**5.2 Clinical manifestations**

Symptoms of chlamydial infection typically appear 1-3 weeks post exposure. Asymptomatic infection is common among both men, approximately ~50%, and women, approximately 70- 80%. When it occurs, symptomatic infection clears spontaneously about 50% of the time. However, both untreated and asymptomatic infections can persist for years; as many as 10% remain infected after 3 years. Symptomatic men might have a urethral discharge and dysuria with burning and itching around the urethral opening. Epididymitis and prostatitis are sometimes present causing pain and swelling of the testes, fever, and rarely sterility. *Chlamydial* infection of the rectum can cause pruritis, rectal pain, discharge, or bleeding. Chlamydia infected women may experience cervicitis, vaginal discharge and dysuria. Infection and inflammation in the cervix may spread to the fallopian tubes and uterus, leading to pelvic inflammatory disease (PID). *Chlamydia* is among the most frequent pathogens associated with PID and up to 40% of women with untreated chlamydia develop PID. Some women with PID report lower abdominal pain, lower back pain, nausea, fever,

Metronidazole, 2 g orally in a single dose or 500 mg orally twice a day for 7 days, is the treatment of choice for trichomoniasis. An estimated 2.5-10% of *T. vaginalis* infections show some degree of resistance to treatment; a resistance rate of 17.4% has been reported in Papua New Guinea. Treatment failures are higher in HIV-positive individuals. Recalcitrant cases may be treated with tinidazole at 2 g orally in a single dose. Consumption of alcohol should be avoided during treatment and for 24 hrs after completion of metronidazole therapy or 72

*Chlamydia trachomatis* is a small, obligate intracellular bacterium that typically infects nonciliated epithelial cells of mucous membranes; urethral epithelial cells in males and columnar epithelial cells of the endocervix in women. However in the lymphogranuloma venereum serovars, macrophages appear to be the principal host cell. *Chlamydia* is organized into multiple serovars that cause a diverse variety of human disease. Serotypes A, B, Ba, and C are the agents of classic blinding trachoma. Serotypes D thru K can cause adult inclusion and neonatal conjunctivitis, pneumonia, urogenital infections and Reiter's syndrome. Serotypes L1, L2, and L3 infect tissues deeper to the epithelium and cause

*Chlamydia* infection is the most common bacterial STI in the world and among STIs, only the prevalences of herpes and trichomoniasis are higher. *Chlamydia* infection is highest in sexually active young adults under 25 years of age. *Chlamydia trachomatis* causes 30-50% of nongonoccal urethritis in men and mucopurulent cervicitis in women. In men less than 35 years of age *Chlamydia* is the principal cause of epididymitis. Although there is no lasting immunity and re-infection is common, women do clear the infection faster with increasing age. Lymphogranuloma venereum (LGV) is an uncommon disease and relatively rare in developed countries. The disease is most common in sub-Saharan Africa and is also reported in areas of the Caribbean, Central America, and Southeast Asia and sporadically in

Symptoms of chlamydial infection typically appear 1-3 weeks post exposure. Asymptomatic infection is common among both men, approximately ~50%, and women, approximately 70- 80%. When it occurs, symptomatic infection clears spontaneously about 50% of the time. However, both untreated and asymptomatic infections can persist for years; as many as 10% remain infected after 3 years. Symptomatic men might have a urethral discharge and dysuria with burning and itching around the urethral opening. Epididymitis and prostatitis are sometimes present causing pain and swelling of the testes, fever, and rarely sterility. *Chlamydial* infection of the rectum can cause pruritis, rectal pain, discharge, or bleeding. Chlamydia infected women may experience cervicitis, vaginal discharge and dysuria. Infection and inflammation in the cervix may spread to the fallopian tubes and uterus, leading to pelvic inflammatory disease (PID). *Chlamydia* is among the most frequent pathogens associated with PID and up to 40% of women with untreated chlamydia develop PID. Some women with PID report lower abdominal pain, lower back pain, nausea, fever,

**4.5 Treatment** 

**5. Chlamydia** 

**5.1 Epidemiology** 

developed nations.

**5.2 Clinical manifestations** 

hours after completion of tinidazole therapy.

lymphogranuloma venereum (LGV).

abnormal bleeding, and dysparenia but many women show no signs of infection. Untreated PID can result in chronic pelvic pain, tubal infertility in 10-20% of women, and occasionally potentially fatal ectopic pregnancy. Repeated infections increase the risk of adverse sequelae in both men and women. In rare cases persons with genital chlamydial infection can develop Reiter's syndrome, a triad of reactive arthritis accompanied by conjunctivitis and urethritis. Chlamydial infection, even asymptomatic disease, increases the risk of adverse pregnancy outcomes: premature rupture of membranes, preterm delivery and low birth weight. *Chlamydia* can easily pass to neonates during childbirth causing neonatal conjunctivitis and afebrile pneumonia in approximately 60% of those with infected mothers. The high levels of *Chlamydia* infection worldwide mean that there is substantial neonatal morbidity from perinatally transmitted chlamydial infection.

The *Chlamydia* serotypes which cause LGV are more virulent and more invasive than other chlamydial serotypes. The initial stage is a painless genital papule which heals rapidly and may be unrecognized. The organism then disseminates to regional lymph nodes, usually the inguinal nodes, where they replicate within macrophages and elicit a systemic response. This produces a painful inguinal lymphadenopathy, usually unilateral, by 2-6 weeks after the primary lesion often accompanied by fever, headache, and arthralgias. Rectal infection with LGV is characterized by a severe febrile proctocolitis, mimicking inflammatory bowel disease, with painful defecation, tenesmus, and less commonly a bloody mucopurulent discharge. Untreated LGV results in chronic inflammation with late fibrotic complications such as fistulas of the penis, urethra, and rectum, strictures, and genital lymphoedema and elephantiasis.

#### **5.3 Diagnosis**

Empirical evidence of *Chlamydia* infection is based on clinical presentation. The presence of greater than 10 polymorphonuclear leukocytes (PMNs) per 1000X field in vaginal discharge or 5 PMNs/field in urethral discharge is indicative of the cervicitis or urethritis characteristic of *Chlamydia* infection. There are currently no widely available point-of-care tests for *Chlamydia* infections. Most *Chlamydia* infections are detected through screening programs based on nucleic acid amplification testing (NAAT), antigen detection by ELISA, and DNA hybridization. Screening is useful for identifying asymptomatic infected individuals and in confirming symptomatic infections, but the delay in obtaining results means that initial diagnosis will be primarily based on clinical presentation. Traditional diagnostic techniques used for bacterial infections, culture and Gram stain, are of limited value for chlamydial infections. *Chlamydia* is an intracellular pathogen that requires tissue culture to propagate and so this approach is infrequently used even in developed countries. The unique cell wall structure of Chlamydia makes it very difficult to stain, although it is considered Gram negative. Direct fluorescent antibody staining can identify *Chlamydia* in clinical specimens but is not widely available. Where testing is available, all sexually active young adults under 25 years should be screened for *Chlamydia*. All pregnant women should be screened for *Chlamydia* as well.

#### **5.4 Treatment**

The recommended regimen for treatment of *Chlamydia* infection is azithromycin, 1 g orally in a single dose, or doxycycline, 100 mg orally twice daily for 7 days. Alternative 7 day regimens are 500 mg erythromycin base orally four times a day, 500 mg levofloxacin orally once daily, or 300 mg ofloxacin orally twice daily. The frequency of *Chlamydia* and

Sexually Transmitted Infections in the Tropics 467

relatively rare but can cause sterility. However a more likely cause of epididymitis in sexually active young men is *C. trachomatis*. Posterior urethritis, urethral stricture and prostatitis in men and Bartholin gland abscesses in women are additional complications of genital infection. In approximately 1- 3% of infected adults, with a higher occurrence in women, gonococci disseminates via the bloodstream to produce characteristic papulopustular lesions, and to infect joints, typically in fingers, wrists, toes, and ankles, causing septic arthritis. These manifestations are accompanied by fever and can range from mild to severe. Other less common complications of disseminated infection include a purulent conjunctivitis from autoinoculation, fatal septic shock, meningitis, perihepatitis, osteomyelitis, rapidly progressing endocarditis, especially of the aortic valve, and adult respiratory distress syndrome. Neonatal gonococcal infections are now an infrequent occurrence in developed countries but remain a serious problem in developing countries. Newborns infected during birth can develop conjunctivitis, known as ophthalmia neonatorum, which may lead to blindness. Neonates can also acquire pharyngeal or rectal

There are currently five available tests for detection of gonorrhea; Gram stain, culture, nucleic acid amplification tests (NAAT), gonorrhea antigen detection tests, and nucleic acid hybridization tests. Clinical signs and symptoms of cervicitis or urethritis and the presence of Gram-negative intracellular diplococci within polymorphonuclear neutrophils from urethral, or less commonly, cervical discharge, are diagnostic for gonorrhea. The sensitivity of gram stain is very high in symptomatic men with urethritis but less so in infected women and in rectal infection. Stained smears are not recommended for diagnosis of pharyngeal gonococcal infection. Culture on specialized media can be used for urethral, cervical, pharyngeal, and rectal infection. This is the only testing technique that permits determination of gonococcal antibiotic sensitivity. In resource rich countries, diagnosis using very sensitive NAAT, gonorrhea antigen detection tests via immunoassay, and nucleic acid hybridization tests has become widespread. This has permitted screening of at risk populations and self referred testing in developed countries. NAAT tests are the most sensitive, and can be used on urine samples as well, but require hours to days to yield results. Rapid, point-of-care gonorrhea antigen detection tests and nucleic acid hybridization tests are in use, but are relatively expensive for settings in developing countries. Both of these tests are less sensitive than NAAT and are primarily designed for testing with cervical and urethral material. Some available NAAT, gonorrhea antigen detection tests, and nucleic acid hybridization tests can detect both *N. gonorrhoeae* and

*Chlamydia* in the same sample and the NAAT test can be combined with Pap smears.

The recommended treatment for gonococcal infections is ceftriaxone in a single 250 mg dose administered intramuscularly (IM). If unavailable cefixime, 400 mg orally in a single dose, or a single dose injectible cephalosporin plus azithromycin, 1 g orally in a single dose, or doxycycline, 100 mg orally twice a day for 7 days, may be used. Resistance to oral third generation cephalosporins has emerged recently and has been reported throughout Asia and in Australia and some European countries. The recent emergence in Japan of a strain, H041, which is extremely resistant to all cephalosporin-class antibiotics will pose a considerable public health challenge as this strain spreads throughout Asia and beyond.

infection and, rarely, develop gonococcal sepsis or pneumonia.

**6.3 Diagnosis** 

**6.4 Treatment** 

gonococcal co-infection is high in many locales and dual treatment should be considered. The recommended treatment for LGV is doxycycline 100 mg orally twice a day for 21 days or alternatively, erythromycin base, 500 mg orally four times a day for 21 days. Azithromycin, 1 g orally once weekly for 3 weeks, may also be effective but clinical data is lacking. LGV buboes may require aspiration.
