The natural history of chlamydia is variable and may include persisting asymptomatic infection, complications, or spontaneous resolution before treatment. Reinfection is common. We evaluated whether spontaneous resolution was associated with decreased reinfection in women returning for treatment of a positive chlamydia screening test. At enrollment, participants were tested for chlamydia, treated with azithromycin, and scheduled for a 6-month follow-up visit for repeat testing. Two hundred participants returned 1 to 12 months after treatment. Spontaneous resolution at enrollment was demonstrated in 44 (22.0%). Reinfection at follow-up occurred in 33 (16.5%), being more frequent in those with persisting infection at enrollment versus spontaneous resolution (31 of 156 [19.9%] vs 2 of 44 [4.5%]; P = .016). Adjusting for age, the odds of reinfection was 4 times higher for participants with persisting infection at enrollment (odds ratio 4.0, 95% confidence interval, 1.1-25.6; P = .034). Chlamydia treatment may attenuate protective immunity in some patients.

Background: Adaptive immune responses that mediate protection against Chlamydia trachomatis (CT) remain poorly defined in humans. Animal chlamydia models have demonstrated that CD4+ Th1 cytokine responses mediate protective immunity against reinfection. To better understand protective immunity to CT in humans, we investigated whether select CT-specific CD4+ Th1 and CD8+ T cell cytokine responses were associated with protection against CT reinfection in women.Methods: Peripheral blood mononuclear cells were collected from 135 CT-infected women at treatment and follow-up visits and stimulated with CT antigens. CD4+ and CD8+ T-cells expressing IFN-γ, TNF-α, and/or IL-2 were assessed using intracellular cytokine staining and cytokine responses were compared between visits and between women with vs. without CT reinfection at follow-up.Results: A CD4+TNF-α response was detected in the majority (77%) of study participants at the treatment visit, but a lower proportion had this response at follow-up (62%). CD4+ IFN-γ and CD4+ IL-2 responses occurred less frequently at the treatment visit (32 and 18%, respectively), but increased at follow-up (51 and 41%, respectively). CD8+ IFN-γ and CD8+ TNF-α responses were detected more often at follow-up (59% for both responses) compared to the treatment visit (30% for both responses). At follow-up, a CD4+IFN-γ response was detected more often in women without vs. with reinfection (60 vs. 33%, P = 0.005).Conclusions: Our findings suggest that a CT-specific CD4+ IFN-γ response is associated with protective immunity against CT reinfection and is thus an important component of adaptive immunity to CT in women.

Associations between human leukocyte antigen (HLA) variants and chlamydia-related outcomes have been inconsistent. We previously identified HLA-DQB1*06 as a risk marker for chlamydia reinfection in a cohort of predominately HIV-infected adolescents. As chlamydia reinfection can lead to reproductive complications, validation of this finding in HIV-seronegative women may help reveal the underlying biology. We performed HLA-DQB1 genotyping in HIV-seronegative, chlamydia-infected African American women who were evaluated for reinfection at 3- and 6-month visits after treatment. Of 185 evaluable women for whom HLA-DQB1 genotyping was performed, only HLA-DQB1*06 was associated with chlamydia reinfection (P = 0.009), with no evidence of a dose-response effect for this allele. African American women with HLA-DQB1*06 may warrant more frequent chlamydia screening. More comprehensive genotyping of HLA class II and neighboring genes is needed to establish whether HLA-DQB1*06 is a causal variant for chlamydia reinfection or a surrogate for other causal variants in the major histocompatibility complex.

infection is the most prevalent bacterial sexually transmitted infection and can cause significant reproductive morbidity in women. There is insufficient knowledge of -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 infection in humans, we stimulated peripheral blood mononuclear cells from 90 chlamydia-infected women with 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 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 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.

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.R epeat detection of Chlamydia trachomatis within months of an initial chlamydia diagnosis and treatment is common, occurring in up to 20% of patients, or more in some studies (1-3). The origins of such repeat C. trachomatis detection (infection persistence versus reinfection from an untreated or new partner) are complex, as are the host and organism characteristics that may predispose humans to have repeat C. trachomatis detection after treatment. C. trachomatis strains can be differentiated by nucleotide sequence analysis of the ompA gene, which encodes an antigenically diverse and abundant outer membrane protein A (OmpA). Of the more than 15 C. trachomatis OmpA genotypes identified, the most common ones isolated from the urogenital tract are genotypes D through K (4). Within the OmpA genotypes, further nucleotide variation occurs, permitting strain-to-strain variation within isolates of the same C. trachomatis genotype; hence, C. trachomatis strains may be differentiated by their ompA sequence, and there may be different C. trachomatis strains...