Live Attenuated B. pertussis as a Single-Dose Nasal Vaccine against Whooping Cough

Pertussis is still among the principal causes of death worldwide, and its incidence is increasing even in countries with high vaccine coverage. Although all age groups are susceptible, it is most severe in infants too young to be protected by currently available vaccines. To induce strong protective immunity in neonates, we have developed BPZE1, a live attenuated Bordetella pertussis strain to be given as a single-dose nasal vaccine in early life. BPZE1 was developed by the genetic inactivation or removal of three major toxins. In mice, BPZE1 was highly attenuated, yet able to colonize the respiratory tract and to induce strong protective immunity after a single nasal administration. Protection against B. pertussis was comparable to that induced by two injections of acellular vaccine (aPV) in adult mice, but was significantly better than two administrations of aPV in infant mice. Moreover, BPZE1 protected against Bordetella parapertussis infection, whereas aPV did not. BPZE1 is thus an attractive vaccine candidate to protect against whooping cough by nasal, needle-free administration early in life, possibly at birth

Experimental Tuberculosis in the Wistar Rat: A Model for Protective Immunity and Control of Infection

BACKGROUND: Despite the availability of many animal models for tuberculosis (TB) research, there still exists a need for better understanding of the quiescent stage of disease observed in many humans. Here, we explored the use of the Wistar rat model for the study of protective immunity and control of Mycobacterium tuberculosis (Mtb) infection. METHODOLOGY/PRINCIPAL FINDINGS: The kinetics of bacillary growth, evaluated by the colony stimulating assay (CFU) and the extent of lung pathology in Mtb infected Wistar rats were dependent on the virulence of the strains and the size of the infecting inoculums. Bacillary growth control was associated with induction of T helper type 1 (Th1) activation, the magnitude of which was also Mtb strain and dose dependent. Histopathology analysis of the infected lungs demonstrated the formation of well organized granulomas comprising epithelioid cells, multinucleated giant cells and foamy macrophages surrounded by large numbers of lymphocytes. The late stage subclinical form of disease was reactivated by immunosuppression leading to increased lung CFU. CONCLUSION: The Wistar rat is a valuable model for better understanding host-pathogen interactions that result in control of Mtb infection and potentially establishment of latent TB. These properties together with the ease of manipulation, relatively low cost and well established use of rats in toxicology and pharmacokinetic analyses make the rat a good animal model for TB drug discovery

Cryptosporidium parvum, a potential cause of colic adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>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 <it>Cryptosporidium </it>infection, especially in the pathophysiology field.</p> <p>Results</p> <p>We developed a model using adult severe combined immunodeficiency (SCID) mice inoculated with <it>Cryptosporidium parvum </it>or <it>Cryptosporidium muris </it>while treated or not with Dexamethasone (Dex) in order to investigate divergences in prepatent period, oocyst shedding or clinical and histopathological manifestations. <it>C. muris</it>-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 <it>C. parvum</it>-infected mice, Dex-treated SCID mice became chronic shedders with a prepatent period of 6.2 days in average. <it>C. parvum</it>-inoculated mice treated with Dex developed glandular cystic polyps with areas of intraepithelial neoplasia, and also with the presence of intramucosal adenocarcinoma.</p> <p>Conclusion</p> <p>For the first time <it>C. parvum </it>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 <it>muris </it>and <it>parvum </it>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 <it>Cryptosporidium </it>species causing infection.</p

Raman microspectrometry of laser-reshaped rabbit auricular cartilage: preliminary study on laser-induced cartilage mineralization

Laser-assisted cartilage reshaping (LACR) is a relatively novel technique designed to noninvasively and permanently restructure cartilaginous tissue. It is believed that heat-induced stress relaxation, in which a temperature-mediated disruption of H2O binding is associated with conformational alterations in the proteoglycan and collagen-rich matrix, constitutes the underlying mechanism of LACR. Several reports have suggested that laser-mediated cartilage mineralization may contribute to the permanent shape change of laser-reshaped cartilage. In an effort to validate these results in the context of Er:glass LACR, we performed a preliminary Raman microspectrometric study to characterize the crystal deposits in laser-irradiated chondrocytes and extracellular matrix. For the first time, we identified intracellular calcium sulfate deposits and extracellular calcium phosphate (apatite) crystals in laser-reshaped rabbit auricular cartilage. Calcium carbonate deposits are localized in both irradiated and nonirradiated samples, suggesting that this mineral plays no role in conformational retention. In our discussion, we elaborate on the possible molecular and cellular mechanisms responsible for intra- and extracellular crystallization, and propose a novel hypothesis on the formation of apatite, inasmuch as the biological function of this mineral (providing structure and rigidity in bones and dental enamel) may be extrapolated to the permanent shape change of laser-irradiated cartilag

Cryptosporidium and Colon Cancer: Cause or Consequence?

International audienceThe number of cancers attributable to infectious agents represents over 20% of the global cancer burden. The apicomplexan intracellular parasite Cryptosporidium is currently considered one of the major causes of mild and severe diarrhea worldwide. However, less attention has been paid to its tumorigenic potential despite the high exposure of humans and animals to this ubiquitous parasite. Herein, we discuss the potential causal link between Cryptosporidium infection and digestive cancer, with particular emphasis on colon cancer, based on increasing clinical, epidemiological and experimental pieces of evidence supporting this association. In addition, we highlight the current knowledge about the potential mechanisms by which this parasite may contribute to cell transformation and parasite-induced cancer

Molecular Characterization of Novel Cryptosporidium Fish Genotypes in Edible Marine Fish

Current knowledge of Cryptosporidium species/genotypes in marine fish is limited. Following phylogenetic analysis at the 18S rDNA locus, a recent study identified six new genotypes of Cryptosporidium colonizing edible fish found in European seas. Of these, five grouped in a clade together (#Cryptofish 1–5) and one grouped separately (#Cryptofish 7). In the present study, after phylogenetic analyses of #Cryptofish1, #Cryptofish2, #Cryptofish4, #Cryptofish5 and #Cryptofish7 at the actin locus, the presence of two major clades was confirmed. In addition, when possible, longer 18S amplicons were generated. In conclusion, the small genetic distances between these genotypes designated as a novel marine genotype I (#Cryptofish 1-5) suggest that they may be genetic variants of the same species, while the designated novel marine genotype 2 (#Cryptofish 7) is clearly representative of a separate species

Ionizing radiation to prevent arterial intimal hyperplasia at the edges of the stent: Induces necrosis and fibrosis

BACKGROUND: Although ionizing radiation has been proposed for the prevention of intimal hyperplasia in coronary and peripheral arteries in multicenter clinical trials, information is lacking on how irradiation affects arterial histology after stenting and especially how it affects the edges of the stent. We investigated intimal hyperplasia recasting with histological changes in arterial wall at the edges of the stent after arterial stenting followed by adequate external radiation for the prevention of intimal hyperplasia in pigs. MATERIALS AND METHODS: The aorta was experimentally stented in 30 pigs who were then assigned to two groups: irradiation with 20 Gy and a control group with no irradiation. The aorta was resected for morphometric and histological studies 6 weeks after procedure. RESULTS: Intimal thickness was reduced and the intima/media ratio was significantly lower in irradiated groups than in control pigs. In the irradiated group histological examination at the edges of the stent showed thin neointimal proliferation with an intact endothelium. In all sections analyzed in the 20-Gy irradiated group the vascular media at 45 days contained necrotic areas and fibrosis with calcifications. CONCLUSIONS: After arterial injury, adequate ionizing radiation effectively reduces neointimal thickening. Irradiation-induced histological changes include previously undetected recasting with necrosis and fibrosis at the arterial edges of the stent. The parietal recasting we observed in animal arteries irradiated at high doses is unclear and a cause of concern especially after clinical spontaneous dissection was recently reported. The use of ionizing radiation for the prevention of arterial restenosis awaits confirmation with a long-term follow-up including specific experimental histological analyse

Acute Blastocystis-Associated Appendicular Peritonitis in a Child, Casablanca, Morocco

Despite increasing reports that Blastocystis infection is associated with digestive symptoms, its pathogenicity remains controversial. We report appendicular peritonitis in a 9-year-old girl returning to France from Morocco. Only Blastocystis parasites were detected in stools, appendix, peritoneal liquid, and recto-uterine pouch. Simultaneous gastroenteritis in 26 members of the child’s family suggested an outbreak

Chronological changes in morphometry and histology in the rabbit vascular wall after external radiation for the prevention of intimal hyperplasia

BACKGROUND: Although ionizing radiation has been proposed for the prevention of intimal hyperplasia in coronary and peripheral arteries, information is lacking on how irradiation affects arterial histology and neointimal smooth-muscle cell proliferation-the hallmark of restenosis. We chronologically investigated early histological changes and quantitative changes in arterial wall cell proliferation after arterial injury followed by external radiation for the prevention of intimal hyperplasia in rabbits. MATERIALS AND METHODS: The aorta was experimentally injured in 26 rabbits who were then assigned to two groups: irradiation with 20 Gy and a control group with no irradiation. The aorta was resected for morphometric and histological studies at 3, 7, 15, 30, and 45 days after experimental injury. RESULTS: Intimal thickness was reduced and the intima/media ratio was significantly lower in irradiated groups than in control rabbits. In the irradiated group histological examination showed delayed neointimal proliferation with an intact endothelium. In the 20-Gy irradiated group the vascular media at 7 days contained necrotic areas and delayed fibrosis with calcifications. There was no statistical difference between the number of proliferating cells in the irradiated groups and the control group. Proliferating cells reached maximum numbers later in irradiated groups than in control rabbits (45 days versus 3 days). CONCLUSION: After arterial injury, external irradiation at 20 Gy effectively reduced aortic neointimal thickening. Irradiation-induced histological changes include recasting with rapid necrosis and delayed fibrosis. Radiation-induced parietal recasting with necrosis, fibrosis, and calcifications might worsen in time. Although irradiation after arterial injury leaves proliferative smooth-muscle cells within the arterial wall quantitatively unchanged in the early days after the procedure, it then induces a delayed reaction (observed over 45 days in our study). Whether neointimal hyperplasia is merely delayed or will ultimately develop causing restenosis awaits confirmation from experimental and clinical studies with a long-term follow-up