clinical presentation of gonorrhea

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Gonorrhoea (Neisseria gonorrhoeae infection)

• Gonorrhoea is a preventable and curable sexually transmitted infection caused by the bacterium Neisseria gonorrhoeae , which is primarily transmitted through vaginal, oral or anal sex.
• In 2020 there were an estimated 82.4 million new infections among adults globally.
• Most women with gonorrhoea do not have symptoms, and when they do, vaginal discharge is common, while most men present with discharge from their penis.
• If left untreated, gonorrhoea can lead to infertility in both men and women and other sexual and reproductive health complications. It also increases the risk of HIV infection.
• Antimicrobial resistance to gonorrhoea is a serious and growing problem, rendering many classes of antibiotics as ineffective with the risk of becoming untreatable.

Gonorrhoea is a common sexually transmitted infection caused by a type of bacteria. It usually spreads through vaginal, oral or anal sex. Gonorrhoea is treatable and curable with antibiotics.

Most cases of gonorrhoea can be prevented with regular and correct condom use.

Gonorrhoea causes different symptoms in women and men. Women often feel no symptoms, but untreated infection can lead to infertility and problems during pregnancy.

Common symptoms in men include pain or burning when urinating, discharge from the penis and sometimes pain in the testes.

Gonorrhoea can be passed from a pregnant mother to her baby.

Gonococcal infection increases the risk of getting and spreading HIV.

Scope of the problem

In 2020, WHO estimated 82.4 million new infections with N. gonorrhoeae among adults aged 15 to 49 years. Prevalence of gonorrhoea is highest among vulnerable populations such as men who have sex with men, sex workers, transgender women and adolescents and young people in high burden countries.

Gonorrhoea is treatable and can be cured with some antibiotics. However, the emergence of N. gonorrhoeae resistant to antibiotics are making treatment of gonorrhoea more and more challenging, with the risk of becoming untreatable. Rational use of antibiotics and the development of new ones are critical to decrease this eminent threat.

Signs and symptoms

Gonorrhoea can cause symptoms in the genitals, anus or throat. Men and women may experience different symptoms. Symptoms usually begin 1–14 days after sexual contact with an infected person.

In men, common symptoms include

• a white, yellow or greenish discharge from the penis
• pain or burn when urinating
• painful or swollen testes.

Most women with gonorrhea do not have symptoms or do not notice them. If they occur, they can include

• vaginal discharge
• pain or burning when urinating
• vaginal bleeding between periods or during sexual intercourse.

Anal infection in women and men can cause

• painful bowel movements.

Throat infections often have no symptoms. If symptoms occur, they can include redness, pain and sore throat.

Infants born to mothers with gonorrhoea may develop an eye infection. This causes redness, pain, soreness, ulcers and tearing. This is preventable with eye medications for newborns.

Possible complications

Untreated N. gonorrhoeae infections can lead to complications and sequelae in women, such as pelvic inflammatory disease (PID), ectopic pregnancy, and infertility.

Complications in men are scrotal swelling, urethral stricture and infertility.

Neonatal conjunctivitis (eye infection) if untreated may lead to blindness.

In rare cases, disseminated gonococcal infection can occur and it is manifested as fever and infection in multiple organs of the body such as skin, heart, joints and meninges.

Infection with gonorrhoea can cause stigma and affect personal relationships. These effects are important but often not quantifiable.

Molecular tests are the gold standard for diagnosing N. gonorrhoeae which can be performed in the laboratory or at the point of care. Rapid diagnostic tests are currently under development.

Gram stain microscopy is used in some laboratories. However, this method is less sensitive in women with vaginal/cervical discharge as well as for throat and anal infections.

In many primary health care settings where diagnostic capacity for detecting N. gonorrhoeae is not available, a syndromic approach for case management is recommended.

Sexual history taking and risk assessment are crucial in evaluating a service user before diagnosis. Clinical examination, speculum examination (in women) and palpation can provide important clues to clinical diagnosis.

Urine samples (preferred for men) are commonly used for diagnosing gonorrhoea, but swabs (preferred for women) from genital and other sites (anus, throat, conjunctiva) can be used depending on the location of symptoms, sexual practices and medical history.

Because majority of cases are without symptoms, screening strategies for populations at increased risk of gonorrhoea to prevent the spread of infection and the development of complications is recommended. Testing is usually coupled with tests for other sexually transmitted infections (such as HIV, syphilis and chlamydia).

Antimicrobial sensitivity testing for N. gonorrhoeae is done in cases of clinical treatment failure to check if the pathogen is resistant to medications. WHO recommends that countries monitor their patterns of antimicrobial resistance to inform treatment recommendations.

People with gonorrhoea should be treated as soon as possible.

Gonorrhoea is treated with antibiotics called cephalosporins. These include:

• ceftriaxone, usually given by injection and is the preferred treatment
• cefixime, usually given orally with another antibiotic, azithromycin, but only when ceftriaxone is not feasible.

People should wait 7 days after taking the medicine before having sex. They should notify their sexual partner(s) to get tested or treated. 

Treatments can fail due to:

• not taking medications as directed
• reinfection
• the bacterium becoming resistant to the drug
• having another untreated infection with similar symptoms.

People with gonorrhoea should continue treatment until the infection is cured.

Most cases of gonorrhoea can be prevented with consistent and correct condom use in every sexual encounter.

People with gonorrhoea should notify current and recent sexual partners to help prevent the spread of the disease.

Antibiotic eye ointment is recommended for newborns to prevent gonococcal eye infection.

There are no specific vaccines for the prevention of gonorrhoea.However, studies are showing promising results with the use of a meningococcal type B vaccine (4CMenB) that seems to offer cross-protection against gonorrhoea. WHO is monitoring vaccine trials results.

WHO response

WHO has recognized gonorrhoea as a significant public health problem and has set ambitious targets to reduce the global burden through prevention, diagnosis, and treatment strategies. The Global Health Sector Strategies on HIV, viral hepatitis and STIs 2022–2030 aims to reduce the incidence of  N. gonorrhoeae  infection by 90% by 2030, compared to 2020 baseline. WHO is working with countries and partners to improve people-centred case management approaches, ensure appropriate treatment recommendations and effective testing and partner services strategies, support the development of new easy to use and affordable diagnostics and treatment, vaccine development and improve surveillance.

WHO also works with countries and partners to improve antimicrobial resistance stewardship through the Enhanced Gonorrhoea Antimicrobial Surveillance Program (EGASP) , which includes the implementation and use of better surveillance systems to detect antimicrobial resistance in N. gonorrhoeae and to inform locally appropriate treatment.

Neisseria gonorrhoeae

Sexually transmitted infections

Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP): general protocol

Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP): supplementary protocols

Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP): surveillance report 2022

• Patient Care & Health Information
• Diseases & Conditions

To determine whether you have gonorrhea, your healthcare professional will analyze a sample of cells. Samples can be collected with:

• A urine test. This can help identify bacteria in your urethra.
• A swab of the affected area. A swab of your throat, urethra, vagina or rectum can collect bacteria that can be identified in a lab.

Testing for other sexually transmitted infections

Your healthcare professional may recommend tests for other sexually transmitted infections. Gonorrhea increases your risk of these infections, particularly chlamydia, which often accompanies gonorrhea.

Testing for HIV also is recommended for anyone diagnosed with a sexually transmitted infection. Depending on your risk factors, tests for other sexually transmitted infections could be beneficial as well.

Gonorrhea treatment in adults

Adults with gonorrhea are treated with antibiotics. Due to emerging strains of drug-resistant Neisseria gonorrhoeae, the bacterium that causes gonorrhea, the Centers for Disease Control and Prevention recommends that uncomplicated gonorrhea be treated with the antibiotic ceftriaxone. This antibiotic is given as a shot, also called an injection.

After getting the antibiotic, you can still spread the infection to others for up to seven days. So avoid sexual activity for at least seven days.

Three months after treatment, the CDC also recommends getting tested for gonorrhea again. This is to make sure people haven't been reinfected with the bacteria, which can happen if sex partners aren't treated, or new sex partners have the bacteria.

Gonorrhea treatment for partners

Your sexual partner or partners from the last 60 days also need to be screened and treated, even if they have no symptoms. If you are treated for gonorrhea and your sexual partners aren't treated, you can become infected again through sexual contact. Make sure to wait until seven days after a partner is treated before having any sexual contact.

Gonorrhea treatment for babies

Babies who develop gonorrhea after being born to someone with the infection can be treated with antibiotics.

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Preparing for your appointment

You'll likely see your primary healthcare professional. Here's some information to help you get ready for your appointment.

What you can do

When you make the appointment, ask if there's anything you need to do in advance, such as restrict your diet.

Make a list of:

• Your symptoms, if you have any, including those that may seem unrelated to the reason for which you scheduled the appointment, and when they began.
• All medicine, vitamins or other supplements you take, including doses.
• Questions to ask your healthcare professional.

For gonorrhea, questions to ask include:

• What tests do I need?
• Should I be tested for other sexually transmitted infections?
• Should my partner be tested for gonorrhea?
• How long should I wait before resuming sexual activity?
• How can I prevent gonorrhea in the future?
• What gonorrhea complications should I be alert for?
• Are there brochures or other printed material that I can have? What websites do you recommend?
• Will I need a follow-up visit?

Don't hesitate to ask other questions.

What to expect from your doctor

Questions your healthcare professional is likely to ask you include:

• Have your symptoms been continuous or occasional?
• How severe are your symptoms?
• Have you been exposed to sexually transmitted infections?

What you can do in the meantime

Avoid sexual activity until you see your healthcare professional. Alert your sex partners that you're having symptoms so that they can arrange to see a member of their healthcare teams for testing.

• Gonorrhea: CDC fact sheet (detailed version). Centers for Disease Control and Prevention. https://www.cdc.gov/std/gonorrhea/stdfact-gonorrhea-detailed.htm. Accessed Sept. 21, 2023.
• Ghanem KG. Clinical manifestations and diagnosis of Neisseria gonorrhoeae infection in adults and adolescents. https://www.uptodate.com/contents/search. Accessed Sept. 21, 2023.
• Gonorrhea. Office on Women's Health. https://www.womenshealth.gov/a-z-topics/gonorrhea. Accessed Sept. 21, 2023.
• Gonorrhea. Merck Manual Professional Version. https://www.merckmanuals.com/professional/infectious-diseases/sexually-transmitted-diseases-stds/gonorrhea. Accessed Sept. 21, 2023.
• AskMayoExpert. Chlamydia, gonorrhea, and nongonococcal urethritis. Mayo Clinic; 2023.
• Speer ME. Gonococcal infection in the newborn. https://www.uptodate.com/contents/search. Accessed Sept. 21, 2023.
• Workowski KA, et al. Sexually transmitted infections treatment guidelines, 2021. Morbidity and Mortality Weekly Reports. 2021; doi:10.15585/mmwr.rr7004a1.
• Bachmann LH, et al. CDC clinical guidelines on the use of doxycycline postexposure prophylaxis for bacterial sexually transmitted infection prevention, United States, 2024. MMWR Recommendations and Report 2024;doi:10.15585/mmwr.rr7302a1.

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• Author: Shahab Qureshi, MD, FACP; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
• Sections Gonorrhea
• Practice Essentials
• Pathophysiology
• Epidemiology
• Patient Education
• Physical Examination
• Approach Considerations
• Smears With Gram Stain
• Isolation Via Culture
• Imaging Studies
• Nucleic Acid Amplification Tests
• Nucleic Acid Probe Signal Amplification
• Antibody-Antigen Testing
• Histologic Findings
• Testing for Gonorrhea in Males
• Testing for Gonorrhea in Females
• Testing for Gonorrhea at Extragenital Sites
• Pharmacologic Treatment Regimens
• Consultations
• Deterrence and Prevention
• HIV Infection
• WHO Guidelines on the Treatment of Neisseria gonorrhoeae Infection
• CDC Guidelines on the Treatment of Gonorrhea
• Medication Summary
• Antibiotics, Other
• Questions & Answers
• Media Gallery

Gonorrhea is a purulent infection of the mucous membrane surfaces caused by Neisseria gonorrhoeae. N gonorrhoeae is spread by sexual contact or through transmission during childbirth. The Centers for Disease Control (CDC) recommends that all patients with gonorrheal infection also be treated for presumed co-infection with Chlamydia trachomatis . [ 1 ]  

See Visual Findings of 9 Sexually Transmitted Infections , a Critical Images slideshow, to help make an accurate diagnosis.

Signs and symptoms

In women, the major genitourinary symptoms of gonorrhea include the following:

Vaginal discharge: The most common presenting symptom of gonorrhea, vaginal discharge from endocervicitis usually is described as thin, purulent, and mildly odorous; however, many patients have minimal or no symptoms from gonococcal cervicitis

Intermenstrual bleeding

Dyspareunia (painful intercourse)

Mild lower abdominal pain

If the infection progresses to pelvic inflammatory disease (PID), symptoms may 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

Fever, chills, nausea, and vomiting (less common)

In males, the major genitourinary symptoms of gonorrhea include the following:

Urethritis: The major manifestation of gonococcal infection in men; initial characteristics include burning upon urination and a serous discharge; a few days later, the discharge usually becomes more profuse, purulent, and, at times, tinged with blood

Acute epididymitis: Usually unilateral and often occurs in conjunction with a urethral exudate

Urethral strictures: Have become uncommon in the antibiotic era, but they can present with a decreased and abnormal urine stream, as well as with the secondary complications of prostatitis and cystitis

Rectal infection: May present with pain, pruritus, discharge, or tenesmus

In all individuals, the classic presentation of disseminated gonococcal infection (DGI) is an arthritis-dermatitis syndrome. Joint or tendon pain is the most common presenting complaint in the early stage of infection. The second stage of DGI is characterized by septic arthritis. The knee is the most common site of purulent gonococcal arthritis.

In neonates, in whom bilateral conjunctivitis (ophthalmia neonatorum) often follows vaginal delivery from an untreated mother with a gonococcal infection, symptoms of gonococcal conjunctivitis include the following:

Purulent discharge

Physical examination

Look for the following genitourinary symptoms during physical examination in females:

Mucopurulent or purulent vaginal, urethral, or cervical discharge

Vaginal bleeding; vulvovaginitis in children

Cervical friability - Tendency to bleed upon manipulation

Cervical motion tenderness during bimanual pelvic examination

Fullness and/or tenderness of the adnexa, unilateral or bilateral (eg, ovaries, fallopian tubes)

Lower abdominal pain/tenderness, with or without rebound tenderness

Possible low back pain - More common in progression to PID

Upper right abdominal tenderness (with perihepatitis)

Look for the following genitourinary symptoms during physical examination in males:

Mucopurulent or purulent urethral discharge: Obtained by milking the urethra along the shaft of the penis

Possible epididymitis: 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 the preantibiotic era with urethral irrigation using caustic liquids

See Clinical Presentation for more detail.

Culture is the most common diagnostic test for gonorrhea, followed by the deoxyribonucleic acid (DNA) probe and then the polymerase chain reaction (PCR) assay and ligand chain reaction (LCR). The DNA probe is an antigen detection test that uses a probe to detect gonorrhea DNA in specimens.

Specific culture of a swab from the site of infection is the gold standard for diagnosis at all potential sites of gonococcal infection. Cultures are particularly useful when the clinical diagnosis is unclear, when a failure of treatment has occurred, when contact tracing is problematic, and when legal questions arise.

In patients who may have DGI, all possible mucosal sites should be cultured (eg, pharynx, cervix, urethra, rectum), as should blood and synovial fluid (in cases of septic arthritis). Three sets of blood cultures also should be obtained.

See Workup for more detail.

For uncomplicated urogenital, anorectal, and pharyngeal gonococcal infection, a drug regimen using ceftriaxone plus either azithromycin or doxycycline may be used. Antimicrobial drugs used alone or in various combinations in other gonococcal infections include the following:

Gonococcal arthritis: Ceftriaxone

Gonococcal conjunctivitis: Ceftriaxone

Gonorrhea contributing to PID: Cefoxitin, ceftriaxone, doxycycline, metronidazole, cefotetan, clindamycin, gentamicin

Gonococcal epididymitis: Ceftriaxone, doxycycline

DGI: Ceftriaxone, cefotaxime, ceftizoxime

Gonococcal meningitis and endocarditis: Ceftriaxone

See Treatment and Medication for more detail.

Gonorrhea, an important public health problem and the second most common notifiable disease in the United States, is a purulent infection of mucous membrane surfaces caused by the gram-negative diplococcus Neisseria gonorrhoeae . Although gonorrhea (known colloquially as the clap and the drip) most frequently is spread during sexual contact, it also can be transmitted from the mother's genital tract to the newborn during birth, causing ophthalmia neonatorum and systemic neonatal infection. 

In people with a cervix, the cervix is the most common site of gonorrhea, resulting in endocervicitis and urethritis , which can be complicated by pelvic inflammatory disease (PID). In people with a penis, gonorrhea causes anterior urethritis. Gonorrhea also can spread throughout the body to cause 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 after 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 sexually transmitted disease (STD) in the sexually active teenage population

As a perinatal infection at childbirth

As a forensic aid in investigating sexual abuse

Gonococcemia

Gonococcemia is defined as the presence of N gonorrhoeae in the bloodstream, which can lead to the development of disseminated gonococcal infection (DGI). Gonococcemia occurs in about 0.5-3% of patients with gonorrhea.

The clinical manifestations of this process are biphasic, with an early bacteremic phase consisting of tenosynovitis, arthralgias, [ 2 ] and dermatitis, followed by a localized phase consisting of localized septic arthritis. Other potentially severe clinical complications include osteomyelitis, meningitis, endocarditis, adult respiratory distress syndrome (ARDS), [ 3 , 4 ] and fatal septic shock. [ 5 ] Polymyositis is also a rare complication of gonococcemia. (See Pathophysiology , Prognosis , and Presentation .)

Patients who are pregnant or menstruating may be particularly prone to gonococcemia. Other populations at risk for infection include women and individuals with complement deficiencies , HIV disease , or systemic lupus erythematosus (SLE). DGI is an important, potentially life-threatening, and easily treatable clinical entity that remains the most common cause of acute septic arthritis in young, sexually active adults.

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. Fluoroquinolone resistance also has 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 children, following direct inoculation of organisms (usually as a result of hand-eye inoculation in adults) and can lead to blindness.

Disseminated gonococcal infection

Disseminated gonococcal infection (DGI) occurs following approximately 1% of genital infections. Patients with DGI may present with symptoms of rash, fever, arthralgias, migratory polyarthritis, septic arthritis, tendonitis, tenosynovitis, endocarditis, or meningitis.

N gonorrhoeae organisms spread from a primary site, such as the endocervix, the urethra, the pharynx, or the rectum, and disseminate to the blood to infect other end organs. Usually, multiple sites, such as the skin and the joints, are infected. Neisserial organisms disseminate to the blood due to a variety of predisposing factors, such as host physiologic changes, virulence factors of the organism itself, and failures of the host's immune defenses. [ 6 ]

For example, changes in the vaginal pH that occur during menses and pregnancy and the puerperium period make the vaginal environment more suitable for the growth of the organism and provide increased access to the bloodstream. (Three fourths of the cases of DGI occur in women; susceptibility is increased if the primary mucosal infection occurs during menstruation or pregnancy.) [ 7 , 8 ]

Defects in the host's immune defenses are also involved in the pathophysiology, with certain patients more likely to develop bacteremia. Specifically, patients with deficiency in terminal complement components are less able to combat infection, as complement plays an important role in the killing of neisserial organisms. As many as 13% of patients with DGI have a complement deficiency.

A study of 22 patients with DGI revealed that total serum complement activity was greater than 25% below the normal mean. Other causes of immunocompromise (eg, HIV, SLE) also predispose to dissemination of infection.

In addition, certain strains of gonorrhea causing asymptomatic genital infections are seen in association with DGI. [ 9 ]

N gonorrhoeae is a gram-negative, intracellular, aerobic diplococcus; more specifically, it is a form of diplococcus known as the gonococcus. N gonorrhoeae is spread by sexual contact or through vertical transmission during childbirth. It mainly affects the host’s columnar or cuboidal epithelium. 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.

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 destruction 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 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. [ 10 , 11 ] 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. [ 10 ]

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 attached to sperm, to secondarily invade lower genital structures (vagina and cervix) and progress to upper genital organs (endometrium, salpinx, ovaries).

Sexually transmitted infection

Gonococcal infection usually follows mucosal inoculation during vaginal, anal, or oral sexual contact. It also may be caused by inoculation of mucosa by contaminated fingers or other objects. Transmission through penile-rectal contact is fairly efficient.

The risk of transmission of N gonorrhoeae from an infected individual to their partner's urethra is approximately 20% per episode of vaginal intercourse, and it rises to 60-80% after 4 or more exposures. In contrast, the risk of transmission from male-to-female or female-to-male partners approximates 50-70% per contact, with little evidence of increased risk with more sexual exposures.

Persons who have unprotected intercourse with new partners frequently enough to sustain the infection in a community are defined as core transmitters.

Neonatal and pediatric gonococcal infection

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.

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.

Autoinoculation

Autoinoculation can occur when a person touches an infected site (genital organ) and contacts skin or mucosa.

Risk factors

Risk factors for gonorrhea include the following:

Sexual exposure to an infected partner without barrier protection (eg, failure to use a condom or condom failure) [ 12 ]

Multiple sex partners

Male homosexuality

Low socioeconomic status

Minority status - Blacks, Hispanics, and Native Americans have the highest rates in the United States

History of concurrent or past 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)

Occurrence in the United States

CDC estimates that approximately 1.6 million new gonococcal infections occurred in the United States in 2018, with a significant number of cases likely unreported. [ 13 ] Per the CDC, gonorrhea is the second most commonly reported communicable disease. [ 14 ] 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. [ 15 , 16 ] Rates of reported gonorrhea have increased 92.0% since the historic low in 2009. [ 17 ]  Men were apparently less likely than women to be tested for gonorrhea, 20.7% vs 50.9%, respectively. [ 18 ] However, the infection rates between men and women were similar (105.8 vs 108.7 cases per 100,000). [ 19 ]  Infection rates in men appear to be on the rise.

CDC report estimated the annual cost of gonorrhea and its complications to be $271 million.

In the United States, the number of gonococcal infections peaked in the 1970s, the era of the sexual revolution. With the onset of the HIV epidemic and the practicing of safe sex techniques, the incidence dramatically decreased from 468 cases per 100,000 population in 1975 to 100-150 cases per 100,000 population at the turn of the century. The rate of reported gonorrhea cases was at its lowest in 2009 but has been increasing overall since then. [ 20 ] The increased numbers have been attributed to increased cases in males and persistently high rates in adolescents, young adults, and certain racial/ethnic groups in defined geographic areas. [ 20 ]

Within the United States, carriage rates highly depend on the geographic area, the racial and ethnic group, and sexual preferences. The rate of gonorrhea is much higher in African Americans than in other racial groups [ 21 ] 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 with social networks.

In 2016, rates of infection ranged from about 479.9 cases per 100,000 population in the District of Columbia to 20.1 cases per 100,000 population in Vermont. [ 22 ] The CDC supports a campaign ( Healthy People 2020 ) that targets a decreased incidence rate of 251.9 cases per 100,000 population among females aged 15-44 years and 194.8 per 100,000 population among males of the same age by the year 2020.

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%.

Resistant gonorrhea

The incidence of antibiotic-resistant strains of N gonorrhoeae has been rising since the late 1940s. Of greatest concern is the rise in the percentage of cases due to N gonorrhoeae with higher minimum inhibitory concentrations (MICs) to ceftriaxone, the current treatment of choice. As per the Gonococcal Isolate Surveillance Project (GISP) only 0.1% of isolates displayed elevated ceftriaxone minimum inhibitory concentrations (MICs) in 2019. [ 1 , 23 ]

In May 2016, the first cluster of highly resistant gonorrhea infections in the United States was identified in Hawaii. Most of the isolates showed decreased susceptibility to ceftriaxone, and all cases had very high-level resistance to azithromycin. [ 24 ]

International occurrence

An estimated 98 million new cases of gonorrhea occur annually, according to World Health Organization estimates. In comparison, an estimated 62 million new cases occurred in 1999 and 88 million in 2005. In 1999, the number of new cases of gonococcal infection diagnosed in North America was 1.56 million; in Western Europe, 1.11 million; in South and Southeast Asia, 27.2 million; and in Latin America and the Caribbean, 7.27 million.

Gonorrhea was the most common STD worldwide for at least most of the 20th century, although since the mid-1970s, public health initiatives in the industrialized world have resulted in declining incidence of the disease. As noted earlier, however, gonococcal infection is still the second most common notifiable disease in the United States, and Western European rates approximate those in the United States. [ 25 , 26 , 27 ]

Although the frequency data are unknown in most developing nations, these countries are considered to have the highest rates of gonorrhea and its complications. Gonococcal infection rates in pregnant women in the Central African Republic and South Africa were 3.1% and 7.8%, respectively.

The incidence of antibiotic-resistant strains has been rising since the late 1940s. Of greatest concern historically has been the high percentage of cases due to penicillinase-producing N gonorrhoeae . 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 ]

Race-related demographics

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 STDs.

Although race has no intrinsic effect on susceptibility to gonorrhea, the frequency of gonorrhea in the United States 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 and STD clinics), as well as true differences in prevalence.

Overall, the African American–to–White ratio of gonococcal infections declined from 23:1 in 2002 to 18:1 in 2006. Infection rates have trended downward since 1998; however, between 2005 and 2006, the CDC noted a 6.3% increase in the rate of gonococcal infections in African Americans. Subsequently, rates have begun to downtrend once again. 

Compared with reported incidence in Whites, the rate of reported cases was 8.6 times higher in Blacks, 3 times higher in native Hawaiians/Pacific Islanders, 1.7 times higher in Hispanics, and 0.5 times higher in Asians. [ 28 ] From 2012-2016, the gonorrhea rate increased among all races and ethnic groups.

Sex-related demographics

The male-to-female ratio for gonorrhea is approximately 1:1.4; however, females may be asymptomatic, whereas males rarely are asymptomatic. From 2015 to 2016, rates among males increased approximately 22%, whereas rates in females increased 13.8%. The large increase in diagnosis in males is attributed to either increased transmission or increased case documentation (increased extra-genital screening) among men who have sex with men (MSM). [ 28 ]

Serious sequelae are much more common in women, in whom pelvic inflammatory disease (PID) may lead to ectopic pregnancy or infertility and in whom DGI is more likely, owing to menstruation, pregnancy, and a higher incidence of occult infection.

Age-related demographics

The highest incidence of gonococcal infection in the United States in 2016 was among adults aged 20-24 years, in both men and women. [ 15 , 16 ] This likely is 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. [ 29 , 30 ]

Gonococcemia remains an important disease in the adolescent and young adult population, with a peak incidence in males aged 20-24 years and in females aged 15-19 years.

With adequate early therapy, complete cure and return to normal function are the rule. Most gonococcal infections respond quickly to cephalosporin therapy. Late, delayed, or inappropriate therapy may lead to significant morbidity or, on rare occasions, death.

Complications in males

Urethral strictures secondary to gonococcal infection in men are less common than previously thought. Some strictures in the preantibiotic era likely resulted from treatment by urethral irrigation using caustic compounds rather than from the gonorrhea itself.

Other complications, such as penile lymphangitis, periurethral abscess, acute prostatitis , seminal vesiculitis, and infection of the Tyson and Cowper glands, now are rare.

Complications in females

Tubal scarring and infertility are the major complications of gonococcal infection in females. The incidence of involuntary infertility is estimated at 15% after one attack of pelvic inflammatory disease (PID) and approximately 50-80% after 3 attacks. (However, infertility may be more common after chlamydial PID than after gonococcal PID, presumably because the more acute inflammatory signs associated with gonorrhea prompt women to seek diagnosis and treatment sooner.) Despite clinical and microbiological cure of infection, one study showed 13% infertility rates in females with PID due to N gonorrhoeae infection . [ 31 ]

Failure to diagnose PID can result in acute morbidity, including tuboovarian abscess, endometritis, Fitz-Hugh-Curtis syndrome (perihepatitis), and other chronic sequelae. Perihepatitis secondary to gonorrhea presents as right upper quadrant pain and nausea.

The incidence of ectopic pregnancy is increased from 7-fold to 10-fold in women with previous salpingitis, with resultant increased fetal and maternal mortality rates.

Gonococcal infections in women also may manifest as gonococcal urethritis or infection of periurethral (Skene) or Bartholin glands.

Pelvic inflammatory disease

PID generally is 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 them. 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. [ 32 ] Ten to twenty percent of patients diagnosed with cervical gonorrhea may develop PID.

Tubo-ovarian abscess and, rarely, tubal perforation with peritonitis and death, can occur, especially if the tubo-ovarian abscess was recurrent. Females with recurrent PID have high rates of ectopic pregnancy and infertility.

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 the drugs are administered for a longer course.

Gonorrhea is the most common cause of arthritis in the adolescent; however, arthritis (septic or reactive) is a rare complication of this disease.

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 N gonorrhoeae .

Endocarditis

Endocarditis is a rare but serious complication of disseminated gonococcal infection, affecting 1-2% of cases. Before the era in which antibiotics were the primary treatment, median survival was 6-8 weeks.

Additional complications

Complications of gonococcal infections also include the following [ 33 ] :

Corneal scarring after ocular gonococcal infections

Destruction of cardiac valves in gonococcal endocarditis

Death from congestive heart failure related to endocarditis

Central nervous system (CNS) complications of gonococcal meningitis

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.

DGI is an acute illness that causes fever, asymmetrical polyarthralgias, and skin pustules overlying small joints in patients with gonorrhea. Disseminated infection also may 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 STD rates and disproportionately acquire anal and oral infections, rather than vaginal infections (the perception being that if an activity is not vaginal sex, it is not sex). Stress that oral or anal sex can also transmit disease.

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 that 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 offering only 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 methodologic limitations, such as comparing different cities as controls, which made drawing conclusions from the data difficult. [ 34 ]

Abstinence education

Although the most effective STD prevention is abstinence from sex, this often is 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 been found to have a 33% higher prevalence rate of STDs than have 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.

Moreover, pledgers are 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).

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 of knowing a potential partner's sexual history (or honesty), strongly recommend the use of condoms as a reasonable alternative to abstinence. [ 12 ]

Risks of unprotected sex

Patients should be counseled about the additional risks of unprotected sex, including the acquisition of more serious or lifelong infections such as herpes, hepatitis B, and HIV, and, of course, about the risks of pregnancy. The emotional aspect of sexual relationships also may 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 the slideshow  Sexually Transmitted Diseases  and the  Gonorrhea  and Chlamydia  reference articles.

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.

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Molina JM, Charreau I, Chidiac C, and the, ANRS IPERGAY Study Group. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial. Lancet Infect Dis . 2018 Mar. 18 (3):308-317. [QxMD MEDLINE Link] . [Full Text] .

Fletcher PS, Shattock RJ. PRO-2000, an antimicrobial gel for the potential prevention of HIV infection. Curr Opin Investig Drugs . 2008 Feb. 9(2):189-200. [QxMD MEDLINE Link] .

[Guideline] Updated recommendations for the treatment of Neisseria gonorrhoeae, Chlamydia trachomatis and Treponema pallidum (syphilis), and new recommendations on syphilis testing and partner services. WHO . 2024. [Full Text] .

[Guideline] World Health Organization. WHO Guidelines for the Treatment of Neisseria gonorrhoeae. World Health Organization . 2016. [QxMD MEDLINE Link] . [Full Text] .

St Cyr S, Barbee L, Workowski KA, Bachmann LH, Pham C, Schlanger K, et al. Update to CDC's Treatment Guidelines for Gonococcal Infection, 2020. MMWR Morb Mortal Wkly Rep . 2020 Dec 18. 69 (50):1911-1916. [QxMD MEDLINE Link] .

US Preventive Services Task Force, Davidson KW, Barry MJ, Mangione CM, Cabana M, Caughey AB, et al. Screening for Chlamydia and Gonorrhea: US Preventive Services Task Force Recommendation Statement. JAMA . 2021 Sep 14. 326 (10):949-956. [QxMD MEDLINE Link] .

• 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.
• Gonorrhea rates, United States, 1941-2016. Courtesy of the Centers for Disease Control and Prevention (CDC).
• Gonorrhea rates by race/ethnicity, United States, 2012-2016. Courtesy of the Centers for Disease Control and Prevention (CDC).
• Rates of gonococcal infection per 100,000 by state and outlying regions (2016). Courtesy of the Centers for Disease Control and Prevention (CDC).
• Disseminated gonococcemia, acral pustules.
• Cytologic smear of cutaneous acral pustule showing gram-negative, intracellular diplococci.
• Rates of reported gonorrhea cases by age group and sex, United States, 2016. Courtesy of the Centers for Disease Control and Prevention (CDC).

Contributor Information and Disclosures

Shahab Qureshi, MD, FACP Attending Physician in General Internal Medicine, St Catharine's General Hospital; Associate Clinical Professor (Adjunct), McMaster University School of Medicine, Canada Shahab Qureshi, MD, FACP is a member of the following medical societies: American College of Physicians , College of Physicians and Surgeons of Ontario , Ontario Medical Association Disclosure: Nothing to disclose.

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians , American Society for Microbiology , International Immunocompromised Host Society , Infectious Diseases Society of America Disclosure: Nothing to disclose.

Brian Wong, MD Assistant Professor of Medicine, Division of Infectious Diseases, Loma Linda University Medical Center Disclosure: Nothing to disclose.

Neal Ammar, MD Staff Physician, Department of Dermatology, UMDNJ-New Jersey Medical School

Neal Ammar, MD is a member of the following medical societies: Alpha Omega Alpha , American Academy of Pediatrics , and Sigma Xi

Disclosure: Nothing to disclose.

Mounir Bashour, MD, CM, FRCS(C), PhD, FACS Assistant Professor of Ophthalmology, McGill University; Clinical Assistant Professor of Ophthalmology, Sherbrooke University; Medical Director, Cornea Laser and Lasik MD

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Nicholas John Bennett, MB, BCh, PhD, Assistant Professor in Pediatrics, Division of Infectious Diseases, Connecticut Children's Medical Center

Nicholas John Bennett, MB, BCh, PhD, is a member of the following medical societies: Alpha Omega Alpha and American Academy of Pediatrics

John L Brusch, MD, FACP Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance

John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha , American Academy of Dermatology , American Medical Association , American Society for Dermatologic Surgery , American Society for MOHS Surgery , Association of Military Dermatologists , and Phi Beta Kappa

Sanda Cebular, MD Fellow, Department of Medicine, Section of Infectious Diseases, State University of New York at Brooklyn

Sanda Cebular, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and American Medical Association

Joseph Domachowske, MD Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha , American Academy of Pediatrics , American Society for Microbiology , Infectious Diseases Society of America , Pediatric Infectious Diseases Society , and Phi Beta Kappa

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

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Renuka Heddurshetti, MD Fellow in Infectious Diseases, Department of Internal Medicine, State University of New York at Brooklyn

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Rajendra Kapila, MD, MBBS Associate Professor, Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Rajendra Kapila, MD, MBBS is a member of the following medical societies: American College of Physicians , American Medical Association , Infectious Diseases Society of America , and Infectious Diseases Society of New Jersey

Simon K Law, MD, PharmD Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology , American Glaucoma Society , and Association for Research in Vision and Ophthalmology

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

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Jeffrey Meffert, MD Assistant Clinical Professor of Dermatology, University of Texas School of Medicine at San Antonio

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Fernando H Murillo-Lopez, MD Senior Surgeon, Unidad Privada de Oftalmologia CEMES

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Christopher J Rapuano, MD Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Co-Chairman of the Cornea Service, Co-Chairman of Refractive Surgery Department, Wills Eye Institute

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Gregory J Raugi, MD, PhD Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle School of Medicine; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle

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Hampton Roy Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

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Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

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• Drug-Resistant Gonorrhea
• Lab Methods

Related Topics:

• Sexually Transmitted Infections (STIs)

About Gonorrhea

• Gonorrhea is a common sexually transmitted infection (STI) that can be treated.
• People who are sexually active can get gonorrhea.
• This fact sheet answers basic questions about gonorrhea.

What is gonorrhea?

Gonorrhea is an STI that can cause infection in the genitals, rectum, and throat. It is very common, especially among young people ages 15-24 years.

Signs and symptoms

How do i know if i have gonorrhea, gonorrhea often has no symptoms, but it can cause serious health problems, even without symptoms., symptoms in women.

Most women with gonorrhea do not have any symptoms. Even when a woman has symptoms, they are often mild and can be mistaken for a bladder or vaginal infection. Symptoms in women can include:

• Painful or burning sensation when peeing
• Increased vaginal discharge
• Vaginal bleeding between periods

Symptoms in men

Men who do have symptoms may have:

• A burning sensation when peeing
• A white, yellow, or green discharge from the penis
• Painful or swollen testicles (although this is less common)

Symptoms from rectal infections

Rectal infections may either cause no symptoms or cause symptoms in both men and women that may include:

• Anal itching
• Painful bowel movements

See your healthcare provider if you notice any of these symptoms. You should also see a provider if your partner has an STI or symptoms of one. Symptoms can include an unusual sore, a smelly discharge, burning when peeing, or bleeding between periods.

Risk factors

Am i at risk for gonorrhea.

Sexually active people can get gonorrhea through vaginal, anal, or oral sex without a condom with a partner who has gonorrhea.

If you are sexually active, have an honest and open talk with your healthcare provider. Ask them if you should get tested for gonorrhea or other STIs.

How it spreads

How is gonorrhea spread.

You can get gonorrhea by having vaginal, anal, or oral sex without a condom with someone who has the infection. A pregnant person with gonorrhea can give the infection to their baby during childbirth.

How can I reduce my risk of getting gonorrhea?

The only way to completely avoid STIs is to not have vaginal, anal, or oral sex.

If you are sexually active, the following things can lower your chances of getting gonorrhea:

• Being in a long-term mutually monogamous relationship with a partner who has been tested and does not have gonorrhea.
• Using condoms the right way every time you have sex.

I'm pregnant. If I have gonorrhea, how can I protect my baby from getting it?

If you are pregnant and have gonorrhea, you can give the infection to your baby during delivery. This can cause serious health problems for your baby. If you are pregnant, talk to your healthcare provider about getting the correct examination, testing, and treatment . Treating gonorrhea as soon as possible will make health problems for your baby less likely.

Testing and diagnosis

Should i be tested for gonorrhea.

If you are a sexually active gay or bisexual man, you should get tested for gonorrhea every year. If you are a sexually active woman, you should get tested for gonorrhea every year if you are:

• Younger than 25 years
• 25 years and older with risk factors, such as new or multiple sex partners, or a sex partner who has a sexually transmitted infection

Testing is also recommended during pregnancy in some cases .

How will my healthcare provider know if I have gonorrhea?

Most of the time, a healthcare provider will use a a urine sample to diagnose gonorrhea. However, if you have had oral and/or anal sex, your healthcare provider may use swabs to collect samples from your throat and/or rectum. In some cases, a healthcare provider may also use a swab to collect a sample from a man's urethra (urine canal) or a woman's cervix (opening to the womb).

Treatment and recovery

Is there a cure for gonorrhea.

Yes, the right treatment can cure gonorrhea. It is important that you take all of the medicine your healthcare provider gives you to cure your infection. Do not share medicine for gonorrhea with anyone. Although medicine will stop the infection, it will not undo any permanent damage caused by the disease.

It is becoming harder to treat some gonorrhea, as drug-resistant strains of gonorrhea are increasing. Return to a healthcare provider if your symptoms continue for more than a few days after receiving treatment.

When can I have sex again after my gonorrhea treatment?

Wait seven days after finishing all medicine before having sex. You and your sex partner(s) should avoid having sex until you have each completed treatment and your symptoms are gone. This will help prevent you and your partner(s) from giving or getting gonorrhea again. Those with gonorrhea should be retested about three months after treatment of an initial infection, even if their partners received successful treatment.

If you've had gonorrhea and took medicine in the past, you can still get it again. This happens if you have sex without a condom with a person who has gonorrhea.

What happens if I don't get treated?

Untreated gonorrhea can cause serious and permanent health problems.

In women, untreated gonorrhea can cause pelvic inflammatory disease (PID) . Some of the complications of PID are:

• Formation of scar tissue that blocks fallopian tubes
• Ectopic pregnancy ( pregnancy outside the womb )
• Infertility (not being able to get pregnant)
• Long-term pelvic/abdominal pain

In men, gonorrhea can cause a painful condition in the tubes attached to the testicles, which can, in rare cases, lead to infertility.

Rarely, untreated gonorrhea can also spread to your blood or joints. This condition can be life-threatening.

Untreated gonorrhea may also increase your chances of getting or giving HIV.

Gonorrhea is very common, especially among young people ages 15-24 years. It can infect the genitals, rectum, and throat.

For Everyone

Health care providers, public health.

• Mammary Glands
• Fallopian Tubes
• Supporting Ligaments
• Reproductive System
• Gametogenesis
• Placental Development
• Maternal Adaptations
• Menstrual Cycle
• Antenatal Care
• Small for Gestational Age
• Large for Gestational Age
• RBC Isoimmunisation
• Prematurity
• Prolonged Pregnancy
• Multiple Pregnancy
• Miscarriage
• Recurrent Miscarriage
• Ectopic Pregnancy
• Hyperemesis Gravidarum
• Gestational Trophoblastic Disease
• Breech Presentation
• Abnormal lie, Malpresentation and Malposition
• Oligohydramnios
• Polyhydramnios
• Placenta Praevia
• Placental Abruption
• Pre-Eclampsia
• Gestational Diabetes
• Headaches in Pregnancy
• Haematological
• Obstetric Cholestasis
• Thyroid Disease in Pregnancy
• Epilepsy in Pregnancy
• Induction of Labour
• Operative Vaginal Delivery
• Prelabour Rupture of Membranes
• Caesarean Section
• Shoulder Dystocia
• Cord Prolapse
• Uterine Rupture
• Amniotic Fluid Embolism
• Primary PPH
• Secondary PPH
• Psychiatric Disease
• Postpartum Contraception
• Breastfeeding Problems
• Primary Dysmenorrhoea
• Amenorrhoea and Oligomenorrhoea
• Heavy Menstrual Bleeding
• Endometriosis
• Endometrial Cancer
• Adenomyosis
• Cervical Polyps
• Cervical Ectropion
• Cervical Intraepithelial Neoplasia + Cervical Screening
• Cervical Cancer
• Polycystic Ovary Syndrome (PCOS)
• Ovarian Cysts & Tumours
• Urinary Incontinence
• Genitourinary Prolapses
• Bartholin's Cyst
• Lichen Sclerosus
• Vulval Carcinoma
• Introduction to Infertility
• Female Factor Infertility
• Male Factor Infertility
• Female Genital Mutilation
• Barrier Contraception
• Combined Hormonal
• Progesterone Only Hormonal
• Intrauterine System & Device
• Emergency Contraception
• Pelvic Inflammatory Disease
• Genital Warts
• Genital Herpes
• Trichomonas Vaginalis
• Bacterial Vaginosis
• Vulvovaginal Candidiasis
• Obstetric History
• Gynaecological History
• Sexual History
• Obstetric Examination
• Speculum Examination
• Bimanual Examination
• Amniocentesis
• Chorionic Villus Sampling
• Hysterectomy
• Endometrial Ablation
• Tension-Free Vaginal Tape
• Contraceptive Implant
• Fitting an IUS or IUD

Original Author(s): Grace Fitzgerald Last updated: 11th June 2019 Revisions: 6

• 1 Pathophysiology
• 2 Risk Factors
• 3.1 Genital infection
• 3.2 Rectal infection
• 3.3 Pharyngeal infection
• 4 Differential Diagnoses
• 5 Investigations
• 6 Management
• 7 Complications
• 8 Gonorrhoea in Pregnancy

Gonorrhoea is a curable sexually transmitted infection caused by the Gram-negative bacterium Neisseria gonorrhoeae . In the UK, gonorrhoea is the second most common bacterial STI (after chlamydia) and predominantly affects people under the age of 25 and men who have sex with men.

Throughout this article we will discuss the pathophysiology of gonorrhoea, its clinical features, management and how it may affect pregnancy and the neonate.

Pathophysiology

Gonorrhoea is transmitted through unprotected vaginal/oral/anal sex and can also be vertically transmitted from mother to child.

Neisseria gonorrhoeae is a Gram-negative diplococcus that has a strong affinity for mucous membranes. The organism can infect the uterus, urethra, cervix, fallopian tubes, ovaries, testicles, rectum, throat and less commonly the eyes. Once adhered to the mucous membrane, it invades the host cell and causes acute inflammation. N. gonorrhoea also has surface proteins that bind to the receptors of immune cells thus preventing an immune response.

Risk Factors

The following are risk factors associated with gonorrhoea, most of which are common to other STIs:

• Aged <25 years
• Men who have sex with men
• Living in high density urban areas
• Previous gonorrhoea infection
• Multiple sexual partners

Clinical Features

While gonorrhoea is often asymptomatic, as occurs in around 50% of female cases, symptoms can usually develop 2-5 days following infection:

Genital infection

Figure 1. Vaginal discharge in female gonorrhoea infection

• Altered/increased vaginal discharge (commonly thin, watery, green or yellow)
• Dyspareunia
• Lower abdominal pain
• Rarely – intermenstrual and/or post-coital bleeding
• Mucopurulent endocervical discharge
• Easily induced cervical bleeding
• Pelvic tenderness

Often examination can be normal.

• Mucopurulent/purulent urethral discharge
• Epididymal tenderness

Rectal infection

• Usually asymptomatic
• Anal discharge
• Anal pain/discomfort

Pharyngeal infection

• Usually asymptomatic (>90%)

Differential Diagnoses

A full STI screen should be undertaken for a patient presenting with gonorrhoea due to the common presenting symptoms of various STIs.

In particular, it is often very difficult to clinically differentiate between gonorrhoea and chlamydia infection. These infections often co-exist and therefore empirical treatment for gonorrhoea has the aim of covering both the causative organisms.

Investigations

If someone has suspected gonorrhoea, they should be referred to a GUM clinic or other specialist sexual health service for specimens to be taken:

• Endocervical/vaginal swab – NAAT
• Endocervical/urethral swab – microscopy and culture
• First pass urine – NAAT
• Urethral/meatal swab – microscopy and culture
• Swabs for NAAT + microscopy & culture can be obtained from the throat, rectum or eye if indicated.

These swabs should then be sent for microscopy , culture or nucleic acid amplification testing (NAAT) . NAATs are the standard investigation for chlamydia and these tests often provide dual testing for both chlamydia and gonorrhea.

While waiting for these laboratory results the patient should be treated with empirical antibiotics if their signs and symptoms are indicative of gonorrhoea.

Following diagnosis of gonorrhoea, a patient should be treated with a single dose of intramuscular ceftriaxone 1g.

Patients should be offered screening for other STIs, especially chlamydia, as co-infections are common. People should be encouraged to contact previous sexual partners to advise them to be screened and treated empirically for gonorrhoea.

Future safe sex should also be encouraged and patients should abstain from sex until both partners have completed treatment. To ensure antibiotics have successfully treated a patient, a test of cure is recommended during a follow up appointment.

For full details please refer to the BASHH UK guidelines for the management of gonorrhoea .

Complications

If gonorrhoea is left untreated in females, it can lead to pelvic inflammatory disease (PID) , which can result in chronic pain, infertility and ectopic pregnancy. In males, gonorrhoea can spread from the urethra to the testes causing epididymo-orchitis which is painful but rarely leads to infertility. It can also lead to prostatitis . Disseminated gonococcal infection (DGI) is uncommon but can lead to joint pain and skin lesions.

A patient should be admitted to hospital if:

• Systemic symptoms are identified (e.g. malaise, joint pain, fever, rash) as this suggests disseminated gonorrhoea which can potentially develop into a life threatening infection such as gonococcal meningitis.
• Females show signs of complicated or severe pelvic inflammatory disease.

Gonorrhoea in Pregnancy

Having gonorrhoea during pregnancy may be associated with complications such as perinatal mortality, spontaneous abortion, premature labour and early fetal membrane rupture.

Figure 2. Neonatal conjunctivitis may develop if born to an untreated woman with gonorrhoea.

Gonorrhoea can be vertically transmitted during delivery from an untreated mother and this can cause the neonate to have gonococcal conjunctivitis, where the neonate will experience eye pain, redness and discharge. Prophylactic antibiotics can prevent this and treatment during pregnancy is the same as for uncomplicated gonorrhoea. For the infected neonate, urgent referal and appropriate treatment is necessary to prevent long term damage and blindness.

• Rarely - intermenstrual and/or post-coital bleeding

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[end-clinical]

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Am Fam Physician. 2022;105(4):388-396

Related Letter to the Editor:   Doxycycline Preferred for the Treatment of Chlamydia

Patient information: See related handouts on chlamydia , written by the authors of this article, and on gonorrhea , which has been adapted from a previously published AFP article.

Author disclosure: No relevant financial relationships.

Infections caused by Chlamydia trachomatis and Neisseria gonorrhoeae are increasing in the United States. Because most infections are asymptomatic, screening is key to preventing complications such as pelvic inflammatory disease and infertility and decreasing community and vertical neonatal transmission. All sexually active people with a cervix who are younger than 25 years and older people with a cervix who have risk factors should be screened annually for chlamydial and gonococcal infections. Sexually active men who have sex with men should be screened at least annually. Physicians should obtain a sexual history free from assumptions about sex partners or practices. Acceptable specimen types for testing include vaginal, endocervical, rectal, pharyngeal, and urethral swabs, and first-stream urine samples. Uncomplicated gonococcal infection should be treated with a single 500-mg dose of intramuscular ceftriaxone in people weighing less than 331 lb (150 kg). Preferred chlamydia treatment is a seven-day course of doxycycline, 100 mg taken by mouth twice per day. All nonpregnant people should be tested for reinfection approximately three months after treatment or at the first visit in the 12 months after treatment. Pregnant patients diagnosed with chlamydia or gonorrhea should have a test of cure four weeks after treatment.

Chlamydia trachomatis and Neisseria gonorrhoeae are the most common sexually transmitted infections (STIs) in the United States and are required to be reported to state health departments. Between 2015 and 2019, reported chlamydial infections increased by 19%, and reported gonococcal infections increased by 53%. 1 These bacteria commonly infect the urogenital, anorectal, and pharyngeal sites but can become disseminated to affect multiple organ systems. Untreated infections may lead to pelvic inflammatory disease; scarring of fallopian tubes, which can increase the risk of ectopic pregnancy; infertility; easier transmission of new HIV infection; and vertical neonatal transmission. 2

Risk Factors

Young people 15 to 24 years of age account for 61% of all newly diagnosed STIs. 1 Racial and ethnic minorities, men who have sex with men (MSM), and transgender and gender diverse people are at higher risk of STIs. Inequitable access to health insurance and physicians, language barriers, and distrust of medical systems because of discrimination account for some of these disparities, independent of individual sexual behavior. 3 , 4 Other risk factors are reviewed in Table 1 . 2

Taking a thorough sexual history is important to identify overall risk of infection, as well as anatomic site-specific risk factors. Physicians should create supportive spaces where patients feel safe sharing information by using open-ended questions; avoiding assumptions regarding sexual preferences, practices, and gender/sex; and normalizing diverse sexual experiences. To obtain a complete sexual history, the five P’s (partners, practices, pregnancy attitudes, previous STIs, and protection from STIs) model can be used as outlined in Table 2 . 2 , 5

The U.S. Preventive Services Task Force (USPSTF) recommends behavioral counseling on condom use, communication strategies for safer sex, and problem solving with those at increased risk of STIs. 6 Adolescents and adults diagnosed with an STI in the past year, people reporting irregular condom use, and those with multiple partners or with partners belonging to a high-risk group are at increased risk. Physicians should emphasize barrier protection as the best way to prevent STIs. 2

The USPSTF and Centers for Disease Control and Prevention (CDC) recommend annual screening for chlamydial and gonococcal infections to prevent infertility and pelvic inflammatory disease in sexually active people 24 years and younger with a cervix and in older people with a cervix who have risk factors. 2 , 7 The CDC also recommends at least annual screening for MSM based on their risk factors. Screening should include the pharynx, urethra, and rectum based on reported anatomic sites of exposure. After discussion with the patient, it may be necessary to screen those sites even without reported exposure because of underreporting of sexual practices. 2 Table 3 summarizes screening recommendations for chlamydial and gonococcal infections. 2 , 8 There are significant gaps in research as it pertains to screening transgender and gender diverse patients. 9 The CDC recommends screening based on an individual’s current anatomy and sexual practices. 2

Screening for urogenital infections only and neglecting pharyngeal and rectal sites of exposure will miss a substantial proportion of chlamydial and gonococcal infections. 10 In one study of women who engaged in oral or anal sex with men, the prevalence of pharyngeal gonorrhea was 3.5%; rectal gonorrhea, 4.8%; and rectal chlamydia, 11.8%. 10 Pharyngeal and rectal screening may be offered to people with female anatomy based on sexual practices and shared decision-making. 2 Current evidence for screening extra-genital sites is strongest for MSM. Urine-only screening in an STI clinic misses 83% of infections among MSM. 11 They should be screened at each anatomic site of sexual exposure, regardless of condom use, at least annually. 2 Routine testing for chlamydial infections of the oropharynx is not recommended, but many laboratories will test for gonococcal and chlamydial infections simultaneously. 2 If oropharyngeal chlamydia is diagnosed, it should be treated to decrease the risk of transmission. 2

Presentation

Most chlamydial and gonococcal infections are asymptomatic. 8 Symptoms of infection are reviewed in Table 4 . 2 Because dysuria may be a symptom of chlamydial and gonococcal infections and causes leukocytes on urinalysis, women presenting with dysuria may be inaccurately diagnosed with a urinary tract infection if STI testing is not performed. 12 , 13 In women at risk for STIs or with a negative urine culture, physicians can consider STI testing in those presenting with dysuria. A pelvic examination is not required for diagnosis and may not improve the diagnosis of chlamydia and gonorrhea beyond history and diagnostic testing. 14 However, if pelvic inflammatory disease is suspected, a pelvic examination should be performed. The differential diagnosis of chlamydial and gonococcal infections is summarized in Table 5 . 2 , 15

Diagnostic Testing

The CDC recommends using nucleic acid amplification testing (NAAT) for the diagnosis of gonococcal or chlamydial infections because it is the most sensitive. 2 Specimens can be taken from a first-stream urine sample without urethral cleansing before collection. 2 Clinician- or patient-collected vaginal or endocervical swabs are also acceptable specimens. Self-collected vaginal swabs are as sensitive as clinician-collected swabs and are preferred by patients. 16 , 17 A recent meta-analysis showed that urine samples and vaginal and endocervical swabs have similar sensitivity. 17 For patients with male genitalia, a patient- or clinician-collected urethral swab may also be obtained, although a urine specimen is preferred. 2

In 2019, the U.S. Food and Drug Administration (FDA) approved the Aptima Combo 2 Assay and Xpert CT/NG, which use NAAT, for extragenital swabs of the throat and rectum. 18 The binx health io CT/NG assay, Visby Medical Sexual Health Test NAAT, and Cepheid Xpert CT/NG (not a waived test by the Clinical Laboratory Improvement Amendments) are point-of-care tests for the diagnosis of chlamydial and gonococcal infections. 19 Point-of-care testing provides same-day results, decreases loss to follow-up, and reduces overtreatment. 20 , 21

All people who test positive or report known exposure to C. trachomatis or N. gonorrhoeae should be treated. Patients and their partners should be advised to abstain from sex for seven days after completing a single-dose regimen or until the completion of a seven-day treatment course and resolution of symptoms. 2 Nonpregnant people should be tested for reinfection approximately three months after treatment or at the first visit in the 12 months after treatment. Follow-up care recommendations are reviewed in Table 6 . 2 , 22 , 23

Patients presenting clinically with nongonococcal urethritis can be treated empirically at the time of evaluation while diagnostic testing is pending. Cervicitis should be treated presumptively in those younger than 25 years or those at high risk of infection if NAAT is not available or follow-up is uncertain.

CHLAMYDIAL TREATMENT

Although spontaneous clearance of chlamydial infections is possible, people with positive test results should always be treated. 24 Because of increasing macrolide resistance, the recommended treatment for non-pregnant people is now doxycycline, 100 mg, twice per day for seven days. 2 Physicians may alternatively choose to treat patients with a single 1-g dose of azithromycin, especially when adherence to a multidose regimen may be a concern. 2 Treatment regimens are reviewed in Table 7 . 2 , 22 , 23

GONOCOCCAL TREATMENT

In 2018, more than one-half of cases of gonococcal infection were estimated to be resistant to at least one drug, leading the CDC to change treatment recommendations to higher doses of ceftriaxone 25 ( Table 8 2 , 15 , 25 ) . Azithromycin is no longer a recommended therapy for nonpregnant individuals because of an observed sevenfold increase in gonococcal resistance between 2013 and 2018. 25

UNRESOLVED SYMPTOMS

Most treatment failures are caused by reinfection from sex partners who have not received adequate treatment, rather than treatment failure from antimicrobial resistance. 2 If symptoms do not resolve or a test is persistently positive in a situation in which reinfection seems unlikely (i.e., the patient has reported no new sexual contact and is taking medication as prescribed), an infectious disease specialist and local health department should be consulted in case of possible antimicrobial resistance. 2

PARTNER EVALUATION AND EXPEDITED PARTNER THERAPY

If seeking care in person is not possible, expedited partner therapy is a strategy in which sex partners of a person diagnosed with a chlamydial or gonococcal infection within the past 60 days can be prescribed treatment without being seen by the physician. This strategy is supported by the American Academy of Family Physicians. 2 , 26 If the diagnosed person has not had a sex partner in the past 60 days, the most recent sex partner can be offered treatment. Sex partners with symptoms should be referred for evaluation and treatment. 2 Laws in 46 states permit expedited partner therapy. 27 Because recommended gonococcal treatment is based on intramuscular administration of medication, every effort should be made to see partners of infected patients in person for treatment and testing for other STIs. 28 If permissible by state law and the partner is highly unlikely to receive care, partners of those with gonococcal infections may be treated with a single dose of cefixime (Suprax), 800 mg orally, with the addition of 100 mg of oral doxycycline twice per day for seven days if chlamydial infection was not excluded. 28 Written instructions should be given to patients to convey to their partners how to take the medication, warnings about side effects and allergies, when to seek medical care, and STI education. 2 The best evidence for use of expedited partner therapy services is for male partners of women with gonococcal or chlamydial infections. 27 The risk of missing concomitant infections in MSM requires a more nuanced discussion, but these patients may be offered expedited partner therapy through shared decision-making. 28

LYMPHOGRANULOMA VENEREUM

Lymphogranuloma venereum is caused by a C. trachomatis serovar and can become invasive and cause colorectal fistulas and strictures. Treatment should be started presumptively at the initial visit to prevent complications if there is clinical suspicion for lymphogranuloma venereum. 2 Partners should be evaluated and treated empirically with a non–lymphogranuloma venereum chlamydial infection regimen. 2

Gonococcal and chlamydial infections in pregnancy are associated with increased risks, including preterm birth, premature rupture of membranes, stillbirth, low-birth-weight infants, and neonatal infection. 29 , 30 Pregnant patients should be screened as outlined in Table 3 . 2 , 8 Those at high risk of infection should be screened again in the third trimester. 2 Anyone diagnosed with a gonococcal or chlamydial infection during pregnancy should have a test of cure approximately four weeks after treatment, at three months after diagnosis, and in their third trimester. 2

NEONATAL INFECTIONS

The prevalence of perinatal gonococcal infections is 0.2 to 0.4 cases per 100,000 live births. 31 The USPSTF recommends universal prophylaxis with ocular erythromycin 0.5% ointment to prevent gonococcal ophthalmia neonatorum. The risk of infection without prophylaxis is 30% to 40%, and it can cause blindness as early as 24 hours after birth. 31 N. gonorrhoeae can also cause septic arthritis, meningitis, rhinitis, vaginitis, urethritis, pneumonia, and skin infections in neonates. 2 Asymptomatic newborns exposed to gonorrhea at birth from an untreated birthing parent should be swabbed for infection at the conjunctiva, oropharynx, vagina, and rectum and presumptively treated for gonorrhea. 2

Neonates are at high risk of contracting an infection if chlamydia is untreated in pregnancy. 2 , 32 Infants exposed during birth do not need to receive chlamydial-specific prophylactic antibiotics but should be monitored clinically for symptoms. 2 Ophthalmia neonatorum presents a few days to several weeks after birth with eyelid edema, discharge, and ocular congestion. 2 , 32 Chlamydial infections of the eye are not prevented by prophylactic erythromycin ointment. 32 Unlike trachoma, which is a chronic infection spread through close contact, clothes, and flies, ophthalmia neonatorum does not result in scarring and blindness. Diagnosis of ophthalmia neonatorum can be made by swabbing the conjunctiva for culture, direct fluorescence antibody testing, or NAAT. 2 The recommended treatment is oral erythromycin. 2 There should be close follow-up because a second course may be required. 2 C. trachomatis can also cause neonatal pneumonia. Infants present between two and 19 weeks of age with a staccato cough, tachypnea, rhinorrhea, and rales. 2 , 32 Exposed infants are at high risk; if they present with pneumonia, they should be treated empirically for chlamydial infection while awaiting test results from culture, direct fluorescence antibody testing (lower sensitivity), or NAAT (not FDA approved for the nasopharynx). 2 , 32

Any child diagnosed with gonococcal or chlamydial infections should be evaluated for sexual abuse. 2 , 32 Although perinatally transmitted chlamydial infections can be found in children up to three years of age, sexual abuse is the most common cause of infection in children. 2

MANAGEMENT DURING THE COVID-19 PANDEMIC

Disparities in STI testing have been more pronounced due to reallocation of resources for SARS-CoV-2 testing and decreased testing due to social distancing and stay-at-home orders. 3 , 19 However, telemedicine use has increased during the COVID-19 pandemic and is well-suited for STI screening because physical examination is not essential for diagnosis or treatment. 14 , 33 At-home C. trachomatis and N. gonorrhoeae self-testing kits are not FDA approved; however, multiple studies have found that when patients are instructed by a physician via telemedicine, self-collected swabs at home will diagnose cases similarly to office-collected samples, with increased volume of testing offsetting a slightly lower test sensitivity. 19 , 34 – 36 Physicians can safely incorporate home-based testing and treatment into telehealth practice.

This article updates previous articles on this topic by Mishori, et al. 23 ; Mayor, et al. 15 ; Miller 37 ; and Miller . 38

Data Sources: The U.S. Preventive Services Task Force, Cochrane Database of Systematic Reviews, Essential Evidence Plus, Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, and American Academy of Family Physicians websites were reviewed for relevant publications. A PubMed search was conducted using the terms Neisseria gonorrhoeae , Chlamydia trachomatis , diagnosis, and treatment for the past 10 years including English language, meta-analysis, randomized controlled trials, reviews, and systematic reviews. Search dates: January 28, 2021; February 14, 2021; March 30, 2021; July 25, 2021; and November 27, 2021.

Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2019. U.S. Department of Health and Human Services; 2021. Accessed November 28, 2021. https://www.cdc.gov/std/statistics/2019/default.htm

• Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187.

Lieberman JA, Cannon CA, Bourassa LA. Laboratory perspective on racial disparities in sexually transmitted infections. J Appl Lab Med. 2021;6(1):264-273.

Hamilton DT, Morris M. The racial disparities in STI in the U.S.: concurrency, STI prevalence, and heterogeneity in partner selection. Epidemics. 2015;11:56-61.

Savoy M, O’Gurek D, Brown-James A. Sexual health history: techniques and tips. Am Fam Physician. 2020;101(5):286-293. Accessed November 28, 2021. https://www.aafp.org/afp/2020/0301/p286.html

• Krist AH, Davidson KW, Mangione CM, et al. Behavioral counseling interventions to prevent sexually transmitted infections: US Preventive Services Task Force recommendation statement. JAMA. 2020;324(7):674-681.
• Cantor A, Dana T, Griffin JC, et al. Screening for chlamydial and gonococcal infections: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2021;326(10):957-966.

Farley TA, Cohen DA, Elkins W. Asymptomatic sexually transmitted diseases: the case for screening. Prev Med. 2003;36(4):502-509.

• Van Gerwen OT, Jani A, Long DM, et al. Prevalence of sexually transmitted infections and human immunodeficiency virus in transgender persons: a systematic review. Transgend Health. 2020;5(2):90-103.
• Bamberger DM, Graham G, Dennis L, et al. Extragenital gonorrhea and chlamydia among men and women according to type of sexual exposure. Sex Transm Dis. 2019;46(5):329-334.
• Marcus JL, Bernstein KT, Kohn RP, et al. Infections missed by urethral-only screening for chlamydia or gonorrhea detection among men who have sex with men. Sex Transm Dis. 2011;38(10):922-924.
• Tomas ME, Getman D, Donskey CJ, et al. Overdiagnosis of urinary tract infection and underdiagnosis of sexually transmitted infection in adult women presenting to an emergency department. J Clin Microbiol. 2015;53(8):2686-2692.
• Shipman SB, Risinger CR, Evans CM, et al. High prevalence of sterile pyuria in the setting of sexually transmitted infection in women presenting to an emergency department. West J Emerg Med. 2018;19(2):282-286.
• Farrukh S, Sivitz AB, Onogul B, et al. The additive value of pelvic examinations to history in predicting sexually transmitted infections for young female patients with suspected cervicitis or pelvic inflammatory disease. Ann Emerg Med. 2018;72(6):703-712.e1.

Mayor MT, Roett MA, Uduhiri KA. Diagnosis and management of gonococcal infections [published correction appears in Am Fam Physician . 2013;87(3):163]. Am Fam Physician. 2012;86(10):931-938. Accessed September 22, 2021. https://www.aafp.org/afp/2012/1115/p931.html

• Lunny C, Taylor D, Hoang L, et al. Self-collected versus clinician-collected sampling for chlamydia and gonorrhea screening: a systemic review and meta-analysis. PLoS One. 2015;10(7):e0132776.
• Rönn MM, Mc Grath-Lone L, Davies B, et al. Evaluation of the performance of nucleic acid amplification tests (NAATs) in detection of chlamydia and gonorrhoea infection in vaginal specimens relative to patient infection status: a systematic review. BMJ Open. 2019;9(1):e022510.

U.S. Food and Drug Administration. FDA news release: FDA clears first diagnostic tests for extragenital testing for chlamydia and gonorrhea. May 23, 2019. Accessed March 10, 2021. https://www.fda.gov/news-events/press-announcements/fda-clears-first-diagnostic-tests-extragenital-testing-chlamydia-and-gonorrhea

• Kersh EN, Shukla M, Raphael BH, et al. At-home specimen self-collection and self-testing for sexually transmitted infection screening demand accelerated by the COVID-19 pandemic: a review of laboratory implementation issues. J Clin Microbiol. 2021;59(11):e0264620.
• Van Der Pol B, Taylor SN, Mena L, et al. Evaluation of the performance of a point-of-care test for chlamydia and gonorrhea. JAMA Netw Open. 2020;3(5):e204819.
• Gaydos CA, Ako MC, Lewis M, et al. Use of a rapid diagnostic for Chlamydia trachomatis and Neisseria gonorrhoeae for women in the emergency department can improve clinical management: report of a randomized clinical trial. Ann Emerg Med. 2019;74(1):36-44.
• Dombrowski JC, Wierzbicki MR, Newman LM, et al. Doxycycline versus azithromycin for the treatment of rectal chlamydia in men who have sex with men: a randomized controlled trial. Clin Infect Dis. 2021;73(5):824-831.

Mishori R, McClaskey EL, WinklerPrins VJ. Chlamydia trachomatis infections: screening, diagnosis, and management. Am Fam Physician. 2012;86(12):1127-1132. Accessed September 22, 2021. https://www.aafp.org/afp/2012/1215/p1127.html

• Geisler WM, Lensing SY, Press CG, et al. Spontaneous resolution of genital Chlamydia trachomatis infection in women and protection from reinfection. J Infect Dis. 2013;207(12):1850-1856.
• St Cyr S, Barbee L, Workowski KA, et al. Update to CDC’s treatment guidelines for gonococcal infection, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(50):1911-1916.

American Academy of Family Physicians. Expedited partner therapy. Accessed August 1, 2021. https://www.aafp.org/about/policies/all/expedited-partner-therapy.html

Centers for Disease Control and Prevention. Expedited partner therapy. U.S. Department of Health and Human Services; 2021. Accessed November 27, 2021. https://www.cdc.gov/std/ept/default.htm

Centers for Disease Control and Prevention. Guidance on the use of expedited partner therapy in the treatment of gonorrhea. U.S. Department of Health and Human Services; 2021. Accessed November 27, 2021. https://www.cdc.gov/std/ept/gc-guidance.htm

• He W, Jin Y, Zhu H, et al. Effect of Chlamydia trachomatis on adverse pregnancy outcomes: a meta-analysis. Arch Gynecol Obstet. 2020;302(3):553-567.
• Vallely LM, Egli-Gany D, Wand H, et al. Adverse pregnancy and neonatal outcomes associated with Neisseria gonorrhoeae: systematic review and meta-analysis. Sex Transm Infect. 2021;97(2):104-111.
• Curry SJ, Krist AH, Owens DK, et al. Ocular prophylaxis for gonococcal ophthalmia neonatorum: US Preventive Services Task Force reaffirmation recommendation statement. JAMA. 2019;321(4):394-398.

Baker CJ. Red Book: Atlas of Pediatric Infectious Diseases . 4th ed. American Academy of Pediatrics; 2020.

• Car J, Koh GCH, Foong PS, et al. Video consultations in primary and specialist care during the COVID-19 pandemic and beyond. BMJ. 2020;371:m3945.
• Fajardo-Bernal L, Aponte-Gonzalez J, Vigil P, et al. Home-based versus clinic-based specimen collection in the management of Chlamydia trachomatis and Neisseria gonorrhoeae infections. Cochrane Database Syst Rev. 2015;(9):CD011317.
• Carnevale C, Richards P, Cohall R, et al. At-home testing for sexually transmitted infections during the COVID-19 pandemic. Sex Transm Dis. 2021;48(1):e11-e14.
• Chow EPF, Bradshaw CS, Williamson DA, et al. Changing from clinician-collected to self-collected throat swabs for oropharyngeal gonorrhea and chlamydia screening among men who have sex with men. J Clin Microbiol. 2020;58(9):e01215-20.

Miller KE. Diagnosis and treatment of Neisseria gonorrhoeae infections. Am Fam Physician. 2006;73(10):1779-1784. Accessed September 22, 2021. https://www.aafp.org/afp/2006/0515/p1779.html

Miller KE. Diagnosis and treatment of Chlamydia trachomatis infection [published correction appears in Am Fam Physician . 2008;77(7) 920]. Am Fam Physician. 2006;73(8):1411-1416. Accessed September 22, 2021. https://www.aafp.org/afp/2006/0415/p1411.html

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Gonorrhea guide: Risk factors and clinical manifestations

• Key information and resources
• Risk factors and clinical manifestations
• Screening and diagnostic testing
• Treatment and follow-up
• Prevention and control
• Etiology and epidemiology

Risk factors and clinical manifestations of Neisseria gonorrhoeae infections

On this page

• Risk Factors

Transmission

Gonorrhea signs and symptoms, complications of gonorrhea infection, risk factors.

Common risk factors for gonorrhea:

• Sexual contact with a person who has gonorrhea
• Sex with a new partner without barrier protection
• Unprotected sex with someone from an area with high gonorrhea burden
• Sexually active people under 25 years of age
• History of STBBI
• Being birthed by a person with gonorrhea
• Unprotected anal intercourse in gay, bisexual and other men who have sex with men (gbMSM)
• Unprotected sex with multiple partners
• Exchange of sex for money or drugs 

Other activities that may increase potential exposure to STBBIs include anonymous sexual partnering, street involvement and substance use. Refer to STBBI prevention guide .

N. gonorrhoeae is transmitted when there is contact with exudates from mucous membranes from people with gonorrhea.

Sexual transmission: Gonorrhea is usually transmitted through oral, vaginal, or anal sexual contact with a partner with gonorrhea Footnote 1 .

Vertical transmission: A person with gonorrhea can transmit the infection to the neonate during vaginal delivery if they have not received treatment during the perinatal period Footnote 2 .

Autoinoculation may also occur from an infected genital site to conjunctivae or rectum.

Clinical manifestations

Gonococcal infection can result in a broad spectrum of clinical presentations depending on the anatomical site of infection and the sex of the individual. Incubation period is usually two to seven days, but it may range from one to 14 days.

Infection is usually symptomatic in males and asymptomatic in females Footnote 3 Footnote 4 but may be asymptomatic in both. In all individuals, rectal and pharyngeal infections are more likely to be asymptomatic Footnote 5 .

Persons with N. gonorrhoeae infection often have a co-infection with C. trachomatis Footnote 6 Footnote 7 Footnote 8 . Signs and symptoms may indicate other STIs. If present, symptoms may include one or more of the following:

• Vaginal discharge
• Lower abdominal pain
• Abnormal vaginal bleeding
• Cervical discharge
• Bartholinitis
• Deep dyspareunia
• Rectal pain and discharge with proctitis
• Urethral discharge
• Urethral itch
• Testicular pain or symptoms of epididymitis

Children over 30 days

All the above signs and symptoms can occur in children. However, children are thought to be more likely than adults to present conjunctivitis or disseminated gonococcal infection (DGI).

• Ophthalmia neonatorum, which is the most common manifestation in infants born to mothers with genital tract infection Footnote 9 . Symptoms include eyelid edema, conjunctival erythema, and profuse purulent discharge.
• Disseminated gonococcal infection (rare)
• If diagnosis and treatment are delayed, inadequate, or no treatment is given, infection can spread from the local site and lead to serious complications or sequelae in both sexes.  
• Pelvic inflammatory disease (PID), which may lead to infertility and an increased risk of ectopic pregnancy
• Chronic pelvic pain
•   Epididymo-orchitis (in rare cases may lead to infertility) 
• DGI (encompasses a spectrum of conditions including arthritis, tenosynovitis, dermatitis, endocarditis and meningitis)
• Reactive arthritis (oculo-urethro-synovial syndrome)
• Perihepatitis

Danby CS, Cosentino LA, Rabe LK, et al. Patterns of Extragenital Chlamydia and Gonorrhea in Women and Men Who Have Sex With Men Reporting a History of Receptive Anal Intercourse.  Sex Transm Dis . 2016; 43(2):105-109. doi:10.1097/OLQ.0000000000000384

Return to footnote 1 referrer

Lewis DA. Global resistance of Neisseria gonorrhoeae: When theory becomes reality. Curr Opin Infect Dis . 2014; 27(1):62-67. doi: 10.1097/QCO.0000000000000025

Return to footnote 2 referrer

Klein EJ, Fisher LS, Chow AW, Guze LB. Anorectal gonococcal infection.  Ann Intern Med . 1977;86 (3):340-346. doi:10.7326/0003-4819-86-3-340

Return to footnote 3 referrer

Komaroff AL, Aronson MD, Pass TM, Ervin CT. Prevalence of pharyngeal gonorrhea in general medical patients with sore throats. Sex Transm Dis . 1980; 7(3):116-119. doi:10.1097/00007435-198007000-00004

Return to footnote 4 referrer

Committee on Infectious Diseases, American Academy of Pediatrics. Gonococcal infections. In: Pickering L, ed. Red book: 2012 report of the committee on infectious diseases. Vol 29th Edition. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012:336-344. https://redbook.solutions.aap.org/DocumentLibrary/RB12_interior.pdf.

Return to footnote 5 referrer

Creighton S, Tenant-Flowers M, Taylor C, Miller R, Low N. Co-infection with gonorrhoea and chlamydia: How much is there and what does it mean? Int J STD AIDS . 2003; 14(2):109-113. doi:10.1258/095646203321156872

Return to footnote 6 referrer

Lyss SB, Kamb ML, Peterman TA, et al. Chlamydia trachomatis among patients infected with and treated for Neisseria gonorrhoeae in sexually transmitted disease clinics in the United States.  Ann Intern Med . 2003;139(3):178-185. doi:10.7326/0003-4819-139-3-200308050-00007

Return to footnote 7 referrer

Mayor MT, Roett MA, Uduhiri KA. Diagnosis and management of gonococcal infections].  Am Fam Physician . 2012;86 (10):931-938. [published correction appears in Am Fam Physician. 2013 Feb 1;87(3):163

Return to footnote 8 referrer

Woods CR. Gonococcal infections in neonates and young children.  Semin Pediatr Infect Dis . 2005;16(4):258-270. doi:10.1053/j.spid.2005.06.006

Return to footnote 9 referrer

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Innoviva Specialty Therapeutics’ Positive Phase 3 Oral Zoliflodacin Data for the Treatment of Uncomplicated Gonorrhea Announced at ESCMID Global 2024

Innoviva specialty therapeutics, inc., a subsidiary of innoviva, inc., announced that positive results from the phase 3 oral zoliflodacin trial will be highlighted in an oral presentation given by the global antibiotic research & development partnership at the european society of clinical microbiology and infectious disease global congress taking place april 27-30, 2024, in barcelona, spain..

• Single-dose, oral zoliflodacin achieved 90.9% microbiological cure rate, demonstrating statistical non-inferiority compared to current global standard of care
• Pivotal Phase 3 data to be presented by the Global Antibiotic Research & Development Partnership (GARDP) in a Scientific Sessions Oral Presentation
• First collaborative study between industry and a non-profit to address a World Health Organization high priority pathogen and U.S. Centers for Disease Control urgent threat

WALTHAM, Mass.--( BUSINESS WIRE )-- Innoviva Specialty Therapeutics, Inc. , a subsidiary of Innoviva, Inc. (NASDAQ: INVA), today announced that positive results from the Phase 3 oral zoliflodacin trial will be highlighted in an oral presentation given by the Global Antibiotic Research & Development Partnership (GARDP) at the European Society of Clinical Microbiology and Infectious Disease Global Congress (ESCMID Global 2024) taking place April 27-30, 2024, in Barcelona, Spain. Zoliflodacin is a first-in-class spiropyrimidinetrione, single dose, oral antibiotic that is being developed in partnership with GARDP for the treatment of uncomplicated gonorrhea.

“As a single dose, oral antibiotic, zoliflodacin, if approved, could have a profound effect on how physicians across the globe approach the treatment of gonorrhea infections, potentially improving patient access and compliance while helping to reduce the spread of antibiotic-resistant strains of gonorrhea,” said David Altarac, M.D., Chief Medical Officer of Innoviva Specialty Therapeutics. “The presentation of these data for this innovative investigational therapy is an important step in advancing our clinical pipeline strategy, as we now turn our focus on regulatory filing requirements in the U.S.”

“Presenting these findings to the scientific community for the first time is a significant milestone in the journey of this important antibiotic in the fight against Neisseria gonorrhoeae , a World Health Organization priority pathogen,” said Dr. Alison Luckey, Senior Medical Lead for GARDP’s Sexually Transmitted Infections programme. “These positive findings not only represent a step forward in the treatment of gonorrhoea if approved, but also demonstrate the pivotal role that this public-private partnership between GARDP and Innoviva Specialty Therapeutics has in addressing the public health failure at the heart of the global antimicrobial resistance (AMR) crisis.”

In November 2023, the two organizations announced that the Phase 3 zoliflodacin trial met its primary endpoint, demonstrating statistical non-inferiority of microbiological cure at the urogenital site when compared to treatment with intramuscular injection of ceftriaxone and oral azithromycin, currently the only remaining global standard of care regimen for the treatment of uncomplicated gonorrhea.

In addition to the Phase 3 topline data, GARDP will also be presenting three additional posters highlighting details of zoliflodacin’s safety profile and additional microbiological data from the Phase 3 trial, as well as data from a drug-drug interaction pharmacokinetic trial. GARDP and Innoviva Specialty Therapeutics plan to submit the Phase 3 zoliflodacin data for future publication in a medical journal.

Beyond the zoliflodacin posters, Innoviva Specialty Therapeutics will also be presenting three additional posters at the meeting that feature new data for XERAVA® and XACDURO®.

Results from the Phase 3 Zoliflodacin Trial

The Phase 3 non-inferiority trial analyzed a total of 930 patients with uncomplicated gonorrhea, including women, adolescents and people living with HIV, making it the largest clinical trial ever conducted for a new treatment against gonorrhea infection, with 16 trial sites in regions with a high prevalence of gonorrhea across five countries, including Belgium, the Netherlands, South Africa, Thailand, and the U.S. The trial compared a single oral 3g dose of zoliflodacin to a globally recognized standard of care regimen (500mg ceftriaxone intramuscular [IM] plus 1g oral azithromycin). The primary efficacy endpoint was microbiological response at the urogenital site (cure or failure) at the Test-of-Cure (ToC) visit 6+/-2 days after treatment. Secondary analyses included microbiological cure at rectal or pharyngeal sites and safety.

The trial met its primary efficacy endpoint, with zoliflodacin (oral, 3g dose) demonstrating non-inferiority to ceftriaxone (IM, 500mg) plus azithromycin (oral, 1g). In the micro-intent-to-treat (micro-ITT) population (n=744), zoliflodacin achieved a microbiological cure rate of 90.9%, a 5.3% difference compared to ceftriaxone and azithromycin which achieved a 96.2% cure rate (95% CI: 1.4%, 8.7%). Microbiological cure rates at extragenital sites were comparable between treatment arms (secondary endpoints).

Oral zoliflodacin 3g was generally well tolerated and emergent adverse events were comparable between treatment arms (46.2% vs 46.4%). No deaths or other serious adverse events were reported.

Details for the ESCMID Global 2024 presentations are as follows:

Oral presentation

Title: Oral zoliflodacin is non-inferior to a combination of ceftriaxone and azithromycin for treatment of uncomplicated urogenital gonorrhoea: results of a large global Phase 3 randomized controlled trial Presenter/Author: Alison Luckey Oral session #: 246 Session: 05. New antibacterial agents, PK/PD & Stewardship – Therapeutic expedition: mining old and new drugs and dosing strategies Date and time: Tuesday, April 30, 2024; 8:30-10:30 CEST Location: Hall H

Poster presentations

Title: Safety profile of oral zoliflodacin for uncomplicated gonorrhoea in a Phase 3 trial Author: Gabrielle Kornman, et al. Poster #: 2724 Session: 5e. Safety, hypersensitivity, and adverse effects of treatment Date and time: Sunday, April 28, 2024; 12:00 CEST Location: Poster Area, Sector A, Row 23, Position 2

Title: Pharmacokinetics of zoliflodacin in healthy participants in the presence of itraconazole suggest no clinically meaningful CYP3A4-mediated drug-drug interactions Author: Alison Luckey, et al. Poster #: 2424 Session: 5b. Pharmacokinetics/pharmacodynamics of antibacterial drugs & therapeutic drug monitoring (incl lab methods, models, in vitro and in vivo studies) Date and time: Sunday, April 28, 2024; 12:00 CEST Location: Poster Area, Sector B, Row 16, Position 26

Title: Antimicrobial susceptibility of baseline Neisseria gonorrhoeae isolates from participants recruited in the global zoliflodacin Phase 3 randomised controlled trial Author: Alison Luckey, et al. Poster #: 2527 Session: 5c. New or repurposed antibacterial agents: clinical studies and randomised trials Date and time: Sunday, April 28, 2024; 12:00 CEST Location: Poster Area, Sector B, Row 18, Position 17

Title: Eravacycline susceptibility against Gram-positive pathogens, collected in Europe during 2022 Author: Stephen Hawser, et al. Poster #: 1281 Session: 3a. Resistance surveillance & epidemiology: MRSA, VRE & other Gram-positives Date and time: Monday, April 29, 2024; 12:00 CEST Location: Poster Area, Sector B, Row 1, Position 8

Title: In vitro activity of eravacycline against Enterobacterales and non-fermenter clinical isolates, including resistant isolates, collected in Europe during 2022 Author: Stephen Hawser, et al. Poster #: 1421 Session: 3b. Resistance surveillance & epidemiology: Gram-negatives Date and time: Monday, April 29, 2024; 12:00 CEST Location: Poster Area, Sector A, Row 4, Position 12

Click here for full XERAVA safety and prescribing information or go to www.xerava.com .

Title: In vitro activity of sulbactam/durlobactam in combination with cefepime against Gram-negative bacterial isolates from a recent Phase 3 clinical trial Author: Sarah McLeod, et al. Poster #: 1816 Session: 3f. Clinical outcome of resistant infections (retrospective and prospective studies, excl clinical trials of new drugs) Date and time: Monday, April 29, 2024; 12:00 CEST Location: Poster Area, Sector B, Row 12, Position 3

Click here for full XACDURO safety and prescribing information or go to www.xacduro.com .

The oral presentation and posters will be available on the “ Events & Presentations ” page of the Investors Relations section of Innoviva’s website following their presentation at ESCMID Global 2024.

About Oral Zoliflodacin

Zoliflodacin is a potential first-in-class, orally administered, single dose antibiotic with a novel mechanism of action that is currently in development for the treatment of uncomplicated gonorrhea. In a Phase 3 clinical trial, zoliflodacin met the primary efficacy endpoint by demonstrating non-inferiority compared to a globally recognized standard of care regimen (500mg ceftriaxone intramuscular [IM] plus 1g oral azithromycin). Zoliflodacin was found to be generally well tolerated with the overall rate of adverse events comparable between the two arms, and the majority of adverse events were mild to moderate. In vitro studies have shown that it is active against multidrug-resistant strains of Neisseria gonorrhoeae , including those resistant to ceftriaxone, and azithromycin, with no cross-resistance with other antibiotics.

About Gonorrhea

Gonorrhea is widely prevalent worldwide, with the World Health Organization estimating 82 million new cases worldwide in 2020 1 , making it the second most prevalent sexually transmitted bacterial infection worldwide after Chlamydia trachomatis . In the U.S., gonorrhea is the second most prevalent sexually transmitted bacterial infection, with an estimated 1.6 million new infections each year. 2 The bacterium Neisseria gonorrhoeae has gradually developed resistance to many classes of antibiotics used to treat these infections and as a result, ceftriaxone, given as a single intramuscular injection, has become the last available recommended treatment for gonorrhea globally.

About GARDP

The Global Antibiotic Research & Development Partnership (GARDP) is a not-for-profit organization that develops new antibiotic treatments for drug-resistant bacterial infections that pose the greatest threat to human health, and makes them accessible to the people who need them. It puts public health needs at the centre of antibiotic drug development to address the immediate crisis of antimicrobial resistance (AMR). Its work is funded by the governments of Australia, Germany, Japan, Monaco, the Netherlands, the Public Health Agency of Canada, South Africa, Switzerland, the United Kingdom, the Canton of Geneva, the European Union (via the Health Emergency Preparedness and Response Authority), as well as the RIGHT Foundation, Wellcome and other private foundations. GARDP was created by the World Health Organization and the Drugs for Neglected Diseases initiative (DNDi) in 2016 and legally registered as the GARDP Foundation in Geneva, Switzerland in 2018. www.gardp.org .

http://www.gardp.org

About Innoviva Specialty Therapeutics, Inc.

Innoviva Specialty Therapeutics, a subsidiary of Innoviva, Inc., is focused on delivering innovative therapies in critical care and infectious disease. Innoviva Specialty Therapeutics’ products, through its affiliate, La Jolla Pharmaceutical Company, include GIAPREZA® (angiotensin II), approved to increase blood pressure in adults with septic or other distributive shock, and XERAVA® (eravacycline) for the treatment of complicated intra-abdominal infections in adults. Innoviva Specialty Therapeutics’ products, through its affiliate, Entasis Therapeutics Inc., include XACDURO® (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use approved for the treatment of adults with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible strains of Acinetobacter baumannii-calcoaceticus complex (Acinetobacter). Our Phase 3 development pipeline includes zoliflodacin, a novel treatment for uncomplicated gonorrhea in adults. For more information about Innoviva Specialty Therapeutics, please visit here and follow us on X (formerly Twitter) and LinkedIn .

About Innoviva, Inc.

Innoviva is a diversified holding company with a core royalties portfolio, a leading critical care and infectious disease platform known as Innoviva Specialty Therapeutics (IST), and a portfolio of strategic investments in healthcare assets. Innoviva’s royalty portfolio includes respiratory assets partnered with Glaxo Group Limited (GSK). Innoviva is entitled to receive royalties from GSK on sales of RELVAR®/BREO® ELLIPTA® and ANORO® ELLIPTA®. Innoviva’s other innovative healthcare assets include infectious disease and critical care assets stemming from acquisitions of Entasis Therapeutics, including XACDURO® (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use approved for the treatment of adults with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible strains of Acinetobacter baumannii-calcoaceticus complex and the investigational zoliflodacin currently being developed for the treatment of uncomplicated gonorrhea, and La Jolla Pharmaceutical Company, including GIAPREZA® (angiotensin II), approved to increase blood pressure in adults with septic or other distributive shock and XERAVA® (eravacycline) for the treatment of complicated intra-abdominal infections in adults.

For more information about Innoviva, please visit here and follow us on LinkedIn .

ANORO®, RELVAR®, BREO® and TRELEGY® are trademarks of the GSK group of companies.

Forward Looking Statements

This press release contains certain “forward-looking” statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives, and future events. Innoviva intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. The words “anticipate”, “expect”, “goal”, “intend”, “objective”, “opportunity”, “plan”, “potential”, “target” and similar expressions are intended to identify such forward-looking statements. Such forward-looking statements involve substantial risks, uncertainties, and assumptions. These statements are based on the current estimates and assumptions of the management of Innoviva as of the date of this press release and are subject to known and unknown risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Innoviva to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, risks related to: expected cost savings; lower than expected future royalty revenue from respiratory products partnered with GSK; the commercialization of RELVAR®/BREO® ELLIPTA®, ANORO® ELLIPTA®, GIAPREZA®, XERAVA® and XACDURO® in the jurisdictions in which these products have been approved; the strategies, plans and objectives of Innoviva (including Innoviva’s growth strategy and corporate development initiatives); the timing, manner, and amount of potential capital returns to shareholders; the status and timing of clinical studies, data analysis and communication of results; the potential benefits and mechanisms of action of product candidates; expectations for product candidates through development and commercialization; the timing of regulatory approval of product candidates; and projections of revenue, expenses and other financial items; the impact of the novel coronavirus (COVID-19); the timing, manner and amount of capital deployment, including potential capital returns to stockholders; and risks related to the Company’s growth strategy. Other risks affecting Innoviva are described under the headings “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” contained in Innoviva’s Annual Report on Form 10-K for the year ended December 31, 2022, and Quarterly Reports on Form 10-Q, which are on file with the Securities and Exchange Commission (SEC) and available on the SEC’s website at www.sec.gov . Past performance is not necessarily indicative of future results. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. The information in this press release is provided only as of the date hereof, and Innoviva assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law.

• https://www.who.int/news-room/fact-sheets/detail/multi-drug-resistant-gonorrhoea#:~:text=Antimicrobial%20resistance%20in%20gonorrhoea%20has,are%20aged%2015%E2%80%9349%20years
• https://www.cdc.gov/std/gonorrhea/arg/public-health-threat/public-health-threat-text-only.htm#:~:text=Gonorrhea%20is%20the%20second%20most,to%20at%20least%20one%20antibiotic

View source version on businesswire.com: https://www.businesswire.com/news/home/20240424323555/en/

Innoviva Specialty Therapeutics David Patti, Corporate Communications +1 908.421.5971 [email protected]

Innoviva, Inc. Investor Relations Argot Partners +1 212.600.1902 [email protected]

Source: Innoviva Specialty Therapeutics

View this news release online at: http://www.businesswire.com/news/home/20240424323555/en

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Screening for chlamydia and/or gonorrhea in primary health care: protocol for systematic review

Jennifer pillay.

1 Alberta Research Centre for Health Evidence, University of Alberta, 11405 87 Avenue, Edmonton, Alberta T6G 1C9 Canada

Ainsley Moore

2 Department of Family Medicine, McMaster University, Hamilton, Canada

Prinon Rahman

3 Global Health and Guidelines Division, Public Health Agency of Canada, Edmonton, Canada

Gabriel Lewin

4 Department of Family Medicine, University of Ottawa, Ottawa, Canada

Donna Reynolds

5 Department of Family and Community Medicine, University of Toronto, Toronto, Canada

Guyléne Thériault

6 Department of Family Medicine, McGill University, Montreal, Canada

Brett Thombs

7 Faculty of Medicine, McGill University, Montreal, Canada

Brenda Wilson

8 Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada

Joan Robinson

9 Division of Infectious Diseases, Department of Pediatrics, University of Alberta, Edmonton, Canada

Amanda Ramdyal

Geneviéve cadieux.

14 Ottawa Public Health, Ottawa, Canada

Robin Featherstone

Anne n. burchell.

10 Dalla Lana School of Public Health, University of Toronto, Toronto, Canada

Jo-Anne Dillon

11 Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Canada

Ameeta Singh

12 Division of Infectious Diseases, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada

13 Public Health Agency of Canada, Edmonton, Canada

Marion Doull

Greg traversy, susan courage, tara macgregor, cydney johnson, ben vandermeer, lisa hartling, associated data.

Not applicable.

Chlamydia trachomatis and Neisseria g onorrhoeae are the most commonly reported sexually transmitted infections in Canada. Existing national guidance on screening for these infections was not based on a systematic review, and recommendations as well as implementation considerations (e.g., population groups, testing and case management) should be explicit and reflect the quality of evidence. The aim of this systematic review is to synthesize research on screening for these infections in sexually active individuals within primary care. We will also review evidence on how people weigh the relative importance of the potential outcomes from screening, rated as most important by the Canadian Task Force on Preventive Health Care (CTFPHC) with input from patients and stakeholders.

We have developed a peer-reviewed strategy to comprehensively search MEDLINE, Embase, Cochrane Library, CINAHL, and PsycINFO for English and French literature published 1996 onwards. We will also search trial registries and conference proceedings, and mine references lists. Screening, study selection, risk of bias assessments, and quality of findings across studies (for each outcome) will be independently undertaken by two reviewers with consensus for final decisions. Data extraction will be conducted by one reviewer and checked by another for accuracy and completeness. The CTFPHC and content experts will provide input for decisions on study design (i.e., when and whether to include uncontrolled studies for screening effectiveness) and for interpretation of the findings.

The results section of the review will include a description of all studies, results of all analyses, including planned subgroup and sensitivity analyses, and evidence profiles and summary of findings tables incorporating assessment based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods to communicate our confidence in the estimates of effect. We will compare our findings to others and discuss limitations of the review and available literature. The findings will be used by the CTFPHC—supplemented by consultations with patients and stakeholders and from other sources on issues of feasibility, acceptability, costs/resources, and equity―to inform recommendations on screening to support primary health care providers in delivering preventive care.

Systematic review registration

International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42018100733.

Electronic supplementary material

The online version of this article (10.1186/s13643-018-0904-5) contains supplementary material, which is available to authorized users.

Background on infections

Chlamydia trachomatis (CT) and Neisseria g onorrhoeae (NG) are the most commonly reported bacterial STIs in Canada. Ten-year trends (2005-2014) in Canada indicate that the number of reported cases of CT infections has increased by 49% (206.0 to 307.4 per 100,000 [total population, not specific to sexually active individuals]), while reported cases of NG have increased by 61% (28.4 to 45.8 per 100,000) [ 1 ]. Although most individuals who are tested and found to be positive for genital CT or NG are reported, the true incidence of these infections is unknown for several reasons. Most infections are asymptomatic (with the exception of NG in males for which symptoms are more common) and, therefore, never tested and diagnosed unless complications arise. Treatment for many people follows syndromic diagnosis (i.e., treatment based on symptoms occurs without testing or waiting for test results), with variation between jurisdictions on whether or not these are reportable. Some higher risk individuals do not seek testing due to stigmatization. Further, these figures largely represent infections diagnosed at genital sites, even though studies have found relatively high rates of NG and CT infection at oropharyngeal and rectal (extragenital) sites. For example, reported rectal incidence rates in men who have sex with men (MSM) are 6-21% (NG) and 1-18% (CT), and in females attending sexually transmitted infection (STI) clinics and other high-risk settings are 0-3% (NG) and 7-17% (CT) [ 2 – 4 ]. In MSM, most extragenital infections occur in the absence of a genital infection (e.g., 91% for CT and 70% for NG [ 2 ]), whereas in women 9-29% of infections are single site anorectal infections without genital infection [ 2 ]. Extragenital infections are very often asymptomatic (e.g., anorectal < 5%) and found in the absence of reported risk behaviors, such as receptive anal and oral intercourse (i.e., influenced by reporting biases, contiguous spread of infection) [ 2 , 5 ]. With increased testing at extragenital sites (e.g., in Quebec since 2014), when more recent (than 2014) data becomes available the rates of CT and NG will likely be higher yet.

Several risk factors and indicators are associated with differing prevalence of CT and NG infections (Additional file  1 ), including sex, age, geography, membership in a vulnerable group, high-risk sexual behaviors, and biological and epidemiological factors.

An estimated $51.4 million per year was spent on CT infections in Canada between 1991 and 2009, which included costs for screening, treatment, and long-term sequelae for untreated infection [ 6 ]. Costs specific for NG were not found, although a preliminary combined estimate for both direct and indirect costs of CT and NG (in 2000 CAN dollars) ranged from approximately $31.5 to $178.4 million [ 7 ]. The majority of costs related to CT and NG have been attributed to drugs (treatment of infections and complications), and acute-care hospital and physician costs, suggesting that much of the burden of these two infections can be reduced through implementation of effective prevention programs [ 7 ].

Factors associated with rising incidence

The rise in CT and NG infections may largely be attributed to improved detection, rather than to an actual increase in incidence. This is attributable to higher diagnostic yield when using nucleic acid amplification tests (NAAT) instead of culture, higher testing volumes because of increased acceptability of NAAT testing (i.e., urine collection or, in women, self-collected vaginal swab versus clinician-collected urethral or cervical swab), and better targeting of screening to high-risk populations [ 8 ]. It may reflect to some extent more testing at extragenital sites. Increased incidence may also be attributed to some extent by more high-risk sexual behaviors [ 8 ]. There is also a hypothesis suggesting that the increased rates of CT may paradoxically be due to increased reinfection rates following aggressive control efforts (“seek and treat”), due to an “arrested immunity (from) the interruption of naturally acquired immunity associated with early initiation of treatment” [ 8 ]. This hypothesis was supported in British Columbia where intensive risk-based screening approaches, human immunodeficiency virus (HIV) infection and syphilis rates, and risk behaviors remained stable during 1996-2009 in the presence of increasing rates of CT. Although rates of CT and NG are increasing in Canada and many other countries, there have been stable or declining reported rates in their complications including pelvic inflammatory disease (PID) [ 1 , 9 – 11 ]. A shift of PID management from hospital (where data on such complications are often collected) to out-patient settings [ 12 , 13 ] may confound (underestimate) this reported complication rate to some extent. Additionally, the same aggressive control efforts for CT may also be arresting the underlying immune-mediated pathological processes that cause PID and ectopic pregnancy [ 8 ]. Nevertheless, preventing reinfection through successful treatment of sexual partners (“partner notification”) and treating reinfection early via retesting may be crucial to reducing infection rates, reinfection rates, and ultimately their complications. CT has a high frequency of transmission, with concordance rates of up to 75% of partners being reported [ 14 ].

Consequences of CT and NG infections

In females, the infections with CT and NG can cause PID (infection/inflammation of the upper reproductive tract), chronic pelvic pain, ectopic pregnancy, and/or infertility. CT and NG are important causes of acute PID, with CT implicated in about one-fifth to one-third of all PID cases and about one-half in women aged 16-19 years [ 15 – 17 ]. Rates attributed to NG are not commonly reported, but PID may be attributed to NG more often than to CT; moreover, when from NG, PID may be associated with more severe symptoms and therefore discovered faster potentially leading to treatment and prevention of further complications such as ectopic pregnancy and infertility [ 18 ]. PID can be asymptomatic, especially when caused by CT. Rarely, other STIs (e.g., herpes simplex virus and trichomonas vaginalis) can cause PID [ 19 ]. Other causes of these complications include Mycoplasma genitalium , microorganisms associated with bacterial vaginosis, and respiratory and enteric pathogens that have colonized the lower genital tract [ 17 , 18 ]. PID may resolve spontaneously, and it may be possible for the infections to cause ectopic pregnancy and infertility without first causing PID [ 9 ]. For example, the infections may be eradicated from the endocervix by the host immune response (“spontaneous resolution” in approximately half of cases at about 1 year after initial testing) [ 20 ], hence halting ascension of the infection, after the immune response has already triggered pathological processes in the fallopian tubes [ 9 , 21 ].

Accurate rates of the above mentioned complications in cases of untreated infection are difficult to establish due to (i) diagnostic uncertainty for the infections (misclassification due to asymptomatic nature, previous reliance on culture for diagnosis which has poor sensitivity [missing cases]) and diagnostic uncertainty of the complications (PID diagnosis is usually clinical, rather than based on invasive and possibly inaccessible diagnostic laparoscopy, and neither sensitive nor specific), (ii) ethical and methodological issues with prospectively following untreated cases, as well as, (iii) the long duration of follow-up necessary to capture ectopic pregnancy and infertility consequences in relatively young populations having the highest prevalence of infection. Estimates of complication rates in females with untreated CT, relying on valid study designs (e.g., longitudinal cohorts and control arms of representative trials), are suggested to be in the range of 10-16% for PID [ 22 , 23 ], 0.02-2% for ectopic pregnancy, and 0.1-4.6% for infertility [ 9 ]. Chronic pelvic pain may affect between a third and half of females with PID (thus 3-8% of those with infection) [ 9 , 24 ]. The risks of PID and its sequelae may be higher when caused by NG (rates unreported) [ 18 ]. Apart from the incidence of these complications, the duration and severity of their effect varies (e.g., PID effects may be less or more severe, and may be of shorter duration than chronic pelvic pain) which may impact the importance people place on them [ 25 ].

In males, reproductive system complications include epididymitis, with or without orchitis, and, rarely [ 26 ], infertility. Extrapolating from a randomized trial of CT screening versus usual care in males aged 21-23 years in Denmark, the rate of epididymitis in untreated CT could be roughly estimated at 40 in 579 (7%), if CT was the major cause of epididymitis. This estimation was calculated from the number of people experiencing epididymitis at 12 months in the usual care group (40 in 9980; 0.4%) and the approximate number in this group having CT (i.e., 579), which (in absence of data) assumes a similar rate to that reported in the screening group (579 in 9980; 5.8%). The prevalence rate of CT in this trial agrees with those reported by population studies in Denmark [ 9 ], although most cases of epididymitis were identified using a proxy of doxycycline prescriptions in general practice, which may overestimate the CT-related incidence [ 27 ].

Other complications can occur in both reproductive (e.g. urethritis [males], cervicitis [females]) and non-reproductive sites (e.g., proctitis, pharyngitis, reactive arthritis, perihepatitis [Fitz-Hugh-Curtis syndrome in females]). Reactive arthritis (development of sterile inflammatory arthritis as a sequel to infection elsewhere, often in the gastrointestinal or urogenital tract) affects approximately 3-8% of people with a CT or NG infection, and in about 1-4% it will persist in the longer term (> 6 months) [ 28 , 29 ]. An estimated 4-14% of patients with PID (possibly higher in adolescence) will experience Fitz-Hugh-Curtis syndrome. Although probably a necessary precursor to PID and its sequelae, approximately 85% of women with cervicitis have neither signs nor symptoms (4). An uncommon complication of NG in both sexes is disseminated gonococcal infection occurring in < 1% of patients, which is usually manifested by skin lesions, fever, arthralgia, acute arthritis and tenosynovitis, but may also lead to endocarditis, meningitis, sepsis and osteomyelitis [ 30 ]. Positive associations have been found between NG and prostate cancer (odds ratio [OR] with 95% confidence intervals [95% CIs]: 1.2 [1.1-1.4] [ 31 ] and 1.3 [1.1-1.5]) [ 31 , 32 ] and between CT and cervical cancer (OR with 95% CI: 1.8 [1.0-3.0] independent of age and human papilloma virus status) [ 33 ] although incidence rates and causation are not easy to determine. Mortality has become a rare outcome, with estimates over the years per 100,000 in women ages 19-44 years decreasing from 0.3 deaths from PID alone in 1979 [ 34 ] to 0.1 deaths from CT and NG, PID, and ectopic pregnancy combined during 1999-2010 in the United States [ 15 ]. CT and NG may both increase the transmissibility of HIV, although findings are inconsistent, most studies have limitations (e.g., few have used actual HIV contact data), and large trials in countries with high HIV prevalence have failed to demonstrate that STI control interventions can reduce HIV incidence [ 1 , 2 , 35 – 38 ].

Recurring infections, or reinfection, increase the risk for complications [ 9 , 39 ]. A meta-analysis of 38 studies found a reinfection rate for CT of 13.9% and for NG of 11.7% [ 39 ].

Little is known about the reproductive consequences from single-site extragenital CT infections, although it is understood that oropharyngeal infection can be transmitted to the genitals [ 40 ], and that infection of the genitals may occur through contiguous spread from extragenital sites [ 5 ].

Consequences of screening, diagnosis and treatment

Screening, with the associated follow up including treatment, aims to reduce the consequences discussed above related to the natural course of infection. However, testing procedures themselves, inaccurate diagnostic tests, being diagnosed with an infection, and being treated with antibiotics may lead to other consequences that may be considered during decisions about screening.

Screening and diagnosis

Even though the diagnostic tests used for screening have good sensitivity and high specificity (see Additional file  2 ), some people will experience a false negative test—whereby treatment would not be provided and transmission to others may occur, or a false positive test informing them of an infection which does not exist. A false positive result may lead to adverse effects from treatment (see next section), and/or a risk for negative psychosocial effects about being infected with an STI (e.g., relationship stress), without any possible benefit to the individual tested. The availability of non-invasive diagnostic tests (urine, vaginal and rectal swabs), including self-sampling, reduces the likelihood of people experiencing discomfort or embarrassment during the procedure.

In those diagnosed with CT or NG, the benefits of treating the previously unknown infection and reducing risks for complications of the infection will be weighed by some individuals against the possible psychosocial effects of having an STI diagnosis. Also, STI stigma, caused by sociocultural norms (e.g., association with taboo and irresponsible or immoral behaviors) and intensified by institutional sources (e.g., media messages, fear-based education and prevention measures, judgemental attitudes of health care providers), can be a source of guilt, embarrassment, isolation, fear and distress [ 41 ]. Stigma hinders uptake of STI testing, disclosure and partner notification, treatment (seeking and adherence) and information seeking. A systematic review of qualitative studies on women’s experiences with CT screening found that most emotions about testing were negative, including fear, anxiety and embarrassment, although some were positive and related to a sense of self-care (“taking care”). A positive diagnosis often led to shock, blame, and anxiety for future reproductive health, relationship uncertainty, isolation and guilt.

Conversely, some felt relief at catching the infection or little concern because of thinking the infection is minor [ 42 ]. There appears to be negative and positive psychosocial consequences of both screening and receiving a positive diagnosis. Likewise, when considering quality of life and well-being, the possibility of a positive impact on these outcomes from reducing infection complications in some may be weighed against the possibility of negative impact from a positive diagnosis in others [ 25 , 43 ]. Apart from psychosocial impacts, failure of screening programs (e.g., inadequate partner notification and treatment) to cure the infection or their possible adverse effect on immune processes (arrested immunity), as described above, may also increase chances for reinfection, which increase the likelihood of sequelae and additional transmission of the infection.

Treatment for cure of CT and NG is effective (> 95% for CT and > 85% for NG, if uncomplicated infection) if properly adhered to, and will reduce the risk for complications of the infections as described above. Antibiotics typically used to treat CT and NG (described in Additional file 2 ) are quite commonly (15-25%) associated with mild adverse effects (AEs) including diarrhea, vomiting, constipation, abdominal pain, vertigo, fatigue and headache [ 44 , 45 ]. The majority of AEs from CT and NG treatment are gastrointestinal in nature and may be severe in some cases particularly for NG where combination treatment or higher-dose single agents are used (e.g., 2 vs. 1 g dose of azithromycin). Very rarely (< 1 in 1000 people treated), people will have serious adverse drug reactions leading to hospitalization, from severe allergy to the antibiotic, Clostridium difficile colitis (possibly with life-threatening diarrhea), liver toxicity, heartbeat irregularities (from azithromycin although mainly for multi-day doses in specific patient subgroups), or other organ complications [ 44 – 48 ].

Rationale for screening programs

Screening is a program, not only a test. Screening therefore includes a series of events initiated by offering of the test to diagnose an infection in those asymptomatic or not purposively seeking care for symptoms, detection of infection, with follow up for treatment and possibly partner notification and treatment, and retesting of cases to detect and treat reinfection [ 49 ].

While CT and NG may present with symptoms based on the location of infection, it is common that these STIs are detected asymptomatically. This increases both the risk of transmission to others and chances for complications when left undetected and untreated. The target groups for screening are usually defined by age and sex, considering prevalence and consequences of untreated infection. Further, although knowledge of behavioral and other risk factors (e.g., inconsistent condom use, multiple sex partners, MSM) will help identify those at a higher risk of becoming infected, there are challenges to accurate identification. People at high-risk may access services infrequently, they may not accurately self-report higher risk behaviors (e.g., because of stigma and often short recall period [e.g., couple of months]) which may lead to inaccurate reporting, results, and missing cases [ 2 ].

In the absence of treatment, infections persist for many weeks or months with the mean duration of CT from modeling estimated at 1.4 years [ 50 ] and NG commonly assumed to last approximately 6 months [ 51 ]. In women, treating the infections before their ascension from the lower to upper reproductive tract appears to be highly beneficial to prevent long-term sequelae [ 9 ]. Nevertheless, reductions in complications within screening trial participants for whom duration of infection is unknown and may be quite long suggests that screening and treating at variable durations of infection may be beneficial.

There are two possible goals of screening for NG and CT infections: first , to control the transmission and reduce the prevalence of the infection(s) in the population; and second , to reduce the risk of complications, especially reproductive tract complications in women [ 49 ]. The priority of these goals may influence what approaches are taken to screening. For example, coverage of a large proportion of the population may be necessary to reduce transmission and support population-based approaches. Without empirical data from randomized controlled trials (RCTs), a recent estimate based on several models found that screening all sexually active young adults (aged 16-44 years) at intervals of 2–5 years (corresponding to a yearly coverage of about 20% of this population) for 5–10 years could potentially reduce the prevalence of CT substantially (i.e., by at least 2-3 times) [ 52 ]. Screening to reduce serious complications may focus on opportunistic forms of screening where testing is offered to people in health care settings such as during visits to clinician offices or other health care sites including pharmacies [ 53 ] or emergency departments [ 54 ]. Other detection strategies focus on high-risk and/or hard-to-reach populations using outreach approaches in non-health community settings such as bars, sex venues, or mobile vans [ 55 – 57 ]. Testing may be provided to the entire population at risk (universal screening of all sexually active persons) or based on a strategy to target high-risk subpopulations.

The purpose of this review is to examine evidence on screening for Chlamydia trachomatis (CT) and Neisseria g onorrhoeae (NG) infections in sexually active individuals within primary health care. Specific rationale for developing this guideline, and recent national guidelines from other countries, are described in Additional files  3 and 4 . The findings will be used by the Canadian Task Force on Preventive Health Care (CTFPHC)—supplemented by consultations with patients on outcome valuation and by information from organizational stakeholders and other sources on issues of feasibility, acceptability, costs/resources, and equity―to inform recommendations on screening to support primary health care providers in delivering preventive care.

Methods/design

The Evidence Review and Synthesis Centre (ERSC) at the University of Alberta’s Alberta Research Centre for Health Evidence, will complete this review. The review will be developed, conducted, and prepared according to the CTFPHC methods [ 58 ] and this protocol follows reporting standards [ 59 ]. A working group of CTFPHC members (AM, GL, DR, GT, BT, BW, JR) and content experts (AB, JD, AS, TM) was formed for development of the topic, refinement of the key questions (KQs) and scope (i.e., population, interventions, comparators, outcomes, timing, setting [PICOTS]). CTFPHC members rated outcomes for their importance for creating a recommendation. The CTFPHC and content experts will not be involved in the conduct of the review including selection of studies and data analysis, but will comment on the draft report and provide input on the interpretations of findings. The Science Team of the Global Health and Guidelines Division at the Public Health Agency of Canada (PHAC) (PR, MD, GT, SC) provided assistance and input on CTFPHC methodological considerations during the topic refinement and development of the protocol; they also provided input on the protocol. Perspectives of patients and members of the public will be incorporated, regarding prioritization of outcomes for the final review. Any changes to the outcomes based on patient input will be reported in the final report. Stakeholder organizations ( n  = 14) reviewed the KQs and PICOTs and a draft version of this protocol was peer-reviewed. All comments were considered when finalizing this protocol. This final version of the protocol has been approved by the entire CTFPHC, and will be registered with the International Prospective Registry of Systematic Reviews (PROSPERO) database.

Key questions

• KQ1: What is the effectiveness of screening compared with no screening for chlamydia and/or gonorrhea in non-pregnant sexually active individuals?
• KQ2: What is the comparative effectiveness of different screening approaches for chlamydia and/or gonorrhea in non-pregnant sexually active individuals?
• KQ3: What is the relative importance that people place on the potential outcomes from screening for chlamydia and/or gonorrhea?

Analytical framework

Figure  1 depicts the relationship between the population, interventions, and outcomes of interest for this review.

Eligibility criteria

Tables  1 and ​ and2 2 outline each KQ’s study eligibility criteria (i.e., PICOTS).

Eligibility criteria using PICOTS for Key Questions 1 and 2: Effectiveness and comparative effectiveness of screening approaches

*An explanation of the process for rating outcomes for inclusion is in the text below Table  2

**Results in death or is life-threatening (i.e., requires inpatient hospitalization or results in prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction) see https://www.ich.org/products/guidelines/efficacy/efficacy-single/article/clinical-safety-data-management-definitions-and-standards-for-expedited-reporting.html

Eligibility criteria using PICOTS for Key Question 3: Outcome valuation

*Studies that are reporting on health state values for people with experience of the outcomes of interest (e.g., PID) that may have been caused by another infectious source do not have to only include sexually active individuals

The population of interest for KQs 1 and 2 is non-pregnant sexually active individuals of any age. For KQ3, participants (i.e., patients, public) do not have to be sexually active if they have experienced one of the outcomes, such as PID, from another infectious source.

The most directly relevant screening approaches for this CTFPHC guideline are those delivered by primary health care providers, where participants are identified for screening via attendance at a clinic, or more systematic means (e.g., mailed invitation via health register), or some other form of screening offered by locations considered a first point of contact with the health system such as clinician offices (e.g., family physician, pediatrician, nurse practitioner) and community health settings (e.g., school health clinics, emergency departments, STI clinics, out-patient clinics, pharmacies, prisons, substance use clinics, family planning/fertility/abortion clinics, public health clinics). Screening undertaken in specialist settings (e.g., inpatient units, obstetrics/gynecology offices, infectious disease clinics), via outreach programming (e.g., sex venues, sports facilities, online), or using regional population register-based approaches (e.g., postal kits delivered to homes, not directly related to primary health care) is less directly relevant, but studies from these settings may inform the guideline and will be included.

For KQ2, comparing screening approaches, we may use direct and/or indirect comparisons. Direct comparisons are preferred, and come from studies having within-study, head-to-head comparisons of different screening approaches (e.g., home-based vs. clinic-based specimen collection in health clinic population, venue-based vs. clinic-based screening), while indirect comparisons can be made, cautiously, between studies where the interventions are different but there are similar comparators (e.g., comparing effects from two different screening programs [studies] each compared with no screening can be used to infer difference between the two screening programs).

Screening is a program, not only a test. Therefore, screening interventions only offering a test with communication of results to participants are not eligible. Interventions where the additional follow up is only a defined treatment referral, without active treatment provision and other activities such as retesting, partner notification, and/or post-test counseling, will be considered for inclusion if they report on one or more of our primary outcomes (e.g., number treated, psychosocial consequences, one or more of the included complications of interest).

Outcome rating

The preliminary outcomes of interest for this review are listed in Table  1 . According to methods of Grading of Recommendations Assessment, Development and Evaluation (GRADE), the outcomes considered most patient-important and critical for making recommendations on screening for CT and/or NG were rated by members of the CTFPHC, and may be modified based on pending findings of an engagement exercise with a sample of sexually active individuals in Canada, conducted by an independent group with expertise in knowledge translation from St. Michael’s Hospital in Toronto, Ontario. All patient-important outcomes rated as critical (7 to 9 out of 9) and important (4 to 6 out of 9) are included, typically up to a maximum number of seven . This follows guidance based on cognitive limits when guideline panels are considering net balance of benefits and harms per question [ 60 ]. The CTFPHC working group rated several outcomes in males (e.g., epididymitis +/− orchitis) as being of lower importance than the outcomes listed in Table ​ Table1, 1 , and hence these are not included at this time. The outcomes related to feasibility, acceptability, cost and process will be considered secondary outcomes (not important or critical for decision making) and will primarily be used for implementation considerations during guideline development. Therefore, to be included in the review the studies must report on at least one or more of the primary outcomes, and findings for secondary outcomes will be drawn from these studies. All outcome ratings will be finalized prior to final study selection and data extraction; that is, the CTFPHC will be blinded to the studies and their results.

Additional eligibility considerations

We do not have a minimum threshold for study quality or inclusion criteria specific to items related to risk of bias (ROB), such as incomplete follow-up or lack of adequate allocation concealment. These factors will be taken into account when analyzing the data (e.g., possible sensitivity analysis) and interpreting the quality of evidence by outcome across studies.

For KQ1 and KQ2, we will not limit inclusion to only studies designed or analyzed using an intention-to-screen approach (e.g., including all patients invited to screen). Studies only using a per protocol design approach (e.g., only enrolling those actually tested) or analysis based on actual participation in screening will be included, but this distinction will be accounted for in the analysis and interpretation of the data (see Data Analysis and Synthesis). The decision to include uncontrolled studies for the outcomes of negative psychosocial impact and serious adverse effects of treatment will be based on the quality of the evidence from controlled/comparative studies. The decision will be made for each outcome-comparison of interest, including subgroups; for example, uncontrolled studies may only be included where controlled evidence is not found or is very low quality for certain populations (e.g., males) or intervention components (e.g., risk-assessment tool used for screening). We recognize that some outcomes (e.g., negative impact of diagnosis) may only be reported, regardless of study design, for screened participants even though they are also relevant to unscreened people. The CTFPHC and content experts will be involved in these decisions.

For assessing our comparison of universal versus risk-based screening approaches, we will include studies directly comparing universal versus risk-based screening strategies, but will also consider using indirect evidence between studies of universal screening and those using a risk-based approach only enrolling at-risk people (both versus no screening). The Additional file  5 describes and illustrates the ideal study designs for this comparison and some limitations when relying on other designs.

Case reports and case series (i.e., group of patients selected based on particular outcome) will be excluded, as will be papers not reporting primary research (e.g. editorials, commentaries, opinion pieces). Systematic reviews will not be eligible for inclusion, but will be examined and may serve to help identify additional relevant studies.

Searching the literature

To build in efficiencies and capitalize on other work conducted, we are following the CTFPHC approach to integrating existing systematic reviews, where suitable (see Additional file  6 ). This approach focuses on examining existing high-quality reviews (key quality criteria being the ability of the search strategy and eligibility criteria to capture all relevant studies) in order to identify studies meeting our criteria, with the addition of an update of the evidence to the present date. The approach primarily uses the review to identify studies; we may also rely on review authors’ ROB assessments or extracted data (both pending quality checks and only if the tool covers the domains of interest [see Risk of Bias Assessment]), but will re-interpret all findings, including assessment of the quality of the body of evidence. This approach is particularly suitable for reviews when all, or a portion of (e.g., studies of a certain design) a KQ is covered by the studies in the available review. A comprehensive search for systematic reviews on this topic was conducted, with careful inspection of potentially suitable reviews for use with this approach. None were considered suitable for KQ 1 or 2 due to differing populations (e.g., reviews that excluded studies with participants that may have had symptoms), interventions (e.g., screening for CT with or without NG, but not only for NG), and settings (e.g., no inclusion of non-health care settings). Hence, a full de novo search is planned for KQ 1 and 2. Of note, our evidence review will differ in some aspects from the one used to inform the guideline of the United States Preventive Services Task Force (USPSTF) guideline [ 61 ]. Only studies or analyses where all participants were asymptomatic were included by the USPSTF, rather than including studies that also tested symptomatic individuals (who were not seeking care for symptoms). Moreover, the CTFPHC outcomes of interest differ to some extent, and it is unclear if studies in all settings defined by our definition of primary care were eligible in the USPSTF review. The CTFPHC is also interested in examining evidence about screening in specialist and non-health settings to help inform their recommendations.

For KQ3, we identified one systematic review [ 25 ] on valuing health states that will be used to answer the portion of this question that is related to people who have experienced the outcomes of interest (e.g., not a screened population and not necessarily due to CT or NG infection). This will enable us to focus our own full search on studies about screening for CT and/or NG, which will also capture other studies relevant to different portions of KQ3 (e.g., valuing complications of CT and NG among people screened or diagnosed with CT or NG but not experiencing the outcomes). Accordingly, we have conducted one search to capture studies for KQ1, KQ2, and a portion of KQ3, and another search to update the evidence from the integrated systematic review to help answer KQ3.

The literature search strategies have been developed and implemented by a research librarian. They consist of both controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords, and have been peer-reviewed using the Peer Review of Electronic Search Strategies (PRESS) checklist [ 62 ]. Because the integrated review on health state valuations also included studies of economic evaluations, we have modified the authors’ search slightly before updating this to the present date (2014 onwards). Searches are being restricted by language to include full texts published in English or French. Literature suggests language restrictions in systematic reviews on conventional medicine topics do not appear to bias results from meta-analyses [ 63 , 64 ].

We have conducted (May 31-June 5, 2018) comprehensive searches in relevant bibliographic databases: Ovid Medline (1946-); Ovid Embase (1996-); Wiley Cochrane Library (inception-); CINAHL via EBSCOhost (1937-); and Ovid PsycINFO (1987-) (Additional file  7 ). Additional search sources will include trial registry records via ClinicalTrials.gov , meeting abstracts via the Conference Proceedings Citation Index – Science edition (Clarivate Analytics), and invitations to Canadian organizational stakeholders and content experts to submit reports/studies or identify websites for searching.

Reviewing the bibliographies of included papers and relevant systematic reviews will supplement the searches. We will contact authors (by email with three attempts over one month) of relevant protocols or trial registries not containing data, to obtain any reports or publications of completed studies. We will also contact authors of studies that are only reported in conference abstracts, reports, and other sources of information (e.g., trial registry sites) where full study details and where peer-review of the results have not been undertaken, to try to obtain enough information to include these studies (i.e., if we can adequately assess their study quality and characterize their PICOTS). Tables ​ Tables1 1 and ​ and2 2 contain our criteria for including studies reported in abstracts and other “gray literature”. Our data analysis section also describes how we will handle these studies.

The bibliographic database searches for all KQs will be updated approximately 4-5 months prior to publication date of the CTFPHC Guideline to identify any new studies.

All results of the database searches will be imported into an EndNote® database (Thomson Reuters, New York, NY) for reference citation and removal of duplicates by the librarian, and into DistillerSR (Evidence Partners Inc., Ottawa, Canada) for screening and selection procedures. Our supplementary search process will be documented (e.g., websites, search terms, dates) and any results passing an initial screen will be entered into Endnote and DistillerSR for full text review.

Screening and selecting studies for inclusion

For the database searches, two reviewers will independently screen the titles and abstracts (when available) using broad inclusion/exclusion criteria. Citations will be classified as “include/unsure,” “exclude,” or “reference” (i.e., conference abstracts, protocols, and systematic reviews). One reviewer will review the “reference” group and will screen results of the supplementary searches (e.g., trial registry sites). The full text of all studies classified as “include/unsure”, identified through review of the reference citations, or screened as relevant from the supplementary searches will be retrieved for full review. Two reviewers will independently assess eligibility of full texts using a standard, piloted, form that outlines the inclusion and exclusion criteria. Disagreements on final inclusion of all studies will be resolved through consensus or a third reviewer. The title/abstract screening and full-text selection processes will be conducted and documented in DistillerSR. We will contact authors via e-mail (3 times over one month) when the details necessary to decide on inclusion have not been adequately documented in the publication. The flow of literature and reasons for full text exclusions will be recorded in a PRISMA Flow Chart, and for each study in an excluded studies list.

Data extraction and reporting

We will use piloted, standardized data extraction forms. One reviewer will independently extract data from each included study into DistillerSR; a second reviewer will verify all data for accuracy and completeness. Disagreements will be resolved through discussion or a third reviewer.

For each key question, we will extract data on the following:

• author(s) and publication date
• funding source
• country of origin
• design and power calculation
• number of participants: assessed for eligibility, allocated to/receiving each intervention, screened [at each round, if applicable], retested, assessed for each outcome
• population(s): eligibility criteria, recruitment strategies, and participant baseline characteristics related to subgroups in Tables ​ Tables1 1 and ​ and2 2
• intervention(s)/exposure(s): screening for CT only, CT and NG, or NG only; risk stratification method (if used), diagnostic test, all reported case management activities, intervention factors listed in Table ​ Table1 1 (e.g., screening interval, personnel, other STIs), co-interventions; for KQ3: presentation or scenarios of outcomes from screening, if applicable
• comparator(s): KQ1, any details about usual care; KQ2, see intervention(s)
• setting(s): including locations of recruitment, screening, case management, other follow-up activities
• outcome measures: name, definition, measurement (i.e., tools, including scale and thresholds where applicable; diagnostic criteria) and ascertainment (e.g., health records and/or self-report), time point(s), as reported by studies
• details of analysis, including adjusted and sub-group analyses
• results (see elaboration below)

When there are multiple publications associated with a study we will consider the earliest report of the main (primary) outcome data to be the primary data source. We will extract data from the primary source first and then add outcome data reported in the secondary/associated publications and data sources. We will reference the primary source throughout the evidence report, but will also cite all associated literature that provided information. We will contact authors of included studies via email (with 3 contacts over one month) for clarification of study, participant, and result details.

We will record intention-to-screen results whenever possible, while recording the number in each arm with missing data. For dichotomous outcomes, we will record counts or proportions, and sample size, by study arm. Only numerical data for outcomes will be extracted; that is, we will make no assumptions on lack or presence of an outcome if this is not reported. If counts by group are not reported we will record the computed effect estimate provided by the author (e.g., RR, OR). If ORs are unadjusted and the sample sizes by group are reported, we will calculate the RR; we may also use the OR as an approximation of the RR if events rates are very low (< 5%). For continuous outcomes measures, we will extract (by arm) the mean baseline and endpoint or change scores, standard deviations (SD) or other measure of variability, and number analyzed. We will not include outcome data from studies that did not provide a follow-up change or endpoint score, or did not provide data/figures that could be used to calculate follow-up scores. If necessary, we will approximate means by medians. If SDs are not given, they will be computed from p -values, 95% confidence intervals (95% CIs), standard errors, z-statistics, or t-statistics. If computation of SDs is not possible they will be estimated from upper bound p-values, ranges, inter-quartile ranges, or (as a last resort) by imputation using the median SD from the other studies reporting on the outcome. When computing SDs for change from baseline values, we will assume a correlation of 0.5, unless other information is present in the study that allows us to compute it more precisely. Authors that report only p-values or narrative findings (e.g., “fewer”, “no difference”) will be contacted (3 times over 1 month) to obtain more specific data, although these studies will still be included when no additional data are obtained, and their results interpreted. We will use information from figures if no numerical values are provided; we will use available software (e.g., Plot Digitizer, http://plotdigitizer.sourceforge.net /) with agreement between two reviewers. We will, if feasible, accept individual patient data and conduct our own analysis.

Any relevant section of the results section of qualitative studies will be pasted into a Microsoft Excel spreadsheet for further analysis.

Data on within-study analysis for our subgroups of interest will be collected, including: subgroups (independent variables), the type of analysis (e.g., subgroup/stratified or regression analysis), the outcomes assessed (dependent variables), and the authors’ conclusions. We will collect data suitable for all patient and intervention subgroups (see Table ​ Table1) 1 ) for performing our own subgroup analyses (e.g., stratified analysis, meta-regression) based on study-level data.

We will provide a narrative summary and tables describing the characteristics of all included studies. When possible, we will enter results from studies into Review Manager 5.3 and provide plots of the study results (regardless of decision to meta-analyze); otherwise results will be tabulated.

Unit of analysis issues

Unit of analysis errors can occur in studies that employ a cluster design (i.e., a clinical practice, school or community) and yet are analyzed at the individual level (i.e., patients), leading to overly precise results and contributing greater weight in a meta-analysis. Moreover, additional biases associated with clustering in this context occur for some outcomes. For example, when screening for STIs is undertaken in geographic clusters, the intervention in a cluster may not only affect the participants, but also their partners and others in their sexual network (indirect effects) which may reduce the level of re-exposure and overall rates of infection in a cluster [ 49 ]. For trials that recruit by cluster, we will perform adjustments for clustering if this was not done in the published report. We will calculate the “effective sample size”, which accounts for the design effect of the unit of analysis and will be based on the average cluster size and intraclass coefficient [ 65 ]. We will use an ICC of 0.028 [ 66 ].

Risk of Bias assessment

Two reviewers will independently assess the ROB of each included study, with disagreements resolved through discussion or a third reviewer. The results for each study and across studies will be reported by each domain. The ROB for each study will be assessed on an outcome basis where needed, particularly when different outcomes are assumed to have different susceptibilities to bias; for example, self-reported outcomes are more prone to bias from non-blinding than objective outcomes. Outcomes at different time points may also differ in their ROB.

RCTs and controlled experimental studies (theoretically only differing from RCTs by lack of random sequence generation and not in other ROB domains) will be appraised using the 2011 version of the Cochrane Risk of Bias tool [ 65 ]. For non-randomized trials, we will add an additional assessment of selection bias (e.g., allocation method unrelated to characteristics associated with the outcomes) using a checklist developed by the National Institutes for Health and Care Excellence [ 67 ], such that some of these studies may receive an unclear rather than high ROB rating for sequence generation. Our assessments will consider the extent to which the possible biases may, or may not, have a meaningful impact on the direction or magnitude of the study findings [ 65 ].

Controlled observational studies will be appraised using the Newcastle-Ottawa Quality Assessment Scale [ 68 ]; three domains (sample selection [4 items], comparability of cohorts [1 item], and assessment of outcomes [3 items]) are evaluated. We will also report, separately, our assessment of the potential for selective outcome reporting for these studies; although protocols for observational studies are not often registered or published (limiting comparison of predetermined and reported outcomes and analysis), selective reporting may be at risk, such as when an outcome that is considered to have high importance for the topic and for patients is not addressed in the study.

Critical appraisal tools from the Critical Appraisal Skills Programme [ 69 ] and the Centre for Evidence-Based Management [ 70 ] will be used for qualitative and cross-sectional/survey studies, respectively. We will not use a specific tool for utility/preference-based studies but rather comment on key study characteristics, which may be associated with biased results (e.g. accounting for confounders, representativeness of population, inclusion of all outcomes in scenarios, presentation of outcomes in unbiased way [e.g., absolute effects]) [ 71 ].

Our assessments of the risk of bias will be incorporated into our assessment of the quality of the evidence across studies for each outcome (see Assessment of the Overall Quality of the Evidence using GRADE).

Data analysis and synthesis

We will provide summaries of intervention effects for each study by calculating the appropriate statistics based on types of outcomes.

Key questions 1 and 2

For pairwise meta-analysis in KQs 1 and 2 (for all primary outcomes), because of anticipated between-study heterogeneity we will employ the DerSimonian Laird random effects model using Review Manager Version 5.3 (The Cochrane Collaboration, Copenhagen, Denmark). For dichotomous outcomes, we will report relative risks (RR) between groups with corresponding 95% CIs. For continuous outcomes, we will report a pooled mean difference (MD) when one measurement tool is used, or a standardized mean difference (SMD) when combining two or more outcome scales measuring similar constructs (based on clinical input). If we are not able to use a study’s data in a meta-analysis (e.g., only adjusted ORs or p values are reported), we will comment on these findings and compare them with results of the meta-analysis.

For outcomes having statistically significant effects, we will calculate absolute risk reduction (ARR) or number needed to screen (NNS) based on comparison with the median control group event rates and RR. We also anticipate reporting estimates of absolute effects for some of our age and our sex subgroups, at a minimum. Age categories that are unlikely to differ greatly in baseline prevalence (e.g., 20-24 vs 25-29 years; but chosen for subgroup consideration based on possibility of differing attendance at health care provider offices) may be combined. We will also consider providing estimates based on general population-level prevalence versus that estimated for high-risk individuals.

When event rates are less than 1%, the Peto odds ratio method will be used. However, when control groups are of unequal sizes, when large magnitude of effect is observed, or when events become more frequent (5%–10%), the Mantel-Haenszel method without correction factor will be used for quantitative synthesis [ 72 ]. Findings on relative effects from studies where no events occurred in either group will be qualitatively summarized; the data will be used for estimating a control event rate for estimation of absolute effects [ 73 ].

The decision to pool studies will not be based on the statistical heterogeneity; the I 2 statistic (indicating heterogeneity rather than sampling error) and p values for heterogeneity will be reported but is recognized that the I 2 is influenced by the number of studies and magnitude and direction of effects [ 73 ]. Rather, we will rely on interpretations of the clinical (related to our PICOTS) and methodological differences between studies.

For findings related to KQ 2, in addition to using studies directly comparing different screening approaches, we will consider using the results of indirect comparisons made between studies used for KQ 1 that differ in their screening programs by our intervention factors of interest but are similar in their “no screening” control group. We will first undertake qualitative assessment by plotting the results from the groups of studies and comparing the direction, magnitude, and 95% CIs of the effects sizes [ 72 ]. If comparable effectiveness is not plausible (e.g., 95% CIs do not overlap moderately), we will consider formal analytical approaches available such as indirect comparison meta-analysis (e.g., Bucher method) [ 74 ] or network meta-analysis (i.e., combining direct and indirect comparisons) [ 75 , 76 ].

We will not directly combine results from trials with observational studies. Observational studies are generally considered to be of higher risks for bias, particularly with respect to selection biases (i.e., preferential screening based on perceptions of risk) making it more likely that groups will be dissimilar at baseline for known, or possibly unknown, confounders; commonly undertaken without a reported protocol, there is also more concern about reporting bias [ 77 ].

When a meta-analysis is not appropriate a narrative synthesis with accompanying tables and/or figures to present the data will be performed.

Sensitivity analysis

When substantial heterogeneity is suspected (i.e., it appears to impact the direction or magnitude of an effect in a clinically meaningful manner), we will conduct sensitivity analyses if appropriate (e.g., findings based only on low ROB studies (i.e.., all domains are assessed to have low ROB), studies screening for CT and/or NG with other STIs, inclusion of abstracts or other non-peer-reviewed outcome data as primary published data source, data requiring computation, analysis by invitation to screening rather than actual screened) or consider whether the heterogeneity is due to differing effects based on our population or intervention subgroups of interest (see Table ​ Table1 1 and section below).

Publication Bias

Where there are at least eight studies of varying size in a meta-analysis, we will analyze publication bias both visually using the funnel plot and quantitatively using Egger’s test [ 78 ].

Subgroup analyses

Our primary approach for evaluating the possibility of differential effects of screening for subgroups (see Tables ​ Tables1 1 and ​ and2) 2 ) will be to record any within-study subgroup analyses performed by study investigators using individual patient data. Because these results are often based on diverse methodologies, may not align with our subgroup variables of interest, and can be difficult to interpret across the body of evidence, we will also perform our own subgroup analyses using study-level data, as possible, using formal statistical approaches (e.g., meta-regressions) or by stratifying the results of the pairwise meta-analyses by subgroup variables. When determining whether entire studies fall into a particular population subgroup category (e.g., high-risk), we will consider ≥80% of the study population meeting the criteria as sufficient. These analyses would rely on study-level data, such that the results would be considered observational in nature. We will test for evidence of subgroup effects quantitatively (significant at p  = 0.05 although acknowledging that multiple subgroups may require lower p values for high certainty) [ 79 ], and also rely on available guidance when interpreting the credibility of the subgroup findings [ 65 , 80 ].

Key question 3

Analysis for this KQ will be largely descriptive although will include narrative synthesis based on comparing and contrasting study findings by study methodology, populations, outcome presentations, and analysis. Additional patterns, with illustrative quotes or other information, may be drawn out from qualitative studies where suitable based on our variables and outcomes of interest. Findings based on differences between studies may also be created (e.g., if common or contrasting findings across studies generate unique patterns). We will report qualitative findings alongside quantitative findings when appropriate (e.g., both indicating relative preference for one outcome compared with another) or to help describe quantitative findings (e.g., why people may have chosen a particular outcome as most/least important). Only findings related to the KQ 1 and 2 primary outcomes will be extracted from each study.

Assessment of the overall quality of the evidence using GRADE

Two reviewers experienced with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach will independently assess the quality of the body of evidence (our confidence that the effect estimate is correct ) for each primary outcome of interest using the GRADE methodology for systematic review authors [ 60 , 80 – 84 ]. Discrepancies will be resolved through discussion or another reviewer to reach consensus.

We will undertake separate GRADE assessments for experimental and observational study designs. Thereafter, we will give plausible reasons for any differences, and note pertinent limitations in both bodies of evidence; if we choose to combine the results into one overall quality grade, we will provide rationale.

Assessments will be entered into the GRADEPro software ( https://gradepro.org /) and summarized in GRADE evidence profiles and Summary of Findings tables [ 85 ], in order for these to be used by the CTFPHC in an Evidence-to-Decision Table. Footnotes to the tables will explain all decisions to down- or upgrade the evidence, and will be organized by outcome. The CTFPHC will then use this evidence on each outcome, to assess the net balance of consequences, e.g., benefits and harms (depending on direction of effect for each outcome) of each option, patient preferences and values, and other elements of the GRADE methodology (feasibility, acceptability, costs, equity) to develop the recommendations on screening for chlamydia and for gonorrhea.

The CTFPHC may consider revising our conclusions about the GRADE quality assessment domains, based on whether or not the findings provide sufficient confidence in an estimate of the effect that is adequate to support a particular recommendation [ 60 ].

Protocol amendments

Protocol amendments, including their description and date and timing within review conduct, will be documented in PROSPERO upon review completion. We will report on any changes to the protocol within the final manuscript.

The results section of the review will include a description of all studies, results of all analyses, including planned subgroup and sensitivity analyses, and evidence profiles and summary of findings tables incorporating assessment based on GRADE methods to communicate our confidence in the estimates of effect. In the discussion, we will summarize the main findings and their implications, compare our findings to others, and discuss limitations of the review and the available literature.

Additional files

Risk Indicators and Factors. (DOCX 24 kb)

Components of a Screening Program. (DOCX 26 kb)

Rationale and Scope of Guideline. (DOCX 24 kb)

Recent National Guidance from Other Countries. (DOCX 19 kb)

Interpreting Evidence Comparing Universal Versus Risk-Based Screening Strategies. (DOCX 149 kb)

Methods for Integrating Existing Systematic Reviews into New Reviews. (DOCX 25 kb)

Search Strategies. (DOCX 57 kb)

Acknowledgements

We would like to acknowledge the CTFPHC members who are not in the CTFPHC Working Group (Ainsley Moore, Gabriel Lewin, Donna Reynolds, John Riva, Guylene Thériault, Brett Thombs, Brenda Wilson) for this topic: Heather Colquhoun, Roland Grad, Stéphane Groulx, Michael Kidd, Scott Klarenbach, Eddy Lang, John Leblanc, Nav Persaud.

This protocol and the subsequent review will be conducted for the Public Health Agency of Canada [PHAC], however, it does not necessarily represent the views of the Government of Canada. Staff of the Global Health and Guidelines Division at the Public Health Agency of Canada (PR, MD, GT, SC) provided input during the development of this protocol and have reviewed the protocol, but will not be taking part in the selection of studies, data extraction, analysis or interpretation of the findings.

Availability of data and materials

Abbreviations.

Authors’ contributions

JP drafted all sections of this manuscript and is the guarantor of the review. AM and LH contributed to the design of the protocol and provided clinical (AM) and methodological input (AM and LH) input across all sections. PR, TM and CJ helped develop sections of the background section and provided input into the design of the protocol. RF developed the search strategy and provided text for the manuscript. BV provided input for the sections on data extraction and analysis, and reviewed these sections of the manuscript. GL, DR, JR, GT, BT, BW, AR, GC, AB, JD, AS, TW provided clinical/content input, assisted with developing the inclusion and exclusion criteria for the review and provided input to all sections of the protocol. MD, GT and SC provided methodological input, related to guideline development, during development of the protocol and MD and GT reviewed the manuscript. All authors approve the submission of this version of the protocol.

Ethics approval and consent to participate

Consent for publication, competing interests.

AS is the Interim Director of the Canadian Guidelines on Sexually Transmitted Infections. TW is a member of the Canadian Guidelines on Sexually Transmitted Infections Expert Working Group, and the WHO STI Guidelines Development Group. AB is section author (Counseling patients about HPV testing) in a publication of the International Centre on Infectious Diseases (ICID, Winnipeg, MN), which is funded by Merck Canada and Roche Diagnostics; no author received honoraria or personal support from the sponsors and authors are the solely responsible for the direction and content of this resource. Other authors declare that they have no competing interests.

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