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Cassone A.,Parasitic and Immune mediated Diseases | Cauda R.,Catholic University of Rome
AIDS | Year: 2012

In this era of efficacious antiretroviral therapy and consequent immune reconstitution, oropharyngeal and esophageal candidiasis (OPC and OEC) still remain two clinically relevant presentations in the global HIV setting. Both diseases are predominantly caused by Candida albicans, a polymorphic fungus which is a commensal microbe in the healthy individual but can become an aggressive pathogen in a debilitated host. Actually, C. albicans commensalism is not the result of a benign behavior of one of the many components of human microbiota, but rather the result of host's potent innate and adaptive immune responses that restrict the growth of a potentially dangerous microrganism on the epithelia. An important asset guarding against the fungus is the Th17 functional subset of T helper cells. The selective loss of these cells with the progression of HIV infection causes the decay of fungal containment on the oral epithelium and allows C. albicans to express its pathogenic potential. An important part of this potential is represented by mechanisms to evade host immunity and enhance inflammation and immunoactivation. In C. albicans, these mechanisms are mostly incorporated into and expressed by characteristic morphogenic transitions such as the yeast-to-hyphal growth and the white-to-opaque switch. In addition, HIV infection generates an 'environment' selecting for overexpression of the virulence potential by the fungus, particularly concerning the secreted aspartyl proteinases (Saps). These enzymes can degrade critical host defense components such as complement and epithelial defensive proteins such as histatin-5 and E-cadherin. It appears that part of this enhanced Candida virulence could be induced by the binding of the fungus to HIV and/or induced by HIV proteins such as GP160 and tat. Both OPC and OEC can be controlled by old and new antimycotics, but in the absence of host collaboration, anticandidal therapy may become ineffective in the long run. For these reasons, new therapeutics targeting virulence factors and specific immune interventions are being addressed. Among these new approaches, vaccination is a promising one. Two subunit vaccines based on antigens dominantly expressed by C. albicans in vivo, that is the Als3 adhesin and Sap2, have recently undergone phase 1 clinical trials. Overall, studies of Candida and candidiasis in the HIV-positive patient while certainly contributing to a more effective control of the microorganism may also provide useful information on HIV-host relationship itself that can assist the fight against the virus. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Pantosti A.,Parasitic and Immune mediated Diseases
Frontiers in Microbiology | Year: 2012

Staphylococcus aureus is a typical human pathogen. Some animal S. aureus lineages have derived from human strains following profound genetic adaptation determining a change in host specificity. Due to the close relationship of animals with the environmental micro-biome and resistome, animal staphylococcal strains also represent a source of resistance determinants. Methicillin-resistant S. aureus (MRSA) emerged 50years ago as a nosoco-mial pathogen but in the last decade it has also become a frequent cause of infections in the community. The recent finding that MRSA frequently colonizes animals, especially livestock, has been a reason for concern, as it has revealed an expanded reservoir of MRSA. While MRSA strains recovered from companion animals are generally similar to human nosocomial MRSA, MRSA strains recovered from food animals appear to be specific animal-adapted clones. Since 2005, MRSA belonging to ST398 was recognized as a colonizer of pigs and human subjects professionally exposed to pig farming. The "pig" MRSA was also found to colonize other species of farmed animals, including horses, cattle, and poultry and was therefore designated livestock-associated (LA)-MRSA. LA-MRSA ST398 can cause infections in humans in contact with animals, and can infect hospitalized people, although at the moment this occurrence is relatively rare. Other animal-adapted MRSA clones have been detected in livestock, such as ST1 and ST9. Recently, ST130 MRSA isolated from bovine mastitis has been found to carry a novel mecA gene that eludes detection by conventional PCR tests. Similar ST130 strains have been isolated from human infections in UK, Denmark, and Germany at low frequency. It is plausible that the increased attention to animal MRSA will reveal other strains with peculiar characteristics that can pose a risk to human health. © 2012 Pantosti.

The immunogenicity and the efficacy of a beta-propiolactone-inactivated caprine herpesvirus 1 (CpHV-1) vaccine adjuvanted with MF59™ were tested in goats. Following two subcutaneous immunizations, goats developed high titers of CpHV-1-specific serum and vaginal IgG and high serum virus neutralization (VN) titers. Peripheral blood mononuclear cells (PBMC) stimulated in vitro with inactivated CpHV-1 produced high levels of soluble IFN-gamma and exhibited high frequencies of IFN-gamma producing cells while soluble IL-4 was undetectable. On the other hand, control goats receiving the inactivated CpHV-1 vaccine without adjuvant produced only low serum antibody responses. A vaginal challenge with virulent CpHV-1 was performed in all vaccinated goats and in naïve goats to assess the efficacy of the two vaccines. Vaginal disease was not detected in goats vaccinated with inactivated CpHV-1 plus MF59™ and these animals had undetectable levels of infectious challenge virus in their vaginal washes. Goats vaccinated with inactivated CpHV-1 in the absence of adjuvant exhibited a less severe disease when compared to naïve goats but shed titers of challenge virus that were similar to those of naïve goats. Detection and quantitation of latent CpHV-1 DNA in sacral ganglia in challenged goats revealed that the inactivated CpHV-1 plus MF59™ vaccine was able to significantly reduce the latent viral load when compared either to the naïve goats or to the goats vaccinated with inactivated CpHV-1 in the absence of adjuvant. Thus, a vaccine composed of inactivated CpHV-1 plus MF59™ as adjuvant was strongly immunogenic and induced effective immunity against vaginal CpHV-1 infection in goats.

Stefanelli P.,Parasitic and Immune mediated Diseases
Expert Review of Anti-Infective Therapy | Year: 2011

The value of monitoring antimicrobial resistance is particularly significant for Neisseria meningitidis and Neisseria gonorrhoeae diseases, even if it is for different reasons. Although there is no global alert for the spread of resistant meningococcal strains, the emergence of resistance is correlated to the outcome of treatment and the successful prophylaxis of close contacts. Few cases of resistance among meningococci have been recorded worldwide; it remains unclear what intriguing mechanism is responsible for maintaining resistance in these cases in the absence of significant antibiotic selective pressure, as in the case of penicillin; on the contrary, although rifampicin is the antibiotic of choice in the prophylaxis of close contacts, there is a very low rate of resistance. The emergence of multidrug-resistant N. gonorrhoeae is a great challenge in controlling gonorrhea as one of the main sexually transmitted bacterial diseases. International surveillance programs permit the monitoring of the susceptibility of the pathogen and allow the revision of the standardized treatment regimen when the situation changes. © 2011 Expert Reviews Ltd.

Garcia-Fernandez A.,Parasitic and Immune mediated Diseases | Carattoli A.,Parasitic and Immune mediated Diseases
Journal of Antimicrobial Chemotherapy | Year: 2010

Objectives: IncHI2 plasmids are frequently encountered in clinical enterobacterial strains associated with the dissemination of relevant antimicrobial resistance genes. These plasmids are usually .250 kb, and technical difficulties can impair plasmid DNA purification and comparison by restriction fragment length polymorphism. We analysed the available IncHI2 whole DNA plasmid sequences to devise a rapid typing scheme to categorize the members of this plasmid family into homogeneous groups. Methods: We compared the available full IncHI2 plasmid sequences, identifying conserved and variable regions within the backbone of this plasmid family, to devise an IncHI2 typing method based on sequence typing and multiplex PCRs. A collection of IncHI2 plasmids carrying extended-spectrum β-lactamase and quinolone resistance genes, identified in strains from different sources (animals and humans) and geographical origins, was tested by these typing systems. Results: We devised a plasmid double locus sequence typing (pDLST) scheme and a multiplex PCR discriminating IncHI2 plasmid variants. These systems were tested on a collection of IncHI2 plasmids, demonstrating that the plasmids carrying blaCTX-M-2 and blaCTX-M-9 belonged to two major plasmid variants, which were highly conserved among different enterobacterial species disseminated in several European countries. Conclusions: The ability to recognize and subcategorize plasmids by pDLST in homogeneous groups on the basis of their phylogenetic relatedness can be helpful to analyse their distribution in nature and to discover of their evolutionary origin. © The Author 2010. Published by Oxford University Press.

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