Forging Collaborative Relationships in Brazil: From AIDS to ZIKV.

The Zika virus (ZIKV) outbreak has stimulated collaborations between Brazilians, researchers from other South American countries, and scientists from around the world. The Brazilian response to the HIV/AIDS epidemic demonstrates capabilities that can be applied to the study of ZIKV and provides lessons for developing effective international infectious disease research collaborations.

SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters.

The recent emergence of B.1.1.529, the Omicron variant1,2, has raised concerns of escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in preclinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of several B.1.1.529 isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. Despite modelling data indicating that B.1.1.529 spike can bind more avidly to mouse ACE2 (refs. 3,4), we observed less infection by B.1.1.529 in 129, C57BL/6, BALB/c and K18-hACE2 transgenic mice than by previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease and pathology with B.1.1.529 were also milder than with historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from the SAVE/NIAID network with several B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.

Vaccine-induced systemic and mucosal T cell immunity to SARS-CoV-2 viral variants.

The first-generation COVID-19 vaccines have been effective in mitigating severe illness and hospitalization, but recurring waves of infections are associated with the emergence of SARS-CoV-2 variants that display progressive abilities to evade antibodies, leading to diminished vaccine effectiveness. The lack of clarity on the extent to which vaccine-elicited mucosal or systemic memory T cells protect against such antibody-evasive SARS-CoV-2 variants remains a critical knowledge gap in our quest for broadly protective vaccines. Using adjuvanted spike protein­based vaccines that elicit potent T cell responses, we assessed whether systemic or lung-resident CD4 and CD8 T cells protected against SARS-CoV-2 variants in the presence or absence of virus-neutralizing antibodies. We found that 1) mucosal or parenteral immunization led to effective viral control and protected against lung pathology with or without neutralizing antibodies, 2) protection afforded by mucosal memory CD8 T cells was largely redundant in the presence of antibodies that effectively neutralized the challenge virus, and 3) "unhelped" mucosal memory CD8 T cells provided no protection against the homologous SARS-CoV-2 without CD4 T cells and neutralizing antibodies. Significantly, however, in the absence of detectable virus-neutralizing antibodies, systemic or lung-resident memory CD4 and "helped" CD8 T cells provided effective protection against the relatively antibody-resistant B1.351 (ß) variant, without lung immunopathology. Thus, induction of systemic and mucosal memory T cells directed against conserved epitopes might be an effective strategy to protect against SARS-CoV-2 variants that evade neutralizing antibodies. Mechanistic insights from this work have significant implications in the development of T cell­targeted immunomodulation or broadly protective SARS-CoV-2 vaccines.

Co-Circulation of 2 Oropouche Virus Lineages, Amazon Basin, Colombia, 2024.

In early 2024, explosive outbreaks of Oropouche virus (OROV) linked to a novel lineage were documented in the Amazon Region of Brazil. We report the introduction of this lineage into Colombia and its co-circulation with another OROV lineage. Continued surveillance is needed to prevent further spread of OROV in the Americas.

Molecular Surveillance Detects High Prevalence of the Neglected Parasite Mansonella ozzardi in the Colombian Amazon.

BACKGROUND: Mansonellosis is an undermapped insect-transmitted disease caused by filarial nematodes that are estimated to infect hundreds of millions of people. Despite their prevalence, there are many outstanding questions regarding the general biology and health impacts of the responsible parasites. Historical reports suggest that the Colombian Amazon is endemic for mansonellosis and may serve as an ideal location to pursue these questions. METHODS: We deployed molecular and classical approaches to survey Mansonella prevalence among adults belonging to indigenous communities along the Amazon River and its tributaries near Leticia, Colombia. RESULTS: Loop-mediated isothermal amplification (LAMP) assays on whole-blood samples detected a much higher prevalence of Mansonella ozzardi infection (approximately 40%) compared to blood smear microscopy or LAMP performed using plasma, likely reflecting greater sensitivity and the ability to detect low microfilaremias and occult infections. Mansonella infection rates increased with age and were higher among men. Genomic analysis confirmed the presence of M. ozzardi that clusters closely with strains sequenced in neighboring countries. We successfully cryopreserved M. ozzardi microfilariae, advancing the prospects of rearing infective larvae in controlled settings. CONCLUSION: These data suggest an underestimation of true mansonellosis prevalence, and we expect that these methods will help facilitate the study of mansonellosis in endemic and laboratory settings.

Diagnosis and case formulation in psychodynamic therapy: a review of current tools / Diagnóstico y formulación de casos en terapia psicodinámica: una revisión sobre herramientas actuales.

In the last two decades, several working groups in the international psychoanalytic community have been interested in the development of systematic tools for psychodynamic diagnosis, case formulation and treatment planning. Such psychodynamic diagnostic manuals are efforts to systematically integrate an enormous and rich amount of historically partialized and dispersed information, but which constitute the substantial contribution of psychoanalysis to the field of mental health. The aim of the present article is to provide an updated review on this kind of systematic tools for diagnosis, case formulation and therapeutic planning, designed for the field of psychodynamic approaches. To this end, we describe the aims and structure of: 1) the Psychodynamic Diagnostic Manual 2 (PDM-2), 2) the Operationalized Psychodynamic Diagnosis (OPD-2/OPD-3) and 3) the Operationalized Psychodynamic Diagnosis for Children and adolescents 2 (OPD-CA-2). The contributions of these current tools to clinical practice and empirical research are discussed, as well as the need to disseminate these types of instruments in our regional context.

En las últimas dos décadas, diversos grupos de trabajo de la comunidad psicoanalítica internacional se han interesado por el desarrollo de herramientas sistemáticas para el diagnóstico, la formulación de los casos y la planificación del tratamiento psicodinámico. Este tipo de manuales diagnósticos psicodinámicos son esfuerzos de integración sistemática de una enorme y rica cantidad de información históricamente parcializada y dispersa, pero que constituye el aporte sustancial del psicoanálisis al campo de la salud mental. El objetivo del presente artículo es ofrecer una revisión actualizada sobre esta clase de herramientas sistemáticas de diagnóstico, formulación del caso y planificación terapéutica, diseñadas para el campo de los abordajes psicodinámicos. A estos fines, se describe la estructura y los objetivos de: 1) el Manual Diagnóstico Psicodinámico 2 (PDM-2), 2) el Diagnóstico Psicodinámico Operacionalizado (OPD-2/OPD-3) y 3) el Diagnóstico Psicodinámico Operacionalizado Infanto-Juvenil 2 (OPD-IJ-2).Se discuten las contribuciones de estas herramientas actuales para la práctica clínica y la investigación empírica, así como la necesidad de difundir este tipo de instrumentos en nuestro contexto regional.

Social effects of rabies infection in male vampire bats (Desmodus rotundus).

Rabies virus (RABV) transmitted by the common vampire bat (Desmodus rotundus) poses a threat to agricultural development and public health throughout the Neotropics. The ecology and evolution of rabies host-pathogen dynamics are influenced by two infection-induced behavioural changes. RABV-infected hosts often exhibit increased aggression which facilitates transmission, and rabies also leads to reduced activity and paralysis prior to death. Although several studies document rabies-induced behavioural changes in rodents and other dead-end hosts, surprisingly few studies have measured these changes in vampire bats, the key natural reservoir throughout Latin America. Taking advantage of an experiment designed to test an oral rabies vaccine in captive male vampire bats, we quantify for the first time, to our knowledge, how rabies affects allogrooming and aggressive behaviours in this species. Compared to non-rabid vampire bats, rabid individuals reduced their allogrooming prior to death, but we did not detect increases in aggression among bats. To put our results in context, we review what is known and what remains unclear about behavioural changes of rabid vampire bats (resumen en español, electronic supplementary material, S1).

Efficacy of high-intensity interval- or continuous aerobic-training on insulin resistance and muscle function in adults with metabolic syndrome: a clinical trial.

PURPOSE: We carried out a randomized, clinical trial in adults of both sexes with metabolic syndrome (MS) to assess the efficacy of high-intensity, low-volume interval training (HIIT) compared to moderate-intensity continuous training (MICT) on insulin resistance (IR), muscle mass, muscle activation, and serum musclin. METHODS: Fasting glycemia, insulinemia, and glycated haemoglobin were determined by conventional methods, IR by Homeostatic model assessment (HOMA), lean mass by Dual-Energy X-ray Absorptiometry, muscle activation through carnosine by Proton Magnetic Resonance Spectroscopy, and musclin by Enzyme-Linked ImmunoSorbent Assay before and after a supervised, three-times/week, 12-week treadmill programme. HIIT (n = 29) consisted of six intervals with one-minute, high-intensity phases at 90% of peak oxygen consumption (VO2peak). MICT (n = 31) trained at 60% of VO2peak for 30 min. RESULTS: Patients had a mean age of 50.8 ± 6.0 years, body mass index of 30.6 ± 4.0 kg/m2, and VO2peak of 29.0 ± 6.3 mL.kg-1.min-1. Compared to MICT, HIIT was not superior at reducing Ln HOMA-IR (adjusted mean difference: 0.083 [95%CI - 0.092 to 0.257]), carnosine or musclin or at increasing thigh lean mass. HIIT increased carnosine by 0.66 mmol/kg.ww (95% CI 0.08-1.24) after intervention. Both interventions reduced IR, body fat percentage and increased total lean mass/height2 and VO2peak. Musclin showed a non-significant reduction with a small effect size after both interventions. CONCLUSION: Compared to MICT, HIIT is not superior at reducing IR, carnosine or musclin or at increasing skeletal muscle mass in adults with MS. Both training types improved IR, muscle mass and body composition. NCT03087721, March 22nd, 2017. TRIAL REGISTRATION NUMBER: NCT03087721. Registered March 22nd, 2017.

Primary infection with dengue or Zika virus does not affect the severity of heterologous secondary infection in macaques.

Zika virus (ZIKV) and dengue virus (DENV) are genetically and antigenically related flaviviruses that now co-circulate in much of the tropical and subtropical world. The rapid emergence of ZIKV in the Americas in 2015 and 2016, and its recent associations with Guillain-Barré syndrome, birth defects, and fetal loss have led to the hypothesis that DENV infection induces cross-reactive antibodies that influence the severity of secondary ZIKV infections. It has also been proposed that pre-existing ZIKV immunity could affect DENV pathogenesis. We examined outcomes of secondary ZIKV infections in three rhesus and fifteen cynomolgus macaques, as well as secondary DENV-2 infections in three additional rhesus macaques up to a year post-primary ZIKV infection. Although cross-binding antibodies were detected prior to secondary infection for all animals and cross-neutralizing antibodies were detected for some animals, previous DENV or ZIKV infection had no apparent effect on the clinical course of heterotypic secondary infections in these animals. All animals had asymptomatic infections and, when compared to controls, did not have significantly perturbed hematological parameters. Rhesus macaques infected with DENV-2 approximately one year after primary ZIKV infection had higher vRNA loads in plasma when compared with serum vRNA loads from ZIKV-naive animals infected with DENV-2, but a differential effect of sample type could not be ruled out. In cynomolgus macaques, the serotype of primary DENV infection did not affect the outcome of secondary ZIKV infection.

Epidemiology and genetic diversity of circulating dengue viruses in Medellin, Colombia: a fever surveillance study.

BACKGROUND: Dengue fever is a major public health problem in Colombia. A fever surveillance study was conducted for evaluation of the clinical, epidemiological, and molecular patterns of dengue, prior to Chikungunya and Zika epidemics. METHODS: In November 2011-February 2014, a passive facility-based surveillance was implemented in Santa Cruz Hospital, Medellin, and enrolled eligible febrile patients between 1 and 65 years-of-age. Acute and convalescent blood samples were collected 10-21 days apart and tested for dengue using IgM/IgG ELISA. RNA was extracted for serotyping using RT-PCR on acute samples and genotyping was performed by sequencing. RESULTS: Among 537 febrile patients enrolled during the study period, 29% (n = 155) were identified to be dengue-positive. Only 7% of dengue cases were hospitalized, but dengue-positive patients were 2.6 times more likely to be hospitalized, compared to non-dengue cases, based on a logistic regression. From those tested with RT-PCR (n = 173), 17 were dengue-confirmed based on PCR and/or virus isolation showing mostly DENV-3 (n = 9) and DENV-4 (n = 7) with 1 DENV-1. Genotyping results showed that: DENV-1 isolate belongs to the genotype V or American/African genotype; DENV-3 isolates belong to genotype III; and DENV-4 isolates belong to the II genotype and specifically to the IIb sub-genotype or linage. CONCLUSIONS: Our surveillance documented considerable dengue burden in Santa Cruz comuna during non-epidemic years, and genetic diversity of circulating DENV isolates, captured prior to Chikungunya epidemic in 2014 and Zika epidemic in 2015. Our study findings underscore the need for continued surveillance and monitoring of dengue and other arboviruses and serve as epidemiological and molecular evidence base for future studies to assess changes in DENV transmission in Medellin, given emerging and re-emerging arboviral diseases in the region.