**3. Chlamydia and it's rainbow spectrum of diseases**

Chlamydia was recognized as STI in the 1970s, became notifiable in the year 1988. New cases were reported routinely in the STI statistics 1990 onwards. After 1995 the noted cases then began to rise steeply [12]. More number of couples started seeking infertility treatment. It became a disease which was turning into a direct threat for the propagation of life on earth. How could the human attention not go towards this gram-negative bacterium then, that has made humans err a lot in its identification as a bacteria. Gradually, more research has unveiled a lot of diseases where intensity of the role of chlamydia is still under constant scrutiny.

**Table 1** is known hosts and their corresponding infective species of the Chlamydiaceae family.

The information in **Table 1** is an established limited knowledge. Multiple reports and research are continuing to highlight the involvement of Chlamydia.

Chlamydia has not spared the newborns. Many infants infected with *C. trachomatis* at birth have remained so for long period of time without appropriate antimicrobial therapy. This may misdirect us to sexual abuse. The cumulative infected proportion of infants at 1 year of age has been noted to be 35% [13]. The account of longest persistence of infection in one child, in the conjunctiva, nasopharynx, and oropharynx, has been around 866 days (28.5 months), until treatment cured it. Same serovars of *C. trachomatis* were reported in specimens from infants and their respective mothers and the serological tests in all infants pointed to the acquisition of infection during birth only [13].

Genital Chlamydia infection: In women it encompasses mucopurulent cervicitis, urethritis, and endometritis. Mucopurulent cervicitis can complicate into—salpingitis, pelvic inflammatory disease (PID), tubal pregnancy, chronic pelvic pain, Fitz Hugh Curtis Syndrome; premature rupture of membrane during pregnancy, chorioamnionitis, premature delivery, puerperal and neonatal infections (like conjunctivitis and interstitial pneumonia) and recurrent spontaneous abortions due to its immune reactions in human body. It's considered to be the leading cause of infertility. Around 20–30% of PID cases have been accredited to *C. trachomatis* in USA [14]. A study from India reported the prevalence of *C. trachomatis* infection around 23% in gynecology OPD (outpatient


#### **Table 1.**

*Host, Chlamydia infective species & their disease sites.*

department) [15] and around 19.9% of total STD patients [16]. In a systematic literature review from India, the rate of prevalence among infertile women was reported as 9–68% based on PCR results which took into account mostly the urban metro cities with only two studies from rural settings [17]. The reason that Chlamydia is an intense threat because, a large reservoir of unknown infected transmitting sources exist while leaving everlasting sequelae. Around 70–80% of females and up to 50% males carry asymptomatic infection [18]. Urethritis and epididymitis is on the male spectrum of genital chlamydia. An uncommon complication of untreated chlamydial infection is Reiter's syndrome, that is more common in females. Intra-articular *C. trachomatis* infection has been found in seronegative spondyloarthropathies using PCR [19].

In the past there has been a huge buzz around female infertility caused due to it, continuing till present. What about male infertility? *C. trachomatis* can lead to male infertility because it causes epididymitis and, consequently prostatitis and orchitis in them. According to Sonnenberg et al., Chlamydia infection can directly damage the sperms as well [20]. It can also cause testicular atrophy and obstructive azoospermia.

STIs are generally known to have good camaraderie with each other. Chlamydia is no exception here to our dismay. *C. trachomatis* infection increases risk of acquiring Human Immunodeficiency Virus infection, it's transmission by 3 to 4 fold and flourishes as co-infection with human papillomavirus (HPV) as well [21, 22]. But this is not a synergistic association. In study done by Martinelli et al., no association was observed between presence of *C. trachomatis* and abnormal Pap smear. In the study, *C. trachomatis* and HPV co-infections were seen in 4.9% and 9.3% of patients with and without cervical cytology abnormalities respectively [23]. This prevalence figure is in line with the rates previously

reported in the literature. The prevalence of chlamydia was more in the normal cytology ones. But one cannot deny that, the co-existence of the *C. trachomatis* and HPV 16 might increase the risk of cervical carcinoma [24]. The carcinomatous changes are more profound with co-infection as compared to monoinfection in various studies. It's intriguing that, the load of *C. trachomatis* DNA has been found to be significabtly higher in cases of co infection as compared to mono infection. This points out to how the relationship between Chlamydia infection and the host immune response makes the foundation to understanding the disease process.

Chlamydia has been implicated in the causation of diseases where its role is still under question and research. Extragenital manifestations of chlamydia have come up with changing societal behavior and acceptance, as compared to the limited data and prevalence in the past. Most extragenital infections in women remain asymptomatic, estimated at—100% of pharyngeal chlamydia, 36–100% of rectal chlamydia, 93% of pharyngeal gonorrhea and 53–100% of rectal gonorrhea [25]. Rectal gonorrhea or chlamydia without history of anal sex has been reported in a significant number of women. Extragenital infections are higher among MSM. The prevalence in MSM (Men who have Sex with Men) ranged from 2.1 to 23% for rectal chlamydia (median 8.9%), 0.2 to 24% for rectal gonorrhea (median 5.9%), 0 to 3.6% for pharyngeal chlamydia (median 1.7%) and 0.5 to 16.5% for pharyngeal gonorrhea (median 4.6%) [26]. The prevalence of extragenital infections among MSW (HIV positive Heterosexual Men) in the studies reviewed ranged from 0 to 11.8% for rectal chlamydia (median 7.7%), 0 to 5.7% for rectal gonorrhea (median 3.4%), 0 to 22.0% for pharyngeal chlamydia (median 1.6%) and 0.4 to 15.5% for pharyngeal gonorrhea (median 2.2%) [26]. *C. pneumoniae* has been shown to have synergistic association with development of Coronary Artery Disease, with higher rate of positivity for *C. pneumoniae* IgA than IgG in positive PCR of CAD patients [27]. *C. pneumoniae* antibody positivity has been found to be independently associated with ischemic stroke in elderly patients without altering stroke outcome [28]. *Chlamydia pneumoniae* also has role in childhood asthma. In a study, anti-*C. pneumoniae* IgM was positive in 25% of patients with uncontrolled and partly controlled bronchial asthma [29]. Also duration of hospital stay was found to be longer in patients of uncontrolled asthma who had anti-Cp IgM positive [29]. *C. pneumoniae* IgG antibody has been found to be independently associated with migraine in Indian patients [30]. *C. trachomatis* has been proposed to play a role in photosensitive dermatoses and melasma, with variable positivity for IgA, IgM and IgG antibodies to *C. trachomatis* [31, 32].

Chlamydia has risen like a huge eagle from past to the present and humans are yet counting the feathers. Mankind does not know the extent but indeed it will be and it has to gear up to face chlamydia.
