Gonorrhea overview

# Overview
Gonorrhea (gonorrhoea in British English) is among the most common sexually transmitted diseases in the world. In the United States, gonorrhea is the second most common STD (after chlamydia).
Neisseria gonorrhoeae is a species of Gram-negative, coffee bean-shaped diplococci bacteria responsible for the sexually transmitted infection gonorrhea.
Gonorrhea can infect mucus-secreting epithelial cells in both men and women.
The first place this bacterium infects is usually the columnar epithelium of the urethra and endocervix. Non-genital sites in which this bacterium thrives include the rectum, the oropharynx, and the conjunctivae of the eyes. 
Established routes of transmission of Neisseria gonorrhoeae include vaginal and rectal intercourse, fellatio, cunnilingus, and perinatal.
The main pathogenicity of the Neisseria gonorrhea stems from the ability of the surface pili to attach to the surface of the urethra, fallopian tubes, and endocervix.
In pregnancy, gonococcus can be transmitted to the fetus at the time of delivery. 
Additionally, development of disseminated gonococcal infection is the result of Neisserial organisms' dissemination to the blood.
Common risk factors in the development of gonorrhea include sexual activity, multiple sex partners, previous history of sexually transmitted diseases, having a sexual partner with a past history of any sexually transmitted disease, and failure to use condoms during sex.
In 50 to 70% of women, the initial infection with Neisseria gonorrhea may be asymptomatic. The most common complication of untreated gonorrhea is pelvic inflammatory disease (PID), which may lead to increased risks of ectopic pregnancy. If left untreated, ectopic pregnancy can be life-threatening to the mother.
In men, gonorrhea usually results in urethritis, which may result in dysuria. If left untreated, gonorrhea may result in inflammation of the epididymis (epididymitis), prostate gland (prostatitis), and urethral structure. Disseminated gonococcal infection (DGI) occurs in about 0.5 to 3% of patients, commonly following asymptomatic mucosal infection in both sexes.
Empiric treatment for gonorrhea is usually initiated prior to receipt of laboratory results. Nucleic acid amplification tests (NAATs) are the test of choice in all individuals who present with urogenital symptoms.
The mainstay of therapy for gonococcal infections is antimicrobial therapy. Gonorrhea treatment is complicated by the ability of N. gonorrhoeae to develop resistance to antimicrobials; accordingly, a combination therapy with azithromycin and a cephalosporin is used to improve treatment efficacy and potentially slow the emergence and spread of antibiotic resistance.
Effective measures for the primary prevention of gonorrhea infection include practicing abstinence, avoiding high-risk sexual behaviors (e.g., having unprotected sex or multiple sexual partners), and using latex condoms. Measure for the secondary prevention of gonorrhea infection include early detection, treatment of sexual partners, and treatment of other sexually transmitted infections (e.g., chlamydia).

# Historical Perspective
Gonorrhea is an ancient disease with biblical references. However, the exact time of onset of gonorrhea in history cannot be accurately determined from the extant historical record. In 1879, gonorrhea was referred to as the clap by German bacteriologist Albert Neisser.

# Classification
Based on anatomic location, gonorrhea may be classified into three subtypes: urogenital, extragenital, and disseminated gonococcal infection.
Additionally, gonococcal infections may be classified into many subtypes according to the affected organ system.

# Pathophysiology
Gonorrhea is a sexually transmitted disease (STD) that is caused by the bacterium Neisseria gonorrhea.
It can infect mucus-secreting epithelial cells in both men and women.
Established routes of transmission of the Neisseria gonorrhoeae include vaginal intercourse, rectal intercourse, fellatio, cunnilingus, and perinatal.
The main pathogenicity of the Neisseria gonorrhea stems from the ability of the surface pili to attach to the surface of the urethra, fallopian tubes, and endocervix.
Another virulence factor of gonorrhea is porin. There are two main porin serotypes: PorB.1A strains (resulting in a disseminated gonococcal infection) and PorB.1B strains (resulting in local genital infections).
In pregnancy, gonococcus can be transmitted to the fetus at the time of delivery. This results in infection of the conjuctiva. This appears 1 to 4 days after birth as severe discharge with marked swelling and redness of the eyelids and conjunctiva.
Additionally, development of disseminated gonococcal infection is the result of Neisserial organisms' dissemination to the blood due to a variety of predisposing factors, such as change in PH, pregnancy, menstruation, PorB.1A strains, and complement deficiencies.

# Causes
Neisseria gonorrhoeae, also known as gonococci (plural), gonococcus (singular), or gonorrhoea (in British English), is a species of Gram-negative, coffee bean-shaped diplococci bacteria that is responsible for the sexually transmitted infection gonorrhea.
Gonorrhea (gonorrhoea in British English) is among the most common sexually transmitted diseases in the world. The term comes from the Ancient Greek word  (gonorrhoia), literally "flow of seed"; in ancient times, it was incorrectly believed that the pus discharge associated with the disease contained semen.

# Differential diagnosis
Gonorrhea must be differentiated from other sexually transmitted pathogens, nongonococcal urethritis, vaginitis, cervicitis, urinary tract infections, prostatitis, and orchitis.
Additionally, disseminated gonococcal infection must be differentiated from herpes simplex virus (HSV), nongonococcal septic arthritis, syphilis, HIV infection,  rheumatic fever, reactive arthritis , and Lyme disease.

# Epidemiology
Gonorrhea is a very common infectious disease. 
In the United State, gonorrhea is the second most common STD (after chlamydia).
In 2012, the incidence of gonorrhea was reported as 106 million cases worldwide.
In 2014, a total 350,062 cases of gonorrhea were reported in United States.

# Risk factors
Common risk factors for the development of gonorrhea include sexual activity, having multiple sex partners, previous history of sexually transmitted diseases, having a partner with a past history of any sexually transmitted disease, and failure to use a condom during sex.

# Screening
The U.S. Preventive Services and Task Force (USSTF) recommends screening for gonorrhea in sexually active women age 24 years and younger and in older women who are at increased risk for infection. Current evidence is insufficient to assess the balance of benefits and harms of screening for gonorrhea in heterosexual men. However, USSTF recommends at least annual screening for gonorrhea among men who have sex with men (MSM).

# Natural history, complications, and prognosis
In 50 to 70% of women, the initial infection with Neisseria gonorrhea may be asymptomatic.
Initial infection is usually observed in the cervical region, but due to the presence of the surface pili, the infection may ascend through the uterus into the fallopian tubes and finally out into the peritoneal cavity.  
The exact incubation period of gonorrhea is unknown. It may result in cervicitis and urethritis, which may present with dysuria, vaginal pruritus, and vaginal mucopurulent discharge.   
If gonococcal infection is left untreated, it can progress to fibrosis. Fibrosis can result in fallopian tube stricture, tubo-ovarian cyst or abscess, pelvic inflammatory disease (PID), Perihepatitis (Fitz-Hugh-Curtis syndrome), and/or bartholinitis. The most common complication of untreated gonorrhea is pelvic inflammatory disease (PID), which may lead to an increased risk of ectopic pregnancy. If left untreated, ectopic pregnancy can be life-threatening for the mother.
In men, gonorrhea usually results in urethritis, which may result in dysuria. If left untreated, gonorrhea may result in inflammation of the epididymis (epididymitis), prostate gland (prostatitis), and urethral structure (urethritis).
Disseminated gonococcal infection (DGI) occurs in about 0.5 to 3% of patients, commonly following asymptomatic mucosal infection in both sexes. 
Disseminated gonococcal infection can lead to the infection of multiple distant sites such as the brain, heart, and joints. The most common signs and symptoms include arthritis or arthralgias, tenosynovitis, and multiple skin lesions.
Common complications of gonococcal infection in women may include salpingitis, pelvic inflammatory disease, Infertility, dyspareunia, and ectopic pregnancy.
Common complications of gonococcal infection in men may include post-inflammatory urethral strictures, urethral abscess, penile lymphangitis, penile edema, urinary tract infection, and kidney failure.
The prognosis of urogenital and disseminated gonococcal infection are generally good with adequate treatment.

# Diagnosis

## History and Symptoms
It is critical to obtain a detailed and thorough sexual history from the patient. Specific areas of focus when obtaining a history from the patient include number and type of sexual partners, contraception use, and previous history of sexually transmitted diseases. The majority of women with gonorrhea are asymptomatic, while some have vaginal discharge, lower abdominal pain, or pain during intercourse. Common symptoms of gonococcal infection among men include urethritis, which is associated with burning with urination and discharge from the penis. Either sex may also acquire gonorrhea of the throat from performing oral sex on an infected partner, usually a male partner. Such infection is asymptomatic in 90% of cases, and produces a sore throat in the remaining 10%. The incubation period is 2 to 14 days, with most of these symptoms occurring between 4 and 6 days after infection. Rarely, gonorrhea may cause skin lesions and joint infection (pain and swelling in the joints) after traveling through the blood stream. Very rarely, it may settle in the heart, causing endocarditis, or in the spinal column, causing meningitis.

## Physical examination
Women with gonococcal infection usually appear to be well until the development of such complications as PID.  Physical examinations of women with gonococcal infection are usually remarkable for mucopurulent urethral, cervical, or vaginal discharge; friable appearance of the cervix; and cervical motion tenderness. Common physical examination finding of gonococcal infection in men include mucopurulent urethral discharge. Less commonly, penile edema and epididymal tenderness and edema (epididymitis) may also be seen as part of a complicated gonococcal infection.
Physical examination of patients with pharyngeal gonococcal infection is usually remarkable for mild pharyngeal exudates and rectal gonococcal infection is usually remarkable for mucopurulent anal discharge.
Physical examination of patients with disseminated gonococcal infection (DGI) is usually remarkable for fever, pustular or vesicular rash, and musculoskeletal findings.

## Images
The following images are associated with gonorrhea physical examination.
- Penile discharge in a patient with gonorrhea - Source: /
- Ophthalmia neonatorum - Source: /
- Lesions of skin and arthritic knee joints due to Neisseria gonorrhea - Source: /

## Laboratory tests
Empiric treatment for gonorrhea is usually initiated prior to the receipt of laboratory result. A microbiologic diagnosis is important for further management in order to determine the need for further testing, partner management, and public health considerations.
Any sexually active man or women presenting with signs and symptoms of urethritis, cervicitis, pelvic inflammatory disease, and epididymitis should undergo diagnostic testing for Neisseria  gonorrhea. Additionally, the possibility of disseminated gonococcal infection (DGI) should be considered in all young sexually active individuals who present with arthralgias or suspected  septic arthritis.
Common laboratory tests for gonococcal infection may include gram stain, culture, nucleic acid amplification tests (NAAT), and non-amplified tests. Nucleic acid amplification tests are the test of choice in all individuals who present with urogenital symptoms.
Additionally, synovial fluid analysis is usually sent for cell count, differential, gram stain, bacterial culture and NAAT in patients with suspected DGI.

## Other diagnostic studies
Other diagnostic studies are used when NAAT or culture are not available. Other diagnostic studies for gonorrhea infection include rapid NAAT assay (modular-cartridge based platform), leukocyte esterase urine test, immunochromatographic tests, nucleic acid hybridization tests, and enzyme immunoassay (EIA).

# Treatment

## Medical therapy
The mainstay of therapy for gonococcal infections is antimicrobial therapy.  Gonorrhea treatment is complicated by the ability of N. gonorrhoeae to develop resistance to antimicrobials; accordingly, a combination therapy with azithromycin and a cephalosporin is used to improve treatment efficacy and potentially slow the emergence and spread of antibiotic resistance.

## Antibiotic resistant
Gonorrhea treatment is complicated by the ability of Neisseria gonorrhoeae to develop resistance to antimicrobials. High-level resistance to expanded-spectrum cephalosporins and azithromycin is now reported, and it seems that developing another effective treatment has become unaffordable for pharmaceutical companies, though new combination antibiotic treatments are being evaluated. There are no affordable alternative therapeutic options currently available for the treatment of gonococcal disease, and it seems even newly developed antibiotics will be short-term solutions, as the bacterium may well develop resistance to them, too.
In 2006, CDC had five recommended treatment options for gonorrhea. Currently, the U.S. has only one remaining option.

## Primary prevention
Effective measures for the primary prevention of gonococcal infection include accurate risk assessment and counseling, practicing abstinence, avoiding high-risk sexual behaviors (e.g., unprotected sex or multiple sexual partners), using latex condoms, and being in a long-term and monogamous relationship with an uninfected partner.

## Secondary prevention
Strategies for the secondary prevention of gonococcal infection include early detection, treatment of sexual partners, and treatment of other sexually transmitted infections (e.g., chlamydia).