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.

Gonorrhoea and chlamydia in persons with HIV: number needed to screen.

OBJECTIVES: Current guidelines recommend screening sexually active persons with HIV (PWH) for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) at least annually. Yet, screening rates in many HIV clinics remain low. In this study, we estimated the number needed to screen (NNS) to detect a NG and/or CT infection at each anatomic site among different subpopulations of PWH. NNS provides a concrete, practical measure to aid in assessing the practical impact of screening. METHODS : We included adults in care at three HIV Research Network sites in 2011-2014. Restricting to first tests within each year, annual NNS was defined as number of persons tested divided by number positive. We computed urogenital and extragenital NNS by age and risk group (women, men who have sex with women (MSW) and men who have sex with men (MSM)). RESULTS : A total of 16 864 NG/CT tests were included. Among patients aged ≤25 years, urogenital NNS was similar among women (15 (95% CI 6 to 71)), MSW (21 (95% CI 6 to 167)) and MSM (20 (95% CI 12 to 36)). Over 25, urogenital NNS increased to a greater extent for women (363 (95% CI 167 to 1000)) and MSW (160 (95% CI 100 to 333)) than MSM (46 (95% CI 38 to 56)). The increase for women versus MSM >25 remained significant (p<0.01) in multivariable analysis. Among MSM, rectal NNS was 5 (95% CI 3 to 7) and 10 (95% CI 9 to 12) for ≤25 and for >25 years and pharyngeal NNS values were 8 (95% CI 5 to 13) and 20 (95% CI 16 to 24). CONCLUSIONS: These findings suggest the importance of regular, at least annual NG/CT screening, particularly extragenital, of HIV positive MSM of all ages. They provide some support for age-based cutoffs for women and MSW (eg, universal screening for those aged ≤25 and targeted screening for those aged >25 years).

Gonorrhea and Chlamydia Case Detection Increased When Testing Increased in a Multisite US HIV Cohort, 2004-2014.

OBJECTIVES: Annual screening for gonorrhea [Neisseria gonorrhoeae (NG)] and chlamydia [Chlamydia trachomatis (CT)] is recommended for all sexually active persons living with HIV but is poorly implemented. Studies demonstrating no increases in NG and/or CT (NG/CT) case detection in clinics that successfully expanded NG/CT screening raise questions about this broad screening approach. We evaluated NG/CT case detection in the HIV Research Network during 2004-2014, a period of expanding testing. METHODS: We analyzed linear time trends in annual testing (patients tested divided by all patients in care), test positivity (patients positive divided by all tested), and case detection (the number of patients with a positive result divided by all patients in care) using multivariate repeated measures logistic regression. We determined trends overall and stratified by men who have sex with men (MSM), men who have sex exclusively with women, and women. RESULTS: Among 15,614 patients (50% MSM, 26% men who have sex exclusively with women, and 24% women), annual NG/CT testing increased from 22% in 2004 to 60% in 2014 [adjusted odds ratio (AOR) per year 1.22 (1.21-1.22)]. Despite the increase in testing, test positivity also increased [AOR per year 1.10 (1.07-1.12)], and overall case detection increased from 0.8% in 2004 to 3.9% in 2014 [AOR per year 1.20 (1.17-1.22)]. Case detection was highest among MSM but increased over time among all 3 groups. CONCLUSIONS: NG/CT case detection increased as testing expanded in the population. This supports a broad approach to NG/CT screening among persons living with HIV to decrease transmission and complications of NG/CT and of HIV.

Neisseria gonorrhoeae and Chlamydia trachomatis among women reporting extragenital exposures.

BACKGROUND: The Centers for Disease Control and Prevention recommends pharyngeal screening of Neisseria gonorrhoeae (GC) and rectal screening of GC and Chlamydia trachomatis (CT) in HIV-infected and at-risk men who have sex with men (MSM). There are currently no recommendations to routinely screen women at extragenital sites. We define the prevalence of extragenital GC and CT in women attending 2 urban sexually transmitted disease clinics in Baltimore City and compare it with the prevalence of extragenital infections in MSM and men who have sex with women. METHODS: All patients who reported extragenital exposures in the preceding 3 months, who presented for care between June 1, 2011, and May 31, 2013, and who were tested for GC and CT using nucleic acid amplification tests at all sites of exposure were included in the analyses. We used logistic regression models to identify risk factors for extragenital infections. RESULTS: A total of 10,389 patients were included in this analysis (88% African American; mean age, 29 years; 42% women; 7% MSM; 2.5% HIV infected). The prevalence estimates of any extragenital GC and CT were as follows: 2.4% GC and 3.7% CT in women, 2.6% GC and 1.6% CT in men who have sex with women, and 18.9% GC and 11.8% CT in MSM. Among women, 30.3% of GC infections and 13.8% of CT infections would have been missed with urogenital-only testing. Unlike MSM, age ≤ 18 years was the strongest predictor of extragenital infections in women. CONCLUSIONS: Although the prevalence of extragenital gonorrhea and chlamydia is highest in MSM, a significant number of GC and CT infections in young women would be missed with genital-only testing. Cost-effectiveness analyses are needed to help inform national guidelines on extragenital screening in young women.

Modeling the impact of quadrivalent HPV vaccination on the incidence of Pap test abnormalities in the United States.

BACKGROUND: We present data on Pap test results and HPV prevalence from the HPV Sentinel Surveillance project, a multiyear surveillance project enrolling women from a diverse set of 26 clinics throughout the US from 2003 to 2005. We use mathematical modeling to illustrate the potential timing and magnitude of decreases in Pap test abnormalities in sexually transmitted disease (STD), family planning, and primary care clinics in the US as a result of HPV vaccination. METHODS: The probability of an abnormal Pap result was based on three factors: (1) infection with HPV 16/18, or both; (2) infection with high-risk HPV types other than HPV 16/18; and (3) infection with HPV 6/11, or both. We estimated the relative reduction in the probability of an abnormal Pap result over the first 25 years of a female-only, quadrivalent HPV vaccination program, compared to a scenario of no HPV vaccination in which the probability of abnormal Pap results was assumed constant. RESULTS: The probability of an abnormal Pap result ranged from 7.0% for the lowest risk group (those without any high-risk HPV types and without HPV 6/11) to 45.2% for the highest risk group (those with HPV 16/18 and at least one other high-risk HPV type). Estimated reductions in abnormal Pap results among women in the 21- to 29-year age group were 0.8%, 10.2%, and 11.3% in years 5, 15, and 25 of the vaccine program respectively, in the lower vaccine coverage scenario, and 7.4%, 21.4%, and 22.2%, respectively, in the higher coverage scenario. CONCLUSIONS: Our results suggest that HPV vaccination will have a discernable impact on the probability of Pap abnormalities, but the timing and magnitude of the reduction will depend substantially on vaccine coverage and the degree of cross-protection against high risk HPV types other than HPV 16/18.

Increased gonorrhoea and chlamydia testing did not increase case detection in an HIV clinical cohort 1999-2007.

OBJECTIVES: Since 2003, US organisations have recommended universal screening, rather than targeted screening, of HIV-infected persons for gonorrhoea and chlamydia. The objective of this study was to determine whether wider testing resulting from these guidelines would produce an increase in gonorrhoea/chlamydia diagnoses. METHODS: 3283 patients receiving HIV care in 1999-2007 in the Johns Hopkins Hospital HIV clinic were studied. The two primary outcomes were the occurrence of any gonorrhoea/chlamydia testing in each year of care and the occurrence of any positive result(s) in years of testing. The proportion of all patients in care who were diagnosed with gonorrhoea/chlamydia was defined as the number of patients with positive results divided by the number of patients in care. Trends were analysed with repeated measures logistic regression. RESULTS: The proportion of patients tested for gonorrhoea/chlamydia increased steadily from 0.12 in 1999 to 0.33 in 2007 (OR per year for being tested 1.17, 95% CI 1.15 to 1.19). The proportion positive among those tested decreased significantly after 2003 (OR per year 0.67, 95% CI 0.55 to 0.81). The proportion of all patients in care diagnosed with gonorrhoea/chlamydia therefore remained generally stable in 1999-2007 (OR per year 0.97, 95% CI 0.91 to 1.04). CONCLUSIONS: Universal annual screening, as implemented, did not increase the proportion of all patients in care who were diagnosed with gonorrhoea/chlamydia. Similarly low implementation rates have been reported in cross-sectional studies. If future efforts to enhance implementation do not yield increases in diagnoses, then guidelines focusing on targeted screening of high-risk groups rather than universal screening may be warranted.

The association of current hormonal contraceptive use with type-specific HPV detection.

BACKGROUND: Increased duration of hormonal contraceptive (HC) use may be positively associated with the risk of invasive cervical cancer. METHODS: This is a secondary analysis from the HPV Sentinel Surveillance Study. The authors examined the association between type-specific human papillomavirus (HPV) detection and current HC use among 7718 women attending 26 sexually transmitted disease, family planning and primary care clinics in the USA. RESULTS: There was an association between HC use and HPV-16 detection (adjusted prevalence rate ratio 1.34 (95% CI 1.05 to 1.71) for oral contraceptive users and 1.41 (1.01 to 2.04) for depot-medroxyprogesterone acetate users); there was no association between HC use and detection of other HPV types or any HPV overall. CONCLUSIONS: Longitudinal studies are needed to better define this type-specific association and its clinical significance.

Condom use and vaginal Y-chromosome detection: the specificity of a potential biomarker.

OBJECTIVE: Detection of vaginal Y-chromosome sequences (YCS) may be a useful biomarker to validate sexual behavior reporting in women. We describe the effects of condom use on the detection of vaginal YCS. METHODS: Fifty-six women were asked to abstain from sexual intercourse for 14 days. On day 15, participants were asked to engage in sexual intercourse with their male partners using condoms. Self-collected vaginal swabs were obtained on days 14, 16, and 17. YCS were detected using the Roche LightCycler with the use of positive controls. RESULTS: Fourty-four of 56 women completed the study. Five women (11.4%) had detectable YCS. The overall specificity of the YCS assay with condom use was 92% (95% CI: 80%-98%). Although women who reported receptive oral sex and digital penetration within 48 hours of swab collection had a higher detection rate of YCS [RR 2.3 (95% CI: 1.1-4.6) and 3.6 (95%CI: 1.6-8.5), respectively], the mean concentration of YCS was much less than that associated with unprotected vaginal intercourse (P <0.001) CONCLUSIONS: Condom use during intercourse appears to prevent vaginal YCS detection; this may be a useful biomarker to validate self-reported condom use.

The role of speculum and bimanual examinations when evaluating attendees at a sexually transmitted diseases clinic.

BACKGROUND: With the advent of molecular techniques, self-collected specimens without a clinician's examination are often adequate to detect common genital infections. OBJECTIVE: To evaluate the additional information that speculum and bimanual examinations provides clinicians in the routine evaluation of genital infections among attendees of a sexually transmitted disease (STD) clinic. METHODS: Cross-sectional study from a database of all visit records to two STD clinics in Baltimore between 1996 and 2002. Women were stratified on the basis of reason for visit. Proportional and likelihood ratio estimates of the speculum examination in detecting clinically relevant cervicovaginal lesions (leading to a diagnosis of other infections or outside referral for further management) and bimanual examination in detecting abnormalities (leading to a diagnosis of pelvic inflammatory disease or referral) are presented. RESULTS: 15 918 of 21 703 records were included: 12 073 were symptomatic (SYM; discharge, rash, abdominal pain, dysuria, genital irritation or odour), 1676 were asymptomatic contacts of an infected partner (CON) and 2169 were asymptomatic and presented for checkup (ASYM). The median age was 26 years; 94% were black. 11.8% of SYM, 4.6% of CON and 3.9% of ASYM patients had clinically meaningful lesions detected on speculum examination. The bimanual examination detected clinically relevant abnormalities in 6.5% of SYM, 0.8% of CON and 0.6% of ASYM patients. CONCLUSION: Symptomatic women are most likely to benefit from speculum and bimanual examinations. However, their yield in evaluating asymptomatic women is low. Prospective studies are needed to determine whether eliminating speculum and bimanual examinations in a subset of women would offer an operational advantage without compromising patient safety.

The effects of illicit drug use and HIV infection on sex hormone levels in women.

Drug use and HIV infection may affect sex hormone levels in women. One hundred and ninety-six women with and without a history of illicit drug use (50 HIV-negative and 148 HIV-infected), with regular menses, who never used antiretrovirals, were evaluated. Luteinizing hormone levels were significantly higher in women with a CD4 cell count <200/microl (p < 0.002). Current methadone use was associated with lower levels of total testosterone (p = 0.03) and higher levels of prolactin (p = 0.002); mean estradiol levels were 43% lower in women who used intravenous drugs (p < 0.001). Alcohol and crack cocaine use was not associated with sex hormone levels. Age, race, body mass index and degree of HIV immunosuppression were also associated with differences in sex hormone levels.

Sexually transmitted infections and prostatic inflammation/cell damage as measured by serum prostate specific antigen concentration.

PURPOSE: Although inflammation and cell damage due to STIs are hypothesized to contribute to the later development of prostate disease, few clinical studies have been done to investigate the extent to which sexually transmitted agents infect and induce an inflammatory immune response in the prostate. We indirectly investigated this question by measuring serum PSA, a possible marker of prostatic inflammation and cell damage, in men with documented STIs. MATERIALS AND METHODS: Archived serum specimens from young men with laboratory confirmed exudative STIs, including gonorrhea, chlamydia and trichomonosis, and young men with no STI diagnoses were identified in 2 prospective studies of patients at Baltimore City STI clinics, that is 84 in the STI Transmission and Acquisition Study, and 61 in the Mucosal Immunity Study. Serum specimens from visits before, during and after STI diagnoses in men with at least 1 exudative STI diagnosis and from all visits in men with no STI diagnoses were tested for total PSA concentration. RESULTS: After combining the studies patients with STIs were more likely to have a 40% or greater increase in PSA than patients with no STI diagnoses (32% vs 2%, p <0.01). CONCLUSIONS: These findings suggest that STIs may contribute to prostatic inflammation and cell damage in a subset of infected men. Further studies are warranted to replicate study findings and determine host and infection characteristics associated with large PSA increases.

Effect of specimen order on Chlamydia trachomatis and Neisseria gonorrhoeae test performance and adequacy of Papanicolaou smear.

STUDY OBJECTIVE: To evaluate the effect of specimen collection order on the performance of diagnostic tests for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC), and the specimen adequacy of ThinPrep Papanicolaou (Pap) smears. DESIGN: Prospective cohort study. SETTING: Public adolescent clinic. POPULATION: 313 women. INTERVENTIONS: The order of five cervical testing specimens was randomized for (1) ligase chain reaction (LCR) and (2) polymerase chain reaction (PCR) for both CT and GC; (3) transcription-mediated amplification (TMA) for CT; (4) culture for CT; and (5) cytology and LCR for GC and CT performed on ThinPrep Pap specimens. For CT and GC, a reference standard was based on three different tests performed on separate specimens. Generalized estimating equations were used to account for repeated measures. MAIN OUTCOME MEASURE: Sensitivity and specificity of diagnostic tests. RESULTS: The proportion of inadequate Pap smears was independent of specimen order. As a group, nucleic acid amplification test (NAAT) sensitivity and specificity for GC and CT were similar in the first two (early) and last three (late) swabs. Although point estimates for sensitivity were higher in the early swabs compared to the late swabs for GC LCR (13% difference), GC PCR (13%), and CT TMA (10%), these differences were not statistically significant. Their clinical significance warrants further investigation. CONCLUSIONS: In clinical settings where both Pap smears and STI testing are performed in adolescents, clinical considerations can influence the order of specimen collection, since neither Pap specimen adequacy nor test performance of NAAT for CT and GC were significantly associated with swab order.

Screening tests for hepatocellular carcinoma in patients with chronic hepatitis C: a systematic review.

This systematic review addresses the following questions: (1) What is the efficacy of using screening tests for hepatocellular carcinoma (HCC) in improving outcomes in chronic hepatitis C, and (2) what are the sensitivity and specificity of screening tests for HCC in chronic hepatitis C? The search strategy involved searching Medline and other electronic databases between January 1985 and March 2002. Additional articles were identified by reviewing pertinent articles and journals and by querying experts. Articles were eligible for review if they reported original human data from studies of screening tests that used virological, histological, pathologic, or clinical outcome measures. Data collection involved paired reviewers who assessed the quality of each study and abstracted data. One nonrandomized prospective cohort study suggested that HCC was detected earlier and was more often resectable in patients who had twice yearly screening with serum alpha-fetoprotein (AFP) and hepatic ultrasound than in patients who had usual care. Twenty-four studies, which included patients with chronic hepatitis C or B or both, addressed the sensitivities and specificities of screening tests. They were relatively consistent in showing that the sensitivity of serum AFP for detecting HCC usually was moderately high at 45% to 100%, with a specificity of 70% to 95%, for a threshold of between 10 and 19 ng/mL. The few studies that evaluated screening with ultrasound reported high specificity, but variable sensitivity. In conclusion, screening of patients with chronic hepatitis C with AFP and ultrasound may improve detection of HCC, but studies are needed to determine whether screening improves clinical outcomes.

Role of liver biopsy in management of chronic hepatitis C: a systematic review.

This systematic review addresses 2 questions pertinent to the need for pretreatment liver biopsy in patients with chronic hepatitis C: how well do liver biopsy results predict treatment outcomes for chronic hepatitis C? How well do biochemical blood tests and serologic measures of fibrosis predict the biopsy findings in chronic hepatitis C? Medline and other electronic databases were searched from January 1985 to March 2002. Additional articles were sought in references of pertinent articles and recent journals and by querying experts. Articles were eligible for review if they reported original human data from a study that used virological, histological, pathologic, or clinical outcome measures. Paired reviewers assessed the quality of each eligible study and abstracted data. Studies suggested that advanced fibrosis or cirrhosis on initial liver biopsy is associated with a modestly decreased likelihood of a sustained virological response (SVR) to treatment. Also, studies relatively consistently showed that serum aminotransferases have modest value in predicting fibrosis on biopsy; that extracellular matrix tests hyaluronic acid and laminin may have value in predicting fibrosis, and that panels of tests may have the greatest value in predicting fibrosis or cirrhosis. Biochemical and serologic tests were best at predicting no or minimal fibrosis, or at predicting advanced fibrosis/cirrhosis, and were poor at predicting intermediate levels of fibrosis. Thus, evidence suggests that liver biopsy may have some usefulness in predicting efficacy of treatment in patients with chronic hepatitis C, and biochemical blood tests and serologic tests currently have only modest value in predicting fibrosis on liver biopsy.

Disseminated acanthamebiasis in a renal transplant recipient with osteomyelitis and cutaneous lesions: case report and literature review.

Disseminated acanthamebiasis is a rare disease that occurs predominantly in patients with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome but also in immunosuppressed transplant recipients. Few reports have focused on non-HIV-infected patients, in whom the disease is more likely to go unsuspected and undiagnosed before death. We describe a renal transplant recipient with Acanthamoeba infection and review the literature. The patient presented with osteomyelitis and widespread cutaneous lesions. No causative organism was identified before death, despite multiple biopsies with detailed histological analysis and culture. Disseminated Acanthamoeba infection was diagnosed after death, when cysts were observed in histological examination of sections of skin from autopsy, and trophozoites were found in retrospectively reviewed skin biopsy and surgical bone specimens. In any immunosuppressed patient, skin and/or bone lesions that fail to show improvement with broad-spectrum antibiotic therapy should raise the suspicion for disseminated acanthamebiasis. Early recognition and treatment may improve clinical outcomes.