**6. Gonorrhea**

*Neisseria gonorrheoae* is an intracellular Gram-negative aerobic diplococcus that is the causative agent of gonorrhea. The adjacent sides of the diplococci pairs are flattened giving a characteristic kidney bean shape. Gonococci initially penetrate mucosal columnar epithelial cells and pass thru to establish infection in the subepithelial space. Cell destruction mediated by gonococci and the host inflammatory response is responsible for the disease pathology. Gonococci frequently change their surface antigens and lasting immunity does not develop. Therefore, re-infection is common.

### **6.1 Epidemiology**

Gonorrhea is the second most common bacterial STI in the world with 62 million cases annually and is most prevalent in south and Southeast Asia with 27 million cases annually, and sub-Saharan Africa with 17 million cases annually. Gonococcal infection is most common among young persons, particularly those 15-24 years old. Women have a 60-80% risk of acquiring gonorrhea from a single act of vaginal intercourse with an infected man; men have only a 20-50% chance of acquiring infection from intercourse with infected women. Transmission among men who have sex with men is more efficient than a man's risk during heterosexual sex and gonorrhea prevalence is several fold higher in this demographic group. Pharyngeal and rectal gonococcal infection is also especially prevalent in this group. Co-infection with *Chlamydia* is common, occurring in up to 50% of gonococcal infections in some countries.

#### **6.2 Clinical manifestations**

Symptoms of infection in men usually appear 2-5 days after exposure with a range of 1-30 days. Women are less likely to have symptomatic infection, up to 70% are subclinical, but those who develop symptoms do so within 10 days of infection. The majority of men with gonococcal infection develop urethritis with a white, yellow, or greenish urethral discharge, dysuria, and sometimes painful and swollen testes. Erythema of the meatus is sometimes observed. Non gonococcal urethritis is usually characterized by less purulent and less copious discharge with little erythema of the meatus. The endocervical canal is the primary site of infection in women. Females with endocervicitis and urethritis experience dysuria, a purulent vaginal discharge, pelvic pain, and pain and bleeding brought on by sexual intercourse. Symptoms of rectal infection include itching, mucopurulent discharge, bleeding, tenesmus, and painful bowel movements. Pharyngeal infection is characterized by exudative pharyngitis and cervical lymphadenopathy. Untreated gonorrhea can lead to severe complications in both men and women. Gonorrhea can spread from the cervix and vagina to the fallopian tubes and uterus leading to chronic salpingitis or pelvic inflammatory disease, ectopic pregnancy, and infertility from scaring of the fallopian tubes. Pregnant women may experience chorioamnionitis and septic abortion. In men epididymitis, usually accompanied by unilateral testicular pain and swelling with fever, is 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 infection and, rarely, develop gonococcal sepsis or pneumonia.

#### **6.3 Diagnosis**

466 Current Topics in Tropical Medicine

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

*Neisseria gonorrheoae* is an intracellular Gram-negative aerobic diplococcus that is the causative agent of gonorrhea. The adjacent sides of the diplococci pairs are flattened giving a characteristic kidney bean shape. Gonococci initially penetrate mucosal columnar epithelial cells and pass thru to establish infection in the subepithelial space. Cell destruction mediated by gonococci and the host inflammatory response is responsible for the disease pathology. Gonococci frequently change their surface antigens and lasting immunity does

Gonorrhea is the second most common bacterial STI in the world with 62 million cases annually and is most prevalent in south and Southeast Asia with 27 million cases annually, and sub-Saharan Africa with 17 million cases annually. Gonococcal infection is most common among young persons, particularly those 15-24 years old. Women have a 60-80% risk of acquiring gonorrhea from a single act of vaginal intercourse with an infected man; men have only a 20-50% chance of acquiring infection from intercourse with infected women. Transmission among men who have sex with men is more efficient than a man's risk during heterosexual sex and gonorrhea prevalence is several fold higher in this demographic group. Pharyngeal and rectal gonococcal infection is also especially prevalent in this group. Co-infection with *Chlamydia* is common, occurring in up to 50% of gonococcal

Symptoms of infection in men usually appear 2-5 days after exposure with a range of 1-30 days. Women are less likely to have symptomatic infection, up to 70% are subclinical, but those who develop symptoms do so within 10 days of infection. The majority of men with gonococcal infection develop urethritis with a white, yellow, or greenish urethral discharge, dysuria, and sometimes painful and swollen testes. Erythema of the meatus is sometimes observed. Non gonococcal urethritis is usually characterized by less purulent and less copious discharge with little erythema of the meatus. The endocervical canal is the primary site of infection in women. Females with endocervicitis and urethritis experience dysuria, a purulent vaginal discharge, pelvic pain, and pain and bleeding brought on by sexual intercourse. Symptoms of rectal infection include itching, mucopurulent discharge, bleeding, tenesmus, and painful bowel movements. Pharyngeal infection is characterized by exudative pharyngitis and cervical lymphadenopathy. Untreated gonorrhea can lead to severe complications in both men and women. Gonorrhea can spread from the cervix and vagina to the fallopian tubes and uterus leading to chronic salpingitis or pelvic inflammatory disease, ectopic pregnancy, and infertility from scaring of the fallopian tubes. Pregnant women may experience chorioamnionitis and septic abortion. In men epididymitis, usually accompanied by unilateral testicular pain and swelling with fever, is

lacking. LGV buboes may require aspiration.

not develop. Therefore, re-infection is common.

**6. Gonorrhea** 

**6.1 Epidemiology** 

infections in some countries.

**6.2 Clinical manifestations** 

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.

#### **6.4 Treatment**

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.

Sexually Transmitted Infections in the Tropics 469

manifestations of secondary syphilis include hepatitis, glomerulonephritis, and keratitis. Neurosyphilis can occur at any stage of syphilis but is classically associated with tertiary syphilis. Clinical manifestations of early neurosyphilis include acute syphilitic meningitis that typically involves cranial nerves III, VI, VII and VIII; or meningovascular syphilis, a stroke-like syndrome with seizures. Secondary syphilis is usually the fist clinical presentation in persons practicing receptive vaginal or anal intercourse as the primary

Whereas some secondary syphilis can spontaneously resolve, if untreated, approximately two thirds of secondary syphilis cases enter into a prolonged period of latency where symptoms of infection are absent. Relapses of secondary symptoms may occur in up to 25% of untreated patients, usually within the first year of infection. The latent stage can last for up to 25-30 years but if untreated, about one third of latent infections will progress to tertiary syphilis. Tertiary syphilis is rare in developed countries due to early diagnosis and treatment of syphilis. Tertiary syphilis is characterized by destructive lesions known as gummas, neurologic involvement, and cardiovascular lesions. Gummas, are highly destructive granulomas, usually in the skin, bone and mucosal areas but are sometimes found in other tissues such as genitals, lung, stomach, liver, spleen, spinal cord, breast, brain, and heart. Onset is 10-15 years after infection. Cardiovascular syphilis generally appears about 20-30 years after infection when lesions in the cardiac vasculature produce ascending aortic aneurysm, aortic insufficiency, or coronary ostial stenosis. In tertiary neurosyphilis focal endoarteritis in the blood vessels of the brain and spinal cord provokes signs and symptoms, usually decades after infection, which may resemble other neurologic diseases. Clinical manifestations typically include general paresis and tabes dorsalis. The presence of oral syphilitic lesions is common, particularly in primary and secondary syphilis, and in regions with a high prevalence of syphilis other health care workers, such as

Worldwide each year over 2 million pregnant women, 1.5% of all pregnancies, test positive for syphilis. *Treponema* spirochetes can cross the placenta to infect the fetus resulting in severe adverse pregnancy outcomes. Untreated maternal syphilis will result in stillbirth, premature birth, neonatal death, or congenital infection in up to 80% of pregnancies in developing countries. An estimated 25% of all stillbirths and 11% of neonatal deaths in developing countries are due to fetal syphilis exposure. Symptoms of early congenital syphilis in children less than 2 year old include cutaneous and mucocutaneous lesions, macropapular rash, hepatosplenomegaly, lymphadenopathy, bone alterations from osteitis and osteochondritis, meningitis, pneumonia, and testicular masses. Hematologic abnormalities such as thrombocytopenia and anemia may occur. Early congenital syphilis is more common than late congenital syphilis. Late congenital syphilis in children >2 year old is characterized by Hutchinson's triad, Saddle nose, and bone deformations such as Saber shins. Hutchinson's triad includes tooth deformations where the crown of the incisors is wider in the cervical portion than at the incisor edge and a crescent-shaped notch is present at the incisor edge, interstitial keratitis which can lead to blindness, and eighth nerve deafness. Saddle nose refers to collapse of the bridge and resulting dorsal depression due to erosion of septal support, giving a saddled appearance. Saber shin is a malformation of the tibia with sharp anterior bowing. Interstitial keratitis is the most common manifestation of

lesions are often not noticed.

dentists, need to be aware of this risk.

**7.3 Congenital syphilis** 

Therapeutic use of sulfonamides, penicillin, erythromycin, and fluoroquinolones has been largely discontinued due to the development of widespread resistance to these agents. Azithromycin, 2 g orally, is effective but concerns over the prior ease of development of macrolide resistance in *N. gonorrhoeae* should limit its use to special circumstances. Gonococcal infections of the pharynx are more difficult to eliminate and are treated with ceftriaxone, 250 mg IM in a single dose, plus azithromycin, 1 g orally in a single dose, or doxycycline, 100 mg orally twice a day. Neonates born to infected mothers are given erythromycin ointment to the eyes to prevent blindness. Patients infected with *N. gonorrhoeae* are frequently co-infected with *Chlamydia*, and additional treatment for this infection may be appropriate, dependent on local prevalence of these STIs.
