Gonorrhoea (Neisseria gonorrhoeae) in the United States
Introduction
With over 600,000 new infections reported each year, Neisseria gonorrhoeae (N. gonorrhoeae) has become the second most common, sexually transmitted infection in the United States. With its incidence only second to Chlamydia trachomatisa [6], the most disturbing fact of N. gonorrhoeae lies in the reality that it shows no discrimination among the unprotected sexually active - anyone and everyone is susceptible. The group most at-risk are sexually active women under the age of twenty-five. Other risk factors include previous gonorrheal infection, diagnosis of other sexually transmitted diseases, new or multiple partners, inconsistent-to-no condom use, commercial sex work, as well as drug use [6]. Notable symptoms include: ??? [???]. However, with the majority of those asymptomatically infected, the ease of unintentional transmission is inevitable. Fearingly, if left untreated, can result in the sterility in both men and women [6]. Thus, the only factor keeping the infection from developing into an epidemic rests upon people routinely getting tested. Fortunately, because N. gonorrhoeae is a bacterium, curable treatment is available. However, this relief is currently being threatened.
History of the Name Neisseria Gonorrhoeae (N. Gonorrhoeae)
Aelius Galenus, a Roman physician and philosopher, first observed the bacterium in the second century and loosely named it the "flow of seed" [18]. The term resurfaced in the sixth century when Aetius Amidenus, a Byzantine physician and medical writer, observed the bacterium in pelvic abscesses. Infectiously spreading to France, the term gained popularity as it became symptomatically renown as "La chaude pisse", which literally translates to "hot piss" [14]. Finally, in 1879, Albert Ludwig Sigesmund Neisser, a German physician and bacteriologist, was the first person to describe the bacterium as the causative agent of gonorrhea and officially named the bacterium Neisseria gonorrhoeae.
Description of the Microbe
Neisseria gonorrhoeae (N. gonorrhoeae) is a gram-negative diplococcus ranging from 0.06 to 1.0 µm in diameter and is usually seen in pairs with adjacent flattened sides. Its outer membrane is composed of proteins, phospholipids, and lipopolysaccharides (LPS). The N. gonorrhoeae lipopolysaccharide can be distinguished from other types of LPS by its highly-branched basal oligosaccharide structure and the absence of repeating O-antigen subunits. Thus, it is referred to as lipooligosaccharide (LOS). During its growth, it releases outer membrane fragments called "blebs," which contains LOS and has a role in pathogenesis when they are spread during an infection [18]. LOS mediates infection by including attachment by pili, evasion of the host’s immune system, tissue damage, and the manifestation of bactericidal antibodies [8].
The organism is typically observed inside polymorphonuclear leukocytes (i.e., neutrophils) that become a part of the gonorrhea pustular exudate. Fimbriae are used by the bacteria for adherence, extending several micrometers from the cell surface [18]. They have antigenic type IV pilus and opacity (Opa) proteins. It moves by long pili that are constituted of repeated peptide subunits (pilin) characterized by both antigenic and phase variations. The bacterium is able to rearrange its chromosomal DNA altering the expression of any one of several silent pilin genes [19]. By doing so, phase variation (pi + to pil-) occurs when the rearrangement involves a defective pilin gene, thus avoiding their host (i.e., humans) immune system [13, 19]. The tight junctions and adherence to the host cell is due to the Opa proteins. The bacterium, like N. meningitidis, is also naturally competent for DNA uptake after attachment [10].
N. gonorrhoeae infect the mucous surfaces that are lined with columnar epithelium cells by the attachment of the bacterium via pili (fimbriae) and the production of lipopolysaccharide endotoxin [13, 18]. Due to the fact that the lipopolysaccharide is highly toxic and contains virulence factors in the form of its antiphagocytic capsule which produces IgA proteases, they contribute to the viral infection [18].
N. gonorrhoeae is a fragile bacterium that is sensitive to environmental conditions including temperature changes, drying, ultraviolet light, and the such. It is a "fastidious" bacterium that requires hemoglobin or blood, several amino acids, and vitamins for nourishment. In the laboratory, cultures must be grown at optimal temperature of 35-36 degrees in an atmosphere of 3-10% CO2 [13].
Statistics
Although a cure exists, statistics show that cases of infection are still on the rise. The reoccurring trend of increasing rates of gonorrhea infection can be seen uniformly across regions, states, sex, age, and race/ethnicity. In 2007, 355,991 cases of gonorrhea were reported in the United States. This equates to roughly 118.9 cases per 100,000 people in 2007 [5]. This rate of gonorrhea infection has remained relatively stable the past decade, especially among women. The gonorrhea rate among women was reported at 123.5 and the rate among men was reported at 113.7 cases per 100,000 people in 2007 [5]. In the same year, the gonorrhea rates continue to be the highest among young adults and adolescents; among females in the ages of 15 – 24 and among males between the ages of 20 – 24. The data suggests that gonorrhea is still on the rise and further development of treatment beyond the boundaries of medication is needed.
Why is the Gonorrhea a Problem in the United States?
Risk Factors
The highest reported rates of infection in the US are among sexually active women and African Americans [3]. It was not long ago that gonorrhea was a serious concern to the public health like many other major STD or STI such as Syphilis, a top priority of all health organizations. However, according to the New York Times article by Lawrence K. Altman, Sex Diseases Still Rising; Chlamydia Is Leader, “From 1975 through 1997 the reported rate of gonorrhea dropped 74 percent, then plateau, only to rise the last two years to 358,366 cases in 2006. The actual numbers are estimated at about twice of that.” This issues raises concern in America especially because the American people have had the luxury of healthcare that many third world countries are not capable of receiving. It is apparent that safe sex practices had been abandoned and thus have resulted in a jump in gonorrhea cases recently. Another risk factor to consider in America is the disproportionately amount of African-Americans having the higher prevalence than any other ethnic groups. In comparison 18 to 1 ratio of African Americans to Whites. “African Americans account for 69 percent of all gonorrhea in this country” [1]. Also it is important to note according to the newsletter written in DRUG WEEK on an MMWR Report on Gonorrhea and Chlamydia Incidence among MSM, that gonorrhea or Chlamydia infections can be significant co-factors in the transmission of HIV [2]. This becomes another issue in America as it is the harbor of many homosexuals living in big cities such as San Francisco, Los Angeles, and New York, that such infections can easily be transmitted to many individuals in a very short amount of time. Often drug use is the highest in these areas, which can further cause a much higher incidence rate due to sharing of potentially infected needles.
Transmission
Gonorrhea, which is caused by the bacterium N. gonorrhoeae, is harbored in warm and moist areas and sexually transmitted through contact of an infected tissue surface on vaginal, penile, anus, or mouth [17,11]. When left untreated, it can severely effect the uterus, cervix, and fallopian tubes in women and the urethra in men, potentially leading to sterility [12]. In addition to being transmitted sexually, it can be transmitted vertically from an infected, pregnant woman to the baby she is carrying. This infection can reach the offspring through the birth canal of the mother during delivery [11].
Symptoms
The symptoms of gonorrhea vary substantially and can be fatal if left untreated. In males, signs of symptoms can appear anywhere from 2 days to 30 days or not appear at all. It is important to seek a doctor if any symptoms such as a white, yellow, or green discharge from the penis, a burning sensation while urinating, or formation of unusual sores or rash arise. Occasionally, males can also get swollen or painful testicles [6]. Among females, it is common that no symptoms show but when symptoms do show, they are very meek. Female symptoms can include painful or burning urination, vaginal bleeding between periods, and increased vaginal discharge [6]. However, their symptoms are often mistaken for a vaginal or bladder infection. Despite the severity or presence of their symptoms, women with gonorrhea are still at great risk of developing serious complications.
Prevention
According to the CDC fact sheet, the best method for prevention is to abstain from sexual intercourse or to be in a long monogamous relationship with a partner that has been tested or treated for Gonorrhea. Other preventive measures include using latex condoms that can reduce the risk of catching gonorrhea. Moreover, to further decrease the spread of this disease it is vital for individuals that have been diagnosed to notify all previous partners to get tested immediately and to further prevent a serious outbreak of infections. It is also critical to get a routine screening for any high risk groups with a constant follow up of there medical history and condition before they further engage in any transmissible activity [4]. Due to the recent expansion of resistance in Neisseria gonorrhea within certain antimicrobial classes as well as its readily infectious capability, prevention is a key element to minimize further outbreaks. A unique prevention strategy implemented include the enhancement of national and international surveillance, to monitor resistance and to better compliment new strategies to essentially maximize the benefit and further prolong the utility of antimicrobials. This can include combination regimens, applying screening recommendations for those that are high risk for infection, and to further continue proper effective treatment for infected persons and their sexual partners. Testing every 3 to 4 months after treatment for initial infection is highly recommended to prevent re-infection [9]. An article in Drug Week published March 20, 2009 tried to identify intervention strategies for prevention and control in San Francisco. They found that there was a substantial gonorrhea increase among young heterosexuals during 2003-2005. The researchers conclusion were based on there case study which focused on, on blacks and incarcerated populations using street-based outreach and expanded screening and treatment” [2].
What is Being Done to Combat the Spread of N. Gonorrhoeae?
As the second most commonly reported sexually transmitted disease, a multitude of prevention and treatment strategies have been developed and enforced to control the spread of gonorrhea. Due to the fact that the prevalence of N. gonorrhoeae infection varies among communities and populations [6], the basic sociological measures for control include preventative solutions such as: (1) increasing the education and awareness of the N. gonorrhoeae microbe and its resulting gonorrhea infection, (2) openly supporting condom use, (3) encouraging those at-risk be tested, (4) stressing the urgency in seeking treatment if diagnosed and refraining from sexual intercourse until remission, and (5) referring the sex partner of the diagnosed be tested [9]. At the clinical front, physicians are doing their part to control N. gonorrhoeae transmission by testing all at-risk groups – the highest at-risk group being sexually active women under the age of twenty-five. Other risk factors include previous gonorrheal infection, diagnosis of other sexually transmitted diseases, new or multiple partners, inconsistent-to-no condom use, commercial sex work, as well as drug use. The effective diagnostic tests at which physicians are currently utilizing to test for N. gonorrhoeae include: Gram stain (reserved for symptomatic patients only), culture, nucleic acid hybridization tests, and nucleic acid amplification tests (NAAT). Each requires the testing of cervical, vaginal, male urethral, and/or urine specimens. Fortunately, if a positive test for N. gonorrhoeae results, due to the fact that the microbe is a bacterium, it can easily be treated and cured with antibiotics such as ceftriaxone, cefixime, ciprofloxacin, ofloxacin, or levofloxacin. However, with N. gonorrhoeae’s rising co-infection with uncomplicated C. trachomatis and health officials’ routine approach to co-treat both bacterial infections, an antimicrobial-resistant N. gonorrhoeae strain known as quinolone-resistant N. gonorrhoeae (QRNG) has developed. As a result, common antidotes containing fluoroquinolones, such as ciprofloxacin, are inadvisable, especially in the United States. Two states of particular concern are California and Hawaii as they both contain the highest prevalence of QRNG as seen in the Centers for Disease Control and Prevention’s Gonococcal Isolate Surveillance Project 2004 study of 6,322 isolates showing 6.8% resistant to ciprofloxacin. Excluding the isolates gathered from California and Hawaii, only 3.6% were QRNG [6]. Overall, this study’s conclusion is critical as it highlights the competitive race between aggressively adapting antibiotic-resistant microbes and the scientific discovery of new antibiotics.
What Else Can be Done to Address this Rising Problem?
As antibiotic-resistant strands of N. gonorrhoeae continue to spread throughout the United States, certain antibiotics are increasingly becoming ineffective in treating gonorrhea. Since 1993, fluoroquinones have been used frequently to treat gonorrhea in the United States because it was the overall drug treatment of choice; fluoroquinones were effective as an easy oral method of treatment that required only a single dose. In 2006, however, the Centers for Disease Control and Prevention (CDC) announced that it no longer recommends fluoroquinones for treatment of gonorrhea because of the bacterium's increasing resistance throughout the United States. Similarly, other antibiotics such as penicillin, tetracycline, and macrolides have not been recommended in the United States because susceptibility to such drugs has been inadequate [6]. Currently, drugs within the cephalosporin class are being used to treat gonorrhea in the United States, but growing resistance and adaptation to antibiotics places heavy emphasis on the development of novel pharmaceuticals for future treatment of gonorrhea. Current research seeks to uncover the genetic and molecular specifics of N. gonorrhoeae, such that particular drugs may be targeted to disrupt it. For example, antigenic variation has been found in N. gonorrhoeae, thus making it hard to develop a vaccine against it [14]. Thus, more focused, pharmaceutical studies geared toward uncovering the molecular basis by which antigenic variation occurs would prove itself useful for combating antibiotic-resistant strands of N. gonorrhoeae [16].
Along with the development of novel drugs for treatment, the development of novel techniques to diagnose individuals with gonorrhea would also be effective toward curbing the spread of the infection. One such recently developed technique that has gained the respect of being the most sensitive and specific test to date for N. gonorrhoeae detection is the nucleic acid amplification test (NAAT)— of which polymerase chain reaction (PCR) falls into categorically. Despite the effectiveness of NAAT, the Food and Drug Administration (FDA) has not cleared for its use on rectal and pharyngeal tissues [4] due to the fact that native microbes that inhabit those areas compromise test results. Future developments may empirically test NAAT to ascertain its usefulness for diagnosing such areas, thereby lifting the FDA restriction.
Another mode for preventing further spread of gonorrhea is through the development of more hubs for disease control (e.g., clinics), particularly in metropolitan areas where infection is most prevalent due to high population density and increased social and sexual interaction. By constructing more clinics, a more accurate representation of the epidemiology of N. gonorrhoeae may be ascertained. The means by which the United States currently monitors and controls N. gonorrhoeae epidemiology is through the Gonococcal Isolate Surveillance Project (GISP). GISP monitors N. gonorrhoeae prevalence and its susceptibility to antibiotics through sexually-transmitted disease (STD) clinics, regional laboratories, and the CDC itself. It was through GISP that resistance to a fluoroquinone was first identified in 1991. In GISP protocol, a representative subset of the cultures positive for N. gonorrhoeae are tested for antibiotic resistance. As a result, specific antibiotics are prescribed based on demographic and regional data such that treatment remains effective. Currently, approximately 28 cities with STD clinics are part of GISP. With more hubs of disease control, the accessibility of preventative education, materials, and treatment would become available to better tailor to regional needs [3].
References
1. Altman, Lawrence K. "Sex Diseases Still Rising; Chlamydia Is Leader." The New York Times 14 Nov. 2007: 21-21. Print.
2. Barry, P. M. "Drug Week." GONORRHEA; Research from P.M. Barry and co-authors yields new data on gonorrhea (20 Mar. 2009): 616. Print.
7. Crosby, R.A., R.J. DiClement, S.L. Rosenthal, and L.F. Salazar. Prevention and Control of Sexually Transmitted Infections Among Adolescents: The Importance of a Socio-Ecological Perspective. ScienceDirect 2005; 119.9:825-36. Print.
10. "Genome Project Result." NCBI HomePage. Web. 25 Aug. 2009.
11. "Gonorrhea." National Institute of Allergy and Infectious Diseases. Web. 26 Aug. 2009.
13. "Gonorrhea." Welcome to the UW-Madison Dept. of Bacteriology. Web. 26 Aug. 2009.
14. Hedges SR, Mayo MS, Mestecky J, Hook EW III & Russell MW (1999) Limited Local and Systemic Antibody Responses to Neisseria Gonorrhoeae During Uncomplicated Genital Infections. Infect Immun 67: 3937–3946. Print.
15. J. O'Dowd, Michael. The History of Medications for Women. New York City: The Parthenon Publishing Group Inc., 2001. Print.
16. Pilin Gene Variation in Neisseria Gonorrhoeae: Reassessing the Old Paradigms. FEMS Microbiology Reviews [0168-6445] Hill, Stuart (2009) volume: 33 issue: 3 page: 521 -30. Print.
17. "STD Facts - Gonorrhea." Centers for Disease Control and Prevention. Web. 26 Aug. 2009.
19. "WHO | Sexually Transmitted Diseases." Web. 25 Aug. 2009.
Edited by: Joelle Abed Elahad, Mykel Anderson, Tim Chiang, Danny Huynh, Fisal Mohsini, and Cuong Huy Nguyen, students of Rachel Larsen, Ph.D.
