Hepatitis A virus monitoring in wastewater: A complementary tool to clinical surveillance.

Monitoring wastewater is an effective tool for tracking information on trends of enteric viral dissemination. This study aimed to perform molecular detection and genetic characterization of HAV in wastewater and to correlate the results with those obtained from clinical surveillance. Wastewater samples (n=811) of the second most populous city in Argentina were collected from the main wastewater treatment plant (BG-WWTP, n=261), and at 7 local neighborhood collector sewers (LNCS, n=550) during 2017-2022. Clinical samples of acute hepatitis A cases (HA, n=54) were also analyzed. HAV molecular detection was performed by real time RT-PCR, and genetic characterization by RT-Nested PCR, sequencing and phylogenetic analysis. RNA-HAV was detected in sewage samples throughout the entire period studied, and detection frequencies varied according to the location and year (2.9% - 56.5%). In BG-WWTP, 23% of the samples were RNA-HAV+. The highest detection rates were in 2017 (30.0%), 2018 (41.7%) and 2022 (56.5%), which coincides with the highest number of HA cases reported. Twenty-eight (28) sequences were obtained (from clinical and sewage samples), and all were genotype IA. Two monophyletic clusters were identified: one that grouped clinical and wastewater samples from 2017-2018, and another with specimens from 2022, evidencing that environmental surveillance might constitute a replica of viral circulation in the population. These findings evidence that WBE, in a centralized and decentralized sewage monitoring, might be an effective strategy to track HAV circulation trends over time, contributing to the knowledge of HAV in the new post-vaccination epidemiological scenarios in Argentina and in Latin America.

High-dimensional analysis of 16 SARS-CoV-2 vaccine combinations reveals lymphocyte signatures correlating with immunogenicity.

The range of vaccines developed against severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) provides a unique opportunity to study immunization across different platforms. In a single-center cohort, we analyzed the humoral and cellular immune compartments following five coronavirus disease 2019 (COVID-19) vaccines spanning three technologies (adenoviral, mRNA and inactivated virus) administered in 16 combinations. For adenoviral and inactivated-virus vaccines, heterologous combinations were generally more immunogenic compared to homologous regimens. The mRNA vaccine as the second dose resulted in the strongest antibody response and induced the highest frequency of spike-binding memory B cells irrespective of the priming vaccine. Priming with the inactivated-virus vaccine increased the SARS-CoV-2-specific T cell response, whereas boosting did not. Distinct immune signatures were elicited by the different vaccine combinations, demonstrating that the immune response is shaped by the type of vaccines applied and the order in which they are delivered. These data provide a framework for improving future vaccine strategies against pathogens and cancer.

Immunogenicity and reactogenicity of heterologous immunization against SARS CoV-2 using Sputnik V, ChAdOx1-S, BBIBP-CorV, Ad5-nCoV, and mRNA-1273.

Heterologous vaccination against coronavirus disease 2019 (COVID-19) provides a rational strategy to rapidly increase vaccination coverage in many regions of the world. Although data regarding messenger RNA (mRNA) and ChAdOx1 vaccine combinations are available, there is limited information about the combination of these platforms with other vaccines widely used in developing countries, such as BBIBP-CorV and Sputnik V. Here, we assess the immunogenicity and reactogenicity of 15 vaccine combinations in 1,314 participants. We evaluate immunoglobulin G (IgG) anti-spike response and virus neutralizing titers and observe that a number of heterologous vaccine combinations are equivalent or superior to homologous schemes. For all cohorts in this study, the highest antibody response is induced by mRNA-1273 as the second dose. No serious adverse events are detected in any of the schedules analyzed. Our observations provide rational support for the use of different vaccine combinations to achieve wide vaccine coverage in the shortest possible time.

Wastewater based epidemiology as a silent sentinel of the trend of SARS-CoV-2 circulation in the community in central Argentina.

Monitoring wastewater for the traces of viruses allows effective surveillance of entire communities, including symptomatic and asymptomatic infected individuals, providing information on whether a specific pathogen is circulating in a population. In the context of the COVID-19 pandemic, 261 wastewater samples from six communities of the province of Córdoba, Argentina were analyzed. From mid-May 2020 to the end of August 2021, raw sewage samples were collected from the central network pipe that enters into the Wastewater Treatment Plants (WWTP) in Córdoba city and five communities in the Punilla Valley. SARS-CoV-2 was concentrated by using the polyethylene glycol-6000 precipitation method. Viral genomes were extracted from concentrated samples, and N- and E-SARS-CoV-2 genes were detected by using real time RT-PCR. Wastewater samples that resulted positive for SARS-CoV-2 genome detection were subjected to viral variants of concern (VOCs) identification by real time RT-PCR. Overall, just by using the identification of the N gene or E gene, the rates of viral genome detection were 43.4% (86/198) and 51.5% (102/198) respectively, and by using both methodologies (positivity criterion: detection of N and / or E gene), the detection rate was 71.2% (141/198). Thereby, the optimal strategy to study the SARS-CoV-2 genome in wastewater would be the use of the combined detection of both genes. Detection of SARS-CoV-2 variants in wastewater reflected their circulation in the community, showing no VOCs detection in the first COVID-19 wave and their co-circulation with Gamma, Alpha and Delta VOCs during 2021. Therefore, SARS-CoV-2 Wastewater Based Epidemiology (WBE) described the introduction, permanence and/or the co-circulation of viral variants in the community. In geographical areas with a stable population, SARS-CoV-2 WBE could be used as an early warning sign of new COVID-19 cases, whereas in localities with a low number of inhabitants and high tourist influx, WBE may only be useful to reflect the circulation of the virus in the community. Overall, the monitoring of SARS-CoV-2 in wastewater can become a silent sentinel of the trend of viral circulation in the community, providing supplementary information for clinical surveillance to support public health measures.

Hepatitis A outbreak affecting men who have sex with men (MSM) in central Argentina, occurred in July 2017-April 2018, later than the European outbreak.

BACKGROUND: During June-2016-May-2017, several outbreaks of HA were recorded in Europe, especially described in MSM. In our area since July-2017, an increase of hepatitis A (HA) notification was reported. OBJECTIVE: In order to understand the unusual increase of cases occurred in the central region of Argentina, the aim of this study was to describe, characterize and contextualize epidemiologically the HA outbreak occurred this area, until April2018. STUDY DESIGN: HA cases (positive anti-HAV IgM) obtained from the calendar week 29/2017 in which the first case of MSM was recognized were included in our study. HAV RNA detection and molecular characterization was performed from serum samples and/or stool by RT - PCR of VP1/2A genomic region (360bp). RESULTS: Of the 32 cases notified, 87.5% of them were unvaccinated men and 69.6% were MSM (mean age 31.9 years). All MSM associated HAV sequences were genotyped as IA, and clustered with the VRD 521-2016 strain, responsible of causing outbreaks mostly in MSM in Europe since mid-2016. CONCLUSION: As a consequence of the implementation of immunization in children, and the improvement in socio-economic, hygienic and sanitation factors, young adults are becoming increasingly susceptible to HAV infections. Here we add evidence in South America to the HA outbreaks described worldwide among young MSM, demonstrating the need to reinforce official policy of vaccination, in this group and adjust epidemiological surveillance, catch-up vaccination for adolescents, young adults and immunosuppressed patients.

Pre-treatment drug resistance and HIV-1 subtypes in infants from Argentina with and without exposure to antiretroviral drugs for prevention of mother-to-child transmission.

OBJECTIVES: To assess the prevalence and patterns of pre-treatment HIV drug resistance (PDR) and HIV-1 subtype in infants from Argentina with exposure to different antiretroviral drugs (ARVs) for the prevention of mother-to-child transmission (PMTCT). PATIENTS AND METHODS: HIV-1 genotyping was performed in 115 infants (median age = 2.3 months) born between 2007 and 2014 to screen for drug resistance mutations (DRMs) before starting first-line ART. HIV-1 subtype was characterized by phylogenetic and recombination analysis. RESULTS: Overall, DRMs were found in 34 of 115 infants (PDR level 30% to any ARV, 3.5% to PIs, 12% to NRTIs and 22% to NNRTIs). Of the 115 infants, 22 (19.1%) were ARV-unexposed. Another 93 were ARV-exposed: 28 (24.3%) to short-course zidovudine monotherapy ARV prophylaxis; 25 (21.7%) to nevirapine-based ARV prophylaxis; 12 (10.4%) to perinatal infant zidovudine prophylaxis + maternal combination ART with NNRTIs; and 28 (24.3%) to perinatal infant zidovudine prophylaxis+maternal combination ART with PIs. Transmitted drug resistance among ARV-unexposed infants was 32% (5% to PIs, 9% to NRTIs and 18% to NNRTIs). ART-exposed infants showed multi-class ARV resistance. Importantly, vertical transmission of a triple-class-resistant virus was confirmed in one case. Patterns of DRMs predicted high-level resistance to NNRTIs in a similar and high proportion (>50%) of infants with at least one DRM independently of ARV exposure. BF recombinants were found in 74%, subtype B in 20%, subtype C in 3% and novel AG and AB recombinants in 3%. CONCLUSIONS: PDR in HIV-1-infected children from Argentina is among the highest reported, jeopardizing successful lifelong suppressive ART as well as the efficacy of current PMTCT regimens.

Analytical report of the 2016 dengue outbreak in Córdoba city, Argentina.

After elimination of the Aedes aegypti vector in South America in the 1960s, dengue outbreaks started to reoccur during the 1990s; strongly in Argentina since 1998. In 2016, Córdoba City had the largest dengue outbreak in its history. In this article we report this outbreak including spatio-temporal analysis of cases and vectors in the city. A total of 653 dengue cases were recorded by the laboratory-based dengue surveillance system and georeferenced by their residential addresses. Case maps were generated from the epidemiological week 1 (beginning of January) to week 19 (mid-May). Dengue outbreak temporal evolution was analysed globally and three specific, high-incidence zones were detected using Knox analysis to characterising its spatio-temporal attributes. Field and remotely sensed data were collected and analysed in real time and a vector presence map based on the MaxEnt approach was generated to define hotspots, towards which the pesticide- based strategy was then targeted. The recorded pattern of cases evolution within the community suggests that dengue control measures should be improved.

Hepatitis C and HIV coinfection in central region of Argentina: prevalence, genotype characterization and risk factors.

BACKGROUND: This is the first study reporting the epidemiological and molecular characterization of HCV/HIV coinfection in the central region of Argentina. METHOD: Cross-sectional, epidemiological study (2003-2004). STATISTICS: multivariate logistic regression analysis. RESULTS: The incidence of HCV/HIV coinfection was 12.3%. HCV genotype 1 was the most prevalent (73%). Intravenous drug use was the main independent risk factor for acquiring HCV infection. However, an alternative route (sexual) for viral transmission was suggested. CONCLUSIONS: These results underscore the potential public health impact of HCV/HIV coinfection in our region.

Hepatitis C and HIV coinfection in central region of Argentina: prevalence, genotype characterization and risk factors

FUNDAMENTOS. Primer reporte epidemiológico y molecular de la coinfección por el virus de la hepatitis C y el virus de la inmunodeficiencia humana (VHC/VIH) en la región central de Argentina. MÉTODO. Estudio epidemiológico transversal (2003-2004).Análisis: regresión logística multivariado. RESULTADOS. La coinfección VHC/VIH fue 12,3%. El genotipo 1 fue el más prevalente (73%). El uso de drogas intravenosas fue el principal factor de riesgo asociado con HCV. Sin embargo, se sugiere una vía alternativa (sexual)de transmisión. CONCLUSIÓN. Estos resultados destacan el potencial impacto sanitario de la coinfección VHC/VIH en nuestra región (AU)

BACKGROUND. This is the first study reporting the epidemiological and molecular characterization of HCV/HIV coinfection in the central region of Argentina. METHOD. Cross-sectional, epidemiological study (2003-2004).Statistics: multivariate logistic regression analysis. RESULTS. The incidence of HCV/HIV coinfection was 12.3%.HCV genotype 1 was the most prevalent (73%). Intravenous drug use was the main independent risk factor for acquiring HCV infection. However, an alternative route(sexual) for viral transmission was suggested. CONCLUSIONS. These results underscore the potential public health impact of HCV/HIV coinfection in our region (AU)

Evaluation of five screening tests licensed in Argentina for detection of hepatitis C virus antibodies.

This study was conducted to compare among the most recent generation of five screening tests licensed in Argentina, in order to evaluate which of the tests has the best sensitivity for detection of antibodies against hepatitis C virus (HCV). The tests analyzed were: Detect-HCV (3.0) Biochem ImmunoSystems, Canada; Hepatitis C EIA Wiener Lab., Argentina; Equipar HCV Ab, Italy; Murex HCV 4.0, UK and Serodia-HCV particles agglutination test, Japan. The results obtained showed high discrepancy between the different kits used and show that some of the tests assessed have a low sensitivity for anti-HCV detection in both chronic infections and early seroconversion, and indicate that among the commercially available kits in Argentina, Murex HCV 4.0 (UK) and Serodia-HCV particles agglutination test (Japan) have the best sensitivity for HCV screening. Although the sensitivity of the assays is the first parameter to be considered for blood screening, more studies should be carried out to assess the specificity of such assays.

Evaluation of five screening tests licensed in Argentina for detection of hepatitis C virus antibodies

This study was conducted to compare among the most recent generation of five screening tests licensed in Argentina, in order to evaluate which of the tests has the best sensitivity for detection of antibodies against hepatitis C virus (HCV). The tests analyzed were: Detect-HCV™ (3.0) Biochem ImmunoSystems, Canada; Hepatitis C EIA Wiener Lab., Argentina; Equipar HCV Ab, Italy; Murex HCV 4.0, UK and Serodia-HCV particles agglutination test, Japan. The results obtained showed high discrepancy between the different kits used and show that some of the tests assessed have a low sensitivity for anti-HCV detection in both chronic infections and early seroconversion, and indicate that among the commercially available kits in Argentina, Murex HCV 4.0 (UK) and Serodia-HCV particles agglutination test (Japan) have the best sensitivity for HCV screening. Although the sensitivity of the assays is the first parameter to be considered for blood screening, more studies should be carried out to assess the specificity of such assays.

[Screening of HIV in blood banks. Evaluation of fourth generation kits]. / Screening de HIV en bancos de sangre. Evaluación de los equipos de cuarta generación.

Use of detection tests for p24 HIV antigen (p24Ag) in blood banks in Argentina is recommended by the Argentinean Society of Hemotherapy and Immunohematology. In the blood bank of the National University of Cordoba (Argentina), the recent implementation of the p24Ag screening test has considerably increased the cost of the battery of screening tests and its use in all blood donations has not produced the benefits expected. A 4th generation EIA was evaluated for the screening of HIV in comparison with the currently used assays in the blood bank of National University of Cordoba (3rd generation EIA + p24Ag assay). For this comparison, 11 serum samples from subjects with early HIV infection (early seroconversion period) were tested, as well as 27 serum samples from asymptomatic HIV-infected subjects and other 39 from non-HIV infected subjects. The 3rd generation EIA and the 4th generation EIA showed the same sensitivity value (100%) but the specificity of the 3rd generation EIA was higher (97.5%) comparing with 4th generation (95.1%). Besides, the p24Ag test failed to detect 2 samples from subjects with early HIV infection. These results indicate a good performance of both 3rd and 4th generation assays for screening of HIV. However, due to the lowest cost of 4th generation EIA kit, it could replace the currently used assays for HIV screening in regional blood banks. This screening assay will lead to gain in effectiveness and reduced costs until the detection of HIV RNA can be implemented in blood banks.

Screening de HIV en bancos de sangre: evaluacion de los equinos de cuarta generacion / Screening of HIV in blood banks: evaluation of fourth generation kits

La determinación de Ag p24 del virus HIV es recomendada por la Asociación Argentina de Hemoterapiae Inmunohematología para el tamizaje de HIV en los bancos de sangre de Argentina. La implementación de dicha determinación en el banco de sangre de la Universidad Nacional de Córdoba (UNC) implicó un costo elevadopara el nulo beneficio obtenido. Se evaluó la eficiencia del ensayo combinado Ag/Ac ELISA de 4ta generaciónpara el screening de HIV, en comparación a la estrategia actualmente utilizada en el banco de sangre de la UNC(ELISA 3ra generación + ELISA Ag p24). Se utilizaron 11 muestras de suero de pacientes infectados con HIV enetapa temprana de seroconversión, 27 muestras de suero de individuos infectados en etapa asintomática de la infección y 39 muestras de suero de individuos no infectados. Se demostró igual sensibilidad (100%) y una especificidad menor para el equipo de 4ta generación (95.1%) frente al equipo de 3ra generación (97.5%). El ensayo de Ag p24 falló en la detección de 2 muestras HIV tempranas. La alta sensibilidad y especificidad demostradas por los equipos de 3ra y 4ta generación, indica que ambos son adecuados para el tamizaje de HIV en bancos de sangre. Sin embargo, el ELISA de 4ta generación podría ser implementado en los bancos de sangre regionales como una alternativa de menor costo a la estrategia actualmente utilizada. Esta alternativa resulta viable hasta tanto sea posible incorporar en los bancos de sangre la detección de ARN de HIV por técnicas moleculares.

Screening de HIV en bancos de sangre: evaluacion de los equinos de cuarta generacion / Screening of HIV in blood banks: evaluation of fourth generation kits

La determinación de Ag p24 del virus HIV es recomendada por la Asociación Argentina de Hemoterapiae Inmunohematología para el tamizaje de HIV en los bancos de sangre de Argentina. La implementación de dicha determinación en el banco de sangre de la Universidad Nacional de Córdoba (UNC) implicó un costo elevadopara el nulo beneficio obtenido. Se evaluó la eficiencia del ensayo combinado Ag/Ac ELISA de 4ta generaciónpara el screening de HIV, en comparación a la estrategia actualmente utilizada en el banco de sangre de la UNC(ELISA 3ra generación + ELISA Ag p24). Se utilizaron 11 muestras de suero de pacientes infectados con HIV enetapa temprana de seroconversión, 27 muestras de suero de individuos infectados en etapa asintomática de la infección y 39 muestras de suero de individuos no infectados. Se demostró igual sensibilidad (100%) y una especificidad menor para el equipo de 4ta generación (95.1%) frente al equipo de 3ra generación (97.5%). El ensayo de Ag p24 falló en la detección de 2 muestras HIV tempranas. La alta sensibilidad y especificidad demostradas por los equipos de 3ra y 4ta generación, indica que ambos son adecuados para el tamizaje de HIV en bancos de sangre. Sin embargo, el ELISA de 4ta generación podría ser implementado en los bancos de sangre regionales como una alternativa de menor costo a la estrategia actualmente utilizada. Esta alternativa resulta viable hasta tanto sea posible incorporar en los bancos de sangre la detección de ARN de HIV por técnicas moleculares.(AU)

Screening de HIV en bancos de sangre. Evaluación de los equipos de cuarta generación. / [Screening of HIV in blood banks. Evaluation of fourth generation kits]

Use of detection tests for p24 HIV antigen (p24Ag) in blood banks in Argentina is recommended by the Argentinean Society of Hemotherapy and Immunohematology. In the blood bank of the National University of Cordoba (Argentina), the recent implementation of the p24Ag screening test has considerably increased the cost of the battery of screening tests and its use in all blood donations has not produced the benefits expected. A 4th generation EIA was evaluated for the screening of HIV in comparison with the currently used assays in the blood bank of National University of Cordoba (3rd generation EIA + p24Ag assay). For this comparison, 11 serum samples from subjects with early HIV infection (early seroconversion period) were tested, as well as 27 serum samples from asymptomatic HIV-infected subjects and other 39 from non-HIV infected subjects. The 3rd generation EIA and the 4th generation EIA showed the same sensitivity value (100

) but the specificity of the 3rd generation EIA was higher (97.5

) comparing with 4th generation (95.1

). Besides, the p24Ag test failed to detect 2 samples from subjects with early HIV infection. These results indicate a good performance of both 3rd and 4th generation assays for screening of HIV. However, due to the lowest cost of 4th generation EIA kit, it could replace the currently used assays for HIV screening in regional blood banks. This screening assay will lead to gain in effectiveness and reduced costs until the detection of HIV RNA can be implemented in blood banks.

Guía para la atención de niños niñas y adolescentes con VIH y con exposición perinatal / Guide for the care of children and adolescents with HIV and with perinatal exposure

la Guía de Atención para niños y niñas expuestas e infectadas con VIH de la Dirección de Sida y ETS DEL Ministerio de Salud de la Nación constituye una oportunidad para quienes consideramos a la salud pública y la calidad de vida de las embarazadas y los niños con VIH con derechos indeclinables. En este sentido, consideramos a las estrategias preventivas de la transmisión perinatal del VIH como medidas de salud pública de alto impacto para la disminución de la morbimortalidad de la mujer embarazada y del niño. Es importante destacar para quienes trabajamos diariamente por esta población que la Argentina es uno de los países del mundo que ofrece mayor accesibilidad a las herramientas diagnosticas y terapéuticas en materia de VIH. El desafío de este material es poder dar cuenta de cuáles son las estrategias que tienen por objeto alcanzar un impacto positivo en la salud pública, y al mismo tiempo actualizar la información científica disponible. Al mismo tiempo, es relevante el compromiso desinteresado de los profesionales y entidades que colaboraron con la redacción de esta guía. Esperamos pueda ser utilizada como una fuente de consulta confiable para todos los miembros del sistema de salud. Convocamos a continuar este camino, y aumentar los esfuerzos para lograr la indetectabilidad virológica de los niños con VIH, y poder acercarnos progresivamente al objetivo de alcanzar la transmisión perinatal del virus del VIH en la Argentina

Guía para la atenciòn de niños, niñas y adolescentes on VIH, con exposiciòn perrinatal / Guide for the attention of children and adolescents with HIV, with perinatal exposure

La Guía de atención para niños y niñas expuestos e infectados por VIH de la Dirección de Sida y ETS del Ministerio de Salud de la Nación constituye una oportunidad para quienes consideramos a la salud pública y la calidad de vida de las embarazadas y las y los niños con VIH como derechos indeclinables. En este sentido, consideremos a las estrategias preventivas de la trasmisión perinatal del VIH como medidas de salud pública de alto impacto para la disminución de la morbimortalidad de la mujer embarazada y el niño. Es importante destacar para quienes trabajamos diariamente por esta población que la Argentina es uno de los países del mundo que ofrece mayor accesibilidad a las herramientas diagnosticas y terapéuticas en materia de VIH. El desafío de este material es poder dar cuenta de cuáles son las estrategias que tienen por objeto alcanzar un impacto positivo en la salud pública y, al mismo tiempo, actualizar la información científica disponible. Al mismo tiempo, es relevante destacar el compromiso desinteresado de los profesionales y entidades que colaboraron en la redacción de esta guía. Esperamos pueda ser utilizada como una fuente de consulta confiable para todos los miembros del sistema de salud. Convocamos a continuar este camino y aumentar los esfuerzos para lograr la indefectibilidad virológica de los ninos con VIH, y poder acercarnos progresivamente al objetivo de alcanzar la eliminación de la trasmisión perinatal del VIH en la Argentina.