Gonorrhea 

Gonorrhea is one of the most common and oldest known sexually transmitted diseases (STDs). This condition is a purulent infection of mucous membrane surfaces caused by Neisseria gonorrhoeae. Gonococcal infection causes urethritis, cervicitis, epididymitis, pharyngitis, proctitis, and pelvic inflammatory disease (PID) and can spread throughout the body to cause both localized and disseminated disease. Complications include ectopic pregnancy and increased susceptibility to human immunodeficiency virus (HIV) infection. Most commonly, the term gonorrhea refers to urethritis and/or cervicitis in a sexually active person.

Gonococcal infections following sexual and perinatal transmission are a major source of morbidity worldwide. In the developed world, where prophylaxis for neonatal eye infection is standard, the vast majority of infections follow genitourinary mucosal exposure.

In the pediatric population, the importance of gonorrhea is 3-fold, as follows:

• As a common and preventable STD in the sexually active teenage population
• As a perinatal infection at childbirth
• As a forensic aid in investigating sexual abuse

See also the following:

• Emergent Management of Gonorrhea
• Gonococcal Infections
• Gonococcemia
• Gonococcus
• Pediatric Chlamydial Infections
• Pelvic Inflammatory Disease
• Pelvic Inflammatory Disease/Tubo-ovarian Abscess

Neisseria gonorrhoeae is a gram-negative, intracellular diplococcus that grows best in the laboratory in an environment rich in carbon dioxide. Organisms are spread by sexual contact and can also be vertically transmitted during childbirth. N gonorrhoeae has a predilection for columnar mucosal cells; virtually any mucous membrane can be infected by this microorganism. The physiologic ectopy of the squamocolumnar junction onto the ectocervix in the adolescent female is one factor that causes particular susceptibility to this infection.

The pathophysiology of N gonorrhoeae and the relative virulence of different subtypes depend on the antigenic characteristics of the respective surface proteins. Certain subtypes are able to evade serum immune responses and are more likely to lead to disseminated (systemic) infection.

Well-characterized plasmids commonly carry antibiotic-resistance genes, most notably penicillinase. Plasmid and nonplasmid genes are transmitted freely between different subtypes. The ensuing exchange of surface protein genes results in high host susceptibility to reinfection. The exchange of antibiotic resistance genes has led to extremely high levels of resistance to beta-lactam antibiotics over the last 2 decades. More recently, fluoroquinolone resistance has also been documented on multiple continents and in widespread populations within the United States.^[1]

Infection of the lower genital tract, the most common clinical presentation, primarily manifests as male urethritis and female endocervicitis. Infection of the pharynx, rectum, and female urethra occur frequently but are more likely to be asymptomatic or minimally symptomatic. Retrograde spread of the organisms occurs in as many as 20% of women with cervicitis, often resulting in pelvic inflammatory disease (PID), with salpingitis, endometritis, and/or tubo-ovarian abscess. Retrograde spread can lead to frank abdominal peritonitis and to a perihepatitis known as Fitz-Hugh-Curtis syndrome.

Long-term sequelae of PID, such as tubal factor infertility, ectopic pregnancy, and chronic pain, may occur in up to 25% of affected patients. Epididymitis or epididymo-orchitis may occur in men after gonococcal urethritis. Lower genital infection is a risk factor for the presence of other sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV).

Conjunctivitis can occur in adults as well as in children following direct inoculation of organisms and can lead to blindness.

Disseminated gonococcal infection (DGI) occurs following approximately 1% of genital infections. Patients with disseminated gonococcal infection may present with symptoms of rash, fever, arthralgias, migratory polyarthritis, septic arthritis, tendonitis, tenosynovitis, endocarditis, or meningitis. Three fourths of the cases of disseminated gonococcal infection occur in women; susceptibility is increased if the primary mucosal infection occurs during menstruation or pregnancy. Changes in the vaginal environment at these times may foster changes in the gonococcal surface features and phenotype that render the organisms more resistant to host defenses in the bloodstream and more likely to disseminate.

Gonococcal infection usually follows mucosal inoculation during vaginal, anal, or oral sexual contact. It also may be due to inoculation of mucosa by contaminated fingers or other objects.

Neonatal infection may follow conjunctival inoculation during birth or direct infection through the scalp at the sites of fetal monitoring electrodes. In children, infection may occur from sexual abuse by an infected individual or possibly nonsexual contact in the child's household or in institutional settings.

Risk factors for gonorrhea include the following:

• Sexual exposure with an infected partner without barrier protection (eg, failure to use a condom or condom failure)^[2]
• Multiple sex partners
• Low socioeconomic status
• Minority status: Blacks, Hispanics, and Native Americans have the highest rates in the United States
• History of concurrent or past sexually transmitted diseases (STDs)
• Exchange of sex for drugs or money
• Use of crack cocaine
• Early age of onset of sexual activity
• Pelvic inflammatory disease (PID): Use of an intrauterine device (IUD)

United States statistics

Gonorrhea is the second most commonly reported infectious disease in the United States, after chlamydia. The actual incidence is difficult to determine due to high rates of asymptomatic carriage as well as underreporting. In 2008, 336,742 cases were reported in the United States; in 2009, 301,174 cases were reported.^{[3, 4]} The national average in 2009 was 99.1 cases per 100,000 population, a 10.5% decrease from 2008, with considerable state-to-state variation.^[3] The rate of gonococcal infection was dropping until 2004, when it was at its lowest level since 1941, but this rate has since stabilized at a plateau. The estimate of total cases is approximately 700,000 cases per year. In children who have been sexually abused, rates of recovery of gonorrhea range from 1% to 30%. In female adolescents who are sexually active, asymptomatic carriage of gonorrhea occurs in 1-5%.

Within the United States, carriage rates highly depend on the geographic area, the racial and ethnic group, and sexual preferences.

The Southeastern states have the highest rates of infection; the rates in the midwest and northeast are much lower. Rates of infection range from about 246.4 cases per 100,000 population in Mississippi to 8 cases per 100,000 population in Vermont. The Centers for Disease Control and Prevention (CDC) set a campaign (Healthy People 2010: http://www.cdc.gov/nchs/healthy_people.htm) that targeted an incidence rate of 19 cases per 100,000 population. Utah, Montana, Idaho, Maine, Vermont, and New Hampshire, are the only states currently exceeding that target, along with Puerto Rico (see the first image below).^[3] Healthy People 2020 is in the process of being developed (http://healthypeople.gov/2020/default.aspx).

International statistics

N gonorrhoeae has been the most common sexually transmitted disease (STD) worldwide for at least most of the 20th century, with an estimated 200 million new cases annually. Public health initiatives in the developed world have resulted in declining incidence of the disease since the mid 1970s, but, as noted earlier, gonococcal infection is still the second most common notifiable disease in the United States, and Western European rates approximate those in the United States. Disease rates are unknown for most developing countries.

The incidence of antibiotic-resistant strains has been rising since the late 1940s. Of greatest concern historically was the high percentage of cases due to penicillinase-producing N gonorrhoeae (PPNG). However, fluoroquinolone resistance has increased rapidly over the past decade on most continents and within the United States. The CDC reported fluoroquinolone resistance in 6.8% of 2004 isolates, 9.4% of 2005 isolates, and 13.3% of 2006 isolates.^[1]

Racial differences in incidence

Although race has no intrinsic effect on susceptibility, in the United States, the frequency of gonorrhea is increased among urban dwellers, individuals of lower socioeconomic status, and minorities of any population. This may be due to decreased access to diagnosis and treatment, lack of adequate care (ie, education, diagnosis, and treatment) leading to increased transmission rates, and/or reflection bias due to data collection site preference (eg, urban emergency departments [EDs] and STD clinics), as well as true differences in prevalence.

All sexually active populations are at risk and the level of risk rises with the number of sex partners and the presence of other STDs.

Sexual differences in incidence

The male-to-female ratio is approximately 1:1.2; however, females may be asymptomatic, whereas males are rarely asymptomatic. Men who have sex with men (MSM) are much more likely to acquire and carry gonorrhea and have far higher rates of antibiotic-resistant bacteria. Serious sequelae are much more common in women, in whom pelvic inflammatory disease (PID) may lead to ectopic pregnancy or infertility and for whom disseminated gonococcal infection (DGI) is more likely.

Age-related differences in incidence

The highest incidence of gonococcal infection in the United States is among persons aged 15-24 years.^[3] This is likely due to the following:

• Increased numbers of sexual partners
• Decreased access to or use of health care
• Physiologic ectopy of the squamocolumnar junction in females
• Decreased use of barrier contraceptives

Infection in children is a marker for child sexual abuse and should be reported as such, although a 2007 review provided some support for nonsexual transmission between children and for transmission from adults to children related to poor hand hygiene.^[5]

The following image depicts US gonorrhea incidence rates by age and sex.

The prognosis for patients with gonorrhea is excellent if the diagnosis is made and treatment is started before progression or complications occur. Most gonococcal infections respond quickly to cephalosporin therapy.

Complications from gonococcal infection may include the following:

• Scarring of the upper reproductive tract in women with pelvic inflammatory disease (PID), possibly leading to infertility, chronic pelvic pain, and ectopic pregnancy
• Urethral scarring in men, possibly leading to decreased fertility or to bladder-outlet obstruction
• Destruction of joint articular surfaces
• Possible prematurity, neonatal infection, and miscarriage resulting from gonococcal infections in pregnant women
• Possible corneal scarring and permanent vision impairment or blindness resulting from gonococcal ophthalmic infection
• Possible sepsis in infants following neonatal exposure to maternal gonorrhea
• Possible permanent neurologic sequelae resulting from gonococcal meningitis
• Destruction of cardiac valves
• Death from congestive heart failure (CHF) or meningitis

Pelvic inflammatory disease

PID is generally the most feared complication of gonococcal infection, because it is one of the leading causes of female infertility and often leads to hospitalization. This can be devastating to any woman, especially an adolescent who potentially has many years of childbearing ahead of her. In a 2011 study, female adolescents with PID were more likely than older women to have a rapid recurrence of PID or to become pregnant despite reporting more consistent condom use.^[6]

Tubo-ovarian abscess and, rarely, tubal perforation with peritonitis and death, especially if recurrent. Females with recurrent PID have high rates of ectopic pregnancy and infertility (approximately 8% after 1 episode, 20% after 2 episodes, and 40% after 3 or more episodes).

Epididymitis and orchitis

Epididymitis and orchitis occur infrequently in males who go untreated. These conditions usually respond well to the same antibiotics used for uncomplicated urethritis but are administered for a longer course.

Arthritis

Gonorrhea is the most common cause of arthritis in the adolescent. However, arthritis (septic or reactive) is a rare complication of this disease; but because it mimics septic arthritis, excluding the possibility of gonococcal infection in any adolescent with acute onset of pyogenic arthritis is important. Adequate diagnosis may require culturing extraarticular sites for Neisseria gonorrhoeae.

Other

Perihepatitis secondary to gonorrhea (Fitz-Hugh-Curtis syndrome) presents as right upper quadrant pain and nausea in patients with untreated gonorrhea.

Disseminated gonococcal infection (DGI) is an acute illness that causes fever, asymmetric polyarthralgias, and skin pustules overlying small joints in patients with gonorrhea. Disseminated infection may also lead to meningitis or endocarditis.

In newborns, vertical transmission can cause conjunctivitis, known as ophthalmia neonatorum, and permanent damage and blindness, if untreated.

Oral sex with an infected partner can result in pharyngitis, and, similarly, anal infection can arise from anal sex or local spread from a vaginal source.

Discuss safe sexual practices with all individuals in whom gonorrhea is suspected.

Proper education to prevent gonorrhea may be more effective than simplistic instructions to avoid sex, especially in the teenaged population. Teenagers involved with abstinence-only campaigns have unchanged sexually transmitted disease (STD) rates and disproportionately acquire anal and oral infections, rather than vaginal infections (the perception is that if an activity is not vaginal sex, it is not sex).

Patients should know the method of disease transmission and the adverse impact of recurrent infections on future fertility; they should be counseled about the risks of complications following gonococcal infection and the risk of other STDs; and they should always be instructed to refer any sex partners for prompt evaluation and treatment. In addition, these individuals should be aware they should avoid sexual contact until medication is finished and until their partners are fully evaluated and treated. Thereafter, they should avoid unprotected contact.

The discussion of responsible sexual behavior should not be limited or withheld because of personal religious or moral views because these may not be shared by the patient, and teenagers are notorious for sexual experimentation; evidence suggests that this limited discussion does the teenage population a huge disservice. This advice is especially pertinent in states where sexual education is almost nonexistent in the school system because of abstinence-only teaching, which is misleading and factually inaccurate.

In one study in Peru, a bundle of interventions that included extensive public health efforts, including training of local medical personnel, specific and presumptive treatment, outreach to female sex workers, and supply of barrier contraception, may have been effective at reducing the prevalence of several STDs, although the effect did not reach statistical significance overall. The effects were more greatly pronounced (and significant) among female sex workers and young adult women. The study was hampered by several methodological limitations, such as comparing different cities as controls, which make drawing conclusions from the data difficult.^[7]

Abstinence education

Although the most effective STD prevention is abstinence from sex, this is oftentimes an unrealistic expectation, especially in the teenaged population; in fact, 88% of teenagers who pledged abstinence in middle and high school still engaged in premarital sex. Moreover, they tend to have riskier, unprotected sex because of their lack of education; those who pledge before having sex have a 33% higher prevalence rate of STDs than those who had sex and then retrospectively pledged, with nonpledgers falling in between. This is despite a lower number of partners and an older age at first intercourse in pledgers.

Of course, abstinence should be explained to be the best option, but a more practical expectation is abstinence from sex with someone known or suspected of having an STD until treatment is obtained and completed. In light of the difficulty in knowing a potential partner's sexual history (or honesty), strongly recommend the use of condoms as a reasonable alternative to abstinence.^[2]

Pledgers are actually less likely to be aware of their STD status and are less likely to seek testing, even if their STD rates are similar overall (again, highlighting a lack of appropriate sexual education). Stress that oral or anal sex can also transmit disease.

Risks of unprotected sex

Patients should also be counseled about the additional risks of unprotected sex, such as the acquisition of more serious or lifelong infections such as herpes, hepatitis B, and human immunodeficiency virus (HIV), and, of course, about the risks of pregnancy. The emotional aspect of sexual relationships may also need to be addressed, especially in teenage girls. Teenagers are vulnerable in that they are sexually mature but not yet emotionally mature.

For patient education information, see Sexual Health Center, Sexually Transmitted Diseases, Gonorrhea, and Chlamydia.

Patient education materials are also available at The Centers for Disease Control and Prevention (CDC) Website (Sexually Transmitted Diseases – Gonorrhea) and from many local public health departments.