Seroprevalence of anti-SARS-CoV-2 IgG in asymptomatic and pauci-symptomatic people over a 5 month survey in Argentina.

OBJECTIVE: To evaluate the seroprevalence of COVID-19 infection in pauci-symptomatic and asymptomatic people, the associated epidemiological factors, and IgG antibody kinetic over a 5-month period to get a better knowledge of the disease transmissibility and the rate of susceptible persons that might be infected. METHODS: Seroprevalence was evaluated by a cross-sectional study based on the general population of Santa Fe, Argentina (non-probabilistic sample) carried out between July and November 2020. A subgroup of 20 seropositive individuals was followed-up to analyze IgG persistence. For the IgG anti-SARS-CoV-2 antibodies detection, the COVID-AR IgG® ELISA kit was used. RESULTS: 3 000 individuals were included conforming asymptomatic and pauci-symptomatic groups (n=1 500 each). From the total sample, only 8.83% (n=265) presented reactivity for IgG anti-SARS-CoV-2. A significant association was observed between positive anti-SARS-CoV-2 IgG and a history of contact with a confirmed case; the transmission rate within households was approximately 30%. In the pauci-symptomatic group, among the seropositive ones, anosmia and fever presented an OR of 16.8 (95% CI 9.5-29.8) and 2.7 (95% CI 1.6-4.6), respectively (p <0.001). In asymptomatic patients, IgG levels were lower compared to pauci-symptomatic patients, tending to decline after 4 months since the symptoms onset. CONCLUSION: We observed a low seroprevalence, suggestive of a large population susceptible to the infection. Anosmia and fever were independent significant predictors for seropositivity. Asymptomatic patients showed lower levels of antibodies during the 5-month follow-up. IgG antibodies tended to decrease over the end of this period regardless of symptoms.

Seroprevalence of anti-SARS-CoV-2 IgG in asymptomatic and pauci-symptomatic people over a 5 month survey in Argentina

[ABSTRACT]. Objective. To evaluate the seroprevalence of COVID-19 infection in pauci-symptomatic and asymptomatic people, the associated epidemiological factors, and IgG antibody kinetic over a 5-month period to get a better knowledge of the disease transmissibility and the rate of susceptible persons that might be infected. Methods. Seroprevalence was evaluated by a cross-sectional study based on the general population of Santa Fe, Argentina (non-probabilistic sample) carried out between July and November 2020. A subgroup of 20 seropositive individuals was followed-up to analyze IgG persistence. For the IgG anti-SARS-CoV-2 antibodies detection, the COVID-AR IgG® ELISA kit was used. Results. 3 000 individuals were included conforming asymptomatic and pauci-symptomatic groups (n=1 500 each). From the total sample, only 8.83% (n=265) presented reactivity for IgG anti-SARS-CoV-2. A significant association was observed between positive anti-SARS-CoV-2 IgG and a history of contact with a confirmed case; the transmission rate within households was approximately 30%. In the pauci-symptomatic group, among the seropositive ones, anosmia and fever presented an OR of 16.8 (95% CI 9.5-29.8) and 2.7 (95% CI 1.6-4.6), respectively (p <0.001). In asymptomatic patients, IgG levels were lower compared to pauci-symptomatic patients, tending to decline after 4 months since the symptoms onset. Conclusion. We observed a low seroprevalence, suggestive of a large population susceptible to the infection. Anosmia and fever were independent significant predictors for seropositivity. Asymptomatic patients showed lower levels of antibodies during the 5-month follow-up. IgG antibodies tended to decrease over the end of this period regardless of symptoms.

[RESUMEN]. Objetivo. Evaluar la seroprevalencia de la infección por el virus causante de la COVID-19 en personas paucisintomáticas y asintomáticas, los factores epidemiológicos asociados y la cinética de los anticuerpos IgG durante un período de cinco meses para conocer mejor la transmisibilidad de la enfermedad y la tasa de personas susceptibles a estar infectadas. Métodos. Se evaluó la seroprevalencia mediante un estudio transversal basado en la población general de Santa Fe, Argentina (muestra no probabilística) llevado a cabo entre julio y noviembre del 2020. Se realizó un seguimiento de un subgrupo de 20 personas seropositivas para analizar la persistencia de los anticuerpos IgG. Para la detección de los anticuerpos IgG contra SARS-COV-2, se empleó el kit ELISA COVID-AR IgG®. Resultados. Hubo 3 000 participantes divididos en un grupo asintomático y un grupo paucisintomático (n=1 500 cada grupo). De la muestra total, solo 8,83% (n=265) presentó una reactividad de IgG contra el SARS-CoV-2. Se observó una asociación significativa entre anticuerpos IgG positivos contra el SARS-CoV-2 y antecedente de contacto con un caso confirmado. La tasa de transmisión en el hogar fue de 30% aproximadamente. En el grupo paucisintomático, entre las personas seropositivas, la anosmia y la fiebre presentaron un OR de 16,8 (IC 95% 9,5-29,8) y 2,7 (IC 95% 1,6-4,6), respectivamente (p <0,001). En los pacientes asintomáticos, los niveles de IgG fueron inferiores en comparación con los pacientes paucisintomáticos, con tendencia a la baja pasados cuatro meses desde la aparición de los síntomas. Conclusiones. Se observó una seroprevalencia baja, indicadora de una gran población susceptible a la infección. La anosmia y la fiebre fueron factores predictivos independientes de relevancia para la seropositividad. Los pacientes asintomáticos mostraron niveles inferiores de anticuerpos durante el seguimiento de cinco meses. Los anticuerpos IgG tendieron a disminuir hacia el final del período con independencia de los síntomas.

[RESUMO]. Objetivo. Avaliar a soroprevalência de anticorpos contra a COVID-19 em indivíduos paucissintomáticos e assintomáticos, os fatores epidemiológicos associados e a cinética dos anticorpos da classe IgG em um período de 5 meses, visando aprimorar o conhecimento sobre a transmissibilidade da doença e a taxa de suscetíveis à infecção. Métodos. Inquérito transversal de soroprevalência realizado na população geral (amostra não probabilística) de Santa Fé, na Argentina, entre julho e novembro de 2020. Um subgrupo de 20 indivíduos soropositivos foi acompanhado para analisar a persistência de anticorpos IgG. O kit de ensaio imunoenzimático (ELISA) COVID-AR IgG® foi usado para a detecção de anticorpos IgG contra SARS-CoV-2. Resultados. A amostra compreendeu 3 000 indivíduos, divididos entre assintomáticos e paucissintomáticos (n = 1.500 por grupo). Deste total, somente 8,83% (n = 265) apresentaram reatividade, com a detecção de anticorpos IgG contra SARS-CoV-2. Observou-se uma associação significativa entre a presença de anticorpos IgG contra SARS-CoV-2 e histórico de contato com caso confirmado. A taxa de transmissão intradomiciliar foi de aproximadamente 30%. No grupo paucissintomático, entre os soropositivos, o odds ratio (OR) para anosmia foi de 16,8 (IC 95% 9,5–29,8), e para febre, 2,7 (IC 95% 1,6–4,6) (p <0,001). Os indivíduos assintomáticos apresentaram níveis de IgG mais baixos que os paucissintomáticos, com uma tendência de declínio após 4 meses do início dos sintomas. Conclusões. Observou-se uma soroprevalência baixa de anticorpos contra a COVID-19 na população estudada, o que indica um grande número de pessoas suscetíveis à infecção. Anosmia e febre foram preditores importantes independentes de soropositividade. Os assintomáticos apresentaram níveis mais baixos de anticorpos aos 5 meses de acompanhamento. Houve uma tendência de redução dos anticorpos IgG ao final deste período, independentemente da presença de sintomas.

Functional Autoreactive Anti-ß2 Adrenergic Antibodies May Contribute to Insulin Resistance Profile in Patients with Chronic Chagas Disease.

Potential activation of ß2 adrenergic receptors (ß2AR) by specific autoreactive antibodies (Abs) that arise during the host reaction to Trypanosoma cruzi, could contribute to the elevated prevalence of metabolic disturbances described in patients with chronic Chagas disease (CCD). This study aimed to determine the prevalence of anti-ß2AR Abs in patients with CCD, as well as the correlation of these Abs with the presence of glucose and lipid metabolism disturbances, in order to explore their association with an insulin resistance profile. Additionally, we tested the functional effects of anti-ß2AR Abs employing an in vitro bioassay with neuroendocrine cells expressing ß2AR. A clinical and metabolic evaluation including an OGTT was performed in 80 CCD patients and 40 controls. Anti-ß2AR Abs were measured by an in-house-developed ELISA, and the ß2 adrenergic activity of affinity-purified IgG fractions from patient' sera were assayed in CRE-Luc and POMCLuc transfected AtT-20 cells. A higher proportion of dysglycemia (72.5% vs. 37.5%; p = 0.001) was observed in the CCD group, accompanied by increased HOMA2-IR (p = 0.019), especially in subjects with Abs (+). Anti-ß2AR Abs reactivity (7.01 (2.39-20.5); p = 0.0004) and age >50 years (3.83 (1.30-11.25); p = 0.014) resulted as relevant for IR prediction (AUC: 0.786). Concordantly, Abs (+) CCD patients showed elevated metabolic risk scores and an increased prevalence of atherogenic dyslipidemia (p = 0.040), as compared to Abs (-) patients and controls. On functional bioassays, Abs exerted specific and dose-dependent ß2-agonist effects. Our findings suggest that anti-ß2AR Abs may induce the activation of ß2AR in other tissues besides the heart; furthermore, we show that in patients with CCD these Abs are associated with an insulin resistance profile and atherogenic dyslipidemia, providing biological plausibility to the hypothesis that adrenergic activation by anti-ß2AR Abs could contribute to the pathogenesis of metabolic disturbances described in CCD patients, increasing their cardiovascular risk.

Increased epicardial adipose tissue thickness associated with increased metabolic risk and the presence of heart failure in patients with Chronic Chagas disease.

BACKGROUND: It has been described that Trypanosoma cruzi is capable of promoting metabolic disturbances currently considered as cardiovascular risk factors. Moreover, it has been observed that the protozoa can remain in adipose tissue and alter its immune endocrine functions. The aim of this study was to characterize the thickness of epicardial adipose tissue (EAT) in patients with chronic Chagas disease (CCD) concerning their cardiovascular metabolic risk profile compared with those without CCD. METHODS: A cross-sectional study was performed including T. cruzi seropositive individuals categorized according to a standard CCD classification and a matched seronegative control group. Complete clinical examination, metabolic laboratory tests and transthoracic echocardiography to assess cardiac function and to quantify EAT were performed. RESULTS: Fifty-five individuals aged 46.7±11.9 y, 34 with CCD and 21 in the control group, were included. The CCD group presented higher EAT thickness in relation to controls (4.54±1.28 vs 3.22±0.99 mm; p=0.001), which was significantly associated with the presence of insulin resistance (OR=3, 95% CI 1.58 to 5.73; p<0.001). This group presented lower levels of plasmatic adiponectin than controls, especially in those patients with EAT ≥4.5 mm (p=0.005) who also presented with heart failure more frequently (p=0.01). CONCLUSION: In patients with CCD, a higher EAT thickness is observed and is associated with an increased metabolic risk profile indicated mainly by insulin resistance.

Congenital chagas disease: Development and assessment of a specific IgM capture-based assay for diagnosis of transmission.

Transplacental transmission by Trypanosoma cruzi (T. cruzi) infection can be effectively treated if parasiticide drugs are administered as early as possible during childhood. Furthermore, an ideal situation would be to diagnose the infection near birth in order to avoid the loss of patients during the subsequent follow-up. These situation are desirable due to the maximum benefit of drugs in early stages which, consequently, implies a relevant contribution to eliminate mother-to-child transmission. However, available techniques for that purpose have limitations as being operator-dependent (microhematocrit), require several months follow-up (IgG detection) or specialized laboratories (PCR). In this study we propose to detect specific IgM antibodies (Ab) by developing a capture-based ELISA employing an improved antigen (Ag) to diagnose the transplacental transmission of T. cruzi, and in consequence, to enhance access to effective treatment. Firstly, a new chimera Ag (CP4) was obtained from the fusion of CP1 and CP3 protein, carrying FRA, SAPA, MAP, TSSAII/V/VI and TcD Ag from T. cruzi. Then, we optimized the assay by capturing IgM Ab with a polyclonal anti-IgM Ab and evaluating three Ag formulations to detect specific IgM bound. The formulations were formed as follows: i) F1: CP1 and CP3; ii) F2: CP1, CP3, B13 and P2ß; iii) F3: by CP4. Detection of Ab-binding Ag was carried out using an anti-His Ab since all Ag were expressed with a His-tag. The evaluation panel consisted of sera from vertically infected children under 1-year-old (6 younger than 15 days, 7 older) and samples from non-infected children of women with chronic Chagas Disease. The ELISA assay employing CP4 showed better performance with notable high sensitivity and specificity (92.3% and 93.9%, respectively). Positive and negative likelihood ratios of the test (15.2 and 0.082) suggest its potential clinical relevance in term of post-test probability of infection. In conclution, we developed a standardized and non-operator dependent test to detect specific anti-T. cruzi IgM Ab. Although increased sample size is needed for its validation, our results indicate that this capture-based technique employing CP4 Ag can certainly improve the diagnosis of connatal infection.

Seroprevalence of anti-SARS-CoV-2 IgG in asymptomatic and pauci-symptomatic people over a 5 month survey in Argentina / Seroprevalencia de anticuerpos IgG contra el SARS-CoV-2 en personas asintomáticas y paucisintomáticas en un estudio de 5 meses en Argentina / Soroprevalência de IgG contra SARS-CoV-2 em indivíduos assintomáticos e paucissintomáticos em um inquérito de 5 meses na Argentina

ABSTRACT Objective. To evaluate the seroprevalence of COVID-19 infection in pauci-symptomatic and asymptomatic people, the associated epidemiological factors, and IgG antibody kinetic over a 5-month period to get a better knowledge of the disease transmissibility and the rate of susceptible persons that might be infected. Methods. Seroprevalence was evaluated by a cross-sectional study based on the general population of Santa Fe, Argentina (non-probabilistic sample) carried out between July and November 2020. A subgroup of 20 seropositive individuals was followed-up to analyze IgG persistence. For the IgG anti-SARS-CoV-2 antibodies detection, the COVID-AR IgG® ELISA kit was used. Results. 3 000 individuals were included conforming asymptomatic and pauci-symptomatic groups (n=1 500 each). From the total sample, only 8.83% (n=265) presented reactivity for IgG anti-SARS-CoV-2. A significant association was observed between positive anti-SARS-CoV-2 IgG and a history of contact with a confirmed case; the transmission rate within households was approximately 30%. In the pauci-symptomatic group, among the seropositive ones, anosmia and fever presented an OR of 16.8 (95% CI 9.5-29.8) and 2.7 (95% CI 1.6-4.6), respectively (p <0.001). In asymptomatic patients, IgG levels were lower compared to pauci-symptomatic patients, tending to decline after 4 months since the symptoms onset. Conclusion. We observed a low seroprevalence, suggestive of a large population susceptible to the infection. Anosmia and fever were independent significant predictors for seropositivity. Asymptomatic patients showed lower levels of antibodies during the 5-month follow-up. IgG antibodies tended to decrease over the end of this period regardless of symptoms.

RESUMEN Objetivo. Evaluar la seroprevalencia de la infección por el virus causante de la COVID-19 en personas paucisintomáticas y asintomáticas, los factores epidemiológicos asociados y la cinética de los anticuerpos IgG durante un período de cinco meses para conocer mejor la transmisibilidad de la enfermedad y la tasa de personas susceptibles a estar infectadas. Métodos. Se evaluó la seroprevalencia mediante un estudio transversal basado en la población general de Santa Fe, Argentina (muestra no probabilística) llevado a cabo entre julio y noviembre del 2020. Se realizó un seguimiento de un subgrupo de 20 personas seropositivas para analizar la persistencia de los anticuerpos IgG. Para la detección de los anticuerpos IgG contra SARS-COV-2, se empleó el kit ELISA COVID-AR IgG®. Resultados. Hubo 3 000 participantes divididos en un grupo asintomático y un grupo paucisintomático (n=1 500 cada grupo). De la muestra total, solo 8,83% (n=265) presentó una reactividad de IgG contra el SARS-CoV-2. Se observó una asociación significativa entre anticuerpos IgG positivos contra el SARS-CoV-2 y antecedente de contacto con un caso confirmado. La tasa de transmisión en el hogar fue de 30% aproximadamente. En el grupo paucisintomático, entre las personas seropositivas, la anosmia y la fiebre presentaron un OR de 16,8 (IC 95% 9,5-29,8) y 2,7 (IC 95% 1,6-4,6), respectivamente (p <0,001). En los pacientes asintomáticos, los niveles de IgG fueron inferiores en comparación con los pacientes paucisintomáticos, con tendencia a la baja pasados cuatro meses desde la aparición de los síntomas. Conclusiones. Se observó una seroprevalencia baja, indicadora de una gran población susceptible a la infección. La anosmia y la fiebre fueron factores predictivos independientes de relevancia para la seropositividad. Los pacientes asintomáticos mostraron niveles inferiores de anticuerpos durante el seguimiento de cinco meses. Los anticuerpos IgG tendieron a disminuir hacia el final del período con independencia de los síntomas.

RESUMO Objetivo. Avaliar a soroprevalência de anticorpos contra a COVID-19 em indivíduos paucissintomáticos e assintomáticos, os fatores epidemiológicos associados e a cinética dos anticorpos da classe IgG em um período de 5 meses, visando aprimorar o conhecimento sobre a transmissibilidade da doença e a taxa de suscetíveis à infecção. Métodos. Inquérito transversal de soroprevalência realizado na população geral (amostra não probabilística) de Santa Fé, na Argentina, entre julho e novembro de 2020. Um subgrupo de 20 indivíduos soropositivos foi acompanhado para analisar a persistência de anticorpos IgG. O kit de ensaio imunoenzimático (ELISA) COVID-AR IgG® foi usado para a detecção de anticorpos IgG contra SARS-CoV-2. Resultados. A amostra compreendeu 3 000 indivíduos, divididos entre assintomáticos e paucissintomáticos (n = 1.500 por grupo). Deste total, somente 8,83% (n = 265) apresentaram reatividade, com a detecção de anticorpos IgG contra SARS-CoV-2. Observou-se uma associação significativa entre a presença de anticorpos IgG contra SARS-CoV-2 e histórico de contato com caso confirmado. A taxa de transmissão intradomiciliar foi de aproximadamente 30%. No grupo paucissintomático, entre os soropositivos, o odds ratio (OR) para anosmia foi de 16,8 (IC 95% 9,5-29,8), e para febre, 2,7 (IC 95% 1,6-4,6) (p <0,001). Os indivíduos assintomáticos apresentaram níveis de IgG mais baixos que os paucissintomáticos, com uma tendência de declínio após 4 meses do início dos sintomas. Conclusões. Observou-se uma soroprevalência baixa de anticorpos contra a COVID-19 na população estudada, o que indica um grande número de pessoas suscetíveis à infecção. Anosmia e febre foram preditores importantes independentes de soropositividade. Os assintomáticos apresentaram níveis mais baixos de anticorpos aos 5 meses de acompanhamento. Houve uma tendência de redução dos anticorpos IgG ao final deste período, independentemente da presença de sintomas.

Objeción de conciencia como necesidad legal: una mirada desde el aborto / Conscientious objection as a legal need: a look from abortion / Objeção de consciência como necessidade legal: um olhar sobre o aborto

Resumen En la comunidad médica existen opiniones muy dispares frente al aborto. Nos proponemos analizar las premisas filosóficas que enmarcan la opinión de los médicos respecto a la legalización del aborto y corroborar cómo varían según la pertenencia generacional de los profesionales; así como establecer qué rol juega la objeción de conciencia para lograr un equilibrio ante la variedad de posturas existentes. Se realizaron entrevistas a médicos y a estudiantes de medicina interrogando si les parecía correcto o no legalizar el aborto y las razones en las cuales basaban sus posturas . Los médicos más jóvenes fueron quienes se mostraron a favor de la legalización en mayor proporción con argumentos brindados con una perspectiva en salud pública. Ante tan variadas posturas e idiosincrasias que conviven en el ámbito médico, la objeción de conciencia se erige como un instrumento legal necesario para proteger la integridad moral de cada persona.

Abstract In medical community there are very different opinions about abortion. We propose to analyze the philosophical premises that frame the opinion of doctors regarding the legalization of abortion and corroborate how they vary according to the generational belonging of professionals; as well as establishing the role that conscientious objection plays to achieve a balance against the variety of existing positions. We conducted semi-structured interviews to doctors and students about their opinion about abortion legalization and the reasons on which they based their positions. Younger physicians were who approved legalization in greater proportion with arguments offered with a public health perspective. Due to the great variability of positions and idiosyncrasies that coexist in the medical field, conscientious objection is established as a necessary legal instrument to protect the moral integrity of each person.

Resumo Na comunidade médica há opiniões muito diferentes sobre o aborto. Propomos analisar as premissas filosóficas que enquadram a opinião dos médicos sobre a legalização do aborto e corroborar como elas variam de acordo com a pertença geracional dos profissionais, bem como estabelecer que papel a objeção de consciência desempenha para alcançar um equilíbrio ante a variedade de posições existentes. Realizamos entrevistas semiestruturadas com médicos e estudantes sobre suas opiniões sobre a legalização do aborto e as razões que basearam suas posições. Os médicos mais jovens foram os que aprovaram a legalização em maior proporção com argumentos apoiados em perspectiva de saúde pública. Devido à grande variabilidade de posições e idiossincrasias que coexistem no campo da medicina, a objeção de consciência é estabelecida como um instrumento legal necessário para proteger a integridade moral de cada pessoa.

Antibody profiles induced by Trypanosoma cruzi in chagasic patients with previous or current exposure to mycobacteria.

Since the immune response mounted by the host to a particular microorganism might be influenced by the acquired immunological experience due to previous contact with other microorganisms, we performed a cross-sectional study to explore the pattern of Trypanosoma cruzi infection-related antibodies in T. cruzi-seropositive individuals presenting concomitant tuberculosis, or the antecedent of BCG vaccination. Sampled individuals were grouped as follows: patients with Chagas disease, not vaccinated with BCG, who further developed pulmonary tuberculosis; individuals with Chagas disease, BCG-vaccinated; and subjects with Chagas disease, presenting neither BCG scar nor tuberculosis disease. Non-vaccinated individuals or without tuberculosis, presented the highest values of anti-PH (P < 0.001), anti-FRA (P < 0.001), anti-p2ß (P = 0.0023) and anti-B13 (P < 0.001) antibodies. The present findings constitute the first demonstration of the potential influence of concomitant tuberculosis on Chagas disease.

IgG Autoantibodies Induced by T. cruzi During Pregnancy: Correlation with Gravidity Complications and Early Outcome Assessment of the Newborns.

Objective The aim of the present research was to evaluate the correlation of vertically transmitted IgG antibodies induced by T. cruzi and newborn early outcome assessment, mainly birth weight and gestational age. Methods We performed a cross-sectional study with 183 pregnant women (64 with asymptomatic Chagas disease) and their newborns. Both were subjected to complete clinical examination. Peripheral parasitemia was assessed in mother and neonates by parasite detection through microscopic examination of the buffycoat from mother's peripheral and cord blood. Antibodies induced by T. cruzi, such as anti-FRA, anti-B13, anti-p2ß and anti-T. cruzi were assessed by immunoassay. Birth weight, general condition evaluation by APGAR Score and gestational age by Capurro Score, were determined in newborns. Results The rate of stillbirth background and pregnancy-induced hypertension were higher in patients with Chagas disease (p = 0.01 and p = 0.02, respectively). Parasitemia was detectable in 17 mothers and 4 newborns. The newborns of mothers with detectable parasitemia presented decreased gestational age (p = 0.006) and body weight (p = 0.04). Mostly all the mothers with Chagas disease and all their newborns have positive values of antibodies induced by T. cruzi; however, only anti-p2ß showed to be related to the presence of complication during pregnancy (OR 2.35, p = 0.036), and to low birth weight (OR 1.55, p = 0.02). Conclusions Low birth weight and decreased postnatal estimation of maturity were related to detectable parasitemia in the mother. Also, vertical transmission of T. cruzi-induced autoantibodies might have clinical implication in newborns given the negative association between anti-p2ß values and weight.

The potential influence of atherogenic dyslipidemia on the severity of chronic Chagas heart disease.

INTRODUCTION: chronic Chagas heart disease (CCHD) is the most common manifestation of American Trypanosomiasis, causing about 50,000 deaths annually. Several factors bear correlation with the severity of CCHD. However, to our knowledge, the assessment on the contribution of major cardiovascular risk factors (CRF), such as hypertension and atherogenic dyslipidemia (AD) to CCHD severity is scarce, despite their well-established role in coronary artery disease, heart failure and stroke. OBJECTIVE: to explore the potential relationship of blood pressure and AD with the clinical profile of patients with CCHD. METHODS: we performed a cross-sectional study in T. cruziseropositive patients categorized according to a standard CCHD classification. All individuals were subjected to complete clinical examination. Autoantibodies induced by T. cruzi were assessed by ELISA. RESULTS: we observed that Atherogenic index (AI) levels rose significantly in relation to the severity of the CCHD stage, with CCHD III cases showing the highest values of AI. Furthermore, those patients with globally dilated cardiomyopathy with reduced ejection fraction showed higher levels of AI. In regard to autoantibodies, anti-B13 also showed relation with the severity of the disease. CONCLUSION: we observed that AI correlated with CCHD stages and contributed, in association with anti-B13 antibodies and age, to the prediction of systolic heart failure.

The potential influence of atherogenic dyslipidemia on the severity of chronic Chagas heart disease / Influencia de la dislipidemia aterogénica en la gravedad de la miocardiopatía chagásica crónica

SUMMARY Introduction: chronic Chagas heart disease (CCHD) is the most common manifestation of American Trypanosomiasis, causing about 50,000 deaths annually. Several factors bear correlation with the severity of CCHD. However, to our knowledge, the assessment on the contribution of major cardiovascular risk factors (CRF), such as hypertension and atherogenic dyslipidemia (AD) to CCHD severity is scarce, despite their well-established role in coronary artery disease, heart failure and stroke. Objective: to explore the potential relationship of blood pressure and AD with the clinical profile of patients with CCHD. Methods: we performed a cross-sectional study in T. cruziseropositive patients categorized according to a standard CCHD classification. All individuals were subjected to complete clinical examination. Autoantibodies induced by T. cruzi were assessed by ELISA. Results: we observed that Atherogenic index (AI) levels rose significantly in relation to the severity of the CCHD stage, with CCHD III cases showing the highest values of AI. Furthermore, those patients with globally dilated cardiomyopathy with reduced ejection fraction showed higher levels of AI. In regard to autoantibodies, anti-B13 also showed relation with the severity of the disease. Conclusion: we observed that AI correlated with CCHD stages and contributed, in association with anti-B13 antibodies and age, to the prediction of systolic heart failure.

RESUMO Introducción: la miocardiopatía chagásica (MCC) es la manifestación más común de la tripanosomiasis americana, causando cerca de 50.000 muertes al año. Varios factores se asocian con la gravedad de MCC. Sin embargo, la evaluación de la contribución de los principales factores de riesgo cardiovascular (FRC), como la hipertensión y la dislipidemia aterogénica (DA), a la gravedad de la MCC es escasa, a pesar de su papel bien establecido en la enfermedad arterial coronaria, insuficiencia cardíaca y accidente cerebrovascular. Objetivo: explorar la posible relación de la presión arterial y la DA con el perfil clínico de los pacientes con MCC. Método: estudio transversal en pacientes con serología positiva para T. cruzi categorizados de acuerdo a la clasificación estándar de MCC. Se realizó en todos los pacientes un examen clínico-cardiológico completo. Los autoanticuerpos inducidos por T. cruzi se evaluaron mediante ELISA. Resultados: se observó que los niveles de índice aterogénico (IA) aumentaron significativamente en relación con la gravedad de la etapa de la MCC, siendo que los pacientes pertenecientes al grupo MCC III mostraron los más altos valores de IA. Por otra parte, los pacientes con miocardiopatía dilatada global con fracción de eyección reducida mostraron mayores niveles de IA. En lo que respecta a autoanticuerpos, anti-B13 también mostró relación con la gravedad de la enfermedad. Conclusión: observamos que el IA se correlacionó con las etapas de MCC y contribuyó, en asociación con anticuerpos anti-B13, a la predicción de insuficiencia cardíaca sistólica.

Función barorrefleja y variabilidad de la presión arterial evaluadas desde el consultorio clínico / Baroreflex function and blood pressure variability evaluated in the clinical consulting room

La variabilidad de la frecuencia cardíaca (FC) y de la presión arterial (PA) se evalúan por lo general mediante Holter y monitorización ambulatoria de la presión arterial (MAPA). Estos exámenes no se encuentran disponibles generalmente en el medio hospitalario. Objetivo: Evaluar los parámetros de la función barorrefleja determinada por electrocardiograma basal y durante la realización de la maniobra de Valsalva (MV), con los indicadores de variabilidad de FC por Holter y PA por MAPA. Métodos: Estudio transversal, observacional. Se incluyeron prospectivamente pacientes adultos, sin enfermedades ni utilización de fármacos que modifiquen la FC o la PA. Se realizó electrocardiograma (ECG) basal de 10 s. La respuesta cronotrópica se evaluó mediante MV estandarizada registrada en ECG. Se realizaron MAPA y Holter de 12 horas. Resultados: Se estudiaron 50 pacientes, observándose que el SDNN del ECG de 10 sy la variación de la FC intra/previa a la MV podrían resultar de utilidad para estimar el valor del SDNN del Holter, parámetro asociado con hipofunción barorrefleja y aumento de riesgo vascular. En cuanto a la PA, no pudo demostrarse mayor variabilidad de PA sistólica por MAPA en los pacientes con disminuciónde la respuesta cronotrópica. Conclusión: Indicadores simples de determinar en el consultorio clínico realizando ECG y MV podrían complementar la evaluación del riesgo cardiovascular y contribuira seleccionar aquellos pacientes en quienes sería conveniente efectuar un estudio de MAPA, tanto paradiagnóstico como para seguimiento...

In-hospital mortality risk factors in community acquired pneumonia: evaluation of immunocompetent adult patients without comorbidities.

OBJECTIVE: several scores were developed in order to improve the determination of community acquired pneumonia (CAP) severity and its management, mainly CURB-65 and SACP score. However, none of them were evaluated for risk assessment of in-hospital mortality, particularly in individuals who were non-immunosuppressed and/or without any comorbidity. In this regard, the present study was carried out. METHODS: we performed a cross-sectional study in 272 immunocompetent patients without comorbidities and with a diagnosis of CAP. Performance of CURB- 65 and SCAP scores in predicting in-hospital mortality was evaluated. Also, variables related to death were assessed. Furthermore, in order to design a model of in-hospital mortality prediction, sampled individuals were randomly divided in two groups. The association of the variables with mortality was weighed and, by multiple binary regression, a model was constructed in one of the subgroups. Then, it was validated in the other subgroup. RESULTS: both scores yielded a fair strength of agreement, and CURB-65 showed a better performance in predicting in-hospital mortality. In our casuistry, age, white blood cell counts, serum urea and diastolic blood pressure were related to death. The model constructed with these variables showed a good performance in predicting in-hospital mortality; moreover, only one patient with fatal outcome was not correctly classified in the group where the model was constructed and in the group where it was validated. CONCLUSION: our findings suggest that a simple model that uses only 4 variables, which are easily accessible and interpretable, can identify seriously ill patients with CAP.

In-hospital mortality risk factors in patients with ascites due to cirrhosis.

INTRODUCTION: ascites is one of the most common complications of cirrhosis associated with a high rate of mortality. Although several scores have been developed in order to assess the prognosis of the disease, they were designed for predicting liver transplantation requirements and mortality in the short term, but not while in hospital. The aim of this study was to weigh risk factors for in-hospital mortality in adult patients with ascites due to alcoholic cirrhosis. MATERIAL AND METHODS: we performed a cross-sectional study in 180 adult patients with diagnosis of cirrhosis with portal hypertension associated with high alcohol intake. The diagnosis of cirrhosis was made by liver echography and portal hypertension was defined by clinical features plus serum-ascites albumin gradient. Sampled individuals were subjected to complete clinical examination. Child Pugh and the MELD scores were applied in all the patients. RESULTS: nineteen patients died while in-hospital. Mortality was associated with increased levels of serum white blood cell, urea, creatinine, prolonged prothrombin time, aspartate aminotransferase and alanine aminotransferase. We conducted a multiple binary logistic to predict in-hospital mortality which yielded that serum urea, creatinine and prothrombin time made a significant contribution to prediction with an OR 14 (95% CI 12.8 - 16.7 p = 0.03), 2 (95% CI 0.5 - 3.47, p = 0.04), and 2 (95% CI 1.03 - 2.31, p = 0.01) linearly-related. CONCLUSIONS: our results suggest that acute renal failure and prolonged prothrombin time are predictors of in-hospital mortality in patients with portal hypertension due to alcoholic cirrhosis.

In-hospital mortality risk factors in community acquired pneumonia: evaluation of immunocompetent adult patients without comorbidities / Fatores de risco para mortalidade intra-hospitalar em pneumonia adquirida em comunidade: avaliação de pacientes imunocompetentes sem comorbidades

Summary Objective: several scores were developed in order to improve the determination of community acquired pneumonia (CAP) severity and its management, mainly CURB-65 and SACP score. However, none of them were evaluated for risk assessment of in-hospital mortality, particularly in individuals who were non-immunosuppressed and/or without any comorbidity. In this regard, the present study was carried out. Methods: we performed a cross-sectional study in 272 immunocompetent patients without comorbidities and with a diagnosis of CAP. Performance of CURB- 65 and SCAP scores in predicting in-hospital mortality was evaluated. Also, variables related to death were assessed. Furthermore, in order to design a model of in-hospital mortality prediction, sampled individuals were randomly divided in two groups. The association of the variables with mortality was weighed and, by multiple binary regression, a model was constructed in one of the subgroups. Then, it was validated in the other subgroup. Results: both scores yielded a fair strength of agreement, and CURB-65 showed a better performance in predicting in-hospital mortality. In our casuistry, age, white blood cell counts, serum urea and diastolic blood pressure were related to death. The model constructed with these variables showed a good performance in predicting in-hospital mortality; moreover, only one patient with fatal outcome was not correctly classified in the group where the model was constructed and in the group where it was validated. Conclusion: our findings suggest that a simple model that uses only 4 variables, which are easily accessible and interpretable, can identify seriously ill patients with CAP .

Resumo Objetivo: diversos escores de gravidade da pneumonia adquirida em comunidade (PAC) foram desenvolvidos com o intuito de melhorar o manejo clínico, em especial os escores CURB-65 e SCAP. Contudo, nenhum dos dois foi avaliado para determinar o risco de morte intra- hospitalar, principalmente em pacientes imunocompetentes e/ou sem comorbidades. Diante disso, propusemo- nos a analisar a utilidade dos escores para prever a mortalidade intra-hospitalar e estudar as variáveis associadas ao desfecho fatal. Métodos: desenvolvemos um trabalho transversal com 272 pacientes imunocompetentes, sem comorbidades e com diagnóstico de PAC. Foi avaliada a eficácia dos escores CURB-65 e SCAP em prever a mortalidade durante a internação. Foram estudadas as variáveis relacionadas a este desfecho. Por fim, a amostra foi dividida em dois subgrupos com o objetivo de desenvolver um modelo de avaliação do risco de morte em um subgrupo, validando-o no outro. Resultados: ambos os escores apresentaram pobre concordância de classificação da gravidade para PAC. O escore CURB-65 mostrou melhor desempenho na avaliação do risco de morte. Em nossa amostra, idade, contagem de glóbulos brancos, ureia sérica e pressão arterial diastólica foram as variáveis que se associaram à mortalidade. O modelo desenvolvido com essas variáveis mostrou eficácia muito boa para prever o desfecho fatal. Inclusive, somente um paciente no grupo de desenvolvimento do modelo e outro no grupo de validação foram classificados de modo incorreto. Conclusão: nossos resultados sugerem que com um modelo de quatro variáveis, de fácil acesso e interpretação, foi possível identificar pacientes gravemente enfermos com PAC. .

In-hospital mortality risk factors in patients with ascites due to cirrhosis / Fatores de risco de mortalidade intra-hospitalar em pacientes com ascite por cirrose hepática

Introduction: ascites is one of the most common complications of cirrhosis associated with a high rate of mortality. Although several scores have been developed in order to assess the prognosis of the disease, they were designed for predicting liver transplantation requirements and mortality in the short term, but not while in hospital. The aim of this study was to weigh risk factors for in-hospital mortality in adult patients with ascites due to alcoholic cirrhosis. Material and methods: we performed a cross-sectional study in 180 adult patients with diagnosis of cirrhosis with portal hypertension associated with high alcohol intake. The diagnosis of cirrhosis was made by liver echography and portal hypertension was defined by clinical features plus serum-ascites albumin gradient. Sampled individuals were subjected to complete clinical examination. Child Pugh and the MELD scores were applied in all the patients. Results: nineteen patients died while in-hospital. Mortality was associated with increased levels of serum white blood cell, urea, creatinine, prolonged prothrombin time, aspartate aminotransferase and alanine aminotransferase. We conducted a multiple binary logistic to predict in-hospital mortality which yielded that serum urea, creatinine and prothrombin time made a significant contribution to prediction with an OR 14 (95% CI 12.8 - 16.7 p = 0.03), 2 (95% CI 0.5 - 3.47, p = 0.04), and 2 (95% CI 1.03 - 2.31, p = 0.01) linearly-related. Conclusions: our results suggest that acute renal failure and prolonged prothrombin time are predictors of in-hospital mortality in patients with portal hypertension due to alcoholic cirrhosis. .

Introdução: ascite é uma das complicações mais comuns de cirrose associadas a uma elevada taxa de mortalidade. Embora vários escores tenham sido desenvolvidos a fim de avaliar o prognóstico da doença, eles foram concebidos para prever requisitos de transplante de fígado e mortalidade a curto prazo, mas não durante a internação. O objetivo deste estudo foi o de pesar fatores de risco para a mortalidade intra-hospitalar em pacientes adultos com ascite decorrente de cirrose alcoólica. Material e métodos: foi realizado um estudo transversal em 180 pacientes adultos com diagnóstico de cirrose com hipertensão portal, associada à alta ingestão de álcool. O diagnóstico de cirrose foi feita por ecografia hepática e a hipertensão portal foi determinada por características clínicas e pelo gradiente de albumina soro-ascite. Indivíduos avaliados foram submetidos a exame clínico completo. A classificação de Child-Pugh e a escala MELD foram aplicadas em todos os pacientes. Resultados: dezenove pacientes morreram durante a internação. A mortalidade foi associada ao aumento dos níveis de glóbulos brancos, ureia, creatinina, aspartato aminotransferase, alanina aminotransferase e tempo de protrombina prolongado. Realizamos uma logística binária múltipla para prever a mortalidade intra-hospitalar, que confirmou que ureia, creatinina e tempo de protrombina contribuíram significativamente para a previsão, com uma OR = 14 (IC 95% 12,8-16,7 p = 0,03), 2 (IC 95% 0,5-3,47, p = 0,04), e 2 (IC 95% 1,03-2,31, p = 0,01), relacionada linearmente. Conclusões: nossos resultados sugerem que a insuficiência renal aguda e de tempo de protrombina prolongado são preditores de mortalidade intra-hospitalar em pacientes com hipertensão portal decorrente de cirrose alcoólica. .

Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease.

Recombinant protein vaccines are safe but elicit low immunological responses. The new generation of adjuvants is currently reversing this situation. Here, a new antigen-adjuvant combination for protection against experimental Chagas disease was assessed. The antigen used in the formulation was a glycosylated mutant inactive trans-sialidase (mTS) that was previously proven to be highly protective against Trypanosoma cruzi infection; here, we show that it can be produced in large quantities and high quality using Pichia pastoris. The adjuvant used in the formulation was ISCOMATRIX (IMX), which was found to be effective and safe in human clinical trials of vaccines designed to control other intracellular infections. Fifteen days after the third immunization, mice immunized with mTS-IMX showed a TS-specific IgG response with titers >10(6) and high avidity, an increased IgG2a/IgG1 ratio, significant delayed-type hypersensitivity (DTH) reactivity, a balanced production of IFN-γ and IL-10 by splenocytes and a strong IFN-γ secretion by CD8(+) T lymphocytes. When these mice where challenged with 1000 trypomastigotes of T. cruzi, all mTS-IMX immunized mice survived, whereas mice immunized with mTS alone, IMX or PBS exhibited high mortality. Remarkably, during acute infection, when the parasitemia is highest in this infection model (day 21), mTS-IMX immunized mice had ∼50 times less parasitemia than non-immunized mice. At this moment and also in the chronic phase, 100 days after infection, tissue presented ∼4.5 times lower parasite load and associated inflammatory infiltrate and lesions. These results indicate that protection against Chagas disease can be achieved by a protein antigen-adjuvant mTS formulation that is compatible with human medicine. Therefore, the current formulation is a highly promising T. cruzi vaccine candidate to be tested in clinical trials.

Preparation and characterization of a Staphylococcus aureus capsular polysaccharide-protein conjugate prepared by a low cost technique: a proof-of-concept study.

Staphylococcus aureus is a worldwide distributed pathogen that produces several diseases in many species and is the major cause of mastitis in dairy cows. S. aureus capsular polysaccharide 5 (CP5) has been widely proposed as a vaccine candidate since it is expressed in a high proportion of isolates from intramammary infections and is able to induce opsonophagocytic antibodies. However, to reach immunological properties, polysaccharides need to be coupled to carrier proteins. The aim of this study was to evaluate a conjugation method employing p-benzoquinone (PBQ), which was not previously reported for the development of vaccine components. Purified S. aureus CP5 was coupled to human serum albumin (HSA) with high efficiency, reaching a rate PS/protein of 0.5. Mice groups were immunized at days 0, 14, 28, and 42, with the conjugate (CP5-HSAPBQ), free CP5, or PBS, formulated with incomplete Freund adjuvant, and after 3 months, they were challenged with free CP5 to evaluate the memory response. IgG and IgM isotypes were measured on serum samples all along the experiment, and IgG subclasses were determined to analyze the humoral profile. In contrast to the response obtained with free CP5, CP5-HSAPBQ induced IgG titers of 1/238,900 after three doses and a memory response was observed after the challenge. Results indicate that immunization with CP5-HSAPBQ effectively induce a T-dependent immune response against CP5. Moreover, besides IgG2a was the main subtype obtained, the joint production of specific IgG1, IgG2b, and IgG3 types indicated a balanced humoral response. As p-benzoquinone conjugation of CPs to proteins is far less expensive and straightforward than other methods commonly used in vaccine preparations, the robust humoral response obtained using this method points out that this can be an interesting alternative to prepare S. aureus CP5 conjugate vaccines.

Chagas disease, a risk factor for high blood pressure.

BACKGROUND: Chagas disease is a parasite infection caused by the protozoan Trypanosoma cruzi. Its most common complications is chronic Chagas heart disease but impairments of the systemic vasculature also has been observed. Although the different mechanisms that regulate blood pressure are disrupted, to our knowledge data on the association of hypertension and chronic Chagas disease are scarce. In this regard we evaluate whether Chagas disease constitutes a high blood pressure risk factor. MATERIALS AND METHODS: We recruited 200 individuals, half of them with positive serology for T. cruzi. They were subjected to a complete clinical examination. RESULTS: The mean age of sampled individuals was 46.7 ± 12.3, and the mean of systolic and diastolic blood pressure were 124 ± 12 mmHg and 82 ± 10 mmHg, respectively. There were no between-group differences regarding age, sex distribution or body mass index. Chagas disease contributed significantly to high blood pressure (OR = 4, 95% CI 1.8323-7.0864, p = 0.0002). CONCLUSION: Our results reveal an important association between Chagas disease and high blood pressure, which should be contemplated by physicians in order to promote preventive cardiovascular actions in patients with Chagas disease.