ingredients to pharmaceutical production plants. Pharmaceutical production and packaging plants can be decentralized and located in developing countries. Local organized integrated health care programs are the clients of the regional pharmaceutical plants. These programs can be coordinated and sponsored by national and international agencies and organizations. It is suggested that the transactions, possibly with the exception of the delivery of the products to the patients, be concluded along principles of the market economy. Dirigism and bureaucracy must be avoided.

Delivery of Health Care↗
PubMed1990

Grazing management strategies for the control of parasitic diseases in intensive sheep production systems.

The effect of forward (F) and lateral (L) creep grazing, as two possible management alternatives of intensive production systems, on the gastro-intestinal nematode epidemiology of ewes and lambs was studied. Two groups of Romanov x Rasa Aragonesa ewes rearing twins and maintained on an autumn-contaminated pasture at a mean stocking density of 35 ewes ha-1, were used. Measurements were made of the population of infective larvae on the pasture, level of serum pepsinogen, worm eggs in faeces of ewes and lambs, and lambs' growth rate. In addition, post-mortem worm counts from 'indicator' lambs were used to establish the level of infection at each rotational grazing cycle. Two different waves of nematode infection were identified. In both treatments, the over-wintering larvae were responsible for the first outbreak of parasitism which was particularly important for lambs on Treatment F. The second wave of infection apparently came up with several overlapped L3 generations and had different effects on the animals of each group. While early pasture contamination was suffered by the lambs of Treatment F, lambs on Treatment L were not seriously affected until the end of the third grazing cycle (end of May). The different grazing behaviour of lambs in both treatments appeared to be related to the outbreak of parasitism in lambs. The general pattern of liveweight gains was similar for both groups of animals. However, during the first 90 days on pasture lamb growth rate under Treatment L (193 g day-1) was significantly higher than that under Treatment F (164 g day-1). The serum pepsinogen values, worm burdens and liveweight gains indicate that under intensive systems where lateral creep grazing is allowed for lambs, the level of parasite infection is maintained within acceptable limits for the first 90 days on pasture with lambs' growth rate close to their potential. However, the parasitic consequences of grazing under a forward creeping system indicate that anthelmintic drenchings should be used at lambing and at 3-week intervals thereafter during the first 42 days on pasture, after which the risk of contamination from the over-wintering population is over.

Animal Husbandry↗
PubMed2005

Indole alkaloid marine natural products: an established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases.

The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets. Historically marine natural products have largely been explored as anticancer agents. The indole alkaloids are a class of marine natural products that show unique promise in the development of new drug leads. This report reviews the literature on indole alkaloids of marine origin and also highlights our own research. Specific biological activities of indole alkaloids presented here include: cytotoxicity, antiviral, antiparasitic, anti-inflammatory, serotonin antagonism, Ca-releasing, calmodulin antagonism, and other pharmacological activities.

Alkaloids↗
PubMed2005

Genetic resistance to malaria in mouse models.

Murine models have proved to be excellent tools in the support of studies of the human genetic bases of malaria resistance and have enabled the mapping of 12 resistance loci, eight of them controlling parasitic levels and four controlling cerebral malaria. Further studies using this method have identified a Pklr variant that confers resistance to murine malaria, a result that shows the potential of this approach to aid the understanding of mechanisms of disease resistance. In the future, the use of murine models for genetic resistance to malaria could lead to the identification of relevant genetic factors that control this devastating disease.

Animals↗
PubMed2006

Developments and hurdles in generating vaccines for controlling helminth parasites of grazing ruminants.

As a direct consequence of rising drug resistance among common nematodes of grazing animals, efforts toward state-of-the-art vaccine development have clearly intensified in recent years, fuelled primarily by the advent of newer technologies in gene discovery, by advancements in antigen identification, characterisation and production. In this regard, it is appropriate to review progress that has been made in generating helminth vaccines and in particular, vaccines against common nematodes of production animals for consumption. In like manner, it is prudent to evaluate barriers that have hindered progress in the past and continue to present obstacles that must be solved when utilizing and depending on host immunity to attenuate parasitic infections.

Animals↗
PubMed1985

Trypanosoma cruzi: possible control of parasite transmission by blood transfusion using amphiphilic cationic drugs.

About 200 clinically used amphiphilic cationic drugs have been shown to be active in vitro against Trypanosoma cruzi at concentrations of less than or equal to 1 mM. Activity against epimastigote and trypomastigote forms was similar, and in both cases the most potent drugs were litracene, maprotiline, thioproperazine, and the acridines: acranil, aminacrine, and mepacrine. Fluorescence microscopy demonstrated that epimastigotes rapidly accumulate acridines initially in discrete subcellular organelles. The amount of drug incorporated during 15 min of incubation was sufficient to produce subsequent lysis of both trypomastigotes and epimastigotes within 24 hr at 4 C. Trypanocidal activity was dependent on the extracellular pH (optimum greater than or equal to 8) and drug exposure time, but was independent of red blood cell density, serum dilution, and temperature (4 to 37 C). Despite their trypanocidal activity, amphiphilic cationic drugs appear to have no significant effect on the energy state of red blood cells at a concentration of 1 mM. These drugs have a possible role in the prevention of Chagas' disease by blood transfusion.

Aminoacridines↗
PubMed1997

Control of parasites in cultured marine finfishes in Southeast Asia--an overview.

Mariculture in Southeast Asia began in the 1970s and expanded rapidly during the 1980s, with the commercial hatchery production of the seabass Lates calcarifer. Other important cultured species were Epinephelus coioides, Epinephelus malabaricus, Lutjanus johni, and Lutjanus argentimaculatus. Intensification in the polyculture of these species and the large-scale international movement of fingerlings or juveniles, as well as the rapid expansion and concentration of fish farms, have caused severe problems resulting from parasitic infections. Infections in maricultured fish are predominantly caused by monoxenous parasites, in particular the capsalid and diplectanid monogeneans. Heteroxenous blood parasites also successfully maintained transmission in the culture system despite their requirement for an intermediate host. Prophylactic chemical treatments helped to reduce parasitic infection but did not eliminate them and once introduced into the floating netcage culture system, these parasites managed to maintain their transmission successfully. Despite the current lack of information regarding the biology of many parasites affecting cultured marine fishes, it nevertheless is possible to develop methodologies to produce an integrated health management system specifically designed to the needs of the mariculture practiced in the Southeast Asian region. This system is important and should include a sequence of prophylaxes, adequate nutrition, sanitation, immunization and an effective system of marketing for farmed fishes.

Animals↗
PubMed2005

Genetic control of parasite clearance leads to resistance to Plasmodium berghei ANKA infection and confers immunity.

Unprecedented cure after infection with the lethal Plasmodium berghei ANKA was observed in an F2 progeny generated by intercrossing the wild-derived WLA and the laboratory C57BL/6 mouse strains. Resistant mice were able to clear parasitaemia and establish immunity. The observed resistance was disclosed as a combinatorial effect of genetic factors derived from the two parental strains. Genetic mapping of survival time showed that the WLA allele at a locus on chromosome 1 (colocalizing with Berghei resistance 1 (Berr1), a locus associated with resistance to experimental cerebral malaria) increases the probability to resist early death. Also, the C57Bl/6 allele at a novel locus on chromosome 9 (Berr3) confers overall resistance to this lethal Plasmodium infection. This report underlines the value of using wild-derived mouse strains to identify novel genetic factors in the aetiology of disease phenotypes, and provides a unique model for studying parasite clearance and immunity associated with malaria.

Animals↗
PubMed2005

Transfection of Trypanosoma cruzi with host CD40 ligand results in improved control of parasite infection.

We have previously shown that infection by Trypanosoma cruzi, a parasitic protozoan, is reduced by injection of CD40 ligand (CD40L)-transfected 3T3 fibroblasts (D. Chaussabel, F. Jacobs, J. de Jonge, M. de Veerman, Y. Carlier, K. Thielemans, M. Goldman, and B. Vray, Infect. Immun. 67:1929-1934, 1999). This prompted us to transfect T. cruzi with the murine CD40L gene and to study the consequences of this transfection on the course of infection. For this, epimastigotes (Y strain) were electroporated with the pTEX vector alone or the pTEX-CD40L construct, and transfected cells were selected for their resistance to Geneticin G418. Then strain Y-, pTEX-, and pTEX-CD40L-transfected epimastigotes were transformed by metacyclogenesis into mammalian infective forms called Y, YpTEX, and YpTEX-CD40L trypomastigotes. Transfection of the CD40L gene and expression of the CD40L protein were assessed by reverse transcription-PCR and Western blot analysis. The three strains of parasites were infective in vitro for mouse peritoneal macrophages. When organisms were inoculated into mice, a very low level of parasitemia and no mortality were seen with the YpTEX-CD40L strain compared to the Y and YpTEX strains. Furthermore, the proliferative capacity and the secretion of gamma interferon were both preserved in spleen cells (SCs) from YpTEX-CD40L-infected mice but not with SCs from Y- and YpTEX-infected mice. These results suggest that the CD40L produced by transfected T. cruzi is involved in the modulation of an antiparasite immune response. Moreover, mice surviving YpTEX-CD40L infection resisted a challenge infection with the wild-type strain. Taken together, our data demonstrate the feasibility of generating a T. cruzi strain expressing a bioactive host costimulatory molecule that counteracts the immunodeficiency induced by the parasite during infection and enhances protective immunity against a challenge infection.

Animals↗