Chlamydia trachomatis infection : a challenge for the urologist

The role of Chlamydia trachomatis (Ct) in everyday clinical practice is now on the increase because Ct infections are the most prevalent sexually transmitted bacterial infections worldwide. Ct can cause urethritis, cervicitis, pharyngitis, or epididymitis, although asymptomatic infections are quite common. Ct infection remains asymptomatic in approximately 50% of infected men and 70% of infected women, with risk for reproductive tract sequelae both in women and men. A proper early diagnosis and treatment is essential in order to prevent persistent consequences. An accurate comprehension of the pathology, diagnosis and treatment of this entity is essential for the urologist. We review the literature about the new findings in diagnosis and treatment of Ct infection in sexually active young men.


Introduction
Sexually transmitted diseases (STDs) are among the first ten causes of unpleasant diseases in young adult males in developing countries and the second major cause of unpleasant diseases in young adult women, with an enormous health and economic consequences. 1mong these, Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterium worldwide 2 with over three million new infections per year. 37] Absence of symptoms increases the risk of infecting sexual partners and may cause long-term complications in men too, such as poor quality of semen and infertili-ty. 5,7Several factors contribute to make difficult detecting Ct by a conventional analysis. 8To date, the DNA recombination techniques are universally accepted as the gold standard to evaluate the presence of Ct in biologic samples. 9owever, immunologic markers of Ct infection such as immunoglobulin A (IgA) antibody and cytokines have been detected in total ejaculate and seminal plasma samples to demonstrate their role in monitoring men with CP. [10][11] Moreover, the proper treatment of urological Ct infection is not totally indicated.For these reasons, Ct represents a challenge for the urologist both for diagnostic and treatment.We summarize the most current developments in the diagnostics and therapeutic approaches in Ct infections in sexually active young men. 12

Methods of searching
We conducted a search of the English-language literature from 1960 through December 2010 with use of the Medline computerized database of the US National Library of Medicine (http://www.ncbi.nlm.nih.gov/pubmed).The Medline search has been divided into two sections: diagnosis and therapy.The first review section about diagnosis has been carried-out by using the following Medical Subject Headings and free text terms: Chlamydia trachomatis, and chlamydia infections (exploded) were combined with the terms diagnosis, urine, urethral swa, total ejaculate, serum, antibodies, prostate massage and then limited to humans, male and young adult: 19-24 years.The second review section about therapy has been carried-out by using the following Medical Subject Headings and free text terms: Chlamydia trachomatis, and chlamydia infections (exploded) were combined with the terms treatment, therapy, antibiotic, drug, quinolones, tetracycline and then limited to humans, male and young adult: 19-24 years.Moreover, we searched reference lists of articles to identify potential additional references.All original paper and review studies of Ct diagnosis and treatment in young adult have been considered for this review.We considered also guidelines from the National Institute for Health and Clinical Excellence and the European Centre for Disease Prevention and Control, the US Centers for Disease Control and Prevention, and World Health Organization.

Chlamydia trachomatis diagnosis
From an initial literature search with 188 unique citations, a total of 27 articles were selected for the present review.A matched research between Chlamydia trachomatis, and chlamydia infections (exploded) and the fol-lowing terms total ejaculated and prostate massage has not found any items.
Diagnosis of Ct infection can be made by using: -Direct detection -Indirect detection

Direct detection
Ct is an obligate intracellular bacterium and cell culture remains a reference method (about 100% specificity). 13However, all Authors are agree that it is not recommended for routine use, due to its lack of sensitivity, its technical complexity and the long turn-around time. 14ther Authors suggest that Ct can be found by using antigen-based detection methods. 13In particular, direct fluorescent staining with monoclonal antibodies (DFA) and enzyme immunoassay (EIA).EIA tests are more reproducible than DFA, and the sensitivity of the best EIA is comparable to that of culture but lower than that of nucleic acid amplification tests (NAATs), due to the cross-reactions with the lipopolysaccharide (LPS) of other microorganisms. 13Recently, Mahilum-Tapay and co-workers, evaluated the performance of the Chlamydia Rapid Test, a new assay developed at the Diagnostics Development Unit, University of Cambridge. 15They compared sensitivity, specificity, positive predictive value, and negative predictive value of the Chlamydia Rapid Test with the gold standard test for Ct infections (NAATs). 15In this study, they found a good diagnostic performance: sensitivity 83.5%, specificity 98.9%, positive predictive value 86.7%, and negative predictive value 98.6%. 15However, NAATs are the tests of choice for the diagnosis of Ct genital infections. 13In everyday clinical practice, several commercial NAATs are available, and make use of Abbott, IL, USA); strand displacement amplification (Becton Dickinson, NJ, USA); transcription-mediated amplification (Gen Probe); and nucleic acid sequence-based amplification (bioMerieux, Nancy L'Etoile, France). 13,16These assays are automated and can be used for screening programmes and for the detection of Ct and Neisseria gonorrhoeae in the same specimen. 13We currently used Roche COBAS AMPLICOR CT/NG reagents kits and instruments (Roche Molecular Systems,Branchburg, NJ, USA) with good level of accuracy. 8NAATs tests generally show two important drawbacks: the cost and the presence of inhibitors in specimens.However, they show a high specificity. 13inally, in 2006, a new C. trachomatis variant belonging to serovar E, with a 377-bp deletion in the cryptic plasmid, was described in Sweden. 17his new variant can obviously not be detected by amplification tests targeting the deleted area, but can be detected by amplification targeting a chromosomal gene, e.g.ompA or a rRNA gene. 17However, new versions of the COBAS Taqman v2.0 test and of the Abbott test allow simultaneous detection of the cryptic plasmid and of ompA, and simultaneous detection of two different regions of the cryptic plasmid, respectively. 17

Indirect detection
A recent review by Persson suggested that serology is useful only in some cases of Ct infection and in seroepidemiological studies. 18n the other hand, recent evidences showed that anti-Ct immunoglobulin A (IgA) in association with interleukin 8 (IL-8) evaluation appear to be the best immunologic markers of chronic chlamydial prostatitis status. 8Mazzoli and co-workers, highlighted, in 78 consecutive patients with a diagnosis of chronic prostatitis due to Ct infection by IPAzyme Chlamydia IgG/IgA by Savyon Diagnostics (Ashdod, Israel), an immune-peroxidase test, the role of immune system activation in the pathophysiology of chronic prostatitis due to Ct infection and that seminal IL-8 and mucosal IgA levels specific to Ct antigens appear to be the best immunologic markers of chronic chlamydial prostatitis status. 8They, however, did not showed any role of serum anti-Ct immunoglobulin in Ct infection diagnosis. 8

Chlamydia trachomatis therapy
From an initial literature search with 164 unique citations, a total of 18 articles were selected for the present review.A matched research between Chlamydia trachomatis and chlamydia infections (exploded) and the following terms quinolones has not found any items.
A recent review by suggested that antimicrobial groups effective against Ct include the macrolides, tetracyclines, quinolones and penicillins. 19The European Urological Association and the Centers for Disease Control and Prevention guidelines suggested that doxycycline and azithromycin are considered to be equally effective in the treatment of chlamydial infections. 2,12However, in management and treatment of patients affected by Ct infections the following factors should be taken into account: i) Chlamydia are only metabolically active in the host cell and therefore only targeted intracellularly by antibiotics; ii) Intracellularly accumulated antibiotics are tetracyclines, macrolides and quinolones. 2,12ven if doxycycline and azithromycin are the most widely prescribed drugs in Ct infections treatment and recommended as the primary approach, other fluoroquinolones such as ofloxacin or levofloxacin are suggested as alternative drugs. 2 Moreover, although little is known about Ct survival in the presence of fluoroquinolones, it is well known that after multiple cultivation passages resistant mutant for some fluoroquinolones were determined. 20In a recent report, Smelov and co-workers suggested that ofloxacin could be recommended as the primary drug in the treatment of chlamydia-infected patients with CP, due to its pharmacokinetic parameters. 20Moreover, the same Authors stated that the decision on the prescription of pefloxacin or lomefloxacin should be made individually, but ciprofloxacin treatment is not suggested. 20he authors, however, concluded that the conditions of in vitro susceptibility studies are incompatible with the infection as it occurs in vivo even if could be useful to include investigations for antibiotic susceptibility in every patient prior to treatment. 20In a recent study Cai et al., by means of a prospective, randomized and open-label study on 221 patients affected by chronic prostatitis due to Ct infection who had undergone oral administered prulifloxacin 600 mg once daily for 14 days or doxycycline 100 mg orally twice daily for 21 days, found that prulifloxacin was equivalent to the standard therapy. 21In this study, moreover, the Authors showed that prulifloxacin was superior over standard therapy in microbiological efficacy rates in terms of mucosal IgA and IL-8 levels decreasing. 21This effect should be probably, due to an anti-inflammatory effect of quinolones.
2][23] Several reports, in fact, suggested that IL-8 evaluation should be used, not only as a Ct infection marker, but also as a marker of therapy efficacy. 8,21The role of molecular markers in the management of Ct infections is, thus, clinically useful and suggested.Mazzoli et al., recently, demonstrated that patients who had reported the higher mean value for IL-8 and massive presence of mucosal IgA, making evident a strong inflammation and a correlation with the higher level of pain and a worse quality of life, with a significant correlation between IL-8 and IgA values and NIH-CPSI subscale scores. 8Moreover, in the clinical practice, Cai et al. found a good relationship between IL-8 and NIH-CPSI, demonstrating that an improvement in QoL (NIH-CPSI decreasing) is related to a decrease in IL-8 levels after theapy. 21In addition, an important role should be given to mucosal IgA anti-Ct evaluation.Some authors have demonstrated, in animal model, that a high production of IgA in genital tract secretions seems related to the presence, persistence, and accumulation of Th2 MoPn cells in the genital tract during chronic infections, with the consequent inability to clear the infection. 23In particular, the presence of an active chronic infection in patients affected by Ct infection is also well correlated to the presence of high levels of anti-Heat Shock Protein 60 (anti-HSP60) mucosal IgA antibodies, as proved by the high percentage of IgA positive patients showing in western blot analysis an immunoreactions towards high molecular weight proteins, especially MOMP2 and HS60. 8This anti-HSP60 immunization suggests chronic or repeated stimulation from an endemic source of the microrganism, 24 proved by the presence of CT DNA found in young sexually active patients affected by chronic prostatitis due to Ct infection.Finally, any correlation between serum IgA or IgG and the other Ct maker of infections, or any significant change before or after therapy, have been reported. 21In fact, the role of serum IgA or IgG anti-Ct in early diagnosis of infection and early treatment has been reported for women's infection, but not, up to the moment, for males. 25Clinical trials carried out with the aim to test the microbiological or clinical efficacy of antibiotics different to quinolones, are very few.In a recent experience, Takahashi and coworkers, showed a good clinical cure rate (77%) by using a single-dose of azithromycin (1000 mg) for 13 patients with urethritis due to Ct infection. 26The Authors concluded that a single-dose azithromycin regimen was well tolerated and eradicated potential pathogens of NGU26.This study, however, has been carried out in a small cohort of patients and in inhomogeneous group of patients.8][29] The Table 1 summarized all randomized, controlled studies in management of Ct infection in young male patients.

Conclusions
In conclusion, additional studies of the effectiveness of the common diagnostic tests for Ct infection would be valuable.In addition, better natural history data on the timing of male genital Ct infection and development of more accurate, noninvasive tools to assess chlamydial sequelae are essential to plan a correct treatment schedule.Finally, clinical trials should be planned in order to evaluate the real frequency of Ct resistance to standard therapy.
different technologies: PCR and real-time PCR (Roche Diagnostics, N o n -c o m m e r c i a l u s e o n l y