The Role of MicroRNAs in HIV Infection.

MicroRNAs (miRNAs), a class of small, non-coding RNAs, play a pivotal role in regulating gene expression at the post-transcriptional level. These regulatory molecules are integral to many biological processes and have been implicated in the pathogenesis of various diseases, including Human Immunodeficiency Virus (HIV) infection. This review aims to cover the current understanding of the multifaceted roles miRNAs assume in the context of HIV infection and pathogenesis. The discourse is structured around three primary focal points: (i) elucidation of the mechanisms through which miRNAs regulate HIV replication, encompassing both direct targeting of viral transcripts and indirect modulation of host factors critical for viral replication; (ii) examination of the modulation of miRNA expression by HIV, mediated through either viral proteins or the activation of cellular pathways consequent to viral infection; and (iii) assessment of the impact of miRNAs on the immune response and the progression of disease in HIV-infected individuals. Further, this review delves into the potential utility of miRNAs as biomarkers and therapeutic agents in HIV infection, underscoring the challenges and prospects inherent to this line of inquiry. The synthesis of current evidence positions miRNAs as significant modulators of the host-virus interplay, offering promising avenues for enhancing the diagnosis, treatment, and prevention of HIV infection.

Multilocus sequence typing of Treponema pallidum pallidum in children with acquired syphilis by nonsexual contact.

Background: There are scarce data of Treponema pallidum subsp. pallidum (TPA) characterization in children with syphilis. Nonsexually acquired transmission (NSAT) of TPA is possible in infants through close contact. Methods: A descriptive study in five families with NSAT of syphilis was conducted. Polymerase chain reaction detection of TPA in pediatric index cases (n = 6) and their relatives (n = 44) were conducted followed by multilocus sequence typing (MLST). Results: TPA was detected in swab samples in 16 cases and 12 were characterized by MLST. Nichols lineage was identified in two of five families and SS14-lineage in three of five. In four families, MLST profiles linked index cases to relatives. Conclusion: This is the first report of TPA characterization in children infected by NSAT.

Syphilis is a disease caused by the bacterium Treponema pallidum subsp. pallidum (TPA). Although it is considered a sexually transmitted disease, syphilis can also be transmitted by nonsexual close contact with active lesions. There are clinical reports of this route of transmissions in children; however, there are no molecular characterizations of TPA in this population. A multidisciplinary study (epidemiological, clinical, social and molecular) was performed in six children from five families with clinical diagnosis of nonsexually transmitted syphilis. As a result, 18 infected persons were detected. In 16 individuals the presence of the bacterium genetic material was confirmed by molecular biology techniques, and in 12, its strain was analyzed. When we compared the data, we observed that in four families, the child's strain coincided with the one found in close contact, while in one family, this could not be determined. To our knowledge, this is the first report of TPA characterization in children, which underscore the importance of including molecular biology techniques in complex clinical scenarios such as these.

High frequency of Nichols-like strains and increased levels of macrolide resistance in Treponema pallidum in clinical samples from Buenos Aires, Argentina.

Globally, 94% of Treponema pallidum subsp. pallidum (TPA) clinical strains belong to the SS14-like group and 6% to the Nichols-like group, with a prevalence of macrolide resistance of 90%. Our goal was to determine whether local TPA strain distribution and macrolide resistance frequency have changed significantly since our last report, which revealed that Buenos Aires had a high frequency of Nichols-like strains (27%) and low levels of macrolide resistance (14%). Swab samples from patients with suspected syphilis were collected during 2015-2019 and loci TP0136, TP0548, TP0705 were sequenced in order to perform multilocus sequence typing. Strains were classified as Nichols-like or SS14-like. The presence of macrolide resistance-associated mutations was determined by examination of the 23S rDNA gene sequence. Of 46 typeable samples, 37% were classified as Nichols-like and 63% as SS14-like. Macrolide resistance prevalence was 45.7%. Seven allelic profiles were found, five were SS14-like and two were Nichols-like. The frequency of Nichols-like strains increased between studies (26.8% vs. 37%, p = 0.36). A dramatic increase was found in the frequency of macrolide resistant strains between studies (14.3% vs. 45.7%, p = 0.005). Our results are in agreement with international trends and underscore the need to pursue further TPA molecular typing studies in South America.

Evaluación de intervenciones durante la pandemia COVID-19: desarrollo de un modelo basado en subpoblaciones con distintas tasas de contacto / Evaluation of interventions during the COVID-19 pandemic: development of a modelbased on subpopulations with different contact rates

Resumen Si bien se han realizado múltiples intentos de modelar matemáticamente la pande-mia de la enfermedad por coronavirus 2019 (COVID-19), causada por SARS-CoV-2, pocos modeloshan sido pensados como herramientas interactivas accesibles para usuarios de distintos ámbitos.El objetivo de este trabajo fue desarrollar un modelo que tuviera en cuenta la heterogeneidadde las tasas de contacto de la población e implementarlo en una aplicación accesible, que per-mitiera estimar el impacto de posibles intervenciones a partir de información disponible. Sedesarrolló una versión ampliada del modelo susceptible-expuesto-infectado-resistente (SEIR),denominada SEIR-HL, que asume una población dividida en dos subpoblaciones, con tasas decontacto diferentes. Asimismo, se desarrolló una fórmula para calcular el número básico dereproducción (R0) para una población dividida en n subpoblaciones, discriminando las tasas decontacto de cada subpoblación según el tipo o contexto de contacto. Se compararon las pre-dicciones del SEIR-HL con las del SEIR y se demostró que la heterogeneidad en las tasas decontacto puede afectar drásticamente la dinámica de las simulaciones, aun partiendo de lasmismas condiciones iniciales y los mismos parámetros. Se empleó el SEIR-HL para mostrar elefecto sobre la evolución de la pandemia del desplazamiento de individuos desde posiciones dealto contacto hacia posiciones de bajo contacto. Finalmente, a modo de ejemplo, se aplicó elSEIR-HL al análisis de la pandemia de COVID-19 en Argentina; también se desarrolló un ejemplode uso de la fórmula del R0. Tanto el SEIR-HL como una calculadora del R0fueron implementadosinformáticamente y puestos a disposición de la comunidad.

Abstract Although multiple attempts have been made to mathematically model the currentepidemic of SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), fewmodels have been conceived as accessible interactive tools for users from various backgrounds.The goal of this study was to develop a model that took into account the heterogeneity incontact rates within the population and to implement it in an accessible application allowingto estimate the impact of possible interventions based on available information. An extendedversion of the Susceptible-Exposed-Infected-Resistant (SEIR) model, named SEIR-HL, was deve-loped, assuming a population divided into two subpopulations, with different contact rates.Additionally, a formula for the calculation of the basic reproduction number (R0) for a popula-tion divided into n subpopulations was proposed, where the contact rates for each subpopulationcan be distinguished according to contact type or context. The predictions made by SEIR-HLwere compared to those of SEIR, showing that the heterogeneity in contact rates can drama-tically affect the dynamics of simulations, even when run from the same initial conditions andwith the same parameters. SEIR-HL was used to predict the effect on the epidemic evolution ofthe displacement of individuals from high-contact positions to low-contact positions. Lastly, byway of example, SEIR-HL was applied to the analysis of the SARS-CoV-2 epidemic in Argentinaand an example of the application of the R0formula was also developed. Both the SEIR-HLmodel and an R0calculator were computerized and made available to the community.

[Evaluation of interventions during the COVID-19 pandemic: development of a model based on subpopulations with different contact rates]. / Evaluación de intervenciones durante la pandemia COVID-19: desarrollo de un modelo basado en subpoblaciones con distintas tasas de contacto.

Although multiple attempts have been made to mathematically model the current epidemic of SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), few models have been conceived as accessible interactive tools for users from various backgrounds. The goal of this study was to develop a model that took into account the heterogeneity in contact rates within the population and to implement it in an accessible application allowing to estimate the impact of possible interventions based on available information. An extended version of the Susceptible-Exposed-Infected-Resistant (SEIR) model, named SEIR-HL, was developed, assuming a population divided into two subpopulations, with different contact rates. Additionally, a formula for the calculation of the basic reproduction number (R0) for a population divided into n subpopulations was proposed, where the contact rates for each subpopulation can be distinguished according to contact type or context. The predictions made by SEIR-HL were compared to those of SEIR, showing that the heterogeneity in contact rates can dramatically affect the dynamics of simulations, even when run from the same initial conditions and with the same parameters. SEIR-HL was used to predict the effect on the epidemic evolution of the displacement of individuals from high-contact positions to low-contact positions. Lastly, by way of example, SEIR-HL was applied to the analysis of the SARS-CoV-2 epidemic in Argentina and an example of the application of the R0 formula was also developed. Both the SEIR-HL model and an R0 calculator were computerized and made available to the community.

Incorporation of the rapid HIV test in a sexually-transmitted disease clinic in Buenos Aires: Dramatic increase in the frequency of HIV diagnosis.

Improving access to diagnosis constitutes a key step in the control of the Human immunodeficiency virus (HIV)/AIDS epidemic. Rapid testing is increasingly gaining interest as a powerful diagnostic tool to achieve this goal. The purpose of this study was to implement the rapid HIV test (RHT) in a clinical setting in order to evaluate its effectiveness in increasing HIV diagnosis and patient linkage to the healthcare system. The RHT was offered to all patients attending a sexually-transmitted disease clinic in the City of Buenos Aires between March and December 2015. A total of 593 RHT were performed. The implementation of the RHT yielded an increase in frequency of diagnosis from 6.9% to 31.4% (p<0.001). The first steps of the care cascade showed high retention rates around 90%. RHT yielded an HIV prevalence of 6.3% (95% CI: 4.2-8.5) in this population. HIV prevalence tended to be higher in individuals with no previous HIV testing (p=0.09). Linkage to the healthcare system was associated with a higher probability of having been tested for HIV (p=0.008). The incorporation of the RHT resulted in a high retention of patients and an increase in both frequency of diagnosis and results reception when compared to the classic methodology.

Evaluation of the utility of a rapid test for syphilis at a sexually transmitted disease clinic in Buenos Aires, Argentina.

Even though syphilis can be easily diagnosed by simple and low-cost laboratory methods, it continues to be an important health problem. Rapid tests (RT) for the detection of treponemal antibodies can facilitate earlier diagnosis, access to treatment and linkage to care. The aim of this study was to analyse the usefulness of the incorporation of a RT in the detection of patients infected with T. pallidum in a sexually-transmitted disease (STD) clinic. Between March and December 2015, a syphilis RT was offered to patients who spontaneously attended the clinic. Conventional serology testing was additionally indicated to every participant. The RT for syphilis was offered to 1887 patients, of whom 31.1% agreed to get tested. VDRL test was performed in 84.0% of patients that were also tested with syphilis RT, with a significantly higher frequency observed among participants with reactive RT (94.3% vs. 79.8%, p < 0.001). These results showed that 33.7% of the participants were reactive for the RT and 27.0% were reactive for the VDRL test. Both tests were reactive in 24.9% and non-reactive in 64.3%. A high prevalence of active syphilis was detected in patients attending the clinic. The use of a syphilis RT had a positive impact, which in combination with the VDRL test increased the number of patients that were effectively diagnosed.