Microorganisms and man. Various characteristics of their coexistence at present

Modern data of literature on microbial associations and their role in human health and diseases are presented. As pointed out in this work, the characteristic feature of the XX century is the emergence and the re-emergence of 36 new infections. The emergence of many infections is associated with such factors as the increased migration of the population, ecological environmental disasters, etc. Grounds for a new view on the etiology of a number of chronic somatic diseases are given. The task of preparation development for the immunoprophylaxis of 25-30 infections has been set by WHO as its target for the year 2025. Prospects of new approaches to the development of new generation vaccines against bacterial, viral and parasitic infections, including HIV/AIDS, tuberculosis, virus hepatitides, malaria, etc., are shown.     

NTBC Treatment of the Pyomelanogenic Pseudomonas aeruginosa Clinical Isolate PA1111 Inhibits Pigment Production and Increases Sensitivity to Oxidative Stress

Pyomelanin is a brown/black extracellular pigment with antioxidant and iron acquisition properties that is produced by a number of different bacteria. Production of pyomelanin in Pseudomonas aeruginosa contributes to increased resistance to oxidative stress and persistence in chronic infections. We demonstrate that pyomelanin production can be inhibited by 2-[2-nitro-4-(trifluoromethyl) benzoyl]-1,3-cyclohexanedione (NTBC). This treatment increases sensitivity of pyomelanogenic P. aeruginosa strains to oxidative stress, without altering the growth rate or resistance to aminoglycosides. As such, NTBC has potential to function as an anti-virulence factor in treating pyomelanogenic bacterial infections.     

The importance of Shigella boydii in shigellosis morbidity in the USSR

The etiological role of S. boydii in Shigella infections registered at different territories of the USSR in 1986-1987 was analyzed. As established by this analysis, S. boydii infection occurred mainly at the territories with unsatisfactory water supply of the population; from these territories the infection spread to ther territories of the USSR. The dominating serovars causing S. boydii dysentery, as well as Shigella infections, at different territories of the USSR was shown to be identical, which was indicative of the fact that the immunological factor had no influence on the etiological structure of Shigella infections, determined by the activity of the main routes of the transfer of infection. On the whole, S. boydii serovars 2, 4 and 1 were found to prevail in the USSR.     

Detection and Genotyping of Human Papillomavirus in Urine Samples from Unvaccinated Male and Female Adolescents in Italy

The introduction of vaccination against Human Papillomavirus (HPV) in adolescent girls in 2006 has focused virological surveillance on this age group. As few studies have evaluated HPV infections in young populations, further data are needed in order to improve and extend prophylactic policy and to monitor epidemiological changes. The present study aimed at evaluating overall and type-specific HPV prevalence in both female and male adolescents in Italy. HPV DNA detection and genotyping was performed on urine samples collected from 870 unvaccinated adolescents (369 females, 501 males, 11-18 years of age) in five cities in Italy. Following DNA extraction by means of a commercial kit (NucliSENS^®-miniMAG^®, bioMérieux), the L1 gene fragment was PCR amplified and genotyped by restriction fragment length polymorphism analysis. HPV DNA was detected in 1.5% of all samples, and in 3% and 0.4% of samples from females and males, respectively. In approximately 70% of HPV DNA positive adolescents, the infection was due to a single genotype, with 88.9% of genotypes belonging to the HR-clade. The only two HPV-positive boys (14 and 18 years old) had HPV-70 genotype. Only one of the 11 HPV-infected girls was in the 11-14 age-group. HPV prevalence was 4.2% in girls aged 15-18 years and 60% of infections were due to vaccine types HPV-16 or HPV-6/-11. This is one of the few studies, the first conducted in Italy, on HPV infection in adolescents. Urine testing is the easier way of detecting HPV infection in younger populations. Our data revealed a very low HPV prevalence, and no infections were observed in the 12-year-old vaccine target population. The majority of infections were seen in females aged 15-18 years. Overall, more than 50% and 30% of the potentially persistent HPV infections detected in this group could have been prevented by the quadrivalent and the bivalent vaccines, respectively.     

Relationship of tadpole stage to location of echinostome cercariae encystment and the consequences for tadpole survival

The effect of echinostome infections on the survival of Rana pipiens tadpoles was examined in relation to developmental stage of tadpoles. Individual tadpoles of Gosner stages 25, 27, 32-33, and 37-39 were exposed to 1 of 4 levels of cercariae (0, 20, 50, or 100). Only tadpoles at stage 25, the earliest stage infected, died within a 5-day experimental period. This stage-specific mortality rate could be explained, in part, by the stage-specific location of encystment of cercariae, which was documented in a separate experiment. In accordance with kidney development, cercariae predominately encysted in the pronephroi during early stages of tadpole development (stages 25 through 31-32) and only in the mesonephroi and associated ducts at later stages (stages 37 through 46). As the mesonephros develops, renal capacity presumably increases. Thus, tadpoles died only when metacercariae concentrated in the functional portion of the kidney with the most limited renal capacity. As tadpoles aged, they also became less susceptible to infections. On average, 69.5% of cercariae that were exposed to stage 25-26 tadpoles successfully encysted. compared with only 8.4% of cercariae exposed to stage 37-38 tadpoles. Exposures of metamorphic frogs (poststage 46) to cercariae revealed that these individuals can become infected with echinostomes. Collectively, our data highlight the host stage-dependent dynamics of tadpole-echinostome interactions.     

Staphylococcus saprophyticus as a urinary pathogen: a six year prospective survey.

Over six years (1978-83, inclusive) weekly laboratory records of organisms causing urinary tract infection in women aged 15-25 not attending hospital were kept prospectively and analysed. The incidence of infection with Staphylococcus saprophyticus defined by age and sex was confirmed. This organism caused an increasing proportion of infections in young women over the six years studied, and these infections showed noticeable seasonality. All but four isolates of S saprophyticus were sensitive to all the commonly used antimicrobial agents that were tested. This might be because the organism is not often present in the body as a commensal and therefore not subject to the selection pressures exerted by such agents. As infection with S saprophyticus has different clinical connotations from infection with other coagulase negative staphylococci it should be differentiated from them in routine laboratory practice.     

TLR9 contributes to antiviral immunity during gammaherpesvirus infection

The human gammaherpesviruses Kaposi's sarcoma-associated herpesvirus and EBV cause important infections. As pathogenetic studies of the human infections are restricted, murine gammaherpesvirus 68 serves as a model to study gammaherpesvirus pathogenesis. TLRs are a conserved family of receptors detecting microbial molecular patterns. Among the TLRs, TLR9 recognizes unmethylated CpG DNA motifs present in bacterial and viral DNA. The aim of this study was to assess the role of TLR9 in gammaherpesvirus pathogenesis. Upon stimulation with murine gammaherpesvirus 68, Flt3L-cultured bone marrow cells (dendritic cells) from TLR9-/- mice secreted reduced levels of IL-12, IFN-alpha, and IL-6, when compared with dendritic cells from wild-type mice. Intranasal infection of TLR9-/- and wild-type mice did not reveal any differences during lytic and latent infection. In contrast, when infected i.p., TLR9-/- mice showed markedly higher viral loads both during lytic and latent infection. Thus, we show for the first time that TLR9 is involved in gammaherpesvirus pathogenesis and contributes to organ-specific immunity.     

布鲁氏菌逃逸宿主的抗感染免疫机制

布鲁氏菌病是由布鲁氏菌引发的世界范围的人兽共患传染病。布鲁氏菌为兼性胞内寄生菌,无典型的毒力因子,但却有很强的致病性,常引发人和动物的慢性感染。逃逸宿主的抗感染免疫反应是慢性感染的先决条件,这种能力对于布鲁氏菌的毒力来说似乎也越来越关键。作为成功的致病性病原菌,布鲁氏菌采用"隐秘的"策略以逃避或抑制固有免疫、调节适应性免疫,从而在宿主细胞内建立长期的持续性感染。本文将围绕布鲁氏菌逃逸宿主的抗感染免疫的分子机制进行阐述,旨为阐明布鲁氏菌毒力的新见解,这很可能为布病的预防开辟新的途径。     

Impairment of the Antibody-Dependent Phagocytic Function of PMNs through Regulation of the FcγRs Expression after Porcine Reproductive and Respiratory Syndrome Virus Infection

Porcine reproductive and respiratory syndrome (PRRS) is identified as one of the most important etiological agents in multifactorial respiratory disease of swine and can predispose pigs to secondary infections by other pathogens, usually bacteria. To understand the mechanism for an increased susceptibility to secondary bacterial infections, we investigated the antibody-dependent phagocytosis behaviour and killing ability of PMNs after infection by PRRSV strains BJ-4 or HN07-1. PMN’s antibody-dependent phagocytosis and their ability to kill E.coli were both noticeably decreased following PRRSV infection, in particular with the highly pathogenic strain HN07-1. As the change in this function of the PMNs may reflect a variation in the expression of FcγRs, the expression profiles of the activating and the inhibitory FcγRs were examined. We found that RNA expression of the inhibitory receptor FcγRIIB was up-regulated post-infection, and this was greater after infection with the more virulent PRRSV strain HN07-1. The activating receptor FcγRIIIA RNA expression was on the other hand inhibited to the same extent by both PRRSV strains. Neutralizing antibody titers post-infection by PRRSV strains BJ-4 or HN07-1 were also detected. All of the pigs in infection groups showed viraemia by the end of the study (56 DPI). These observations may help to understand the mechanism of increased susceptibility to secondary bacterial infections following PRRSV infection.     

Comparison of methods to investigate microbial populations in soils under different agricultural management

As water is a source of nosocomial infections in hospitals, the presence of fastidious Gram-negative bacteria in water samples taken in a university hospital was investigated. Water samples were inoculated onto agar plates and into amoebal microplates for co-culture. Sixty-eight alpha proteobacteria isolates were obtained and characterized using phenotypic methods and 16S rRNA gene sequence comparison. The latter approach divided the strains into seven clusters. Of these, one corresponded to previously recognized Afipia felis and it is likely that six were closely related new species. As these bacteria are fastidious and can not be cultivated on standard microbiological media, their possible role in hospital-acquired human infections should be investigated.     

Strongyloides ratti infection modulates B and T cell responses to third party antigens

It is estimated that over one third of the world population is infected with helminths, Strongyloides ssp. accounting for approximately 30-100 million cases. As helminth infections often result in a modulation of the host's immune system, infected people may display impaired responses to concurrent infections and to third party antigens. Here, we employ the experimental system of murine Strongyloides ratti infection to investigate the impact of helminth infections on experimental vaccinations. We demonstrate that concurrent infection with S. ratti strongly affected the humoral response to a thymus dependent model antigen, whereby predominantly Th1 associated IgG2b production was suppressed. We provide evidence that this suppression was due to modulation of T helper cell and not B cell function as the responses to a thymus independent model antigen remained unchanged in S. ratti infected mice. Moreover, using an adoptive transfer system, we show that infection with S. ratti directly interfered with antigen-specific proliferation of T cell receptor transgenic CD4(+) T helper cells in vivo. Finally, using IL-10 deficient mice and mice that selectively lack T helper cell derived IL-10 we rule out a role for host-derived IL-10 in mediating the suppression of thymus dependent model antigen response in S. ratti infected mice.     

Immunomodulatory Agents as Adjunctive Therapy for the Treatment of Resistant Candida Species

Invasive Candida infections have increased fivefold over the past 20 years. During this time, the incidence of antifungal resistance and infection due to non-albicans species has risen with the increasing use of broad spectrum antifungals. As few new antifungal agents are in development, strategies to improve outcomes in the treatment of Candida infections are sorely needed. The use of immunotherapy to augment the host immune response as an adjunctive treatment for Candida infections is a potentially robust and promising approach. The purpose of this review is to focus on new developments in the use of adjunctive immunotherapy for the treatment of Candida infections, and discuss the potential impact of antifungal resistance on the host immune response.     

The spread of rotavirus gastroenteritis in the Republic of Tajikistan

The article deals with the results of the investigation which has demonstrated the spread of rotavirus infection on the territory of the Republic of Tajikistan. This infection has gained an important place in the regional pathology and requires increased epidemiological surveillance on its spread. As established in the course of this investigation, in patients with the clinical manifestations of pronounced gastroenteritis rotavirus plays the role of the etiological agent in 25.8% of cases in children aged up to 14 years and in 11.0% of cases in adults. Synchronism in the seasonal dynamics of morbidity in acute enteric infections of unclear etiology and rotavirus gastroenteritis among children aged 0-2 years, annually reaching morbidity peak in October, has been revealed. Rotavirus gastroenteritis requires close attention as regards its prophylaxis as one of the main nosological forms of acute enteric infections in the Republic.     

Foodborne viruses

Foodborne and waterborne viral infections are increasingly recognized as causes of illness in humans. This increase is partly explained by changes in food processing and consumption patterns that lead to the worldwide availability of high-risk food. As a result, vast outbreaks may occur due to contamination of food by a single foodhandler or at a single source. Although there are numerous fecal-orally transmitted viruses, most reports of foodborne transmission describe infections with Norwalk-like caliciviruses (NLV) and hepatitis A virus (HAV), suggesting that these viruses are associated with the greatest risk of foodborne transmission. NLV and HAV can be transmitted from person to person, or indirectly via food, water, or fomites contaminated with virus-containing feces or vomit. People can be infected without showing symptoms. The high frequency of secondary cases of NLV illness and - to a lesser extent - of hepatitis A following a foodborne outbreak results in amplification of the problem. The burden of illness is highest in the elderly, and therefore is likely to increase due to the aging population. For HAV, the burden of illness may increase following hygienic control measures, due to a decreasing population of naturally immune individuals and a concurrent increase in the population at risk. Recent advances in the research of NLV and HAV have led to the development of molecular methods which can be used for molecular tracing of virus strains. These methods can be and have been used for the detection of common source outbreaks. While traditionally certain foods have been implicated in virus outbreaks, it is clear that almost any food item can be involved, provided it has been handled by an infected person. There are no established methods for detection of viruses in foods other than shellfish. Little information is available on disinfection and preventive measures specifically for these viruses. Studies addressing this issue are hampered by the lack of culture systems. As currently available routine monitoring systems exclusively focus on bacterial pathogens, efforts should be made to combine epidemiological and virological information for a combined laboratory-based rapid detection system for foodborne viruses. With better surveillance, including typing information, outbreaks of foodborne infections could be reported faster to prevent further spread.     

Emerging helminth zoonoses

As our ability to recognise and diagnose human disease caused by helminth parasites has improved, so our understanding of the epidemiology and clinical manifestations of these diseases has improved. Humans can develop patent infection with a wide range of helminth parasites, whose natural host is another vertebrate. Rather than focusing on a comprehensive review of zoonotic helminth infections, this review describes in detail examples of zoonotic helminth infections that have newly appeared in human populations, or have existed but are increasing in incidence or geographic range. Examples include intestinal capillariasis, anisakidosis, eosinophilic enteritis, oesophagostomiasis and gnathostomiasis. Potential reasons for the emergence of these infections, including changes in social, dietary or cultural mores, environmental changes, and the improved recognition of heretofore neglected infections often coupled with an improved ability to diagnose infection are discussed.     

Clinical usefulness of continuous administration ofNocardia rubra cell wall skeleton (N-CWS) in diffuse panbronchiolitis (DPB)

Eight patients with diffuse panbronchiolitis (DPB) who had repeated intractable airway infections were continuously treated withNocardia rubra cell wall skeleton (N-CWS), a biological response modifier. As a result, subjective symptoms were reduced in 6 patients. Antibiotics therapy could be discontinued completely in two patients and the dose of antibiotics could be reduced considerably in two other patients. No adverse reactions in relation to N-CWS were observed. These results suggest that N-CWS is effective in treating erythromycin-resistant DPB.Abbreviations BRM Biological response modifier - DPB Diffuse panbronchiolitis - EM erythromycin - N-CWS Nocardia rubra cell wall skeleton     

Hypoxia and HIF-1 activation in bacterial infections

For most of the living beings, oxygen is one of the essential elements required to sustain life. Deprivation of oxygen causes tissue hypoxia and this severely affects host cell and organ functions. Tissue hypoxia is a prominent microenvironmental condition occurring in infections and there is a body of evidence that hypoxia and inflammation are interconnected with each other. The primary key factor mediating the mammalian hypoxic response is hypoxia inducible factor (HIF)-1, which regulates oxygen homeostasis on cellular, tissue and organism level. Recent studies show that HIF-1 plays a central role in angiogenesis, cancer and cardiovascular disease but also in bacterial infections. Activation of HIF-1 depends on the nature of the pathogen and the characteristics of infections in certain hosts. Up to date, it is not completely clear whether the phenomenon of HIF-1 activation in infections has a protective or detrimental effect on the host. In this review, we give an overview of whether and how hypoxia and HIF-1 affect the course of infections.     

Seroepidemiological study of coronavirus infection in children and adults in St. Petersburg

As the result of prolonged (17 years) observations of patients with acute respiratory infections hospitalized in basic departments of clinics of the Research Institute of Influenza, coronavirus infection was found to be the cause of respiratory diseases, on the average, in 12% of cases (in some years in 6.8% to 28.6% of cases). The analysis of extensive morbidity rates among different age groups of the population showed that children were affected by coronavirus infection 5-7 times more often than adults. Three year cycles of this infection were established. The periods of coronaviruses activation were accompanied by their detection in patient material by electron-microscopy, a sharp increase of immune response of patients as well as in the number of nosocomial infections and the proportion of the monoinfection of the coronavirus nature. Coronaviruses played the leading role among other viruses in the etiology of hospital respiratory infections. Mucosal antibodies to coronaviruses in the secretions of the nasal cavity proved to be more important than serum antibodies not only in protection from infection, but also in the pattern of clinical manifestations of the disease.