Novel gonorrhea strain in the United States of America leading to increase of sexually transmitted diseases load: is it an outcome of inexorable process of developing antibiotic resistance?

Sexually transmitted infections (STIs) are a major global public health concern, affecting the quality of life and causing serious morbidity and mortality1. STIs have a direct impact on reproductive and child health through infertility, cancers and pregnancy complications, etc., and an indirect impact through their roles towards the tendency of sexual transmission of human immunodeficiency virus (HIV)1. Gonorrhoea as a form of STI is caused by Neisseria gonorrhoeae (N. gonorrhoeae). In recent years, the organism has developed antimicrobial resistance to all drugs previously used as first-line treatments2. The inability of acid amplification tests to detect gonorrhea strains for antibiotic resistance3, is a major global concern as to why the emergence of novel gonorrhea strains is a threat. Other concerns include the potential for major health issues such as the inflammation of the reproductive tract, ectopic pregnancy, infertility in both men and women, infections in infants that can result in blindness, systemic illness, and a higher risk of HIV infection3,4. Research showed that more than a million STIs are acquired every 24 hours. In the year 2012, an estimated 357 million incident cases of curable STIs; gonorrhea, chlamydia, syphilis, and trichomoniasis occurred among 15–49 years old worldwide, including 78 million cases of gonorrhea1. In the USA, gonorrhea cases have been found that do not respond to therapy with all available antibiotics5. Due to increased sexual activity and a decrease in normal screenings, the coronavirus disease 2019 pandemic has resulted in a rise in sexually transmitted illnesses. According to the Centers for Disease Control and Prevention (CDC), syphilis cases surged by about 70% in the USA between 2019 and 2021, and while chlamydia and gonorrhea infections have increased less dramatically, they have nonetheless increased5. In 2020, 677,000 US populations were diagnosed with gonorrhea6. In 2021 alone, there were 2.5 million instances of these three STIs reported. With 333 004 new cases reported to the (CDC) in 20137, gonorrhea is the second most frequently reported notifiable disease in the USA8. However, the exact impact of gonococcal infection is probably much higher because many infections go undiagnosed or unreported4. Around 800, 000 new gonococcal infections are thought to arise yearly in the USA9. Although the national gonorrhea rate peaked in 1975 (464.1 cases per 100 000 000 population) but has significantly decreased thereafter. Several populations and geographical areas in the USA continue to have high gonorrhea prevalence. The highest disease burden is specifically seen in children and young adults aged 15–19 (337.5 cases per 100,000 population), young adults aged 20–24 (500.5 cases per 100,000 population), non-Hispanic blacks (426.6 cases per 100,000 population), and people living in the Southern United States (128.6 cases per 100,000 population)7. Sexual contact with the mouth, vagina, penis, or anus of a partner who is sick can lead to gonorrhea. Also, a pregnant woman can transmit it to her unborn child through vertical transmission. The majority of women, according to the CDC, are asymptomatic5. Even when symptoms do exist, they are sometimes so mild that they are misinterpreted for bladder or vaginal infections. However, women may have increased vaginal discharge, vaginal bleeding between periods, or uncomfortable urination as the earliest signs. Although many males are likewise asymptomatic5. Their symptoms differ from those of women. Men can experience scrotal or testicular pain, white, yellow, or green discharge that emerges 1–14 days after infection, as well as uncomfortable urination. Men and women both experiences itching, soreness, painful bowel motions, and discharge as signs of rectal infection10. Women who have gonorrhea complications run the risk of having their infection move to their uterus or fallopian tubes, which can result in pelvic inflammatory disease. Pelvic inflammatory illness can result in internal cysts, chronic pelvic pain, damage to the fallopian tubes, infertility issues, and an increased chance of ectopic pregnancy (when the egg grows outside the main uterine cavity). A pregnant woman who has gonorrhea can pass it on to her unborn child during vaginal delivery11, increasing the risk of the child developing joint infections, blindness, or potentially fatal blood infections. Gonorrhea can cause epididymitis in men (swelling or pain in the back of the testicle in the epididymis, the tube that stores and carries sperm) and, in rare instances, contributes to reproductive issues. Gonococcal infections, which are common in both men and women, are life-threatening conditions and if it is super-imposed on, by untreated gonorrhea, it could result in septic arthritis, meningitis, skin sores, endocarditis, etc. Moreso, untreated gonorrhea raises the possibility of HIV acquisition or transmission. Unfortunately, antibiotic resistance has made gonorrhea therapy more difficult. Perhaps owing to the frequency of sexually transmitted diseases, which have grown around the world especially in the USA as a result of the increased sexual activity that occurred during the coronavirus disease-19 pandemic, including the irrational use of antibiotics as well as a decline in the number of persons who underwent regular health screenings. This is likely to further explain the novel gonorrhea strains in the country. Current therapeutic options are highly constrained since N. gonorrhoeae has progressively developed resistance to all of the antibiotics that were recommended as first-line treatment regimens4,12. According to the CDC, 30% of gonorrhea infections in the USA exhibit some form of antibiotic resistance. The World Health Organization (WHO) and the (CDC) both published updated reports on antibiotic resistance in recent years13. With the decreasing availability of antibiotics that can effectively treat the disease, both reports indicated that gonorrhea is a serious burden to the public’s health. The bacteria have consistently developed resistance to all antibiotics used against it, 83 years ago, when sulfonamides and penicillin were previously used to treat gonorrheal infections, and several more recently advanced ones such as fluoroquinolones, for example, chloramphenicol, tetracycline, and oral cephalosporins, for example, ceftriaxone14. The rate of antibiotic resistance has then increased due to improper and irrational use of antibiotics as well as gonorrhea’s capacity to mutate and how it responds to therapy3,13. The problem of antibiotic-resistant infections, for example, this novel gonorrhea has gained increasing attention in recent years and in the reproductive health arena. This threat has taken the form of antibiotic-resistant strains of gonorrhea15. To meet that threat, it is crucial to step up research into the development of new treatment and testing options as well as better prevention technologies, especially in the USA15. Of recent, the CDC recommends only ceftriaxone, an injectable drug, along with azithromycin or doxycycline as a first-line treatment for gonorrhea in the USA. In July 2013, studies were indicated revealing that 2 antibiotic regimens using gentamicin and azithromycin were effective at treating gonorrhea. However, these regimens have not yet been incorporated into treatment guidelines in the USA16. Although these regimens may obviate the threat of untreatable gonorrhea for a time, it is likely that gonorrhea will develop resistance to these medications as well15. Presently, only a few promising antibiotics are in the timeline for development at a time when antibiotic resistance is increasing worldwide17. Also, most cases of gonorrhea in the USA are diagnosed through the use of nucleic acid amplification tests (NAATs). However, these tests do not provide same-visit results and cannot test gonorrhea strains for antibiotic resistance15. Because of this, we are urging the US government through its health authorities, physicians, and laboratory scientists to collaborate together to develop a new mechanism for testing for rapid diagnostic tests for gonorrhea that could improve treatment provision against antibiotic resistance, for example, microbicides that could potentially have a significant public health impact by reducing gonorrhea infections and associated antibiotic treatment across the country15. The US government should emphasize more on sex education programs and the appropriate and consistent use of condoms among the youths in the country. Because the vast majority of gonorrhea infections in the USA occur between the ages of 15 and 24 years old15. The US government should collaborate with the CDC, the WHO, and the United Nations Populations Fund in ensuring and implementing insurance coverage for condoms including behavioral modifications and vaccinations against human papillomavirus among this age group for the prevention of gonorrhea and other STIs. The use of condoms has been proven to be effective against gonorrhea by the CDC15. The United Nations Population Fund could educate the US citizens including the health care providers in the country about sexual and reproductive health programs, such as HIV/acquired immune deficiency syndrome, family planning, maternal and child health, and adolescent health, to ensure appropriate STI diagnosis and management. As a multisectoral collaboration with the WHO, the US government should upgrade their health policy among the health care providers especially the physicians, obstetricians, and gynecologists in adopting the STI syndromic approach as part of their treatment guidelines for gonorrhea1. This approach would entail a high index of suspicion by the clinicians, prompt diagnosis, which is often made clinically and based on the presence of signs and symptoms such as vaginal and urethral discharge. Presumptive treatment should be provided to individuals at high risk of gonococcal infection, if indicated based on local epidemiological patterns in the USA. N. gonorrhoeae can be diagnosed by culture or NAATs and, in some instances, Gram stain1. NAATs are highly sensitive and specific diagnostic tests that can be conducted on a wide range of samples, including urine, vulvovaginal, cervical, and urethral swabs. NAATs are said to have a sensitivity of over 90%, which is higher than for culture (>85%). We, therefore, recommend that laboratory scientists in the USA, especially in the local areas of the country, should do cultures in parallel with NAATs to allow for susceptibility testing. These scientists should also collect specimens from all cases of suspected gonococcal infection for microbiological culture and antimicrobial susceptibility testing, to the extent possible considering the local availability of resources in the country. Microbiological cultures of N. gonorrhoeae are specific and inexpensive. They have a reasonable sensitivity of 85%–95% for urethral and endocervical infection1. Although, optimal isolation of N. gonorrhoeae requires good specimen collection, timely inoculation into adequate and appropriate culture media, proper transportation, and appropriate incubation1, which laboratory scientists in the USA should put into consideration. Overall, in combating novel gonorrhea in the USA, all hands must be on deck. Proper public health measures should be put in place such as good policy-making on STIs, mass awareness campaigns on sexual rights and reproductive health among adolescents, promotion of wide use of condoms, vaccinations against human papillomavirus infection, as well prompt diagnosis, and the use of novel treatment regimens. Ethical approval Not applicable. Sources of funding No funding for this work.