Yes / Background. Increased availability of Next Generation Sequencing (NGS) techniques allows, for the first time, to distinguish relapses from reinfections in patients with multiple Buruli ulcer (BU) episodes. Methodology. We compared the number and location of single nucleotide polymorphisms (SNPs) identified by genomic screening between four pairs of Mycobacterium ulcerans isolates collected at the time of first diagnosis and at recurrence, derived from a collection of almost 5000 well characterized clinical samples from one BU treatment center in Benin. Principal Findings. The findings suggest that after surgical treatment—without antibiotics—the second episodes were due to relapse rather than reinfection. Since specific antibiotics were introduced for the treatment of BU, the one patient with a culture available from both disease episodes had M. ulcerans isolates with a genomic distance of 20 SNPs, suggesting the patient was most likely reinfected rather than having a relapse. Conclusions. To our knowledge, this study is the first to study recurrences in M. ulcerans using NGS, and to identify exogenous reinfection as causing a recurrence of BU. The occurrence of reinfection highlights the contribution of ongoing exposure to M. ulcerans to disease recurrence, and has implications for vaccine development. / This work was supported by the UBS Optimus Foundation (Zurich, Switzerland) and the Department of Economy, Science and Innovation of the Flemish Government (Belgium). KV was supported by a VLADOC PhD scholarship of VLIRUOS (Belgium).

The purpose of this study was to investigate the association between Chlamydia trachomatis reinfection rates of Puerto Rican adolescents and failure to follow the retesting protocol, failure of sexual partners to receive treatment, and failure to participate in the sexual orientation program about risk factors. Secondary data analysis, from a historical prospective study from the Health Department of Puerto Rico, was used in this study. Data analysis was restricted to adolescents 15 to 19-years-old who had a positive chlamydia result and reinfection pattern since January 2008 through December 2012. Multiple logistic regression analyses were run to predict Chlamydia trachomatis reinfection. Results showed a statistically significant association association between Chlamydia trachomatis reinfection and not having followed the retesting protocol (OR=1.243, 95% CI 1.089-2.930, p-value 0.038). A statistically significant association association was found between Chlamydia trachomatis reinfection and sexual partners having not received treatment (OR=1.713, 95% CI 0.761-2.024, p-value 0.029). A statistically significant association was found between Chlamydia trachomatis reinfection and having not participated in the Puerto Rico Department of Health's sexual orientation program (OR=1.243, 95% CI 0.762-2.026, p-value 0.034). The contribution to social change is identifying factors significantly associated with Chlamydia trachomatis reinfection. Study findings provide useful guidance for clinicians and public health professionals on how to reduce Chlamydia trachomatis reinfection rates among at risk Puerto Rican adolescents.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-11-19T18:49:36Z No. of bitstreams: 1 Elisangela Trindade Santos. Schistosoma mansoni....pdf: 19009500 bytes, checksum: 95969f49b90dc351f686bd6dde25898c (MD5) / Made available in DSpace on 2012-11-19T18:49:36Z (GMT). No. of bitstreams: 1 Elisangela Trindade Santos. Schistosoma mansoni....pdf: 19009500 bytes, checksum: 95969f49b90dc351f686bd6dde25898c (MD5) Previous issue date: 2011 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / A esquistossomose mansônica é uma doença parasitária tropical. Causadas por helmintos do gênero Schistosoma. Com a intenção de conter a doença, diversos institutos e organizações vêm desenvolvendo medidas de controle para tratar indivíduos infectados e evitar a ocorrência de novas infecções. Estratégias de administração de medicamentos em massa são eficazes na cura da doença, entretanto o tratamento com drogas anti-helmínticas não previnem a possibilidade da ocorrência de reinfecções. Diante desta questão, neste trabalho propusemo-nos a analisar a cinética da fibrose hepática em camundongos esquistossomóticos tratados e submetidos à reinfecção. Para alcançar este objetivo, 70 camundongos Swiss foram infectados com 50 cercárias de S.mansoni, posteriormente tratados com Oxamniquine ou Praziquantel e reinfectados quatro meses após tratamento. Os fígados destes animais foram submetidos a técnicas de imunohistoquímica e imunofluorescência e microscopia eletrônica de transmissão para avaliação da expressão e participação de componentes envolvidos no processo fibrogênico. Para verificar os índices de colágeno entre os grupos utilizou-se a análise morfométrica. A análise histológica revelou que camundongos esquistossomóticos submetidos à quimioterapia específica desenvolveram altos índices de fibrose durante a reinfecção. A imunomarcação para alfa actina de músculo liso (α-SMA) revelou que grande parte do parênquima hepático dos animais tratados e reinfectados exibiam células com perfil miofibloblástico. A imunofluorescência demonstrou que o padrão de marcação para laminina estava alterado em animais com esquistossomose. A análise morfométrica revelou que reinfecção destes animais ocasionou uma intensa deposição de fibras colágenas no parênquima hepático. Os dados obtidos demonstraram que a reinfecção em animais previamente tratados, foi capaz de induzir uma resposta fibrótica semelhante a encontrada nos animais com infecção primária. / Schistosomiasismansoni is a tropical parasitic disease. Caused by helminths of the genus Schistosoma. In an attempt to contain the disease, various institutes and organizations are developing control measures to treat infected individuals and prevent new infections. Strategies of mass drug administration are effective in curing the disease, whereas treatment with anthelmintic drugs do not prevent the possibility of the occurrence of reinfection. Faced with this question, in this work we decided to analyze the kinetics of hepatic fibrosis in schistosomiasis treated mice and subjected to reinfection. To achieve this goal, 70 Swiss mice were infected with 50 cercariaeS.mansoni subsequently treated with oxamniquine or praziquantel and reinfected four months after treatment. The livers of these animals were subjected to immunohistochemistry and immunofluorescence techniques and transmission electron microscopy to evaluate the expression and participation of constituents involved in the fibrogenic process. To check the rates of collagen between the groups used the morphometric analysis. Histological analysis revealed that mice submitted to specific chemotherapy schistosomiasis developed fibrosis during high rates of reinfection. Immunostaining for alpha smooth muscle actin (α-SMA) revealed that much of the liver parenchyma of animals treated and reinfected cells exhibited myofibloblastic profile. Immunofluorescence showed that the labeling pattern for laminin was abnormal in animals with schistosomiasis. Morphometric analysis revealed that reinfection of animals caused an intense collagen deposition in the liver parenchyma. The data obtained showed that reinfection in animals previously treated, was able to induce a fibrotic response similar to that found in animals with primary infection

Recent findings by Public Health Ontario (PHO) state that there were approximately 36, 346 confirmed cases of chlamydia in Ontario as of 2011. This represents an incidence rate that increased by 54% since 2006 rising from 177 to 272 per 100,000 in 2011. National rates only increased by 38% (210 to 290 per 100,000), meaning that Brant County rates surpassed both, increasing by over 100% (150 to 395 per 100,000). The main objective of this series of manuscripts is to develop a clear profile of re-infected individuals in comparison to non-repeaters, while considering co-infections wit gonorrhea. The secondary objective was to determine the sexual network as well as spatial distribution patterns of cases in Brant County. The study period is from January 1st, 2006 until December 31st, 2015, Data were extracted from the integrated public health information system (iPHIS). Basic descriptive statistics will be performed followed by a Cox-regression analysis in order to compare individuals who are repeaters with those who are not repeaters. Within the study period, there were 2,829 cases of chlamydia and 328 were reinfections. We identified twelve hotspots with high chlamydia infection rates of which, 58 per cent occurred within the previously identified core group, in the urban core of Brant County.

IV. ABSTRACT The human metapneumovirus is a novel paramyxovirus associated with acute respiratory infections in children, adults, elderly and immunocompromised individuals. It has a worldwide distribution and the prevalence range between 1.5% to 25% in individuals with respiratory infections. Based on phylogenetic analysis 2 distinct genetic groups (A and B) that are sub-divided into four subgroups (A1, A2, B1 and B2) have been shown to circulate. Until recently, there was no information on the molecular epidemiology and the clinical characteristics of the hMPV in Africa, including South Africa, a region with a high prevalence of paediatric human immunodeficiency virus type-1 (HIV) infection. The molecular epidemiology and clinical characteristics of the hMPV in South Africa was investigated over a three period (2000-2002) in children hospitalized with lower respiratory tract infection. The children were part of a cohort participating in a phase 3 clinical trial investigating the efficacy of a 9-valent-pneumocococcal protein-polysaccharide conjugate vaccine (PCV). The objectives of the study were: i. to investigate the molecular epidemiology of hMPV in South Africa; ii. characterize the burden of hMPV disease and determine the clinical features of hMPV-LRTI in children infected and not infected by HIV; iii. probe the role of Streptococcus pneumoniae in the pathogenesis of hMPV-LRTI. The overall prevalence of hMPV in children hospitalized with lower respiratory tract infections (LRTI) was 7.4%. The mean age of children with hMPV associated LRTI (hMPV-LRTI) in South Africa was 13.3 months (range 1.4-49.2 months), with HIV infected children being older than children not infected with HIV (mean [range] 17.6 [4.5-44.3] vs. 12.3 [1.4-49.2] months; P=0.007). The incidence of hMPV-LRTI was 5.0 (95%C.I.3.3-7.5) fold greater in HIV infected children (incidence rate: 2 504 [95%C.I. 1 683-3 577] per 100 000) than in HIV uninfected children (incidence rate: 505 [95%C.I. 409-618] per 100 000, P<0.0001). Human metapneumovirus was identified less frequently than RSV but more commonly than other studied respiratory viruses. The double-blind PCV-9 vs. placebo controlled trial was used to probe the role of pneumococcal co-infections contributing to the pathogenesis of severe hMPV-LRTI. The incidence of hospitalization for hMPV-LRTI was reduced by 46% (95%, CI, 25-63; P=0.0002) in PCV-9 vaccinees compared to placebo recipients. This inferred that coinfection with Streptococcus pneumoniae was integral to the pathogenesis of hMPV-LRTI requiring hospitalization. Both groups of the hMPV circulated during the three year period including concurrent circulation of multiple subtypes of the virus. There was a transition from group B to group A subtype virus as the dominant circulating virus over sequential years. Sequence analysis of the two attachment glycoproteins (F and G), showed the F gene protein to be highly conserved, in contrast the attachment protein gene (G protein) was highly variable particularly in the extracellular domain between lineages. Repeat hMPV-LRTI by either homologous or heterologous strains within 3 months of each other suggested that natural infection did not confer complete immunity to hMPV. The present study demonstrated that hMPV is a leading pathogen associated with LRTI among children in Africa and indicated that occult pneumococcal co-infections’ were integral in the pathogenesis of hMPV-LRTI requiring hospitalization. Additionally, this is the first study to have characterized the molecular epidemiology of hMPV in Africa and provides insight as to issues that may exist regarding the design of an hMPV vaccine.

No description available.

Le virus de l’hépatite C (VHC) est une des causes majeures de carcinome hépatocellulaire (CHC), dont les traitements ont une efficacité modéré. La transplantation hépatique (TH) est l’option thérapeutique de choix mais est limitée, chez les patients chroniquement infectés par le VHC, par une réinfection systématique du greffon. Nous proposons d’utiliser des lymphocytes génétiquement modifiés (LGM) issus de donneurs sains qui ont fait leurs preuves pour le traitement d’hémopathies malignes et qui,exprimant un gène suicide, peuvent être éliminés en cas d’effets secondaires. Nous montrons maintenant que ces LGM présentent d’une part une activité anti-tumorale vis-à-vis du CHC, et d’autre part un effet anti-viral envers le VHC. L’objectif est la création d’une banque de LGM allogéniques prêts-à-l’emploi, avec des avantages en termes de coût, de logistique et de disponibilité immédiate par rapport aux approches classiques d’immunothérapies, autologues pour la plupart. Parallèlement, nous avons étudié in vivo l’effet anti-viral d’un anticorps monoclonal anti-claudin-1 dirigé contre un co-récepteur duVHC et inhibant l’entrée du VHC dans les hépatocytes humains. Grâce à un modèle d’infection par VHC de souris présentant un foie chimérique humanisé, nous montrons que cet anticorps permet de prévenir efficacement l’infection par le VHC. Nos résultats apportent les preuves de concept de l’utilisation de deux produits, anticorps anti-claudin-1 et LGM, pour la prévention de la réinfection du greffon hépatique par le VHC, les LGM pouvant également être envisagés en association avec les thérapies actuelles du CHC. / The hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC),whose treatments are of limited efficacy. The liver transplantation (LT) is the optimal therapy but is limited by a very rapid and universal HCV reinfection of the liver graft. We propose to use healthy donor-derived suicide gene modified lymphocytes (GML), known to be efficient for the treatment of hematological malignancies and that can be eliminated in case of adverse events. We show now that GML have a strong anti-tumoral activity against HCC and an anti-viral effect on HCV. Our objective is to create a bank of ready for-use allogeneic GML which could have numerous advantages in terms of costs,logistics and immediate availability, as compared with autologous immunotherapies. In parallel, we have studied the in vivo anti-viral effect of a monoclonal antibody (mAb) directed against an HCV coreceptor, claudin-1, inhibiting HCV entry in human hepatocytes. Using a human liver-chimeric mouse model of HCV infection, we show that this mAb can efficiently prevent HCV infection in vivo. Our results provide the proofs of concept that these two products, anti-claudin-1 mAb and GML, could be used for the prevention of liver graft HCV reinfection, while GML could further be used for the treatment of HCC, in combination with current HCC therapies

The course of microsporidiosis caused by Encephalitozoon cuniculi in immunocompetent BALB/c mice and immunodeficient SCID mice was screened using molecular methods. The site of infection in organs was located using molecular and histology methods. The effectiveness of albendazole treatement and possibility of infection relapse after immunosuppresion (cyclosporine A, tacrolimus, mycofenolate mofetil) was also studied. Moreover, the course of excretion of microsporidial spores in feces was monitored during the whole time of experiment.

Pour compléter leur cycle de vie, les virus interagissent avec de nombreux facteurs de la cellule-hôte. Le virus Herpès simplex de type 1 (HSV-1) ne fait pas exception. Une récente étude protéomique du virus effectuée par notre laboratoire a permis d’identifier 49protéines cellulaires potentiellement incorporées dans les virions matures d’HSV-1 [1]. Étant donné que certaines de ces protéines peuvent jouer des rôles importants au cours du cycle de vie du virus, elles constituent des cibles de choix pour identifier et caractériser de nouvelles interactions hôte-pathogène dans le contexte d’HSV-1. D’ailleurs le laboratoire a été effectué un criblage aux petits ARN d’interférence qui a démontré qu'au moins 15 des protéines incorporées sont impliqués dans le cycle de réplication de HSV-1 en culture cellulaire (Annexe 1). Des nombreuses études rapportent l'incorporation des protéines de l'hôte dans les virions matures mais très peu abordent l'importance de la fraction des protéines cellulaires incorporée dans les virions pour le cycle virale. Pour vérifier ça, nous avons déplété ces protéines des virions matures extracellulaires en utilisant des petits ARN d’interférence. Par la suite, nous avons utilisé ces virus déplétés pour réinfecter des cellules déplétées ou normales. Cette méthode nous a permis d'identifier pour la première fois 8 protéines (DDX3X, HSPA8, KRT10, MIF, Rab5A, Rab6A, Rab10 et 14-3-3ζ) dont l'absence dans les virions réduit la production virale d'au moins 50%. Pour mieux comprendre à quelle étape du cycle viral ces protéines sont nécessaires, nous avons aussi quantifié les virus intracellulaires, produits des cellules déplétées individuellement des quinze protéines cellulaires. Ainsi, nous avons trouvé que dans nos conditions 7 de ces 8 protéines cellulaires (DDX3X, HSPA8, KRT10, MIF, Rab5A, Rab6A et Rab10) semblent impliquées dans la production des virus intracellulaires, ce qui nous a stimulés à débuter une série de tests plus approfondis de l’entrée d’HSV-1. Les résultats préliminaires, démontrent l’implication dans l’entrée d’HSV-1 d’au moins 3 à 4 de ces protéines (HSPA8, KRT10, Rab5A et Rab10). / To complete their life cycle viruses interact with many factors of the host cell. Herpes simplex virus type 1 (HSV-1) is no exception. A recent proteomic study of the virus carried by our laboratory has identified up to 49 cellular proteins potentially incorporated into the mature virions of HSV-1[1]. Since some of these proteins may play important roles during the viral life cycle, they are interesting targets for identification and characterization of new host-pathogen interactions in the context of HSV-1. To target the proteins that are relevant to the viral life cycle of Herpes, the laboratory performed a screening with small interfering RNAs (siRNAs), which showed that at least 15 incorporated proteins are involved in the replication cycle of HSV- 1 in cell culture (Appendix 1). Numerous studies report the incorporation of host proteins in mature virions but few addresses the importance for the viral infectivity of the fractions of cellular proteins incorporated into the virions. To verify this, we depleted these proteins from the mature extracellular virions using siRNAs. Subsequently, we used these viruses to re-infect depleted or normal cells. This method allowed us to identify for the first time eight proteins (DDX3X, HSPA8, KRT10, MIF, Rab5A, Rab6A, Rab10 and 14-3-3ζ) whose absence in virions reduced viral production by at least 50%. As part of understanding at what stage of the life cycle these proteins are necessary for HSV-1, we tested the infectivity of intracellular depleted viruses. Thus, we found at least seven cellular proteins (DDX3X, HSPA8, KRT10, MIF, Rab5A, Rab6A and Rab10) to have a pronounced effect on the replication of herpes virus, which has stimulated us to begin a series of more in-depth tests of the entry of HSV-1. Preliminary results demonstrate the involvement in the entry of HSV-1 of at least three to four proteins (HSPA8, KRT10, Rab5A and Rab10).

Praziquantel ist das Mittel der Wahl bei der Behandlung der Bilharziose. Für die Wirksamkeit des Medikaments spielt die Immunantwort des Wirts eine wichtige Rolle. Mikronährstoffe sind wichtig für die Funktion des Immunsystems. In Endemiegebieten der Bilharziose findet sich meist ein Mikronährstoffmangel. In dieser Studie wurde untersucht, ob ein Ausgleich des Mikronährstoffmangels das Behandlungsergebnis optimieren kann und Reinfektionen vermindert werden können. Für die randomisierte Interventionsstudie wurden 331 infizierte Kinder zwischen acht und 14 Jahren mit einer Eiausscheidung von über 30 Schistosoma haematobium Eiern pro 10 ml Urin ausgewählt. Die Kinder wurden zuvor in einer an zehn Grundschulen erhobenen Querschnittsstudie in einem blasenbilharzioseendemischen Gebiet in Tansania identifiziert. Die Interventionsgruppe erhielt vier Wochen lang ein Mikronährstoffpräparat und wurde danach mit Praziquantel behandelt, die Kontrollgruppe erhielt nur Praziquantel. Bei der Kontrolle des Therapierfolgs fanden sich keine signifikanten Unterschiede zwischen der Interventions- und der Kontrollgruppe hinsichtlich der Heilungsraten und der Infektionsstärke der Nichtgeheilten. Nach zehn Monaten wurden die Kinder nochmalig auf Eier im Urin untersucht, um Reinfektionen festzustellen. Fehlende bzw. spärliche Niederschläge machten jedoch Neuinfektionen fast unmöglich, da sich kaum Wasserstellen gebildet hatten, welche die Habitate von Bulinus nasutus - dem Zwischenwirt von S. haematobium im Untersuchungsgebiet - darstellen. Es waren nur 10 % der Kinder reinfiziert mit sehr geringen Infektionsstärken ohne signifikante Unterschiede zwischen den Studiengruppen. Es konnte nicht nachgewiesen werden, dass eine Mikronährstoffgabe den Therapieerfolg nach der Behandlung mit Praziquantel verbessern kann. Ob Reinfektionen verringert werden können, ließ sich aufgrund der anhaltenden Dürre in den Jahren 1999 und 2000 in dieser Studie nicht feststellen, sollte aber Gegenstand weiterer Studien sein. / Praziquantel is the drug of choice for schistosomiasis chemotherapy. The immune response of the host is an important factor in drug efficacy. Micronutrients are essential for an effective response of the immune system. In areas endemic for S. haematobium people often suffer from micronutrient deficiency. It was investigated whether a compensation of micronutrient deficiency can improve chemotherapy and reduce the rate and levels of reinfection. 331 children aged 8 to 14, highly infected with S. haematobium were selected for the randomised intervention-study. Children were identified in a cross-sectional study in 10 primary schools in Tanzania in an area endemic for S. haematobium. The intervention-group received a four weeks micronutrient supplementation followed by treatment with Praziquantel. The control-group was only treated with Praziquantel. The results showed no significant differences concerning cure rate and intensity of infection between the two study groups. The children were examined for reinfection ten months after treatment. Only ten percent of the children were reinfected with rather low levels of infection. There were no significant differences between the studied groups. Scarce rain during the rainy season inhibited the formation of the usual puddles, that form the essential habitat for Bulinus nasutus - the intermediate host of S. heamatobium. This substantially reduced the probability for new infections. It could not be confirmed whether micronutrient supplementation could improve the results after chemotherapy with Praziquantel. A decrease of reinfections due to micronutrient supplementations could not be confirmed due to the drought in 1999 and 2000, but should be a field for further investigations.