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Mycobacterium asiaticum as a potential pulmonary pathogen for humans. A clinical and bacteriologic review of five cases.

Mycobacterium asiaticum was isolated from pulmonary material from 5 persons residing in Queensland, Australia. All patients had repeated positive specimens, but the organism was considered responsible for pulmonary mycobacteriosis in only 2 of them. This is the first report of disease caused by M. asiaticum. Clinical, bacteriologic, and epidemiologic details are presented.

Aged↗

Siderophores of the human pathogenic fluorescent pseudomonads.

Bacteria need a sufficient supply of iron in ionic form for their metabolism. When living in an environment where this is not possible (as in the soil due to the presence of highly unsoluble ferric oxide hydrates, or in living organisms where iron is bound to peptidic chelators) Fe3+ complexing compounds, called siderophores, are produced. The siderophores of Pseudomonas aeruginosa, a dangerous opportunistic human pathogen, and of related potentially pathogenic species will be presented.

Fluorescence↗

[Enterotoxin production as a diagnostic test in intestinal dysbacterioses ].

The new approach to advancing diagnostic of dysbacterioses grounded on determination of the pathogenic factors of potential-pathogenic microflora is proposed. The method of reacting of an indirect hemagglutination with usage of erythrocital diagnosticums ostend availability of production of staphylococcal enterotoxines of types A and B in 40% of the strains of staphylococcuses, isolated at dysbacterioses. The intensity of production of staphylococcal enterotoxines for strains of microorganisms, isolated at dysbacterioses and carrying of S. aureus, and at food borne diseases, is various. The availability of clinical developments of an intestinal dysfunction in faeces of the patients contacts with persistence of enterotoxigenics S. aureus, and their elimination--with successful police of the disturbed microbiocenosis.

Bacterial Infections↗

Mycobacterium xenopi, a potential human pathogen.

Mycobacterium xenopi is infrequently recognized as a cause of pulmonary disease. During a 12-year survey (1978-89),. 108 strains of this Mycobacterium were isolated from 90 persons and 6 hot water samples. From 87 patients 89 occasional strains of M. xenopi were isolated, and 3 patients were diagnosed as having pulmonary mycobacteriosis caused by it. The treatment and the response in these three cases were variable, depending on clinical conditions and sensitivity to drugs. Most of the strains isolated came from patients hospitalized at the Barzilai Hospital, Ashkelon, therefore a local environmental contamination was suspected. The suspicion was confirmed by the isolation of this thermophile organism from the hot water samples of the above hospital.

Aged↗

A monoclonal antibody to a cross-reactive idiotype on cationic human anti-DNA antibodies expressing lambda light chains: a new reagent to identify a potentially differential pathogenic subset.

Anti-double-stranded DNA antibodies are commonly found in the serum of patients with systemic lupus erythematosus (SLE). They are a heterogeneous group of antibodies thought to differ in pathogenicity. The degree of heterogeneity and the structural correlates of pathogenicity, however, remain poorly defined. To address these questions we have been generating anti-idiotypic antibodies to the anti-DNA antibodies found in the serum of SLE patients. In this paper we report the generation and characterization of a new murine monoclonal anti-idiotype, 8.12, that recognizes a subset of anti-DNA antibodies that is present in serum of approximately 50% of patients with SLE. The 8.12 anti-idiotype recognizes uniquely cationic anti-DNA antibodies, all of which express lambda light chains. In murine models of SLE, it has been suggested that cationic anti-DNA antibodies are preferentially deposited in the kidney. It may be, therefore, that 8.12 recognizes a subset of anti-DNA antibodies of particular pathogenic significance.

Antibodies, Anti-Idiotypic↗

Blastocystis hominis in a pig-tailed macaque: a potential enteric pathogen for nonhuman primates.

Large numbers of Blastocystis hominis were found in fecal samples from a pig-tailed macaque (Macaca nemestrina) with chronic diarrhea that was refractory to conventional therapy. The animal's condition improved and fecal samples showed minimal numbers of Blastocystis hominis following therapy with an antiprotozoal agent. This organism, recently reclassified as a protozoa, appeared to be causally related to the diarrhea. The cytologic and ultrastructural features of the monkey Blastocystis were comparable to those reported for similar organisms from man.

Animals↗

Immunosuppressive potential and pathogenicity of an avian adenovirus isolate involved in hydropericardium syndrome in broilers.

The role of avian adenovirus isolate PARC-1 as an immunosuppressive agent was investigated using a Newcastle disease virus (NDV) vaccine immune response procedure. The immunosuppressive effect on the humoral immune response was investigated up to 21 days after inoculation with adenovirus. Infected chickens showed a serologic response to NDV that was reduced compared with that of the controls. To further investigate the effect of the virus on major lymphoid organs, the pattern of virus dissemination in various organs was studied at various time intervals after inoculation. Spleen, thymus, bursa of Fabricius, and cecal tonsils of broilers were examined using a dot-immunobinding assay. The virus was found to have a predilection for lymphoid organs, and virus from lymphoid organs was capable of producing disease when inoculated into healthy chickens. The relationship of virus predilection to its immunosuppressive effect also was studied.

Adenoviridae Infections↗

[Serologic studies of domestic cats for potential human pathogenic virus infections from wild rodents].

For several viral infections a reservoir in wild rodents has been demonstrated. Some of the agents are known or suspected to be pathogenic for humans. Because improvements in hygiene have reduced direct human contact with rodents, domestic cats could be acting as active transmitters of these viruses from rodents to man. We selected 4 such pathogens--ortho- and parapox-, hanta- and encephalomyocarditis viruses--which, in different ways, may lead to serious human illness: Ortho- and parapoxvirus infections may cause localized pox lesions following direct skin contact. In general, the lesions heal without complications; in immunosuppressed or -deficient individuals, however, infection may generalize and take a dramatic course. Hantaviruses exist in various serotypes with different pathogenicity for human beings, varying from asymptomatic infection to highly fatal disease. In central and northern Europe the Puumala serotype is predominant causing influenza-like symptoms and renal dysfunction. Human infections arise from inhalation of aerosolized excreta of persistently infected rodents. Infections of man associated with encephalomyocarditis virus were demonstrated sporadically in cases of encephalitis and meningitis. In the present study, we investigated in 200 feline serum samples the prevalence of antibodies to ortho- and parapox-, hanta- and encephalomyocarditis virus. All serum samples were from cats that had been allowed to roam outside and to hunt. They were submitted from all parts of Austria for routine diagnosis in 1993. Four per cent of cats showed antibodies to orthopoxviruses with haemagglutination inhibition (HI) titres of 16-512; because of extensive cross-reactivity, positive samples reacted with all investigated orthopoxviruses (a feline orthopoxvirus recently isolated in Vienna, the reference strain of cowpox virus, Brighton, and vaccinia virus, strain IHD), only varying in titre. The specificity of the results was confirmed by virus neutralisation (VN) test, in which the same sera showed titres of 4-32. These data imply that, at least in Austria, unrecognized or subclinical orthopoxvirus infection in cats is more common than previously thought. In contrast to orthopoxviruses, all serum samples proved negative to parapoxvirus (parapoxvirus bovis 1) in VN test. In the same 200 samples, a seroprevalence of 5% was found to hantavirus (immunofluorescence antibody assay), indicating that domestic cats are susceptible to this virus and that infection is not uncommon in cat populations. Because higher titres were obtained against the Puumala serotype compared to the more pathogenic serotype Hantaan, it is most likely that the cats had experienced Puumala infections. Using HI test, antibodies to encephalomyocarditis virus (EMCV) were demonstrated in only 1.5% of the feline serum samples; although the antibody titres were low (16 and 32, respectively) we consider them specific, because these sera proved positive in VN test as well. Nevertheless, EMCV infection in domestic cats seems to be of low importance. The serological results presented in this paper, together with virological and epidemiological data, indicate that the domestic cat plays an important role only in the transmission of orthopoxviruses to human beings, but not in the case of parapox-, hanta-, and encephalomyocarditis virus.

Animals↗

Histamine synthesis by respiratory tract micro-organisms: possible role in pathogenicity.

Five bacterial species considered to be potential pathogens in acute exacerbations of chronic bronchitis, cystic fibrosis, and pneumonia--Branhamella catarrhalis, Haemophilus parainfluenzae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae--were evaluated for their potential to synthesise histamine in vitro. Bacterial species commonly isolated from infected sputum but generally not considered to be pathogenic--Enterobacteriacae, Neisseria pharyngis, coagulase negative staphylococci, alpha-haemolytic streptococci, and Candida albicans--were similarly studied. Of the "pathogens", the Gram negative species B catarrhalis, H parainfluenzae and Ps aeruginosa synthesised clinically important amounts of histamine; this was not the case for the Gram positive species S aureus and S pneumoniae. Of the "non-pathogenic" species, only the Enterobacteriacae, as a group, were found to synthesise clinically important amounts of histamine. These results show that some Gram negative bacteria, associated with acute exacerbations in respiratory infections, produce histamine and possibly other inflammatory mediators, which may contribute to their pathogenecity in the lower respiratory tract in vivo.

Bacteria↗

Otitis media in Greenland. Studies on historical, epidemiological, microbiological, and immunological aspects.

This thesis describes the different aspects of otitis media (OM) in the population of Greenland viewed in a historical and modern clinical perspective. Chapter 1 outlines the addressed problems and aims while chapters 2 and 3 deal with historical studies and an evaluation of the present knowledge based on the literature. Physical anthropological studies, using skeletal samples of adult Eskimo crania from before and after the colonization of Greenland in 1721 and information about modern living Eskimos (Inuit), have shown that OM sequelae of the temporal bones were significantly less common in pre-colonization Eskimos and that the mean area size of the pneumatized cell system in the temporal bone was significantly larger in pre-colonization Eskimos. These findings indicated an increase in OM after the colonization most likely caused by the social, cultural, habitary, and dietary changes due to increased contact with the outside world. Historical reports after the colonization confirm a high prevalence of OM especially in children. Modern epidemiological studies from the 1960's to 1980's in the Arctic region of Alaska, Canada, and Greenland along with reports from visiting consultant otologists in Greenland almost uniformly mention prevalent OM problems in children as well as in adults. The aim was therefore to further describe the epidemiological pattern of the different OM disease entities (acute OM (AOM), chronic OM (COM), COM with suppuration (CSOM), secretory OM (SOM), and cholesteatoma) and investigate the potentially associated risk factors in especially Greenlandic children because these diseases are primarily established and problematical in childhood. Chapter 4 describes the definitions used in the thesis and chapter 5 describes the studies included. Section 5.1 describes a study of cholesteatoma in Greenlanders. The study revealed an almost similar incidence of hospital treated children with cholesteatoma (6.6 per 100,000) as seen in comparable studies from other parts of the world. Furthermore, childhood cholesteatomas were the most aggressive. The frequency of residuals or recurrences after otosurgical treatment was high with a trend for better results when using the extensive canal wall-down procedure. It could be concluded that these patients urgently need close follow-up for at least five years postoperatively, if not lifelong. Section 5.2 describes a hearing screening survey of 167 school children using school registration charts. A high prevalence of hearing loss (HL) was found. A total of 43% of the children had hearing thresholds exceeding 20 dB at one or more frequencies between 250-8000 Hz in one or both ears, and 19% had the same type of HL in the frequencies 500-2000 Hz. HL was significantly associated with episodes of OM. These findings were in accordance with reports from Alaska and Canada. It is therefore concluded that a hearing screening programme of school children is important and that OM seems to have an impact on hearing in school children in Greenland. In section 5.3 an epidemiological survey is described concerning the prevalence of the different OM disease entities. The survey was carried out in Nuuk and Sisimiut and involved 740 children aged 3, 4, 5, and 8 years. A total of 591 children participated and selection bias was not found when controlling for age, sex, and episodes of AOM. The survey revealed that 52% of children in Nuuk and 54% in Sisimiut had some kind of pathological affection of their middle ear. COM and CSOM were found in 9%, but more prevalent among children in Sisimiut (12%) than in Nuuk (7%). Middle ear effusion (MEE) diagnosed by tympanometry was found in 23% in Nuuk and 28% in Sisimiut while simple tubal dysfunction (STD) was found in 13% and 8%, respectively. MEE and STD were associated with young age. Sequelae of OM was apparent in 11% in both towns. When comparing the results with a 10-year-older, almost similar survey of 142 children, it was evident that the OM situation had not changed in the period between the studies. The survey underlines the need for increased focus on the different OM entities in Greenlandic children. Section 5.4 deals with microbiological aspects. The nasopharyngeal microflora and ear discharge microflora of potential pathogens were evaluated in 54 children with AOM and in 201 control children without AOM. Very high carriage rates expressed qualitatively and semiquantitatively of potentially pathogenio bacteria were found in the nasopharynx of children with AOM (98%) but also in that of the control children (91%) and even in children denoted as being very healthy (94%). However, the same bacterial species were cultured from the nasopharynx and ear discharge as in comparable studies world-wide. Only S. pneumoniae was carried significantly more often in the nasopharynx of AOM children compared with age matched control children. Chlamydiae, M. pneumoniae, adenovirus, respiratory syncytial virus, parainfluenza- type 1, 2, and 3 virus, and influenza- type A and B virus were not major pathogens. In contrast, entero- and rhinoviruses were detected significantly more frequent in nasopharyngeal specimens from AOM children (59%) compared with age matched controls (33%) and also in 29% of the examined ear discharge specimens. It is therefore concluded that the potentially pathogenic bacterial load is early and massive. This alone or in interplay with entero- and rhinovirus infection and occasionally with other viruses may play an important role in the high prevalence of OM among children in Greenland. Section 5.5 deals with an examination of potential risk factors for AOM, recurrent AOM (rAOM), and COM in the same 591 children as studied in section 5.3. Early age at first AOM episode was associated with rAOM episodes (> or = 5 episodes since birth). Thus, the relative risk of developing rAOM was eight times higher if the first episode of AOM occurred before 7 months of age than after 24 months of age. Furthermore, compared with studies elsewhere in the world, a high proportion (40%) of the children in this survey had their first AOM episode during their first year of life and 41% of these children developed rAOM. It was also found that children had an increased risk of AOM, rAOM, or COM when both parents were born in Greenland, when parents also have had OM, when living in very crowded households, and when having experienced a long period of exclusive breast feeding, or when recalling of breast feeding was not possible. Gender, type, and size of housing, insulation standard of housing, daycare, exposure to passive cigarette smoking, and dietary habits were not associated with AOM, rAOM, or COM in the surveyed children. It is concluded that early onset of AOM occurs frequently in Greenlandic children and that a high proportion of these children develop rAOM. The study confirms that AOM is a highly multifactorial disease determined by a number of genetic and environmental factors. Finally, section 5.6 is a hypothesis generating study attempting to explain the high prevalence of early episodes of AOM in community-based children in Nuuk. The hypothesis is based on a possible association between findings of mannose-binding lectin genotypes, early Epstein-Barr virus infections and episodes of AOM, rAOM, or nasopharyngeal colonization with potentially pathogenic bacteria. However, the study does not support any of this hypothesis. In chapter 6, future studies are suggested and chapter 7 presents concluding remarks.

Carrier Proteins↗

[Intestinal parasites in African asylum seekers: prevalence and risk factors].

OBJECTIVE: To determine the prevalence of potentially pathogenic intestinal parasites in asylum seekers coming from a highly endemic area, and to identify groups of asylum seekers from Africa with a high risk of an intestinal parasitic infestation which is potentially harmful of their own health or that of those in their vicinity. DESIGN: Prospective. METHOD: In the period January 1996-May 1999, 956 asylum seekers from Africa were checked for intestinal parasites by means of a stool examination within one month of arriving in the Netherlands. Independent variables for data analysis were sex, age and area of origin. RESULTS: Pathogenic intestinal parasites were found in 40.6% of the 956 African asylum seekers coming from areas south and east of the Sahara. Double-infection was found in 9.5% and triple-infection in 0.9% of the study population. The most common pathogenic parasite was Trichuris trichiura (13.6%) followed by Entamoeba histolytica/dispar (8.8%), hookworms (7.8%), Schistosoma (7.0%) and Giardia lamblia (5.0%). G. lamblia was the most commonly found potentially pathogenic parasite in children less than 13 years old (19.0%). In the population from Western Africa, 15.6% had a hookworm and 12.8% a Schistosoma. Both these helminthic infestations were three times as prevalent in men as in women. CONCLUSION: Sex, age and area of origin were important indicators for the species of parasite. On the basis of this, risk groups can be selected for screening for potentially pathogenic intestinal parasites.

Adolescent↗

Colonization of denture plaque by respiratory pathogens in dependent elderly.

OBJECTIVES: Recently, there has been a resurgence of interest in the interactions between oral conditions and a number of prevalent systemic diseases. The morbidity and mortality of the dependent elderly that result from aspiration pneumonia have been recognized as a major geriatric health problem. The purpose of this study was to gain more information on the microflora of plaque on dentures and to assess the existence of oral infectious pathogens potentially causing the respiratory disease in the dependent elderly. SUBJECTS AND METHODS: The denture bacterial flora of 50 dependent elderly were examined to identify microorganisms by the culture method. RESULTS: 18 species of microorganisms were detected in denture plaque in this study. A variety of pathogens with the potential to cause respiratory infection pathogens colonized on the dentures of dependent elderly. CONCLUSION: The results of the present study revealed that bacteria that commonly cause respiratory infection colonized on the dentures of dependent elderly, suggesting that denture plaque may function as a reservoir of potential respiratory pathogens to facilitate colonization on the oropharynx.

Aged↗

Evaluation of O-antigen inactivation on Pla activity and virulence of Yersinia pseudotuberculosis harbouring the pPla plasmid.

Yersinia pestis is a species that emerged recently from Yersinia pseudotuberculosis and gained an exceptional pathogenicity potential. Among the major genetic differences between the plague bacillus and its ancestor is the acquisition of the pPla plasmid, which has been associated with the increased virulence of Y. pestis. In a previous study, introduction of pPla into Y. pseudotuberculosis did not lead to any modification of the virulence of the host bacterium. However, it was subsequently demonstrated that the presence of smooth lipopolysaccharide (LPS) inhibits the activity of Pla. In this study, pPla was introduced into a Y. pseudotuberculosis strain expressing smooth LPS, and into a variant in which a mutation that abrogates the formation of O-antigen (O-Ag) repeats (as in natural isolates of Y. pestis) was generated. It was found that in both strains, Pla was synthesized, exported to the bacterial membrane and processed as in Y. pestis. However, the ability of Pla to activate plasminogen was weak and observed only at 37 degrees C in the smooth strain, while this activity was similar to that of Y. pestis and expressed at both 28 and 37 degrees C in the O-Ag mutant strain. Similarly, Pla-mediated inactivation of the antiprotease alpha2-antiplasmin was not detected in the smooth Y. pseudotuberculosis strain grown at 28 degrees C, but was expressed at both temperatures in the O-Ag mutant strain. Despite the more efficient activity of Pla, the Y. pseudotuberculosis O-Ag mutant strain exhibited a lower pathogenicity upon subcutaneous infection of mice. The results thus indicate that, although abrogation of O side chain synthesis in a Y. pseudotuberculosis strain harbouring pPla potentiates the two proteolytic activities of Pla, this is not sufficient to confer to Y. pseudotuberculosis a higher pathogenicity potential. These results also suggest that acquisition of pPla may not have been sufficient to confer an immediate higher pathogenic potential to the ancestor Y. pestis strain.

Animals↗

Pathogenicity of Beauveria bassiana in mice.

The potential pathogenicity of Beauveria bassiana was examined by intramuscular injection of high (2 x 10(8)) or low (2 x 10(5)) concentrations of conidia spores, into the left or right quadriceps muscles of CD-1 mice, respectively. The injection sites were monitored over a period of 28 days by both microbiological and histopathological methods. Focal muscle necrosis, edema and inflammation occurred rapidly (within 12 hours) at the high dose application (2 x 10(8)) site, but such lesions were far less severe with the low dose spore application (2 x 10(5)). Fungal spores in the high dose site persisted in normal shape for 2 weeks, after which time they began to degenerate. Almost all spores were cleared from the injection site within the 28-day observation period. Spread to other organs of the body was not observed, except by macrophage transport to regional lymph nodes. At the low dose rate, most spores were cleared within 12 h to 2 d, leaving only mild focal edema and inflammation. Viable fungal colonies could be recovered up to 3 d after injection from the high dose site, but only up to 12 h from the low dose site. It was concluded that B. bassiana does not cause infection, nor multiply, nor survive for more than 3 days when injected intramuscularly into healthy mice.

Animals↗

Campylobacteriosis in man: pathogenic mechanisms and review of 91 bloodstream infections.

Five patients with Campylobacter fetus(previously called "Vibrio fetus") bacteremia are presented with enteric symptoms in four patients, a self-limited course in three, and with possible nosocomial infection in one patient who had disseminated malignancy. The clinical syndromes of 91 bacteremic patients with campylobacteriosis and C. fetus taxonomy and pathogenicity are reviewed. Studies of potential pathogenic mechanisms in enteric infections failed to reveal the production of either heat-stable or heat-labile, cholera-like enterotoxin, cytotoxicity or invasiveness. In comparison with different species of vibrio infections, C. fetus appears to produce disease by a different mechanism, one which involves a bloodstream infection, perhaps following penetration through the intestinal mucosa as has been demonstrated experimentally with salmonellae and yersinia. Such a pattern is consistent with the clinical pattern of C. fetus infections and the experimental studies reported herein.

Adult↗

Functional epitopes on porcine endogenous retrovirus envelope protein interacting with neutralizing antibody combining sites.

Porcine cell and organ transplantation provides promise for maintaining normal physiological conditions in patients with end-stage organ failure. The approach however poses serious risk of transmitting pig pathogens to humans. Among many potential pathogens, porcine endogenous retroviruses (PERV) are of particular concern due to their ubiquitous nature in pigs and capability of infecting human cells. Major antigenic determinants and receptor binding domains on PERV remain unclear until now. Two monoclonal antibodies (mAb), named 8E10 and 7C4 capable of neutralizing PERV infection in HEK293 cells are isolated at an IC(50) of 3.0 and 2.7 microg/ml, respectively, in this work. Epitope location for mAb 8E10 was mapped to amino acids 427-434, residing at the C-terminal region of the gp70 component of type A PERV Env protein. The mAb 8E10 bound directly to the PERV indicating that the epitope is exposed on the virion surface. The mAb 7C4 epitope was assigned to the region comprising amino acids 517-537 on the p15E component of PERV. In contrast to mAb 8E10, the 7C4 mAb bound native PERV inefficiently suggesting that its epitope is accessible only after the virus interacts with its receptor. Finally, both mAbs variable regions were cloned and nucleotide sequence determined. All together, these results reveal that both mAbs 8E10 and 7C4 effectively neutralize PERV infection and may be used as a mean to prevent PERV infection in patients receiving xenotransplantation.

Amino Acid Sequence↗