Sequence variation and immunogenicity of the Mycoplasma genitalium MgpB and MgpC adherence proteins during persistent infection of men with non-gonococcal urethritis.

Mycoplasma genitalium is a sexually transmitted bacterial pathogen that infects men and women. Antigenic variation of MgpB and MgpC, the immunodominant adherence proteins of M. genitalium, is thought to contribute to immune evasion and chronic infection. We investigated the evolution of mgpB and mgpC sequences in men with non-gonococcal urethritis persistently infected with M. genitalium, including two men with anti-M. genitalium antibodies at enrollment and two that developed antibodies during follow-up. Each of the four patients was persistently infected with a different strain type and each patient produced antibodies targeting MgpB and MgpC. Amino acid sequence evolution in the variable regions of MgpB and MgpC occurred in all four patients with changes observed in single and multiple variable regions over time. Using the available crystal structure of MgpC of the G37 type strain we found that predicted conformational B cell epitopes localize predominantly to the variable region of MgpC, amino acids that changed during patient infection lie in these epitopes, and variant amino acids are in close proximity to the conserved sialic acid binding pocket. These findings support the hypothesis that sequence variation functions to avoid specific antibodies thereby contributing to persistence in the genital tract.

Sustained influence of infections on prostate-specific antigen concentration: An analysis of changes over 10 years of follow-up.

BACKGROUND: To extend our previous observation of a short-term rise in prostate-specific antigen (PSA) concentration, a marker of prostate inflammation and cell damage, during and immediately following sexually transmitted and systemic infections, we examined the longer-term influence of these infections, both individually and cumulatively, on PSA over a mean of 10 years of follow-up in young active duty U.S. servicemen. METHODS: We measured PSA in serum specimens collected in 1995-7 (baseline) and 2004-6 (follow-up) from 265 men diagnosed with chlamydia (CT), 72 with gonorrhea (GC), 37 with non-chlamydial, non-gonococcal urethritis (NCNGU), 58 with infectious mononucleosis (IM), 91 with other systemic or non-genitourinary infections such as varicella; and 125-258 men with no infectious disease diagnoses in their medical record during follow-up (controls). We examined the influence of these infections on PSA change between baseline and follow-up. RESULTS: The proportion of men with any increase in PSA (>0 ng/mL) over the 10-year average follow-up was significantly higher in men with histories of sexually transmitted infections (CT, GC, and NCNGU; 67.7% vs 60.8%, P = 0.043), systemic infections (66.7% vs 54.4%, P = 0.047), or any infections (all cases combined; 68.5% vs 54.4%, P = 0.003) in their military medical record compared to controls. CONCLUSIONS: While PSA has been previously shown to rise during acute infection, these findings demonstrate that PSA remains elevated over a longer period. Additionally, the overall infection burden, rather than solely genitourinary-specific infection burden, contributed to these long-term changes, possibly implying a role for the cumulative burden of infections in prostate cancer risk.

Insight into infection-mediated prostate damage: Contrasting patterns of C-reactive protein and prostate-specific antigen levels during infection.

BACKGROUND: To investigate mechanisms underlying our previous observation of a large rise in serum prostate-specific antigen, a marker of prostate pathology, during both sexually transmitted and systemic infections, we measured serum high-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, in our previous case-control study of young, male US military members and compared our findings to those for PSA. METHODS: We measured hsCRP before and during infection for 299 chlamydia, 112 gonorrhea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases; before and after infection for 55 infectious mononucleosis (IM) and 90 other systemic/non-genitourinary cases; and for 220-256 controls. RESULTS: Only gonorrhea cases were significantly more likely to have a large hsCRP rise (≥1.40 mg/L or ≥239%) during infection than controls (P < 0.01). However, gonorrhea, IM, and other systemic/non-genitourinary cases were more likely to have a rise of any magnitude up to one year post-diagnosis than controls (p = 0.038-0.077). CONCLUSIONS: These findings, which differ from those for PSA, suggest distinct mechanisms of elevation for hsCRP and PSA, and support both direct (eg, prostate infection) and indirect (eg, systemic inflammation-mediated prostate cell damage) mechanisms for PSA elevation. Future studies should explore our PSA findings further for their relevance to both prostate cancer screening and risk.

Chlamydia trachomatis serovar G infection in a bisexual male with urethritis.

We report a case of Chlamydia trachomatis serovar G urogenital tract infection in a 33-year-old human immunodeficiency virus-1 (HIV-1) seropositive Indian bisexual male. This case highlights the emergence of a new serovar in India. The patient was tested positive for C. trachomatis by both cryptic plasmid and omp A gene polymerase chain reaction (PCR). On further characterization using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) and omp A gene sequencing, the strain was found to be C. trachomatis serovar G. His spouse was also found to be infected with C. trachomatis serovar G. Phylogenetic analysis was performed on the clinical isolates obtained from both partners and were found to be identical to the isolates available in GenBank. The sexual network could not be traced further. Detection of a new genotype suggests importation of a new strain into the population probably by sexual contact with a person from a geographical area where the strain is common. Identifying circulating genotypes in the community can assist in developing strategies for improved sexually transmitted disease control.

Diagnosing Chlamydia Trachomatis Urinary Tract Infections--Preliminary Report.

BACKGROUND: Chlamydia trachomatis is mentioned among the etiologic factors for urinary tract infections. Chlamydias are parasites inside a cell. A very significant problem of C. trachomatis infections is their asymptomatic character. The most frequent infections caused by these bacteria are inflammations of the urethra and bladder; of the vagina, cervix, vaginal cavity and adnexa in women; and of the epididymis, testicles and prostate in men. In the diagnosis of C. trachomatis infections, the following methods are used: immunofluorescent techniques, immunoenzymatic assays, serological examinations and genetic techniques (for example PCR). OBJECTIVES: The aim of the study was to detect C. trachomatis among patients with symptoms of non-gonorrheal urethritis using diagnostic serologic methods and direct immunofluorescence. The purpose was to assess the connection between the incidence of urinary tract infections caused by C. trachomatis and symptoms that patients report as well as other data from interviews. MATERIAL AND METHODS: Blood serum and urethral smears were taken from each of 57 patients. The ELISA method was used to mark specific IgG and IgGcHSP60 anti-chlamydia antibodies in the blood serum. In the urethral smear, antigens were marked using the direct immunofluorescence method. RESULTS: Evidence for urinary tract infection caused by C. trachomatis was found in 15.79% of the examined patients using the immunofluorescence method. In the blood serum, positive results for IgGcHSP60 were obtained in 17.54% of the patients and for IgG in 8.77%. CONCLUSIONS: The studies carried out so far suggest that C. trachomatis has a significant role in the etiology of urethritis in adults and children. Other serological tests should be conducted in all the patients in order to study the immune responses in infected individuals and to confirm C. trachomatis infection using genetic methods such as PCR.

Prediction of the persistence of Mycoplasma genitalium after antimicrobial chemotherapy by quantification of leukocytes in first-void urine from patients with non-gonococcal urethritis.

Mycoplasma genitalium is regarded as another pathogen of male non-gonococcal urethritis (NGU). Failure to eradicate this mycoplasma is associated with persistent or recurrent NGU, but this mycoplasma is not routinely examined in clinical practice. In cases of M. genitalium-positive NGU, therefore, some criteria are needed to assess the success or failure of antimicrobial chemotherapy other than microbiological outcomes. We enrolled 49 men with M. genitalium-positive non-chlamydial NGU. At successive visits after treatment, we inquired about their symptoms, observed their urethral meatus for urethral discharge, and examined their first-void urine (FVU) for quantification of leukocytes and for the persistence of M. genitalium. M. genitalium was eradicated in 34 patients after treatment, whereas the mycoplasma persisted in 15. Urethritis symptoms and urethral discharges were not found to be predictors of the persistence of M. genitalium up to the 25th day after the start of treatment. Leukocyte counts in FVU from the patients with persistence of M. genitalium were significantly higher than those from the patients with eradication of the mycoplasma. Leukocyte counts of 10 leukocytes/µl or more between the 18th and 24th day after the start of treatment were most significantly associated with the persistence of M. genitalium. Quantification of leukocytes in FVU would appear to be crucial to judge the outcome of treatment in patients with non-chlamydial NGU and could be helpful to predict the persistence of M. genitalium after treatment when M. genitalium is not routinely examined in clinical specimens in clinical practice.

Clinical efficacy of levofloxacin 500 mg once daily for 7 days for patients with non-gonococcal urethritis.

To confirm the efficacy of the treatment regimen with oral levofloxacin (LVFX) 500 mg once daily for 7 days for patients with non-gonococcal urethritis (NGU), we evaluated the microbiological and clinical outcomes of the regimen in those patients. We finally evaluated 53 patients with symptomatic NGU and 5 patients with asymptomatic NGU. As a result of microbiological examinations, 19 of the symptomatic patients were diagnosed as having non-gonococcal chlamydial urethritis (NGCU); 13 had non-gonococcal non-chlamydial urethritis (NGNCU), and 21 had urethritis without any microbial detection. Five of the asymptomatic patients were diagnosed as having NGCU. Microbiological cure was achieved in 91% of the 32 patients with symptomatic NGU and in 80% of the 5 patients with asymptomatic NGCU. Clinical cure was obtained in 92% of the 53 patients with symptomatic NGU. The microbiological eradication rate for Chlamydia trachomatis was 92% in 24 patients. As for other organisms, the microbiological eradication rate for Mycoplasma genitalium was 60% in 5 patients and that for Ureaplasma urealyticum was 100% in 10. The microbiological and clinical efficacy of oral LVFX 500 mg once daily for 7 days for the patients with NGU was the same for the azithromycin (AZM) 1,000 mg single dose that we previously reported. The eradication rates of C. trachomatis and U. urealyticum in the treatment regimen with LVFX 500 mg were high enough in the clinical setting; however, for M. genitalium, the rate was relatively inferior to that with AZM.

[Open population comparative randomized clinical trial of lavomax efficacy and safety in combined treatment of non-gonococcal urethritis].

A total of 40 patients with non-gonococcal urethritis (NGU) were divided into two groups. Twenty patients of group 1 received standard antibacterial treatment while 20 patients of group 2 received the same treatment plus an immunotropic drug based on tiloron (lavomax) in a course dose 1.25 g. Patients of group 2 had no recurrences while in group 1 recurrences were seen in 25% patients. Addition of lavomax resulted in clinical and etiological cure and activation of local (secretory IgA) and systemic (interferons alpha and gamma in blood serum) factors in anti-infection defense in NGU patients.

Association of antibodies to Chlamydia trachomatis heat-shock protein 60 kD with chronic nongonococcal urethritis.

Ninety male patients with acute nongonococcal urethritis (NGU) who presented for follow-up 10-92 days after initiation of treatment were evaluated. A polymerase chain reaction assay and direct fluorescence antibody test were used to detect Chlamydia trachomatis at presentation and during follow-up. Chlamydial heat-shock protein 60 kD (hsp60) serology with an enzyme-linked immunosorbent assay and C. trachomatis serology with a microimmunofluoresence test were undertaken. In 62 (69%) of the men, evidence of chronic urethritis was noted during follow-up. C. trachomatis was detected in only two patients during follow-up. Chlamydial hsp60 antibody was associated with the development of chronic urethritis between 10 and 92 days after treatment began (P < .04), that is, at 10-29 days (P < .02) and at 30-92 days (P < .008). These results are consistent with the theory that immune response to hsp60 is important in the development of this chronic disease. The results also suggest that chronic NGU is not a consequence of continued production of hsp60 by C. trachomatis.

Male urethritis with and without discharge: a clinical and microbiological study.

BACKGROUND: The definition of male urethritis in the absence of urethral discharge has not been well established. The sensitivity of urethral swabs and first-catch urine is controversial. GOAL OF THIS STUDY: To correlate clinical data (discharge or not), urethral swabs, and first-catch urine examinations with the microorganisms found within the urethra in a cohort of men attending the sexually transmitted disease clinic of Hôpital Saint Louis (Paris) for treatment of urethral symptoms with or without discharge. STUDY DESIGN: Two-hundred-seventy-three consecutive male patients entered this prospective study between October 1, 1992 and November 30, 1992. Fifty-two patients were excluded because they had been treated with antibiotics in the previous 3 months. All patients were screened for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, and Candida albicans. RESULTS: Two-hundred-nineteen patients were eligible for the study (122 with discharge and 97 with no discharge). The prevalence of microorganisms was as follows: Chlamydia trachomatis in 13%, Neisseria gonorrhoeae in 11%, Ureaplasma urealyticum in 7%, Mycoplasma genitalium in 17%, Trichomonas vaginalis in 1%, and indeterminate pathogens alone in 20%. All major pathogens and Mycoplasma genitalium were more common in patients with discharge. Stratification of results according to the presence of polymorphonuclear leukocytes on the urethral swab and first-catch urine showed a low sensitivity of both tests for Chlamydia trachomatis (29%), Mycoplasma genitalium (50% and 62%), and Ureaplasma urealyticum (33%) in patients with no discharge. CONCLUSION: A specific and sensitive search for Chlamydia trachomatis should be done in every patient with urethral symptoms whether or not the classic symptoms of urethritis are present (discharge, presence of polymorphonuclear leukocytes in the urethra or first-catch urine).

Occurrence of antibodies against chlamydial lipopolysaccharide in human sera as measured by ELISA using an artificial glycoconjugate antigen.

An artificial glycoconjugate containing, as a ligand, the deacylated carbohydrate backbone of a recombinant Chlamydia-specific lipopolysaccharide was used as a solid-phase antigen in ELISA to measure antibodies against chlamydial LPS. The specificity and reproducibility of the assay was shown by using a panel of prototype monoclonal antibodies representing the spectrum of antibodies also occurring in patient sera. These mAbs recognized Chlamydia-specific epitopes [alpha 2-->8-linked disaccharide of 3-deoxy-D-manno-octulosonic acid (Kdo) or the trisaccharide alpha Kdo-(2-->8)-alpha Kdo-(2-->4)-alpha Kdo] or those shared between chlamydial and Re-type LPS (alpha Kdo, alpha 2-->4-linked Kdo disaccharide). The assay was used to measure IgG, IgA and IgM antibodies against chlamydial LPS in patients with genital or respiratory tract infections. In comparison to the results obtained with sera from blood donors, it became evident that both types of infection result in significant changes in the profile of LPS antibodies.

Clinical trial of norfloxacin in the treatment of uncomplicated gonococcal urethritis: preliminary report.

Fifteen male outpatients with uncomplicated gonococcal urethritis were treated by a single oral dose of norfloxacin (800 mg). Fourteen patients completely recovered from infection and a recurrence was noted in only one. Five of the Neisseria gonorrhoeae isolated (33.3%) were penicillin-resistant. However, the extremely low MICs confirm that norfloxacin possesses high antibacterial activity against N. gonorrhoeae. Norfloxacin was well tolerated with only a transient nausea occurring in four patients.

[The level of penicillin in the blood serum during treatment of gonococcal infection with various doses of bicillin-3 and its combination with etamid]. / Soderzhanie penitsillina v syvorotke krovi pri lechenii gonokokkovoi infektsii razlichnymi dozami bitsillina-3 i kombinatsiei ego s étamidom.

Bicillin-3 has been administered to patients with new gonorrheal urethritis in doses of 3,000,000 U, 2,400,000 U, and 2,400,000 U + ethamide. The latter combination has proved to be the most effective.

[Tantalum is contrast material for the better presentation of the ureter in retrograde pyelography (author's transl)]. / Tantalum als Röntgenkontrastmittel zur besseren Darstellung des Harnleiters bei der retrograden Pyelographie.

Suspension of Tantalum dust can be used as contrast material. It helps in producing X-ray films which are rich in contrast and details. The composition of the suspension and the technique of retrograde pyelography with the suspension is described.