Lymphogranuloma Venereum Strains Research Articles

OmpA Sequencing and Multilocus Sequence Typing of Lymphogranuloma Venereum Cases in Buenos Aires Reveal New Chlamydia trachomatis Genotypes.

Since the Lymphogranuloma venereum (LGV) outbreak was first described in Buenos Aires in 2017, the detected strains presented peculiar characteristics. Our goal was to increase the understanding of the strains involved in the LGV outbreak in Argentina. We characterized the ompA gene sequences, using Sanger sequencing, of 88 LGV strains from 239 symptomatic patients in Buenos Aires enrolled between 2017 and 2019, and selected 20 C. trachomatis strains for further characterization using Multilocus Sequence Typing (MLST). Following the ompA gene analysis of the 88 LGV strains, we detected 43% L2b, 31% L1-like, and 26% L2. Among the 38 L2b samples analyzed, there were 7 distinct sequences, 3 of them not previously reported (L2bv12, L2bv13, and L2bv14). Additionally, we detected a strain with a new mutation (AM884176.1:g.59122A>T) found in the position defining L2 or L2b, proposed as L2i. Using MLST, five different sequence types (STs) were detected, including the ST2 (corresponding to the L1-like strains) and a new one (ST60). ST58 was associated with the concomitant presence of another STI and HIV. A high genetic diversity in C. trachomatis LGV strains in Argentina was observed in a short period of time, with a relatively low number of samples from a limited geographical area.

Lymphogranuloma venereum: a retrospective analysis of an emerging sexually transmitted disease in a Lisbon Tertiary Center.

Lymphogranuloma venereum (LGV) is a sexual transmitted infection (STI), currently endemic within the population of men who have sex with men (MSM) of Western Countries. L2B variant has been reported as the predominant strain in the current LGV epidemics, although a shift towards L2-434 has been observed in some European countries. To evaluate and characterize the population with LGV infection diagnosed in Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal. A retrospective analysis of all LGV diagnoses between 2016 and 2019 was performed. The diagnosis was established through ompA-genotyping of samples yielding a positive result to Chlamydia trachomatis (CT). All considered samples were retrieved from the clinician activity, through swabbing and urine analysis and CT infection diagnosis was obtained using real-time PCR. During the period studied 16279 CT diagnostics tests were employed, with a striking increase from 2016 (n=467) to 2019 (n=9362). A total of 1602 diagnoses of CT were established, from which 168 (10.5%) corresponded to LGV, with both infections showing a rising evolution, between 2016 and 2019, of 2.9 and 2.7 times, respectively. The majority of the LGV strains were genotyped as L2/434 (67.3%; n=113). LGV predominantly affected MSM and men who have sex with men and women (97.0%; n=163). Anorectal infection was the most prevalent one (90.5%; n=152), being proctitis the main clinical presentation (76.2%; n=128). Absence of symptoms was reported in almost 15% of the cases (n=24). The presence of concomitant infection with human immunodeficiency virus was dominant (73.2%; n=123) and the prevalence of one or more STI co-infections was about 60.1% (n=99). An increasing evolution of CT and LGV testing and diagnosing was observable throughout the studied period. Characteristics of the population are similar with those described within LGV epidemics. In accordance with recent European studies, predominance towards L2 genotype was identified.

Chlamydia trachomatis L2c Infection in a Porcine Model Produced Urogenital Pathology and Failed to Induce Protective Immune Responses Against Re-Infection.

The current study was designed to evaluate the pathogenesis, pathology and immune response of female genital tract infection with Chlamydia trachomatis L2c, the most recently discovered lymphogranuloma venereum strain, using a porcine model of sexually transmitted infections. Pigs were mock infected, infected once or infected and re-infected intravaginally, and samples were obtained for chlamydial culture, gross and microscopic pathology, and humoral and cell-mediated immunity. Intravaginal inoculation of pigs with this bacterium resulted in an infection that was confined to the urogenital tract, where inflammation and pathology were caused that resembled what is seen in human infection. Re-infection resulted in more severe gross pathology than primary infection, and chlamydial colonization of the urogenital tract was similar for primary infected and re-infected pigs. This indicates that primary infection failed to induce protective immune responses against re-infection. Indeed, the proliferative responses of mononuclear cells from blood and lymphoid tissues to C. trachomatis strain L2c were never statistically different among groups, suggesting that C. trachomatis-specific lymphocytes were not generated following infection or re-infection. Nevertheless, anti-chlamydial antibodies were elicited in sera and vaginal secretions after primary infection and re-infection, clearly resulting in a secondary systemic and mucosal antibody response. While primary infection did not protect against reinfection, the porcine model is relevant for evaluating immune and pathogenic responses for emerging and known C. trachomatis strains to advance drug and/or vaccine development in humans.

Chlamydia trachomatis: when the virulence-associated genome backbone imports a prevalence-associated major antigen signature.

Chlamydia trachomatis is the most prevalent sexually transmitted bacterium worldwide and the causative agent of trachoma. Its strains are classified according to their ompA genotypes, which are strongly linked to differential tissue tropism and disease outcomes [ocular disease, urogenital disease and lymphogranuloma venereum (LGV)]. While the genome-based species phylogenetic tree presents four main clades correlating with tropism/prevalence, namely ocular, LGV, urogenital T1 (more prevalent genotypes) and urogenital T2 (less prevalent genotypes), inter-clade exchange of ompA is considered a rare phenomenon probably mediating marked tropism alterations. An LGV epidemic, associated with the clonal expansion of the L2b genotype, has emerged in the last few decades, raising concerns particularly due to its atypical clinical presentation (ulcerative proctitis) and circulation among men who have sex with men (MSM). Here, we report an LGV outbreak, mostly affecting human immunodeficiency virus-positive MSM engaging in high-risk sexual practices, caused by an L2b strain with a rather unique non-LGV ompA signature that precluded the laboratory notification of this outbreak as LGV. C. trachomatis whole-genome capture and sequencing directly from clinical samples was applied to deeply characterize the genomic backbone of this novel LGV outbreak-causing clone. It revealed a chimeric genome structure due to the genetic transfer of ompA and four neighbouring genes from a serovar D/Da strain, likely possessing the genomic backbone associated with the more prevalent urogenital genotypes (T1 clade), to an LGV (L2b) strain. The hybrid L2b/D-Da strain presents the adhesin and immunodominant antigen MOMP (major outer membrane protein) (encoded by ompA) with an epitope repertoire typical of non-invasive genital strains, while keeping the genome-dispersed virulence fingerprint of a classical LGV strain. As previously reported for inter-clade ompA exchange among non-LGV clades, this novel C. trachomatis genomic mosaic involving a contemporary epidemiologically and clinically relevant LGV strain may have implications on its transmission, tissue tropism and pathogenic capabilities. The emergence of variants with epidemic and pathogenic potential highlights the need for more focused surveillance strategies to capture C. trachomatis evolution in action.

Rapid detection and strain typing of Chlamydia trachomatis using a highly multiplexed microfluidic PCR assay.

Nucleic acid amplification tests (NAATs) are recommended by the CDC for detection of Chlamydia trachomatis (Ct) urogenital infections. Current commercial NAATs require technical expertise and sophisticated laboratory infrastructure, are time-consuming and expensive, and do not differentiate the lymphogranuloma venereum (LGV) strains that require a longer duration of treatment than non-LGV strains. The multiplexed microfluidic PCR-based assay presented in this work simultaneously interrogates 13 loci to detect Ct and identify LGV and non-LGV strain-types. Based on amplified fragment length polymorphisms, the assay differentiates LGV, ocular, urogenital, and proctocolitis clades, and also serovars L1, L2, and L3 within the LGV group. The assay was evaluated in a blinded fashion using 95 clinical swabs, with 76 previously reported as urogenital Ct-positive samples and typed by ompA genotyping and/or Multi-Locus Sequence Typing. Results of the 13-plex assay showed that 51 samples fell within urogenital clade 2 or 4, 24 samples showed both clade 2 and 4 signatures, indicating possible mixed infection, gene rearrangement, or inter-clade recombination, and one sample was a noninvasive trachoma biovar (either a clade 3 or 4). The remaining 19 blinded samples were correctly identified as LGV clade 1 (3), ocular clade 3 (4), or as negatives (12). To date, no NAAT assay can provide a point-of-care applicable turnaround time for Ct detection while identifying clinically significant Ct strain types to inform appropriate treatment. Coupled with rapid DNA processing of clinical swabs (approximately 60 minutes from swab-in to result-out), the assay has significant potential as a rapid POC diagnostic for Ct infections.

Genome expansion in bacteria: the curios case of Chlamydia trachomatis.

BackgroundRecent findings indicated that a correlation between genomic % AT and genome size within strains of microbial species was predominantly associated with the uptake of foreign DNA. One species however, Chlamydia trachomatis, defied any explanation. In the present study 79 fully sequenced C. trachomatis genomes, representing ocular- (nine strains), urogenital- (36 strains) and lymphogranuloma venereum strains (LGV, 22 strains), in three pathogroups, in addition to 12 laboratory isolates, were scrutinized with the intent of elucidating the positive correlation between genomic AT content and genome size.ResultsThe average size difference between the strains of each pathogroup was largely explained by the incorporation of genetic fragments. These fragments were slightly more AT rich than their corresponding host genomes, but not enough to justify the difference in AT content between the strains of the smaller genomes lacking the fragments. In addition, a genetic region predominantly found in the ocular strains, which had the largest genomes, was on average more GC rich than the host genomes of the urogenital strains (58.64 % AT vs. 58.69 % AT), which had the second largest genomes, implying that the foreign genetic regions cannot alone explain the association between genome size and AT content in C. trachomatis. 23,492 SNPs were identified for all 79 genomes, and although the SNPs were on average slightly GC rich (~47 % AT), a significant association was found between genome-wide SNP AT content, for each pathogroup, and genome size (p < 0.001, R2 = 0.86) in the C. trachomatis strains.ConclusionsThe correlation between genome size and AT content, with respect to the C. trachomatis pathogroups, was explained by the incorporation of genetic fragments unique to the ocular and/or urogenital strains into the LGV- and urogential strains in addition to the genome-wide SNP AT content differences between the three pathogroups.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-015-1464-6) contains supplementary material, which is available to authorized users.

Bioinformatic Analysis of Chlamydia trachomatis Polymorphic Membrane Proteins PmpE, PmpF, PmpG and PmpH as Potential Vaccine Antigens.

Chlamydia trachomatis is the most important infectious cause of infertility in women with important implications in public health and for which a vaccine is urgently needed. Recent immunoproteomic vaccine studies found that four polymorphic membrane proteins (PmpE, PmpF, PmpG and PmpH) are immunodominant, recognized by various MHC class II haplotypes and protective in mouse models. In the present study, we aimed to evaluate genetic and protein features of Pmps (focusing on the N-terminal 600 amino acids where MHC class II epitopes were mapped) in order to understand antigen variation that may emerge following vaccine induced immune selection. We used several bioinformatics platforms to study: i) Pmps’ phylogeny and genetic polymorphism; ii) the location and distribution of protein features (GGA(I, L)/FxxN motifs and cysteine residues) that may impact pathogen-host interactions and protein conformation; and iii) the existence of phase variation mechanisms that may impact Pmps’ expression. We used a well-characterized collection of 53 fully-sequenced strains that represent the C. trachomatis serovars associated with the three disease groups: ocular (N=8), epithelial-genital (N=25) and lymphogranuloma venereum (LGV) (N=20). We observed that PmpF and PmpE are highly polymorphic between LGV and epithelial-genital strains, and also within populations of the latter. We also found heterogeneous representation among strains for GGA(I, L)/FxxN motifs and cysteine residues, suggesting possible alterations in adhesion properties, tissue specificity and immunogenicity. PmpG and, to a lesser extent, PmpH revealed low polymorphism and high conservation of protein features among the genital strains (including the LGV group). Uniquely among the four Pmps, pmpG has regulatory sequences suggestive of phase variation. In aggregate, the results suggest that PmpG may be the lead vaccine candidate because of sequence conservation but may need to be paired with another protective antigen (like PmpH) in order to prevent immune selection of phase variants.

Deep comparative genomics among Chlamydia trachomatis lymphogranuloma venereum isolates highlights genes potentially involved in pathoadaptation

Lymphogranuloma venereum (LGV) is a human sexually transmitted disease caused by the obligate intracellular bacterium Chlamydia trachomatis (serovars L1–L3). LGV clinical manifestations range from severe ulcerative proctitis (anorectal syndrome), primarily caused by the epidemic L2b strains, to painful inguinal lymphadenopathy (the typical LGV bubonic form). Besides potential host-related factors, the differential disease severity and tissue tropism among LGV strains is likely a function of the genetic backbone of the strains. We aimed to characterize the genetic variability among LGV strains as strain- or serovar-specific mutations may underlie phenotypic signatures, and to investigate the mutational events that occurred throughout the pathoadaptation of the epidemic L2b lineage. By analyzing 20 previously published genomes from L1, L2, L2b and L3 strains and two new genomes from L2b strains, we detected 1497 variant sites and about 100 indels, affecting 453 genes and 144 intergenic regions, with 34 genes displaying a clear overrepresentation of nonsynonymous mutations. Effectors and/or type III secretion substrates (almost all of those described in the literature) and inclusion membrane proteins showed amino acid changes that were about fivefold more frequent than silent changes. More than 120 variant sites occurred in plasmid-regulated virulence genes, and 66% yielded amino acid changes. The identified serovar-specific variant sites revealed that the L2b-specific mutations are likely associated with higher fitness and pointed out potential targets for future highly discriminatory diagnostic/typing tests. By evaluating the evolutionary pathway beyond the L2b clonal radiation, we observed that 90.2% of the intra-L2b variant sites occurring in coding regions involve nonsynonymous mutations, where CT456/tarp has been the main target. Considering the progress on C. trachomatis genetic manipulation, this study may constitute an important contribution for prioritizing study targets for functional genomics aiming to dissect the impact of the identified intra-LGV polymorphisms on virulence or tropism dissimilarities among LGV strains.

In silico scrutiny of genes revealing phylogenetic congruence with clinical prevalence or tropism properties of Chlamydia trachomatis strains.

Microbes possess a multiplicity of virulence factors that confer them the ability to specifically infect distinct biological niches. Contrary to what is known for other bacteria, for the obligate intracellular human pathogen Chlamydia trachomatis, the knowledge of the molecular basis underlying serovars’ tissue specificity is scarce. We examined all ~900 genes to evaluate the association between individual phylogenies and cell-appetence or ecological success of C. trachomatis strains. Only ~1% of the genes presented a tree topology showing the segregation of all three disease groups (ocular, urogenital, and lymphatic) into three well-supported clades. Approximately 28% of the genes, which include the majority of the genes encoding putative type III secretion system effectors and Inc proteins, present a phylogenetic tree where only lymphogranuloma venereum strains form a clade. Similarly, an exclusive phylogenetic segregation of the most prevalent genital serovars was observed for 61 proteins. Curiously, these serovars are phylogenetically cosegregated with the lymphogranuloma venereum serovars for ~20% of the genes. Some clade-specific pseudogenes were identified (novel findings include the conserved hypothetical protein CT037 and the predicted α-hemolysin CT473), suggesting their putative expendability for the infection of particular niches. Approximately 3.5% of the genes revealed a significant overrepresentation of nonsynonymous mutations, and the majority encode proteins that directly interact with the host. Overall, this in silico scrutiny of genes whose phylogeny is congruent with clinical prevalence or tissue specificity of C. trachomatis strains may constitute an important database of putative targets for future functional studies to evaluate their biological role in chlamydial infections.

2013 European guideline on the management of lymphogranuloma venereum

WHAT IS NEW IN THIS UPDATED GUIDELINE?: This is the update version of the 2010 European guideline on the management of lymphogranuloma venereum (LGV). New issues are: Based on clonal relatedness of prevalent LGV strains there is evidence that the LGV epidemic among men who have sex with men (MSM) in the Western world prevailed already in the United States in the 1980s and was introduced into Europe by the end of the last century. A new LGV variant causing severe proctitis was unveiled and designated L2c. The L2b LGV variant causing the vast majority of infections among MSM is now also found among a few heterosexual women. Apart from HIV and STI screening, Hepatitis C Virus (HCV) testing should be offered to all LGV patients. To exclude reinfections, STI screening during a follow-up visit 3months after an LGV diagnosis should be offered.

Clinical and epidemiological characterization of a lymphogranuloma venereum outbreak in Madrid, Spain: co-circulation of two variants

The lymphogranuloma venereum (LGV) outbreak described in the Netherlands in 2003, increased the interest in the genotyping of Chlamydia trachomatis. Although international surveillance programmes were implemented, these studies slowly decreased in the following years. Now data have revealed a new accumulation of LGV cases in those European countries with extended surveillance programmes. Between March 2009 and November 2011, a study was carried out to detect LGV cases in Madrid. The study was based on screening of C. trachomatis using commercial kits, followed by real-time pmpH-PCR discriminating LGV strains, and finally ompA gene was sequenced for phylogenetic reconstruction. Ninety-four LGV infections were identified. The number of cases increased from 10 to 30 and then to 54 during 2009-2011. Incidence of LGV was strongly associated with men who have sex with men; but in 2011, LGV cases were described in women and heterosexual men. Sixty-nine patients were also human immunodeficiency virus (HIV) positive, with detectable viral loads at the moment of LGV diagnosis, suggesting a high-risk of co-transmission. In fact, in four patients the diagnosis of HIV was simultaneous with LGV infection. The conventional treatment with doxycycline was prescribed in 75 patients, although in three patients the treatment failed. The sequencing of the ompA gene permitted identification of two independent transmission nodes. One constituted by 25 sequences identical to the L2b variant, and a second node including 37 sequences identical to L2. This epidemiological situation characterized by the co-circulation of two LGV variants has not been previously described, reinforcing the need for screening and genotyping of LGV strains.

Assessment of the load and transcriptional dynamics of Chlamydia trachomatis plasmid according to strains’ tissue tropism

Chlamydia trachomatis maintain a conserved plasmid, which is a primary regulator of chromosomal genes, but there is no experimental evidences associating it with the strains’ differential tissue tropism (ocular and genital mucosae, and lymph nodes). We investigated if the number of plasmids per strain correlate with expression profiles of plasmid ORFs and small anti-sense RNAs (sRNAs), and also if these molecular features underlie tropism dissimilarities. We performed absolute and relative qPCR to determine both the plasmid load and expression throughout C. trachomatis development. Our findings suggest that plasmid load (never exceeding 8 copies) is not a function of expression needs and does not reflect tissue tropism. However, for most ORFs, ocular strains presented lower expression than genital or lymphogranuloma venereum (LGV) strains, and ORF6/pgp4 (transcriptional regulator of virulence associated genes) presented the highest mean expression among strains, followed by the virulence factor ORF5/pgp3 (also regulated by ORF6/pgp4). More, the mean expression levels of the sRNA-2 (anti-sense to ORF2/pgp8) were up to 100-fold higher than those of the ORFs, and up to 12-fold higher than that of sRNA-7 (anti-sense to ORF7/pgp5) for the LGV strains. Overall, besides the known regulatory role of C. trachomatis plasmid, its transcriptional dynamics sustains tropism differences.

Polymorphisms in Inc Proteins and Differential Expression ofincGenes among Chlamydia trachomatis Strains Correlate with Invasiveness and Tropism of Lymphogranuloma Venereum Isolates

Chlamydia trachomatis is a human bacterial pathogen that multiplies only within an intracellular membrane-bound vacuole, the inclusion. C. trachomatis includes ocular and urogenital strains, usually causing infections restricted to epithelial cells of the conjunctiva and genital mucosa, respectively, and lymphogranuloma venereum (LGV) strains, which can infect macrophages and spread into lymph nodes. However, C. trachomatis genomes display >98% identity at the DNA level. In this work, we studied whether C. trachomatis Inc proteins, which have a bilobed hydrophobic domain that may mediate their insertion in the inclusion membrane, could be a factor determining these different types of infection and tropisms. Analyses of polymorphisms and phylogeny of 48 Inc proteins from 51 strains encompassing the three disease groups showed significant amino acid differences that were mainly due to variations between Inc proteins from LGV and ocular or urogenital isolates. Studies of the evolutionary dynamics of inc genes suggested that 10 of them are likely under positive selection and indicated that most nonsilent mutations are LGV specific. Additionally, real-time quantitative PCR analyses in prototype and clinical strains covering the three disease groups identified three inc genes with LGV-specific expression. We determined the transcriptional start sites of these genes and found LGV-specific nucleotides within their promoters. Thus, subtle variations in the amino acids of a subset of Inc proteins and in the expression of inc genes may contribute to the unique tropism and invasiveness of C. trachomatis LGV strains.

Hypervirulent Chlamydia trachomatis Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L 2 ) and D Lineages

ABSTRACTChlamydia trachomatis is an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence factors associated with these organisms. Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L2/434 and outbreak strain L2b/UCH-1/proctitis. We characterized an unusual LGV strain, termed L2c, isolated from an MSM with severe hemorrhagic proctitis. L2c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, unlike the LGV strains described to date. Deep genome sequencing revealed that L2c was a recombinant of L2 and D strains with conserved clustered regions of genetic exchange, including a 78-kb region and a partial, yet functional, toxin gene that was lost with prolonged culture. Indels (insertions/deletions) were discovered in an ftsK gene promoter and in the tarp and hctB genes, which encode key proteins involved in replication, inclusion formation, and histone H1-like protein activity, respectively. Analyses suggest that these indels affect gene and/or protein function, supporting the in vitro and disease phenotypes. While recombination has been known to occur for C. trachomatis based on gene sequence analyses, we provide the first whole-genome evidence for recombination between a virulent, invasive LGV strain and a noninvasive common urogenital strain. Given the lack of a genetic system for producing stable C. trachomatis mutants, identifying naturally occurring recombinants can clarify gene function and provide opportunities for discovering avenues for genomic manipulation.

Phylogenetic Analysis ofChlamydia trachomatisTarp and Correlation with Clinical Phenotype

Chlamydia trachomatis is the leading cause of infectious blindness worldwide and is the most commonly reported pathogen causing sexually transmitted infections. Tarp (translocated actin recruiting phosphoprotein), a type III secreted effector that mediates actin nucleation, is central to C. trachomatis infection. The phylogenetic analysis of tarP from reference strains as well as ocular, genital, and lymphogranuloma venereum (LGV) clinical isolates demonstrated an evolutionary relationship with disease phenotype, with LGV and ocular isolates branched into clades that were separate from the urogenital isolates. The sequence analysis of Tarp indicated a high degree of variability and identified trends within clinical groupings. Tarps from LGV strains contained the highest number of tyrosine-rich repeat regions (up to nine) and the fewest (two) predicted actin binding domains. The converse was noted for Tarp proteins from ocular isolates that contained up to four actin binding domains and as few as one tyrosine-rich repeat region. The results suggest that Tarp is among the few known genes to play a role in C. trachomatis adaptations to specific niches within the host.

Candidate vaginal microbicides with activity against Chlamydia trachomatis and Neisseriagonorrhoeae

Vaginal microbicides with activity towards organisms that cause sexually transmitted infections have been proposed as a strategy to reduce transmission. Small-molecule inhibitors of Chlamydia trachomatis serovar D belonging to the class of salicylidene acylhydrazides (INPs) have been shown to work through a mechanism that involves iron restriction. Expanding on this work, ten INPs were tested against a lymphogranuloma venereum strain of C. trachomatis (serovar L2), Neisseria gonorrhoeae, and hydrogen peroxide-producing Lactobacillus crispatus and Lactobacillus jensenii. Seven INPs had minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations of <50 μM towards C. trachomatis L2. Three INPs had a MIC <12.5 μM against N. gonorrhoeae. Inhibition was reversed by iron, holo-transferrin and holo-lactoferrin but not by the iron-poor forms of these compounds. The compounds exhibited no bactericidal activity toward Lactobacillus. The INPs were not cytotoxic to HeLa 229 cells. When INP 0341 was tested in a mouse model of a Chlamydia vaginal infection there was a significant reduction in the number of mice shedding C. trachomatis up to 4 days after infection ( P < 0.01). In summary, select INPs are promising vaginal microbicide candidates as they inhibit the growth of two common sexually transmitted organisms in vitro, are active in a mouse model against C. trachomatis, are not cytotoxic and do not inhibit organisms that compose the normal vaginal flora.

Predicting Phenotype and Emerging Strains amongChlamydia trachomatisInfections

Chlamydia trachomatis is a global cause of blinding trachoma and sexually transmitted infections (STIs). We used comparative genomics of the family Chlamydiaceae to select conserved housekeeping genes for C. trachomatis multilocus sequencing, characterizing 19 reference and 68 clinical isolates from 6 continental/subcontinental regions. There were 44 sequence types (ST). Identical STs for STI isolates were recovered from different regions, whereas STs for trachoma isolates were restricted by continent. Twenty-nine of 52 alleles had nonuniform distributions of frequencies across regions (p<0.001). Phylogenetic analysis showed 3 disease clusters: invasive lymphogranuloma venereum strains, globally prevalent noninvasive STI strains (ompA genotypes D/Da, E, and F), and nonprevalent STI strains with a trachoma subcluster. Recombinant strains were observed among STI clusters. Single nucleotide polymorphisms (SNPs) were predictive of disease specificity. Multilocus and SNP typing can now be used to detect diverse and emerging C. trachomatis strains for epidemiologic and evolutionary studies of trachoma and STI populations worldwide.

Absence of Lymphogranuloma Venereum Strains Among Rectal Chlamydia trachomatis Outer Membrane Protein A Genotypes Infecting Women and Men Who Have Sex With Men in Birmingham, Alabama

Chlamydia trachomatis (CT) STRAINS can be differentiated by their major outer membrane protein (OmpA) composition, which has been traditionally performed by serotyping, but more recently by genotyping with determination of the ompA gene sequence. At least 20 OmpA types and variants have been identified, 1-4 with genital tract isolates primarily being genotypes D-K; genotypes D, E, and F are most prevalent in the United States. 5-8 Lymphogranuloma venereum (LGV) OmpA types are less frequently identified in the United States, yet are of clinical importance because of their invasive nature and need for longer treatment. In contrast to numerous studies on genital OmpA genotypes, studies on rectal genotypes in the United States are sparse, especially in women, and have primarily evaluated subjects in the western United States. 9-11 Recent rectal OmpA surveillance efforts have focused on detecting LGV strains, 12-14 which commonly cause asymptomatic disease, 15 and their identification relies on OmpA typing as it does for non-LGV strains. Although LGV-associated morbidity underscores the importance of rectal OmpA genotype surveillance, knowledge gained through surveillance can also improve our understanding of the epidemiology of the more abundant non-LGV strains. Studies from the Northwest United States have demonstrated differences in the OmpA distribution of rectal versus genital isolates, such as genotype G being more frequently detected in rectal infection. 9-11

Chlamydia trachomatis infection and photosensitive dermatoses

Background: Photosensitivity to Chlamydia trachomatis has been described in almost 50% of chronic cases of lymphogranuloma venereum (LGV) caused by L1, L2 or L3 serovars. Photosensitivity in non LGV strains of C trachomatis has not been studied. We studied the association of various photosensitive dermatoses with C trachomatis infection in non LGV cases. Methods: Sera of all the cases of photosensitivity, melasma, chronic actinic dermatitis (CAD), polymorphic light eruption (PLE), actinic prurigo (AP) and rosacea were tested for the presence of IgM, IgG and IgA antibodies to C trachomatis by ELISA method. The results were compared with 30 healthy controls. Result: Seventeen (25.53%) of 57 cases of photosensitivity as against two (6.67%) controls were seropositive for IgM/IgG/IgA antibodies, a statistically significant difference (χ 2 6.18, p 0.013). Similarly, significantly higher seropositivity was observed in 12 (25.53%) of 47 cases of melasma (χ 2 4.38, p 0.0363) and six (46.15%) of 13 cases with CAD (χ 2 6.91, p 0.0086). Although higher proportion of patients of rosacea [five (31.25%) of 16 cases] and PLE [four (25.0%) of 16 cases] were seropositive, the difference was not statistically significant (χ 2 3.23, p >0.05, OR 6.36, CI 95% 0 to 48 and χ 2 3.09, p 0.078, OR 4.67, CI 95% 5 to 41 respectively). There was no association of AP. Conclusion: The observations suggest that C trachomatis infection in non LGV cases is an important cause of PS, melasma and CAD. It appears to be an important cause of rosacea and PLE. We recommend that all cases of photosensitivity, melasma, CAD, PMLE and rosacea and their spouses/sexual contacts be investigated for C trachomatis infection.

Rectal lymphogranuloma venereum surveillance in France 2004-2005.

Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by Chlamydia trachomatis strains belonging to the L1, L2 or L3 genotype. An alert about an outbreak of LGV among MSM in the Netherlands was published in January 2004. The first cases of rectal LGV in France were retrospectively diagnosed in March 2004 and sentinel surveillance for LGV was implemented in April 2004. Most of the participating centres were located in the cities of Paris and Bordeaux. Only confirmed rectal LGV cases were included in the surveillance. Rectal specimens from men that were found to be positive for C trachomatis by PCR were sent to the National Reference Centre for Chlamydia infection for genotyping. Simple epidemiological data provided by clinicians and genotyping results were sent to the Institut de Veille Sanitaire (InVS) where data were anonymously recorded. A total of 328 C. trachomatis rectal strains isolated in men were genotyped by the end of December 2005. Of these, 244 (74%) were LGV strains belonging to the L2 genotype. No L1 or L3 C. trachomatis genotype was found. Diagnosis was made retrospectively for 46 cases. The median age of patients with LGV was 39 years. HIV status was known for 96 patients: 82/96 (85%) were HIV-infected. Most LGV cases were diagnosed in the Paris area (92%). Among the remaining 26% C. trachomatis strains, genotypes Da and G were the most frequent. As with syphilis in recent years, the emergence of LGV in Europe is mainly affecting HIV-infected MSM. The screening and treatment of STIs should be included in the clinical follow-up of all HIV-infected MSM.