Toxoplasmose congênita em ovelhas reinfectadas experimentalmente

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Parasitos e comensais intestinais em pacientes neoplásicos submetidos à quimioterapia

The objective of this study was to verify the prevalence of intestinal parasites and/or commensals in the neoplastic patients undergoing chemotherapy. Stool samples were analyzed by the method of Lutz (1919) and Rugai (1954), in triplicate. This work was composed of three groups, the first one (GI) formed by neoplastic patients that are not undergoing chemotherapy, the second (GII) comprised patients who were undergoing chemotherapy, and the third group (GIII) consisting of patients who completed chemotherapy. A total of 30 patients (GI-5, GII-18 and GIII-7) were screened at the Assis Regional Hospital of the Unified Health System of Assis, São Paulo.Additional information on antiparasitic treatment and tumor type were obtained by questionnaire. The positivity was 66.7% (20 cases) for intestinal parasites and/or commensals. The helminths were Ascaris lumbricoides (36.7%), Hookworms (20%) and Hymenolepis diminuta (3.3%). Among the highlights are protozoan Giardia lamblia (46.7%), Entamoeba coli (6.7%), E. histolytica /dispar (3.3%), Endolimax nana (3.3%) and Iodameba butschlii (3.3%). The high frequency of intestinal parasites and/or commensals in the neoplastic patients can be attributed to poor personal hygiene and lack of immunity to reinfection and poor knowledge of the prophylaxis of infection by protozoa and helminths. The results indicate the necessity of adopting a new criterion for neoplastic patients undergoing chemotherapy, primarily performing parasitological diagnosis, treatment and monitoring of cure of intestinal parasitic infections in this risk group.

Helicobacter pylori em boca: epidemiologia e associação com doenças bucais

The association of Helicobacter pylori with different gastric diseases has been continuously discussed in the literature, whereas the last 20 years a large body of publications was intended to characterize the ecological niches and habitats of this pathogen being the mouth a possible habitat for that rod. The present study aimed to discuss the occurrence of this organism as part of the supplemental or transient microbiota of the mouth. Thus, an extensive review of literature covering the period 1990-2014 was carried out with different databases, yielding 5024 articles discussing transmission and occurrence of H. pylori, in English or Portuguese. Articles were selected according to the inclusion and exclusion criteria and data were tabulated and analyzed. Despite the significant heterogeneity of the literature, it was found this microaerophilic has a worldwide distribution, even in the mouth, which behaves as a reservoir for gastric reinfection. The role of oral hygiene and periodontal disease in the distribution of this microorganism remains unclear, but most studies support the hypothesis that oral biofilms and inflammation of periodontium may facilitate the installation of this pathogen in the mouth. Studies suggest that this microorganism could collaborate as a predisposing factor for oral cancer.

Transmissão congênita em cabras reinfectadas com Toxoplasma gondii

This study evaluated the potential of congenital transmission in goats experimentally infected and reinfected with Toxoplasma gondii, in three gestational stages (initial, intermediate and final). Of the 25 non-pregnant females negative for T. gondii, 20 were orally inoculated with 2.5 x 103 T. gondii ME49 oocysts. Of these, 15 pregnant females chronically infected were reinoculated, via oral, with 2.5 x 103 T. gondii VEG oocysts. Five experimental groups were formed (n=5): I, II and III (reinoculations in the initial, intermediate and final gestational stage, respectively), IV (inoculation) and V (no inoculation). Clinical and serological exams (IgG IFAT [indirect immunofluorescence antibody test]) in different days of evaluation, and bioassay and PCR were performed in all goats. In the infected goats with T. gondii a peak of 40.2°C (IV) at nine, seroconversion (IgG≥64) at 21 and stabilization (IgG<1024) at 119 days postinoculation were observed. In the reinfected goats with T. gondii occurred an increase in IgG titers (≥1,024) at 28 (I), 7 (II) and 3 (III) days post-reinoculation. During kidding were observed only in the reinfected groups: dystocia, malformation body, stillbirth and weakness, and IgG anti-Toxoplasma were detected in all and in some offsprings of the reinfected and infected goats, respectively. Tissue parasitism by T. gondii was diagnosed by bioassay and PCR in infected and reinfected goats and in their offspring. The congenital toxoplasmosis was possible in goats chronically infected and reinfected with T. gondii. The primary infection with T. gondii did not protect the pregnant goats against congenital disease resulting from toxoplasmic reinfection, in different gestational stages (initial, intermediate and final).

Características genotípicas de Staphylococcus coagulase-negativos e taxas de cura da mastite ovina

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeito da associação de antimicrobiano e óleo essencial na atividade antimicrobiana e propriedades físico-químicas de cimentos endodônticos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Studio immunologico per l'individuazione di pazienti trapiantati per cirrosi HBV relata che potrebbero sospedere la terapia con immunoglobine specifiche (HBIG)

Hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) is associated with poor graft and patient survival. Treatment with HBV-specific immunoglobulins (HBIG) in combination with nucleos(t)ide analogs is effective in preventing HBV reinfection of the graft and improving OLT outcome. However, the combined immunoprophylaxis has several limitations, mainly the high cost and the lack of standard schedules about duration. So far, the identification of markers able to predict the reinfection risk is needed. Although the HBV-specific immune response is believed to play an essential role in disease outcome, HBV-specific cellular immunity in viral containment in OLT recipients is unclear. To test whether or not OLT recipients maintain robust HBV-specific cellular immunity, the cellular immune response against viral nucleocapsid and envelope-protein of HBV was assessed in 15 OLT recipients and 27 individuals with chronic and 24 subjects with self-limited HBV infection, respectively. The data demonstrate that OLT recipients mounted fewer but stronger clusters of differentiation (CD)8 T cell responses than subjects with self-limited HBV infection and showed a preferential targeting of the nucleocapsid antigen. This focused response pattern was similar to responses seen in chronically infected subjects with undetectable viremia, but significantly different from patients who presented with elevated HBV viremia and who mounted mainly immune responses against the envelope protein. In conclusion, virus-specific CD4 T cell–mediated responses were only detected in subjects with self-limited HBV infection. Thus, the profile of the cellular immunity against HBV was in immune suppressed patients similar to subjects with chronic HBV infection with suppressed HBV-DNA.

In vivo- und in vitro-Untersuchungen zur Immunantwort und Parasitenentwicklung bei Infektionen mit dem Darmparasiten Cryptosporidium parvum

Cryptosporidium parvum ist ein intrazellulärer protozoischer Darmparasit (Apikomplexa), der weltweit zu den bedeutendsten Erregern von Diarrhöen beim Menschen und einer Reihe von Nutztieren zählt. Vor allem immunkompromittierte Personen wie zum Beispiel AIDS-Patienten erleiden schwere, chronische bis lebensbedrohende Erkrankungen. Da nach wie vor keine effektive Therapie gegen eine Kryptosporidiose in Form eines spezifisch wirkenden Chemotherapeutikums oder einer Vakzine existiert, ist es notwendig, die Immunantwort des Wirtes gegen den Parasiten und dessen Bindung, Invasion und die intrazelluläre Entwicklung in den Epithelzellen eingehend zu studieren, um neue Ansatzpunkte zu entwickeln. Wohingegen Menschen zeitlebens suszeptibel für eine Infektion mit C. parvum sind, entwickeln Mäuse eine natürliche Resistenz und können als adulte Tiere nicht mehr infiziert werden. Daher sind Mausmodelle der Kryptosporidiose auf neonatale oder immunsupprimierte und immundefiziente adulte Mäuse beschränkt. Bei der Überwindung einer C. parvum-Infektion sind Effektoren der natürlichen und adaptiven Immunität beteiligt. Die zentrale Rolle spielen CD4+-T-Zellen, sowie Interferon-gamma und Interleukin-12. Im Rahmen dieser Arbeit wurden Infektionen in IFN-gamma (GKO)- und IL-12 p40 (IL12KO)-Knockout-Mäusen (C57BL/6) etabliert, für die bereits gezeigt wurde, dass sie eine Suszeptibilität gegenüber einer Erstinfektion besitzen. Erstmals wurden die beiden Infektionsmodelle parallel unter denselben Bedingungen analysiert, um Rückschlüsse auf die Funktion und die Bedeutung der beiden Th1-Zytokine IFN-gamma und IL-12 bei der Auseinandersetzung mit dem Parasiten und der Überwindung einer Infektion ziehen zu können. Es wurden deutliche Unterschiede im Infektionsverlauf, bei der Höhe und Dauer der Parasitenausscheidung und der induzierten systemischen und mukosalen Antikörperantwort beobachtet. Zum ersten Mal konnte gezeigt werden, dass neben IL12KO auch GKO in der Lage sind, eine erste Infektion zu überwinden und eine Resistenz gegenüber einer erneuten Konfrontation mit dem Parasiten zu entwickeln. Alle Ergebnisse deuten darauf hin, dass die Etablierung einer protektiven Immunität gegen eine Kryptosporidiose generell unabhängig von der Anwesenheit der Zytokine IFN-gamma und IL-12 ist, der Verlust von IFN-gamma jedoch schwerer wiegt. Bei GKO-Mäusen persistierte der Parasit in Form einer niedriggradigen chronischen Infektion. Die beiden Infektionsmodelle stellten sich als ideales System für die Etablierung einer effektiven Immunisierungsstrategie heraus. Intranasale Immunisierungen, welche neben einer systemischen auch eine mukosale Immunantwort induzieren können, schienen einen richtigen Ansatz darzustellen. Intraperitoneale und subkutane Immunisierungen führten zwar zur Ausbildung einer starken spezifischen IgG-Antwort im Serum, diese war jedoch nicht in der Lage, einen Schutz vor einer Infektion zu vermitteln. Neben den in vivo Untersuchungen wurde des Weiteren auch die intrazelluläre Entwicklung von C. parvum in einem in vitro Kultursystem verfolgt. Zum ersten Mal wurde die Genexpression von vier Oberflächenproteinen der invasiven Zoitenstadien und eines Oozystenwandproteins parallel durch RT-PCR analysiert. Es konnte gezeigt werden, dass alle untersuchten Gene während der intrazellulären Entwicklung differentiell exprimiert werden, was eine unterschiedliche Funktion der Proteine während des Entwicklungszyklus nahe legt. Das Expressionsmuster der verschiedenen Gene charakterisiert bestimmte Abschnitte innerhalb des Entwicklungszyklus. Dabei wurden Marker für die Invasion (CP17) sowie für die asexuelle (GP900) und sexuelle Replikation (COWP) identifiziert.

Ten-year results of a three-arm prospective cohort study on implants in periodontally compromised patients. Part 1: implant loss and radiographic bone loss

OBJECTIVES: The aim of this study was to compare the long-term outcomes of implants placed in patients treated for periodontitis periodontally compromised patients (PCP) and in periodontally healthy patients (PHP) in relation to adhesion to supportive periodontal therapy (SPT). MATERIAL AND METHODS: One hundred and twelve partially edentulous patients were consecutively enrolled in private specialist practice and divided into three groups according to their initial periodontal condition: PHP, moderate PCP and severe PCP. Perio and implant treatment was carried out as needed. Solid screws (S), hollow screws (HS) and hollow cylinders (HC) were installed to support fixed prostheses, after successful completion of initial periodontal therapy (full-mouth plaque score <25% and full-mouth bleeding score <25%). At the end of treatment, patients were asked to follow an individualized SPT program. At 10 years, clinical measures and radiographic bone changes were recorded by two calibrated operators, blinded to the initial patient classification. RESULTS: Eleven patients were lost to follow-up. During the period of observation, 18 implants were removed because of biological complications. The implant survival rate was 96.6%, 92.8% and 90% for all implants and 98%, 94.2% and 90% for S-implants only, respectively, for PHP, moderate PCP and severe PCP. The mean bone loss was 0.75 (+/- 0.88) mm in PHP, 1.14 (+/- 1.11) mm in moderate PCP and 0.98 (+/- 1.22) mm in severe PCP, without any statistically significant difference. The percentage of sites, with bone loss > or =3 mm, was, respectively, 4.7% for PHP, 11.2% for moderate PCP and 15.1% for severe PCP, with a statistically significant difference between PHP and severe PCP (P<0.05). Lack of adhesion to SPT was correlated with a higher incidence of bone loss and implant loss. CONCLUSION: Patients with a history of periodontitis presented a lower survival rate and a statistically significantly higher number of sites with peri-implant bone loss. Furthermore, PCP, who did not completely adhere to the SPT, were found to present a higher implant failure rate. This underlines the value of the SPT in enhancing the long-term outcomes of implant therapy, particularly in subjects affected by periodontitis, in order to control reinfection and limit biological complications.

Poor performance of microbiological sampling in the prediction of recurrent arthroplasty infection

During a two-stage revision for prosthetic joint infections (PJI), joint aspirations, open tissue sampling and serum inflammatory markers are performed before re-implantation to exclude ongoing silent infection. We investigated the performance of these diagnostic procedures on the risk of recurrence of PJI among asymptomatic patients undergoing a two-stage revision. A total of 62 PJI were found in 58 patients. All patients had intra-operative surgical exploration during re-implantation, and 48 of them had intra-operative microbiological swabs. Additionally, 18 joint aspirations and one open biopsy were performed before second-stage reimplantation. Recurrence or persistence of PJI occurred in 12 cases with a mean delay of 218 days after re-implantation, but only four pre- or intraoperative invasive joint samples had grown a pathogen in cultures. In at least seven recurrent PJIs (58%), patients had a normal C-reactive protein (CRP, < 10 mg/l) level before re-implantation. The sensitivity, specificity, positive predictive and negative predictive values of pre-operative invasive joint aspiration and CRP for the prediction of PJI recurrence was 0.58, 0.88, 0.5, 0.84 and 0.17, 0.81, 0.13, 0.86, respectively. As a conclusion, pre-operative joint aspiration, intraoperative bacterial sampling, surgical exploration and serum inflammatory markers are poor predictors of PJI recurrence. The onset of reinfection usually occurs far later than reimplantation.

Imatinib mesylate selectively impairs expansion of memory cytotoxic T cells without affecting the control of primary viral infections

Imatinib mesylate (imatinib) is a potent inhibitor of defined tyrosine kinases (TKs) and is effective in the treatment of malignancies characterized by constitutive activation of these TKs such as chronic myeloid leukemia and gastrointestinal stromal tumors. TKs also play an important role in T-cell receptor (TCR) signal transduction. Inhibitory as well as stimulating effects of imatinib on T cells and dendritic cells have been described. Here, we analyzed the effects of imatinib treatment on antiviral immune responses in vivo. Primary cytotoxic T-cell (CTL) responses were not impaired in imatinib-treated mice after infection with lymphocytic choriomeningitis virus (LCMV) or after immunization with a tumor cell line expressing LCMV glycoprotein (LCMV-GP). Similarly, neutralizing antibody responses to vesicular stomatitis virus (VSV) were not affected. In contrast, secondary expansion of LCMV-specific memory CTLs was reduced in vitro and in vivo, resulting in impaired protection against reinfection. In addition, imatinib treatment delayed the onset of diabetes in a CTL-induced diabetes model. In summary, imatinib treatment in vivo selectively inhibits the expansion of antigen-experienced memory CTLs without affecting primary T- or B-cell responses. Therefore, imatinib may be efficacious in the suppression of CTL-mediated immunopathology in autoimmune diseases without the risk of acquiring viral infections.

Polyclonal and specific antibodies mediate protective immunity against enteric helminth infection

Anti-helminth immunity involves CD4+ T cells, yet the precise effector mechanisms responsible for parasite killing or expulsion remain elusive. We now report an essential role for antibodies in mediating immunity against the enteric helminth Heligmosomoides polygyrus (Hp), a natural murine parasite that establishes chronic infection. Polyclonal IgG antibodies, present in naive mice and produced following Hp infection, functioned to limit egg production by adult parasites. Comparatively, affinity-matured parasite-specific IgG and IgA antibodies that developed only after multiple infections were required to prevent adult worm development. These data reveal complementary roles for polyclonal and affinity-matured parasite-specific antibodies in preventing enteric helminth infection by limiting parasite fecundity and providing immune protection against reinfection, respectively. We propose that parasite-induced polyclonal antibodies play a dual role, whereby the parasite is allowed to establish chronicity, while parasite load and spread are limited, likely reflecting the long coevolution of helminth parasites with their hosts.

Complex interaction between proliferative kidney disease, water temperature and concurrent nematode infection in brown trout

Proliferative kidney disease (PKD) is a temperature-dependent disease caused by the myxozoan Tetracapsuloides bryosalmonae. It is an emerging threat to wild brown trout Salmo trutta fario populations in Switzerland. Here we examined (1) how PKD prevalence and pathology in young-of-the-year (YOY) brown trout relate to water temperature, (2) whether wild brown trout can completely recover from T. bryosalmonae-induced renal lesions and eliminate T. bryo - salmonae over the winter months, and (3) whether this rate and/or extent of the recovery is influenced by concurrent infection. A longitudinal field study on a wild brown trout cohort was conducted over 16 mo. YOY and age 1+ fish were sampled from 7 different field sites with various temperature regimes, and monitored for infection with T. bryosalmonae and the nematode Raphidascaris acus. T. bryosamonae was detectable in brown trout YOY from all sampling sites, with similar renal pathology, independent of water temperature. During winter months, recovery was mainly influenced by the presence or absence of concurrent infection with R. acus larvae. While brown trout without R. acus regenerated completely, concurrently infected brown trout showed incomplete recovery, with chronic renal lesions and incomplete translocation of T. bryosalmonae from the renal interstitium into the tubular lumen. Water temperature seemed to influence complete excretion of T. bryosalmonae, with spores remaining in trout from summer-warm rivers, but absent in trout from summer-cool rivers. In the following summer months, we found PKD infections in 1+ brown trout from all investigated river sites. The pathological lesions indicated a reinfection rather than a proliferation of remaining T. bryosalmonae. However, disease prevalence in 1+ trout was lower than in YOY.

Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling

BACKGROUND Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification. OBJECTIVE To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs). DESIGN Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness. SETTING General population and genitourinary medicine clinic attenders. PARTICIPANTS Heterosexual women and men. INTERVENTIONS Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT). MAIN OUTCOME MEASURES Population prevalence; index case reinfection; and partners treated per index case. RESULTS Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, > 10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage. CONCLUSIONS There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making. FUNDING The National Institute for Health Research Health Technology Assessment programme.

The cement prosthesis-like spacer: an intermediate halt on the road to healing.

BACKGROUND Periprosthetic infections remain a devastating problem in the field of joint arthroplasty. In the following study, the results of a two-stage treatment protocol for chronic periprosthetic infections using an intraoperatively molded cement prosthesis-like spacer (CPLS) are presented. METHODS Seventy-five patients with chronically infected knee prosthesis received a two-stage revision procedure with the newly developed CPLS between June 2006 and June 2011. Based on the microorganism involved, patients were grouped into either easy to treat (ETT) or difficult to treat (DTT) and treated accordingly. Range of motion (ROM) and the knee society score (KSS) were utilized for functional assessment. RESULTS Mean duration of the CPLS implant in the DTT group was 3.6 months (range 3-5 months) and in the ETT group 1.3 months (range 0.7-2.5 months). Reinfection rates of the final prosthesis were 9.6% in the ETT and 8.3% in the DTT group with no significant difference between both groups regarding ROM or KSS (P = 0.87, 0.64, resp.). CONCLUSION The results show that ETT patients do not necessitate the same treatment protocol as DTT patients to achieve the same goal, emphasizing the need to differentiate between therapeutic regimes. We also highlight the feasibility of CLPS in two-stage protocols.