Gonorrhea caused by Neisseria gonorrhoeae may also lead to complications like gonococcal arthritis. NAAT helps diagnose chlamydia and Neisseria gonorrhoeae.

Gonorrhea

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Ismail Munir

Overview

Gonorrhea is a sexually transmitted infection (STI) caused by an obligate human pathogen Neisseria gonorrhea. An obligate human pathogen means that the organism cannot survive outside the human body for a long period. It is also called gonococcus, which is a specie of gram-negative diplococci bacteria. Moreover, gonorrhea has been seen to take an inclination towards the younger population worldwide and affects developing and developed nations alike. Gonorrhea has an ancient history, and in slang language is called &ldquo;The Clap&rdquo;<a href="#accordion">[1]</a>. 
&nbsp;

Gonorrhea is becoming a massive public health concern as it is the second most common bacterial sexually transmitted infection worldwide<a href="#accordion">[1]</a>.&nbsp;As discussed earlier, gonorrhea takes a specific interest in affecting the younger population. Research proves that in developed countries, younger, unmarried individuals, and people who live on their own are affected more by STIs in general. However, in Pakistan this is the complete opposite; married, comparatively older, and people living with their families are more prone to contract the disease. According to the reports compiled by the World Health Organization (WHO), around 106 million new cases are registered every year globally, out of which more than 500,000 are contributed by the United States alone<a href="#accordion">[1]</a>.

Statistics about Pakistan are alarming. The prevalence rate showed a range of 13%<a href="https://www.researchgate.net/publication/51175208_Sexually_transmitted_infections_in_Pakistan" style="letter-spacing: 0.2px; background-color: rgb(255, 255, 255);"> </a>and 27.5%,&nbsp;with heterosexuality being the number one contributor (55%)<a href="#accordion">[2]</a><a href="#accordion">[3]</a>.

&nbsp;

Signs And Symptoms

Gonorrhea can be of the following three types:

<ol>
	<li>Urogenital Gonorrhea</li>
	<li>Oral Gonorrhea</li>
	<li>Disseminated Gonorrhea</li>
</ol>

However, the cause of all these types remains the same i.e. Neisseria gonorrhea. 
&nbsp;

<h5>1. Urogenital Gonorrhea</h5>

Urogenital gonorrhea is the type in which the organism, N. gonorrhea attacks the mucous membranes of the reproductive and urinary systems of males and females. This includes the cervix, uterus, and fallopian tubes of women and the urethra of both males and females.

According to the research gathered by the Centers for Disease Control and Prevention (CDC), gonorrhea remains asymptomatic in both males&nbsp;and females<a href="#accordion">[4]</a><a href="#accordion">[5]</a>. However, if at all, the following set of symptoms can be seen:

Males can complain of painful urination (dysuria) and discharge that can be either white, yellow, or green. This discharge can be characteristically seen one to fourteen days after the onset of the infection<a href="#accordion">[5]</a>.&nbsp;If epididymitis is involved as well, then the patients can also complain of scrotal pain. Epididymitis is inflammation of a tube-like structure in the testicle that stores and carries sperm.

Females can complain about symptoms similar to bladder or vaginal infection. Hence, it can be very confusing. It includes dysuria, increased vaginal discharge, and intermenstrual bleeding<a href="#accordion">[6]</a>.&nbsp; &nbsp; 
&nbsp;

<h5>2. Oral Gonorrhea</h5>

It is also called pharyngeal gonorrhea and is essentially caused by the bacteria&rsquo;s decision to affect the tissue of the throat instead of the clich&eacute;d sites, i.e., the urogenital system or rectum.

Research has proved that having oral sex can increase the incidence of oral gonorrhea. It can be possible for the diseased person to be asymptomatic but still be a potential threat to others as it can be transmitted through saliva. A relatively recent study shows that even kissing can be dangerous enough to transmit the disease<a href="#accordion">[7]</a>.

Symptoms of oral gonorrhea include difficulty in swallowing, swollen or painful throat, and redness of the throat. 
&nbsp;

<h5>3. Disseminated Gonorrhea</h5>

It is a complication of oral gonorrhea that warrants immediate medical intervention. If the oral variant is not treated properly, the bacteria can seep into the bloodstream and cause an independent set of symptoms. This is called DGI or disseminated gonococcal infection. Symptoms may include sore throat, rashes, fever, and chills.

This can give rise to serious conditions, such as gonococcal arthritis and gonococcal endocarditis if left untreated. The severity of these conditions requires effective management. However, the incidence of DGI is under 3%<a href="#accordion">[8]</a>. 
&nbsp;

Causes

Gonorrhea is most likely caused by unprotected sexual contact, either through vaginal penetration or through oral sexual contact. Other reasons that might aggravate or cause a different set of symptoms may include incomplete treatment and improper knowledge about the disease. For example, being asymptomatic does not essentially mean being disease-free.

&nbsp;

Urine Nucleic Acid Amplification Tests (NAATs) can be used to screen asymptomatic males. It can be done by collecting first void urine and is the test of choice. For asymptomatic females, vaginal swabs are highly recommended<a href="#accordion">[13]</a>. Annual screening is recommended for women who are less than 25 years of age and homosexual men. 
&nbsp;

Diagnosis

There are multiple tools by which gonorrhea can be diagnosed or the presence of N. gonorrhea&nbsp;can be confirmed. The following are the methods that can be used: 
&nbsp;

<ul>
	<li>Detailed History: Since gonorrhea can very easily be mistaken for some other infection, a detailed history becomes highly important. History of sexual partners and lifestyle may help your doctor reach closer to your diagnosis<a href="#accordion">[13]</a>.</li>
	<li>NAAT (Nucleic Acid Amplification Tests): It is considered to be the gold standard diagnostic modality for gonorrhea<a href="#accordion">[9]</a>. The bacterial genome is evaluated through this test and confirms the presence of N. gonorrhea. It has a high specificity compared to all the other diagnostic tests, up to 95-100%, and a sensitivity of up to 95%<a href="#accordion">[9]</a>.</li>
	<li>Culture Of The Discharge: The sample is taken through a urethral or a vaginal swab by a medical practitioner and then sent for culture.</li>
	<li>Urine Test: Practitioners can also take a urine sample to diagnose gonorrhea.</li>
</ul>

&nbsp;

Treatment

Gonorrhea may sound very dangerous but is resolvable. According to the 2021 treatment guidelines submitted by the CDC, a specific antibiotic, called ceftriaxone is administered as a single 500 mg intramuscular dose<a href="#accordion">[10]</a>. Ceftriaxone is a third-generation cephalosporin. However, if the patient has an allergy to ceftriaxone, alternative treatments must be followed.

Moreover, if co-infection with chlamydia has not been ruled out, doxycycline 100 mg should be administered two times a day for 7 days in total. Re-evaluation is necessary for people with oral gonorrhea to see if the treatment worked or not.

Previously azithromycin was also administered with ceftriaxone, but it was discontinued from the current treatment guidelines due to the increased resistance development.

&nbsp;

Gonorrhea needs to be treated quickly to prevent the development of complications as those can lead to an extensively hazardous state of health. The following are the most important complications that need to be avoided by timely medicinal intervention: 
&nbsp;

<ul>
	<li>Pelvic Inflammatory Disease (PID): If a woman gets gonorrhea and is not treated efficiently, it may give rise to PID because of the ability of the disease to move into the reproductive organs, such as the fallopian tubes, ovaries, and uterus. PID is responsible for causing severe pain and damage to the reproductive system of the female.</li>
	<li>Vertical Transmission: Vertical transmission is the passing of a medical condition from the mother to the newborn during delivery. If a mother is in an active state of gonorrhea, there is a strong possibility that the newborn child might catch it, too.</li>
	<li>Fertility Issues: Women can face fertility issues if the fallopian tubes are affected, specifically as gonorrhea may cause scarring or blocking. Males are not exempted as well. Abscess inside the penis is usually painful&nbsp;and affects your sexual efficiency.</li>
	<li>DGI: Although it is very rare, it should be given due importance, especially in the case of pharyngeal gonorrhea. Inadequate treatment of gonorrhea can lead to this disseminated disease. This essentially means that the disease has spread into the bloodstream, and can cause gonococcal arthritis and gonococcal endocarditis.</li>
</ul>

&nbsp;

Certain factors play a vital role in determining which people are at greater risk to get a specific disease. Reasons can vary from culture, religion, society, race, etc. In light of what has been studied about gonorrhea, the following are the risk factors that have been established:

<ul>
	<li>Having A New Sex Partner:&nbsp;It is less likely to know an entire medical history of a new partner; therefore, details regarding an STI can be missed very easily.</li>
	<li>Intercourse With A Non-Monogamous Partner: If you have intercourse with someone non-monogamous, there is a higher chance for him or her to contract the infection from someone else. Gonorrhea&rsquo;s likeliness is directly proportional to the exposure of sexual partners.</li>
	<li>Any Previous Infection: If you have a history of gonorrhea or any other STI such as chlamydia, the chances of recurrences increase. 
	&nbsp;</li>
</ul>

There is no vaccine yet that can help to avoid gonorrhea as a whole but the preventive measures otherwise have proved to be extremely beneficial. Since the major contributor to the causative factors is sexual contact, the best way of prevention is to avoid sexual contact completely. This does not only include penetration but also oral sex and anal penetration as well.

In cases of oral gonorrhea, kissing should be avoided as well. If avoidance of intercourse is not possible, it should be taken care that barrier methods are used, i.e., condoms. Moreover, both partners should be open about getting themselves tested and sharing the results.

&nbsp;

Due to the easy transmission and rapidly developing resistance to different antibiotics, gonorrhea has become an area of concern for doctors globally and especially in Canada. A specie of gonorrhea, called the multi-drug resistant or MDR-Gonorrhea, has been isolated because of its ability to resist fluoroquinolones, and shows lesser sensitivity against cephalosporin and at least two other antibiotics<a href="#accordion">[13]</a>. It has been seen that between 2012 and 2016, there was a rise of 2.7% in the isolates of MDR-Gonorrhea, from 6.2% to 8.9%<a href="#accordion">[13]</a>. This issue must be addressed as the complications that gonorrhea brings can be severe. Conditions like infertility and chronic pelvic pain can make it difficult to live life efficiently at a social, societal, and even psychological level. Moreover, untreated infection from N. gonorrhea can make a person more prone to get infected by <a href="https://merisehat.pk/disease/hiv">HIV</a>.

However, the latest research done by the scientists at Microbiotix, the Uniformed Services University, and Florida State promises the development of a new compound that can help combat the MDR strain of the organism N. gonorrhea. The compound is a trans-translation inhibitor and after some tweaking, showed promising results in mice. The compound was named MBX-4132 and the strain was called the WHO-X, which was a highly virulent organism resistant to almost every antibiotic available at the moment. Results showed that a single oral dose of the compound completely cleared the infection in 80% of mice within six days, and the bacterial load in the remaining 20% was dramatically reduced<a href="#accordion">[14]</a>.

&nbsp;

Key Points

<ul>
	<li>Gonorrhea is the second most common sexually transmitted Infection (STI). Every year globally 106 million new cases are reported, with more than 500,000 contributed by the US alone.</li>
	<li>There are essentially three types of gonorrhea, depending on the site of infection. A rare, but dangerous, type is the DGI also known as disseminated gonococcal Infection.</li>
	<li>Signs and symptoms vary according to the site. Urogenital disease will be predominated by dysuria, pelvic pain, and vaginal or urethral discharge, whereas, pharyngeal gonorrhea will exhibit throat pain.</li>
	<li>Annual screening is recommended for women who are less than 25 years of age and are sexually active. Regular screening is also advised for homosexual men.</li>
	<li>Multiple diagnostic modalities can be used to diagnose gonorrhea, such as NAAT, urethral or vaginal swabs, and even urine tests.</li>
	<li>CDC-approved treatment includes a single dose of ceftriaxone 500 mg intramuscularly. However, if chlamydia is not excluded, doxycycline is also administered.</li>
	<li>Any medication, before being started, should be approved by a healthcare professional.</li>
	<li>Dangerous complications include DGI, PID, <a href="https://www.merisehat.pk/disease/infertility-in-men" target="_blank">fertility issues</a>, and chronic pelvic pain.</li>
	<li>People with multiple sexual partners and with a history of a previous STI are at risk for developing gonorrhea. But this can be prevented by using barrier methods while having sex or abstaining as a whole.</li>
	<li>Multidrug-resistant strain of N. gonorrhea&nbsp;has been a concern worldwide. It has developed resistance against fluoroquinolones and reduced sensitivity to cephalosporin as well.</li>
	<li>Latest research shows a promising new compound that has cleared 80% of the MDR version of gonorrhea in mice.</li>
	<li>Gonorrhea is a notification priority disease in Pakistan and any presenting cases should be notified to the concerned authorities immediately. 
	&nbsp;</li>
</ul>

[1] Springer C, Salen P. Gonorrhea. [Updated 2022 Apr 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.

[2] Maan, Muhammad & Hussain, Fatma & Iqbal, Javed & Akhtar, Shahid. (2011). Sexually transmitted infections in Pakistan. Annals of Saudi medicine. 31. 263-9. 10.4103/0256-4947.81541.

[3]   Rehan N. Profile of men suffering from sexually transmitted infections in Pakistan. JPMA. The Journal of the Pakistan Medical Association. 2006 Jan;56(1 Suppl 1):S60-5. PMID: 16689488.

[4]  Handsfield HH, Lipman TO, Harnisch JP, Tronca E, Holmes KK. Asymptomatic gonorrhea in men. N Engl J Med, 290(3), 117–123 (1974)

[5] Wallin J. Gonorrhea in 1972: a 1-year study of patients attending the VD unit in Uppsala. Brit J Vener Dis, 51, 41–47 (1974)

[6] McCormack WM, Johnson K, Stumacher RJ, Donner A, Rychwalski R. Clinical spectrum of gonococcal infection in women. Lancet, 1(8023), 1182–1185 (1977)

[9] Sood, Seema et al. “Nucleic acid amplification tests (NAATs) for gonorrhoea diagnosis in women: experience of a tertiary care hospital in north India.” The Indian journal of medical research vol. 140,5 (2014): 649-52.

[7]  Chow EP, Fairley CK. The role of saliva in gonorrhoea and chlamydia transmission to extragenital sites among men who have sex with men: new insights into transmission. J Int AIDS Soc. 2019;22 Suppl 6(Suppl Suppl:e25354.

[8]   Health Alert Template for Disseminated Gonococcal Infection (DGI). Centers for Disease Control and Prevention.

[10] Barbee, Lindley A, and Sancta B St Cyr. “Management of Neisseria gonorrhoeae in the United States: Summary of Evidence From the Development of the 2020 Gonorrhea Treatment Recommendations and the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infection Treatment Guidelines.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America vol. 74,Suppl_2 (2022): S95-S111.

[11] Raypole C. Gonorrhea: Symptoms, treatment, causes, and more. Healthline.

[12] Gonorrhea. Mayo Clinic.

[13] Bodie, M et al. “Addressing the rising rates of gonorrhea and drug-resistant gonorrhea: There is no time like the present.” Canada communicable disease report = Releve des maladies transmissibles au Canada vol. 45,2-3 54-62.

[14] Zachary D. Aron, Atousa Mehrani, Eric D. Hoffer, Kristie L. Connolly, Pooja Srinivas, Matthew C. Torhan, John N. Alumasa, Mynthia Cabrera, Divya Hosangadi, Jay S. Barbor, Steven C. Cardinale, Steven M. Kwasny, Lucas R. Morin, Michelle M. Butler, Timothy J. Opperman, Terry L. Bowlin, Ann Jerse, Scott M. Stagg, Christine M. Dunham, Kenneth C. Keiler. trans-Translation inhibitors bind to a novel site on the ribosome and clear Neisseria gonorrhoeae in vivo. Nature Communications, 2021; 12 (1)

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