Direct targeting of host microtubule and actin cytoskeletons by a chlamydial pathogenic effector protein.

To propagate within a eukaryotic cell, pathogenic bacteria hijack and remodulate host cell functions. The Gram-negative obligate intracellular Chlamydiaceae, which pose a serious threat to human and animal health, attach to host cells and inject effector proteins that reprogram host cell machineries. Members of the conserved chlamydial TarP family have been characterized as major early effectors that bind to and remodel the host actin cytoskeleton. We now describe a new function for the Chlamydia pneumoniae TarP member CPn0572, namely the ability to bind and alter the microtubule cytoskeleton. Thus, CPn0572 is unique in being the only prokaryotic protein that directly modulates both dynamic cytoskeletons of a eukaryotic cell. Ectopically expressed GFP-CPn0572 associates in a dose-independent manner with either cytoskeleton singly or simultaneously. In vitro, CPn0572 binds directly to microtubules. Expression of a microtubule-only CPn0572 variant resulted in the formation of an aberrantly thick, stabilized microtubule network. Intriguingly, during infection, secreted CPn0572 also colocalized with altered microtubules, suggesting that this protein also affects microtubule dynamics during infection. Our analysis points to a crosstalk between actin and microtubule cytoskeletons via chlamydial CPn0572.

Doxycycline Prophylaxis to Prevent Sexually Transmitted Infections in Women.

BACKGROUND: Doxycycline postexposure prophylaxis (PEP) has been shown to prevent sexually transmitted infections (STIs) among cisgender men and transgender women, but data from trials involving cisgender women are lacking. METHODS: We conducted a randomized, open-label trial comparing doxycycline PEP (doxycycline hyclate, 200 mg taken within 72 hours after condomless sex) with standard care among Kenyan women 18 to 30 years of age who were receiving preexposure prophylaxis against human immunodeficiency virus (HIV). The primary end point was any incident infection with Chlamydia trachomatis, Neisseria gonorrhoeae, or Treponema pallidum. Hair samples were collected quarterly for objective assessment of doxycycline use. RESULTS: A total of 449 participants underwent randomization; 224 were assigned to the doxycycline-PEP group and 225 to the standard-care group. Participants were followed quarterly over 12 months. A total of 109 incident STIs occurred (50 in the doxycycline-PEP group [25.1 per 100 person-years] and 59 in the standard-care group [29.0 per 100 person-years]), with no significant between-group difference in incidence (relative risk, 0.88; 95% confidence interval [CI], 0.60 to 1.29; P = 0.51). Among the 109 incident STIs, chlamydia accounted for 85 (78.0%) (35 in the doxycycline-PEP group and 50 in the standard-care group; relative risk, 0.73; 95% CI, 0.47 to 1.13). No serious adverse events were considered by the trial investigators to be related to doxycycline, and there were no incident HIV infections. Among 50 randomly selected participants in the doxycycline-PEP group, doxycycline was detected in 58 of 200 hair samples (29.0%). All N. gonorrhoeae-positive isolates were resistant to doxycycline. CONCLUSIONS: Among cisgender women, the incidence of STIs was not significantly lower with doxycycline PEP than with standard care. According to hair-sample analysis, the use of doxycycline PEP among those assigned to receive it was low. (Funded by the National Institutes of Health; dPEP ClinicalTrials.gov number, NCT04050540.).

Elimination of Chlamydia muridarum from the female reproductive tract is IL-12p40 dependent, but independent of Th1 and Th2 cells.

Chlamydia vaccine approaches aspire to induce Th1 cells for optimal protection, despite the fact that there is no direct evidence demonstrating Th1-mediated Chlamydia clearance from the female reproductive tract (FRT). We recently reported that T-bet-deficient mice can resolve primary Chlamydia infection normally, undermining the potentially protective role of Th1 cells in Chlamydia immunity. Here, we show that T-bet-deficient mice develop robust Th17 responses and that mice deficient in Th17 cells exhibit delayed bacterial clearance, demonstrating that Chlamydia-specific Th17 cells represent an underappreciated protective population. Additionally, Th2-deficient mice competently clear cervicovaginal infection. Furthermore, we show that sensing of IFN-γ by non-hematopoietic cells is essential for Chlamydia immunity, yet bacterial clearance in the FRT does not require IFN-γ secretion by CD4 T cells. Despite the fact that Th1 cells are not necessary for Chlamydia clearance, protective immunity to Chlamydia is still dependent on MHC class-II-restricted CD4 T cells and IL-12p40. Together, these data point to IL-12p40-dependent CD4 effector maturation as essential for Chlamydia immunity, and Th17 cells to a lesser extent, yet neither Th1 nor Th2 cell development is critical. Future Chlamydia vaccination efforts will be more effective if they focus on induction of this protective CD4 T cell population.

Infection of human organoids supports an intestinal niche for Chlamydia trachomatis.

Several reports suggest that intestinal tissue may be a natural niche for Chlamydia trachomatis infection and a reservoir for persistent infections in the human body. Due to the human specificity of the pathogen and the lack of suitable host models, there is limited knowledge on this topic. In our study, we modelled the course of the chlamydial infection in human primary gastrointestinal (GI) epithelial cells originating from patient-derived organoids. We show that GI cells are resistant to apical infection and C. trachomatis needs access to the basolateral membrane to establish an infection. Transmission electron microscopy analysis reveals the presence of both normal as well as aberrant chlamydial developmental forms in the infected cells, suggesting a possible cell-type specific nature of the infection. Furthermore, we show that the plasmid-encoded Pgp3 is an important virulence factor for the infection of human GI cells. This is the first report of C. trachomatis infection in human primary intestinal epithelial cells supporting a possible niche for chlamydial infection in the human intestinal tissue.

Chlamydia trachomatis induces disassembly of the primary cilium to promote the intracellular infection.

Chlamydia trachomatis is a clinically important bacterium that infects epithelial cells of the genitourinary and respiratory tracts and the eye. These differentiated cells are in a quiescent growth state and have a surface organelle called a primary cilium, but the standard Chlamydia cell culture infection model uses cycling cells that lack primary cilia. To investigate if these differences are relevant, we performed infections with host cells that have a primary cilium. We found that C. trachomatis caused progressive loss of the primary cilium that was prevented by disrupting Aurora A (AurA), HDAC6 or calmodulin, which are components of the cellular cilia disassembly pathway. Stabilization of the primary cilium by targeting this pathway caused a large reduction in infectious progeny although there were no changes in chlamydial inclusion growth, chlamydial replication or the ultrastructural appearance of dividing and infectious forms (RBs and EBs, respectively). Thus, the presence of a primary cilium interfered with the production of infectious EBs at a late step in the developmental cycle. C. trachomatis infection also induced quiescent cells to re-enter the cell cycle, as detected by EdU incorporation in S-phase, and Chlamydia-induced cilia disassembly was necessary for cell cycle re-entry. This study therefore describes a novel host-pathogen interaction in which the primary cilium limits a productive Chlamydia infection, and the bacterium counteracts this host cell defense by activating the cellular cilia disassembly pathway.

Serine deamination by human serine racemase synergizes with antibiotics to curtail the replication of Chlamydia trachomatis.

The obligate intracellular bacterium, Chlamydia trachomatis, has evolved to depend on its human host for many metabolites, including most amino acids and three of the four nucleotides. Given this, it is not surprising that depletion of a single amino acid in the host cell growth medium blocks chlamydial replication. Paradoxically, supra-normal levels of some amino acids also block productive replication of Chlamydia. Here, we have determined how elevated serine levels, generated by exogenous supplementation, impede chlamydial inclusion development and reduce the generation of infectious progeny. Our findings reveal that human serine racemase, which is broadly expressed in multiple tissues, potentiates the anti-chlamydial effect of elevated serine concentrations. In addition to reversibly converting l-serine to d-serine, serine racemase also deaminates serine via ß-elimination. We have determined that d-serine does not directly impact Chlamydia; rather, ammonia generated by serine deamination limits the productive chlamydial replication. Our findings imply that ammonia produced within host cells can traverse the chlamydial inclusion membrane. Further, this property of serine deaminase can be exploited to sensitize Chlamydia to concentrations of doxycycline that are otherwise not bactericidal. Because exogenously elevated levels of serine can be tolerated over extended periods, the broad expression pattern of serine racemase indicates it to be a host enzyme whose activity can be directed against multiple intracellular bacterial pathogens. From a therapeutic perspective, demonstrating host metabolism can be skewed to generate an anti-bacterial metabolite that synergizes with antibiotics, we believe our results provide a new approach to target intracellular pathogens.

Chlamydia trachomatis T3SS Effector CT622 Induces Proinflammatory Cytokines Through TLR2/TLR4-Mediated MAPK/NF-κB Pathways in THP-1 Cells.

BACKGROUND: The pathogenesis of Chlamydia trachomatis is associated with the induction of the host inflammatory response; however, the precise underlying molecular mechanisms remain poorly understood. METHODS: CT622, a T3SS effector protein, has an important role in the pathogenesis of C trachomatis; however, whether CT622 can induce a host inflammatory response is not understood. Our findings demonstrate that CT622 induces the expression of interleukins 6 and 8 (IL-6 and IL-8). Mechanistically, these effects involve the activation of the MAPK/NF-κB signaling pathways (mitogen-activated protein kinase/nuclear factor κB). RESULTS: Interestingly, we demonstrated that the suppression of toll-like receptor 4 using small interfering RNA markedly reduced the phosphorylation of ERK, p38, JNK, and IκBα, concomitant with a significant decrease in IL-6 and IL-8 secretion. Conversely, disruption of toll-like receptor 2 abrogated the CT622-induced upregulation of IL-8 and activation of ERK, whereas IL-6 expression and p38, JNK, and IκBα phosphorylation were unaffected. CONCLUSIONS: Taken together, these results indicate that CT622 contributes to the inflammatory response through the toll-like receptor 2/4-mediated MAPK/NF-κB pathways, which provides insight into the molecular pathology of C trachomatis infection.

Neisseria gonorrhoeae drives Chlamydia trachomatis into a persistence-like state during in vitro co-infection.

Chlamydia trachomatis and Neisseria gonorrhoeae are the most prevalent bacterial sexually transmitted infections (STIs) globally. Despite frequent co-infections in patients, few studies have investigated how mono-infections may differ from co-infections. We hypothesized that a symbiotic relationship between the pathogens could account for the high rates of clinical co-infection. During in vitro co-infection, we observed an unexpected phenotype where the C. trachomatis developmental cycle was impaired by N. gonorrhoeae. C. trachomatis is an obligate intracellular pathogen with a unique biphasic developmental cycle progressing from infectious elementary bodies (EB) to replicative reticulate bodies (RB), and back. After 12 hours of co-infection, we observed fewer EBs than in a mono-infection. Chlamydial genome copy number remained equivalent between mono- and co-infections. This is a hallmark of Chlamydial persistence. Chlamydial persistence alters inclusion morphology but varies depending on the stimulus/stress. We observed larger, but fewer, Chlamydia during co-infection. Tryptophan depletion can induce Chlamydial persistence, but tryptophan supplementation did not reverse the co-infection phenotype. Only viable and actively growing N. gonorrhoeae produced the inhibition phenotype in C. trachomatis. Piliated N. gonorrhoeae had the strongest effect on C. trachomatis, but hyperpiliated or non-piliated N. gonorrhoeae still produced the phenotype. EB development was modestly impaired when N. gonorrhoeae were grown in transwells above the infected monolayer. C. trachomatis serovar L2 was not impaired during co-infection. Chlamydial impairment could be due to cytoskeletal or osmotic stress caused by an as-yet-undefined mechanism. We conclude that N. gonorrhoeae induces a persistence-like state in C. trachomatis that is serovar dependent.

Regulation of chlamydial spreading from the small intestine to the large intestine by IL-22-producing CD4+ T cells.

Following an oral inoculation, Chlamydia muridarum descends to the mouse large intestine for long-lasting colonization. However, a mutant C. muridarum that lacks the plasmid-encoded protein pGP3 due to an engineered premature stop codon (designated as CMpGP3S) failed to do so even following an intrajejunal inoculation. This was because a CD4+ T cell-dependent immunity prevented the spread of CMpGP3S from the small intestine to the large intestine. In the current study, we found that mice deficient in IL-22 (IL-22-/-) allowed CMpGP3S to spread from the small intestine to the large intestine on day 3 after intrajejunal inoculation, indicating a critical role of IL-22 in regulating the chlamydial spread. The responsible IL-22 is produced by CD4+ T cells since IL-22-/- mice were rescued to block the CMpGP3S spread by donor CD4+ T cells from C57BL/6J mice. Consistently, CD4+ T cells lacking IL-22 failed to block the spread of CMpGP3S in Rag2-/- mice, while IL-22-competent CD4+ T cells did block. Furthermore, mice deficient in cathelicidin-related antimicrobial peptide (CRAMP) permitted the CMpGP3S spread, but donor CD4+ T cells from CRAMP-/- mice were still sufficient for preventing the CMpGP3S spread in Rag2-/- mice, indicating a critical role of CRAMP in regulating chlamydial spreading, and the responsible CRAMP is not produced by CD4+ T cells. Thus, the IL-22-producing CD4+ T cell-dependent regulation of chlamydial spreading correlated with CRAMP produced by non-CD4+ T cells. These findings provide a platform for further characterizing the subset(s) of CD4+ T cells responsible for regulating bacterial spreading in the intestine.

Recognition of Chlamydia trachomatis by Toll-like receptor 9 is altered during persistence.

Toll-like receptor 9 (TLR9) is an innate immune receptor that localizes to endosomes in antigen presenting cells and recognizes single stranded unmethylated CpG sites on bacterial genomic DNA (gDNA). Previous bioinformatic studies have demonstrated that the genome of the human pathogen Chlamydia trachomatis contains TLR9 stimulatory motifs, and correlative studies have implied a link between human TLR9 (hTLR9) genotype variants and susceptibility to infection. Here, we present our evaluation of the stimulatory potential of C. trachomatis gDNA and its recognition by hTLR9- and murine TLR9 (mTLR9)-expressing cells. Utilizing reporter cell lines, we demonstrate that purified gDNA from C. trachomatis can stimulate hTLR9 signaling, albeit at lower levels than gDNA prepared from other Gram-negative bacteria. Interestingly, we found that while C. trachomatis is capable of signaling through hTLR9 and mTLR9 during live infections in HEK293 reporter cell lines, signaling only occurs at later developmental time points. Chlamydia-specific induction of hTLR9 is blocked when protein synthesis is inhibited prior to the RB-to-EB conversion, exacerbated by the inhibition of lipooligosaccharide biosynthesis, and is significantly altered during the induction of aberrance/persistence. Our observations support the hypothesis that chlamydial gDNA is released during the conversion between the pathogen's replicative and infectious forms and during treatment with antibiotics targeting peptidoglycan assembly. Given that C. trachomatis inclusions do not co-localize with TLR9-containing vacuoles in the pro-monocytic cell line U937, our findings also hint that chlamydial gDNA is capable of egress from the inclusion, and traffics to TLR9-containing vacuoles via an as yet unknown pathway.

Metabolic dormancy in Chlamydia trachomatis treated with different antibiotics.

Diseases caused by Chlamydia spp. are often associated with persistent infections. Chlamydial persistence is commonly associated with a unique non-infectious intracellular developmental form, termed an aberrant form. Although infectious chlamydiae can be cultured consistently in cells stressed to aberrancy, their role in persistence is not clear. Recovery from antibiotic stress was explored as a model to determine how survival of non-aberrant chlamydiae, in the presence of fully inhibitory drug concentrations, may participate in persistence. Assays included incubation in quinolones, tetracyclines, or chloramphenicol for differing lengths of time, followed by an extended recovery period in antibiotic-free media. Culturable elementary bodies were not detected during treatment with each antibiotic, but viable and culturable Chlamydia trachomatis emerged after the drug was removed. Time-lapse imaging of live, antibiotic-treated infected cells identified metabolically dormant developmental forms within cells that emerged to form typical productive inclusions. The effects of the increasing concentration of most tested antibiotics led to predictable inhibitory activity, in which the survival rate decreased with increasing drug concentration. In contrast, in fluoroquinolone-treated cells, there was a paradoxical increase in productive development that was directly correlated with drug concentration and inversely associated with aberrant form production. This model system uncovers a unique chlamydial persistence pathway that does not involve the chlamydial aberrant form. The association between productive latency and metabolic dormancy is consistent with models for many bacterial species and may lead to a different interpretation of mechanisms of chlamydial persistence in patients.IMPORTANCEThe life history of most pathogens within the genus Chlamydia relies on lengthy persistence in the host. The most generally accepted model for Chlamydia spp. persistence involves an unusual developmental stage, termed the aberrant form, which arises during conditions that mimic a stressful host environment. In this work, we provide an alternate model for chlamydial persistence in the face of antibiotic stress. This model may be relevant to antibiotic treatment failures in patients infected with C. trachomatis.

Analyzing RNA-Seq data from Chlamydia with super broad transcriptomic activation: challenges, solutions, and implications for other systems.

BACKGROUND: RNA sequencing (RNA-Seq) offers profound insights into the complex transcriptomes of diverse biological systems. However, standard differential expression analysis pipelines based on DESeq2 and edgeR encounter challenges when applied to the immediate early transcriptomes of Chlamydia spp., obligate intracellular bacteria. These challenges arise from their reliance on assumptions that do not hold in scenarios characterized by extensive transcriptomic activation and limited repression. RESULTS: Standard analyses using unique chlamydial RNA-Seq reads alone identify nearly 300 upregulated and about 300 downregulated genes, significantly deviating from actual RNA-Seq read trends. By incorporating both chlamydial and host reads or adjusting for total sequencing depth, the revised normalization methods each detected over 700 upregulated genes and 30 or fewer downregulated genes, closely aligned with observed RNA-Seq data. Further validation through qRT-PCR analysis confirmed the effectiveness of these adjusted approaches in capturing the true extent of transcriptomic activation during the immediate early phase of chlamydial infection. CONCLUSIONS: This study highlights the limitations of standard RNA-Seq analysis tools in scenarios with extensive transcriptomic activation, such as in Chlamydia spp. during early infection. Our revised normalization methods, incorporating host reads or total sequencing depth, provide a more accurate representation of gene expression dynamics. These approaches may inform similar adjustments in other systems with unbalanced gene expression dynamics, enhancing the accuracy of transcriptomic analysis.

Clustering of Polymorphic Membrane Protein E Clade in Chlamydia trachomatis Lineages from Men Who Have Sex with Men.

Several Chlamydia trachomatis lineages identified through outer membrane protein A genotyping or multilocus sequence typing have been circulating worldwide among men who have sex with men. In a study in Tokyo, Japan, we demonstrate that such lineages commonly belong to a specific polymorphic membrane protein E clade across genotypes.

Infection-driven activation of transglutaminase 2 boosts glucose uptake and hexosamine biosynthesis in epithelial cells.

Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme with transamidating activity. We report here that both expression and activity of TG2 are enhanced in mammalian epithelial cells infected with the obligate intracellular bacteria Chlamydia trachomatis. Genetic or pharmacological inhibition of TG2 impairs bacterial development. We show that TG2 increases glucose import by up-regulating the transcription of the glucose transporter genes GLUT-1 and GLUT-3. Furthermore, TG2 activation drives one specific glucose-dependent pathway in the host, i.e., hexosamine biosynthesis. Mechanistically, we identify the glucosamine:fructose-6-phosphate amidotransferase (GFPT) among the substrates of TG2. GFPT modification by TG2 increases its enzymatic activity, resulting in higher levels of UDP-N-acetylglucosamine biosynthesis and protein O-GlcNAcylation. The correlation between TG2 transamidating activity and O-GlcNAcylation is disrupted in infected cells because host hexosamine biosynthesis is being exploited by the bacteria, in particular to assist their division. In conclusion, our work establishes TG2 as a key player in controlling glucose-derived metabolic pathways in mammalian cells, themselves hijacked by C. trachomatis to sustain their own metabolic needs.

Neonatal Chlamydia muridarum respiratory infection causes neuroinflammation within the brainstem during the early postnatal period.

Respiratory infections are one of the most common causes of illness and morbidity in neonates worldwide. In the acute phase infections are known to cause wide-spread peripheral inflammation. However, the inflammatory consequences to the critical neural control centres for respiration have not been explored. Utilising a well characterised model of neonatal respiratory infection, we investigated acute responses within the medulla oblongata which contains key respiratory regions. Neonatal mice were intranasally inoculated within 24 h of birth, with either Chlamydia muridarum or sham-infected, and tissue collected on postnatal day 15, the peak of peripheral inflammation. A key finding of this study is that, while the periphery appeared to show no sex-specific effects of a neonatal respiratory infection, sex had a significant impact on the inflammatory response of the medulla oblongata. There was a distinct sex-specific response in the medulla coincident with peak of peripheral inflammation, with females demonstrating an upregulation of anti-inflammatory cytokines and males showing very few changes. Microglia also demonstrated sex-specificity with the morphology of females and males differing based upon the nuclei. Astrocytes showed limited changes during the acute response to neonatal infection. These data highlight the strong sex-specific impact of a respiratory infection can have on the medulla in the acute inflammatory phase.

Overcoming analytical and preanalytical challenges associated with extragenital home collected STI specimens.

Home sample collection for sexually transmitted infection (STI) screening options can improve access to sexual healthcare across communities. For Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), genital infections have classically been the focus for remote collection options. However, infections may go undiagnosed if sampling is limited to urogenital sites because some individuals only participate in oral and/or anal intercourse. Here we evaluated samples for CT/NG detection after several pre-analytical collection challenges. A paired provider to self-collection validation was performed on rectal [n = 162; 22 + for CT and 9 + for NG by provider-collected (PC)] and throat (N = 158; 2 + for CT and 11 + for NG by provider-collected) swabs. The positive percent agreement for CT and NG ranged from 90.9% to 100%. The discrepancies were more often positive on self-collected (SC) (n = 9 SC+/PC-; n = 1 PC+/SC-; n = 1 PC+/SC Equiv.; n = 2 PC-/SC Equiv.). An empirical limit of detection (LoD) lower than the manufacturer's claim (0.031 vs 2.5 IFU/mL for CT and 0.063 vs 124.8 CFU/ml for NG, respectively) was used to challenge additional variables. Common hand contaminants, including soap, hand sanitizer, lotion, and sunscreen were added to known positive (3× empirical LoD) or negative samples and did not influence detection. Samples at 2× and 10× the empirical LoD were challenged with extreme temperature cycling and extended room temperature storage. Detection was not affected by these conditions. These results indicate that remote self-collection is an appropriate method of sample acquisition for detecting extragenital CT/NG infections. Additionally, they provide a foundation towards meeting the regulatory standards for commercial testing of home collected extragenital samples. IMPORTANCE: There is a clinical need for expanded extragenital bacterial sexually transmitted infection (STI) testing options, but the current regulatory landscape limits the wide-spread promotion and adoption of such services. Improved access, particularly for the LGBTQ+ community, can be achieved by validating testing for specimens that are self-collected at a remote location and arrive at the laboratory via a postal carrier or other intermediary route. Here we provide valuable data showing that self-collected samples for anal and oropharyngeal STI testing are equally or increasingly sensitive compared with those collected by a provider. We systematically consider the effects of storage time, exposure to temperature extremes, and the addition of common toiletries on results.

Th1 cells are dispensable for primary clearance of Chlamydia from the female reproductive tract of mice.

Protective immune responses to Chlamydia infection within the female reproductive tract (FRT) are incompletely understood. MHC class II-restricted CD4 Th1 responses are believed to be vital for bacterial clearance due to their capacity to secrete IFN-γ, but an essential requirement for T-bet-expressing Th1 cells has yet to be demonstrated in the mouse model of Chlamydia infection. Here, we investigated the role of T-bet and IFN-γ in primary clearance of Chlamydia after FRT infection. Surprisingly, IFN-γ producing CD4 T cells from the FRT expressed low levels of T-bet throughout infection, suggesting that classical T-bet-expressing Th1 cells are inefficiently generated and therefore unlikely to participate in bacteria clearance. Furthermore, mice deficient in T-bet expression or with a CD4-specific T-bet deficiency cleared FRT infection similarly to wild-type controls. T-bet-deficient mice displayed significant skewing of FRT CD4 T cells towards Th17 responses, demonstrating that compensatory effector pathways are generated in the absence of Th1 cells. In marked contrast, IFN-γ-, and IFN-γR-deficient mice were able to reduce FRT bacterial burdens, but suffered systemic bacterial dissemination and 100% mortality. Together, these data demonstrate that IFN-γ signaling is essential to protect mice from fatal systemic disease, but that classical T-bet-expressing Th1 cells are non-essential for primary clearance within the FRT. Exploring the protective contribution of Th1 cells versus other CD4 effector lineages could provide important information for the generation of new Chlamydia vaccines.

Anal HPV prevalence in individuals with and without other concomitant sexually transmitted infections.

The association between human papillomavirus (HPV) and other sexually transmitted infections (STIs) in anal lesions still remains unclear. Aim of the study was to evaluate the prevalence of simultaneous infection of HPV and Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis in individuals screened for HPV anal infection. A total of 507 anal samples were tested for both anal HPV and STIs: 16% resulted positive for one or more non-HPV STIs. Specifically, C. trachomatis, M. genitalium, and N. gonorrhoeae were detected in 8%, 5%, and 4% of cases, respectively. Two groups were considered, including a positive STI group and a negative STI group. The prevalence of HPV was similar in patients in both groups: high risk (HR)-HPV and low risk (LR)-HPV were 67% and 53% versus 62% (p = 0.361) and 54% (p = 0.864) of patients, respectively. However, HPV 16, 18, 35, 51, 59, and 69 were significantly more frequent in patients tested positive for other STIs versus HPV infection alone (p < 0.05). No significant differences between the two groups were observed in vaccination coverage, 28% versus 32% (p = 0.463), and HIV status, 86% versus 84% (p = 0.658). The study shows that the overall HPV status is not directly correlated to other STIs in the investigated population, except for certain HPV types, including HR-HPV 16, reinforcing the urge for a greater vaccination coverage.

Association between bacterial vaginosis, Chlamydia trachomatis infection and tubal factor infertility in Bukavu, Democratic Republic of Congo.

BACKGROUND: Tubal factor infertility (TFI) is common in sub-Saharan Africa and often secondary to pelvic inflammatory disease (PID). Anaerobes associated with bacterial vaginosis (BV) are also found in PIDs widely dominated by Chlamydia trachomatis (C. trachomatis), whose role in TFI is better demonstrated than that of BV. OBJECTIVES: To determine the prevalence of BV and C. trachomatis and to investigate the association between BV, C. trachomatis and TFI. METHODS: We included 137 patients treated for infertility between January 2020 and November 2021. Cases were defined as women with infertility aged 18-45 years presenting with TFI (n = 52), and controls as infertile women in the same age groups without TFI (n = 85). Data on social habits, life style and infertility parameters were collected, and we performed screening for BV and C. trachomatis. Multiple regression was used to measure associations. RESULTS: The prevalence of BV and C. trachomatis was 42.3% (58/137) and 23.4% (32/137), respectively. BV (61.5% vs 30.6%, p<0.001) and C. trachomatis (48.1 vs 8.2%, p<0.001) were more frequent in cases of TFI. BV and C. trachomatis increased the risk of TFI approximately 4-fold [aOR: 3.77 (1.61-8.83), p=0.002] and 14-fold [aOR: 13.77 (4.59-41.27), p<0.001], respectively. CONCLUSION: BV and C. trachomatis infection are strongly associated with TFI in Bukavu. Prevention and screening should be implemented to reduce the risk of TFI.

Prevalence of Four Sexually Transmitted Infection Pathogens Detected in Urine and Genital Tract Secretion in Hangzhou, China.

BACKGROUND: Sexually transmitted infections (STIs) increase gradually and have become a public health problem in the world. UU, CT, NG, and MG are four common STI pathogens. Our retrospective study analyzed the clinical situation and the laboratory data of patients infected with the four pathogens. The prevalence of the four pathogens, detected in urine and genital tract secretion, was studied in Hangzhou, China. METHODS: A total of 3,168 male and female patients were randomly selected from February 2023 to February 2024. Urine and genital secretions were collected, and four STI pathogens were controlled for detection. Data were collected from the hospital's electronic medical records, and SPSS 25.0 software was used to perform a statistical analysis. RESULTS: Among 3,168 patients, a total of 1,527 were detected as positive, and the positive rate was 48.20%. The age of patients ranged from 13 - 98 years, with an average age of 45.6. The total of patients consisted of 2,191 males and 977 females, which had a significant difference (p < 0.05). Specimens were mainly collected from the Department of Dermatovenerology, Urological Surgery, Obstetrics and Gynecology, and so on. The positive rate was statistically different between male and female patients (p < 0.05). Single infection performed a main role and accounted for 79.57% of all of the positive patients. In the ≤ 20 age group, the positive rate was the highest and was as high as 77.65%. In detail, single infection caused by UU dominated, especially in the 21 - 30 age group. Double infection caused by UU and CT and triple infection caused by UU, CT, and NG were the majority, both especially in the 21 - 30 age group. There were significant differences in the positive rates in the different age groups and in the four pathogens (p < 0.05). Quadruple infection was very rare and had only been detected in one patient. CONCLUSIONS: The prevalence of the four pathogens in Hangzhou was different from other regions. More male than female patients, more single than multiple infections, and more single and multiple infections occurring in young people were the features in Hangzhou. The study would provide reference for prevention, diagnosis, and treatment of STI.