Fatal encephalitis caused by Mycoplasma pneumoniae in a 9-year-old girl.

A case of fatal encephalitis in a 9-year-old girl is described. Serology showed high titre antibodies against Mycoplasma pneumoniae. In addition M. pneumoniae was detected in cerebrospinal fluid by polymerase chain reaction. Direct invasion of the central nervous system as opposed to a secondary immunologic reaction to a M. pneumoniae infection of the respiratory tract in the pathogenesis of encephalitis is discussed.

[Detection of Mycoplasma infection in the postpartum period]. / Vyiavlenie mikoplazmennoi infektsii u zhenshchin v poslerodovom periode.

The comparative results of microbiological and serological testing of parturients with uneventful and complicated course of the postpartum period were presented. The data justified the etiological role of M. hominis and U. urealyticum in the development of postpartum complications.

Biochemical and histologic findings in experimental pyelonephritis due to Ureaplasma urealyticum.

Ureaplasma urealyticum has previously been shown to be capable of persisting in the rat kidney for up to 6 months following a single reflux challenge. We examined kidney tissue from infected animals for evidence of renal damage by using standard cytochemical and immunoenzyme methods. We also monitored changes in renal function during a 6-month study period with standard biochemical assays of plasma and urine. Histologic examination showed tubular atrophy, interstitial fibrosis, and a mononuclear infiltrate in proportion to ureaplasma counts from renal tissue. The most severe damage was accompanied by hyaline cast formation within tubules which gave rise to the typical thyroidlike appearance of chronic pyelonephritis involving conventional urinary pathogens. Macroscopic renal scarring occurred in some animals. Although damage to the renal medulla was moderate to severe, only minor changes were seen in the cortex, and glomeruli were invariably spared. Biochemical tests of renal function showed similar changes in infected and uninfected animals during the study period. Interstitial inflammation was characterized by a mononuclear cell infiltrate in which polymorphonuclear leukocytes were not conspicuous. It is evident that U. urealyticum is capable of producing chronic pyelonephritis in the rat after a single reflux challenge. The results of this study have obvious implications for the pathogenicity of these bacteria in human pyelonephritis.

[Ocular findings in infection-linked immune phenomena and secondary diseases (the so-called Reiter's syndrome)]. / Okuläre Befunde bei infektionsassoziierten Immunphänomenen und Nachkrankheiten (sog. "Reiter-Syndrome").

Between 1981 and 1987 the authors saw 12 patients with Reiter's syndrome. Lesions included 6 cases of bilateral conjunctivitis in patients with chlamydial infection, 3 of unilateral serofibrinous iridocyclitis in patients with Yersinia enterocolitica, 1 case of bilateral iridocyclitis in a patient with positive chlamydial complement-binding reaction, 1 case of bilateral follicular conjunctivitis following acute gonococcal urethritis, and one case of unilateral serofibrinous iridocyclitis, in a patient with Ureaplasma urealyticum. Immunohistologic work-up of the conjunctival biopsy from the patient with Urea-plasma urealyticum urethritis revealed IgM deposits in the vascular endothelium of conjunctival vessels, C-3 deposits in the conjunctival stroma, and intercellular IgG in the conjunctival epithelium. Since Reiter's syndrome is interpreted as a sequela of secondary immune diseases following a primary infection that may persist in HLA-B27-positive patients, the patients were treated with both topical and systemic anti-infectious and anti-inflammatory agents.

Humoral immune response to polypeptides of Ureaplasma urealyticum in women with postpartum fever.

We investigated the antibody response in women with postpartum fever from whom Ureaplasma urealyticum had been isolated from the bloodstream. Acute- and convalescent-phase sera were tested for immunoglobulin G to the polypeptides of five serovars (1, 2, 3, 4, and 8), representing the two genomic clusters of U. urealyticum, by the immunoblotting (Western) method. Convalescent-phase sera from the five patients reacted more intensely and with more (up to 27) polypeptides from each of the five serovars, whereas acute-phase sera reacted weakly and with few polypeptides. Although antibody responses in these women with systemic infection could be detected by the use of any of the five different serovars as antigens, the patterns that were produced differed clearly between the two genetic clusters (serovars 1 and 3 versus serovars 2, 4, and 8). Apparently, a single serovar could be used to detect ureaplasmal antibodies in humans regardless of the serovar of the infecting strain.

Evidence of an immune response to Ureaplasma urealyticum in perinatal morbidity and mortality.

Ureaplasma urealyticum has been associated with spontaneous pregnancy loss, neonates requiring intensive care, neonatal death and more recently respiratory disease. Due to high colonization rates it has been difficult to determine whether Ureaplasmas cause infection in humans. Therefore in this overview sera from over 300 cases were assessed to determine the prevalence of an elevated antibody response to U. urealyticum. Prospectively 22 cases of stillbirth, 75 neonatal deaths and 46 normal cases were studied, in addition to 259 retrospective cases of neonates with respiratory disease of which 56 were term gestations. An antibody response greater than or equal to 1:32 to at least 1 of the 8 serovars of U. urealyticum occurred in 77.3% of stillbirths, 58.3% of respiratory disease cases, 69.3% of neonatal deaths and 80.4% of term neonates, compared to 6.5% of well term neonates (P less than 0.001 each). Elevated titers were detected in the mothers in 65.0, 54.7, 62.9, and 64.5% of each group, respectively, compared to 8.5% in mothers of healthy control cases (P less than 0.001 each). When all groups were combined the mortality rate was 61.3% among the 155 neonates who had at least one Ureaplasma titer of greater than or equal to 1:32 compared to 27.1% of 168 with a maximum titer of 1:16 (P less than 0.001). Thus in humans the prevalence of antibody response to any of 8 U. urealyticum serovars was significantly higher in potentially infected cases such as stillbirth and neonatal respiratory disease, particularly among those born at term or who die, compared to normal mothers and neonates. Presence of an elevated antibody response correlated significantly with an increased mortality rate.

Ureaplasma urealyticum in the immunocompromised host.

The lack of antibody in hypogammaglobulinemic patients probably results in failure of mycoplasmas to be "neutralized" and accounts for the diminished ability of the patients to cope with these organisms escaping hematogenously from the respiratory and urogenital tracts. Furthermore Ureaplasma urealyticum and other mycoplasmas are ingested by neutrophils in the absence of opsonins, indicated by the fact that they are able to trigger the release of chemiluminescence from these cells; ureaplasmas are not killed during this process and it is possible that carriage occurs within phagocytes to various sites. Several mycoplasmal species have localized in joints and U. urealyticum organisms are no exception. They have been isolated from the purulent synovial fluids of at least three hypogammaglobulinemic patients in Canada, England and the United States, respectively, the arthritides responding to appropriate antibiotic therapy. In one male patient, however, repeated and prolonged episodes of arthritis over several years, associated with antibiotic-resistant ureaplasmas, responded only to the administration of specific hyperimmune serum. Apart from joint involvement subcutaneous abscesses have been seen, and in the latter patient persistent urethritis was caused by ureaplasmas, these being the only organisms recovered from the urethra. Chronic urethrocystitis/cystitis in hypogammaglobulinemic patients has been associated also with ureaplasmal infection. In addition polyarthritis with recovery of both ureaplasmas and Mycoplasma hominis from the joints has been seen in a kidney allograft patient on an immunosuppressive regimen. However, further evidence that ureaplasmas cause a problem in immunosuppressed patients or in those with the acquired immunodeficiency syndrome is lacking.

Problems associated with serotyping strains of Ureaplasma urealyticum.

We sought to identify problems associated with serotyping Ureaplasma urealyticum, a human genital tract mycoplasma. We examined the results of serotyping isolates from cases of nongonococcal urethritis and asymptomatic controls and found no indication of correlation between serotype(s) and pathogenic potential. Reproducibility in serotype determination was generally good, i.e., overall agreement of 83% between primary and secondary plating and 87% on multiple, secondary cultures. We examined the reasons for variation in reproducibility and also the selection of a minor antigenic component in a culture. We provide no evidence of changes in the antigenicity of an isolate. We have indicated the means for standardizing reagents and the interpretation of results and have suggested improvements in methodology to allow more objective serotype determination.

Human mycoplasmal infections: serologic observations.

Three species of mycoplasmas have been implicated in human disease. Mycoplasma pneumoniae, which causes upper respiratory infections, pneumonia, and other complications, is an uncommon isolate from the ororespiratory tract except during outbreaks of disease. Mycoplasma hominis and Ureaplasma urealyticum are the two principal species of genital mycoplasmas. These are responsible for some cases of urogenital infections, and more recent studies show that they are associated with perinatal disorders. Glycolipid antigens of M. pneumoniae dominated serologic studies of mycoplasmas until recently, when protein antigens were isolated. The latter isolations, the production of monoclonal antibodies to attachment proteins, and the demonstration of antibodies to these proteins will make it possible to identify specific pathogenic components involved in infection due to M. pneumoniae and will permit evaluation of the relative roles of the glycolipid and protein antigens. Serologic studies of the genital mycoplasmas have demonstrated seven serotypes of M. hominis and at least 16 serotypes of U. urealyticum, the latter falling into two large serogroups. Type-specific tissue invasion with genital mycoplasmas has been demonstrated, particularly in relation to perinatal morbidity. Surface antigens of genital mycoplasmas are in the early stages of definition and purification. Present data indicate that there are specific protein antigens, but other possible antigenic forms may exist.

Immunoblotting for determination of the antigenic specificities of antibodies to the Mycoplasmatales.

Determination of the nature of antigens towards which specific antibodies are directed has caused great difficulties in studies of the antigenic structure of the Mycoplasmatales. In immunoblotting, polypeptides are separated first by SDS polyacrylamide gel electrophoresis and transferred to cellulose nitrate electrophoretically. The resultant pattern is stained by enzyme-linked staining techniques. This permits direct detection of the antigenic specificities recognized by human and animal immune serum. For example, human convalescent sera from patients with Mycoplasma pneumoniae pneumonia recognize 2 to 7 polypeptides in M. pneumoniae, whereas human sera from patients with postpartum fever from whom Ureaplasma urealyticum has been isolated from the bloodstream detect 15 to 25 polypeptides. A comparison of M. pneumoniae with M. genitalium using rabbit antisera demonstrated that these two organisms show strong cross-reactions, although the organisms can be distinguished. Although certain antigens (epitopes) are destroyed in the procedure, it appears that about two-thirds of the polypeptides retain antigenicity. Immunoblotting provides a powerful means for identifying and subsequently fractionating antigens important to the human immune response.

Mycoplasmas and bovine respiratory disease: studies related to pathogenicity and the immune response--a selective review.

Three species of mycoplasma have been established as being of importance as causes of pneumonia in housed calves, based on pathogenicity studies and frequency of association with the disease. These three species are Mycoplasma bovis, M. dispar, and Ureaplasma diversum. M. bovis is the most pathogenic of these species but the disease outbreaks with which it is associated are sporadic. M. dispar is regularly isolated from pneumonic calves but is also found causing mild superficial and asymptomatic infections of the respiratory mucosa. The bovine ureaplasmas are serologically complex. They are distinct from ureaplasmas isolated from other non-ruminants by PAGE analysis, G + C content of DNA, and serology. A second species within the genus ureaplasma has been proposed to accommodate the bovine ureaplasmas, U. diversum. Control of mycoplasma respiratory infections of cattle based on immunization might be possible. Calves have been immunized against M. bovis and immunity has been related to antibody in the lung. M. dispar appears less immunogenic in calves than M. bovis and this may contribute to its pathogenicity.

Serological evidence of Ureaplasma urealyticum infection in neonatal respiratory disease.

Since up to 80 percent of pregnant women and 30 percent of neonates may be colonized with genital mycoplasmas, it is difficult to determine whether true infection occurs. The antibody responses to eight serotypes of U. urealyticum were assessed in mothers and infants in 21 cases of neonatal respiratory disease (RD) and 24 normal cases. Among the normal population of mothers and infants, a titer of greater than or equal to 1:32 occurred in 0.25 percent (1/394). In mother-infant paired titers, a fourfold difference occurred in 2.6 percent (5/192). Among 54 RD neonates, 55.6 percent had a titer of greater than or equal to 1:32 compared to only 4.2 percent of normal neonates (p less than .001). Fourfold elevations in antibody titers of greater than 1:32 were observed in the neonate in 52.4 percent of RD cases compared to 0 percent of 24 normal pairs (p less than .001) and in 28.6 percent of mothers of RD neonates compared to 0 percent in normal cases (p = .013). We observed that 43.3 percent of RD neonates with titers greater than or equal to 1:32 died compared to 16.6 percent of RD neonates exhibiting no elevation of antibody response over the maternal level. Among the six who died, 66.7 percent of neonates and 16.7 percent of their mothers had elevated titers, compared to 33.3 percent of 15 surviving infants and 40.0 percent of their mothers. These elevated antibody responses strongly support the concept that U. urealyticum causes infection in the perinatal period in association with neonatal respiratory disease. Since the elevation in titers was detected close to delivery in many cases, the infection may occur in utero.

Serological investigation of horse sera for antibodies against mycoplasmas and acholeplasmas.

Sera from horses with respiratory disease (RD) have been investigated using the complement fixation test, indirect hemagglutination test, enzyme immune assay, and the metabolic inhibition test, and sera from mares after abortion, using the complement fixation test, indirect hemagglutination test and enzyme immune assay, for antibodies against Mycoplasma equirhinis, M subdolum, M. equigenitalium, M. pulmonis, M. felis, Acholeplasma laidlawii, A. hippikon and A. equifetale. Antibodies were found against all mycoplasma and acholeplasma species tested, more often against acholeplasmas. The antibody pattern was quite similar for horses with RD and for mares after abortion. The results of the four serological tests performed showed only a limited correlation and the percentage of sera with antibodies detected by the four tests used differed widely.

Immunological and functional activity of spleen lymphocytes from mice infected by Acholeplasma laidlawii cells and Rauscher virus.

The duration of Acholeplasma laidlawii antigen persistence in mice, resistant to Rausher leukemia virus, after infection with both A. laidlawii cells and Rausher virus has been studied. The antigen persistence was accompanied by marked depression of immune response which was especially severe in case of mixed acholeplasmavirus infection. Such immunosuppression and observed infiltration of the spleen with immature leukemic cells can be regarded as a preleukosis. Immunosuppression was accompanied by an increase of the transport of carbohydrates inthe lymphocytes. This stimulation an be explained by the exchange of lipid components between acholeplasma and lymphocyte membranes resulted in increase of lymphocyte membrane fluidity, or it may be due to the mitogenic effect of A. laidlawii cells and virus, accompanied by the same membrane effect.

[Blast transformation in response to plant mitogens in Wistar rats infected with Mycoplasma arthritidis or Acholeplasma laidlawii]. / Blasttransformatsiia v otvet na rastitel'nye mitogeny u krys Wistar, infitsirovannykh Mycoplasma arthritidis ili Acholeplasma laidlawii.

The response of lymphocytes of M. arthritidis- or A. laidlawii-infected rats to PHA and ConA was studied. Mycoplasma infection was shown to stimulate the DNA synthesis in lymphocytes of the spleen and lymph nodes and to depress the responses to mitogenes one week after infection. By the same time splenocytes of A. laidlawii-infected rats were shown to only slightly proliferate in response to PHA. After 4 weeks of infection the lymphocyte transformation was greatly increased in both mycoplasma- and acholeplasma-infected rats. The first to be stimulated by the mitogenes were cells from the lymph nodes followed by those from the spleen. By the 65th day of infection no stimulation occurred. Possible mechanisms of the phenomena described are discussed.

Experimental infection of the respiratory tract with Mycoplasma pneumoniae.

M. pneumoniae, a common human respiratory pathogen, has been studied experimentally for years using intranasal inoculation of the golden Syrian hamster. Because of recent evidence outlining the role in pulmonary immune development of particle size and depth of mycoplasma deposition in the hamster lung, we developed an aerosol chamber for the reproducible aerosolization of radiolabeled M. pneumoniae. Organisms were labeled to high specific activity by the incorporation of 3H-oleic acid and aerosolized under airflow and humidity conditions creating a mean particle diameter of 2.0 micrometers. Under these conditions, viable mycoplasmas were reproducibly and evenly distributed to all major lobes of the lung. Examination of radioactive clearance and organism viability within the lung during the first 48 hr after aerosolization have suggested a minimal role for macrophage mycoplasmacidal activity and a more prominent role for ciliary clearance. Data from aerosol infections of hamsters with radio-labeled M. pneumoniae should provide a unique opportunity to examine in a highly controlled manner the effects of air pollutants on the initial stages of infection as well as effects on the development of pulmonary immunity and histologic alterations.

[Acholeplasma laidlawii--a pathogenic or apathogenic species?]. / Acholeplasma laidlawii--eine pathogene oder apathogene Spezies?

The question is discussed, whether Acholeplasma laidlawii is a pathogenic or apathogenic species. Studies have shown that it is a species of potential pathogenicity, however, with virulence properties differing greatly by strains. Nothing so far has become known of contributive factors which might be needed for an infectious disease to develop.