Publications (13)34.74 Total impact
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Article: Fulminant cryptosporidiosis after near-drowning: a human Cryptosporidium parvum strain implicated in invasive gastrointestinal adenocarcinoma and cholangiocarcinoma in an experimental model.
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ABSTRACT: In the present work, we report the characterization of a Cryptosporidium parvum strain isolated from a patient who nearly drowned in the Deule River (Lille, France) after being discharged from the hospital where he had undergone allogeneic stem cell transplantation. After being rescued and readmitted to the hospital, he developed fulminant cryptosporidiosis. The strain isolated from the patient's stools was identified as C. parvum II2A15G2R1 (subtype linked to zoonotic exposure) and inoculated into SCID mice. In this host, this virulent C. parvum isolate induced not only severe infection but also invasive gastrointestinal and biliary adenocarcinoma. The observation of adenocarcinomas that progressed through all layers of the digestive tract to the subserosa and spread via blood vessels confirmed the invasive nature of the neoplastic process. These results indicate for the first time that a human-derived C. parvum isolate is able to induce digestive cancer. This study is of special interest considering the exposure of a large number of humans and animals to this waterborne protozoan, which is highly tumorigenic when inoculated in a rodent model.Applied and environmental microbiology 03/2012; 78(6):1746-51. · 3.69 Impact Factor -
Article: Cryptosporidium parvum Infection in SCID Mice Infected with Only One Oocyst: qPCR Assessment of Parasite Replication in Tissues and Development of Digestive Cancer.
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ABSTRACT: Dexamethasone (Dex) treated Severe Combined Immunodeficiency (SCID) mice were previously described as developing digestive adenocarcinoma after massive infection with Cryptosporidium parvum as soon as 45 days post-infection (P.I.). We aimed to determine the minimum number of oocysts capable of inducing infection and thereby gastrointestinal tumors in this model. Mice were challenged with calibrated oocyst suspensions containing intended doses of: 1, 10, 100 or 10(5) oocysts of C. parvum Iowa strain. All administered doses were infective for animals but increasing the oocyst challenge lead to an increase in mice infectivity (P = 0.01). Oocyst shedding was detected at 7 days P.I. after inoculation with more than 10 oocysts, and after 15 days in mice challenged with one oocyst. In groups challenged with lower inocula, parasite growth phase was significantly higher (P = 0.005) compared to mice inoculated with higher doses. After 45 days P.I. all groups of mice had a mean of oocyst shedding superior to 10,000 oocyst/g of feces. The most impressive observation of this study was the demonstration that C. parvum-induced digestive adenocarcinoma could be caused by infection with low doses of Cryptosporidium, even with only one oocyst: in mice inoculated with low doses, neoplastic lesions were detected as early as 45 days P.I. both in the stomach and ileo-caecal region, and these lesions could evolve in an invasive adenocarcinoma. These findings show a great amplification effect of parasites in mouse tissues after challenge with low doses as confirmed by quantitative PCR. The ability of C. parvum to infect mice with one oocyst and to develop digestive adenocarcinoma suggests that other mammalian species including humans could be also susceptible to this process, especially when they are severely immunocompromised.PLoS ONE 01/2012; 7(12):e51232. · 4.09 Impact Factor -
Article: Cryptosporidium infection in a veal calf cohort in France: molecular characterization of species in a longitudinal study.
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ABSTRACT: ABSTRACT: Feces from 142 animals were collected on 15 farms in the region of Brittany, France. Each sample was directly collected from the rectum of the animal and identified with the ear tag number. Animals were sampled three times, at 5, 15 and 22 weeks of age. After DNA extraction from stool samples, nested PCR was performed to amplify partial 18S-rDNA and 60 kDa glycoprotein genes of Cryptosporidium. The parasite was detected on all farms. One hundred out of 142 calves (70.4%) were found to be parasitized by Cryptosporidium. Amplified fragments were sequenced for Cryptosporidium species identification and revealed the presence of C. parvum (43.8%), C. ryanae (28.5%), and C. bovis (27%). One animal was infected with Cryptosporidium ubiquitum. The prevalence of these species was related to the age of the animal. C. parvum caused 86.7% of Cryptosporidium infections in 5-week-old calves but only 1.7% in 15-week-old animals. The analysis of the results showed that animals could be infected successively by C. parvum, C. ryanae, and C. bovis for the study period. C. parvum gp60 genotyping identifies 6 IIa subtypes of which 74.5% were represented by IIaA15G2R1. This work confirms previous studies in other countries showing that zoonotic C. parvum is the dominant species seen in young calves.Veterinary Research 12/2011; 42(1):116. · 4.06 Impact Factor -
Article: Fulminant cryptosporidiosis associated with digestive adenocarcinoma in SCID mice infected with Cryptosporidium parvum TUM1 strain.
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ABSTRACT: We recently demonstrated that Cryptosporidium parvum IOWA strain induces in situ ileo-caecal adenocarcinoma in an animal model. Herein, the ability of another C. parvum strain to induce digestive neoplasia in dexamethasone-treated SCID mice was explored. SCID mice infected with C. parvum TUM1 strain developed a fulminant cryptosporidiosis associated with intramucosal adenocarcinoma, which is considered an early histological sign of invasive cancer. Both evidence of a role of C. parvum in adenocarcinoma induction and the extended prevalence of cryptosporidiosis worldwide, suggest that the risk of C. parvum-induced gastro-intestinal cancer in humans should be assessed.International journal for parasitology 11/2010; 40(13):1469-75. · 3.39 Impact Factor -
Article: Development of Cryptosporidium parvum-induced gastrointestinal neoplasia in severe combined immunodeficiency (SCID) mice: severity of lesions is correlated with infection intensity.
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ABSTRACT: We reported previously that Cryptosporidium parvum was able to induce intestinal tumors in severe combined immunodeficiency (SCID) mice treated with corticoids. To further characterize this Cryptosporidium-induced cell transformation, SCID mice treated with dexamethasone were challenged with C. parvum oocysts, and euthanatized sequentially after infection for histologic examination. Ki-67 was used as a marker of cellular proliferation. Our previous results were confirmed, and it was also found that mice receiving higher inocula (10(6)-10(7)) experienced more severe neoplastic development. Additionally, neoplastic changes were observed not only in the caecum but also in the stomach and duodenum of some animals. Interestingly, SCID mice (6/6) inoculated with 10(5)-10(7) oocysts showed high grade intraepithelial neoplasia or adenomas with high grade dysplasia in the caecum after Day 46 post-infection (PI). Immunohistochemistry for Ki-67 staining indicated the neoplastic process associated to cryptosporidiosis, and evidenced the first immunohistochemical alterations at early stages of the process, even at 3 weeks PI.The American journal of tropical medicine and hygiene 02/2010; 82(2):257-65. · 2.59 Impact Factor -
Chapter: Infectious Forms of Parasites in Food: Man Embedded in Ecosystems
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ABSTRACT: Foodborne parasites have usually environmental infectious stages. In developing countries, high concentrations of parasite infectious forms contaminate the environment entailing high prevalence of foodborne parasitic diseases with significant impact on health and economy. Complex interactions among exposure to contaminated food and water, disease, poverty and malnutrition take place. In developed countries, food- or waterborne parasitic infections keep also a considerable importance, as shown by the persistence of infectious water- or foodborne outbreaks and the occurrence of infections due to emergent or reemergent eukaryotic pathogens. Since parasite infections are usually rare in developed areas, a breakdown in prevention measures and specific health staff training often occur. Most emerging or reemerging parasite species are agents of foodborne infections. Considering only parasite “protists”, most emerging or reemerging species can be foodborne, waterborne or contagious as Giardia, Cryptosporidium species or, likely, Microsporidia. These pathogens belong to taxonomically unrelated Eukaryotic groups but they share common features: (a) mostly monoxenous; (b) ubiquitous; (c) challenging taxonomy; (d) unclear notions on transmission, infection source or reservoir; (e) highly resistant infectious life stages; (f) lack of efficient experimental models; (g) uncertain pathogenic power to immunocompetent hosts. Regarding emerging or reemerging helminthes, those transmitted by foodborne route are: Anisakis simplex, Echinococcus granulosus, Diphyllobothrium species, Metorchis conjunctus, Taenia solium and Trichinella spiralis. To consume exotic meals could increase foodborne parasitic risk in Europe. Although common representations of human daily life show a humanity that has in some way “escaped” from ecosystems, men take on their role of top level consumers, and are therefore exposed to the associated highly diversified parasitological risk. Keywordsparasites-fungi-emerging-reemerging-opportunistic-foodborne-cryptosporidiosis-foodborne parasite infections- Anisakis - Trichinella -eukaryotic pathogens12/2009: pages 299-332; -
Article: Molecular characterization of Cryptosporidium isolates from humans and animals in Iran.
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ABSTRACT: Isolates of Cryptosporidium spp. from human and animal hosts in Iran were characterized on the basis of both the 18S rRNA gene and the Laxer locus. Three Cryptosporidium species, C. hominis, C. parvum, and C. meleagridis, were recognized, and zoonotically transmitted C. parvum was the predominant species found in humans.Applied and Environmental Microbiology 03/2007; 73(3):1033-5. · 3.83 Impact Factor -
Article: Cryptosporidium parvum, a potential cause of colic adenocarcinoma.
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ABSTRACT: Cryptosporidiosis represents a major public health problem. This infection has been reported worldwide as a frequent cause of diarrhoea. Particularly, it remains a clinically significant opportunistic infection among immunocompromised patients, causing potentially life-threatening diarrhoea in HIV-infected persons. However, the understanding about different aspects of this infection such as invasion, transmission and pathogenesis is problematic. Additionally, it has been difficult to find suitable animal models for propagation of this parasite. Efforts are needed to develop reproducible animal models allowing both the routine passage of different species and approaching unclear aspects of Cryptosporidium infection, especially in the pathophysiology field. We developed a model using adult severe combined immunodeficiency (SCID) mice inoculated with Cryptosporidium parvum or Cryptosporidium muris while treated or not with Dexamethasone (Dex) in order to investigate divergences in prepatent period, oocyst shedding or clinical and histopathological manifestations. C. muris-infected mice showed high levels of oocysts excretion, whatever the chemical immunosuppression status. Pre-patent periods were 11 days and 9.7 days in average in Dex treated and untreated mice, respectively. Parasite infection was restricted to the stomach, and had a clear preferential colonization for fundic area in both groups. Among C. parvum-infected mice, Dex-treated SCID mice became chronic shedders with a prepatent period of 6.2 days in average. C. parvum-inoculated mice treated with Dex developed glandular cystic polyps with areas of intraepithelial neoplasia, and also with the presence of intramucosal adenocarcinoma. For the first time C. parvum is associated with the formation of polyps and adenocarcinoma lesions in the gut of Dex-treated SCID mice. Additionally, we have developed a model to compare chronic muris and parvum cryptosporidiosis using SCID mice treated with corticoids. This reproducible model has facilitated the evaluation of clinical signs, oocyst shedding, location of the infection, pathogenicity, and histopathological changes in the gastrointestinal tract, indicating divergent effects of Dex according to Cryptosporidium species causing infection.Infectious Agents and Cancer 02/2007; 2:22. -
Article: Cryptosporidium population genetics: evidence of clonality in isolates from France and Haiti.
Journal of Eukaryotic Microbiology 02/2006; 53 Suppl 1:S33-6. · 2.66 Impact Factor -
Article: First molecular data on cryptosporidiosis in Venezuela.
Journal of Eukaryotic Microbiology 02/2006; 53 Suppl 1:S30-2. · 2.66 Impact Factor -
Article: Platelet dysfunction-eosinophilia syndrome in parasitized Venezuelan children.
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ABSTRACT: Platelet dysfunction was detected in six children with purpura and eosinophilia. We conducted clinical evaluations, hematologic and platelet function tests, clotting studies (bleeding time, prothrombin time, partial thromboplastin time, thrombin time, factor XIII, factor VIII, and von Willebrand factor), assays for IgG and IgM antibodies to platelets, and a search for stool parasites. Mild bleeding phenomena (ecchymoses, petechiae, epistaxis, and gingival) were transient. All children showed intestinal parasites and marked eosinophilia (mean count = 2,615.2 cells/muL, 95% confidence interval = 1,259.6-5,429.8). Main abnormalities included prolonged bleeding times (50%) and defective aggregation with collagen (100%) adrenaline (66%), or ADP (66%). Antibodies to platelets were not detected. Anti-parasite therapy reversed the hemorrhagic manifestations and normalized eosinophil counts and platelet alterations. No relationship could be established between excess eosinophils, intensity of bleeding, or type and degree of platelet abnormalities. Thrombocytopathic features mimicked the intrinsic defect of storage pool disease. The possible pathogenic roles of eosinophilia and parasitism are reviewed. This is the first report of this pathologic combination in Latin American children.The American journal of tropical medicine and hygiene 09/2005; 73(2):381-5. · 2.59 Impact Factor -
Article: Cryptosporidiosis in HIV-infected Venezuelan adults is strongly associated with acute or chronic diarrhea.
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ABSTRACT: A cross-sectional study was undertaken to determine the prevalence of cryptosporidiosis and its clinical and laboratory pattern in Venezuelan HIV-infected patients (N = 397). At enrollment, they underwent thorough clinical history and physical examination and provided stool specimens for the identification of Cryptosporidium sp. and other parasites. Cryptosporidium sp. was identified in 59 subjects (15%). This infection was strongly associated with acute and chronic diarrhea, weight loss, CD4(+) counts below 100 cells/mm(3), older age in patients with leukopenia, and more than 5 stools per day when CD4(+) counts were below 100 cells/mm(3). In addition, patients with Cryptosporidium infection were less likely to be coinfected with Isospora belli (OR = 0.05, P = 0.001). In fact, results of the current study confirm the worldwide importance of cryptosporidiosis as a clinically significant opportunistic infection associated with an advanced stage of immunosuppression.The American journal of tropical medicine and hygiene 08/2005; 73(1):54-7. · 2.59 Impact Factor -
Article: Isosporiasis in Venezuelan adults infected with human immunodeficiency virus: clinical characterization.
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ABSTRACT: A cross-sectional study was undertaken to determine the prevalence of isosporiasis and its clinical and laboratory pattern in Venezuelan patients infected with human immunodeficiency virus (HIV) (n = 397). At enrollment, they underwent a thorough clinical history and physical examination, and provided stool specimens for the identification of Isospora belli and other parasites. Isospora belli was identified in 56 subjects (14%) and diarrhea, either acute or chronic, was present in 98% of these cases (P < 0.001). Eosinophilia was strongly associated with isosporiasis (P = 0.01). It was also found that the presence of eosinophilia was more common in I. belli-infected patients without weight loss (P < 0.001). Twenty-six (81.25%) subjects with I. belli infection had CD4+ cell counts < 200 cells/mm3 (P = 0.03). In addition, the data and its description shows the association to be < 100 cells/mm3. This infection seems to be seasonal because the recovery of oocysts occurred mainly in months with significant rainfall. In fact, isosporiasis should be suspected in HIV-infected patients from tropical countries with diarrhea, weight loss, eosinophilia, and low CD4+ cell counts.The American journal of tropical medicine and hygiene 09/2003; 69(2):217-22. · 2.59 Impact Factor
Top co-authors
Top Journals
Institutions
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2010–2012
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Université Lille Nord de France
Lille, Nord-Pas-de-Calais, France
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2007–2010
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Université du Droit et de la Santé Lille 2
Lille, Nord-Pas-de-Calais, France
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2003–2005
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Central University of Venezuela
Caracas, Distrito Capital, Venezuela
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