Diagnosis and Treatment of Sexually Transmitted Infections: A Review.

Importance: Approximately 1 in 5 adults in the US had a sexually transmitted infection (STI) in 2018. This review provides an update on the epidemiology, diagnosis, and treatment of gonorrhea, chlamydia, syphilis, Mycoplasma genitalium, trichomoniasis, and genital herpes. Observations: From 2015 to 2019, the rates of gonorrhea, chlamydia, and syphilis increased in the US; from 1999 to 2016, while the rates of herpes simplex virus type 1 (HSV-1) and HSV-2 declined. Populations with higher rates of STIs include people younger than 25 years, sexual and gender minorities such as men and transgender women who have sex with men, and racial and ethnic minorities such as Black and Latinx people. Approximately 70% of infections with HSV and trichomoniasis and 53% to 100% of extragenital gonorrhea and chlamydia infections are asymptomatic or associated with few symptoms. STIs are associated with HIV acquisition and transmission and are the leading cause of tubal factor infertility in women. Nucleic acid amplification tests have high sensitivities (86.1%-100%) and specificities (97.1%-100%) for the diagnosis of gonorrhea, chlamydia, M genitalium, trichomoniasis, and symptomatic HSV-1 and HSV-2. Serology remains the recommended method to diagnose syphilis, typically using sequential testing to detect treponemal and nontreponemal (antiphospholipid) antibodies. Ceftriaxone, doxycycline, penicillin, moxifloxacin, and the nitroimidazoles, such as metronidazole, are effective treatments for gonorrhea, chlamydia, syphilis, M genitalium, and trichomoniasis, respectively, but antimicrobial resistance limits oral treatment options for gonorrhea and M genitalium. No cure is available for genital herpes. Effective STI prevention interventions include screening, contact tracing of sexual partners, and promoting effective barrier contraception. Conclusions and Relevance: Approximately 1 in 5 adults in the US had an STI in 2018. Rates of gonorrhea, chlamydia, and syphilis in the US have increased, while rates of HSV-1 and HSV-2 have declined. Ceftriaxone, doxycycline, penicillin, moxifloxacin, and the nitroimidazoles are effective treatments for gonorrhea, chlamydia, syphilis, Mycoplasma genitalium, and trichomoniasis, respectively, but antimicrobial resistance limits oral therapies for gonorrhea and Mycoplasma genitalium, and no cure is available for genital herpes.

Mycoplasma genitalium Infections With Macrolide and Fluoroquinolone Resistance-Associated Mutations in Heterosexual African American Couples in Alabama.

BACKGROUND: Mycoplasma genitalium (MG) is a sexually transmitted pathogen associated with inflammatory syndromes in men and women. Macrolides and fluoroquinolones are recommended MG treatments. The frequency of MG strains with macrolide resistance-associated mutations (MRMs) and quinolone resistance-associated mutations (qRMs) is increasing worldwide, however these data are sparse in populations in the United States. METHODS: We investigated the prevalence of MG infections with MRMs and qRMs and MG infection concordance within African American couples in Birmingham, AL. We used a real-time polymerase chain reaction to detect MG and identify MRMs. quinolone resistance-associated mutations were detected using traditional polymerase chain reactions amplifying regions in gyrA, gyrB, parC, and parE. The MG concordance in couples was evaluated by MG positivity and MG genotypes. RESULTS: Oral, anal, urine, and/or vaginal specimens were tested from 116 couples. Twenty-eight (12.1%) participants comprising 22 couples tested MG-positive (11.2% in men and 12.9% in women). Macrolide resistance-associated mutations were detected in 17 (60.7%) MG-positive participants, with gender-specific resistance rates of 69.2% for men and 53.3% for women. quinolone resistance-associated mutations were detected in 3 (11.1%) MG-positive participants, all of whom also had MRMs. By MG positivity status, 27.3% of couples were concordant. If MG strain genotypes are also considered, then concordance was 20.0%. CONCLUSIONS: Among heterosexual African Americans with MG infection, about 60% had strains with MRMs and 11% had strains with both MRMs and qRMs, highlighting the potential for MG treatment failure to not only macrolides, but also quinolones. These findings may help to guide clinicians in MG testing and treatment decisions in the United States.

Routine testing of Mycoplasma genitalium and Trichomonas vaginalis.

BACKGROUND: Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) are common sexual transmitted infections (STI). However, most STI screening programmes do not include routinely detection of these pathogens. Consequently, epidemiological data about MG and TV in the general population is lacking. The current study aims to give insight into the prevalence of both infections, thereby guiding decisions whether testing for these pathogens should be included routinely. METHODS: Between February 2013 and August 2015, all samples sent to the laboratory of Diakonessenhuis Utrecht for STI testing (i.e. testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG)) were additionally examined for the presence of MG and TV by means of a laboratory-developed RT-PCR. Samples were collected by our hospital or by regional general practitioners. RESULTS: A total of 5628 PCR's were evaluated. In 7.5%, one or more STI were detected. CT was found in 5% and MG was positive in 1.9%. NG was detected in 0.5% and TV was detected in 0.6% of the samples. CT was found more often in primary care than in hospital setting (9.7% vs. 3.0%, p < .05). The same was shown for NG (1.1% vs. 0.2%, p < .05). More men than women were positive for CT (11.2% vs. 3.8%, p < .05) and NG (1.4% vs. 0.3%, p < .05). CONCLUSION: MG is more prevalent than NG and TV in a regional Dutch population. Furthermore, TV is equally common as NG. Based on our prevalence data, including MG and TV in STI testing protocols should be considered in the future.

Epidemiology of Mycoplasma genitalium in British men and women aged 16­44 years: evidence from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

BACKGROUND: There are currently no large general population epidemiological studies of Mycoplasma genitalium (MG), which include prevalence, risk factors, symptoms and co-infection in men and women across a broad age range. METHODS: In 2010-­12, we conducted the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a probability sample survey in Britain. Urine from 4507 sexually-experienced participants, aged 16­44 years, was tested for MG. RESULTS: MG prevalence was 1.2% [95% confidence interval (CI): 0.7­1.8%] in men and 1.3% (0.9­1.9%) in women. There were no positive MG tests in men aged 16­19, and prevalence peaked at 2.1% (1.2­3.7%) in men aged 25­34 years. In women, prevalence was highest in 16­19 year olds, at 2.4% (1.2­4.8%), and decreased with age. Men of Black ethnicity were more likely to test positive for MG [adjusted odds ratio (AOR) 12.1; 95% CI: 3.7­39.4). For both men and women, MG was strongly associated with reporting sexual risk behaviours (increasing number of total and new partners, and unsafe sex, in the past year). Women with MG were more likely to report post-coital bleeding (AOR 5.8; 95%CI 1.4­23.3). However, the majority of men (94.4%), and over half of women (56.2%) with MG did not report any sexually transmitted infection (STI) symptoms. Men with MG were more likely to report previously diagnosed gonorrhoea, syphilis or non-specific urethritis, and women previous trichomoniasis. CONCLUSIONS: This study strengthens evidence that MG is an STI. MG was identified in over 1% of the population, including in men with high-risk behaviours in older age groups that are often not included in STI prevention measures.

Mycoplasma genitalium in male urethritis: diagnosis and treatment in Japan.

Male urethritis is a common disease for urologists, with the most common pathogens being, Chlamydia trachomatis and Neisseria gonorrhoeae. When the tests fail to detect these pathogens, the presented urethritis is called non-chlamydial non-gonococcal urethritis. Mycoplasma genitalium is one of the pathogens for non-chlamydial non-gonococcal urethritis. The test for detecting M. genitalium, which is commercially available in Japan, is not accepted by the Japanese insurance system now. The detection rate of M. genitalium from patients with non-gonococcal urethritis is 10-20% in Japan. Antimicrobial susceptibility testing for M. genitalium showed that macrolide has the strongest activity and the minimum inhibitory concentrations of tetracyclines were not substantially lower. Some kinds of fluoroquinolones, such as sitafloxacin and moxifloxacin, have stronger activities against M. genitalium. For non-gonococcal urethritis, macrolides and tetracycline are recommended in some guidelines. In clinical studies, tetracyclines are less effective against M. genitalium than azithromycin, and azithromycin regimens including 1 g stat or 2 g stat are now recommended for urethritis with M. genitalium. However, macrolide-resistant M. genitalium strains have recently emerged and are spreading worldwide. This macrolide-resistance is closely related to mutations on the 23S rRNA gene. Sitafloxacin and moxifloxacin have shown good efficacies for M. genitalium in some clinical studies. If the azithromycin regimens fail, we must consider the use of fluoroquinolones, such as sitafloxacin, in Japan. The most important issues include the acceptance of M. genitalium examinations by the national insurance system and the individual treatment of C. trachomatis and M. genitalium in the not-too-distant future.

Racial variation in toll-like receptor variants among women with pelvic inflammatory disease.

BACKGROUND: Racial disparities exist in gynecological diseases. Variations in Toll-like receptor (TLR) genes may alter signaling following microbial recognition. METHODS: We explored genotypic differences in 6 functional variants in 4 TLR genes (TLR1, TLR2, TLR4, TLR6) and the adaptor molecule TIRAP between 205 African American women and 51 white women with clinically suspected pelvic inflammatory disease (PID). A permutated P < .007 was used to assess significance. Associations between race and endometritis and/or upper genital tract infection (UGTI) were explored. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The TT genotype for TLR1 rs5743618, the GG genotype for TLR1 rs4833095, the CC genotype for TLR2 rs3804099, the TLR6 rs5743810 T allele, and the CC genotype for TIRAP rs8177374 significantly differed between races (P < .007). African American race was associated with endometritis and/or UGTI (OR, 4.2 [95% CI, 2.0-8.7]; P = .01). Among African Americans, the TLR6 rs5743810 T allele significantly decreased endometritis and/or UGTI (OR, 0.4 [95% CI, .2-.9]; P = .04). Additionally, rs5743618, rs4833095, and rs8177374 increased endometritis and/or UGTI, albeit not significantly. CONCLUSIONS: Among women with PID, TLR variants that increase inflammation are associated with African American race and may mediate the relationship between race and endometritis and/or UGTI.

Mycoplasma genitalium symptoms, concordance and treatment in high-risk sexual dyads.

The objective of this study was to determine the prevalence and concordance of Mycoplasma genitalium (MG) among Mexican American and African American women and their male sexual partners. Secondary objectives were to determine symptoms of MG infection and persistence of MG after antibiotic therapy. Heterosexual couples were tested for MG and interviewed separately regarding symptoms and behavioural/epidemiologic variables at baseline, six and 12 months. The overall prevalence of MG among women and men was 9.5% and 10.6%, respectively. Subjects were five times more likely to be infected with MG if their sexual partner was MG positive. Among men and women, MG prevalence and mean bacterial loads were similar after receiving single-dose azithromycin, doxycycline or no antibiotics. MG was associated with current urethral discharge in men. No clinical symptoms were specifically diagnostic of MG infection in women.

Association of Mycoplasma genitalium with acute non-gonococcal urethritis.

Chlamydia trachomatis is known to be a cause of acute non-gonococcal urethritis (NGU), though the aetiology of this disorder is not fully understood. Mycoplasma genitalium has been isolated from a few men with NGU, but culture has remained difficult and reliable detection became possible only with a specific polymerase chain reaction (PCR). We have used the PCR to examine the role of M genitalium in NGU. M genitalium was detected in urethral samples from 24 (23%) of 103 men with symptoms, signs, or both, of acute NGU, but from only 3 (6%) of 53 men without NGU (p < 0.006). This association was independent of the presence of C trachomatis and could not be explained by differences in age, ethnic, origin, lifetime number of sexual partners or a change in sexual partner during the previous 3 months. The clinical response of the mycoplasma-positive men to doxycycline treatment was at least as satisfactory as that of the chlamydia-positive men. These findings suggest that the association of M genitalium with NGU is likely to be causal, a notion consistent with the known virulence characteristics of this microorganism and its ability to cause urethritis in male sub-human primates.

Sociocultural factors in puerperal infectious morbidity among Navajo women.

From 1980 to 1982, a sample of 968 pregnant Navajo women in New Mexico was enrolled in a prospective study of biologic and sociocultural factors in puerperal infectious morbidity. Past studies have independently implicated both genital infection and psychosocial stressors in perinatal complications, but, to the authors' knowledge, no previous work has concurrently investigated the interactive effects of genital pathogens and psychosocial processes. Endocervical cultures for Mycoplasma hominis and Chlamydia trachomatis were obtained during prenatal visits, and structured interviews were conducted assessing social support and the degree of cultural traditionality, in this context a proxy measure of acculturative stress. The incidences of postpartum fever, endometritis, and premature rupture of membranes were significantly associated with the concurrence of two factors: the presence of genital tract M. hominis and a highly traditional cultural orientation. When demographic and conventional obstetric risk factors were controlled for, women with both M. hominis and high traditionality experienced infectious complications at a rate twice that of women with either factor alone. Among the plausible explanations for this result is the possibility that acculturative stress undermines physiologic resistance to infectious genital tract disease.

Predominant sexually transmitted diseases among different age and ethnic groups of indigent sexually active adolescents attending a family planning clinic.

The present study analyzed a group of 113 sexually active, indigent female adolescents attending a family planning clinic, for age, ethnic, or racial trends in the recovery of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma species, and Ureaplasma urealyticum. The overall recovery rate for N. gonorrhoeae was 8/112 (7.1%), with the highest rate occurring in black patients (7/82, 8.5%). The overall recovery rate for C. trachomatis was 31/113 (27.4%), with the highest rate occurring in Hispanics (7/21, 33.3%). The isolation of C. trachomatis was evenly divided among patients grouped by reason for visit. Neisseria gonorrhoeae, on the other hand, was isolated more frequently from patients coming for a sexually transmitted disease screen than from those attending for other reasons. There was a significant (p less than 0.05) increase in isolation of Mycoplasma species from 18-19-year-old patients, but no such difference was observed for U. urealyticum when compared to younger age groups. Factors associated with venereal disease prevalence in our teenage indigent population as well as implications for the future reproductive health of such patients are discussed.

PIP: The present study analyzed a group of 113 sexually active US indigent female adolescents attending a family planning clinic in a large urban area for age, ethnic, or racial trands in the recovery of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma species, and Ureaplasma urealyticum. The overall recovery rate for N. gonorrhoeae was 8/112 (7.1%), with the highest rate occurring in black patients (7/82, 8.5%). The overall recovery rate for C. trachomatis was 31/113 (27.4%), with the highest rate occurring in Hispanics (7/21, 33.3%). The isolation of C. trachomatis was evenly divided among patients grouped by reason for visit. Neisseria gonorrhoeae, on the other hand, was isolated more frequently from patients coming for a sexually transmitted disease screen than from those attending for other reasons. There was a significant (p 0.05 increase in isolation of Mycoplasma species from 18-19-year-old patients, but no such difference was observed for U. urealyticum when compared to younger age groups. C. Trachomatis may be a relatively common cause of pelvic inflammatory disease (PID) and PID attributed to Chlaymdia may have mild intial manifestations. Hence, many sexually active young females may unknowingly be infected and at risk for developing PID and its potential sequelae. Thus the high incicence of C. trachomatis when compared to gonorrhea suggests that rountine screening for C. trachomatis is as important as gonorrhoeae screening in adolescents. Culture for specimens of Mycoplasma species in patients with PID is a prudent measure if a laparoscopy specimen is available but it is impractical to screen all patients routinely for these organisms. Further research should focus on variables associated with racial/ethnic differences in relation to different aspects of sexual behavior and attitudes.