Richa Kapil

Investigating the Epidemiology of Repeat Chlamydia trachomatis Detection after Treatment by Using C. trachomatis OmpA Genotyping

ABSTRACT Repeat Chlamydia trachomatis detection frequently occurs within months after C. trachomatis infection treatment. The origins of such infection (persistence versus reinfection from untreated or new partners) are varied and difficult to determine. C. trachomatis strains can be differentiated by sequencing the ompA gene encoding the outer membrane protein A (OmpA). We used OmpA genotyping to investigate the epidemiology of repeat C. trachomatis detection after treatment in C. trachomatis-infected subjects seen at a sexually transmitted diseases clinic. Subjects were enrolled, tested for C. trachomatis, treated with azithromycin, and scheduled for a 6-month follow-up for repeat C. trachomatis testing. OmpA genotyping was performed on C. trachomatis-positive urogenital specimens obtained from patients at enrollment and follow-up. The enrollment visit OmpA genotypes for C. trachomatis were determined for 162 subjects (92% female, 94% African American). C. trachomatis was detected at follow-up in 39 subjects (24%). The OmpA genotype distribution at enrollment did not differ in those with versus those without repeat C. trachomatis detection. Of the 35 subjects with C. trachomatis strains genotyped at enrollment and follow-up, 7 (20%) had the same ompA sequence at both visits, while 28 (80%) had discordant sequences. A new sexual partner was reported more often in subjects with discordant C. trachomatis strains than in those with concordant strains (13 [46%] versus 1 [14%]; P = 0.195). Half of the subjects with discordant C. trachomatis strains who reported sexual activity since treatment denied a new sexual partner; 62% of these subjects reported that their partner was treated. Our study demonstrates that most repeat C. trachomatis detections after treatment were new infections with a different C. trachomatis strain rather than reinfection with the same strain. OmpA genotyping can be a useful tool in understanding the origins of repeat C. trachomatis detection after treatment.

The Predominant CD4+ Th1 Cytokine Elicited to Chlamydia trachomatis Infection in Women is Tumor Necrosis Factor-Alpha, not Interferon-Gamma.

ABSTRACT Chlamydia trachomatis infection is the most prevalent bacterial sexually transmitted infection and can cause significant reproductive morbidity in women. There is insufficient knowledge of C. trachomatis-specific immune responses in humans, which could be important in guiding vaccine development efforts. In contrast, murine models have clearly demonstrated the essential role of T helper type 1 (Th1) cells, especially interferon gamma (IFN-γ)-producing CD4+ T cells, in protective immunity to chlamydia. To determine the frequency and magnitude of Th1 cytokine responses elicited to C. trachomatis infection in humans, we stimulated peripheral blood mononuclear cells from 90 chlamydia-infected women with C. trachomatis elementary bodies, Pgp3, and major outer membrane protein and measured IFN-γ-, tumor necrosis factor alpha (TNF-α)-, and interleukin-2 (IL-2)-producing CD4+ and CD8+ T-cell responses using intracellular cytokine staining. The majority of chlamydia-infected women elicited CD4+ TNF-α responses, with frequency and magnitude varying significantly depending on the C. trachomatis antigen used. CD4+ IFN-γ and IL-2 responses occurred infrequently, as did production of any of the three cytokines by CD8+ T cells. About one-third of TNF-α-producing CD4+ T cells coproduced IFN-γ or IL-2. In summary, the predominant Th1 cytokine response elicited to C. trachomatis infection in women was a CD4+ TNF-α response, not CD4+ IFN-γ, and a subset of the CD4+ TNF-α-positive cells produced a second Th1 cytokine.

Chlamydia trachomatis infection in African American women who exclusively have sex with women.

Little is known about whether Chlamydia trachomatis can be sexually transmitted between women or how often it occurs in women who have sex with women (WSW). We investigated Chlamydia trachomatis prevalence and serum Chlamydia trachomatis-specific antibody responses among African American WSW who reported a lifetime history of sex only with women (exclusive WSW) (n = 21) vs. an age-matched group of women reporting sex with women and men (WSWM) (n = 42). Participants completed a survey, underwent a pelvic examination in which a cervical swab was collected for Chlamydia trachomatis nucleic acid amplification testing (NAAT), and had serum tested for anti-Chlamydia trachomatis IgG1 and IgG3 antibodies using a Chlamydia trachomatis elementary body-based ELISA. No exclusive WSW had a positive Chlamydia trachomatis NAAT vs. 5 (11.9%) WSWM having a positive Chlamydia trachomatis NAAT (p = 0.16). Compared with WSWM, WSW were significantly less likely to be Chlamydia trachomatis seropositive (7 [33.3%] vs. 29 [69%], p = 0.007). Among Chlamydia trachomatis seropositive women, all were seropositive by IgG1, and the magnitude of Chlamydia trachomatis-specific IgG1 responses did not differ in Chlamydia trachomatis-seropositive WSW vs. WSWM. In conclusion, Chlamydia trachomatis seropositivity was relatively common in exclusive African American WSW, though significantly less common than in African American WSWM.

Lower sexually transmissible infection prevalence among lifetime exclusive women who have sex with women compared with women who have sex with women and men

UNLABELLED Background Sexually transmissible infection (STI) history, prevalence and seroprevalence among lifetime exclusive women who have sex with women (WSW) and an age-matched group of women who have sex with women and men (WSWM) was evaluated. METHODS Participants completed a study questionnaire and had genital specimens and sera collected for STI testing. RESULTS Twenty-one lifetime exclusive WSW and 42 WSWM were included. WSWM were more likely to report a history of prior STIs and be seropositive for chlamydia and HSV-2. Prevalent STIs were less common among WSW. CONCLUSIONS While lifetime exclusive WSW are at risk of contracting STIs, WSWM are disproportionally affected. Healthcare providers should consider routine STI screening among WSW.

Chronic Rectal Bleeding due to Lymphogranuloma Venereum Proctocolitis

To the Editor: Lymphogranuloma venereum (LGV) is an invasive sexually transmitted infection caused by Chlamydia trachomatis strains of the LGV outer membrane protein A (OmpA) type (i.e., LGV serovar). The typical presentation of LGV in endemic regions (Africa, India, Southeast Asia, South America, and the Caribbean) is a genital ulcer and/or painful erythematous inguinal lymphadenopathy (“buboes”). In the early 1980s in the United States, LGV proctitis mimicking inflammatory bowel disease among men who have sex with men (MSM) participating in receptive anal intercourse was reported (1,2), but was uncommon. More recently, outbreaks of LGV proctocolitis due to a novel LGV OmpA variant L2b have occurred in Europe since 2003, primarily involving HIV-infected MSM (3). LGV proctocolitis may cause significant complications if not recognized and treated. LGV proctocolitis remains rarely reported in the United States (4), but is likely underdiagnosed. We report on a patient self-referred to a gastroenterologist in Birmingham, Alabama for evaluation of chronic rectal bleeding, who was found to have LGV proctocolitis.

O01.1 Association of Genetic Variants with Chlamydia Trachomatis Reinfection

Background Up to 20% of Chlamydia trachomatis (CT)-infected patients are reinfected within months after treatment, suggesting some fail to develop protective immunity. Genetic determinants influencing CT reinfection risk have not been fully elucidated. Our primary research objective is to identify genetic determinants of CT reinfection. Based on previously reported associations of HLA class II alleles with CT complications, our initial investigations focus on HLA class II genes. Methods In an ongoing prospective natural history study, CT-infected subjects are enrolled, treated with azithromycin 1 g single dose, and return for a 6-month follow-up visit for repeat CT testing using the Gen-Probe APTIMA Combo 2 assay (Gen-Probe, Inc., San Diego, CA). HLA class II alleles are resolved by a combination of PCR-based techniques. Genomic DNA is stored for further genotyping. Results A total of 199 African American subjects have been studied to date: 90% women and median age 23. CT reinfection at follow-up was noted in 18%. Subjects with HLA-DQB1*05 more often had reinfection (20 [26%] vs. 16 [13%], P = 0.018), which remained significant after controlling for age and gender (OR 2.6, 95% CI 1.2–5.6, P = 0.012). Other HLA-DQB1 alleles were not significantly associated with reinfection (P ≥ 0.1). Conclusion HLA-DQB1* 05was associated with CT reinfection, suggesting it could influence protective immunity. More comprehensive genotyping from larger prospectively studied cohorts should help confirm or refine this observation. Analysis of additional HLA class II genes and genes beyond the human MHC is in progress.

T cell phenotypes in women with Chlamydia trachomatis infection and influence of treatment on phenotype distributions

T cell phenotypes involved in the immune response to Chlamydia trachomatis (CT) have not been fully elucidated in humans. We evaluated differences in T cell phenotypes between CT-infected women and CT-seronegative controls and investigated changes in T cell phenotype distributions after CT treatment and their association with reinfection. We found a higher expression of T cell activation markers (CD38+HLA-DR+), T helper type 1 (Th1)- and Th2-associated effector phenotypes (CXCR3+CCR5+ and CCR4+, respectively), and T cell homing marker (CCR7) for both CD4+ and CD8+ T cells in CT-infected women. At follow-up after treatment of infected women, there were a lower proportion of CD4+ and CD8+ T cells expressing these markers. These findings suggest a dynamic interplay of CD4+ and CD8+ T cells in CT infection, and once the infection is treated, these cell markers return to basal expression levels. In women without reinfection, a significantly higher proportion of CD8+ T cells co-expressing CXCR3 with CCR5 or CCR4 at follow-up was detected compared to women with reinfection, suggesting they might play some role in adaptive immunity. Our study elucidated changes in T cell phenotypes during CT infection and after treatment, broadening our understanding of adaptive immune mechanisms in human CT infections.

Distinct peripheral vs mucosal T-cell phenotypes in chlamydia-infected women

Differences in circulating (peripheral) and mucosal T‐cell phenotypes in chlamydia‐infected women remain largely unknown.

Lymphogranuloma Venereum Proctitis and Clostridium difficile Colitis in an HIV-Infected Patient

A human immunodeficiency virus–infected man who has sex with men presentedwith several months of abdominal pain, diarrhea, rectal pain, and rectal discharge of bright red blood and pus. He reported receptive anal intercourse with multiple casual male partners. He was subsequently diagnosed with lymphogranuloma venereum proctitis and Clostridium difficile colitis. It is possible thatC. difficilewas sexually transmitted in this case because the patient did not have any of the traditional risk factors for C. difficile. Clinicians should be cognizant of the diagnosis of lymphogranuloma venereum, particularly among high risk men who have sex with men, and its potential association with other gastrointestinal pathogens such as C. difficile that may be sexually transmitted. Failure to identify and treat these pathogens can lead to significant complications and the potential for transmission to others.

P3.258 Investigating the Epidemiology of Repeat Chlamydia Trachomatis Detection After Treatment Using Chlamydia Trachomatis Omp A Genotyping

Background Detection of Chlamydia trachomatis (CT) infection within months of initial diagnosis and treatment is a common occurrence. Origins of such infection (persistence vs. reinfection from an untreated or a new partner) are complex. CT strains can be differentiated by complete nucleotide sequence analysis of the ompA gene, encoding an antigenically diverse surface protein outer membrane protein A (OmpA). We are evaluating urogenital CT OmpA genotypes in an ongoing prospective CT natural history study in order to investigate the epidemiology of repeat CT detection after treatment. Methods CT-infected subjects are prospectively enrolled, treated with azithromycin, and return for a 6-month follow-up visit for repeat CT testing using the Gen-Probe APTIMA Combo 2 (Gen-Probe, Inc., San Diego, CA). Urogenital specimens are collected at enrollment and follow-up, from which CT strains are genotyped by ompA amplification and sequencing. Results Enrollment visit genotypes have been determined for 145 subjects to date (91% female, 93% African American). CT infection was detected at follow-up in 39 (27%). Enrollment genotype distribution did not significantly differ in those without versus with repeat CT detection at follow-up (major genotypes: D/Da 25%,23%; E 22%,28%; F 13%,15%; I/Ia 17%,15%; J/Ja 12%,13%). Of 35 subjects with CT strains genotyped from both enrollment and follow-up visits, 7 (20%) had the same CT strain at both visits versus 28 (80%) with a different strain at follow-up. Sexual activity post-treatment was reported in 32 subjects with strains genotyped at both visits; a new sexual partner was reported more often in subjects with discordant vs. concordant strains (52% vs. 14%, p = 0.1). Conclusion Baseline CT Omp A genotype did not predict repeat CT detection. Most repeat CT infection detections were new infections with a different CT strain. Genotyping will be a useful tool in understanding the origins of repeat CT infection detection after treatment.