[Show abstract][Hide abstract] ABSTRACT: Background
This study is a component of a large research project on five major neglected zoonotic diseases (NZDs) including cystic echinococcosis and was undertaken in the Province of Sidi Kacem over a period of four years (April 2009-March 2013).
Questionnaires were administered at community level in a total of 27 communes and visits were made to all of the 10 abattoirs situated in the Province, to collect qualitative data on determinants of transmission for disease in humans and animals. More specifically, community knowledge, attitudes and practices related to cystic echinococcosis were assessed, as well as the extent to which local customs and behaviours may promote transmission. Abattoir infrastructure and practices, and their role in perpetuating disease transmission were also critically evaluated.
The results show that only 50 % of people have heard of the disease, and of those, only 21 % are aware of the dog’s role in disease transmission. Sixty-seven per cent of respondents stated that dogs are fed ruminant organs deemed unfit for human consumption. Owned dogs have access to the family home, including the kitchen, in 39 % of households. The extent of this close proximity between humans and animals is even more pertinent when one considers that dogs are omnipresent in the community, with an average of 1.8 dogs owned per household. The unrestricted access of dogs to abattoirs is a huge issue, which further promotes disease transmission.
This study would suggest that the high prevalence of cystic echinococcosis in humans and animals in Morocco is largely due to three factors: 1) abundance of dogs 2) engagement in risky behaviour of the local population and 3) poor abattoir infrastructure and practices. This has serious implications in terms of the socio-economic impact of the disease, especially for rural poor communities.
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The online version of this article (doi:10.1186/s40249-015-0082-9) contains supplementary material, which is available to authorized users.
[Show abstract][Hide abstract] ABSTRACT: Dogs are the main source of human cystic echinococcosis. An oral vaccine would be an important contribution to control programs in endemic countries. We conducted two parallel experimental trials in Morocco and Tunisia of a new oral vaccine candidate against Echinococcus granulosus in 28 dogs. The vaccine was prepared using two recombinant proteins from adult worms, a tropomyosin (EgTrp) and a fibrillar protein similar to paramyosin (EgA31), cloned and expressed in a live attenuated strain of Salmonella enterica serovar typhimurium. In each country, five dogs were vaccinated with the associated EgA31 and EgTrp; three dogs received only the vector Salmonella; and six dogs were used as different controls. The vaccinated dogs received two oral doses of the vaccine 21 d apart, and were challenged 20 d later with 75,000 living protoscoleces. The controls were challenged under the same conditions. All dogs were sacrificed 26–29 d postchallenge, before the appearance of eggs, for safety reasons. We studied the histological responses to both the vaccine and control at the level of the duodenum, the natural localization of the cestode. Here we show a significant decrease of parasite burden in vaccinated dogs (70% to 80%) and a slower development rate in all remaining worms. The Salmonella vaccine EgA31-EgTrp demonstrated a high efficacy against E. granulosus promoting its potential role in reducing transmission to humans and animals. Copyright: ß 2008 Petavy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by INCO-MED (ICFP599A3PR01) 2000-2004. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.
[Show abstract][Hide abstract] ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
[Show abstract][Hide abstract] ABSTRACT: Dogs are the main source of human cystic echinococcosis. An oral vaccine would be an important contribution to control programs in endemic countries. We conducted two parallel experimental trials in Morocco and Tunisia of a new oral vaccine candidate against Echinococcus granulosus in 28 dogs. The vaccine was prepared using two recombinant proteins from adult worms, a tropomyosin (EgTrp) and a fibrillar protein similar to paramyosin (EgA31), cloned and expressed in a live attenuated strain of Salmonella enterica serovar typhimurium.
In each country, five dogs were vaccinated with the associated EgA31 and EgTrp; three dogs received only the vector Salmonella; and six dogs were used as different controls. The vaccinated dogs received two oral doses of the vaccine 21 d apart, and were challenged 20 d later with 75,000 living protoscoleces. The controls were challenged under the same conditions. All dogs were sacrificed 26–29 d postchallenge, before the appearance of eggs, for safety reasons.
We studied the histological responses to both the vaccine and control at the level of the duodenum, the natural localization of the cestode. Here we show a significant decrease of parasite burden in vaccinated dogs (70% to 80%) and a slower development rate in all remaining worms. The Salmonella vaccine EgA31-EgTrp demonstrated a high efficacy against E. granulosus promoting its potential role in reducing transmission to humans and animals.
[Show abstract][Hide abstract] ABSTRACT: Its natural resistance to antiprotozoal chemotherapy characterizes the intestinal protozoan parasite Cryptosporidium parvum and the P-glycoprotein-related multidrug resistance proteins such as CpABC3 could be involved. In order to design and study specific inhibitors of the CpABC3 nucleotide-binding domain, a hexahistidine-tagged recombinant protein encompassing the N-terminal cytosolic NBD1 domain was overexpressed in E. coli and purified. The 45 kDa H6-NBD1 displayed intrinsic fluorescent properties consistent with the presence of two Trp residues in a hydrophobic environment. The binding of ATP and the fluorescent analogue TNP-ATP produced a dose-dependent quenching as well as progesterone and the flavone quercetin. The extrinsic fluorescence of TNP-ATP was enhanced upon binding to H6-NBD1, which was only partially displaced by the natural substrate ATP. The recombinant protein hydrolyzed ATP (K(m)=145.4+/-18.2 microM), but ADP (K(m)=4.3+/-0.6mM) and AMP (K(m)=5.4+/-1.5 microM) were also substrates. TNP-ATP is a competitive inhibitor of the catalytic activity (K(i)=36.6+/-4.5 microM), but quercetin and progesterone were not inhibitors, evidencing different binding sites. The recombinant C. parvum H6-NBD1 should be a valuable tool for rational drug design and will allow the discrimination between specific inhibitors of the catalytic site and molecules binding to other sites.
[Show abstract][Hide abstract] ABSTRACT: The main of this study was to show the rapidity of the protoscolicide action of a synthetic compound, dipeptide methyl ester when it is injected under echographic control into hydatid cyst of sheep.
Fourthty sheep with hydatid cysts, repaired at echography and punctionable are treated by dipeptide methyl ester injection at the dose of 110 mM.
In vitro tests have allowed to define the efficacy dose of dipeptide methyl ester which is 110 mM. At echography, after injection of the drug, from the first minutes, a detachment of the inner membrane, a diminution of the size of the treated cyst were observed. The cyst content is modified. The sheep autopsy was realized after 4.6.12 and 17 weeks after the injection and showed a size reduction, a treated cyst calcification.
The dipeptide methyl ester injection into hydatid cyst induces rapidly a morphological alteration, they are calcified. The advantage of this compound is its very rapidity action, this could decrease dissemination risks of hydatid liquid in the organism during operation. Also, this drug permits to reduce the operation time.
[Show abstract][Hide abstract] ABSTRACT: The study of purified alkaline phosphatase and crude extract antigen immunogenicity from Echinococcus multilocularis was carried out on BALB/c mice. The animals were immunized, then infected with E. multilocularis metacestode. The immune response against purified alkaline phosphatase was studied. Flow cytometry analysis of the CD4+ and CD8+ lymphocyte populations showed a predominance of CD4+ populations in infected immunized mice. The specific humoral response to purified alkaline phosphatase was analyzed by enzyme-linked immunosorbent assay method. We noted a stimulation of an immunoglobulin IgG response. The isotypic profile showed a prevalence of IgG1 and IgG3 in immunized infected mice compared to IgG2a and IgG2b. In addition, analysis of the profiles of the in vitro secreted cytokines, after stimulation of the splenocytes from immunized mice, was performed. The cytokine profile was a mix of Th1/Th2 types in the infected and uninfected immunized mice. The results of this study suggest a humoral mixed Th1/Th2 response, with a high predominance of Th2 response. A similar study was conducted in mice immunized with crude total antigen. The comparison of the immune response showed an important immune response in mice immunized with purified alkaline phosphatase compared to mice immunized with the crude total antigen.
Parasitology Research 03/2006; 98(3):218-26. DOI:10.1007/s00436-005-0041-7 · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The in vitro cultivation of Cryptosporidium parvum in the non-adherent cell line THP-1 was evaluated for its capability as a useful additional model to investigate the effect of drugs on this parasite. The purine analog antiviral 2′,3′-dideoxyinosine (ddI) was evaluated and compared to the reference molecule paromomycin in sequential 24 hour experiments beginning at 24 and 72 hour post-infection. The ability of this technique to evaluate the various parasite stages showed that ddI displayed a dose-dependent efficacy especially on the trophozoite and sexual stages. Paromomycin displayed a lower efficacy than previously reported. Both drugs induced a decrease in the number of multiparasitized cells. These results indicate that the purine salvage pathway should be a key chemotherapeutic target against C. parvum.
[Show abstract][Hide abstract] ABSTRACT: In a previous work, we have showed in mice infected with an avirulent strain of Toxoplasma gondii and receiving a didanosine treatment, an important decrease of brain cysts. It is why, the purpose of this study was to investigate the effect of didanosine treatment on AIDS patients having developed Toxoplasma encephalitis. 60 patient reports were analyzed: 22 patients (group 1) did not received didanosine in their antiretroviral treatment and 38 (group 2) were treated with didanosine. The results showed that an antiretroviral therapy was prescribed for 93% of patients, 50% of them received only zidovudine and protease inhibitors were prescribed for 37%. The regimens given most frequently were those including zidovudine plus lamivudine or zidovudine plus indinavir. Among the group 1, 18% have had a relapse of Toxoplasma encephalitis. In the group 2, 37% of the patients suffered from one episode of TE while 16% have had two TE after the pause in their didanosine treatment, the maximum occurring between 4 and 24 months after the pause of didanosine. This study showed that didanosine seems to have an effect on cerebral cysts. Also, this work made a synthesis about the different treatment used in AIDS patients and the new molecules yet in development against T. gondii.
Current HIV Research 11/2004; 2(4):301-7. DOI:10.2174/1570162043351101 · 1.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: EgA31 is a fibrillar protein from Echinococcus granulosus that behaves as a potent antigen during infestation of dogs. The localization of this antigen during development of the parasite was investigated by immunohistochemistry in optical and electron microscopy. The protein is mostly abundant in the microtriches and subtegumental cells of the adult, whereas it is absent from protoscolex microtriches. Eggs, the periphery of calcareous corpuscles, and the germinal layer were other sites of accumulation. Immunogenicity of different domains of the protein was assessed during experimental infection of dogs. It was shown that the polypeptide encoded by the Pst I-Hind III fragment of the complete cDNA is the most antigenic during the infection. The uses of such polypeptide for infection diagnosis and as a candidate vaccine protein are discussed.
[Show abstract][Hide abstract] ABSTRACT: Quinonic derivatives were tested against a virulent RH strain of Toxoplasma gondii maintained in cell culture in THP-1, a human myelomonocytic cell line. The derivatives were tested at various doses (0.5-4 microg/ml) and compared with the reference molecules clindamycine, sulfadiazine, pyrimethamine and atovaquone. The percentage of parasite growth inhibition was observed after 72 h of incubation. The tested derivatives are bicyclic, tricyclic or tetracyclic quinones. Eight of these compounds exhibit over 70% inhibition of parasite growth; and two were nearly equipotent to pyrimethamine. These data indicate that the most active compounds against the RH strain of T. gondii are bis-heterocyclic quinones.
Parasitology Research 12/2002; 88(11):969-71. DOI:10.1007/s00436-002-0615-6 · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cryptosporidium parvum is a coccidian parasite responsible for severe diarrhea in immunocompromised patients. At present, only therapies of limited efficacies are available and despite recent improvements, an easy to perform and reproducible in vitro model is still lacking. The present study shows that the human monocyte cell line THP-1 supports the growth of C. parvum. After inoculation with oocysts, all the asexual and sexual developmental stages were found. Immunofluorescence controls showed that few oocysts remained after infection, disappeared within the first 24 h and that sexual stages reappeared after the second day postinoculation. A continuous asexual life-cycle proceeded throughout the experiments, with at least 15-day cultures. Ultrastructural studies evidenced that the parasites were usually localized at the cell surface and also in the cytoplasm, a feature found in vivo with M cells and macrophages. This culture system is easy to initiate and to maintain with adjustable parasitemias and duration which will allow time-dependent drug-testing and also facilitate the study of the biology of this parasite.
[Show abstract][Hide abstract] ABSTRACT: The alkaline phosphatases (EC 188.8.131.52) from Echinococcus granulosus and E. multilocularis (Cestoda) were compared to each other and to a liver-type enzyme. The purified proteins (210 and 220 kDa, respectively) had a tetrameric structure composed of 4, 56/53 kDa subunits. Enzymatic removal of their N-linked sugar moieties abolished the differences in their apparent molecular weight under reducing conditions. After phase separation in Triton X-114, the E. multilocularis enzyme was the most amphiphilic, and treatment with PI-PIC reduced the amount of the parasite alkaline phosphatases that were in a hydrophobic form by about 50%. Both parasite enzymes were highly resistant to heat denaturation and insensitive to the inhibitors l-phenylalanine and l-leucine. In addition, l-homoarginine, levamisole and ZnCl2 can be used to differentiate the parasite and mammalian liver-type enzymes from each other. The Echinococcus alkaline phosphatases have original biochemical properties when compared to the mammalian liver-type enzyme.
Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology 11/1995; 112(2-112):295-301. DOI:10.1016/0305-0491(95)00091-7 · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The biological effects of Phe-Phe-OMe (1) were evaluated in gerbils against the causative agent of alveolar echinococcosis, Echinococcus multilocularis. Morphological damage to the parasite was examined by transmission electron microscopy. Administration of (1) led to a considerable alteration of the laminated layer. Although a histoenzymatic study showed a decrease in alkaline phosphatase activity in the parasite, a precise mode of action for (1) cannot be proposed.
International Journal of Pharmaceutics 11/1993; 100(1-3):271-277. DOI:10.1016/0378-5173(93)90102-L · 3.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thiadiazole derivatives were synthesized and their anthelmintic activities were tested against a nematode: Syphacia obvelata and a cestode: Hymenolepis nana. The effect of electronic parameters and lipophilicity on activity was determined by means of a multivariate analysis method: the principal components analysis.
European Journal of Medicinal Chemistry 09/1987; 22(5):467–471. DOI:10.1016/0223-5234(87)90038-9 · 3.45 Impact Factor