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.

Chlamydia trachomatis anorectal infections by LGV (L1, L2 and L2b) and non-LGV serotypes in symptomatic patients in Buenos Aires, Argentina.

BACKGROUND: Chlamydia trachomatis (CT) can infect the anorectum producing various signs and symptoms. There is scarce literature regarding the differences between LGV and non-LGV CT anorectal manifestations. We compare the clinical spectrum of LGV and non-LGV infections. METHODS: Patients over 18 years with presumptive infectious anorectal symptoms were examined in two healthcare centres in Buenos Aires. The patients were studied and treated according to current sexually transmitted infection guidelines. Anorectal swabs were collected to detect and genotype CT. RESULTS: A three-year-long study on 317 patients with anorectal symptoms showed 45.11% CT infection (85% LGV strains). Of 140 samples, 92 were sequenced: 80/119 LGV (L2b 45%, L1 32.5% and L2 22.5%) and 12/21 non-LGV. Older age and HIV+ status were significantly higher in the LGV group. Anal discharge, bleeding, severe proctitis and anal ulcers were more common in the LGV group. Multivariate logistic regression analysis revealed that HIV infection, anorectal bleeding and oro-anal sex are independent predictors of LGV infection. CONCLUSIONS: In patients with anorectal symptoms, LGV serovars predominate over non-LGV ones. Clinical manifestations are not pathognomonic of a specific biovar. If genotyping is not available, having clinical predictors may help to presume an LGV infection and define length of treatment.

High Plasticity of New Granule Cells in the Aging Hippocampus.

During aging, the brain undergoes changes that impair cognitive capacity and circuit plasticity, including a marked decrease in production of adult-born hippocampal neurons. It is unclear whether development and integration of those new neurons are also affected by age. Here, we show that adult-born granule cells (GCs) in aging mice are scarce and exhibit slow development, but they display a remarkable potential for structural plasticity. Retrovirally labeled 3-week-old GCs in middle-aged mice were small, underdeveloped, and disconnected. Neuronal development and integration were accelerated by voluntary exercise or environmental enrichment. Similar effects were observed via knockdown of Lrig1, an endogenous negative modulator of neurotrophin receptors. Consistently, blocking neurotrophin signaling by Lrig1 overexpression abolished the positive effects of exercise. These results demonstrate an unparalleled degree of plasticity in the aging brain mediated by neurotrophins, whereby new GCs remain immature until becoming rapidly recruited to the network by activity.

A disynaptic feedback network activated by experience promotes the integration of new granule cells.

Experience shapes the development and connectivity of adult-born granule cells (GCs) through mechanisms that are poorly understood. We examined the remodeling of dentate gyrus microcircuits in mice in an enriched environment (EE). Short exposure to EE during early development of new GCs accelerated their functional integration. This effect was mimicked by in vivo chemogenetic activation of a limited population of mature GCs. Slice recordings showed that mature GCs recruit parvalbumin γ-aminobutyric acid-releasing interneurons (PV-INs) that feed back onto developing GCs. Accordingly, chemogenetic stimulation of PV-INs or direct depolarization of developing GCs accelerated GC integration, whereas inactivation of PV-INs prevented the effects of EE. Our results reveal a mechanism for dynamic remodeling in which experience activates dentate networks that "prime" young GCs through a disynaptic feedback loop mediated by PV-INs.

Proctitis infecciosa por Chlamydia Trachomatis / Infectious proctitis by Chlamydia Trachomatis

Introducción: Las infecciones transmisibles sexualmente (ITS) son motivo de consulta frecuente, encontrándose Chlamydia trachomatis (CT) entre las prevalentes. Este germen provoca proctitis de diversa gravedad según el biovar involucrado. Los casos más floridos suelen ser ocasionados por el biovar LGV, responsable de la entidad linfogranuloma venéreo. Se desconocen la prevalencia de CT como causa de proctitis en Argentina y los biovares implicados. Con el objetivo de estudiar estas variables, se diseñó un protocolo para detectar y genotipificar CT en pacientes con proctitis infecciosa. Pacientes y métodos: Se incluyeron pacientes mayores de 18 años con cuadro de proctitis infecciosa atendidos en un centro público y otro privado. Se excluyeron pacientes con enfermedad inflamatoria intestinal y radioterapia pelviana. El estudio fue aprobado por un Comité de Ética y los pacientes firmaron un consentimiento informado. En las muestras de hisopado anal se realizó detección y tipificación molecular de CT. Resultados: Entre 31de agosto de 2017 y 31 de mayo de 2018, se incluyeron 56 pacientes (1 mujer, 53 hombres, 2 mujeres trans), 79% HIV+. En 29 casos (52%) se detectó CT. Todos eran hombres que tienen sexo con hombres (HSH) y refirieron practicar sexo anal u oral receptivo no protegido. La mediana de edad de este subgrupo fue de 31 años; 83% HIV+ en tratamiento antirretroviral y mediana de CD4 637 cel/mm3. La coinfección con otras ITS fue del 41% (siendo las más frecuentes HPV, gonococia y sífilis). Los motivos de consulta más frecuentes fueron proctorragia, pujo y tenesmo, proctalgia y secreción. Las manifestaciones clínicas fueron variadas: proctitis, úlcera perianal, tumor endoanal/rectal y absceso/fístula. El 86% de las proctitis correspondió al biovar LGV, siendo 62% moderadas a graves. La mediana de tiempo de evolución hasta el diagnóstico fue 21 días. Los casos más prolongados correspondieron a cuadros clínicos y endoscópicos más graves. La duración del tratamiento se adecuó al biovar involucrado. Todos los pacientes respondieron favorablemente; sin embargo, las dos fístulas perianales requirieron resolución quirúrgica. Conclusiones: Proctitis, úlceras y fístulas son manifestaciones inespecíficas; el hallazgo clínico y endoscópico per se no son suficientes para definir la etiología; sólo una anamnesis minuciosa permite presumir una ITS como agente causal. La tipificación logra definir el biovar, dato fundamental para adecuar el tratamiento, cortar la cadena de transmisión y contar con datos epidemiológicos a nivel local. Como resultado de esta investigación, el Ministerio de Salud de Nación proyectó la emisión de una alerta sobre la presencia de LGV en nuestro medio. Tipo de estudio: Observacional, transversal, analítico, multicéntrico.

Introduction: Sexually transmitted infections (STI) are a frequent reason for consultation, being Chlamydia trachomatis (CT) among the most prevalent ones. It causes proctitis of varying severity depending on the biovar involved. The most severe cases are usually caused by the LGV biovar, responsible for the entity called lymphogranuloma venereum. The prevalence of CT as a cause of proctitis in Argentina and the biovars involved are unknown. In order to study these variables, a protocol was designed to detect and genotype CT in patients with infectious proctitis. Patients and methods: Patients over 18 years old with infectious proctitis were attended in a public and private center. Patients with inflammatory bowel disease and pelvic radiation therapy were excluded. The study was approved by an Ethics Committee and the patients signed an informed consent. The detection and molecular typing of CT was performed in anal swab samples. Results: Between 31-08-2017 and 31-05-2018, 56 patients were included (1 woman, 53 men, 2 trans women), 79% HIV +. In 29 cases (52%) CT was detected. All were MSM and reported to practice unprotected receptive oral or anal sex. The median age of this subgroup was 31 years; 83% HIV + on antiretroviral treatment and median CD4 637 cel / mm3. The coinfection with other STIs was present 41% (the most frequent were HPV, gonococcal and syphilis). The most frequent symptoms were bleeding, tenesmus, proctalgia and secretion. The clinical manifestations were varied: proctitis, perianal ulcer, endoanal / rectal tumor and abscess / anal fistula. 86% of the proctitis corresponded to the LGV biovar, being 62% moderate to severe. The median time of evolution until the diagnosis was 21 days. The most prolonged cases corresponded to more severe clinical and endoscopic symptoms. The duration of the treatment was adapted to the biovar involved. All patients responded favorably; however, the two perianal fistulas required surgical resolution. Conclusions: Proctitis, ulcers and fistulas are nonspecific manifestations; the clinical and endoscopic findings per se are not sufficient to define the etiology; only a meticulous anamnesis allows us to presume an STI as a causative agent. The typification allows to define the biovar, a fundamental data to adapt the treatment, stop chain of transmission and provides local epidemiological data. As a result of this investigation, the Ministry of Health of the Argentina issued an alert about the presence of LGV in our country. Type of study: Observational, cross-sectional, analytical, multicenter study.