Dengue en paciente de 32 días de vida. Reporte de un caso poco habitual / Dengue fever in a 32-day-old patient. A rare case report

El dengue es una enfermedad viral transmitida por la picadura del mosquito Aedes aegypti. El comportamiento del dengue en Argentina es epidémico; la mayoría de los casos se observan en los meses de mayor temperatura. Hasta la semana epidemiológica (SE) 20/2023, se registraron en Argentina 106 672 casos; se vieron afectadas 18 de las 24 provincias que conforman el país. Dentro de los principales grupos de riesgo, se incluyen los menores de 2 años. Reconocer los signos, síntomas e identificar los factores de riesgo es fundamental para el manejo de casos con mayor riesgo de gravedad. Presentamos el caso de una paciente de 32 días de vida que se internó por síndrome febril sin foco, con diagnósticos diferenciales de meningitis viral y sepsis, evolucionó con leucocitosis, plaquetopenia, hipoalbuminemia, asociado a exantema y edemas. Se llegó al diagnóstico de dengue por la clínica, epidemiologia e IgM positiva.

Dengue fever is a viral disease transmitted by the Aedes aegypti mosquitoes. In Argentina, dengue fever is an epidemic disease; most cases are reported during the hot months.Until epidemiological week (EW) 20/2023, 106 672 cases were reported across 18 of the 24 provinces of Argentina. Children younger than 2 years are among the main groups at risk. Recognizing signs and symptoms and identifying risk factors is fundamental for the management of cases at a higher risk of severity. Here we describe the case of a 32-day-old female patient who was hospitalized due to febrile syndrome without a source, who had a differential diagnosis of viral meningitis and sepsis and progressed to leukocytosis, thrombocytopenia, hypoalbuminemia in association with rash and edema. The diagnosis of dengue fever was established based on clinical, epidemiological, and positive IgM data.

Resistencia a los inhibidores de la integrasa en niños con el virus de la inmunodeficiencia humana por transmisión vertical: primeros casos en Uruguay / Resistance to integrase inhibitors in children with vertically-transmitted human immunodeficiency virus: First cases in Uruguay

La resistencia a los antirretrovirales (ARV) es un problema de salud pública. Con el uso de inhibidores de la integrasa (INSTI) en pediatría, también comienzan a aparecer resistencias. El objetivo de esta comunicación es describir 3 casos con resistencia a los INSTI. Se describen 3 pacientes pediátricos con transmisión vertical del virus de la inmunodeficiencia humana (VIH). Iniciaron ARV de lactantes y preescolares, con mala adherencia al tratamiento, cursaron con diferentes planes secundarios a comorbilidades asociadas y fallas virológicas por resistencia. Los 3 casos clínicos describen la rápida aparición de resistencia frente a la falla virológica y el compromiso de los INSTI. La adherencia debe ser supervisada para detectar precozmente el aumento de la viremia. La falla virológica en un paciente tratado con raltegravir obliga a un rápido cambio de esquema ARV, ya que continuar utilizándolo podría favorecer nuevas mutaciones y resistencia a los INSTI de segunda generación.

Antiretroviral (ARV) drug resistance is a public health issue. Resistance has also been observed in the case of integrase strand transfer inhibitors (INSTIs) used in pediatrics. The objective of this article is to describe 3 cases of INSTI resistance. These are the cases of 3 children with vertically-transmitted human immunodeficiency virus (HIV). They were started on ARVs as infants and preschoolers, with poor treatment adherence, and had different management plans due to associated comorbidities and virological failure due to resistance. In the 3 cases, resistance developed rapidly as a result of virological failure and INSTI involvement. Treatment adherence should be monitored so that any increase in viremia can be detected early. Virological failure in a patient treated with raltegravir forces to a rapid change in ARV therapy because its continued use may favor new mutations and resistance to second-generation INSTIs.

Manifestaciones cutáneas comunes de las principales enfermedades hepáticas / Common cutaneous manifestations of major liver diseases

Las enfermedades hepáticas presentan múltiples manifestaciones sistémicas, entre las cuales se destacan los hallazgos en piel, siendo los más comunes el prurito y la ictericia; así mismo, se pueden encontrar angiomas en araña, eritema palmar, xantomas, vasculitis y cambios en anexos. Este artículo tiene como objetivo describir los principales signos y síntomas cutáneos en las enfermedades hepáticas para brindar herramientas semiológicas al clínico en su práctica diaria

Liver disease present multiple systemic manifestations, among which skin findings stand out, being the most common pruritus and jaundice. Other findings can also be manifested like spider angiomas, palmar erythema, xanthomas, vasculitis and changes in skin appendages. The objective of this article is to describe the main skin signs and symptoms of liver diseases to provide semiological tools to the physician in his daily practice.

Biological principles for "homotherapy for heteropathy" / 药学学报

Non-infectious chronic diseases in human including diabetes, non-alcoholic fatty liver disease (NAFLD), atherosclerosis (AS), neurodegenerative diseases, osteoporosis, as well as malignant tumors may have some common pathogenic mechanisms such as non-resolved inflammation (NRI), gut microbiota dysfunction, endoplasmic reticulum stress, mitochondria dysfunction, and abnormality of the mammalian target of rapamycin (mTOR) pathway. These pathogenic mechanisms could be the basis for "homotherapy for heteropathy" in clinic. Some commonly used clinical drugs, such as metformin, berberine, aspirin, statins, and rapamycin may execute therapeutic effect on their targeted diseases,and also have the effect of "homotherapy for heteropathy". The mechanisms of the above drugs may include anti-inflammation, modulation of gut microbiota, suppression of endoplasmic reticulum stress, improvement of mitochondria function, and inhibition of mTOR. For virus infectious diseases, as some viruses need certain commonly used replicases, the inhibitors of the replicases become examples of "homotherapy for heteropathy" for antiviral therapy in clinic (for example tenofovir for both AIDS and HBV infection). Especially, in case of outbreak of new emerging viruses, these viral enzyme inhibitors such as azvudine and sofibuvir, could be rapidly used in controlling viral epidemic or pandemic, based on the principle of "homotherapy for heteropathy". In this review article, we show the research progress of the biological basis for "homotherapy for heteropathy" and the possible mechanisms of some well-known drugs, in order to provide insights and new references for innovative drug R&D.

Virus spectrum of inpatients with acute respiratory infection in Pudong New Area , Shanghai / 公共卫生与预防医学

Objective To understand the viral spectrum of inpatients with acute respiratory infection in Pudong New Area, and to explore the composition of pathogens in hospitalized children and adults. Methods Samples of acute respiratory infection cases from 10 medical institutions were collected from 2011 to 2020 and tested for human influenza virus, human adenovirus, rhinovirus, human parainfluenza virus, respiratory syncytial virus, human coronavirus, human metapneumovirus and human boca virus. Results A total of 3 145 inpatients were monitored, with a median age of 61 years. The positive rate of any virus was 32.43% (1 020/3 145), and the single virus infection accounted for 85.98% (877/1 020). In single virus infection, the positive rate of human influenza virus was the highest (9.67%, 304/3 145), with influenza A (80.26%, 244/304) as the main virus. The second was rhinovirus (3.97%, 125/3 145). The positive rate of any virus in different age groups was statistically significant (χ2=103.38，P2=123.06，P2=90.37，P<0.001). Conclusion The positive rate of virus in hospitalized patients with acute respiratory infection is relatively high in Pudong New Area, Shanghai, with human influenza virus being the main virus. The virus spectrum of hospitalized children and adults is inconsistent. In the future, in-depth research should be strengthened, focusing on the distribution of pathogens in different populations and seasonal prevention and treatment.

Significance of high-sensitivity polymerase chain reaction in detecting hepatitis B virus in chronic hepatitis B patients with a very low viral load / 临床肝胆病杂志

ObjectiveTo investigate the significance of high-sensitive polymerase chain reaction （PCR） in detecting hepatitis B virus （HBV） among the population with a very low viral load （HBV DNA 10‍ — ‍99 IU/mL）. MethodsThis study was conducted among the chronic hepatitis B （CHB） patients who were treated with nucleos（t）ide analogues for ≥48 weeks in The Fifth Affiliated Hospital of Guangzhou Medical University from September 2019 to February 2022 and had an HBV DNA load below the lower limit of ordinary-sensitivity detection （100 IU/mL）. Then high-sensitivity HBV DNA detection was performed for all patients， and according to these results， the patients were divided into very low viral load group （VLVL group with an HBV DNA load of 10‍ — ‍99 IU/mL） and complete virologic response group （CVR group with an HBV DNA load of <10 IU/mL or without HBV DNA detected）. The two groups were compared in terms of general characteristics， serum virological indicators， biochemical parameters， and noninvasive fibrosis markers； the value of related serum virological indicators in predicting the results of high-sensitivity HBV DNA above the lower limit of detection were assessed； the influencing factors for failure to achieve CVR were analyzed. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The receiver operating characteristic （ROC） curve was used to investigate the value of related serum virological indicators in predicting the results of high-sensitivity HBV DNA above the lower limit of detection， and a binary logistic regression analysis was used to investigate the influencing factors for failure to achieve CVR. ResultsA total of 106 CHB patients were enrolled， with 24 in the VLVL group and 82 in the CVR group. Compared with the CVR group， the VLVL group had a significantly younger age （P=0.004） and significantly higher quantitative hepatitis B surface antigen （qHBsAg） level （P=0.002）， HBeAg positive rate （P=0.002）， pgRNA positive rate （P=0.010）， and alanine aminotransferase level （P=0.017）. The qHBsAg level had an area under the ROC curve of 0.717 （P=0.002） in predicting the results of high-sensitivity HBV DNA above the lower limit of detection （>10 IU/mL）， with an optimal cut-off value of 1 214.5 IU/mL， a sensitivity of 95.5%， and a specificity of 53.9%. Positive HBeAg （odds ratio ［OR］=3.654， 95% confidence interval ［CI］： 1.162‍ —‍ ‍11.489， P=0.027） and qHBsAg （OR=2.985， 95%CI： 1.058‍ — ‍8.422， P=0.039） were independent influencing factors for failure to achieve CVR. ConclusionSome CHB patients have an HBV DNA load of <100 IU/mL by ordinary-sensitivity detection， but with the presence of VLVL determined by high-sensitivity PCR. The VLVL group had significantly higher level of inflammatory damage and positive rates of pgRNA and HBeAg. Positive HBeAg and high qHBsAg level are independent influencing factors for failure to achieve CVR. Clinicians should not ignore the presence of VLVL in CHB patients， and high-sensitivity HBV DNA detection should be performed in a timely manner.

Clinical follow-up study of SARS-CoV-2 Omicron infection / 上海预防医学

ObjectiveTo observe the clinical course and explore the risk factors for SARS-CoV-2 RNA negative conversion duration （NCD） in asymptomatic and mild-symptomatic patients infected with the SARS-CoV-2 Omicron variant. MethodsClinical data were collected from 244 confirmed cases of corona virus disease （COVID-19） with Omicron variant infection admitted to a temporal makeshift hospital in Shanghai from April 9， 2022 to May 20， 2022. Demographic and clinical data were analyzed， with a primary focus on the time of COVID-19 nucleic acid conversion. Univariate and multivariate Cox regression analysis were used to determine identify risk factors associated with NCD. ResultsThe median duration of negative RNA conversion was 9 days （ranged 7‒12 days）. The percentage of patients with positive nucleic acid results on the 5th， 7th， 10th， and 14th days after confirmed infection was 68.4%， 47.1%， 20.1%， and 5.7%， respectively. Kaplan-Meier curves indicated a median nucleic acid conversion time of 12 days （ranged 10‒14 days） for patients with hypertension， 9 days （ranged 7‒11 days） in patients without hypertension， and 11 days （ranged 9‒13 days） for patients aged ≥60 years， and 9 days （ranged 7‒11 days） for patients aged <60 years. Multivariate Cox regression analysis showed that only hypertension was an independent risk factor of NCD （RR=1.60； 95% CI： 1.03‒2.49， P=0.036）. ConclusionIn asymptomatic or mildly symptomatic patients infected with the Omicron variant， 20.1% patients continue to exhibit positive viral nucleic acid on the 10th days of infection. The independent risk factor associated with the conversion of SARS-CoV-2 nucleic acid to negative is hypertension.

Long-term outcomes for epidemic viral pneumonia survivors after discharge from the intensive care unit: a systematic review

ABSTRACT Objective To review the long-term outcomes (functional status and psychological sequelae) of survivors of critical illnesses due to epidemic viral pneumonia before the COVID-19 pandemic and to establish a benchmark for comparison of the COVID-19 long-term outcomes. Methods This systematic review of clinical studies reported the long-term outcomes in adults admitted to intensive care units who were diagnosed with viral epidemic pneumonia. An electronic search was performed using databases: MEDLINE®, Web of Science™, LILACS/IBECS, and EMBASE. Additionally, complementary searches were conducted on the reference lists of eligible studies. The quality of the studies was assessed using the Newcastle-Ottawa Scale. The results were grouped into tables and textual descriptions. Results The final analysis included 15 studies from a total of 243 studies. This review included 771 patients with Influenza A, Middle East Respiratory Syndrome, and Severe Acute Respiratory Syndrome. It analyzed the quality of life, functionality, lung function, mortality, rate of return to work, rehospitalization, and psychiatric symptoms. The follow-up periods ranged from 1 to 144 months. We found that the quality of life, functional capacity, and pulmonary function were below expected standards. Conclusion This review revealed great heterogeneity between studies attributed to different scales, follow-up time points, and methodologies. However, this systematic review identified negative long-term effects on patient outcomes. Given the possibility of future pandemics, it is essential to identify the long-term effects of viral pneumonia outbreaks. This review was not funded. Prospero database registration: (www.crd.york.ac.uk/prospero) under registration ID CRD42021190296.

Prevención de las hepatitis virales crónicas como contenido de la superación del Equipo Básico de Salud

Introducción: Entre las causas más frecuentes de mortalidad se encuentran las enfermedades infecciosas, en particular en el tercer mundo. Y entre estas, están las hepatitis virales crónicas, las cuales aumentan su incidencia en Cuba. Objetivo: Exponer elementos de un sistema de superación dirigido al desarrollo de los conocimientos en los miembros del Equipo Básico de Salud del Policlínico Docente José Martí de la provincia de Camagüey, Cuba, sobre la prevención de las hepatitis virales crónicas en la Atención Primaria de Salud. Método: Se desarrolló una investigación participativa cuanticualitativa de carácter explicativo causal, mediante la ejecución del proyecto de investigación no asociado a programa Sistema de estrategias para la prevención de las hepatitis virales crónicas, desde la consulta provincial, ejecutado entre 2017 y 2022. El universo involucró 137 profesionales para una muestra de 68. Resultados: Los profesionales adquirieron nuevas experiencias, reconocieron la necesidad de capacitación, así como la comprensión de su vínculo con los pacientes que padecen estas enfermedades para advertir el riesgo que corren al no acudir a los servicios de salud para ser diagnosticados y tener un seguimiento con los servicios de la Atención Primaria de Salud. Predominó el índice alto como calificación de las preguntas del instrumento de salida para todos los participantes. Conclusiones: El sistema favorece el desarrollo de los conocimientos sobre la prevención de las hepatitis virales crónicas del Equipo Básico de Salud objeto de estudio. Las acciones potencian la participación de los actores de la comunidad y sus sesiones de intercambio se distinguen por su carácter activo, dinámico y funcional, en pos de una mejor práctica asistencial, preventiva de las hepatitis virales crónicas en el nivel primario.

Introduction: Among the most frequent causes of mortality are infectious diseases, particularly in the third world. And among these are chronic viral hepatitis, which increases its incidence in Cuba. Objective: To present elements of an improvement system aimed at developing knowledge in the members of the Basic Health Team of the José Martí Teaching Polyclinic in the province of Camagüey, Cuba, on the prevention of chronic viral hepatitis in Primary Health Care. Method: A quantitative participatory research of a causal explanatory nature was developed, through the execution of the research project not associated with the System of Strategies for the Prevention of Chronic Viral Hepatitis program, from the provincial consultation, executed between 2017 and 2022. The universe involved 137 professionals for a sample of 68. Results: Professionals acquired new experiences, recognized the need for training, as well as understanding their relationship with patients who suffer from these diseases to warn of the risk they run by not going to health services, to be diagnosed and have follow-up with Primary Health Care services. The high index predominated as the rating of the output instrument questions for all participants. Conclusions: The system favors the development of knowledge on the prevention of chronic viral hepatitis of the Basic Health Team under study. The actions enhance the participation of community actors and their exchange sessions are distinguished by their active, dynamic and functional nature, in pursuit of better care practice, preventive of chronic viral hepatitis at the primary level.

Introdução: Entre as causas mais frequentes de mortalidade estão as doenças infecciosas, principalmente no terceiro mundo. E entre estas estão as hepatites virais crónicas, que aumentam a sua incidência em Cuba. Objetivo: Apresentar elementos de um sistema de melhoria que visa desenvolver conhecimentos nos membros da Equipe Básica de Saúde da Policlínica Escolar José Martí, na província de Camagüey, Cuba, sobre a prevenção das hepatites virais crônicas na Atenção Primária à Saúde. Método: Desenvolveu-se uma pesquisa quantitativa participativa de natureza causal explicativa, através da execução do projeto de pesquisa não vinculado ao programa Sistema de Estratégias de Prevenção das Hepatites Virais Crônicas, a partir da consulta provincial, executada entre 2017 e 2022. O universo envolveu 137 profissionais para uma amostra de 68. Resultados: Os profissionais adquiriram novas experiências, reconheceram a necessidade de capacitação, bem como compreenderam sua relação com os pacientes que sofrem dessas doenças para alertar sobre o risco que correm ao não procurarem os serviços de saúde. ser diagnosticado e ter acompanhamento nos serviços de Atenção Primária à Saúde. O índice alto predominou na classificação das questões do instrumento de saída para todos os participantes. Conclusões: O sistema favorece o desenvolvimento do conhecimento sobre a prevenção das hepatites virais crônicas da Equipe Básica de Saúde em estudo. As ações potenciam a participação dos atores comunitários e as suas sessões de intercâmbio distinguem-se pelo seu caráter ativo, dinâmico e funcional, na procura de melhores práticas assistenciais, preventivas das hepatites virais crónicas no nível primário.

Aspects that facilitate access to care for viral hepatitis: An evaluative research

ABSTRACT BACKGROUND: Viral hepatitis is a major public health concern worldwide. OBJECTIVES: This study aimed to analyze the factors that facilitate access to care for viral hepatitis. DESIGN AND SETTING: Using a sequential mixed method, this evaluation research was conducted in the state of Mato Grosso, Brazil. METHODS: Mapping of references and selection of regions were made based on the quantity and heterogeneity of services. The stakeholders, including the managers of the State Department of Health and professionals from reference services, were identified. Nine semi-structured interviews were conducted using content analysis and discussions guided by the dimensions of the analysis model of universal access to health services. RESULTS: In the political dimension, decentralizing services and adhering to the Intermunicipal Health Consortium are highly encouraged. In the economic-social dimension, a commitment exists to allocate public funds for the expansion of referral services and subsidies to support users in their travel for appointments, medications, and examinations. In the organizational dimension, the availability of inputs for testing, definition of user flow, ease of scheduling appointments, coordination by primary care in testing, collaboration following the guidelines and protocols, and engagement in extramural activities are guaranteed. In the technical dimension, professionals actively commit to the service and offer different opening hours, guarantee the presence of an infectious physician, expand training opportunities, and establish intersectoral partnerships. In the symbolic dimension, professionals actively listen to the experiences of users throughout their care trajectory and demonstrate empathy. CONCLUSIONS: The results are crucial for improving comprehensiveness, but necessitate managerial efforts to enhance regional governance.

Descemet's membrane endothelial keratoplasty for primary graft failure after penetrating keratoplasty / Transplante endotelial de membrana de Descemet para falência primária após transplante penetrante

ABSTRACT Primary graft failure (PGF) is a known complication following penetrating keratoplasty (PKP). The usual approach to treat this complication is to repeat a penetrating keratoplasty. Here, we report a case of Descemet's membrane endothelial keratoplasty (DMEK) for the treatment of PGF after PKP. A patient that underwent PKP, developed PGF with persistent graft edema and very poor visual acuity despite aggressive steroid use and a proof anti-viral treatment. Three months after the initial surgery, a DMEK was performed under the PKP graft. There was progressive early corneal clearing and, by the end of the first month, the patient already had no corneal edema. Uncorrected visual acuity (UCVA) improved to 20/40 and best corrected visual acuity (BCVA) to 20/20. DMEK may be an alternative to a second PKP for the treatment of PGF. This technique is a less invasive option when compared to the standard PKP procedure.

RESUMO A falência primária do enxerto é uma complicação conhecida que pode ocorrer após o transplante penetrante de córnea. O tratamento usual dessa complicação é com um novo transplante penetrante. Apresentamos um caso em que foi usado o transplante endotelial de membrana de Descemet (DMEK - do inglês Descemet membrane endo-thelial keratoplasty) para o tratamento da falência primária após o transplante penetrante. Uma paciente submetida a transplante penetrante evoluiu com falência primária do enxerto a despeito do uso intenso de corticoide tópico e uma prova terapêutica de antivirais. Três meses após a cirurgia inicial, foi optado pela realização do transplante endotelial de membrana de Descemet sob o transplante penetrante. Houve um clareamento precoce e progressivo do enxerto com melhora importante da visão. Após um mês, a visão sem correção era de 20/40 melhorando para 20/20 com refração. O transplante endotelial de membrana de Descemet pode ser uma alternativa a um novo transplante penetrante como tratamento da falência primária.

SARS-CoV-2 and the ocular surface: test accuracy and viral load / SARS-CoV-2 e a superfície ocular: acurácia dos testes e carga viral

ABSTRACT Purpose: This study aimed to evaluate the pre-sence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the ocular surface of individuals clinically suspected of coronavirus disease 2019 (COVID-19) and determine the accuracy of different approaches of molecular testing on the ocular surface based on the nasopharyngeal positivity status for COVID-19. Methods: A total of 152 individuals with suspected COVID-19 symptoms who simultaneously underwent nasopharyngeal and two different tear film collection techniques for quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) were included. Tears were collected and randomized: one eye had the filter strip for the Schirmer test and the contralateral eye had conjunctival swab/cytology in the inferior fornix. All patients underwent slit lamp biomicroscopy. The accuracy of various ocular surface collection techniques used for the detection of SARS-CoV-2 RNA was determined. Results: Of the 152 patients enrolled in the study, 86 (56.6%) had COVID-19 confirmed by nasopharyngeal PCR. Both tear film collection techniques detected viral particles: the Schirmer test was positive in 16.3% (14/86) and the conjunctival swab/cytology in 17.4% (15/86), with no statistically significant differences. No positive ocular tests were found among those with negative nasopharyngeal PCR tests. The overall agreement of the ocular tests was 92.7%, and in combination, the sensitivity would increase to 23.2%. The mean cycle threshold values in the nasopharyngeal, Schirmer, and conjunctival swab/cytology tests were 18.2 ± 5.3, 35.6 ± 1.4, and 36.4 ± 3.9, respectively. Compared with the nasopharyngeal test, the Schirmer (p=0.001) and conjunctival swab/cytology (p<0.001) tests had significantly different Ct values. Conclusion: The Schirmer (16.3%) and conjunctival swab (17.4%) tests were comparably capable of detecting SARS-CoV-2 RNA in the ocular surface by RT-PCR accurately based on nasopharyngeal status and demonstrated indistinct sensitivity and specificity. Simultaneous specimen sampling and processing from the nasopharyngeal, Schirmer, and conjunctival swab/cytology tests demonstrated significantly lower viral load in both ocular surface approaches than in the nasopharyngeal test. Ocular manifestations detected by slit lamp biomicroscopy were not associated with ocular RT-PCR positivity.

RESUMO Objetivo: Avaliar a presença de RNA de coronavírus 2 causador de síndrome respiratória aguda grave (SARS-CoV-2) na superfície ocular de indivíduos clinicamente suspeitos com COVID-19 e determinar a precisão de diferentes abordagens de testes moleculares na superfície ocular com base no status de positividade do RT-qPCR de nasofaringe para COVID-19. Métodos: 152 indivíduos com sintomas suspeitos para a COVID-19 foram submetidos a coleta de reação em cadeia da polimerase de nasofaringe simultaneamente a duas técnicas diferentes de coleta de filme lacrimal para RT-qPCR: aleatoriamente, um olho com a tira filtro do teste de Schirmer e, o olho contralateral, com citologia (swab) conjuntival no fórnice inferior. Todos os indivíduos foram submetidos à biomicroscopia com lâmpada de fenda. Resultados: Dos 152 pacientes, 86 (56,6%) tiveram a COVID-19 confirmada por PCR de nasofaringe. Ambas as técnicas de coleta detectaram partículas virais: o teste de Schirmer foi positivo em 16,3% (14/86) e a citologia conjuntival em 17,4% (15/86), sem diferenças estatisticamente significativas. Não houve testes oculares positivos entre aqueles com reação em cadeia da polimerase de nasofaringe negativo. A concordância geral dos testes oculares foi de 92,7% e, em combinação, a sensibilidade aumentaria para 23,2%. Os valores médios do limiar de ciclo nos testes de nasofaringe, Schirmer e citologia conjuntival foram 18,2 ± 5,3, 35,6 ± 1,4 e 36,4 ± 3,9, respectivamente. Conclusão: Os testes de Schirmer (16,3%) e swab conjuntival (17,4%) foram igualmente capazes de detectar RNA de SARS-CoV-2 na superfície ocular por RT-PCR e demonstraram sensibilidade e especificidade indistintas. A coleta simultânea de amostras ao processamento dos testes de RT-PCR de nasofaringe, Schirmer e citologia (swab) conjuntival demonstraram carga viral significativamente menor em ambas as abordagens da superfície ocular em comparação com o teste de nasofaringe. As manifestações oculares detectadas pela biomicroscopia com lâmpada de fenda não foram claramente associadas à positividade do RT-PCR ocular.

Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells

BACKGROUND: Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection. RESULTS: Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimer:monomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimer:monomer ratio. These effects were prevented by combined administration of IFN-ß, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimer:monomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimer:monomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimer:monomer equilibrium. CONCLUSIONS: Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related biological response which partakes in the suppression of viral replication. Further studies are needed to replicate our findings in neuronal cells as well as animal models, and to ascertain the nature of such α-syn conformations.

Phylogenetic relationship between rabies virus (Lyssavirus rabies) variants from two different species / Relações filogenéticas do vírus da raiva (Lyssavirus rabies) em duas diferentes espécies / Relaciones filogenéticas del virus de la rabia (Lyssavirus rabies) en dos especies diferentes

Rabies is a fatal zoonotic disease that affects several mammals. Hematophagous bats are recognized hosts of the rabies virus, and their main food source is the blood of other mammals, particularly cattle. During feeding, bats transmit the virus to cattle, which are victims of the disease, contributing to economic losses and increasing the risk of infection for humans. Based on this affinity in the rabies cycle between bats and cattle, the objective of this study was to analyze the phylogenetic relationships of rabies virus samples in cattle and bats. The G gene of the rabies virus was chosen for this study because it is directly related to the infection process. Nucleotide sequences of the viral G gene were selected from GenBank for samples obtained from infected cattle and bats. Maximum parsimony analyses were conducted using the Molecular Evolutionary Genetics Analysis software. The Maxima Parsimony tree indicated a phylogenetic relationship between the G genes of both hosts, indicating that the virus evolved from bats to cattle. Analysis of parsimoniously informative sites revealed that the viral G gene carried specific mutations in each host. Knowledge of the evolutionary relationships between the rabies virus and its hosts is critical for identifying potential new hosts and the possible routes of infection for humans.

A Raiva é uma zoonose fatal que infecta várias espécies de mamíferos. Os morcegos hematófagos são reconhecidos como hospedeiros do vírus da Raiva e sua principal fonte de alimento é o sangue de outros mamíferos, especialmente os bovinos. Quando se alimentam, os morcegos transmitem o vírus para o bovino os quais são vítimas da doença, contribuindo para perdas econômicas e riscos de infecção para humanos. Baseado nesta afinidade do ciclo da Raiva entre morcegos e bovinos, o objetivo deste estudo foi analisar as relações filogenéticas de amostras do vírus da Raiva em ambos os hospedeiros, bovinos e morcegos. O gene G do vírus da Raiva foi escolhido para esta pesquisa porque ele está diretamente relacionado ao processo de infecção. Sequências de nucleotídeos do gene G viral foram selecionadas no GenBank a partir de amostras obtidas de bovinos e morcegos infectados. Análises de Máxima Parcimônia foram conduzidas utilizando o software Molecular Evolutionary Genetics Analysis. A árvore de Máxima Parcimônia indicou uma relação filogenética entre o gene G de ambos os hospedeiros, indicando que o vírus evoluiu dos morcegos para os bovinos. A análise dos sítios parcimoniosamente informativos revelou que o gene G viral apresentou mutações específicas em cada hospedeiro. O conhecimento sobre as relações evolutivas do vírus da Raiva e seus hospedeiros é crucial para identificar nos hospedeiros potenciais e novas rotas possíveis de infecção para humanos.

La rabia es una zoonosis fatal que infecta a varias especies de mamíferos. Los murciélagos hematófagos son reconocidos como huéspedes del virus de la rabia y su principal fuente de alimentación es la sangre de otros mamíferos, especialmente del ganado. Al alimentarse, los murciélagos transmiten el virus al ganado que es víctima de la enfermedad, contribuyendo a pérdidas económicas y riesgos de infección para los humanos. Basado en esta afinidad del ciclo de la rabia entre murciélagos y ganado, el objetivo de este estudio fue analizar las relaciones filogenéticas de las muestras de virus de la rabia tanto en huéspedes, ganado y murciélagos. El gen G del virus de la rabia fue elegido para esta investigación porque está directamente relacionado con el proceso de infección. Las secuencias de nucleótidos del gen G viral se seleccionaron en GenBank a partir de muestras obtenidas de bovinos y murciélagos infectados. Los análisis de parsimonia máxima se realizaron utilizando el software Molecular Evolutionary Genetics Analysis. El árbol de Máxima Parsimônia indicó una relación filogenética entre el gen G de ambos huéspedes, indicando que el virus evolucionó de murciélagos a bovinos. El análisis de los sitios parsimoniosamente informativos reveló que el gen G viral presentaba mutaciones específicas en cada huésped. El conocimiento sobre las relaciones evolutivas del virus de la rabia y sus huéspedes es crucial para identificar huéspedes potenciales y nuevas posibles rutas de infección para humanos.

Impacto de la movilidad poblacional en el comportamiento de virus respiratorios durante la pandemia COVID-19 / Impact of population mobility on the behavior of respira tory viruses during the COVID-19 pandemic

Resumen Introducción : Durante la pandemia de SARS-CoV-2 en Argentina se implementaron intervenciones no farma cológicas que produjeron cambios en la movilidad de la población. El objetivo de este estudio fue relacionar los porcentajes de positividad y la diversidad viral con la movi lidad poblacional durante parte del período de restricciones. Métodos : Estudio retrospectivo analítico realizado en el Instituto Médico Platense durante los años 2020 a 2022 que incluyó 458 pacientes a los que se les tomó un hisopado nasofaríngeo para la búsqueda de patóge nos respiratorios por PCR multiplex. Se analizaron los cambios en la movilidad de la población utilizando los "Informes de Movilidad Local", herramienta desarrollada por Google, cuyos datos son de público acceso. Resultados : La movilidad poblacional se correlacionó significativamente con el porcentaje de positividad de las muestras (p = <0.01; R2 = 0.89) y la diversidad viral (p = 0.04; R2 = 0.78). Discusión : Las intervenciones no farmacológicas destinadas a limitar la propagación del SARS-CoV-2 tuvieron efecto en la circulación de otros virus respi ratorios, hallándose mayor porcentaje de positividad y diversidad a medida que las mismas disminuyeron su grado de restricción.

Abstract Introduction : During the SARS-CoV-2 pandemic, Ar gentina population suffered from significant changes in population mobility due to non-pharmaceutical interventions. The aim of this study was to describe the impact of the mobility restrictions to the rates of positivity and diversity among different respiratory viruses. Methods : Retrospective analytical study per formed at Instituto Médico Platense in La Plata that included 458 patients with nasopharyngeal swab to search for respiratory pathogens by multiplex PCR. Changes in mobility were studied using "Community Mobility Reports", data set developed by Google and publicly available. Results : Community mobility had significant cor relation with the percentages of viral test positiv ity (p = < 0.01; R2=0.89) and viral diversity (p = 0.04; R2 = 0.78). Discussion : Non-pharmaceutical interventions estab lished to contain SARS-CoV-2 spread had a significant impact in the circulation patterns of other respiratory viruses.

Vacunas contra el virus chikungunya: avances y perspectivas

El virus chikungunya (CHIKV) es un alfavirus cuya infección provoca una enfermedad caracterizada principalmente por fiebre y dolores articulares/musculares. Entre 25-50% de las infecciones se presentan con enfermedad crónica que puede durar de meses a años. El primer brote de CHIKV en Paraguay corresponde al año 2015, siendo el último en el año 2022/2023. Diversos candidatos vacunales contra CHIKV se encuentran en diferentes etapas de desarrollo, e incluso recientemente (noviembre/2023) fue aprobada la primera vacuna contra CHIKV llamada VLA1553 (Ixchiq). Adicionalmente, al menos 30 candidatos vacunales se encuentran en ensayos preclínicos/clínicos. Con la aprobación de la primera vacuna contra CHIKV y la posibilidad de otras que lleguen al mercado prontamente, debido al estado avanzado de otros candidatos vacunales, se abrirá un nuevo escenario en esta enfermedad. Se espera que la introducción de vacunas efectivas genere un avance importante para la prevención de esta enfermedad, disminuyendo los casos agudos y los efectos crónicos de la infección por el virus. En este trabajo de revisión se analiza el avance de las vacunas contra CHIKV, además de examinar los desafíos de vigilancia epidemiológica que plantean la introducción de estas vacunas.

Chikungunya virus (CHIKV) is an alphavirus that causes an illness characterized mainly by fever and joint/muscle pain. Between 25-50% of infections present with chronic diseases that can last from months to years. The first outbreak of CHIKV in Paraguay occurred in 2015, with the last outbreak occurring in 2022/2023. Several vaccine candidates against CHIKV are in different stages of development, and even recently (November/2023), the first vaccine against CHIKV, called VLA1553 (Ixchiq), was approved. In addition, at least 30 vaccine candidates are available for preclinical and clinical trials. With the approval of the first vaccine against CHIKV and the possibility of others coming to the market soon, due to the advanced status of other vaccine candidates, a new scenario will open for this disease. The introduction of effective vaccines is expected to generate an important advance in the prevention of this disease, reducing acute cases and the chronic effects of viral infection. This review analyzes the progress of CHIKV vaccines and examines the epidemiological surveillance challenges posed by the introduction of these vaccines.

Proctitis y úlcera ano-rectal como presentación inicial en pacientes con Viruela símica

Objetivo: Describir hallazgos clínicos, quirúrgicos e imagenológicos de la patología anorrectal en pacientes con Viruela Símica. Materiales y Métodos: Reporte de serie de casos clínicos, observacional, en pacientes con Viruela Símica tratados en un centro de salud privado desde agosto 2022 a diciembre 2022. Resultados: El 100% de los casos pertenecía al sexo masculino, la edad promedio fue de 32 años, todos los pacientes mantuvieron relaciones sexuales con otros hombres, la mayoría debuto con síntomas rectales, incluyendo proctalgia, prurito anal y heces diarreicas con mucosidad. El diagnóstico se confirmó mediante PCR (reacción de polimerasa en cadena) y el tratamiento fue sintomático, con mejoría en todos los pacientes en un seguimiento de 10 días. Discusión: La Viruela Símica es una enfermedad viral que se encuentra, principalmente, en regiones remotas de África Central, con brotes esporádicos en países africanos. Está relacionada con el virus de la viruela y se transmite, principalmente, del contacto con animales infectados o fluidos corporales. La enfermedad presenta síntomas similares a la gripe, seguidos del desarrollo de una erupción cutánea que progresa a pústulas y costras. No hay tratamiento específico para la viruela símica, el manejo medico alivia los síntomas. El brote de viruela símica en 2022 presentó características novedosas y atípicas en su forma de presentación. Conclusión: Los síntomas rectales asociados a una historia clínica compatible con viruela símica se deben considerar como diagnóstico diferencial a la proctitis por esta etiología específica y emergente.

Objective: To describe clinical, surgical and imaging findings of anorectal pathology in patients with monkeypox. Materials and Methods: Observational clinical case series report in patients with monkeypox treated in a private health center from August 2022 to December 2022. Results: 100% of the cases were male, the average age was 32 years old, all patients had sexual intercourse with other men, most debuted with rectal symptoms, including proctalgia, anal itching, and diarrheal stools with mucus. Diagnosis was confirmed by PCR (polymerase chain reaction) and treatment was symptomatic, with improvement in all patients at a 10-day follow-up. Discussion: Monkeypox is a viral disease found mainly in remote regions of Central Africa, with sporadic outbreaks in African countries. It is related to the smallpox virus and is transmitted primarily from contact with infected animals or bodily fluids. The disease presents with flu-like symptoms, followed by the development of a skin rash that progresses to pustules and scabs. There is no specific treatment for monkeypox; medical management alleviates the symptoms. The monkeypox outbreak in 2022 presented novel and atypical characteristics in its presentation. Conclusion: Rectal symptoms associated with a clinical history compatible with monkeypox should be considered as a differential diagnosis of proctitis due to this specific and emerging etiology.

Caracterización clínica de la Nefropatía por Poliomavirus BK en pacientes trasplantados renales / Clinical characterization of Polyomavirus BK nephropathy in kidney transplanted patients

INTRODUCCIÓN. La nefropatía por poliomavirus BK resulta un problema emergente en el trasplante renal, pues contribuye a la pérdida temprana de los injertos renales. OBJETIVO. Caracterizar clínicamente a los pacientes trasplantados renales con nefropatía por poliomavirus BK. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, realizado en el Hospital de Especialidades Carlos Andrade Marín en el período 2013-2022, se obtuvo una base de datos anonimizada, 479 pacientes trasplantados renales, de estos se identificaron 37 pacientes que corresponde a un 7,7% con nefropatía por poliomavirus BK, se realizó un análisis con el programa estadístico SPSS v26®. RESULTADOS. La población estuvo caracterizada por pacientes del sexo masculino (56,8%), con una edad media de 48,2 años, el donante cadavérico fue el más frecuente (94,5%), la mayor parte del tratamiento de la nefropatía por poliomavirus BK consistió en cambio de micofenolato sódico a everolimus y se mantuvo con 50% de Tacrolimus y Prednisona (40,5%); al valorar el cambio de los valores de creatinina, los niveles más elevados fueros a los 12 meses cuando la pérdida renal fue temprana (p: 0,042), y de la misma manera a los 12 meses, fueron más elevados los niveles de creatinina cuando el diagnóstico histopatológico fue Nefropatía por Poliomavirus Clase 3 (p: 0,01). DISCUSIÓN. La prevalencia de la nefropatía se mantuvo por debajo del 10% reportado a nivel global, la creatinina empeoró en pacientes con pérdida temprana del injerto renal y con una clase patológica avanzada, hecho reportado en la fisiopatología de la enfermedad. CONCLUSIÓN. La pérdida del injerto renal temprano presentó una creatinina más alta que la tardía. Es recomendable un tamizaje adecuado para la detección temprana del virus BK siendo crucial para prevenir el deterioro de la función renal y limitar la posterior pérdida del injerto.

INTRODUCTION: BK polyomavirus nephropathy is emerging as a significant concern in kidney transplantation, as it contributes to the early loss of renal grafts. OBJECTIVE: The aim of this study was to clinically characterize renal transplant recipients with BK polyomavirus nephropathy. MATERIALS AND METHODS: An observational and descriptive study was conducted at Carlos Andrade Marín Specialties Hospital during the period of 2013 to 2022. An anonymized database comprising 479 renal transplant patients was utilized. Among these, 37 patients, constituting 7.7%, were identified with BK polyomavirus nephropathy. Data analysis was performed using the statistical program SPSS v26®. RESULTS: The study population was predominantly composed of male patients (56.8%) with a mean age of 48.2 years. Deceased donors accounted for the majority (94.5%) of cases. The primary approach for managing BK polyomavirus nephropathy involved transitioning from mycophenolate sodium to everolimus, alongside maintaining a regimen of 50% tacrolimus and 40.5% prednisone. When assessing changes in creatinine values, the highest levels were observed at 12 months, coinciding with early renal loss (p: 0.042). Similarly, at the 12-month mark, elevated creatinine levels were associated with a histopathological diagnosis of Polyomavirus nephropathy Class 3 (p: 0.01). DISCUSSION: The prevalence of nephropathy remained below the globally reported threshold of 10%. Creatinine levels worsened in patients experiencing early graft loss and an advanced pathological classification, aligning with established disease pathophysiology. CONCLUSION: Early renal graft loss was associated with higher creatinine levels compared to delayed loss. Adequate screening for early detection of BK virus is recommended, as it plays a crucial role in preventing renal function deterioration and limiting subsequent graft loss.

Atypical perianal and buttocks epidermal-dermal necrosis in Human Monkeypox. Histopathological study of the lesion in Peru

We report the histopathological study of a large, black, crusted lesion with symmetrical distribution in both buttocks and perineum, never described, in a man who has sex with men (MSM) and proctitis associated with Human Monkey Pox Virus (hMPXV) and HIV-AIDS infection never treated. A 39-year-old male, homosexual, HIV-AIDS without Highly Active Antiretroviral Therapy (HAART), was admitted to a hospital in Lima, Peru, with papulopustular lesions on the body and perianal area. Days later, a large, crusty, black lesion with a symmetrical distribution appeared on the buttocks and perineum. The tissue culture was negative. Wedge biopsy of the lesion showed typical MPXV cytopathogenics lesions in addition to fibrin micro thrombosis in the underlying papillary dermis. The histopathological findings of the scabby and black lesion are the classic ones described by Stagles, except for the phenomenon of fibrin micro thrombosis in the papillary dermis, a novel cytopathogenic effect of MPXV with clinical relevance (epidermal-dermal necrosis).

Reportamos el estudio histopatológico de una gran lesión costrosa, negra, de distribución simétrica en ambas nalgas y periné, nunca descrito, en un hombre que tiene sexo con hombres (HSH) y proctitis asociado a Viruela del Mono Humana (hMPXV) e infección por VIH-SIDA nunca tratado. Un varón de 39 años, homosexual, VIH-SIDA sin Terapia Antirretroviral de Gran Actividad (TARGA), ingresó en un hospital de Lima, Perú, con lesiones papulopustulosas en el cuerpo y el area perianal. Días después apareció una gran lesión negra, costrosa de distribución simétrica en las nalgas y periné. El cultivo de tejidos fue negativo. La biopsia en cuña de la lesión mostró lesiones citopatogénicas típicas de MPXV, además de microtrombosis de fibrina en la dermis papilar subyacente. Los hallazgos histopatológicos de la lesión costrosa y negra que reportamos son los clásicos descritos por Stagles, a excepción del fenómeno de microtrombosis de fibrina en la dermis papilar, un efecto citopatogénico novedoso de MPXV con relevancia clínica (necrosis epidermo-dérmico).

COVID-19 in the nervous system: physiopathology and neurological manifestations / Covid-19 no sistema nervoso: fisiopatologia e manifestações neurológicas

Abstract Background Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although respiratory manifestations have received greater visibility during the pandemic caused by this virus, numerous neurological complaints related to coronavirus 2 infection have been documented in several countries. These records suggest that this pathogen presents neurotropism, and it can cause different neurological conditions of varying intensity. Objective To investigate the ability of coronavirus 2 to invade the central nervous system (CNS) and its neurological clinical outcomes. Methods The present study consists in a comprehensive literature review of the records available in the PubMed, SciELO, and Google Scholar databases. The descriptors COVID-19, brain and physiopathology, associated with the Boolean operator AND, were used in the search. Regarding the inclusion and exclusion criteria, we selected the papers published since 2020 with the highest number of citations. Results We selected 41 articles, most of them in English. The main clinical manifestation associated with COVID-19 patients was headache, but cases of anosmia, hyposmia, Guillain-Barré syndrome, and encephalopathies were also described with considerable frequency. Conclusion Coronavirus-2 presents neurotropism, and it can reach the CNS by hematogenous dissemination and by direct infection of the nerve endings. It causes brain injuries through several mechanisms, such as cytokine storm, microglial activation, and an increase in thrombotic factors.

Resumo Antecedentes A doença do coronavírus 2019 (coronavirus disease 2019, Covid-19, em inglês) é uma infecção viral provocada pelo coronavírus 2 da síndrome respiratória aguda grave (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, em inglês). Embora as manifestações respiratórias tenham recebido maior visibilidade ao longo da pandemia provocada por esse vírus, inúmeras queixas neurológicas relacionadas à infecção pelo coronavírus 2 foram documentadas em diversos países. Tais registros sugerem que esse patógeno apresenta neurotropismo, e é capaz de provocar quadros neurológicos diversos e de intensidade variáveis. Objetivo Investigar a capacidade de invasão do sistema nervoso central (SNC) pelo coronavírus 2 e seus principais desfechos clínicos neurológicos. Métodos O presente estudo consiste em uma ampla revisão de literatura a partir dos registros das bases de dados PubMed, SciELO e Google Acadêmico. Nesse contexto, os descritores COVID-19, cérebro e fisiopatologia, associados com o operador booleano AND, foram utilizados na busca. Quanto aos critérios de inclusão e exclusão, selecionou-se os trabalhos publicados a partir de 2020 com o maior número de citações. Resultados Foram selecionados 41 artigos, a maioria na língua inglesa. A principal manifestação clínica associada a pacientes acometidos pela COVID-19 foi a cefaleia, mas casos de anosmia, hiposmia, síndrome de Guillain-Barré e encefalopatias também foram descritos com frequência considerável. Conclusão O coronavírus 2 apresenta neurotropismo, e é capaz de alcançar o SNC por disseminação hematogênica e por infecção direta das terminações nervosas. Ele provoca injúria cerebral por meio de variados mecanismos, como tempestade de citocinas, ativação da micróglia e aumento dos fatores trombóticos.