Is it time to switch to doxycycline from azithromycin for treating genital chlamydial infections in women? Modelling the impact of autoinoculation from the gastrointestinal tract to the genital tract

Craig, Andrew P.; Kong, Fabian Yuh Shiong; Yeruva, Laxmi; Hocking, Jane S; Rank, Roger G.; Wilson, David; Donovan, Basil

doi:10.1186/s12879-015-0939-3

Cited by 43 publications

(35 citation statements)

References 17 publications

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“…However, C. trachomatis has been transmitted sexually among humans, forcing C. trachomatis to adapt to the human genital mucosa and allowing the cytotoxin genes to be lost or significantly shortened in C. trachomatis (49). Nevertheless, C. trachomatis has been frequently detected in the GI tract in humans but without any significant association with GI pathologies (14)(15)(16)(17)50). C. trachomatis may have experienced selection pressures from both the genital and GI tracts.…”

Section: Discussionmentioning

confidence: 99%

Antigen-Specific CD4⁺T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for ClearingChlamydiafrom the Small Intestine but Not the Large Intestine

Lin

Koprivsek

et al. 2019

Infect Immun

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The genital tract pathogen Chlamydia trachomatis is frequently detected in the gastrointestinal tract, but the host immunity that regulates chlamydial colonization in the gut remains unclear. In a Chlamydia muridarum-C57 mouse model, chlamydial organisms are cleared from the genital tract in ϳ4 weeks, but the genital organisms can spread to the gastrointestinal tract. We found that the gastrointestinal chlamydial organisms were cleared from the small intestine by day 28, paralleling their infection course in the genital tract, but persisted in the large intestine for long periods. Mice deficient in ␣/␤ T cells or CD4 ϩ T cells but not CD8 ϩ T cells showed chlamydial persistence in the small intestine, indicating a critical role for CD4 ϩ T cells in clearing Chlamydia from the small intestine. The CD4 ϩ T cell-dependent clearance is likely mediated by gamma interferon (IFN-␥), since mice deficient in IFN-␥ but not interleukin 22 (IL-22) signaling pathways rescued chlamydial colonization in the small intestine. Furthermore, exogenous IFN-␥ was sufficient for clearing Chlamydia from the small intestine but not the large intestine. Mice deficient in developing Chlamydia-specific Th1 immunity showed chlamydial persistence in the small intestine. Finally, IFN-␥-producing CD4 ϩ but not CD8 ϩ T cells from immunized donor mice were sufficient for eliminating Chlamydia from the small intestine but not the large intestine of recipient mice. Thus, we have demonstrated a critical role for Th1 immunity in clearing Chlamydia from the small intestine but not the large intestine, indicating that chlamydial colonization in different regions of the gastrointestinal tract is regulated by distinct immune mechanisms.

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Section: Discussionmentioning

confidence: 99%

Antigen-Specific CD4⁺T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for ClearingChlamydiafrom the Small Intestine but Not the Large Intestine

Lin

Koprivsek

et al. 2019

Infect Immun

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“…24,25 Gratix, et al 18 reported that when CT testing was expanded to include evaluation of rectal swabs, case detection for CT increased by 44%, leading them to support universal screening of women attending STI clinics.…”

Section: Discussionmentioning

confidence: 99%

Patterns of Extragenital Chlamydia and Gonorrhea in Women and Men Who Have Sex With Men Reporting a History of Receptive Anal Intercourse

Danby¹,

Cosentino²,

Rabe³

et al. 2016

Sexually Transmitted Diseases

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Background Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) in men who have sex with men (MSM) is risk-based. Despite high frequencies of oral and receptive anal intercourse (RAI) among women, extragenital screening is not recommended. Methods Women (n=175) and MSM (n=224) primarily recruited from a sexually transmitted infections clinic reporting a lifetime history of RAI completed a structured questionnaire and clinician collected swab samples from the rectum, pharynx, vagina (women) and urine (men). CT and GC were detected using two commercial nucleic acid amplified tests (Aptima Combo 2, Hologic, Inc., Bedford, MA; Xpert CT/NG, Cepheid Innovation, Sunnyvale, CA). Results The median age of the population was 26 years, 62% were Caucasian, and 88% were enrolled from a Sexually Transmitted Diseases clinic. Men were more likely than women to have GC (22.8% vs. 3.4%) and CT (21.9% vs. 12.6%). In men vs. women, GC was detected in 16.5% vs. 2.3% of pharyngeal swabs, 11.6% vs. 2.3% of rectal swabs and 5.4% vs. 2.9% of urine samples or vaginal swabs. CT was detected in 2.2% vs. 1.7% of pharyngeal swabs, 17.4% vs. 11.4% of rectal swabs, and 4.5% vs 10.3% for urogenital sites in men vs. women. Overall 79.6% of CT and 76.5% of GC in men and 18.2% of CT and 16.7% of GC in women were detected only in the pharynx or rectum. Conclusion Reliance on urogenital screening alone misses the majority of GC and CT in men and more than 15% of infections in women reporting RAI.

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“…C. trachomatis is frequently detected in human GI tracts (29)(30)(31)(32)51) and can infect human enteroendocrine cells (52). Women practicing oral or anal sex could introduce C. trachomatis into their GI tracts (30,32), while those not practicing these behaviors were also found positive for C. trachomatis in their rectal swabs (29,31), suggesting that C. trachomatis may spread from women's genital tracts to the GI tracts via sexual behavior-independent pathways, as shown in mice (36).…”

Section: Discussionmentioning

confidence: 99%

Intravenous Inoculation with Chlamydia muridarum Leads to a Long-Lasting Infection Restricted to the Gastrointestinal Tract

et al. 2016

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cChlamydia has been detected in the gastrointestinal tracts of both animals and humans. However, it remains unclear whether the chlamydial organisms can be introduced into the gastrointestinal tract via pathways independent of the oral and anal routes. We have recently shown that Chlamydia muridarum spreads from the genital tract to the gastrointestinal tract potentially via the circulatory system. To test whether hematogenous C. muridarum can spread to and establish a long-lasting colonization in the mouse gastrointestinal tract, we inoculated mice intravenously with a luciferase-expressing C. muridarum strain and monitored its distribution. After tail vein inoculation, most luciferase-generated bioluminescence signals were detected in the mouse abdominal area throughout the experiment. The ex vivo imaging revealed that the abdominal signals came from the gastrointestinal tract tissues. Simultaneous monitoring of chlamydial organisms in individual organs or tissues revealed an initial stage of systemic spreading followed by a long-lasting infection in the gastrointestinal tract. A retro-orbital vein inoculation of the C. muridarum organisms at a lower dose in a different mouse strain also led to colonization of the gastrointestinal tract. We have demonstrated that intravenous C. muridarum inoculation can result in colonization of the gastrointestinal tract, suggesting that the chlamydial organisms may use the sexual behavior-independent circulation pathway to infect the gastrointestinal tract.C hlamydia muridarum infection in the mouse genital tract model has been used for investigation of the mechanisms of Chlamydia trachomatis pathogenesis and immune responses (1-6). This is because a single inoculation of C. muridarum organisms in the mouse lower genital tract can cause hydrosalpinx and infertility (7-9), closely mimicking the tubal adhesion, hydrosalpinx, and infertility observed in women urogenitally infected with C. trachomatis (10-12). Although C. muridarum is not a natural sexually transmitted agent of mice, chlamydiologists have used this model not only to identify both chlamydial (13-17) and host (1, 5, 18-24) pathogenic determinants but also to define the roles of ascending infection and tubal inflammation in chlamydial induction of hydrosalpinx (9,16,25,26). Nevertheless, questions such as how a self-limited infection with C. muridarum in the mouse genital tract can trigger tubal fibrosis or hydrosalpinx that lasts long after the tubal infection is resolved (9, 25) remain unanswered.Although C. trachomatis is a sexually transmitted bacterial pathogen that causes pathologies in the genital tract (27, 28), it has also been detected in the gastrointestinal (GI) tract of humans (29-32). C. muridarum colonized the mouse GI tract when it was introduced to multiple mucosae (33) and established a long-lasting infection when directly inoculated into the mouse GI tract (34,35). The question is whether persistent colonization of the mouse GI tract can fill in the temporal gap between the self-limited infection...

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Is it time to switch to doxycycline from azithromycin for treating genital chlamydial infections in women? Modelling the impact of autoinoculation from the gastrointestinal tract to the genital tract

Cited by 43 publications

References 17 publications

Antigen-Specific CD4⁺T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for ClearingChlamydiafrom the Small Intestine but Not the Large Intestine

Antigen-Specific CD4⁺T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for ClearingChlamydiafrom the Small Intestine but Not the Large Intestine

Patterns of Extragenital Chlamydia and Gonorrhea in Women and Men Who Have Sex With Men Reporting a History of Receptive Anal Intercourse

Intravenous Inoculation with Chlamydia muridarum Leads to a Long-Lasting Infection Restricted to the Gastrointestinal Tract

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Is it time to switch to doxycycline from azithromycin for treating genital chlamydial infections in women? Modelling the impact of autoinoculation from the gastrointestinal tract to the genital tract

Cited by 43 publications

References 17 publications

Antigen-Specific CD4+T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for ClearingChlamydiafrom the Small Intestine but Not the Large Intestine

Antigen-Specific CD4+T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for ClearingChlamydiafrom the Small Intestine but Not the Large Intestine

Patterns of Extragenital Chlamydia and Gonorrhea in Women and Men Who Have Sex With Men Reporting a History of Receptive Anal Intercourse

Intravenous Inoculation with Chlamydia muridarum Leads to a Long-Lasting Infection Restricted to the Gastrointestinal Tract

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Antigen-Specific CD4⁺T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for ClearingChlamydiafrom the Small Intestine but Not the Large Intestine

Antigen-Specific CD4⁺T Cell-Derived Gamma Interferon Is Both Necessary and Sufficient for ClearingChlamydiafrom the Small Intestine but Not the Large Intestine