74 research outputs found

    Impact of Waddlia chondrophila infection on pregnancy in the mouse.

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    The intracellular bacterium Waddlia chondrophila, which belongs to the Chlamydiales order, was found to be associated with miscarriage in humans. There is little to no knowledge regarding the mode of infection, impact on the neonate and pathophysiology of this emerging bacterium. We have previously shown that W. chondrophila induces a systemic infection, organ pathology and elicits T helper type 1-associated humoral immunity in a murine model of genital infection. In the present study, we took advantage of this model of infection to evaluate the impact of this bacterium on the mouse pregnancy. We used two routes of inoculation, vaginal and intrauterine, to introduce infection before and after mating. Our results show that genital infection by W. chondrophila did not have any significant impact on gestation length and maternal weight gain, nor on the number of offspring and their weight. This observation indicates that the mouse model of infection is not suitable to study the effect of W. chondrophila on pregnancy and alternative models of infection, including in vitro ones, should be used. Moreover, an indirect immunopathological mechanism activated by this bacterium should be further explored

    Antibiotic susceptibility of Neochlamydia hartmanellae and Parachlamydia acanthamoebae in amoebae.

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    Parachlamydia acanthamoebae and Neochlamydia hartmanellae are Chlamydia-related bacteria naturally infecting free-living amoebae. These strict intracellular bacteria might represent emerging pathogens. Recent studies report an association with lower respiratory tract infections, especially with pneumonia where they have been identified as a potential causative agent in 1-2% of cases. In this study, we defined the antibiotic susceptibility of N. hartmanellae, two strains of P. acanthamoebae and two yet unclassified Parachlamydiaceae strains using a quantitative approach. We confirmed the results obtained earlier for P. acanthamoebae strain Bn9 in an observational study. Macrolides (MICs < 0.06-0.5 μg/ml), rifampicin (MICs 0.25-2) and doxycycline (2-4 μg/ml) were active against P. acanthamoebae strains and Neochlamydia. All strains were resistant to amoxicillin, ceftriaxone and imipenem (MIC ≥32 μg/ml). Similarly to other Chlamydia-related bacteria, all investigated Parachlamydiaceae were resistant to quinolones (MICs ≥ 16 μg/ml). Therefore, we recommend a treatment with macrolides for Parachlamydia-associated pneumonia

    Congenital Zika virus syndrome…what else? Two case reports of severe combined fetal pathologies.

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    Zika virus (ZIKV) has recently emerged as a teratogenic infectious agent associated with severe fetal cerebral anomalies. Other microorganisms (TORCH agents) as well as genetic disorders and toxic agents may lead to similar anomalies. In case of fetal anomalies, the exact etiology might be difficult to establish, especially in ZIKV endemic countries. As the risks associated with maternal infection remain unclear adequate parental counseling is difficult. We present two cases of severe fetal pathologies managed in our multidisciplinary center during the ZIKV outbreak in Martinique, a French Caribbean Island. Both fetuses had congenital ZIKV infection confirmed by RT-PCR. While one case presented with significant cerebral anomalies, the other one presented with hydrops fetalis. A complete analysis revealed that the fetal lesions observed resulted from a combination of ZIKV congenital infection and a genetic disorder (trisomy 18) in case 1 or congenital Parvovirus B19 infection in case 2. We highlight the difficulties related to adequate diagnosis in case of suspected ZIKV congenital syndrome. Additional factors may contribute to or cause fetal pathology, even in the presence of a confirmed ZIKV fetal infection. An exact diagnosis is mandatory to draw definitive conclusions. We further emphasize that, similarly to other congenital infections, it is very likely that not all infected fetuses will become symptomatic

    Rationale, design and methodology for Intraventricular Pressure Gradients Study: a novel approach for ventricular filling assessment in normal and falling hearts

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    <p>Abstract</p> <p>Background</p> <p>Intraventricular pressure gradients have been described between the base and the apex of the left ventricle during early diastolic ventricular filling, as well as, their increase after systolic and diastolic function improvement. Although, systolic gradients have also been observed, data are lacking on their magnitude and modulation during cardiac dysfunction. Furthermore, we know that segmental dysfunction interferes with the normal sequence of regional contraction and might be expected to alter the physiological intraventricular pressure gradients. The study hypothesis is that systolic and diastolic gradients, a marker of normal left ventricular function, may be related to physiological asynchrony between basal and apical myocardial segments and they can be attenuated, lost entirely, or even reversed when ventricular filling/emptying is impaired by regional acute ischemia or severe aortic stenosis.</p> <p>Methods/Design</p> <p><it>Animal Studies: </it>Six rabbits will be completely instrumented to measuring apex to outflow-tract pressure gradient and apical and basal myocardial segments lengthening changes at basal, afterloaded and ischemic conditions. Afterload increase will be performed by abruptly narrowing or occluding the ascending aorta during the diastole and myocardial ischemia will be induced by left coronary artery ligation, after the first diagonal branch.</p> <p><it>Patient Studies: </it>Patients between 65-80 years old (n = 12), both genders, with severe aortic stenosis referred for aortic valve replacement will be selected as eligible subjects. A high-fidelity pressure-volume catheter will be positioned through the ascending aorta across the aortic valve to measure apical and outflow-tract pressure before and after aortic valve replacement with a bioprosthesis. Peak and average intraventricular pressure gradients will be recorded as apical minus outflow-tract pressure and calculated during all diastolic and systolic phases of cardiac cycle.</p> <p>Discussion</p> <p>We expect to validate the application of our method to obtain intraventricular pressure gradients in animals and patients and to promote a methodology to better understand the ventricular relaxation and filling and their correlation with systolic function.</p

    Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

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    Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.We thank S. Lecher, S. Li and J. Zallet for technical support. Calculations were performed at the sciCORE scientific computing core facility at the University of Basel. This work was supported by the Swiss National Science Foundation (grants 310030_166687 (S.G.) and 320030_153442 (M.E.) and Swiss HIV Cohort Study grant 740 to L.F.), the European Research Council (309540-EVODRTB to S.G.), TB-PAN-NET (FP7-223681 to S.N.), PathoNgenTrace projects (FP7-278864-2 to S.N.), SystemsX.ch (S.G.), the German Center for Infection Research (DZIF; S.N.), the Novartis Foundation (S.G.), the Natural Science Foundation of China (91631301 to Q.G.), and the National Institute of Allergy and Infectious Diseases (5U01-AI069924-05) of the US National Institutes of Health (M.E.)
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