Chlamydia trachomatis is the most common sexually transmitted bacterium worldwide, with over three million new infections per year [9, 10]. The World Health Organization estimates that 92 million new cases of Ct occur worldwide every year [11]. In particular, Chlamydia trachomatis is the most frequently reported sexually transmitted infection in Europe, and the number of cases is steadily increasing, with more than 25,5000 cases in people below 25 years of age [12] (Fig. 11.4).

The rate of transmission between sexual partners may be as high as 75 % [13]. However, approximately 75 % of Chlamydia trachomatis infections in women and up to 50 % of those in men are asymptomatic [14, 15]. This aspect is extremely important due to the fact that although up to 13.3 % of young men may have a genital chlamydial infection, only half of these will present with any symptoms, and even fewer are likely to pursue treatment [16]. Moreover, the absence of symptoms increases the risk of infecting sexual partners and may also cause long-term complications in men, such as poor semen quality and infertility [17–19].

In men, Chlamydia trachomatis is responsible for urethritis, epididymitis, orchitis, and prostatitis [20–22]. In addition, Chlamydia trachomatis infection has been reported to be a major cause of reactive arthritis [23]. Furthermore, it has been shown that 21 % of patients with unexplained arthritis have a history of urogenital chlamydial infection [24, 25]. On the other hand, the consequences of Chlamydia trachomatis infection for male fertility are still under debate, with some reports arguing no effect on male fertility and others reporting decreased semen quality and impaired sperm fertilizing capacity and DNA integrity [26–28]. However, the most common clinical presentation is an asymptomatic infection [1]. In fact, although Chlamydia trachomatis induces local inflammation and triggers the host immune response, infection remains subclinical in most infected individuals [1, 29]. Several times patients present with mucopurulent discharge, dysuria, and pruritus 1–3 weeks after intercourse (Fig. 11.5).

The factors that determine whether infections develop as symptomatic or asymptomatic are unknown. However, a high prevalence of serotype E and its lack of associated clinical symptoms may suggest that this serotype might be more successful in maintaining a subclinical infection than other, less prevalent serotypes. Indeed, a successful serotype would be one that remains undetected for a longer period of time, enhancing dissemination. Variability of the main Ct antigen MOMP is presumably the result of host selection and bacterial adaptation [1]. Thus, the MOMP sequence that elicits a milder immune response in the infected host could be an adaptive mode of evolution to escape immune pressure and might therefore confer a transmission advantage over other MOMP serotypes [1].

As a consequence, little attention has been paid to Chlamydia trachomatis infection of the male genital tract, as it is underestimated and mainly considered to be a reservoir for transmission and reinfection [1, 30]. Although in men Chlamydia trachomatis mainly affects the urethra and epididymis, it has also been reported to infect other tissues such as the prostate and seminal vesicles [1, 31, 32]. Here, we will focus on prostatic infection.

In males, after the first infection of the single-cell columnar layer of the urethral epithelium, Chlamydia trachomatis infects nearby epithelial cells leading to an ascending infection and can cause retrograde epididymitis and epididymo-orchitis [1, 33, 34]. Moreover, the ascending infection from the urethra can reach the prostate epithelium and cause prostate and seminal vesicle infections [1, 32, 33] (Fig. 11.6).

Even if chronic prostatitis/chronic pelvic pain syndrome (CPPS) is the most common prostatitis syndrome, constituting 90–95 % of prostatitis cases, the CPPS etiology and pathogenesis are uncertain [35]. The etiology of CPPS remains unknown and few hypotheses are currently under consideration. One such hypothesis postulates a microbial etiology due to a cryptic undetected microbial pathogen, suggesting that these patients should be classified as having bacterial prostatitis [1, 35]. In this regard, several studies have focused on Chlamydia trachomatis as an etiological agent of CPPS [3, 36–38].

For diagnostic purposes, microbiological analysis, as well as evaluation of the presence of leukocytes, is performed in expressed prostatic secretion, semen, and/or urine pre- and post-prostatic massage samples [1]. After negative conventional microbiological cultures, physicians perform microbiological, cell culture, or molecular tests for diagnosis of specific pathogens [1]. Assays to detect antibodies specific for microorganisms in seminal plasma and serum may be valid for seroepidemiological studies, but not for diagnostic purposes [39]. The cross-reactivity of antibodies between Chlamydia trachomatis and some Chlamydophila species and the persistence of antibody titers over time impair the possibility of performing an accurate diagnosis and make it difficult to distinguish between past and current infections [40].

The prevalence of Chlamydia trachomatis infection in CP/CPPS patients has been reported to range from 8.3 to 27 % [1]. Some authors have raised concerns about the reliability of the samples used in these studies [37]. They postulated that bacterial isolation from prostate diagnostic material presents a potential risk of contamination while going through the urethra, thus limiting the interpretation of the test [37]. However, a number of studies indicate that semen/expressed prostatic secretion specimens are often positive for Chlamydia trachomatis in patients with negative urethral swabs [41, 42]. Also, pure prostatic biopsies from CP/CPPS have demonstrated the presence of Chlamydia trachomatis in the absence of urethral infection [32]. These findings undoubtedly support the role of Chlamydia trachomatis as a causative or triggering agent of CP/CPPS.

Chlamydia trachomatis infection of the prostate gland may cause inflammation within the prostatic tissue, thus impairing the normal functionality of the gland, and as is well known, prostate secretions account for up to 60 % of the volume of seminal plasma [43].

The clinical management of Chlamydia trachomatis infection should include:

The indications for treatment are:

On the basis of clinical presentation or on the results of the laboratory examinations, we consider three clinical settings:

First-line regimens include azithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice a day for 7 days. Several alternative regimens have been proposed: erythromycin base 500 mg orally four times a day for 7 days, ofloxacin 200 mg orally twice a day for 7 days, roxithromycin 150 mg orally twice a day for 7 days, clarithromycin 250 mg orally twice a day for 7 days, levofloxacin 500 mg once daily for 7 days, or ofloxacin 300 mg twice a day for 7 days [49]. In cases of rectal non-lymphogranuloma venereum chlamydial infections, the first choice should be a course of doxycycline, 100 mg twice daily for 7 days [49, 50].

There are few published trials about the therapy of prostatitis due to Chlamydia trachomatis infection. Recently, Cai et al. evaluated the efficacy of a 14-day course of prulifloxacin 600 mg with standard antibiotic therapy (doxycycline 100 mg twice daily for 21 days) for the treatment of chronic prostatitis due to Chlamydia trachomatis infection [51]. By using a non-inferiority RCT, they concluded that prulifloxacin is equivalent to standard therapy regarding clinical success, as demonstrated by a decrease in the number of patients affected by CP due to Chlamydia trachomatis infection [51]. Recently, Miyashita et al. demonstrated the efficacy of a new-generation fluoroquinolone, sitafloxacin, against Chlamydia trachomatis infection [52]. Its antimicrobial activity is unique compared to conventional fluoroquinolones, although few clinical studies have been reported [53, 54].

It is well known that chronic prostatitis due to Chlamydia trachomatis infection not only decreases the quality of life [55] but also has a significant impact on a couple’s reproductive health [28]. Indeed, Chlamydia trachomatis has a significant role in male infertility, and eradication of the infection is critical for the recovery of the man’s fertility [56]. However, eradication of the infection after antibiotic therapy does not always result in recovery of semen quality, and other treatment compounds may be needed. Recently, Cai et al., using a prospective, randomized, and controlled study, demonstrated that L-arginine, L-carnitine, acetyl-L-carnitine, and ginseng extracts, together with prulifloxacin, improved semen parameters in patients with Chlamydia trachomatis genital infection and oligoasthenoteratozoospermia compared to treatment with prulifloxacin therapy alone [57]. The improved quality of spermatozoa from an infertile status to a normal fertility index was demonstrated by two sets of findings. The anti-inflammatory and antioxidative effects of ginseng improved the shape and concentration of spermatozoa, and L-arginine, L-carnitine, and acetyl-L-carnitine enhanced sperm motility and function by stimulating the activity of endothelial nitric oxide synthase [57–59]. Two important aspects in the treatment of male infertility in patients affected by chronic prostatitis and oligoasthenoteratozoospermia due to Chlamydia trachomatis infection should be discussed. Firstly, specific treatment of infertility should be started concurrently with the antibiotic treatment. Then, the association of antibiotic therapy with L-arginine, L-carnitine, acetyl-L-carnitine, and ginseng extracts together can produce good results in terms of recovery of semen quality [57].