Gonococcal Infections

E. Lori

R. Patterson

Although gonorrhea is most familiar as a urogenital infection in sexually active adults, disease caused by Neisseria gonorrhoeae occurs at a variety of anatomic sites in all age groups. Improved diagnostic methods and aggressive treatment have contributed to an overall decline in incidence, but changing patterns of antibiotic susceptibility pose treatment challenges. In children beyond the neonatal period, the infection usually is a marker for sexual abuse or contact.

MICROBIOLOGY

N. gonorrhoeae is a small, gram-negative, aerobic, nonmotile, oxidase-positive diplococcus with flattened adjacent surfaces. Its ultrastructure is typical of the gram-negative organisms. The outer lipid membrane contains pili, lipooligosaccharide, and several distinct proteins. The most prevalent of these, porin, acts as an anion channel through the hydrophobic cell membrane. Other outer membrane proteins facilitate adherence and block host humoral immunity to the gonococcus. Pili also contribute to adherence; nonpiliated strains are avirulent.

Differentiating gonococcal strains aids in epidemiologic study. In addition to being serotyped by its porin antigen pattern, a strain may be classified by its ability to grow on various nutrient-deficient media, a system known as auxotyping. Combined auxotype and serotype data have defined more than 100 distinct strains of N. gonorrhoeae. Antibiotic resistance patterns also can distinguish strains, although this property may not remain fixed. Resistance may be conferred either by chromosomal alterations (producing intrinsic resistance to a variety of antimicrobials) or by plasmid-mediated mechanisms (important for penicillin and tetracycline).

EPIDEMIOLOGY

The number of new gonorrhea infections reported in the United States has declined from a peak in the mid 1970s, but the incidence has remained steady at about 130 cases per 100,000 population in recent years. This far exceeds the Centers for Disease Control and Prevention’s (CDC’s) Healthy People 2010 goal of 19 cases per 100,000, and it renders gonorrhea second only to chlamydia in cases reported. Authorities estimate that approximately 600,000 infections actually occur each year. Young adults account for most cases, followed closely by older adolescents. Young women aged 15 to 19 years have the highest incidence of any group. In young adults, more episodes are reported in men, possibly because of underrecognition of infection in asymptomatic women. Demographic risk factors for gonorrhea include young age, unmarried status, nonwhite race, urban residence, low socioeconomic status, and men having sex with men. Asymptomatic men and prostitutes are important reservoirs of infection and contribute to the difficulty in eradicating the disease.

Gonorrhea is found in humans only and is transmitted through direct physical contact with infected mucosa or secretions. In adolescents and young adults, this spread occurs via sexual contact. Neonates and young children usually are infected intrapartum or by sexual abuse, respectively. Conjunctivitis in older children occurs by autoinoculation. Rectal gonorrhea may be acquired by receptive anal intercourse or by perineal contamination by genitourinary secretions. Pharyngeal infection presumably occurs after orogenital contact. Transmission by fomites has been implicated in nursery outbreaks but is rare. The incubation period generally is 2 to 7 days.

Since the late 1970s, the prevalence of antibiotic-resistant strains of N. gonorrhoeae has risen markedly. The U.S. Gonococcal Isolate Surveillance Project monitors trends in antimicrobial susceptibility, and data are used to formulate treatment strategies. Although the proportion of gonococci exhibiting plasmid-mediated or chromosomally mediated resistance to penicillin and/or tetracycline has declined since the mid-1990s, these strains still account for approximately 16% of isolates. Resistance to quinolones is endemic in Hawaii and California and is becoming an increasingly common occurrence in other areas; azithromycin resistance has been identified recently in a small number of isolates. Cephalosporin resistance has not been clinically significant.

PATHOGENESIS

Once introduced to a mucosal surface, the gonococcus adheres to the host cell, aided by its outer membrane pili. The bacteria penetrate tissue by endocytosis through or between epithelial cells, disrupting the mucosal integrity. Lipooligosaccharide exerts a toxic effect on the ciliated epithelial cells. An intense inflammatory response with influx of neutrophils and other phagocytes produces the characteristic profuse exudate; gonococcal peptidoglycan contributes to inflammation by activating complement. As gonococci invade the subepithelial space, deeper tissue destruction occurs through the action of extracellular enzymes and the cytotoxic and endotoxin-like effects of lipooligosaccharide. Invasion of local blood vessels and lymphatics may lead to dissemination. Eventually, scarring and fibrosis develop in the untreated patient.

The host’s mucus production, pH, hormonal milieu, and normal flora probably influence progress of infection in the early stages. Prepubertal girls, whose vaginal secretions are alkaline and whose epithelium lacks the effects of estrogen, are more likely to develop vulvovaginitis than are adolescents, in whom cervicitis occurs more commonly. Disseminated or complicated gonorrhea occurs more commonly during menses and with the use of intrauterine devices and less commonly during pregnancy or with the use of oral contraceptives.

Although specific host defenses against gonococcal infection are not understood fully, clinical and laboratory observations give important clues. Humoral and secretory immunoglobulins against N. gonorrhoeae appear in response to infection, but they are not totally protective against subsequent episodes. One possible explanation is that gonococci readily alter
the antigenic structure of pili (i.e., phase variation) and certain outer membrane proteins, thus evading recognition by the host. Pili themselves appear to interfere with host cell phagocytosis. All gonococci produce a protease that cleaves immunoglobulin A1, thwarting the protective action of this mucosal surface antibody. Complement activation may play a role in protecting against disseminated disease, because complement-deficient patients are at increased risk for developing gonococcemia. The role of cellular immunity in defense against the gonococcus is unknown.

Most strains of N. gonorrhoeae are susceptible to the bactericidal action of normal serum. Strains that cause invasive disease lack this serum sensitivity, have different growth characteristics and nutritional requirements, and are more likely to be highly sensitive to penicillin than are serum-sensitive strains.

CLINICAL MANIFESTATIONS AND COMPLICATIONS

Gonococcal infection may be localized to a mucosal surface or disseminated hematogenously. Many infected adults are asymptomatic, but how this fact translates to pediatric infection is uncertain.

Ophthalmia Neonatorum and Other Neonatal Disease

Gonococcal ophthalmia neonatorum (GON), the most common form of neonatal gonorrhea, usually occurs after intrapartum contact with the mother’s infected genital secretions, but cesarean delivery does not preclude its development. Risk factors include prematurity, prolonged rupture of amniotic membranes, lack of prenatal care, lack of postpartum antimicrobial prophylaxis, and a maternal history of drug abuse or sexually transmitted disease. Onset of the conjunctivitis usually occurs when the infant is 2 to 5 days old. The ocular discharge is classically bilateral, mucopurulent, and profuse; marked eyelid edema and chemosis are present. Unilateral and milder cases also are seen. Without prompt treatment, corneal ulceration, invasion of deeper ocular structures, and globe perforation occur, with subsequent loss of vision.

Other localized disease in the neonate includes rhinitis, funisitis, vaginitis, anorectal infection, and scalp abscess after fetal monitoring. Invasive infection (sepsis, meningitis) rarely occurs. A form of neonatal septic arthritis usually appears 1 to 4 weeks after delivery and after several days of prodromal symptoms, involves one to four distal joints, and is not associated with skin lesions.

Vaginitis and Cervicitis

Uncomplicated gonococcal infection of the female genital tract presents with mild to profuse vaginal discharge, local pruritus, and dysuria. In young girls, urinary symptoms may predominate, and edema, erythema, and tenderness of the vulva are common findings. Once a girl undergoes puberty, her infection is more likely to be endocervical and often is silent. In addition to having vaginal discharge and dysuria, she may have localized labial swelling and tenderness that reflect infection of the Bartholin and Skene glands. Systemic symptoms and signs are rare findings.

The most serious complication of genital gonorrhea, seen in 10% to 20% of infected female patients, is pelvic inflammatory disease (PID). Children and adolescents are more likely to develop this syndrome than are adults. Risk factors include multiple sexual partners, use of an intrauterine device, and vaginal douching. Ascent of the gonococcus from the vagina or cervix leads to endometritis, salpingitis, and, occasionally, pelvic or abdominal abscesses. Frequently, other genital microbes (particularly chlamydia and anaerobes) are found in the diseased structures, with or without gonococci; the relative role of each of these organisms in the pathogenesis of PID is undefined. The resultant fallopian tube fibrosis leads to obstruction and sterility in 12% of first-time infections, increasing to 50% to 75% after three episodes. Other women later have an increased incidence of ectopic pregnancy or chronic pelvic pain. PID is suggested clinically by lower abdominal pain, discomfort on motion of the cervix, and tenderness of the adnexal structures, which may show a masslike enlargement. Fever and genital bleeding or discharge also may be present. Alternatively, symptoms may be minimal or absent. More extensive spread of the gonococcus, with or without other organisms, leads to perihepatitis (i.e., Fitz-Hugh–Curtis syndrome), with fever and right upper quadrant pain or tenderness.

Urethritis

Purulent urethral discharge and dysuria are hallmarks of gonococcal infection of the urethra in either gender, although the infection rarely is confined to this structure in female patients. Urinary frequency and urgency are not seen. Asymptomatic men constitute a small percentage of cases. Epididymitis and prostatitis are rare complications, but scarring may result in urethral strictures.

Other Localized Disease

Gonococcal conjunctivitis in older children and adolescents resembles that in neonates. Pharyngeal and anorectal gonorrhea most often are asymptomatic, although the latter may present with tenesmus, rectal bleeding, and pruritus. Cervical adenitis may accompany gonococcal pharyngitis. Mucopurulent exudate may be seen with pharyngitis or proctitis.

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