Diagnostic Tests for Detecting Chlamydia trachomatis and Neisseria gonorrhoeae in Rectal and Pharyngeal Specimens.

Chlamydia trachomatis and Neisseria gonorrhoeae are two of the most often reported bacterial infections in the United States. The rectum and oropharynx are important anatomic sites of infection and can contribute to ongoing transmission. Nucleic acid amplification tests (NAATs) are the mainstays for the detection of C. trachomatis and N. gonorrhoeae infections owing to their high sensitivity and specificity. Several NAATs have been evaluated for testing in rectal and pharyngeal infections. A few assays recently received clearance by the Food and Drug Administration, including one point-of-care test. Those assays can be used for testing in symptomatic individuals, as well as for asymptomatic screening in certain patient populations. Routine screening for C. trachomatis in pharyngeal specimens is not recommended by the Centers for Disease Control and Prevention, though it is often performed due to the use of multiplex assays. While expanding the types of settings for screening and using self-collected rectal and pharyngeal specimens can help to increase access and uptake of testing, additional research is needed to determine the potential benefits and costs associated with increased screening for rectal and pharyngeal C. trachomatis and N. gonorrhoeae infections on a population level.

Multicenter Comparison of Nucleic Acid Amplification Tests for the Diagnosis of Rectal and Oropharyngeal Chlamydia trachomatis and Neisseria gonorrhoeae Infections.

Research using nucleic acid amplification tests (NAATs) have repeatedly found rectal and oropharyngeal infections with Chlamydia trachomatis and Neisseria gonorrhoeae to be common and potentially more difficult to treat than genital infections. Unfortunately, public health and patient care efforts have been hampered by the lack of FDA-cleared NAATs with claims for anorectal or oropharyngeal samples. At the time of the initiation of this study, no commercially available assays had these claims. We formed a novel partnership among academic institutions and diagnostic manufacturers to address this public health need. From May 2018 through August 2019, we recruited 1108 women, 1256 men, and 26 transgender persons each of whom provided 3 anal and 3 oropharyngeal swab specimens. The 3 anal swabs were pooled into a single transport tube as were the 3 oropharyngeal swabs. The performance of each of three study assays was estimated by comparison to the composite result and relative to one another. Percent positivity for chlamydia was 5.9 and 1.2% from anal and oropharyngeal specimens, respectively, compared to 4.2 and 4.1% for gonorrhea. Sensitivity for chlamydia detection ranged from 81.0 to 95.1% and 82.8 to 100% for anal and oropharyngeal specimens, respectively. Gonorrhea sensitivity ranged from 85.9 to 99.0% and 74.0 to 100% for anal and oropharyngeal samples, respectively. Specificity estimates were ≥ 98.9% for all assays, organisms, and sample types. Although there was heterogeneity between sensitivity estimates, these assays offer better ability to detect extragenital infections than culture and potential solutions for providing appropriate sexual health care for populations in which these infections are of concern.

Doxycycline Versus Azithromycin for the Treatment of Rectal Chlamydia in Men Who Have Sex With Men: A Randomized Controlled Trial.

BACKGROUND: Azithromycin and doxycycline are both recommended treatments for rectal Chlamydia trachomatis (CT) infection, but observational studies suggest that doxycycline may be more effective. METHODS: This randomized, double-blind, placebo-controlled trial compared azithromycin (single 1-g dose) versus doxycycline (100 mg twice daily for 7 days) for the treatment of rectal CT in men who have sex with men (MSM) in Seattle and Boston. Participants were enrolled after a diagnosis of rectal CT in clinical care and underwent repeated collection of rectal swabs for nucleic acid amplification testing (NAAT) at study enrollment and 2 weeks and 4 weeks postenrollment. The primary outcome was microbiologic cure (CT-negative NAAT) at 4 weeks. The complete case (CC) population included participants with a CT-positive NAAT at enrollment and a follow-up NAAT result; the intention-to-treat (ITT) population included all randomized participants. RESULTS: Among 177 participants enrolled, 135 (76%) met CC population criteria for the 4-week follow-up visit. Thirty-three participants (19%) were excluded because the CT NAAT repeated at enrollment was negative. Microbiologic cure was higher with doxycycline than azithromycin in both the CC population (100% [70 of 70] vs 74% [48 of 65]; absolute difference, 26%; 95% confidence interval [CI], 16-36%; P < .001) and the ITT population (91% [80 of 88] vs 71% [63 of 89]; absolute difference, 20%; 95% CI, 9-31%; P < .001). CONCLUSIONS: A 1-week course of doxycycline was significantly more effective than a single dose of azithromycin for the treatment of rectal CT in MSM. CLINICAL TRIALS REGISTRATION: NCT03608774.

Zika Virus Mucosal Infection Provides Protective Immunity.

Zika virus (ZIKV) is a major human pathogen. ZIKV can replicate in female and male reproductive organs, thus facilitating the human-human transmission cycle. Viral shedding in the semen can increase the risk of ZIKV transmission through sexual mode. Therefore, the vaginal and anorectal mucosa are relevant sites for ZIKV infection. However, the pathobiology of ZIKV transmission through the rectal route is not well understood. Here, we utilize a mouse model system to investigate the immunopathological consequences following ZIKV infection of the rectal mucosa compared to a subcutaneous route of infection. We show that ZIKV-rectal inoculation results in viremia with subclinical infection. ZIKV infects the mucosal epithelium and submucosal dendritic cells, inducing immune and inflammatory cell infiltration. Rectal transmission of ZIKV resulted in the generation of serum-neutralizing antibody responses. Mass cytometry analyses of splenocytes showed a significantly reduced level of inflammatory monocyte and neutrophil cellular responses in the rectal route group. Furthermore, immunological priming through the rectal mucosa with an attenuated ZIKV strain resulted in significant protection from lethal subcutaneous ZIKV challenge, further eliciting robust memory CD4-positive (CD4+) and CD8+ T-cell and ZIKV-specific serum-neutralizing antibody responses. Thus, our study provides deeper immunopathobiological insights on rectal transmission and highlights a rational strategy for mucosal immunization. This model system recapitulates clinical aspects of human ZIKV disease outcome, where most infections are well controlled and result in subclinical and asymptomatic outcomes.IMPORTANCE Zika virus is a clinically significant human pathogen that is primarily transmitted and spread by Aedes species mosquitoes but is also sexually transmissible. The recent pandemic in the Americas led to an unprecedented increase of newborn babies with developmental brain and eye abnormalities. To date, there is no licensed vaccine or therapeutic intervention available for the fight against ZIKV. Understanding the sexual transmission of ZIKV through vaginal and rectal routes is necessary to restrict virus transmission and spread. This study examines the early immunological and pathological consequences of rectal and subcutaneous routes of ZIKV infection using a mouse model. We characterized the primary target cells of ZIKV infection and the subsequent mucosal immune responses to infection, and we demonstrate the protective effect of mucosal rectal immunization using an attenuated ZIKV strain. This mucosal vaccination approach can be further developed to prevent future ZIKV outbreaks.

HIV status and viral loads among men testing positive for rectal gonorrhoea and chlamydia, Maricopa County, Arizona, USA, 2011-2013.

OBJECTIVES: Men diagnosed with rectal gonorrhoea (GC) and chlamydia (CT) have engaged in unprotected receptive anal intercourse. We reviewed the HIV positivity and HIV viral loads (VLs) of men who had rectal GC and CT testing to evaluate potential HIV acquisition and transmission risk. METHODS: Rectal GC and CT testing data for men attending the Maricopa County STD clinic during the period from 1 October 2011 to 30 September 2013 were cross-matched with HIV surveillance data to identify men with HIV coinfection. We examined HIV status, HIV diagnosis date, and the values of VL collected nearest to the date of reported rectal infection. RESULTS: During the 2-year time period, 1591 men were tested for rectal GC and CT. Of the men tested, 506 (31.8%) were positive for GC (13.2%), CT (12.2%) or both (6.4%); 119 (23.5%) of those with rectal GC or CT were coinfected with HIV. Among the 275 men with HIV at the time of rectal testing, 54 (19.6%) had no reported VL; 63 (22.9%) had an undetectable VL (< 20 HIV-1 RNA copies/mL) and 158 (57.4%) had a detectable VL collected within 1 year of rectal diagnosis. Mean VL was higher among HIV and rectal GC/CT coinfected cases compared with men with HIV alone (174 316 vs. 57 717 copies/mL, respectively; P = 0.04). CONCLUSIONS: Approximately one-third of men undergoing rectal testing were positive for GC or CT and one-quarter of men with rectal GC or CT also had HIV infection. Of the HIV-infected men tested for rectal GC or CT, more than half had a detectable VL collected near the time of rectal testing, demonstrating a risk for transmitting HIV.

High Prevalence of Rectal Chlamydia trachomatis Infection With the Same Genotype as Urogenital Infection in Female Outpatients in Sexually Transmitted Disease Clinics in China.

BACKGROUND: Little is known about rectal Chlamydia trachomatis (CT) infection in outpatients attending sexually transmitted disease (STD) clinics in China. In this study, we aimed to explore the clinical and epidemiologic features of rectal CT infection in this population. METHODS: A cross-sectional study was conducted among patients attending STD clinics in Tianjin and Guangxi provinces of China from June 2018 to August 2020. Bivariate and multivariate logistic regression analysis were developed to explore the association of different risk factors for urogenital and rectal CT infection. RESULTS: The prevalence of urogenital and rectal CT was 11.2% (154/1374) and 4.9% (68/1377), respectively. The rectal CT prevalence among female and male patients was 7.8% (60/767) and 1.3% (8/610), respectively. The most common genotype in urogenital CT-positive samples was genotype E (29.9%), while the most common genotype among rectal CT-positive samples was genotype J (23.4%). More than 85% (52/60) of women infected with rectal CT were co-infected with urogenital CT. About 90.0% (36/40) of women shared similar genotypes between rectal and urogenital samples. Females and patients infected with urogenital CT were deemed to be at an increased risk for rectal CT infection. A high proportion of rectal CT infection had concurrent urogenital CT infection, especially in women, and most of the co-infections were shared among the same genotypes. CONCLUSIONS: It would be prudent to encourage awareness and introduce detection tests and treatment strategies for rectal CT infection particularly in female patients visiting STD clinics in China.

Azithromycin in the treatment of rectogenital Chlamydia trachomatis infections: end of an era?

INTRODUCTION: Azithromycin was recommended as the first-line therapeutic regimen for treatment of genital infections in men and women by the Centers for Disease Control in 1998. A series of studies of azithromycin for treatment of rectal chlamydial infection in men who have sex with men (MSM) found that azithromycin was significantly less effective than doxycycline. AREAS COVERED: Literature on treatment of rectal C. trachomatis from 2000 through May 2020 was searched using PubMed. Retrospective and observational studies were identified documenting the frequency and treatment of rectal chlamydial infection in MSM, heterosexual men and women that reported lower efficacy of single-dose azithromycin compared to doxycycline. Literature on possible reasons for the lower efficacy were also reviewed including studies of antibiotic resistance, impact of organism load, and persistent infection in rectal specimens and pharmacokinetics and pharmacodynamics of azithromycin in rectal tissue. EXPERT OPINION: The available data suggests that single-dose azithromycin is not as effective as azithromycin for the treatment of rectal infection in MSM and women. Most of these data have been retrospective or from observational studies. Final recommendations will depend on the outcome of prospective, randomized, treatment studies. We may also need to examine other dosage regimens for azithromycin.

Rectal Mycoplasma genitalium in Patients Attending Sexually Transmitted Disease Clinics in China: An Infection That Cannot Be Ignored.

BACKGROUND: Previous studies have investigated rectal Mycoplasma genitalium (MG) in men who have sex with men (MSM), while little is known about the prevalence of rectal MG infection in individuals attending sexually transmitted disease (STD) clinics in China. We aimed to estimate the prevalence of rectal MG infection in this population and identified the potential risk factors for rectal MG infection. METHODS: A cross-sectional study was conducted among individuals attending STD clinics located in China from June 2018 to August 2020. Univariate and multivariate logistic regression analyses were conducted to explore the association of different risk factors for rectal MG infection. RESULTS: A total of 1,382 patients were included in the final analyses. A total of 30 of 1377 rectal swabs (2.2%) and 77 of 1374 urogenital samples (5.6%) were positive for MG. In Guangxi, 18 of 47 patients (38.3%) infected with urogenital MG and 5 of 19 patients (26.3%) infected with rectal MG received the recommended treatment. Factors found to be significantly associated with rectal MG infection included: male (adjusted odds ratio (AOR) 0.232, [95% CI: 0.072-0.745]) compared to female, homosexual or bisexual (AOR 40.427, [95% CI: 3.880-421.196]) compared to heterosexual, and those infected with urogenital MG (AOR 7.215, [95% CI: 2.898-17.965]) compared to those who did not get infected with urogenital MG. CONCLUSION: Rectal MG infection should be thought of not only in MSM population but also in STD clinic patients, especially females who have urogenital MG infection. Appropriate strategy for rectal MG screening and treatment needs to be developed for these patients in China.

Nonclassical Pathogens as Causative Agents of Proctitis in Men who Have Sex With Men.

BACKGROUND: This study aimed to identify enteric and sexually acquired rectal pathogens, other than chlamydia and gonorrhea, associated with symptomatic proctitis in men who have sex with men (MSM). METHODS: Anorectal swab samples were obtained from MSM presenting with rectal symptoms and a clinical diagnosis of proctitis at the Melbourne Sexual Health Centre between January 2017 and March 2019. Samples that tested positive for Neisseria gonorrhoeae and Chlamydia trachomatis were excluded. As a comparison group, anorectal samples were also obtained from MSM not reporting symptoms of proctitis between November 2018 and February 2019. Samples from both groups were tested for 15 viral, bacterial, and protozoal enteric pathogens using polymerase chain reaction. RESULTS: Anorectal samples from 499 men with symptomatic proctitis and 506 asymptomatic men were analyzed. Age, HIV status, and pre-exposure prophylaxis (PrEP) use did not differ between men with proctitis and asymptomatic men. Treponema pallidum was more common in men with proctitis (risk difference [RD], 3.6%; 95% CI, 2.0%-5.2%). Most men with anorectal T. pallidum presented with painful anal primary infections. Shigella spp. was more common among men with proctitis compared with asymptomatic men (RD, 1.8%; 95% CI, 0.1%-3.5%). Most men with Shigella did not report diarrhea. Mycoplasma genitalium was more common in men with proctitis (RD, 4.3%; 95% CI, 1.1%-7.5%). Herpes simplex virus (HSV)-1 (RD, 10.1%; 95% CI, 6.8%-13.3%) and HSV-2 (RD, 7.2%; 95% CI, 4.5%-10.0%) were more common with proctitis. CONCLUSIONS: Testing for T. pallidum, Shigella, and HSV should be considered in MSM presenting with symptomatic proctitis. These data provide support for M. genitalium as a significant cause of proctitis. A comprehensive diagnostic evaluation is required for MSM with proctitis.

Etiologic and clinical analysis of chronic complex anal and rectal inflammation in children less than 3 years old.

OBJECTIVE: To analyze the etiology and clinical diagnostic method for chronic complex anal and rectal inflammation in children less than 3 years old. METHOD: Seven children (5 males and 2 females; 1 year 8 months to 3 years of age at the time of physician evaluation) with chronic complex anal and rectal inflammation were enrolled between May 2008 and May 2013 at our hospital. Clinical history, results of auxiliary examinations, and empirical treatment of the children were analyzed retrospectively combined with the etiologic diagnosis. RESULTS: Four patients were confirmed to have Crohn's disease and one patient was confirmed to have intestinal tuberculosis; two patients were suspected to have Crohn's disease. Anemia and low pre-albumin level were common (seven patients); serologic testing revealed four patients with elevated IgG levels and seven patients with elevated IgA levels; there were no patients with positive tuberculosis antibody titers and two patients were weakly positive for C-ANCA (one patient with Crohn's disease and one patient intestinal tuberculosis). Colonoscopies revealed that the entire colon was affected in one patient, the left hemicolon was affected in four patients, and the sigmoid colon and rectum were affected in two patients. Two patients with Crohn's disease and one patient with intestinal tuberculosis were diagnosed by colonoscopies in combination with histopathologic examinations. Two patients with Crohn's disease were confirmed after empirical drug treatment, and two other patients were not definitely diagnosed. CONCLUSION: The possibility of Crohn's disease or intestinal tuberculosis should be considered in the clinical diagnosis of complex chronic anal and rectal inflammation in younger children. Local surgery is sometimes unnecessary. Empirical drug treatment should be used if necessary.