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.

Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4⁺ T-cell Count?

Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4⁺ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1ß correlated directly with CD4⁺ T-cell activation (p < 0.05). However, none of these cytokines had good predictive values to distinguish "progressors" from "non-progressors". Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/µL (accuracy = 0.93, κ-Cohen = 0.85). Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied.

Presence of IgG anti-gp160/120 antibodies confers higher HIV capture capacity to erythrocytes from HIV-positive individuals.

BACKGROUND: HIV binding has been demonstrated in erythrocytes from HIV-positive and HIV-negative individuals. However, the presence of immunoglobulins G anti-HIV (IgG anti-HIV) in erythrocytes from HIV-positive individuals is still to be elucidated. Moreover, the capacity of erythrocytes from HIV-positive individuals to capture an additional amount of HIV has not been studied. Indeed, it is unknown if HIV binding to erythrocytes in HIV-positive persons could have consequences on the cell-free infectious virus available. METHODOLOGY/PRINCIPAL FINDINGS: IgGs anti-HIV associated to erythrocytes were found in 77.3% (58/75) of the HIV-positive individuals studied and the IgGs anti-gp160 and anti-p24 were the most frequently found. We found a positive association between detectable plasma viral load (pVL) and presence of IgGs anti-HIV associated to erythrocyte (p<0.005), though the anti-p24/160 were present with or without detectable pVL. The HIV capture capacity was higher in erythrocytes from HIV-positive than HIV-negative individuals (p<0.0001). Furthermore, among the HIV-positive individuals the higher viral capture capacity was associated with the presence of anti-gp160/gp120 on erythrocytes. Moreover, the viral capture by erythrocytes was independent of pVL (rho=0.022, p=0.8817). Additionally, reduction of cell-free infectious virus and available viral load was observed in the presence of erythrocytes from HIV-positive individuals. CONCLUSIONS/SIGNIFICANCE: Results suggest that in HIV-positive individuals, erythrocytes are capable of capturing high amounts of HIV by the presence of IgGs anti-gp160/120 on their membranes and this may produce a reduction in the available free virus. Finally, the current measurement of pVL would underestimate the real viral quantity due to the HIV binding through specific antibodies to erythrocytes.

Presence of p24-antigen associated to erythrocyte in HIV-positive individuals even in patients with undetectable plasma viral load.

BACKGROUND: HIV adherence to erythrocytes has been demonstrated in vitro, and it has been suggested that erythrocytes may be carriers of the virus. However, the association between HIV particles or viral proteins and erythrocytes in HIV-infected individuals is still to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: HIV-positive participants (n =112) were classified into two groups according to values of three plasma viral loads (pVL) determined during the 12-month period prior to the study. The first group included 71 individuals with detectable pVL, whereas the second group included 41 individuals with undetectable pVL. Plasma viral load, erythrocyte-associated p24-antigen and p24-antigen in plasma were determined at the moment of the study. A total of 51 out of the 71 patients with detectable pVL showed erythrocyte-associated p24-antigen whereas 13 showed p24-antigen in plasma. Twenty-two out of the 51 patients with erythrocyte-associated p24-antigen showed pVL<10,000 copies/ml and undetectable p24-antigen in plasma. The data indicates that the amount of erythrocyte-associated p24-antigen was not related to p24-antigen in plasma or pVL levels in this group. Among the 41 patients with prior undetectable pVL, eight presented detectable pVL and erythrocyte-associated p24-antigen at the moment of the study. The other 33 showed undetectable pVL and five of these presented erythrocyte-associated p24-antigen. A positive relationship was found between the presence of erythrocyte-associated p24-antigen and the detectable pVL at the moment of the study (p<0.00001). Even more, in another series of assays, a detectable viral load associated to erythrocytes was determined and it was always accompanied by erythrocyte-associated p24-antigen detection. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the presence of erythrocyte-associated p24-antigen in HIV-infected individuals. Since erythrocyte-associated p24-antigen is not always related to pVL or p24-antigen in plasma, erythrocyte-associated p24-antigen showed viral expression not represented in plasma. Therefore, the determination of erythrocyte-associated p24-antigen may contribute to better understand the kinetics and/or evolution of HIV infection.

Centrifugation improves the detection of HIV-1 p24 antigen in plasma from children born to mothers infected with HIV-1.

Detection of HIV proteins and/or nucleic acids is necessary for the diagnosis of perinatal HIV infection. Despite its low sensitivity, detection of p24 antigen in plasma is a simple and economic method for the diagnosis of HIV in exposed children. The aim of this study was to improve the sensitivity of detection of p24 using centrifugation of plasma. Forty-seven selected stored samples from 37 children (23 infected, 14 uninfected, median age of 137 days) were examined. Plasma samples (volume 0.3-1.5 ml) were defrosted, centrifuged at 23,500 x g at 4 degrees C for 60 min and determination of p24 was carried out in the resuspended pellet (0.12 ml). In 32 plasma samples from infected children, p24 was found originally in 6 (18.7%) and resulted positive in 24 (75%) pellets. When only one sample per child was considered, sensitivity was significantly higher in pellets, 3/23 uncentrifuged plasma samples and 15/23 pellets (McNemar Test, p<0.001). Specificity was 100%. The absorbance/cut-off ratio was always higher in the pellets from positive children (p=0.028). Plasma samples with volumes of 1 ml or more achieved a higher sensitivity (91.7% vs. 36.4%, p=0.009). Centrifugation of plasma samples prior to determination of p24 in pediatric patients resulted in a significant increase in sensitivity.