Chlamydia and gonorrhea…
Below some observations from Holmes et al.‘s chapters about the sexually transmitted bacterial infections chlamydia and gonorrhea. A few of these chapters covered some really complicated stuff, but I’ve tried to keep the coverage reasonably readable by avoiding many of the technical details. I’ve also tried to make the excerpts easier to read by adding relevant links and by adding brief explanations of specific terms in brackets where this approach seemed like it might be helpful.
“Since the early 1970s, Chlamydia trachomatis has been recognized as a genital pathogen responsible for an increasing variety of clinical syndromes, many closely resembling infections caused by Neisseria gonorrhoeae […]. Because many practitioners have lacked access to facilities for laboratory testing for chlamydia, these infections often have been diagnosed and treated without benefit of microbiological confirmation. Newer, molecular diagnostic tests have in part now addressed this problem […] Unfortunately, many chlamydial infections, particularly in women, are difficult to diagnose clinically and elude detection because they produce few or no symptoms and because the symptoms and signs they do produce are nonspecific. […] chlamydial infections tend to follow a fairly self-limited acute course, resolving into a low-grade persistent infection which may last for years. […] The disease process and clinical manifestations of chlamydial infections probably represent the combined effects of tissue damage from chlamydial replication and inflammatory responses to chlamydiae and the necrotic material from destroyed host cells. There is an abundant immune response to chlamydial infection (in terms of circulating antibodies or cell-mediated responses), and there is evidence that chlamydial diseases are diseases of immunopathology. […] A common pathologic end point of chlamydial infection is scarring of the affected mucous membranes. This is what ultimately leads to blindness in trachoma and to infertility and ectopic pregnancy after acute salpingitis. There is epidemiologic evidence that repeated infection results in higher rates of sequelae.”
“The prevalence of chlamydial urethral infection has been assessed in populations of men attending general medical clinics, STD clinics, adolescent medicine clinics, and student health centers and ranges from 3–5% of asymptomatic men seen in general medical settings to 15–20% of all men seen in STD clinics. […] The overall incidence of C. trachomatis infection in men has not been well defined, since in most countries these infections are not officially reported, are not microbiologically
confirmed, and often may be asymptomatic, thus escaping detection. […] The prevalence of chlamydial infection has been studied in pregnant women, in women attending gynecology or family planning clinics, in women attending STD clinics, in college students, and in women attending general medicine or family practice clinics in school-based clinics and more recently in population-based studies. Prevalence of infection in these studies has ranged widely from 3% in asymptomatic women in community-based surveys to over 20% in women seen in STD clinics.[31–53] During pregnancy, 3–7% of women generally have been chlamydia positive […] Several studies in the United States indicate that approximately 5% of neonates acquire chlamydial infection perinatally, yet antibody prevalence in later childhood before onset of sexual activity may exceed 20%.”
“Clinically, chlamydia-positive and chlamydia-negative NGU [Non-Gonococcal Urethritis] cannot be differentiated on the basis of signs or symptoms. Both usually present after a 7–21-day incubation period with dysuria and mild-to-moderate whitish or clear urethral discharge. Examination reveals no abnormalities other than the discharge in most cases […] Clinical recognition of chlamydial cervicitis depends on a high index of suspicion and a careful cervical examination. There are no genital symptoms that are specifically correlated with chlamydial cervical infection. […] Although urethral symptoms may develop in some women with chlamydial infection, the majority of female STD clinic patients with urethral chlamydial infection do not have dysuria or frequency. […] the majority of women with chlamydial infection cannot be distinguished from uninfected women either by clinical examination or by […] simple tests and thus require the use of specific diagnostic testing. […] Since many chlamydial infections are asymptomatic, it has become clear that effective control must involve periodic testing of individuals at risk. As the cost of extensive screening may be prohibitive, various approaches to defining target populations at increased risk of infection have been evaluated. One strategy has been to designate patients attending specific high prevalence clinic populations for universal testing. Such clinics would include STD, juvenile detention, and some family planning clinics. This approach, however, fails to account for the majority of asymptomatic infections, since attendees at high prevalence clinics often attend because of symptoms or suspicion of infection. Consequently, selective screening criteria have been developed for use in various clinical settings.[204–208] Among women, young age (generally, <24 years) is a critical risk factor for chlamydial infection in almost all studies. […] The practical implementation of screening programs in settings with low-to-moderate chlamydia prevalence requires that the prevalence at which selective screening becomes cost effective relative to universal screening must be defined. Toward this end, a number of investigators have undertaken cost-effectiveness analyses. Most of these analyses have concluded that universal screening is preferred in settings with chlamydia prevalence above 3–7%.”
If you’re a woman who’s decided not to have children and so aren’t terribly worried about infertility, it should be emphasized that untreated chlamydia can cause other really unpleasant stuff as well, like chronic pelvic pain from pelvic inflammatory disease, or ectopic pregnancy, which may be life-threatening. This is the sort of infection you’ll want to get treated even if you’re not bothered by symptoms.
Neisseria gonorrhoeae (gonococci) is the etiologic agent of gonorrhea and its related clinical syndromes (urethritis, cervicitis, salpingitis, bacteremia, arthritis, and others). It is closely related to Neisseria meningitidis (meningococci), the etiologic agent of one form of bacterial meningitis, and relatively closely to Neisseria lactamica, an occasional human pathogen. The genus Neisseria includes a variety of other relatively or completely nonpathogenic organisms that are principally important because of their occasional diagnostic confusion with gonococci and meningococci. […] Many dozens of specific serovars have been defined […] By a combination of auxotyping and serotyping […] gonococci can be divided into over 70 different strains; the number may turn out to be much larger.”
“Humans are the only natural host for gonococci. Gonococci survive only a short time outside the human body. Although gonococci can be cultured from a dried environment such as a toilet seat up to 24 hours after being artificially inoculated in large numbers onto such a surface, there is virtually no evidence that natural transmission occurs from toilet seats or similar objects. Gonorrhea is a classic example of an infection spread by contact: immediate physical contact with the mucosal surfaces of an infected person, usually a sexual partner, is required for transmission. […] Infection most often remains localized to initial sites of inoculation. Ascending genital infections (salpingitis, epididymitis) and bacteremia, however, are relatively common and account for most of the serious morbidity due to gonorrhea.”
“Consideration of clinical manifestations of gonorrhea suggests many facets of the pathogenesis of the infection. Since gonococci persist in the male urethra despite hydrodynamic forces that would tend to wash the organisms from the mucosal surface, they must be able to adhere effectively to mucosal surfaces. Similarly, since gonococci survive in the urethra despite close attachment to large numbers of neutrophils, they must have mechanisms that help them to survive interactions with polymorphonuclear neutrophils. Since some gonococci are able to invade and persist in the bloodstream for many days at least, they must be able to evade killing by normal defense mechanisms of plasma […] Invasion of the bloodstream also implies that gonococci are able to invade mucosal barriers in order to gain access to the bloodstream. Repeated reinfections of the same patient by one strain strongly suggest that gonococci are able to change surface antigens frequently and/or to escape local immune mechanisms […] The considerable tissue damage of fallopian tubes consequent to gonococcal salpingitis suggests that gonococci make at least one tissue toxin or gonococci trigger an immune response that results in damage to host tissues. There is evidence to support many of these inferences. […] Since the mid-1960s, knowledge of the molecular basis of gonococcal–host interactions and of gonococcal epidemiology has increased to the point where it is amongst the best described of all microbial pathogens. […] Studies of pathogenesis are [however] complicated by the absence of a suitable animal model. A variety of animal models have been developed, each of which has certain utility, but no animal model faithfully reproduces the full spectrum of naturally acquired disease of humans.”
“Gonococci are inherently quite sensitive to antimicrobial agents, compared with many other gram-negative bacteria. However, there has been a gradual selection for antibioticresistant mutants in clinical practice over the past several decades […] The consequence of these events has been to make penicillin and tetracycline therapy ineffective in most areas. Antibiotics such as spectinomycin, ciprofloxacin, and ceftriaxone generally are effective but more expensive than penicillin G and tetracycline. Resistance to ciprofloxacin emerged in SE Asia and Africa in the past decade and has spread gradually throughout much of the world […] Streptomycin (Str) is not frequently used for therapy of gonorrhea at present, but many gonococci exhibit high-level resistance to Str. […] Resistance to fluoroquinolones is increasing, and now has become a general problem in many areas of the world.”
“The efficiency of gonorrhea transmission depends on anatomic sites infected and exposed as well as the number of exposures. The risk of acquiring urethral infection for a man following a single episode of vaginal intercourse with an infected woman is estimated to be 20%, rising to an estimated 60–80% following four exposures. The prevalence of infection in women named as secondary sexual contacts of men with gonococcal urethritis has been reported to be 50–90%,[16,17] but no published studies have carefully controlled for number of exposures. It is likely that the single-exposure transmission rate from male to female is higher than that from female to male […] Previous reports saying that 80% of women with gonorrhea were asymptomatic were most often based on studies of women who were examined in screening surveys or referred to STD clinics because of sexual contact with infected men. Symptomatic infected women who sought medical attention were thus often excluded from such surveys. However […] more than 75% of women with gonorrhea attending acute care facilities such as hospital emergency rooms are symptomatic. The true proportion of infected women who remain asymptomatic undoubtedly lies between these extremes […] Asymptomatic infections occur in men as well as women […] Asymptomatically infected males and females contribute disproportionately to gonorrhea transmission, because symptomatic individuals are more likely to cease sexual activity and seek medical care.”
“the incidence of asymptomatic urethral gonococcal infection in the general population also has been estimated at approximately 1–3%. The prevalence of asymptomatic infection may be much higher, approaching 5% in some studies, because untreated asymptomatic infections may persist for considerable periods. […] The prevalence of gonorrhea within communities tends to be dynamic, fluctuating over time, and influenced by a number of interactive factors. Mathematical models for gonorrhea within communities suggest that gonorrhea prevalence is sustained not only through continued transmission by asymptomatically infected patients but also by “core group” transmitters who are more likely than members of the general population to become infected and transmit gonorrhea to their sex partners. […] At present, gonorrhea prevention and control efforts are heavily invested in the concept of vigorous pursuit and treatment of infected core-group members and asymptomatically infected individuals.”
“Relatively large numbers (>50) of gonococcal A/S [auxotype/serotype] classes usually are present in most communities simultaneously […] and new strains can be detected over time. The distribution of isolates within A/S classes tends to be uneven, with a few A/S classes contributing disproportionately to the total number of isolates. These predominant A/S classes generally persist within communities for months or years. […] Interviews of the patients infected by [a specific] strain early in [an] outbreak identified one infected female who acknowledged over 100 different sexual partners over the preceding 2 months, suggesting that she may have played an important role in the introduction and establishment of this gonococcal strain in the community. Thus the Proto/IB-3 strain may have become common in Seattle not because of specific biologic factors but because of its chance of transmission to members of a core population by a high-frequency transmitter.” [100+ partners over a 2 month period! I was completely dumbstruck when I’d read that.]
“clinical gonorrhea is manifested by a broad spectrum of clinical presentations including asymptomatic and symptomatic local infections, local complicated infections, and systemic dissemination. […] Acute anterior urethritis is the most common manifestation of gonococcal infection in men. The incubation period ranges from 1 to 14 days or even longer; however, the majority of men develop symptoms within 2–5 days […] The predominant symptoms are urethral discharge or dysuria [pain on urination]. […] Without treatment, the usual course of gonococcal urethritis is spontaneous resolution over a period of several weeks, and before the development of effective antimicrobial therapy, 95% of untreated patients became asymptomatic within 6 months. […] The incubation period for urogenital gonorrhea in women is less certain and probably more variable than in men, but most who develop local symptoms apparently do so within 10 days of infection.[51,52] The most common symptoms are those of most lower genital tract infections in women […] and include increased vaginal discharge, dysuria, intermenstrual uterine bleeding, and menorrhagia [abnormally heavy and prolonged menstrual period], each of which may occur alone or in combination and may range in intensity from minimal to severe. […] The clinical assessment of women for gonorrhea is often confounded […] by the nonspecificity of these signs and symptoms and by the high prevalence of coexisting cervical or vaginal infections with Chlamydia trachomatis, Trichomonas vaginalis, Candida albicans, herpes simplex virus, and a variety of other organisms […] Among coinfecting agents for patients with gonorrhea in the United States, C. trachomatis [chlamydia] is preeminent. Up to 10–20% of men and 20–30% of women with acute urogenital gonorrhea are coinfected with C. trachomatis.[10,46,76,139–141] In addition, substantial numbers of women with acute gonococcal infection have simultaneous T. vaginalis infections.”
“Among patients with gonorrhea, pharyngeal infection occurs in 3–7% of heterosexual men, 10–20% of heterosexual women, and 10–25% of homosexually active men. […] Gonococcal infection is transmitted to the pharynx by orogenital sexual contact and is more efficiently acquired by fellatio than by cunnilingus.”
“In men, the most common local complication of gonococcal urethritis is epididymitis […], a syndrome that occurred in up to 20% of infected patients prior to the availability of modern antimicrobial therapy. […] Postinflammatory urethral strictures were common complications of untreated gonorrhea in the preantibiotic era but are now rare […] In acute PID [pelvic inflammatory disease], the clinical syndrome comprised primarily of salpingitis, and frequently including endometritis, tubo-ovarian tuboovarian abscess, or pelvic peritonitis is the most common complication of gonorrhea in women, occurring in an estimated 10–20% of those with acute gonococcal infection.[75,76] PID is the most common of all complications of gonorrhea, as well as the most important in terms of public-health impact, because of both its acute manifestations and its longterm sequelae (infertility, ectopic pregnancy, and chronic pelvic pain).”
“A major impediment to use of culture for gonorrhea diagnosis in many clinical settings are the time, expense, and logistical limitations such as specimen transport to laboratories for testing, a process that may take several days and result in temperature variation or other circumstances that can jeopardize culture viability. In recent years, reliable nonculture assays for gonorrhea detection have become available and are being used increasingly. […] recently, nucleic acid amplification tests (NAATs) for gonorrhea diagnosis have become widely available.[116,117] Assays based on polymerase chain reaction (PCR), transcription-mediated amplification (TMA), and other nucleic acid amplification technologies have been developed. As a group, commercially available NAATs are more sensitive than culture for gonorrhea diagnosis and specificities are nearly as high as for culture. […] Emerging data suggest that most currently available NAATs are substantially more sensitive for gonorrhea detection than conventional culture.”
“Prior to the mid-1930s, when sulfanilamide was introduced, gonorrhea therapy involved local genital irrigation with antiseptic solutions such as silver nitrate […] By 1944 […] many gonococci had become sulfanilamide resistant […] Fortunately, in 1943 the first reports of the near 100% utility of penicillin for gonorrhea therapy were published, and by the end of World War II, as penicillin became available to the general public, it quickly became the therapy of choice. Since then, continuing development of antimicrobial resistance by N. gonorrhoeae[128,129] led to regular revisions of recommended gonorrhea therapy. From the 1950s until the mid-1970s, gradually increasing chromosomal penicillin resistance led to periodic increases in the amount of penicillin required for reliable therapy. […] by the late 1980s, penicillins and tetracyclines were no longer recommended for gonorrhea therapy.
In addition to resistance to penicillin, tetracyclines, and erythromycin, in 1987, clinically significant chromosomally mediated resistance to spectinomycin — another drug recommended for gonorrhea therapy — was described in U.S. military personnel in Korea. In Korea, because of the high prevalence of PPNG [spectinomycin-resistant Penicillinase-Producing Neisseria Gonorrhoeae], in 1981, spectinomycin had been adopted as the drug of choice for gonorrhea therapy. By 1983, however, spectinomycin treatment failures were beginning to occur in patients with gonorrhea […] Following recognition of the outbreak of spectinomycin-resistant gonococci in Korea, ceftriaxone became the drug of choice for treatment of gonorrhea in U.S. military personnel in that country. […] Beginning in 1993, fluoroquinolone antibiotics were recommended for therapy of uncomplicated gonorrhea in the United States […] [However] in 2007 the CDC opted to no longer recommend fluoroquinolone antibiotics for therapy of uncomplicated gonorrhea. This change meant that ceftriaxone and other cephalosporin antibiotics had become the sole class of antibiotics recommended as first-line therapy for gonorrhea. […] For over two decades, ceftriaxone — a third-generation cephalosporin—has been the most reliable single-dose regimen used for gonorrhea worldwide. […] there are currently few well-studied therapeutic alternatives to ceftriaxone for gonorrhea treatment.”
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