Detection of three of these criteria has been correlated with results by Gram stain. Other tests, including a DNA probe-based test for high concentrations of *G. vaginalis* (Affirm VP III, Becton Dickinson, Sparks, Maryland), a proline-aminopeptidase test card (Pip Activity TestCard, Quidel, San Diego, California), and the OSOM BVBlue test have acceptable performance characteristics compared with Gram stain. Although a card test is available for the detection of elevated pH and trimethylamine, it has low sensitivity and specificity and therefore is not recommended. PCR has been used in research settings for the detection of a variety of organisms associated with BV, but evaluation of its clinical utility is uncertain. Detection of one organism or group of organisms might be predictive of BV by Gram stain. However, additional evaluations are needed to confirm these associations. Culture of *G. vaginalis* is not recommended as a diagnostic tool because it is not specific. Cervical Pap tests

Treatment is recommended for women with symptoms. The established benefits of therapy in nonpregnant women are to relieve vaginal symptoms and signs of infection. Other potential benefits to treatment include reduction in the risk for acquiring *C. trachomatis* or *N.*

**Recommended drugs:** Metronidazole 500 mg orally twice a day for 7 days, Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, once a day for 5 days; Clindamycin cream

homogeneous, thin, white discharge that smoothly coats the vaginal walls;

have no clinical utility for the diagnosis of BV because of their low sensitivity.

2%, one full applicator (5 g) intravaginally at bedtime for 7 days.

the recurrence of BV.

three of the following symptoms or signs:

pH of vaginal fluid >4.5;

presence of clue cells on microscopic examination;

**6.2 Diagnosis**

test).

**6.3 Treatment**

*gonorrhoeae*, HIV, and other viral STDs.

Trichomoniasis is caused by the protozoan *T. vaginalis*.(Nanda et al., 2006) Few men who are infected with *T. Vaginalis* might not have symptoms; others have NGU. Few women have symptoms characterized by a diffuse, malodorous, yellow-green vaginal discharge with vulvar irritation. However, many women have minimal or no symptoms. Because of the high prevalence of trichomoniasis in clinical and nonclinical settings, testing for *T. vaginalis* should be performed in women seeking care for vaginal discharge. Screening for *T. vaginalis* in women can be considered in those at high risk for infection (i.e., women who have new or multiple partners, have a history of STDs, indulge in sexual activity for payment, and use injection drugs).

#### **7.1 Treatment**

Metronidazole 2 g orally in a single dose or Tinidazole 2 g orally in a single dose or Metronidazole 500 mg orally twice a day for 7 days*.*

## **8. Vulvovaginal Candidiasis (VVC)**

VVC is usually caused by *C.albicans*, but occasionally is caused by other *Candida* sp. or yeasts. Typical symptoms of VVC include pruritus, vaginal soreness, dyspareunia, external dysuria, and abnormal vaginal discharge. However, none of these symptoms is specific for VVC. An estimated 75% of women will have at least one episode of VVC, and 40%–45% will have two or more episodes within their lifetime. On the basis of clinical presentation, microbiology, host factors, and response to therapy, VVC can be classified as either uncomplicated or complicated. Approximately 10%–20% of women will have complicated VVC that necessitates diagnostic and therapeutic considerations.

#### **8.1 Uncomplicated VVC**

*Diagnostic Considerations:* A diagnosis of *Candida* vaginitis is suggested clinically by the presence of external dysuria and vulvar pruritus, pain, swelling, and redness. Signs include vulvar edema, fissures, excoriations, or thick, curdy vaginal discharge. The diagnosis can be made in a woman who has signs and symptoms of vaginitis when either 1) a wet preparation (saline, 10% KOH) or Gram stain of vaginal discharge demonstrates yeasts, hyphae, or pseudohyphae or 2) a culture or other test yields a yeast species. *Candida* vaginitis is associated with a normal vaginal pH (<4.5), and therefore, pH testing is not a useful diagnostic tool. Use of 10% KOH in wet preparations improves the visualization of yeast and mycelia by disrupting cellular material that might obscure the yeast or pseudohyphae. Examination of a wet mount with KOH preparation should be performed for all women with symptoms or signs of VVC, and women with a positive result should receive treatment. For women with negative wet mounts who are symptomatic, vaginal cultures for *Candida* should be considered. If the wet mount is negative and *Candida* cultures cannot be done, empiric treatment can be considered for symptomatic women with any sign of VVC on examination. Identifying *Candida* by culture in the absence of symptoms or signs is not an indication for treatment, because approximately 10%–20% of

Sexually Transmitted Infections: An Overview 25

Soreness Dyspareunia

Scant/moderate White Clumped, adherent

**pH** 4.0-4.5 4.0-4.5 5.0-6.0 >4.5

**(Fish odour)** None None Usually positive Positive

PMN:EC ratio <1 Pseudohyphae (~40%)

Pseudohyphae (~70%)

PID comprises a spectrum of inflammatory disorders of the upper female genital tract, including any combination of endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis. Sexually transmitted organisms, especially *N. gonorrhoeae* and *C. trachomatis*, are implicated in many cases; however, microorganisms that comprise the vaginal flora e.g., anaerobes, *G. vaginalis, Haemophilus influenzae*, enteric Gram-negative rods, and *Streptococcus agalactiae,* also have been associated with PID. In addition, *M. hominis*, *U. urealyticum*, and *M. genitalium* might be associated with some cases of PID. All women who have acute PID should be tested for *N. gonorrhoeae* and *C. trachomatis* and should be screened for HIV infection. Symptoms of PID include abnormal cervical or vaginal discharge, abdominal pain and fever. On examination there may be cervical motion and adnexal and lower abdominal tenderness. It is important to diagnose and treat PID as early as possible. For patients requiring hospitalization, intravenous cefoxitin or cefotetan plus doxycyline (i/v or oral) can be given. Alternatively clindamycin plus gentamicin can be given followed by oral doxycycline. Outpatient treatments include oral ofloxacin plus metronidazole or ceftriaxone (or cefixitin and oral probenecid) plus oral doxycycline. Duration of intravenous treatment is dependent on the severity of the clinical presentation

**candidiasis Trichomoniasis Bacterial**

Soreness Dyspareunia Often asymptomatic

Profuse Green-yellow Homogenous, frothy

PMN:EC ratio >1 Motile trichomonads PMNs predominate

Negative

**Vaginosis**

Often asymptomatic Occasional abdominal pain

Moderate White/gray Homogenous adherent

PMN:EC ratio <1 Clue cells Coccobacilli

Negative

**Normal Vulvovaginal**

**Symptoms** None Pruritis

Variable Clear/white Nonhomogenous floccular

PMN:EC ratio <1 Lactobacilli predominate

Negative

**9. Pelvic Inflammatory Disease (PID)**

Table 3. Summary of clinical features of vaginitis (Wilson and Sande).

**Discharge Amount Color Consistency**

**Vaginal fluid**

**Amine test**

**Microscopy Saline**

**10% KOH**

(Romanowski, 1993).

women harbor *Candida* sp. and other yeasts in the vagina. VVC can occur concomitantly with STDs. Most healthy women with uncomplicated VVC have no identifiable precipitating factors.

## **8.2 Treatment**

Short-course topical formulations e.g. Butoconazole 2% cream, Clotrimazole 2% cream, Miconazole 2% cream (i.e., single dose and regimens of 1–3 days) effectively treat uncomplicated VVC. The topically applied azole drugs are more effective than nystatin. Treatment with azoles results in relief of symptoms and negative cultures in 80%–90% of patients who complete therapy.

## **8.3 Complicated VVC**

#### *Recurrent Vulvovaginal Candidiasis (RVVC)*

RVVC, usually defined as four or more episodes of symptomatic VVC in 1 year, affects a small percentage of women (<5%).(STD guidelines 2010) The pathogenesis of RVVC is poorly understood, and most women with RVVC have no apparent predisposing or underlying conditions. Vaginal cultures should be obtained from patients with RVVC to confirm the clinical diagnosis and to identify unusual species (including nonalbicans species), particularly *Candida glabrata*. Although *C. glabrata* and other nonalbicans *Candidia* species are observed in 10%–20% of patients with RVVC conventional antimycotic therapies are not as effective against these species as they are against *C. albicans*.

## **8.4 Treatment**

Each individual episode of RVVC caused by *C. albicans* responds well to short-duration oral or topical azole therapy. However, to maintain clinical and mycologic control, some specialists recommend a longer duration of initial therapy (e.g., 7–14 days of topical therapy or a 100-mg, 150-mg, or 200-mg oral dose of fluconazole every third day for a total of 3 doses [day 1, 4, and 7]) to attempt mycologic remission before initiating a maintenance antifungal regimen.

**Maintenance Regimens:** Oral fluconazole (i.e., 100-mg, 150-mg, or 200-mg dose) weekly for 6 months is the first line of treatment. If this regimen is not feasible, topical treatments used intermittently as a maintenance regimen can be considered. Suppressive maintenance antifungal therapies are effective in reducing RVVC. However, 30%–50% of women will have recurrent disease after maintenance therapy is discontinued. Routine treatment of sex partners is controversial. *C. albicans* azole resistance is rare in vaginal isolates, and susceptibility testing is usually not warranted for individual treatment guidance.

#### *Non albicans VVC*

The optimal treatment of nonalbicans VVC remains unknown. Options include longer duration of therapy (7–14 days) with a nonfluconazole azole drug (oral or topical) as firstline therapy. If recurrence occurs, 600 mg of boric acid in a gelatin capsule is recommended, administered vaginally once daily for 2 weeks. This regimen has clinical and mycologic eradication rates of approximately 70%. If symptoms recur, referral to a specialist is advised.

women harbor *Candida* sp. and other yeasts in the vagina. VVC can occur concomitantly with STDs. Most healthy women with uncomplicated VVC have no identifiable

Short-course topical formulations e.g. Butoconazole 2% cream, Clotrimazole 2% cream, Miconazole 2% cream (i.e., single dose and regimens of 1–3 days) effectively treat uncomplicated VVC. The topically applied azole drugs are more effective than nystatin. Treatment with azoles results in relief of symptoms and negative cultures in 80%–90% of

RVVC, usually defined as four or more episodes of symptomatic VVC in 1 year, affects a small percentage of women (<5%).(STD guidelines 2010) The pathogenesis of RVVC is poorly understood, and most women with RVVC have no apparent predisposing or underlying conditions. Vaginal cultures should be obtained from patients with RVVC to confirm the clinical diagnosis and to identify unusual species (including nonalbicans species), particularly *Candida glabrata*. Although *C. glabrata* and other nonalbicans *Candidia* species are observed in 10%–20% of patients with RVVC conventional antimycotic therapies

Each individual episode of RVVC caused by *C. albicans* responds well to short-duration oral or topical azole therapy. However, to maintain clinical and mycologic control, some specialists recommend a longer duration of initial therapy (e.g., 7–14 days of topical therapy or a 100-mg, 150-mg, or 200-mg oral dose of fluconazole every third day for a total of 3 doses [day 1, 4, and 7]) to attempt mycologic remission before initiating a maintenance

**Maintenance Regimens:** Oral fluconazole (i.e., 100-mg, 150-mg, or 200-mg dose) weekly for 6 months is the first line of treatment. If this regimen is not feasible, topical treatments used intermittently as a maintenance regimen can be considered. Suppressive maintenance antifungal therapies are effective in reducing RVVC. However, 30%–50% of women will have recurrent disease after maintenance therapy is discontinued. Routine treatment of sex partners is controversial. *C. albicans* azole resistance is rare in vaginal isolates, and

The optimal treatment of nonalbicans VVC remains unknown. Options include longer duration of therapy (7–14 days) with a nonfluconazole azole drug (oral or topical) as firstline therapy. If recurrence occurs, 600 mg of boric acid in a gelatin capsule is recommended, administered vaginally once daily for 2 weeks. This regimen has clinical and mycologic eradication rates of approximately 70%. If symptoms recur, referral to a specialist is advised.

susceptibility testing is usually not warranted for individual treatment guidance.

are not as effective against these species as they are against *C. albicans*.

precipitating factors.

patients who complete therapy.

*Recurrent Vulvovaginal Candidiasis (RVVC)*

**8.3 Complicated VVC**

**8.4 Treatment**

antifungal regimen.

*Non albicans VVC*

**8.2 Treatment**

Table 3. Summary of clinical features of vaginitis (Wilson and Sande).

## **9. Pelvic Inflammatory Disease (PID)**

PID comprises a spectrum of inflammatory disorders of the upper female genital tract, including any combination of endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis. Sexually transmitted organisms, especially *N. gonorrhoeae* and *C. trachomatis*, are implicated in many cases; however, microorganisms that comprise the vaginal flora e.g., anaerobes, *G. vaginalis, Haemophilus influenzae*, enteric Gram-negative rods, and *Streptococcus agalactiae,* also have been associated with PID. In addition, *M. hominis*, *U. urealyticum*, and *M. genitalium* might be associated with some cases of PID. All women who have acute PID should be tested for *N. gonorrhoeae* and *C. trachomatis* and should be screened for HIV infection. Symptoms of PID include abnormal cervical or vaginal discharge, abdominal pain and fever. On examination there may be cervical motion and adnexal and lower abdominal tenderness. It is important to diagnose and treat PID as early as possible. For patients requiring hospitalization, intravenous cefoxitin or cefotetan plus doxycyline (i/v or oral) can be given. Alternatively clindamycin plus gentamicin can be given followed by oral doxycycline. Outpatient treatments include oral ofloxacin plus metronidazole or ceftriaxone (or cefixitin and oral probenecid) plus oral doxycycline. Duration of intravenous treatment is dependent on the severity of the clinical presentation (Romanowski, 1993).

Sexually Transmitted Infections: An Overview 27

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50.

## **10. Epididymitis**

In men under age 35, the most common pathogens are *N. gonorrhoeae* and *C. trachomatis(Trojian et al., 2009).* Homosexual men may have enteric pathogens from rectal intercourse. Unilateral testicular pain and tenderness are common. There is usually palpable swelling of the epididymis. The evaluation and diagnostic tests are the same as those for urethritis. Treatment includes ceftriaxone plus doxycyline or ofloxacin (Berger, 1991).

## **11. Proctitis**

Proctitis acquired through receptive anal intercourse can be caused by *N. gonorrhoeae, C. trachomatis* (including LGV serovars), *T. pallidum* (syphilis) and HSV. Treatment includes ceftriaxone plus doxycyline.

## **12.  Male latex condoms, when used consistently and correctly, are highly effective in reducing the transmission of HIV and other sexually transmitted infections, including gonorrhoea, chlamydial infection and trichomoniasis. Prompt diagnosis and treatment of both the partners is the key for an effective management.

## **13. References**

In men under age 35, the most common pathogens are *N. gonorrhoeae* and *C. trachomatis(Trojian et al., 2009).* Homosexual men may have enteric pathogens from rectal intercourse. Unilateral testicular pain and tenderness are common. There is usually palpable swelling of the epididymis. The evaluation and diagnostic tests are the same as those for urethritis. Treatment includes ceftriaxone plus doxycyline or ofloxacin (Berger, 1991).

Proctitis acquired through receptive anal intercourse can be caused by *N. gonorrhoeae, C. trachomatis* (including LGV serovars), *T. pallidum* (syphilis) and HSV.  Male latex condoms, when used consistently and correctly, are highly effective in reducing the transmission of HIV and other sexually transmitted infections, including gonorrhoea, chlamydial infection and trichomoniasis. Prompt diagnosis and treatment of both the partners is the key for an

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**13. References**

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**Part 2**

**Bacterial Infections**

## **Part 2**

**Bacterial Infections**

28 Sexually Transmitted Infections

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**2**

Sabina Mahmutovic Vranic *School of Medicine, University of Sarajevo/Department of Microbiology*

*Bosnia and Herzegovina*

*Chlamydia trachomatis* **Infections of the Adults**

*Chlamydiae* are obligate intracellular bacteria and consist of four species, including *Chlamydia trachomatis*, *C. pneumoniae*, *C. psittaci* and *C. pecorum*, which cause many types of diseases. The word chlamys is Greek for "cloaked" or "draped", descriptive of the intracytoplasmic

*C. trachomatis* is a Gram-negative bacteria, therefore its cell wall components retain the counter-stain safranin and appear pink under a light microscope. Identified in 1907, *C.*

*Chlamydia trachomatis* (CT) is one of the major bacterial agent of the sexually transmitted diseases (STDs) worldwide. It is a causative agent of urogenital, ocular and pneumonic infections, causing annually 92 million new infections worldwide*.* It is responsible for a wide range of infections, including trachoma (a chronic conjuctivitis, which is the leading preventable cause of blidness worldwide), newborn conjuctivitis, and genital infections in women and men. CT has a unique life cycle, dependent on the host cell's adenosine triphosphate (ATP) production, which differentiates it from all other microorganisms.

Chlamydial genital infection is the most frequently reported infectious disease in the United States, and prevalence is highest in persons aged ≤25 years (Centers for Disease Control and

Asymptomatic infection is common among both, women and men. The fact is that as many as 70 to 80% of women and up to 50% of men who are infected do not experience any symptoms. The most serious sequelae as the CT infection in women include pelvic inflammatory disease- PID, tubal infertility, chronic pelvic pain and ectopic pregnancy.

In pregnant women, CT infection is associated with preterm birth and other complications

Since chlamydial infections first become a reportable disease in the United States in 1986, the number of reported cases in both men and women has increased each year. It is currently estimated that about 4 million new chlamydial infections occur each year in the United

such as stillbirth, premature rupture of membranes, and post-partum endometritis.

States at an estimated annual cost exceeding \$ 2.4 billion (CDC, 2003).

inclusion bodies that are "draped" around the host cell nucleus.

*trachomatis* was the first chlamydial agent discovered in humans.

**1. Introduction**

Prevention CDC, 2009).

## *Chlamydia trachomatis* **Infections of the Adults**

## Sabina Mahmutovic Vranic

*School of Medicine, University of Sarajevo/Department of Microbiology Bosnia and Herzegovina*

## **1. Introduction**

*Chlamydiae* are obligate intracellular bacteria and consist of four species, including *Chlamydia trachomatis*, *C. pneumoniae*, *C. psittaci* and *C. pecorum*, which cause many types of diseases. The word chlamys is Greek for "cloaked" or "draped", descriptive of the intracytoplasmic inclusion bodies that are "draped" around the host cell nucleus.

*C. trachomatis* is a Gram-negative bacteria, therefore its cell wall components retain the counter-stain safranin and appear pink under a light microscope. Identified in 1907, *C. trachomatis* was the first chlamydial agent discovered in humans.

*Chlamydia trachomatis* (CT) is one of the major bacterial agent of the sexually transmitted diseases (STDs) worldwide. It is a causative agent of urogenital, ocular and pneumonic infections, causing annually 92 million new infections worldwide*.* It is responsible for a wide range of infections, including trachoma (a chronic conjuctivitis, which is the leading preventable cause of blidness worldwide), newborn conjuctivitis, and genital infections in women and men. CT has a unique life cycle, dependent on the host cell's adenosine triphosphate (ATP) production, which differentiates it from all other microorganisms.

Chlamydial genital infection is the most frequently reported infectious disease in the United States, and prevalence is highest in persons aged ≤25 years (Centers for Disease Control and Prevention CDC, 2009).

Asymptomatic infection is common among both, women and men. The fact is that as many as 70 to 80% of women and up to 50% of men who are infected do not experience any symptoms. The most serious sequelae as the CT infection in women include pelvic inflammatory disease- PID, tubal infertility, chronic pelvic pain and ectopic pregnancy.

In pregnant women, CT infection is associated with preterm birth and other complications such as stillbirth, premature rupture of membranes, and post-partum endometritis.

Since chlamydial infections first become a reportable disease in the United States in 1986, the number of reported cases in both men and women has increased each year. It is currently estimated that about 4 million new chlamydial infections occur each year in the United States at an estimated annual cost exceeding \$ 2.4 billion (CDC, 2003).

*Chlamydia trachomatis* Infections of the Adults 33

1. Chlamydia is the most commonly reported bacterial infection, with an estimated four

4. Untreated chlamydial infections may lead to PID, ectopic pregnancy, and infertility. 5. The purpose of at least annually screening all sexually active women aged 25 years and

Because of their unique developmental life cycle, all chlamydiae were placed into their own order, *Chlamydiales*, family *Chlamydiaceae,* within one genus, *Chlamydia* (Pudjitamoko et al., 1997, as cited in Int J Syst Bacteriol, 1984). *C. trachomatis* is one of the four recognized species of the genus *Chlamydia*, with *C. pneumoniae*, *C. psittaci* and *C. pecorum. Chlamydia* species are readily identified and distinguished from other chlamydial species using DNA-based tests and on the basis unique growth cycle. *Chlamydia psitaci* is a common pathogen of avian species and domestic mammals, but only involves humans as a zoonosis. *Chlaymdia pneumoniae* is a common respiratory pathogen of humans that has been implicated as a possible cause of coronary artery disease*. Chlamydia pecorum* is a pathogen of domestic animals.  Molecular techniques such as PCR or DNA hybridization or the use of monoclonal antibodies are required to

There are 15 serovars of *C. trachomatis*, which are divided into the trachoma serotypes A, B, Ba, and C, the oculogenital serovars, D-K, and the lymphogranuloma venereum (LGV) serovars L1-L3 (table 1.). Most strains of *C. trachomatis* are recognized by monoclonal antibodies (mAbs) to epitopes in the VS4 region of MOMP (major outer membrane protein). Serovars can be distinguished by serological typing using monoclonal antibodies or by molecular gene typing methods. Typing is useful for epidemiological studies, which focus on transmission and geographical differences. In the developed world, the oculogenital strains are predominantly the strains that are routinely prevalent, while trachoma is a sequelae of ocular disease in developing countries and countinues to be a leading cause of preventable blidness. LGV is sporadic in North America and Europe, and endemic in Africa, India, Southeast Asia, South America, and the Caribbean. Occasional cases or clusters of cases suggest ongoing low-level transmission in these areas. Few countries require official notification of LGV cases, and the lack of standard diagnostic criteria renders reported cases somewhat suspect. Likeother sexually transmitted diseases LGV is more common in urban than in rural areas, among the sexually active, and among the lower socioeconomic groups. Much of the reported epidemiology on LGV was based on cases diagnosed using clinical criteria or the results of serologic tests and/or Frei skin tests that were not specific for the

Urogenital chlamydial infections occur primarily among young sexually active persons. Prevalence rates encompass all socioeconomic groups and geographical areas, and may

range from 5-20% in various groups of young adults (Eng & Butler, 1997).

2. Adolescents and adults are most commonly infected with *C. trachomatis.* 3. Asymptomatic infection is common among both, women and men.

younger is to reduce the incidence of upper tract infection.

**1.1 Facts**

**2. Etiology**

differentiate the species.

disease.

million new cases each year.

Worldwide, it is estimated that there are more than 50 million new cases CT infection annually (CDC, 2003).

The prevalence of CT infection in sexually active adolescent women, the population considered most at risk, generally exceeds 10%, and in some adolescent and STD clinic populations of women, the prevalence can reach 40%.

The incidence of asymptomatic infection, it's impact on individuals, and it's influence on the prevalence of disease in the community has led multiple professional organizations to recommend that all sexually active women aged 25 years and younger and all asymptomatic women at risk infection be screened for CT genital infection. Chlamydial infections may increase susceptibility to and transmission of human immunodeficiency virus-HIV in both women and men (Westrom et al., 1999).

As far as Central and Eastern European ("CEE") countries are concerned, the epidemiological picture of chlamydial genital infections cannot be reliably estimated since there is no systematic registration, prevalence studies are sporadic and methodologically hardly comparable, and prevention programs focusing on asymptomatic population are scarce.

The incidence of chlamydial genital infections in CEE is estimated to be 21 to 276 cases per 100,000 inhabitants. The public health importance of chlamydial genital infections lies in the fact that their prevalence is the highest in young population, that they are mostly asymptomatic and that, if left untreated, they may later result in chronic pelvic infl ammatory disease, sterility or ectopic pregnancy.

 Because these infections are easy to diagnose and curable with a single dose of oral antibiotics, early detection and treatment are an important component of efforts to reduce the disease burden.

Chlamydia is often found as a co-infection with gonorrhea in both women and men. Between 30 and 50% of patients who have gonococcal infections also have infection with *C. trachomatis.* However, because the background incidence of gonorrhea is so much lower (<0.5%), it is far less likely that a person infected with *C. trachomatis* will also have gonoccocal infection. In the National Longitudinal Study, only 0.3% of young adults were co-infected (Miller et al., 2004). Although screening for *C. trachomatis* is widely recommended among young adult women, little information is available regarding the prevalence of chlamydial infections in the general young adult population. Screening programs have been demonstrated to reduce both the prevalence of *C. trachomatis* infection and rates of PID in women (Scholes et al., 1996).

Today chlamydial infections are diagnosed by simple, reliable and non-invasive tests, and the therapy of choice is a single dose of 1 g azithromycin, which has proven to be safe and effective, especially in acute infections. Azithromycin also proved to be the drug of choice in the treatment of chronic infections, chlamydial prostatitis, and in the treatment of major complications, such as pelvic inflammatory disease.

### **1.1 Facts**

32 Sexually Transmitted Infections

Worldwide, it is estimated that there are more than 50 million new cases CT infection

The prevalence of CT infection in sexually active adolescent women, the population considered most at risk, generally exceeds 10%, and in some adolescent and STD clinic

The incidence of asymptomatic infection, it's impact on individuals, and it's influence on the prevalence of disease in the community has led multiple professional organizations to recommend that all sexually active women aged 25 years and younger and all asymptomatic women at risk infection be screened for CT genital infection. Chlamydial infections may increase susceptibility to and transmission of human immunodeficiency virus-HIV in both

As far as Central and Eastern European ("CEE") countries are concerned, the epidemiological picture of chlamydial genital infections cannot be reliably estimated since there is no systematic registration, prevalence studies are sporadic and methodologically hardly comparable, and prevention programs focusing on asymptomatic population are

The incidence of chlamydial genital infections in CEE is estimated to be 21 to 276 cases per 100,000 inhabitants. The public health importance of chlamydial genital infections lies in the fact that their prevalence is the highest in young population, that they are mostly asymptomatic and that, if left untreated, they may later result in chronic pelvic infl

Unfortunately, symptoms of genital infection are often completely absent or very mild among infected patients, especially women, creating a large reservoir of infected persons who continue transmission to new sexual partners. Because these infections are easy to diagnose and curable with a single dose of oral antibiotics, early detection and treatment are

Chlamydia is often found as a co-infection with gonorrhea in both women and men. Between 30 and 50% of patients who have gonococcal infections also have infection with *C. trachomatis.* However, because the background incidence of gonorrhea is so much lower (<0.5%), it is far less likely that a person infected with *C. trachomatis* will also have gonoccocal infection. In the National Longitudinal Study, only 0.3% of young adults were co-infected (Miller et al., 2004). Although screening for *C. trachomatis* is widely recommended among young adult women, little information is available regarding the prevalence of chlamydial infections in the general young adult population. Screening programs have been demonstrated to reduce both the prevalence of *C. trachomatis* infection

Today chlamydial infections are diagnosed by simple, reliable and non-invasive tests, and the therapy of choice is a single dose of 1 g azithromycin, which has proven to be safe and effective, especially in acute infections. Azithromycin also proved to be the drug of choice in the treatment of chronic infections, chlamydial prostatitis, and in the treatment of major

annually (CDC, 2003).

scarce.

populations of women, the prevalence can reach 40%.

women and men (Westrom et al., 1999).

ammatory disease, sterility or ectopic pregnancy.

and rates of PID in women (Scholes et al., 1996).

complications, such as pelvic inflammatory disease.

an important component of efforts to reduce the disease burden.

## **2. Etiology**

Because of their unique developmental life cycle, all chlamydiae were placed into their own order, *Chlamydiales*, family *Chlamydiaceae,* within one genus, *Chlamydia* (Pudjitamoko et al., 1997, as cited in Int J Syst Bacteriol, 1984). *C. trachomatis* is one of the four recognized species of the genus *Chlamydia*, with *C. pneumoniae*, *C. psittaci* and *C. pecorum. Chlamydia* species are readily identified and distinguished from other chlamydial species using DNA-based tests and on the basis unique growth cycle. *Chlamydia psitaci* is a common pathogen of avian species and domestic mammals, but only involves humans as a zoonosis. *Chlaymdia pneumoniae* is a common respiratory pathogen of humans that has been implicated as a possible cause of coronary artery disease*. Chlamydia pecorum* is a pathogen of domestic animals.  Molecular techniques such as PCR or DNA hybridization or the use of monoclonal antibodies are required to differentiate the species.

There are 15 serovars of *C. trachomatis*, which are divided into the trachoma serotypes A, B, Ba, and C, the oculogenital serovars, D-K, and the lymphogranuloma venereum (LGV) serovars L1-L3 (table 1.). Most strains of *C. trachomatis* are recognized by monoclonal antibodies (mAbs) to epitopes in the VS4 region of MOMP (major outer membrane protein). Serovars can be distinguished by serological typing using monoclonal antibodies or by molecular gene typing methods. Typing is useful for epidemiological studies, which focus on transmission and geographical differences. In the developed world, the oculogenital strains are predominantly the strains that are routinely prevalent, while trachoma is a sequelae of ocular disease in developing countries and countinues to be a leading cause of preventable blidness. LGV is sporadic in North America and Europe, and endemic in Africa, India, Southeast Asia, South America, and the Caribbean. Occasional cases or clusters of cases suggest ongoing low-level transmission in these areas. Few countries require official notification of LGV cases, and the lack of standard diagnostic criteria renders reported cases somewhat suspect. Likeother sexually transmitted diseases LGV is more common in urban than in rural areas, among the sexually active, and among the lower socioeconomic groups. Much of the reported epidemiology on LGV was based on cases diagnosed using clinical criteria or the results of serologic tests and/or Frei skin tests that were not specific for the disease.

Urogenital chlamydial infections occur primarily among young sexually active persons. Prevalence rates encompass all socioeconomic groups and geographical areas, and may range from 5-20% in various groups of young adults (Eng & Butler, 1997).

*Chlamydia trachomatis* Infections of the Adults 35

The round to oval, optically dense elementary bodies have a diameter 300 nm. Infection begins when EBs attach to specific receptors found on nonciliated columnar or cuboidal epithelium of the host. This type of epithelium is located in the endocervix, endometrium,

After phagocytosis, the EB exists within a cytoplasmic vacuole or phagosome, where it is protected from host defense systems. Within the phagosome, the EB transforms into a reticulate body in order to myltiply. It has a diameter of aproximately 1000 nm. At the end of the life cycle, RBs are transformed back into EBs. The cell breaks open and releases the

Chlamydial genital infection is the most frequently reported infectious disease in the United States, and prevalence is highest in persons aged 25 years (CDC, 2009). The Centers for Diseases Control and Prevention (CDC), Atlanta, GA, has not changed its age cutoff, and thus continues to recommend annual chlamydia screening of sexually active women aged 25 years. The CDC estimates that 2.8 million new cases occur in the United States each year

Fig. 1. Chlamydial Biological Cycle (Jones et al.,1994).

fallopian tube, and urethra, making those sites vulnerable to infection.

EBs to continue the cycle by attaching themselves to new host cells.

**3.1 Elementary bodies**

**3.2 Reticulate bodies**

**4. Prevalence and Incidence**

Table 1. Human infections caused by *Chlamydia trachomatis.*

## **3. Chlamydial biological cycle**

Chlamydiae are obligate cell parasites and cannot be cultured on arteficial media. They have the ability to establish long-term associations with host cells. They are also restricted to an intracellular life style because chlamydiae lack the ability to synthesize high-energy compounds. When an infected host cell is starved for various nutrients such as amino acids (tryptophan) iron, or vitamins, this has a negative consequence for *Chlamydiae* since the organism is dependent on the host cell for these nutrients. They depend on the host cell to supply them with ATP and necessary nutrients.

It is developmental cycle of chlamydiae that sets them apart form all other bacteria. There are some differences in inclusion morphology within the chlamydiae, but all species appear to have essentially identical developmental cycles.

They go through two stages in their reproductive cycle; the elementary bodies (EBs) are optimized to survive outside of host cells. In the form of the reticular bodies (RBs), the chlamydiae reproduce inside the host cells. This cycle involves an alternation between two highly specialized morphologic forms, one adopted to an intracellular and the other to an extra cellular environment.

The cycle may be divided into several steps: (1) initial attachment of the infectious particle, or elementary body, to the host cell; (2) entry into the cell; (3) morphological change to the reticulate particle, with intracellular growth and replication; (4) morphologic change of reticulate particles to Ebs; and finally (5) release of the infectious particles (figure 1.).

The entire cycle takes place within a chlamydia –modified intracellular vacuole, which undergoes a large increase in size.

Disease/Syndrome Biovar Most frequent serovars

Inclusion conjunctivits trachoma D, Da, E, F, G, H, I, Ia, J, K

lymphogranuloma

Chlamydiae are obligate cell parasites and cannot be cultured on arteficial media. They have the ability to establish long-term associations with host cells. They are also restricted to an intracellular life style because chlamydiae lack the ability to synthesize high-energy compounds. When an infected host cell is starved for various nutrients such as amino acids (tryptophan) iron, or vitamins, this has a negative consequence for *Chlamydiae* since the organism is dependent on the host cell for these nutrients. They depend on the host cell to

It is developmental cycle of chlamydiae that sets them apart form all other bacteria. There are some differences in inclusion morphology within the chlamydiae, but all species appear

They go through two stages in their reproductive cycle; the elementary bodies (EBs) are optimized to survive outside of host cells. In the form of the reticular bodies (RBs), the chlamydiae reproduce inside the host cells. This cycle involves an alternation between two highly specialized morphologic forms, one adopted to an intracellular and the other to an

The cycle may be divided into several steps: (1) initial attachment of the infectious particle, or elementary body, to the host cell; (2) entry into the cell; (3) morphological change to the reticulate particle, with intracellular growth and replication; (4) morphologic change of reticulate particles to Ebs; and finally (5) release of the infectious

The entire cycle takes place within a chlamydia –modified intracellular vacuole, which

venereum

Table 1. Human infections caused by *Chlamydia trachomatis.*

trachoma B, C, D, E, F, G, H, I, K, L3

L1, L2, L2a, L3

Trachoma trachoma A, B, Ba, C

Urethritis, cervicitis,

Lymphogranuloma venereum (syn. Lymphogranuloma inguinale, lymphopathia venerea, Favre-Durand-Nicolas disease)

**3. Chlamydial biological cycle**

extra cellular environment.

undergoes a large increase in size.

particles (figure 1.).

supply them with ATP and necessary nutrients.

to have essentially identical developmental cycles.

(pharyngitis, otitis media)

salpingitis

Fig. 1. Chlamydial Biological Cycle (Jones et al.,1994).

#### **3.1 Elementary bodies**

The round to oval, optically dense elementary bodies have a diameter 300 nm. Infection begins when EBs attach to specific receptors found on nonciliated columnar or cuboidal epithelium of the host. This type of epithelium is located in the endocervix, endometrium, fallopian tube, and urethra, making those sites vulnerable to infection.

#### **3.2 Reticulate bodies**

After phagocytosis, the EB exists within a cytoplasmic vacuole or phagosome, where it is protected from host defense systems. Within the phagosome, the EB transforms into a reticulate body in order to myltiply. It has a diameter of aproximately 1000 nm. At the end of the life cycle, RBs are transformed back into EBs. The cell breaks open and releases the EBs to continue the cycle by attaching themselves to new host cells.

#### **4. Prevalence and Incidence**

Chlamydial genital infection is the most frequently reported infectious disease in the United States, and prevalence is highest in persons aged 25 years (CDC, 2009). The Centers for Diseases Control and Prevention (CDC), Atlanta, GA, has not changed its age cutoff, and thus continues to recommend annual chlamydia screening of sexually active women aged 25 years. The CDC estimates that 2.8 million new cases occur in the United States each year

*Chlamydia trachomatis* Infections of the Adults 37

The relationship between the use of condoms and other barrier contraceptives (diaphragm), and genital chlamydial infection is inconsistent across the studies. Use of a barrier method was shown to be associated with reduced risk of infection compared with the use of other

Age at first intercourse may be casually related to sexually transmitted infections through the biological mechanisms affecting adolescents that and also be an indicator of other aspects of sexual activity that will directly increase risk, including multiple partnerships and

Although the pathologic consequences of infection are well established, the mechanism of chlamydia-induced tissue damage are not fully understood. Emerging knowledge of the immune response to infection suggests that many of the complications of chlamydial infection are accompanied by important alterations in immunoregulation; both antibodymediated and cell-mediated immune effectors may be significant in eliminatory or limiting

The ways of spreading are different; sexually, perinatal, although are not exclusive the other ways of transmission through the chloride water of swimming pool, wet towel as well as the possibility of intrahospital infections, by gynecological exam, are not keep the necessary protection measures. It is supposed, statistically, that about 10% percent of women in

*C. trachomatis* is the most common sexually transmitted bacterial agent, which infects only humans. The single exposure male-to-female transmission rate has been estimated to be 40%, and the female-to-male transmission rate has been estimated to be 32% (Sweet & Gibbs, 2002). Other investigators have found that transmission rates between sexes are

Vertical transmission of *C. trachomatis* is more efficient than horizontal transmission. More than 60% of newborns who delivered through a chlamydia-infected cervix will aquire the

As well as the infection with human papilloma virus, chlamydial infection is very important promoter of cervical intraepithelial neoplasm, which result with bad Papanicolaou test, with salpingitis with consequently opturation tuba incompletely or completely, which finally results as extrauterine pregnancy and sterility. During pregnancy, *C. trachomatis* causes disorders and ruptures of the fertile membranes with consequent delayed spontaneous

Genital infections caused by *C. trachomatis* closely parallel those due to *N. gonorrhoeae* in terms of clinical manifestations. Both preferentially infect columnar or transitional epithelium of the urethra, with extension to the epididymis; the endocervix, with extension to the endometrium, salpinx, and peritoneum; and the rectum. *C. trachomatis* are naturally found living only inside human cells. Chlamydia can be transmitted during vaginal, anal, or

methods of contraception in two of five studies in females.

**6. Pathogenesis, infectivity and transmission**

reproductive age are infected with *C. trachomatis*.

equivalent (Quinn et al., 1996).

infection (Sweet & Gibbs, 2002).

abortion or the earlier delivery.

**7. Clinical manifestations**

the recruitment of nonregular partners.

chlamydial infection.

(CDC, 2005). Nearly 75% of cases occur in the 15-to 24-year-old age group (Grosecloseet et al., 1999). The World Heath Organization (WHO) estimated that 92 million new infections with *C. trachomatis* occured worldwide in 1999 (WHO, 2001). The prevalence of active infection in sexually active, asymptomatic, non-pregnant women in the general population is between 3 and 5% (Sweet & Gibbs, 2002). The highest age-specific rates were reported in women age 15-26. In the general population, men have the same prevalence of chalmydial infections as women (3-5%). Among men, the highest rates occurs in 20- to 24- year-old (CDC, 2005). However, accurate time trends in the incidence of chlamydia are difficult to define because of changes in reporting, increased detection due to improved laboratory tests and increasing laboratory surveillance. Gerbes et al. (Gerbes et al., 1998) estimated that the average annual incidence rates for people aged 15 to 49 years were similar in North America, Western Europe and Australasia at 2146/100,000 for males and 3073/100,000 for females in 1995.

Chlamydia causes more than 250,000 cases of epididymitis in the U.S. each year. Chlamydia causes 250,000 to 500,000 cases of PID every year in the United States. Women infected with chlamydia are up to five times more likely to become infected with human immunodeficiency virus (HIV), if exposed.

## **5. Risk factors**

The risk factors for chlamydial infection include: age younger than 26, low socioeconomic status, minority group member, contraceptive use, age at first intercourse, multiple sexual partners and new partners, and other risk factors as well.

Younger age is shown consistently to be asociated with increased risk of chlaymdial infection among the sexually active population. Age is an important risk factor because *C. trachomatis* typically infects the columnar cells of the cervix; in younger women, columnar cells are more likely to be on the ectocervix (ectopy), where they can be exposed to semen carrying the organism. As women age, the columnar cells are located higher in the cervical canal. Combination hormonal contraceptive use apparently increases cervical ectopy and has been a proposed risk factor for chlamydial infection (Jocobson et al., 2000). The highest incidence rates of infection are reported in adolescents and young adults in Canada and the United States. Differences in the prevalence of infection between adolescents and adults are also often attributed to differences in sexual behaviours.

Race/ethnicity and socioeconomic status are often considered together because they are strongly interrealted (van de Hoek, 1999). Only 10 of 23 studies in females and one of four studies in males indicated a higher risk of chlamydial infection in nonwhite people compared with white people in multivariate analysis. Socioeconomic status was not associate with chlamydia in multivariate analysis using any measure for males and females, including employment status income level of parents education use of Medicaid or occupation.

Multiple partnerships may increase the likelihood of encountering a sexually transmitted pathogen through the increased probability of choosing a partner with infection, while having new or casual sexual contacts may be related to increased risk because of a reduced familiarity between partners.

(CDC, 2005). Nearly 75% of cases occur in the 15-to 24-year-old age group (Grosecloseet et al., 1999). The World Heath Organization (WHO) estimated that 92 million new infections with *C. trachomatis* occured worldwide in 1999 (WHO, 2001). The prevalence of active infection in sexually active, asymptomatic, non-pregnant women in the general population is between 3 and 5% (Sweet & Gibbs, 2002). The highest age-specific rates were reported in women age 15-26. In the general population, men have the same prevalence of chalmydial infections as women (3-5%). Among men, the highest rates occurs in 20- to 24- year-old (CDC, 2005). However, accurate time trends in the incidence of chlamydia are difficult to define because of changes in reporting, increased detection due to improved laboratory tests and increasing laboratory surveillance. Gerbes et al. (Gerbes et al., 1998) estimated that the average annual incidence rates for people aged 15 to 49 years were similar in North America, Western Europe and Australasia at 2146/100,000 for males and 3073/100,000 for

Chlamydia causes more than 250,000 cases of epididymitis in the U.S. each year. Chlamydia causes 250,000 to 500,000 cases of PID every year in the United States. Women infected with chlamydia are up to five times more likely to become infected with human

The risk factors for chlamydial infection include: age younger than 26, low socioeconomic status, minority group member, contraceptive use, age at first intercourse, multiple sexual

Younger age is shown consistently to be asociated with increased risk of chlaymdial infection among the sexually active population. Age is an important risk factor because *C. trachomatis* typically infects the columnar cells of the cervix; in younger women, columnar cells are more likely to be on the ectocervix (ectopy), where they can be exposed to semen carrying the organism. As women age, the columnar cells are located higher in the cervical canal. Combination hormonal contraceptive use apparently increases cervical ectopy and has been a proposed risk factor for chlamydial infection (Jocobson et al., 2000). The highest incidence rates of infection are reported in adolescents and young adults in Canada and the United States. Differences in the prevalence of infection between adolescents and adults are

Race/ethnicity and socioeconomic status are often considered together because they are strongly interrealted (van de Hoek, 1999). Only 10 of 23 studies in females and one of four studies in males indicated a higher risk of chlamydial infection in nonwhite people compared with white people in multivariate analysis. Socioeconomic status was not associate with chlamydia in multivariate analysis using any measure for males and females, including employment status income level of parents education use of Medicaid or

Multiple partnerships may increase the likelihood of encountering a sexually transmitted pathogen through the increased probability of choosing a partner with infection, while having new or casual sexual contacts may be related to increased risk because of a reduced

females in 1995.

**5. Risk factors**

occupation.

familiarity between partners.

immunodeficiency virus (HIV), if exposed.

partners and new partners, and other risk factors as well.

also often attributed to differences in sexual behaviours.

The relationship between the use of condoms and other barrier contraceptives (diaphragm), and genital chlamydial infection is inconsistent across the studies. Use of a barrier method was shown to be associated with reduced risk of infection compared with the use of other methods of contraception in two of five studies in females.

Age at first intercourse may be casually related to sexually transmitted infections through the biological mechanisms affecting adolescents that and also be an indicator of other aspects of sexual activity that will directly increase risk, including multiple partnerships and the recruitment of nonregular partners.

## **6. Pathogenesis, infectivity and transmission**

Although the pathologic consequences of infection are well established, the mechanism of chlamydia-induced tissue damage are not fully understood. Emerging knowledge of the immune response to infection suggests that many of the complications of chlamydial infection are accompanied by important alterations in immunoregulation; both antibodymediated and cell-mediated immune effectors may be significant in eliminatory or limiting chlamydial infection.

The ways of spreading are different; sexually, perinatal, although are not exclusive the other ways of transmission through the chloride water of swimming pool, wet towel as well as the possibility of intrahospital infections, by gynecological exam, are not keep the necessary protection measures. It is supposed, statistically, that about 10% percent of women in reproductive age are infected with *C. trachomatis*.

*C. trachomatis* is the most common sexually transmitted bacterial agent, which infects only humans. The single exposure male-to-female transmission rate has been estimated to be 40%, and the female-to-male transmission rate has been estimated to be 32% (Sweet & Gibbs, 2002). Other investigators have found that transmission rates between sexes are equivalent (Quinn et al., 1996).

Vertical transmission of *C. trachomatis* is more efficient than horizontal transmission. More than 60% of newborns who delivered through a chlamydia-infected cervix will aquire the infection (Sweet & Gibbs, 2002).

As well as the infection with human papilloma virus, chlamydial infection is very important promoter of cervical intraepithelial neoplasm, which result with bad Papanicolaou test, with salpingitis with consequently opturation tuba incompletely or completely, which finally results as extrauterine pregnancy and sterility. During pregnancy, *C. trachomatis* causes disorders and ruptures of the fertile membranes with consequent delayed spontaneous abortion or the earlier delivery.

## **7. Clinical manifestations**

Genital infections caused by *C. trachomatis* closely parallel those due to *N. gonorrhoeae* in terms of clinical manifestations. Both preferentially infect columnar or transitional epithelium of the urethra, with extension to the epididymis; the endocervix, with extension to the endometrium, salpinx, and peritoneum; and the rectum. *C. trachomatis* are naturally found living only inside human cells. Chlamydia can be transmitted during vaginal, anal, or

*Chlamydia trachomatis* Infections of the Adults 39

Premature rupture of

membranes

Cervicitis Perihepatitis Preterm labor Urethritis Conjunctivitis Preterm delivery

Proctitis Infertility Postpartum endometritis

In women, *C. trachomatis* can cause urethritis, proctitis, or infections of the genital organs. It has even been known to cause pelvioperitonitis and perihepatitis. Massive perinatal

*C. trachomatis* is responsible for 30 to 60% of cases of nongonococcal urethritis (NGU) in men. Possible complications include prostatitis and epididymitis. The pathogens are communicated by venereal transmission. The source of infection is the female sexual

Urogenital chlamydial infections occur primarily among young sexually active persons. Prevalence rates encompass all socioeconomic groups and geographical areas, and more range from 5-20% in various groups of young adults (Eng & Butler, 1997; Tamm, 1999). Because symptoms are absent in most infected individuals, the prevalence in population groups may be severely underestimated. So, widespread screening of individuals at greatest risk, e.g. those individuals who are young, sexually active, and have new or multiple

Genital infections caused by the *C. trachomatis* is the most frequently reported STD's worldwide, with the highest prevalence in aged category of 25 years (CDC, 2009). In women*, C. trachomatis* has been shown to cause both lower and upper genital tract

Urethritis Proctitis Epididymitis Infertility Prostatitis Conjunctivitis

Conjunctivitis Pneumonia

partner, who often shows no clinical symptoms.

partners, has been recommended.

**7.3.1 Genital infections in women**

Table 2. Clinical manifestations of *Chlamydia trachomatis.*

infection of a neonate may lead to an interstitial chlamydial pneumonia.

syndrome Ectopic pregnancy

Endometritis Chronic pelvic pain Salpingitis Reiter' s syndrome

Acute urethral

Reiter' s syndrome

Newborns

Otitis media

Women

Men

oral sex, and can be passed from an infected mother to her baby during vaginal childbirth. Between half and three-quarters of all women who have a chlamydia infection of the neck of the womb (cervicitis) have no symptoms and do not know that they are infected.

*C. trachomatis* serovars A, B, Ba, and C are associated with endemic trachoma, the most common preventable form of blidness, while serovars L1, L2, and L3 are associated with LGV. Serovars D through K are the major causes of nongonococcal urethritis and epididymitis in men and may induce Reiter's syndrome, proctitis, and conjuctivitis in both men and women and cervicitis, urethritis, endometritis, with salpingitis with tubal obstruction which could be complete or incomplete, and perihepatitis in women. During pregnancy CT can cause "premature" rupture of membranes, spontaneous abortions and preterm delivery.

### **7.1 Trachoma**

Trachoma is a follicular keratoconjuctivitis. The disease occurs in all climatic zones, although it is more frequent in warmer, less-developed countries. The pathogen is transmitted by direct contact and indirectly via objects in daily use. Untreated, the initially acute inflammation could develop a chronic course lasting months or years and leading to formation of a corneal scar, which can than cause blidness.

The laboratory diagnostics procedure involves detection of *C. trachomatis* in conjuctival smears using direct immunofluorescence microscopy. The fluorochrome-marked monoclonal antibodies are directed against the MOMP of *C. trachomatis*.

The pathogen can also be grown in cell cultures. The therapeutic method of choice is systemic and local application of tetracyclines over a period of several weeks.

Chlamydia conjunctivitis or trachoma is a common cause of blindness worldwide. The WHO estimates that it accounted for 15% of blindness cases in 1995, but only 3.6% in 2002 (WHO, 2002).

#### **7.2 Inclusion conjuctivitis**

This is an acute, purulent papillary conjuctivits that may affect neonates, children, and adults (swiming-pool conjuctivitis). Newborn children are infected during birth by pathogenes colonizing the birth canal. Untreated, a pannus may form as in trachoma, followed by corneal scarring. Laboratory diagnosis and therapy as in trachoma.

#### **7.3 Genital infections**

Chlamydial infections of the genital tract have a worldwide distribution and are prevalent both in the industrialized countries and in the developing world. C*. trachomatis* as the bacterial agent is responsible for the huge number of genital infections, which is spreading especially among younger (table 2.). Adults are defined as persons between 15 and 49 years of age. Almost four million new cases of chlamydial infections on genital plane are registrated every year in the United States, and three million in Europe (CDC, 1997). Epidemiological investigations of a large number of women in the United States and Scandinavia confirm chlamydiae as the most prevalent STDs for developed countries. Considered the prevalence infections, hard consequences and huge bills for the treatment in the United States is implement screening methods, which include persons with high risk:

oral sex, and can be passed from an infected mother to her baby during vaginal childbirth. Between half and three-quarters of all women who have a chlamydia infection of the neck of

*C. trachomatis* serovars A, B, Ba, and C are associated with endemic trachoma, the most common preventable form of blidness, while serovars L1, L2, and L3 are associated with LGV. Serovars D through K are the major causes of nongonococcal urethritis and epididymitis in men and may induce Reiter's syndrome, proctitis, and conjuctivitis in both men and women and cervicitis, urethritis, endometritis, with salpingitis with tubal obstruction which could be complete or incomplete, and perihepatitis in women. During pregnancy CT can cause

Trachoma is a follicular keratoconjuctivitis. The disease occurs in all climatic zones, although it is more frequent in warmer, less-developed countries. The pathogen is transmitted by direct contact and indirectly via objects in daily use. Untreated, the initially acute inflammation could develop a chronic course lasting months or years and leading to

The laboratory diagnostics procedure involves detection of *C. trachomatis* in conjuctival smears using direct immunofluorescence microscopy. The fluorochrome-marked

The pathogen can also be grown in cell cultures. The therapeutic method of choice is

Chlamydia conjunctivitis or trachoma is a common cause of blindness worldwide. The WHO estimates that it accounted for 15% of blindness cases in 1995, but only 3.6% in 2002

This is an acute, purulent papillary conjuctivits that may affect neonates, children, and adults (swiming-pool conjuctivitis). Newborn children are infected during birth by pathogenes colonizing the birth canal. Untreated, a pannus may form as in trachoma,

Chlamydial infections of the genital tract have a worldwide distribution and are prevalent both in the industrialized countries and in the developing world. C*. trachomatis* as the bacterial agent is responsible for the huge number of genital infections, which is spreading especially among younger (table 2.). Adults are defined as persons between 15 and 49 years of age. Almost four million new cases of chlamydial infections on genital plane are registrated every year in the United States, and three million in Europe (CDC, 1997). Epidemiological investigations of a large number of women in the United States and Scandinavia confirm chlamydiae as the most prevalent STDs for developed countries. Considered the prevalence infections, hard consequences and huge bills for the treatment in the United States is implement screening methods, which include persons with high risk:

the womb (cervicitis) have no symptoms and do not know that they are infected.

"premature" rupture of membranes, spontaneous abortions and preterm delivery.

formation of a corneal scar, which can than cause blidness.

monoclonal antibodies are directed against the MOMP of *C. trachomatis*.

systemic and local application of tetracyclines over a period of several weeks.

followed by corneal scarring. Laboratory diagnosis and therapy as in trachoma.

**7.1 Trachoma**

(WHO, 2002).

**7.2 Inclusion conjuctivitis**

**7.3 Genital infections**

Table 2. Clinical manifestations of *Chlamydia trachomatis.*

In women, *C. trachomatis* can cause urethritis, proctitis, or infections of the genital organs. It has even been known to cause pelvioperitonitis and perihepatitis. Massive perinatal infection of a neonate may lead to an interstitial chlamydial pneumonia.

*C. trachomatis* is responsible for 30 to 60% of cases of nongonococcal urethritis (NGU) in men. Possible complications include prostatitis and epididymitis. The pathogens are communicated by venereal transmission. The source of infection is the female sexual partner, who often shows no clinical symptoms.

Urogenital chlamydial infections occur primarily among young sexually active persons. Prevalence rates encompass all socioeconomic groups and geographical areas, and more range from 5-20% in various groups of young adults (Eng & Butler, 1997; Tamm, 1999). Because symptoms are absent in most infected individuals, the prevalence in population groups may be severely underestimated. So, widespread screening of individuals at greatest risk, e.g. those individuals who are young, sexually active, and have new or multiple partners, has been recommended.

#### **7.3.1 Genital infections in women**

Genital infections caused by the *C. trachomatis* is the most frequently reported STD's worldwide, with the highest prevalence in aged category of 25 years (CDC, 2009). In women*, C. trachomatis* has been shown to cause both lower and upper genital tract

*Chlamydia trachomatis* Infections of the Adults 41

North America, but outbreaks have occurred. A herpetiform primary lesion develops at the site of invasion in the genital area, which then becomes an ulcus with accompanying lymphadenitis. Laboratory diagnosis is based on isolating the proliferating pathogen in cell cultures from purulent material obtained from the ulcus or from matted lymph nodes. The antibodies can be identified using the complement binding reaction or the

*C. trachomatis* is a biosafety level 2 agent and should be handled appropriately, although it is not considered a particularly dangerous pathogen. *C. trachomatis* urogenital infection in women can be diagnosed by testing urine or by collecting swab specimens from the endocervix or vagina. Diagnosis of *C. trachomatis* urethral infection in men can be made by testing a urethral swab or urine specimen. Rectal *C. trachomatis* infections in persons that engage in receptive anal intercourse can be diagnosed by testing a rectal swab specimen.

Today, culture-independent tests have revolutionized chlamydia diagnostics. Comercially available antigen detection methods and nucleic acid hybridization tests, when introduced in the 1980s, largely replaced the technically more demanding isolation

Although originally chlamydia was grown in embroyonated chicken eggs, growth and detection of chlamydia is now accomplished by staining of chlamydial inclusions grown in tissue culture cells. The cell line the most commonly used is McCoy cells**.** The other cell lines have been used as well as monkey kidney, HeLa, and HEp-2. It is confirmed that the culture is technically difficult and has been shown to be not as sensitive as previously thought**.** Recent studies have indicated that culture sensitivity compared to molecular techniques can range from 50-100%, while specificity is considered to be nearly 100%

Other non-culture diagnostic tests include: direct cytological examination, direct fluorescent

Cytology was used to detect chlamydial infections before more sensitive tests were developed. Specimens obtained from the genital tract were diagnosed for the presence/absence of inclusion bodies. The sensitivity of cytology testing is very low with

DFA using commercial monoclonal antibodies which detect the major outer membrane protein (MOMP) of *C. trachomatis*, which stains only this organism. The test involves the specimen swab being rolled onto a glass slide air dried and fixed with methanol. Fluorescein-conjugated monoclonal antibody is applied to the slide, which after incubation is mounted in mounting medium, coverslipped and read for the presence of EBs with a

antibody (DFA) test and antigen detection using the enzyme immunoassay (EIA).

Tetracyclines and macrolides are the potentially useful antibiotic types.

**8. Laboratory diagnostics of** *Chlamydia trachomatis*

microimmunofluorescence test.

procedures (table 3.).

(Van Der Pol et al., 2001).

**8.2 Non-culture diagnostic test**

only 20% cases being detected.

**8.1 Culture**

infections. Untreated, chlamydial infection can lead to severe reproductive complications. Chlamydia is known as the "silent epidemic" because in women, it may not cause any symptoms in 75% of cases, and can linger for months or years before being discovered. Symptoms that may occur include unusual vaginal bleeding or discharge, pain in the abdomen, painful sexual intercourse (dyspareunia), fever, painful urination or the urge to urinate more frequently than usual (urinary urgency).

*C trachomatis* is an important causal agent in pelvic inflammatory disease, with sequelae including infertility, ectopic pregnancy, and chronic pelvic pain. Up to two thirds of cases of tubal-factor infertility and one third of cases of ectopic pregnancy may be attributable to *C. trachomatis* infection.

Chlamydial infection during pregnancy is associated with a number of adverse outcomes of pregnancy including preterm labor, premature rupture of the membranes, low birth weight, neonatal death, and postpartum endometritis. Chlamydial infection during pregnancy may be transmitted to the infant during delivery.

An infant born to a mother with active infection has a risk of acquiring infection at any anatomical site of 50 to 75%. Approximately 30 to 50% of infants born to chlamydia-positive mothers will have conjunctivitis, and at least 50 percent of infants with chlamydial conjunctivitis will also have nasopharyngeal infection. Chlamydial pneumonia develops in about 30% of infants with nasopharyngeal infection.

#### **7.3.2 Genital infections in men**

In men, the most common clinical manifestation of *C. trachomatis* infection is nongonococcal urethritis. In fact, *C. trachomatis* causes approximately 35 to 50 % of all cases of nongonococcal urethritis in heterosexual men. Symptoms of nongonococcal urethritis may develop after an incubation period of 7 to 21 days and include dysuria and mild-tomoderate whitish or clear urethral discharge. In most cases, physical examination reveals no abnormalities other than the discharge. Other clinical syndromes in men include acute epididymitis, acute proctitis, acute proctocolitis, conjunctivitis, and Reiter's syndrome. Male infertility, chronic prostatitis, and urethral strictures are possible results of infection. Both Reiter's syndrome (urethritis, conjunctivitis, arthritis, and mucocutaneous lesions) and reactive tenosynovitis or arthritis (without the other components of Reiter's syndrome) have been associated with genital *C. trachomatis* infection. Infection with *C. trachomatis* is also believed to be a cofactor for the transmission of human immunodeficiency virus in both men and women (Nelson & Helfand, 2001).

 If left untreated, it is possible for chlamydia in men to spread to the testicles causing epididymitis, which in rare cases can cause sterility if not treated within 6 to 8 weeks. Chlamydia is also a potential cause of prostatitis in men, although the exact relevance in prostatitis is difficult to ascertain due to possible contamination from urethritis.

#### **7.4 Lymphogranuloma venereum**

Lymphogranuloma venereum-LGV is distinct venereal disease caused by three serotypes of *C. trachomatis* that are not associated with other chlamydial infections.

Lymphogranuloma venereum is frequently observed in the inhabitants of warm climatic zones and occurs principally in South America and Africa. The disease is uncommon in North America, but outbreaks have occurred. A herpetiform primary lesion develops at the site of invasion in the genital area, which then becomes an ulcus with accompanying lymphadenitis. Laboratory diagnosis is based on isolating the proliferating pathogen in cell cultures from purulent material obtained from the ulcus or from matted lymph nodes. The antibodies can be identified using the complement binding reaction or the microimmunofluorescence test.

Tetracyclines and macrolides are the potentially useful antibiotic types.

## **8. Laboratory diagnostics of** *Chlamydia trachomatis*

*C. trachomatis* is a biosafety level 2 agent and should be handled appropriately, although it is not considered a particularly dangerous pathogen. *C. trachomatis* urogenital infection in women can be diagnosed by testing urine or by collecting swab specimens from the endocervix or vagina. Diagnosis of *C. trachomatis* urethral infection in men can be made by testing a urethral swab or urine specimen. Rectal *C. trachomatis* infections in persons that engage in receptive anal intercourse can be diagnosed by testing a rectal swab specimen.

Today, culture-independent tests have revolutionized chlamydia diagnostics. Comercially available antigen detection methods and nucleic acid hybridization tests, when introduced in the 1980s, largely replaced the technically more demanding isolation procedures (table 3.).

#### **8.1 Culture**

40 Sexually Transmitted Infections

infections. Untreated, chlamydial infection can lead to severe reproductive complications. Chlamydia is known as the "silent epidemic" because in women, it may not cause any symptoms in 75% of cases, and can linger for months or years before being discovered. Symptoms that may occur include unusual vaginal bleeding or discharge, pain in the abdomen, painful sexual intercourse (dyspareunia), fever, painful urination or the urge to

*C trachomatis* is an important causal agent in pelvic inflammatory disease, with sequelae including infertility, ectopic pregnancy, and chronic pelvic pain. Up to two thirds of cases of tubal-factor infertility and one third of cases of ectopic pregnancy may be attributable to *C.*

Chlamydial infection during pregnancy is associated with a number of adverse outcomes of pregnancy including preterm labor, premature rupture of the membranes, low birth weight, neonatal death, and postpartum endometritis. Chlamydial infection during pregnancy may

An infant born to a mother with active infection has a risk of acquiring infection at any anatomical site of 50 to 75%. Approximately 30 to 50% of infants born to chlamydia-positive mothers will have conjunctivitis, and at least 50 percent of infants with chlamydial conjunctivitis will also have nasopharyngeal infection. Chlamydial pneumonia develops in

In men, the most common clinical manifestation of *C. trachomatis* infection is nongonococcal urethritis. In fact, *C. trachomatis* causes approximately 35 to 50 % of all cases of nongonococcal urethritis in heterosexual men. Symptoms of nongonococcal urethritis may develop after an incubation period of 7 to 21 days and include dysuria and mild-tomoderate whitish or clear urethral discharge. In most cases, physical examination reveals no abnormalities other than the discharge. Other clinical syndromes in men include acute epididymitis, acute proctitis, acute proctocolitis, conjunctivitis, and Reiter's syndrome. Male infertility, chronic prostatitis, and urethral strictures are possible results of infection. Both Reiter's syndrome (urethritis, conjunctivitis, arthritis, and mucocutaneous lesions) and reactive tenosynovitis or arthritis (without the other components of Reiter's syndrome) have been associated with genital *C. trachomatis* infection. Infection with *C. trachomatis* is also believed to be a cofactor for the transmission of human immunodeficiency virus in both men

 If left untreated, it is possible for chlamydia in men to spread to the testicles causing epididymitis, which in rare cases can cause sterility if not treated within 6 to 8 weeks. Chlamydia is also a potential cause of prostatitis in men, although the exact relevance in

Lymphogranuloma venereum-LGV is distinct venereal disease caused by three serotypes of

Lymphogranuloma venereum is frequently observed in the inhabitants of warm climatic zones and occurs principally in South America and Africa. The disease is uncommon in

prostatitis is difficult to ascertain due to possible contamination from urethritis.

*C. trachomatis* that are not associated with other chlamydial infections.

urinate more frequently than usual (urinary urgency).

be transmitted to the infant during delivery.

**7.3.2 Genital infections in men**

and women (Nelson & Helfand, 2001).

**7.4 Lymphogranuloma venereum**

about 30% of infants with nasopharyngeal infection.

*trachomatis* infection.

Although originally chlamydia was grown in embroyonated chicken eggs, growth and detection of chlamydia is now accomplished by staining of chlamydial inclusions grown in tissue culture cells. The cell line the most commonly used is McCoy cells**.** The other cell lines have been used as well as monkey kidney, HeLa, and HEp-2. It is confirmed that the culture is technically difficult and has been shown to be not as sensitive as previously thought**.** Recent studies have indicated that culture sensitivity compared to molecular techniques can range from 50-100%, while specificity is considered to be nearly 100% (Van Der Pol et al., 2001).

#### **8.2 Non-culture diagnostic test**

Other non-culture diagnostic tests include: direct cytological examination, direct fluorescent antibody (DFA) test and antigen detection using the enzyme immunoassay (EIA).

Cytology was used to detect chlamydial infections before more sensitive tests were developed. Specimens obtained from the genital tract were diagnosed for the presence/absence of inclusion bodies. The sensitivity of cytology testing is very low with only 20% cases being detected.

DFA using commercial monoclonal antibodies which detect the major outer membrane protein (MOMP) of *C. trachomatis*, which stains only this organism. The test involves the specimen swab being rolled onto a glass slide air dried and fixed with methanol. Fluorescein-conjugated monoclonal antibody is applied to the slide, which after incubation is mounted in mounting medium, coverslipped and read for the presence of EBs with a

*Chlamydia trachomatis* Infections of the Adults 43

The diagnosis of genital chlamydial infections evolved rapidly from the 1990s. The most important advance came from the introduction of nucleic acid amplification tests (NAATs), such as polymerase chain reaction (PCR), transcription mediated amplification (TMA), and the DNA strand displacement amplification (SDA). NAATs for chlamydia may be performed on swab specimens collected from the cervix (women) or urethra (men), on selfcollected vaginal swabs, or on voided urine. Urine and self-collected swab testing facilitates the performance of screening tests in settings where genital examination is impractical. At present, the NAATs have regulatory approval only for testing urogenital specimens, although rapidly evolving research indicates that they may give reliable results on rectal specimens.The most sensitive and accurate of the non-culture tests are the NAATs and are highly specific, as well. Because they can be used with noninvasively collected specimens such as first catch urines from either sex, or vaginal swabs, NAATs are well suited for screening as well as diagnosis. There are several types of NAATs. The two most commonly used tests are the PCR and LCR tests. These tests offer greatly expanded sensitivities of detection, usually well above 90%, while maintaining very high specificity. Choice of test is mainly dependent upon cost and preference of the laboratory, as all of these NAATs are

Because NAATs detect DNA and RNA targets, they do not require viable organisms to

Chlamydial infections are often asymptomatic, so diagnosis generally requires chlamydiaspecific laboratory test identification or confirmation. Treating infected patients prevents sexual transmission of the disease, and treating all sexual partners of those testing positive for Chlamydia can prevent reinfection of the index patient and infection of other partners. There is no universally accepted protocol for testing the antibiotic susceptibility of *C. trachomatis*. Because of the unique intracellular characteristics of *C. trachomatis*, only certain antibiotics are effective in treatment. The CDC treatment guidelines for chlamydial

**8.4 New molecular diagnostic tests for detection of** *C. trachomatis*

closely comparable in sensitivity and specificity (Gaydos et al., 2004).

infections are summarized in tables 4. and 5. (CDC, 2009).

Azithromycin 1 g orally in a single dose

Doxycycline 100 mg orally twice a day for 7 days

Levofloxacin 500 mg orally once a day for 7 days

Ofloxacin 300 mg orally twice a day for 7 days

Table 4. Recommended regimens (CDC, 2009).

Erythromycin base 500 mg orally four times a day for 7 days

Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days

Recommended Regimens

Alternative Regimens

detect infection.

or

Or

Or

Or

**9. Diagnosis and treatment**

fluorescent microscope under 1,000 x. The test requires the experience of a trained microscopist and has a sensitivity of 80-85% with specificity of 98-99% compared to culture (Mahoney &Chernesky, 2003).

EIA was the one of the earliest non-culture developed tests. EIA was widely used before the advent of molecular tests and is still used as the most prevalent non-culture detection test for chlamydia (Gaydos et al., 1990).There are several EIAs commercially available using either polyclonal or monoclonal antibodies to detect chlamydia LPS. The sensitivity of the EIAs range from approximately 53-76%, with specificities of about 95%, especially when antibody blocking confirmatory assays is used to confirm the positive EIA result.

Because older non-culture tests, such as DFA and EIA, were traditionally compared to culture as a gold standard, the sensitivities reported in the older literature can no longer be viewed as accurate. The antigen detection techniques are generally less expensive and easier to perform than newer molecular tests.

## **8.3 Serology**

The microimmunofluorescence test (MIF) has been the gold standard test for the detection of antibody for Chlamydia (Wang et al., 1985). The assay is useful for population studies but is not useful for the diagnosis of active *C. trachomatis* ocular or urogenital disease.

Table 3. Sensitivity and specificity of diagnostic tests for the detection of *Chlamydia trachomatis.*

fluorescent microscope under 1,000 x. The test requires the experience of a trained microscopist and has a sensitivity of 80-85% with specificity of 98-99% compared to culture

> 94.4-96.4% 93-98% 96.4%

89.7% 89.2% 90.3%

92.8% 80.5% 93.1%

94.2% 94.7% 97% 95.2%

Table 3. Sensitivity and specificity of diagnostic tests for the detection of *Chlamydia*

antibody blocking confirmatory assays is used to confirm the positive EIA result.

not useful for the diagnosis of active *C. trachomatis* ocular or urogenital disease.

EIA was the one of the earliest non-culture developed tests. EIA was widely used before the advent of molecular tests and is still used as the most prevalent non-culture detection test for chlamydia (Gaydos et al., 1990).There are several EIAs commercially available using either polyclonal or monoclonal antibodies to detect chlamydia LPS. The sensitivity of the EIAs range from approximately 53-76%, with specificities of about 95%, especially when

Because older non-culture tests, such as DFA and EIA, were traditionally compared to culture as a gold standard, the sensitivities reported in the older literature can no longer be viewed as accurate. The antigen detection techniques are generally less expensive and easier

The microimmunofluorescence test (MIF) has been the gold standard test for the detection of antibody for Chlamydia (Wang et al., 1985). The assay is useful for population studies but is

99.5-100% 99-100% 94-100%

99.4% 99.0% 98.4%

98.1% 98.4% 93.8%

97.6% 98.9% 99.1% 98.2%

Diagnostic method Sensitivity Specificity Tissue Culture 70-85% 100% Direct Fluorescence Assay 80-85% >99% Enzyme Immunoassay 53-76% 95% Hybridization (Pace 2) 65-83% 99%

(Mahoney &Chernesky, 2003).

Ligase Chain Reaction

Polymerase Chain Reaction (COBAS)

Strand Displacement Amplification

Transcriptional Mediated Amplification

to perform than newer molecular tests.

Cervical Female Urine Male Urine

Cervical Female Urine Male Urine

Cervical Female Urine Male Urine

Cervical Female Urine Male Urine Male Urethral

*trachomatis.*

**8.3 Serology**

#### **8.4 New molecular diagnostic tests for detection of** *C. trachomatis*

The diagnosis of genital chlamydial infections evolved rapidly from the 1990s. The most important advance came from the introduction of nucleic acid amplification tests (NAATs), such as polymerase chain reaction (PCR), transcription mediated amplification (TMA), and the DNA strand displacement amplification (SDA). NAATs for chlamydia may be performed on swab specimens collected from the cervix (women) or urethra (men), on selfcollected vaginal swabs, or on voided urine. Urine and self-collected swab testing facilitates the performance of screening tests in settings where genital examination is impractical. At present, the NAATs have regulatory approval only for testing urogenital specimens, although rapidly evolving research indicates that they may give reliable results on rectal specimens.The most sensitive and accurate of the non-culture tests are the NAATs and are highly specific, as well. Because they can be used with noninvasively collected specimens such as first catch urines from either sex, or vaginal swabs, NAATs are well suited for screening as well as diagnosis. There are several types of NAATs. The two most commonly used tests are the PCR and LCR tests. These tests offer greatly expanded sensitivities of detection, usually well above 90%, while maintaining very high specificity. Choice of test is mainly dependent upon cost and preference of the laboratory, as all of these NAATs are closely comparable in sensitivity and specificity (Gaydos et al., 2004).

Because NAATs detect DNA and RNA targets, they do not require viable organisms to detect infection.

## **9. Diagnosis and treatment**

Chlamydial infections are often asymptomatic, so diagnosis generally requires chlamydiaspecific laboratory test identification or confirmation. Treating infected patients prevents sexual transmission of the disease, and treating all sexual partners of those testing positive for Chlamydia can prevent reinfection of the index patient and infection of other partners. There is no universally accepted protocol for testing the antibiotic susceptibility of *C. trachomatis*. Because of the unique intracellular characteristics of *C. trachomatis*, only certain antibiotics are effective in treatment. The CDC treatment guidelines for chlamydial infections are summarized in tables 4. and 5. (CDC, 2009).

Table 4. Recommended regimens (CDC, 2009).

*Chlamydia trachomatis* Infections of the Adults 45

levels of testing among females and males make an important reservoir for chlamydial

It is clear that single infections will not result in solid immunity to reinfection. Multiple

Unfortunately, the natural infection is not readily quantifiable in terms of inoculum size, and thus relative degrees of immunity may exist which are overcome with a sufficiently

In screening studies, younger women are found to have higher cervical infection rates than older women, who often have higher antibody levels. In addition, many isolate-negative individuals attending STD clinics have IgM to the organism. This antibody may result from recent exposure and rapid resolution of the infection or its ablation by an immune response. Having in mind that many chlamydial infections are asymptomatic, it has become clear that

Centers for Disease Control and Prevention. (1997). Chlamydia trachomatis, In: *Genital*

Centers for Disease Control and Prevention.( 2002*). Sexually Transmitted Disease Treatment*

Centers for Diseases Control and Prevention. (2004). Trends in reportable sexually

Centers for Diseases Control and Prevention. (2008). *Sexually Transmitted Diseases*

Eng, TR. & Butler, WT. (1997). The neglected health and economic impact of STDs, In: *The*

Gaydos, CA.; Reichart, C. & Long, J. ( 1990). Evaluation of syva enzyme immunoassay for

Gaydos, CA.; Theodore, M. & Dalesio, N. ( 2004). Comparison of three nucleic acid

Gerbes, AC.; Rowley, JT. & Heymann DHL. (1996). Global prevalence and incidence estimates of selected curable STDs*. Sex Transm Infect*, Vol.74, pp.S12-S16. Groseclose, SL.; Zaidi, AA. & DeLisle, SJ. (1996). Estimated Incidence and prevalence of

Jocobson, DL.; Peralta, L.& Graham, NM. (2000). Histologic development of cervical ectopy: relationship to reproductive hormones. *Sex Transm Dis* , Vol. 27, pp. 252-258.

transmitted diseases in the United States, 2004*: National surveillance data for Chlamydia*, *gonorrhoea and syphilis*. Atlanta, GA: Centers for Disease Control and Prevention, 2005. Available from: http://www.cdc.gov/std/stats. Accessed Nov,

*Hidden Epidemic, Confronting Sexually transmitted Diseases*, (Ed.), 28-68, National

detection of Chlamydia trachomatis in genital specimens. *J Clin Microbiol*, Vol. 28,

amplification tests for detection of Chlamydia trachomatis in urine specimens*. J*

genital Chlamydia trachomatis infections in the United States. *Sex Transm Dis*, Vol

infection. Immunity induced by chlamydial infection is not well understood.

effective control must involve periodic testing of individuals at risk.

*Guidelines.* MMWR,Vol. 51, No.RR-6, pp.:1-78.

Academy Press, Washington, D.C.

*Clin Microbiol*, Vol. 42, pp. 3041-3045.

*Infection*-United States. MMWR, Vol.46, No.9, pp.193-198.

Atlanta, GA: US Department of Health and Human Services, CDC; 2009.

infections, homo- or heterotypic, are common.

large challenge.

**13. References**

24,2006

*Surveillance*.

pp.1541-1544.

26, pp.339-344.

Table 5. Recommended regimens in pregnancy (CDC, 2009**).**

## **10. Follow-up**

The validity of chlamydial diagnostic testing at <3 weeks after completion of therapy has not been established. False-negative results might occur in the presence of persistent infections involving limited numbers of chlamydial organisms, as well as false-positive results because of the continued presence of nonviable organisms.

In addition, NAATs conducted at <3 weeks after completion of therapy in persons who were treated successfully could yield false-positive results because oh the continued presence of nonviable organisms (CDC, 2009). Routine repeat testing is also encouraged at every other examination done 3-12 months after treatment regardless of whether the patient believes that her sex partner(s) was treated.

## **11. Recommendations for chlamydial screening and re-screening**

In the United States, the CDC recommends that all sexually active adolescent women should be screened for chlamydia infection at least annually, even if symptoms are not present. Also recommended is annually screening of sexually active women 20-25 years of age and older women with risk factors such as a new sex partner or multiple sex partners.

Since the risk of re-infections is very high, especially in women, the CDC recommends that previously infected women are at a high risk and constitute a priority for repeat testing and should be re-screened 3-4 months after treatment.

## **12. Conclusion**

*Chlamydia trachomatis* has been recognized as a genital pathogen responsible for an increasing variety of clinical syndromes. CT infection is the STD most strongly associated with adolescents. Adolescents, young women and men are consistently at higher risk of being infected with chlamydia than others. The high level of asymptomaticity and the low levels of testing among females and males make an important reservoir for chlamydial infection. Immunity induced by chlamydial infection is not well understood.

It is clear that single infections will not result in solid immunity to reinfection. Multiple infections, homo- or heterotypic, are common.

Unfortunately, the natural infection is not readily quantifiable in terms of inoculum size, and thus relative degrees of immunity may exist which are overcome with a sufficiently large challenge.

In screening studies, younger women are found to have higher cervical infection rates than older women, who often have higher antibody levels. In addition, many isolate-negative individuals attending STD clinics have IgM to the organism. This antibody may result from recent exposure and rapid resolution of the infection or its ablation by an immune response.

Having in mind that many chlamydial infections are asymptomatic, it has become clear that effective control must involve periodic testing of individuals at risk.

## **13. References**

44 Sexually Transmitted Infections

Recommended regimens

Alternative regimens

Or

Or

Or

Or

**10. Follow-up**

**12. Conclusion**

Azithromycin 1 g orally in a single dose

500 mg orally four times a day for 7 days

Table 5. Recommended regimens in pregnancy (CDC, 2009**).**

results because of the continued presence of nonviable organisms.

**11.

Amoxicillin 500 mg orally three times a doa for 7 days

Erythromycin base 500 mg orally four times a day for 7 days

Erythromycin base 250 mg orally four times a day for 14 days

Erythromycin ethylsuccinate 800 mg orally four times a day for 7 daysbase

The validity of chlamydial diagnostic testing at <3 weeks after completion of therapy has not been established. False-negative results might occur in the presence of persistent infections involving limited numbers of chlamydial organisms, as well as false-positive

In addition, NAATs conducted at <3 weeks after completion of therapy in persons who were treated successfully could yield false-positive results because oh the continued presence of nonviable organisms (CDC, 2009). Routine repeat testing is also encouraged at every other examination done 3-12 months after treatment regardless of whether the patient

In the United States, the CDC recommends that all sexually active adolescent women should be screened for chlamydia infection at least annually, even if symptoms are not present. Also recommended is annually screening of sexually active women 20-25 years of age and

Since the risk of re-infections is very high, especially in women, the CDC recommends that previously infected women are at a high risk and constitute a priority for repeat testing and

*Chlamydia trachomatis* has been recognized as a genital pathogen responsible for an increasing variety of clinical syndromes. CT infection is the STD most strongly associated with adolescents. Adolescents, young women and men are consistently at higher risk of being infected with chlamydia than others. The high level of asymptomaticity and the low

Erythromycin ethylsuccinate 400 mg orally four times a day for 14 days

**3**

**Gonorrhea in Men Sex**

*Faculty of Pharmacy and Biochemistry*

*University of Buenos Aires*

*Argentina*

**Men and Heterosexual Men**

Ángela María Rosa Famiglietti and Susana Diana García

Gonorrhea is a sexually transmitted infectious disease known since ancient times, with biblical (Old Testament) references. The etiologic agent is *Neisseria gonorrhoeae,* commonly called gonococcus. *N. gonorrhoeae* has accumulated mechanisms of antimicrobial resistance so that from the year 2007 it joined the list of multi-resistant, informally called "Superbugs"

*Neisseria gonorrhoeae* was described by Neisser in 1879 and first cultivated in 1882 by Leistikow and Loeffler. At this time, members of the genus *Neisseria* are classified in the family *Neisseriaceae* with the genera *Kingella*, *Eikenella*, *Simonsiella*, and *Alysiella*. This family is now placed in the β-subgroup of the Phylum *Proteobacteria* (Janda and Gaydos *in* Manual

*N. gonorrhoeae* is a gram-negative diplococci with adjacent sides flattened, like coffee beans, do not form spores, oxidizes dimethil or tetramethil-phenylenediamine (oxidase test positive) and catalase positive (superoxol test with 30% H2O2); not to reduce nitrites. It may grow optimally at 35-37ºC, but it's unable to grow at low temperature (22ºC). The most of gonococcus have an obligate requirement for CO2 (5%) and humidity of 70-80%, it does not tolerate drying out. Clinical specimens should be collected with Dacron or rayon swabs. These swabs should be inoculated immediately on appropriate media. Calcium alginate may have inhibitory effect and cotton swabs contain fatty acids that inhibit the growth of gonococci. *N. gonorrhoeae* grows on selective media, modified Thayer Martin, as *Neisseria meningitidis.* Cysteine is an essential aminoacid for their growth. Some strains have specific requirements of certain amino acids, pyrimidines and purines as a result of defective or altered biosynthetic pathways. These particular nutritional requirements form the basis for a typing method for gonococci called auxotyping. *N. gonorrhoeae* differs from other species of the genus by oxidizing glucose and do not use maltose, sucrose, lactose or fructose in cysteine-tryptic digest semisolid agar-base medium (CTA) containing 1% carbohydrate and a phenol red pH indicator, or rapid carbohydrate test; not to reduce nitrites and their

(Shafer *in Neisseria* Molecular Mechanisms of Pathogenesis, 2010).

**1. Introduction**

**1.1 General description**

of Clinical Microbiology, 2007).

inability to grow at low temperatures (22ºC).

## **Gonorrhea in Men Sex Men and Heterosexual Men**

Ángela María Rosa Famiglietti and Susana Diana García

*Faculty of Pharmacy and Biochemistry University of Buenos Aires Argentina*

## **1. Introduction**

46 Sexually Transmitted Infections

Jones, RB. (1995). Chlamydia trachomatis (trachoma, perinatal infections, lymphogranuloma

Mahoney, JB. & Chernesky, MA. (2003). *Chlamydia and Chalymydophila*, In: Murray, PR.,

Miller, WC. ; Ford, CA.& Morris, M. (2004). Prevalence of chlamydial and gonococcal

Nelson, HD.& Helfand, M. (2001). Screening for chlamydial infection. *Am J Prev Med*, Vol.

Pudjitamoko, H., Fukushi, Y. & Ochiai, Y. (1997). Phylogenetic analysis of the genus

Quinn, TC. ; Gaydos, C.& Shepard, L. (1996). Epidemiologic and microbiologic correlates of

Scholes, D.; Stergachis, A.& Heindrich, FE. (1996). Prevention of pelvic inflammatory disease by screening for cervical chlamydial infection*. N Engl J Med*, Vol.334, pp. 1362-6. Stamm WE. (1999). Chlamydia trachomatis infections of the adult, In: KK Holmes, KK.,

Sweet ,WC.& Gibbs, RS. (2002). Chlamydial infections. In: Sweet, RL., Gibbs, RS., *Infectious*

Van de Hoek, A. (1999). STDs, HIV/AIDS, ethnicity, and migrant populations*.* In: Aral, SO.,

Van Der Pol, BD., Ferrero, L. & Buck-Barrington, E. (2001). Multicenter evaluation of the BD

Wang, SP., Kuo, CC & *Barnes RC. (1985). Immunotyping of Chlamydia trachomatis with*

Westrom, L.& Eschenbach, D. (1999). Pelvic inflammatory disease. In: Holmes, KK., Mardh,

World Health Organization. (2001). *Global prevalence and incidence of selected curable sexually transmitted infections: overview and estimates*. Geneva: World Health Organization World Health Organization. (2002). "Global data on visual impairment in the year 2002". *Bull World Health Organ,* Vol. 82, pp. 844–851.Geneva: World Health Organization

Livingstone

20, pp. 95-107.

Hill, New York

Williams & Wilkins

York:McGraw-Hill

McGrow-Hill

swabs*. J Clin Microbiol*, Vol.39, pp. 108-1016.

*monoclonal antibodies. J infect Dis*, Vol. 152, pp. 791-800.

431.

Press, Washington, DC.

venereum and other genital infections), In: V: Mandel, GL.; Bennet, JE., & Dolin, R. ur. *Principles and practise of Infections diseases*, pp. 1679-1693. New York. Churchill

Barron, EJ. & Jorgensen, JH. *Manual of Clinical microbiology*, (Ed.), 991-1004, ASM

infections among young adults in the United States. *JAMA*, Vol. 291, pp. 2229-2236

Chlamydia based on 16S rRNA gene sequences.  *JAMA*, Vol. 276, pp.1737-1742.

Sparling, PF. & Mardh, PA. *Sexually Transmitted Diseases*, (Ed.), 407-422, Mc-Graw-

*Diseases of the Female Genital Tract,* (4 th Ed.), 57-100, Philadelphia, PA: Lippincott

Sparling, PF.& Mardh, PA. *Sexually Transmitted Diseases*, (Ed.), 163-70, New

ProbeTec ET System for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine specimens, female endocervical swabs, and male urethral

PA. & Sparling, PF.*Sexually Transmitted Diseases*., (3rd ed.), 783-809, New York, NY:

Gonorrhea is a sexually transmitted infectious disease known since ancient times, with biblical (Old Testament) references. The etiologic agent is *Neisseria gonorrhoeae,* commonly called gonococcus. *N. gonorrhoeae* has accumulated mechanisms of antimicrobial resistance so that from the year 2007 it joined the list of multi-resistant, informally called "Superbugs" (Shafer *in Neisseria* Molecular Mechanisms of Pathogenesis, 2010).

### **1.1 General description**

*Neisseria gonorrhoeae* was described by Neisser in 1879 and first cultivated in 1882 by Leistikow and Loeffler. At this time, members of the genus *Neisseria* are classified in the family *Neisseriaceae* with the genera *Kingella*, *Eikenella*, *Simonsiella*, and *Alysiella*. This family is now placed in the β-subgroup of the Phylum *Proteobacteria* (Janda and Gaydos *in* Manual of Clinical Microbiology, 2007).

*N. gonorrhoeae* is a gram-negative diplococci with adjacent sides flattened, like coffee beans, do not form spores, oxidizes dimethil or tetramethil-phenylenediamine (oxidase test positive) and catalase positive (superoxol test with 30% H2O2); not to reduce nitrites. It may grow optimally at 35-37ºC, but it's unable to grow at low temperature (22ºC). The most of gonococcus have an obligate requirement for CO2 (5%) and humidity of 70-80%, it does not tolerate drying out. Clinical specimens should be collected with Dacron or rayon swabs. These swabs should be inoculated immediately on appropriate media. Calcium alginate may have inhibitory effect and cotton swabs contain fatty acids that inhibit the growth of gonococci. *N. gonorrhoeae* grows on selective media, modified Thayer Martin, as *Neisseria meningitidis.* Cysteine is an essential aminoacid for their growth. Some strains have specific requirements of certain amino acids, pyrimidines and purines as a result of defective or altered biosynthetic pathways. These particular nutritional requirements form the basis for a typing method for gonococci called auxotyping. *N. gonorrhoeae* differs from other species of the genus by oxidizing glucose and do not use maltose, sucrose, lactose or fructose in cysteine-tryptic digest semisolid agar-base medium (CTA) containing 1% carbohydrate and a phenol red pH indicator, or rapid carbohydrate test; not to reduce nitrites and their inability to grow at low temperatures (22ºC).

Gonorrhea in Men Sex Men and Heterosexual Men 49

performed culture.  The assay may be divided into three types: (i) direct detection probe hybridization to the target nucleic acid with direct detection of the hybrid; (ii) nucleic acid amplification tests (NAATs); and (iii) amplified-signal probe test, which hybridize with nucleic acid and then amplify the signal of the probe. These assays are generally much more sensitive that culture and are highly specific for urogenital infections, however, depending on the assay used (e.g. PCR) some concerns have arisen about the specificity of these tests from other anatomic sites. The advantages of the test are specimens may be transportes from geographically distant areas and stored for several days prior to testing. The NAATs also allow use non-invasive specimen types such as urine and vaginal swabs. The disadvantages of using nonculture nucleic acid probe or amplification tests include unavailability of a viable isolate for antimicrobial susceptibility testing and the possibility of a positive test after treatment, since nucleic acids from organism may persist

Gonococcal infection is more common among young persons, particularly those aged 15-24 years, persons with lower socio-economic status, men who have sex with men (MSM), illicit

Gonococcal infections are among the most common reportable infections around the World. In the Unite Stated, gonorrhea is consistently the second-most frequently reported notifiable

In the United States, some European countries and Australia, the incidence of gonorrhea decreased at the end of the 1.980s to mid of 1.990s it was mainly attributed to changes in sexual behaviour produced after the appearance of HIV and the introduction of fluoroquinolone treatment (Famiglietti, 2000; Griemberg, 1997; Trotter *in Neisseria* Molecular

Gonococcal infection has increased over previous years, although not consistently in all countries. In the United States the incidence of gonorrhea in recent years shows an upward

The World Health Organization (WHO) estimated that, globally, there were 62 million new cases of gonorrhea in 1999, with 27 million (44%) in South and South-East Asia, 17 million (27%) in Sub-Saharan Africa and 7.5 million (12%) in Latin America and the Caribbean

The penicillin introduction by the end of 1940s led to the eradication of *N. gonorrhoeae* sulfonamides resistant and it was the antimicrobial agent that kept its effectiveness for nearly forty years (approximately 1945-1985), although it required increasing the dose in

trend, while the rate of gonorrhea in 2009 decreased 10.5% respect 2008 (Diez, 2011).

**2.1** *Neisseria gonorrhoeae***: Antimicrobial resistance and clinic impact**

drug users, commercial workers an racial/ethnic minority groups (Barry, 2009).

infection with more than 350,000 reported in 2006 (Barry, 2009; CDC, 2006).

of *N. gonorrhoeae* from body sites harboring an endogenous bacterial flora.

for a period of time after successful therapy (Barry, 2009).

**1.4 Epidemiology of gonococcal infections**

Mechanisms of Pathogenesis, 2010).

(WHO, 2001).

**2. Currents problems**

The use of enzyme substrates that demonstrate the presence of prolyl-hydroxyprolyl aminopeptidase and the abscense of β-galactosidase and γ-glutamyl aminopeptidase also to confirm the identification. Currently there are commercially available rapid tests to confirm the isolation of *N. gonorrhoeae* such as immune reactions by using fluorescent monoclonal antibodies or coagglutination tests, as well as molecular techniques using specific probes or specific primers **(**Janda and Gaydos *in* Manual of Clinical Microbiology, 2007).

## **1.2 Transmission and clinical manifestations**

*N. gonorrhoeae* is an exclusive human pathogen and this is their only reservoir. The transmission is from person to person through sexual intercourse, so the primary infection in adults is installed in the genital area, anal and/ or pharynx, where there is susceptible epithelium: cubic or cylindrical not stratified.

In males, *N. gonorrhoeae* causes an acute urethritis with dysuria and urethral discharge. The incubation period averages 2 to 7 days. About 2.5 to 5 % of men are asyntomatic. Complications of untreated gonococcal urethritis are: epididymitis, periurethral abscesses, infections of the Tyson's glands and Cowper's glands, orchitis and prostatitis (Janda and Gaydos *in* Manual of Clinical Microbiology, 2007). In women, gonococcal infections cause cervicitis, only approximately half of which occur with symptoms and which can go on to cause pelvic inflammatory disease, ectopic pregnancies, and infertility. In addition, in both men and women exposed orally or anally, gonococcal infections can cause a predominantly asyntomatic pharyngiti*s* or proctitis. Less commonly, *N. gonorrhoeae* can cause conjunctivitis, endocarditis, tenosynovitis, arthritis, meningitis, inflammation of the liver capsule and disseminated blood stream infections (Barry, 2009).

Conjunctival infection occurs in adult and neonatal by accidental inoculation or contamination in the birth canal and causes ophthalmia neonatorum, which if not treated properly can lead to blindness (Marrazo *in* Principle and Practice of Infections Disease, 2010).

Asymptomatic infection in women has been linked to the biofilm production, which includes nature complex mixes of exopolysaccharides, proteins and DNA. Bacteria living in biofilms are more resistant to biocides and antimicrobial agents. Also, the horizontal transfer of resistance genes is more likely and increases the spread of resistance genes (Apicella *in Neisseria* Molecular Mechanisms of Pathogenesis, 2010). Gonococcal infection may facilite transmission of human immunodeficiency virus (HIV), increasing the number of target cells for HIV in the inflammatory exudate present in symptomatic patients (Bala, 2010)

## **1.3 Diagnosis of gonococcal infections**

Diagnosis of gonococcal infection has historically been a combination of clinical signs and symptoms plus the microbiologic study. The diagnosis of urethritis in men can be made by observing gram-negative intracellular diplococci associated with polymorphonuclear leukocites on a smear prepared from the urethral discharge. The Gram stain has a sensitivity of 90 to 95% and specificity of 95 to 100% for diagnosing genital gonorrhea in symptomatic men. In cervicitis, the sensitivity of this test is less than 50%, when compared with properly

The use of enzyme substrates that demonstrate the presence of prolyl-hydroxyprolyl aminopeptidase and the abscense of β-galactosidase and γ-glutamyl aminopeptidase also to confirm the identification. Currently there are commercially available rapid tests to confirm the isolation of *N. gonorrhoeae* such as immune reactions by using fluorescent monoclonal antibodies or coagglutination tests, as well as molecular techniques using specific probes or

*N. gonorrhoeae* is an exclusive human pathogen and this is their only reservoir. The transmission is from person to person through sexual intercourse, so the primary infection in adults is installed in the genital area, anal and/ or pharynx, where there is susceptible

In males, *N. gonorrhoeae* causes an acute urethritis with dysuria and urethral discharge. The incubation period averages 2 to 7 days. About 2.5 to 5 % of men are asyntomatic. Complications of untreated gonococcal urethritis are: epididymitis, periurethral abscesses, infections of the Tyson's glands and Cowper's glands, orchitis and prostatitis (Janda and Gaydos *in* Manual of Clinical Microbiology, 2007). In women, gonococcal infections cause cervicitis, only approximately half of which occur with symptoms and which can go on to cause pelvic inflammatory disease, ectopic pregnancies, and infertility. In addition, in both men and women exposed orally or anally, gonococcal infections can cause a predominantly asyntomatic pharyngiti*s* or proctitis. Less commonly, *N. gonorrhoeae* can cause conjunctivitis, endocarditis, tenosynovitis, arthritis, meningitis, inflammation of the

Conjunctival infection occurs in adult and neonatal by accidental inoculation or contamination in the birth canal and causes ophthalmia neonatorum, which if not treated properly can lead to blindness (Marrazo *in* Principle and Practice of Infections

Asymptomatic infection in women has been linked to the biofilm production, which includes nature complex mixes of exopolysaccharides, proteins and DNA. Bacteria living in biofilms are more resistant to biocides and antimicrobial agents. Also, the horizontal transfer of resistance genes is more likely and increases the spread of resistance genes (Apicella *in Neisseria* Molecular Mechanisms of Pathogenesis, 2010). Gonococcal infection may facilite transmission of human immunodeficiency virus (HIV), increasing the number of target cells

Diagnosis of gonococcal infection has historically been a combination of clinical signs and symptoms plus the microbiologic study. The diagnosis of urethritis in men can be made by observing gram-negative intracellular diplococci associated with polymorphonuclear leukocites on a smear prepared from the urethral discharge. The Gram stain has a sensitivity of 90 to 95% and specificity of 95 to 100% for diagnosing genital gonorrhea in symptomatic men. In cervicitis, the sensitivity of this test is less than 50%, when compared with properly

for HIV in the inflammatory exudate present in symptomatic patients (Bala, 2010)

specific primers **(**Janda and Gaydos *in* Manual of Clinical Microbiology, 2007).

liver capsule and disseminated blood stream infections (Barry, 2009).

**1.2 Transmission and clinical manifestations**

epithelium: cubic or cylindrical not stratified.

**1.3 Diagnosis of gonococcal infections**

Disease, 2010).

performed culture. Culture on selective media, modified Thayer Martin, it allows recovery of *N. gonorrhoeae* from body sites harboring an endogenous bacterial flora.

At the last years, nucleic acid detection techniques allow direct detection of *N. gonorrheae* in clinical samples and do not require viable organisms. The assay may be divided into three types: (i) direct detection probe hybridization to the target nucleic acid with direct detection of the hybrid; (ii) nucleic acid amplification tests (NAATs); and (iii) amplified-signal probe test, which hybridize with nucleic acid and then amplify the signal of the probe. These assays are generally much more sensitive that culture and are highly specific for urogenital infections, however, depending on the assay used (e.g. PCR) some concerns have arisen about the specificity of these tests from other anatomic sites. The advantages of the test are specimens may be transportes from geographically distant areas and stored for several days prior to testing. The NAATs also allow use non-invasive specimen types such as urine and vaginal swabs. The disadvantages of using nonculture nucleic acid probe or amplification tests include unavailability of a viable isolate for antimicrobial susceptibility testing and the possibility of a positive test after treatment, since nucleic acids from organism may persist for a period of time after successful therapy (Barry, 2009).

## **1.4 Epidemiology of gonococcal infections**

Gonococcal infection is more common among young persons, particularly those aged 15-24 years, persons with lower socio-economic status, men who have sex with men (MSM), illicit drug users, commercial workers an racial/ethnic minority groups (Barry, 2009).

Gonococcal infections are among the most common reportable infections around the World. In the Unite Stated, gonorrhea is consistently the second-most frequently reported notifiable infection with more than 350,000 reported in 2006 (Barry, 2009; CDC, 2006).

In the United States, some European countries and Australia, the incidence of gonorrhea decreased at the end of the 1.980s to mid of 1.990s it was mainly attributed to changes in sexual behaviour produced after the appearance of HIV and the introduction of fluoroquinolone treatment (Famiglietti, 2000; Griemberg, 1997; Trotter *in Neisseria* Molecular Mechanisms of Pathogenesis, 2010).

Gonococcal infection has increased over previous years, although not consistently in all countries. In the United States the incidence of gonorrhea in recent years shows an upward trend, while the rate of gonorrhea in 2009 decreased 10.5% respect 2008 (Diez, 2011).

The World Health Organization (WHO) estimated that, globally, there were 62 million new cases of gonorrhea in 1999, with 27 million (44%) in South and South-East Asia, 17 million (27%) in Sub-Saharan Africa and 7.5 million (12%) in Latin America and the Caribbean (WHO, 2001).

## **2. Currents problems**

#### **2.1** *Neisseria gonorrhoeae***: Antimicrobial resistance and clinic impact**

The penicillin introduction by the end of 1940s led to the eradication of *N. gonorrhoeae* sulfonamides resistant and it was the antimicrobial agent that kept its effectiveness for nearly forty years (approximately 1945-1985), although it required increasing the dose in

Gonorrhea in Men Sex Men and Heterosexual Men 51

days , VO (CDC, 2010). However there are regions where resistance to cefixime does not

Azithromycin and doxycycline are intended to cover the presence of *Chlamydia trachomatis* non gonococcal urethritis . The recommended dose of azithromycin for treatment of

About the antimicrobial agents which are recommended by the CDC, there were treatment failures with azithromycin when it was given in a single dose of 1g VO for uncomplicated gonorrhea, with isolates had MICs between 0.125 and 0.5 µg / ml (Zarantonelli , 1999; Ehret, 1996). Recently, in several countries are emerging of high-level resistance to azithromycin

Ceftriaxone (third-generation cephalosporin, parenteral) retains its activity against *N. gonorrhoeae*, but recently have been appearing isolates with decreased sensitivity in various regions of the world (Martin, 2006; Barry, 2009, Tapsall, 2009; Chisholm, 2010; Deguchi,

The STD Program of the National Hospital of Clinics, "José de San Martín" University of Buenos Aires, Argentina, deals with 80% patients from the city and 20% from the suburban areas. In a period of 10 years (2000-2009), was investigated the presence of *Neisseria*

The average age of MSM was 33 years (range 14-75 years) and HET was 34 years (range 15- 82 years). The incidence of gonorrhea was 10.3% and 9.5% in MSM and HET respectively (p> 0.05) and it was more frequent in men between 20 and 29 years old in both groups of

In MSM urethral location was the most frequent (70%), followed by rectal (34%) and lastly the pharynx (17%). This increase in the incidence of gonorrhea in HET in 2008 and 2009 compared to 2007, was significant (p <0.05) and has also been reported by other authors (Velicko, 2009). It could be due to increased in this population of *N. gonorrhoeae* fluoroquinolone resistant in this population, since it was initially installed in the MSM.

Fluctuations were observed in the annual incidence of gonorrhea in MSM and heterosexual men between 1995 and 2009, with a decrease at the end of the 1990s and beginning of the new millennium but then it continued to increase slowly in recent years, specially among

The analysis of results was divided into two periods: 2000-04 (first period), the emergence of *N. gonorrhoeae* fluoroquinolone resistant in 2005 in our Hospital pointed the beginning of the second period: 2005-09 (second period). The Table 1 shows the incidence of *N. gonorrhoeae*

The National Health Surveillance of the Ministry of Health of Argentina (SNVS) had registered 28.517 and 17.017 cases of gonorrhea in the periods 2000-4 and 2005-09

gonorrhea is 2g VO to prevent the emergence of resistance (CDC, 2010).

strains (Galarza 2009; Palmer, 2008; Chisholm, 2009; Starnino, 2009).

**3. Present study with review of literature**

*gonorrhoeae* in 4273 male patients (52% MSM and 48% HET).

from clinical specimens according to patient's sex habits.

allow its use (Barry, 2009).

2010; Garcia, 2010a).

patients.

heterosexual men.

respectively.

**3.1 Incidence of gonorrhea**

response to the emergence of chromosomal resistance and the use of alternative drugs for the treatment of isolates penicillinase producers (PPNG), since its appearance in 1976 (Ashford, 1976). In the mid of 1980s the prevalence of these strains exceeded 40% for what should no longer be used for empiric treatment of gonorrhea. At that time, the percentage of isolates tetracycline resistant was high, greater than 50% (Famiglietti, 2001). To the high prevalence of isolates with chromosomal resistance to tetracycline (CMRNG), originated in 1970, joined the plasmid resistance (TRNG) which is mediated by the *tetM* determinant in conjugative plasmid that confers high level resistance (Morse, 1986).

The market introduction of fluoroquinolones in the middle of 1980s, was the ideal replacement of penicillin, not only be used as a single-dose and would be highly effective, but also has advantage on the route of administration of drug and fewer adverse effects.

In the United States, due to increased resistance to penicillin and tetracycline, the Centers for Disease Control and Prevention (CDC) recommended the use of extended- spectrum cephalosporin or a fluoroquinolone as firt line treatment for the uncomplicated gonococcal infection (CDC, 1993).

The use of highly effective fluoroquinolone against PPNG helped limit rapid spread of these strains (Janda and Gaydos *in* Manual of Clinical Microbiology, 2007). However, in 1986 resistance to enoxacin was reported in Netherlands and the first treatment failures to fluorquinolones were documented in Japan in 1.994. (Tapsall, 1992; Deguchi, 2010). Such isolates emerged in Argentina in 2000 (Fiorito, 2001).