eMedicine Specialties > Infectious Diseases > Sexually Transmitted Diseases

Gonococcal Infections

Author: Brian Wong, MD, Assistant Professor of Medicine, Division of Infectious Diseases, Loma Linda University Medical Center
Coauthor(s): Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus; Renuka Heddurshetti, MD, Fellow in Infectious Diseases, Department of Internal Medicine, State University of New York at Brooklyn; Sanda Cebular, MD, Fellow, Department of Medicine, Section of Infectious Diseases, State University of New York at Brooklyn
Contributor Information and Disclosures

Updated: Apr 21, 2009

Introduction

Background

Gonorrhea (also called the clap and the drip), which is caused by Neisseria gonorrhoeae, is an important public health problem and is the most common reportable infectious disease. Gonorrhea is most frequently spread during sexual contact. However, it can also be transmitted from the mother's genital tract to the newborn during birth, causing ophthalmia neonatorum and systemic neonatal infection. The incubation period is usually 2-8 days.

In women, the cervix is the most common site of gonorrhea, resulting in endocervicitis and urethritis, which can be complicated by pelvic inflammatory disease (PID). In men, gonorrhea causes anterior urethritis.

Pathophysiology

N gonorrhoeae is a gram-negative, intracellular, aerobic diplococcus. It mainly affects the host’s columnar or cuboidal epithelium.

Many factors influence the manner in which gonococci mediate their virulence and pathogenicity. Pili help in attachment of gonococci to mucosal surfaces and contribute to resistance by preventing ingestion and killing by neutrophils. Opacity-associated (Opa) proteins increase adherence between gonococci and phagocytes, promote invasion into host cells, and possibly down-regulate the immune response. Porin channels (porA, porB) in the outer membrane play key roles in virulence. Gonococcal strains with porA may have inherent resistance to normal human serum and an increased ability to invade into epithelial cells, explaining their association with bacteremia.

Certain acquired plasmids and genetic mutations enhance virulence. TEM-1–type beta-lactamase (penicillinase) affects penicillin binding and efflux pumps and confers resistance to penicillin.^1,2 TetM protects the ribosome and confers resistance to tetracycline. Alterations in gyrA and parC genes result in fluoroquinolone resistance by efflux activation and decreased antibiotic cell permeation.¹

Gonococci attach to the host mucosal cell (pili and Opa proteins play major roles) and, within 24-48 hours, penetrate through and between cells into the subepithelial space. A typical host response is characterized by invasion with neutrophils, followed by epithelial sloughing, formation of submucosal microabscesses, and purulent discharge. If left untreated, macrophage and lymphocyte infiltration replaces the neutrophils. Some gonococcal strains cause an asymptomatic infection, leading to an asymptomatic carrier state in persons of either sex. The ability to grow anaerobically allows gonococci, when mixed with refluxed menstrual blood or attachment to sperm, to secondarily invade lower genital structures (vagina and cervix) and progress to upper genital organs (endometrium, salpinx, ovaries).

Frequency

United States

An estimated 700,000 new gonococcal infections occur annually in the United States.³ Only about half of these infections are actually reported. The reported rate is approximately 121 cases per 100,000 population. Since the 1970s, the overall incidence of gonococcal infections has declined considerably in modern Western countries. In recent years, the trend has been creeping slightly upward (5.5% rate increase from 2005 to 2006).⁴ The rate of gonorrhea is much higher in African Americans than in other racial groups⁵ and is much higher in the rural southeastern United States and in inner cities, presumably because of an association with socioeconomic and behavioral factors, as well as social networks. Some experts estimate the annual cost of gonorrhea and its complications at $1.1 billion.

International

In 1999, an estimated 62.35 million cases of gonococcal infection were diagnosed, predominantly in males.⁶ Although the frequency data are unknown in most developing countries, gonococcal infection rates in pregnant women in the Central African Republic and South Africa were found to be 3.1% and 7.8%, respectively. In 1999, the number of new cases of gonococcal infection diagnosed in North America was 1.56 million, 1.11 million in Western Europe, 27.2 million in South and Southeast Asia, and 7.27 million in Latin American and the Caribbean. Developing countries have the highest rates of gonorrhea and its complications.

Mortality/Morbidity

• Symptomatic and asymptomatic gonococcal infection in women may lead to tubal scarring and infertility. The incidence of involuntary infertility is estimated to be 15% after one attack of PID and approximately 50%-80% after 3 attacks. The incidence of ectopic pregnancy is increased 7-fold to 10-fold in women with previous salpingitis, increasing both fetal and maternal mortality rates. Failure to diagnose PID can result in acute morbidity, including tuboovarian abscess, endometritis, or Fitz-Hugh-Curtis syndrome (perihepatitis), and the chronic sequelae noted above.
• Gonococcal infections in women may also manifest as gonococcal urethritis or infection of periurethral (Skene) or Bartholin glands.
• Infertility may be more common after chlamydial PID than after gonococcal PID, possibly because the significant acute inflammatory signs associated with gonorrhea prompt women to seek a diagnosis, thereby leading to sooner treatment.
• Urethral strictures caused by gonorrhea in men are less common than once believed. Some strictures in the preantibiotic era likely resulted from treatment by urethral irrigation using caustic compounds rather than from the actual gonorrhea infection.
• It has been suggested that a person with a gonococcal infection may be at a 3- to 5-fold increased risk of acquiring HIV infection, if exposed to the virus.

Race

• All sexually active populations are at risk for gonococcal infection, and the level of risk rises with the number of sexual partners and the presence of other sexually transmitted diseases (STDs).
• Overall, the African American–to–white ratio of gonococcal infections declined from 23:1 in 2002 to 18:1 in 2006. Infection rates have been trending downward since 1998. However, between 2005 and 2006, the Centers for Disease Control and Prevention (CDC) noted an increased rate of gonococcal infections in African Americans by 6.3%.
• Similarly, in other ethnic groups, rates increased from 2002 to 2006—by 22.8% in American Indian/Alaskan Natives, by 17.7% in whites, and by 11.8% in Hispanics. On the other hand, the rate decreased by 1.4% in Asian/Pacific Islanders.

Sex

• Since 1987, infection rates have downtrended in the United States in both males and females.
• An asymptomatic carrier state can occur in both sexes but is believed to occur more frequently in females than in males. Symptomatic gonococcal disease, found more often in males than in females, prompt many men to obtain prompt curative treatment, usually preventing permanent sequelae.
• Serious complications of gonococcal infection are much more common in women than in men. PID in women may lead to ectopic pregnancy or infertility. Females may be more likely than males to develop disseminated gonococcal infection (DGI) possibly because of hormonal differences, menstruation, and alteration in vaginal pH. Women younger than 25 years are at the highest risk for gonococcal infection.

Age

• In the United States, the highest rates of gonorrhea are found in young (15-30 y) unmarried persons and in groups of low educational and socioeconomic status.⁷
• Infection in children is a marker for child sexual abuse.

Clinical

History

In all patients who present with a possible STD, the history should include a past history of STDs (including HIV infection and viral hepatitis), treatment history for known STDs, known symptoms of STDs in current or past sexual partners, type of contraception used, and any history of sexual assault. In women, the history should also include the date of the last menstrual period and the details of parity, including any history of ectopic pregnancies.

• Female genitourinary tract
  • The most common site of gonococcal infection in women is the endocervix (80%-90%), followed by the urethra (80%), rectum (40%), and pharynx (10%-20%). If symptoms develop, they often manifest within 10 days of infection.
  • Major symptoms include vaginal discharge, dysuria, intermenstrual bleeding, dyspareunia, and mild lower abdominal pain.
  • When gonococcal cervicitis is either asymptomatic or unrecognized, the patient may progress to PID, often in proximity to a menstrual period. PID may also be asymptomatic or silent and occurs in 10-20% of infected women. Symptoms of PID include the following:
    • Lower abdominal pain (most consistent symptom of PID)
    • Increased vaginal discharge or mucopurulent urethral discharge
    • Dysuria (usually without urgency or frequency)
    • Cervical motion tenderness
    • Adnexal tenderness (usually bilateral) or adnexal mass
    • Intermenstrual bleeding
    • Fever, chills, nausea, and vomiting (less common)
  • Acute perihepatitis (Fitz-Hugh-Curtis syndrome) occurs primarily through direct extension of N gonorrhoeae or Chlamydia trachomatis from the fallopian tube to the liver capsule and overlying peritoneum.
• Male genitourinary tract
  • In men, urethritis is the major manifestation of gonococcal infection.
  • Initial characteristics include burning upon urination and a serous discharge. A few days later, the discharge usually becomes more profuse, purulent, and, at times, blood-tinged. Acute epididymitis may also be caused by N gonorrhoeae, especially in men younger than 35 years. This is usually unilateral and often occurs in conjunction with a urethral exudate.
• Sex-independent manifestations
  • Both men and women may exhibit gonococcal infection of the pharynx, rectum, and eye.
  • Gonococcal pharyngitis is most commonly acquired during orogenital contact, with fellatio predisposing to infection more so than cunnilingus. Pharyngitis is often asymptomatic; however, it may present as exudative pharyngitis with cervical lymphadenopathy.
  • Although rectal cultures are positive for gonorrhea in up to 40% of women with cervical gonorrhea (a similar percentage noted in infected homosexual men), symptoms of proctitis are unusual.
  • Eye involvement in adults occurs by autoinoculation of gonococci into the conjunctival sac from a primary site of infection, such as the genitals. The most common form of presentation is a purulent conjunctivitis, which may rapidly progress to panophthalmitis and loss of the eye unless promptly treated.
    
    

    

    This patient presented with gonococcal urethritis, which became systemically disseminated, leading to gonococcal conjunctivitis of the right eye. Courtesy of the CDC/Joe Miller, VD.

    [ CLOSE WINDOW ]

    

    This patient presented with gonococcal urethritis, which became systemically disseminated, leading to gonococcal conjunctivitis of the right eye. Courtesy of the CDC/Joe Miller, VD.

• Neonates
  • In neonates, bilateral conjunctivitis (ophthalmia neonatorum) often follows vaginal delivery from an infected mother. However, transmission to the newborn can also occur in utero or in the postpartum period.
  • Symptoms of gonococcal conjunctivitis include eye pain, redness, and a purulent discharge. Neonates may also acquire pharyngeal, respiratory, or rectal infection or disseminated gonococcal infection (DGI).
  • The organism can cause permanent injury to the eye very quickly. Prompt recognition and treatment are essential to avoid blindness. Blindness due to neonatal gonococcal infection is a serious problem in developing countries but is now uncommon in the United States and in other countries where neonatal conjunctival prophylaxis with antimicrobial therapy is routine.
• Disseminated gonococcal infection
  • DGI follows 1%-2% of mucosal gonococcal infections and is caused by hematogenous dissemination of gonococci from the primary site. The symptoms vary greatly from patient to patient. By the time the symptoms of DGI appear, many patients no longer have any localized symptoms of mucosal infection.
  • Risk factors of DGI include the following:
    • Complement deficiency
    • Female sex: Disseminated infection may be more common in women, as gonorrhea in women is often asymptomatic, allowing for dissemination before symptoms occur.³
    • Menses: In menstruating females, the illness is observed shortly after the end of menstruation.
    • Pharyngeal infection and pregnancy: These may also be predisposing factors to gonococcal bacteremia.
    • Specific serotypes: Certain strains of gonorrhea causing asymptomatic genital infections are seen in association with DGI.⁸
  • The classic presentation of DGI is an arthritis dermatitis syndrome. Joint or tendon pain is the most common presenting complaint in the early stage of infection. Many patients with DGI describe migratory polyarthralgia, especially of the knees, elbows, and more distal joints, and may also have tenosynovitis. The early tenosynovitis most commonly affects the flexor tendon sheaths of the wrist or the Achilles tendon ("lovers' heels"). The dermatitis consists of lesions varying from maculopapular to pustular, often with a hemorrhagic component. Lesions usually number 5-40, are peripherally located, and may be painful before they are visible. Fever is common but rarely exceeds 38°C.
  • The second stage of DGI is characterized by septic arthritis, by which time the skin lesions have disappeared and blood culture results are nearly always negative. The knee is the most common site of purulent gonococcal arthritis.
  • Rare complications of DGI include gonococcal meningitis and endocarditis.
  • Gonococcal meningitis may be clinically indistinguishable from meningococcal meningitis upon presentation, although the course of gonococcal meningitis is usually less rapid than that of meningococcal meningitis.
  • Gonococcal endocarditis is more common in men than in women, with the aortic valve affected most commonly. A subacute onset of fever, chills, sweats, and malaise may indicate the presence of gonococcal endocarditis. Patients with endocarditis may develop atypical chest pain, cough, and dyspnea and may also develop the arthralgias and rash typical of DGI. Gonococcal endocarditis can cause severe valvular damage and death if not recognized and treated rapidly.

Physical

Patients with gonococcal infection may have the typical signs and symptoms of gonococcal diseases, especially in the genital tract. Sometimes, however, patients may have no localized signs or symptoms.

• Female genitourinary tract
  • Mucopurulent or purulent cervical discharge
  • Vaginal discharge or bleeding; vulvovaginitis in children
  • Lower abdominal tenderness with or without rebound tenderness
  • Adnexal tenderness (associated with ascending infection)
  • Cervical motion tenderness (associated with ascending infection)
  • Fever
  • Right upper abdominal tenderness (with Fitz-Hugh-Curtis syndrome)
• Male genitourinary tract
  • Mucopurulent or purulent urethral discharge
  • Unilateral epididymal tenderness and edema with or without penile discharge or dysuria
  • Penile edema without other overt inflammatory signs
  • Urethral stricture (uncommon; more often seen in preantibiotic era with urethral irrigation using caustic liquids)
• Rectal
  • Mucopurulent or purulent discharge with or without rectal bleeding
  • Mucopurulent exudate and inflammatory in the rectal mucosa
  • Rectal abscess (less common)
• Eyes
  • Purulent conjunctivitis (usually bilateral in ophthalmia neonatorum but usually unilateral when caused by secondary self-inoculation)
  • Corneal ulceration (in untreated ocular disease)
• Disseminated gonococcal infection
  • Patients with DGI may present with any of the following nonspecific findings:
  • Fever (usually <39°C)
  • Polyarthralgia, mainly of knees, elbows, and distal joints; rare involvement of axial skeleton
  • Asymmetric oligoarthritis or tenosynovitis of usually two or more joint regions
  • Septic joints, which may be warm, tender, and edematous
  • Skin lesions, characteristically few in number and found mostly on the distal extremities as small papulopustular lesions with an erythematous periphery; may progress to hemorrhagic bullae or necrotic pustular lesions
  • Usually no urogenital symptoms

Causes

Gonococcal infection usually follows mucosal inoculation during vaginal, anal, or oral sexual contact or perinatally.

• Sexual contact
  • The risk of transmission of N gonorrhoeae from an infected woman to the urethra of her male partner is approximately 20% per episode of vaginal intercourse and rises to 60%-80% after 4 or more exposures.
  • In contrast, the risk of male-to-female transmission approximates 50%-70% per contact, with little evidence of increased risk with more sexual exposures.
  • Transmission through penile-rectal contact is fairly efficient.
  • Persons who have unprotected intercourse with new partners frequently enough to sustain the infection in a community are defined as core transmitters.
• Neonatal gonococcal infection may follow conjunctival infection, which is obtained during passage through the birth canal. In addition, direct infection may occur through the scalp at the sites of fetal monitoring electrodes.
• Autoinoculation can occur when a person touches an infected site (genital organ) and contacts skin or mucosa.

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