**3.** *Chlamydia trachomatis*

In 1907*, Chlamydia* was first observed in the epithelium of a conjunctival scraping from an infected orangutan. This discovery is attributed to Halberstaedter and von Prowazek [25]. However, for years, trachoma was known as a blinding ocular disease in humans [26]. Although, Macchiavello reported the culture of trachoma agent in 1944, Tang and coworkers have the credit for their culture. The use of McCoy cells by Gordon and Quan was a major step to understanding chlamydial infections [27, 28]. Nowadays, it is well known that *Chlamydia trachomatis* is an intracellular pathogen and a gram-negative bacterium. In order to infect new cells, it must complete a bi-phasic developmental cycle. It contains approximately 1MB of DNA and 1000 open-reading frames (ORFs), which is considered a small genome [28]. The main features of *Chlamydia trachomatis* are listed in Table 1.

*Chlamydia trachomatis* can cause several clinical complications, especially in women. This bacteria not only affects the health of individuals in certain countries, it is a worldwide problem with high prevalence. For instance, it has been reported as the most common infection in the United States since 1994. The costs and the consequences of the *Chlamydia trachomatis* infection, make it a major health problem [27, 28, 29, 30]. In most cases it is asymptomatic leading to an untreated infection. It is reported that in approximately 50% of men and in 75% of women the primary infection does not show any symptoms [31]. However, it is estimated that the ratio of infected people with *Chlamydia* who develop symptoms vary depending on the study and the methodology. One major consequence in women is the pelvic inflammatory disease (PID), which is a cause of infertility. Also, there is the risk of passing the infection to the fetus in pregnant women [32, 33]. Main complications in women, which are the most affected, include: urethritis, endometritis and mucopurulent cervicitis. In men it can cause urethritis [29].

According to the World Health Organization (WHO), 101 million chlamydial infections are detected annually worldwide [34]. In adolescents and young adults between 12 and 24 years old the prevalence of *Chlamydia* is higher. For example, it was reported that in the United States the cases of *Chlamydia Trachomatis* were frequent in the young population (< 25 years old) [11]. Since young adults are in an age of sexual activity, it is a population with high-risk, therefore a higher susceptibility. In general, there are few data on the prevalence of *Chlamydia* in certain parts of the world. Most of the studies usually focus on some populations with small samples. For example, in a study carried out in Argentina (2015), 204 participants with an average age of 19 were screened for *Chlamydia trachomatis*. It was found that the prevalence was of 3.5% [31]. In Germany (2012) they studied a population of 1003 sexually active volunteers, they found a prevalence of 4.3% in women and 4.6 % in men [35].

Among the most studied area of HPV is the association with penile, larynx, head and neck

In the review of Silva *et al.*, 2013 data show a prevalence in men, for different anatomical regions, in this order: penis, glans/corona, scrotum, perianal area, urethra and semen (Figure 1). This author also mentions that prevalence depends on the area, the technique used in

In 1907*, Chlamydia* was first observed in the epithelium of a conjunctival scraping from an infected orangutan. This discovery is attributed to Halberstaedter and von Prowazek [25]. However, for years, trachoma was known as a blinding ocular disease in humans [26]. Although, Macchiavello reported the culture of trachoma agent in 1944, Tang and coworkers have the credit for their culture. The use of McCoy cells by Gordon and Quan was a major step to understanding chlamydial infections [27, 28]. Nowadays, it is well known that *Chlamydia trachomatis* is an intracellular pathogen and a gram-negative bacterium. In order to infect new cells, it must complete a bi-phasic developmental cycle. It contains approximately 1MB of DNA and 1000 open-reading frames (ORFs), which is considered a small genome [28]. The main

*Chlamydia trachomatis* can cause several clinical complications, especially in women. This bacteria not only affects the health of individuals in certain countries, it is a worldwide problem with high prevalence. For instance, it has been reported as the most common infection in the United States since 1994. The costs and the consequences of the *Chlamydia trachomatis* infection, make it a major health problem [27, 28, 29, 30]. In most cases it is asymptomatic leading to an untreated infection. It is reported that in approximately 50% of men and in 75% of women the primary infection does not show any symptoms [31]. However, it is estimated that the ratio of infected people with *Chlamydia* who develop symptoms vary depending on the study and the methodology. One major consequence in women is the pelvic inflammatory disease (PID), which is a cause of infertility. Also, there is the risk of passing the infection to the fetus in pregnant women [32, 33]. Main complications in women, which are the most affected, include: urethritis, endometritis and mucopurulent cervicitis. In men it can cause urethritis [29].

According to the World Health Organization (WHO), 101 million chlamydial infections are detected annually worldwide [34]. In adolescents and young adults between 12 and 24 years old the prevalence of *Chlamydia* is higher. For example, it was reported that in the United States the cases of *Chlamydia Trachomatis* were frequent in the young population (< 25 years old) [11]. Since young adults are in an age of sexual activity, it is a population with high-risk, therefore a higher susceptibility. In general, there are few data on the prevalence of *Chlamydia* in certain parts of the world. Most of the studies usually focus on some populations with small samples. For example, in a study carried out in Argentina (2015), 204 participants with an average age of 19 were screened for *Chlamydia trachomatis*. It was found that the prevalence was of 3.5% [31].

cancers. It is estimated that HPV is the causative agent of 5% of human cancers [24].

detection and the geographical location of the patient [23].

features of *Chlamydia trachomatis* are listed in Table 1.

**3.** *Chlamydia trachomatis*

72 Genital Infections and Infertility

As a mention before, *Chlamydia* can be a 'silent' infection. However, symptoms can appear after several weeks of the first exposure with the bacterium. Symptomatic infected men typically present a mucoid or watery urethral discharge and dysuria. An uncommon clinical signal is the development of epididymitis with unilateral testicular pain, tenderness and swelling. In women, some clinical signs include mucopurulent endocervical discharge, pyuria, dysuria and urinary frequency. If the infection spreads to the upper reproductive tract, the typical symptom is abdominal and/or pelvic pain, along with signs of cervical motion tender‐ ness and uterine or adnexal tenderness on examination. It is worth mentioning that *Chlamy‐ dia* can also be found in the throats of women and men. Also, chlamydial conjunctivitis can be found in both men and women due to contact with infected genital secretions [28].

The effects of *Chlamydia trachomatis* infection in men have focused on semen parameters. However, the results of these studies have shown opposite outcomes. Some claim that there is not an association between the infection and the poorest semen quality. On the other hand, in some literature it has been reported that *Chlamydia trachomatis* affects semen quality. These contradictory results could be due to the different methodologies and techniques used, which can be difficult to compare [36, 37].

There are several methods available to detect *Chlamydia Trachomatis*. Cell culture is one of the traditional screening techniques to identify this pathogen. Briefly, this method consists of inoculate specimens (i.e., urethral swabs) in a monolayer cell culture. A stain is used to observe chlamydial inclusions. The specificity is 100%, however it can take up to 72 hours to observed sufficient viable microorganisms [38]. Recently, the molecular methods of detection have proved to be a useful tool in diagnosis. One of the first molecular methods was the *in situ* hybridiza‐ tion. However, this technique was not sensitive enough. Polymerase chain reaction (PCR) and ligase chain reaction (LCR) are useful to detect *Chlamydia trachomatis* infections in asymptomat‐ ic patients and populations with low prevalence [39]. Other methods include the identifica‐ tion of antibodies in serological samples. However, serological tests have several limitations, one example of these is that there is no specific *Chlamydia trachomatis* antibody test [40].

The most recent development is the real-time or quantitative PCR that detects *Chlamydia trachomatis* DNA copy numbers. The advantage of this method includes high sensitivity and specificity, also it is a less time-consuming method. It is very clear that there have been improvements in *Chlamydia* detection. However, there are still several challenges such as the creation of lower cost tests without sacrificing any accuracy or speed obtaining results [39].
