RESUMO
Introducción: La diarrea con sangre es un motivo frecuente de admisión hospitalaria en niños, con gastroenteritis aguda; en la mayoría de los casos se tratan de infecciones leves y autolimitadas, pero pueden producirse complicaciones graves. Objetivos: Describir la etiología y características clínico- evolutivas de los niños menores de 15 años hospitalizados por diarrea con sangre en el Hospital Pediátrico, Centro Hospitalario Pereira Rossell entre los años 2012- 2023. Materiales y métodos: Estudio retrospectivo mediante revisión de historias y registros de laboratorio. Variables: demográficas, estado nutricional, hidratación, motivos de hospitalización, ingreso unidades de cuidados intensivos (UCI), enteropatógenos, tratamientos, evolución. Resultados: Se incluyeron 229 niños, mediana de edad de 8 meses; sexo masculino 61%; eutróficos 88%, bien hidratados 55%, con comorbilidades 11%, prematurez 6,5%. El motivo de hospitalización fue diarrea con sangre/disentería sin otro síntoma 45%. Se solicitó coprovirológico/coprocultivo en 98% y detección por técnicas de ácidos nucleicos en materia fecal 5,2%. Se identificó al menos un agente patógeno en 34,3%: Shigella sp. 38%; Salmonella sp. 19,5%; coinfecciones en 12%. Se indicaron antibióticos a 86%; ceftriaxona 62%, azitromicina 35%. Ingresaron a UCI 6,5% (15), presentaron complicaciones 10/14, fallo renal agudo 5 y alteraciones del medio interno 3. La mayoría presentó buena evolución. Conclusiones: La diarrea con sangre/disentería continúa siendo una causa importante de hospitalización afectando en su mayoría a niños sanos menores de 5 años. Los patógenos detectados con mayor frecuencia fueron bacterias principalmente Shigella sp., Salmonella sp. y E coli diarreogénicas. Se reportó alta prescripción de antibióticos, cumpliendo en la mayoría de los casos con las recomendaciones.
Introduction: Bloody diarrhea is a common reason for hospital admission in children with acute gastroenteritis; In most cases these are mild and self-limiting infections, but serious complications can occur. Goals: To describe the etiology and clinical-evolutionary characteristics of children under 15 years of age hospitalized for bloody diarrhea at the Pediatric Hospital, Centro Hospitalario Pereira Rossell between the years 2012-2023. Materials and methods: Retrospective study through review of histories and laboratory records. Variables: demographics, nutritional status, hydration, reason for hospitalization, intensive care unit (ICU) admission, enteropathogens, treatments, evolution. Results: 229 children were included, median age 8 months; male sex 61%; eutrophic 88%, well hydrated 55%, with comorbidities 11%, prematurity 6.5%. The reason for hospitalization was bloody diarrhea/dysentery without other symptoms 45%. Coprovirological/coproculture was requested in 98% and detection by nucleic acid techniques in fecal matter was requested in 5,2%. At least one pathogenic agent was identified in 34,3%: Shigella sp. 38%; Salmonella sp 19,5%; coinfections in 12%. Antibiotics were indicated for 86%; ceftriaxone 62%, azithromycin 35%. Were admitted to the ICU 6,5% (15), 10/14 had complications, 5 had acute kidney failure and 3 had alterations in the internal environment. The majority had a good evolution. Conclusions: Bloody diarrhea/dysentery continues to be an important cause of hospitalization, affecting mostly healthy children under 5 years of age. The most frequently detected pathogens were bacteria, mainly Shigella sp., Salmonella sp. and diarrheagenic E coli. High prescription of antibiotics was reported, complying in most cases with the recommendations.
Introdução: A diarreia com sangue é um motivo comum de internação hospitalar em crianças com gastroenterite aguda; Na maioria dos casos, estas são infecções leves e autolimitadas, mas podem ocorrer complicações graves. Metas: Descrever a etiologia e as características clínico-evolutivas de crianças menores de 15 anos internadas por diarreia sanguinolenta no Hospital Pediátrico Centro Hospitalario Pereira Rossell entre os anos de 2012-2023. Materiais e métodos: Estudo retrospectivo por meio de revisão de histórias e registros laboratoriais. Variáveis: dados demográficos, estado nutricional, hidratação, motivo da internação, internação em unidade de terapia intensiva (UTI), enteropatógenos, tratamentos, evolução. Resultados: foram incluídas 229 crianças, mediana de idade 8 meses; sexo masculino 61%; eutrófico 88%, bem hidratado 55%, com comorbidades 11%, prematuridade 6,5%. O motivo da internação foi diarreia sanguinolenta/disenteria sem outros sintomas 45%. O estudo coprovirologico/coprocultivo foi solicitado em 98% e a detecção por técnicas de ácidos nucleicos em matéria fecal foi solicitada em 5,2%. Pelo menos um agente patogênico foi identificado em 34,3%: Shigella sp. 38%; Salmonella sp. 19,5%; coinfecções em 12%. Os antibióticos foram indicados para 86%; ceftriaxona 62%, azitromicina 35%. Foram internados em UTI 6,5% (15), 10/14 apresentaram complicações, 5 tiveram insuficiência renal aguda e 3 apresentaram alterações no meio interno, a maioria teve boa evolução. Conclusões: A diarreia/disenteria com sangue continua a ser uma causa importante de hospitalização, afetando sobretudo crianças saudáveis ââcom menos de 5 anos de idade. Os patógenos mais frequentemente detectados foram bactérias, principalmente Shigella sp., Salmonella sp. e E. coli diarreiogênica. Foi relatada elevada prescrição de antibióticos, cumprindo na maioria dos casos as recomendações.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Infecções por Rotavirus/complicações , Infecções por Campylobacter/complicações , Diarreia Infantil/etiologia , Diarreia Infantil/sangue , Disenteria/etiologia , Disenteria/sangue , Infecções por Enterobacteriaceae/complicações , Infecções por Rotavirus , Infecções por Rotavirus/tratamento farmacológico , Infecções por Campylobacter/diagnóstico , Infecções por Campylobacter/tratamento farmacológico , Criança Hospitalizada/estatística & dados numéricos , Estudos Retrospectivos , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/tratamento farmacológicoRESUMO
Group A rotaviruses (RVAs) are the major cause of severe acute gastroenteritis (AGE) in children under 5 years of age, annually resulting in nearly 130,000 deaths worldwide. Social conditions in developing countries that contribute to decreased oral rehydration and vaccine efficacy and the lack of approved antiviral drugs position RVA as a global health concern. In this minireview, we present an update in the field of antiviral compounds, mainly in relation to the latest findings in RVA virion structure and the viral replication cycle. In turn, we attempt to provide a perspective on the possible treatments for RVA-associated AGE, with special focus on novel approaches, such as those representing broad-spectrum therapeutic options. In this context, the modulation of host factors, lipid droplets, and the viral polymerase, which is highly conserved among AGE-causing viruses, are analyzed as possible drug targets.
Assuntos
Antivirais/uso terapêutico , Desenvolvimento de Medicamentos , Infecções por Rotavirus/tratamento farmacológico , Rotavirus/efeitos dos fármacos , Criança , Genoma Viral , Genótipo , Humanos , Filogenia , Rotavirus/genéticaRESUMO
Rotavirus is one of the leading causes of severe acute gastroenteritis in children under 5 years of age, mainly affecting developing countries. Once the disease is acquired, no specific treatment is available; as such, the development of new drugs for effective antirotaviral treatment is critical. Ursolic acid is a pentacyclic triterpenoid with antiviral activity, which has been studied extensively in vitro and in vivo. To study the potential antirotaviral activity of ursolic acid, its toxic potential for viral particles (virucidal effect) and cultured cells (cytotoxicity) was analysed. No effect on virion infectivity was observed with treatments of up to 40 µM ursolic acid, while incipient cytotoxicity started to be evident with 20 µM ursolic acid. The antiviral potential of ursolic acid was evaluated in in-vitro rotavirus infections, demonstrating that 10 µM ursolic acid inhibits rotavirus replication (observed by a decrease in viral titre and the level of the main viral proteins) and affects viral particle maturation (a process associated with the endoplasmic reticulum) 15 h post infection. Interestingly, ursolic acid was also found to hamper the early stages of the viral replication cycle, as a significant reduction in the number and size of viroplasms, consistent with a decrease in VP6 and NSP2 viral proteins, was observed 4 h post infection. As such, these observations demonstrate that ursolic acid exhibits antiviral activity, suggesting that this chemical could be used as a new treatment for rotavirus.
Assuntos
Antivirais/uso terapêutico , Gastroenterite/tratamento farmacológico , Infecções por Rotavirus/tratamento farmacológico , Rotavirus/efeitos dos fármacos , Triterpenos/uso terapêutico , Animais , Antígenos Virais/metabolismo , Antivirais/efeitos adversos , Proteínas do Capsídeo/metabolismo , Linhagem Celular , Pré-Escolar , Chlorocebus aethiops , Gastroenterite/virologia , Humanos , Testes de Sensibilidade Microbiana , Proteínas de Ligação a RNA/metabolismo , Triterpenos/efeitos adversos , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/efeitos dos fármacos , Ácido UrsólicoRESUMO
Species A Rotaviruses (RVA) remain a leading cause of mortality in children under 5 years of age. Current treatment options are limited. We assessed the efficacy of two VP6-specific llama-derived heavy chain antibody fragments (VHH) -2KD1 and 3B2- as an oral prophylactic and therapeutic treatment against RVA-induced diarrhea in a neonatal mouse model inoculated with virulent murine RVA (ECw, G16P[16]I7). Joint therapeutic administration of 2KD1+3B2 (200 µg/dose) successfully reduced diarrhea duration, RVA infection severity and virus shedding in feces. While the same dose of 2KD1 or 3B2 (200 µg) significantly reduced duration of RVA-induced diarrhea, 2KD1 was more effective in diminishing the severity of intestinal infection and RVA shedding in feces, perhaps because 2KD1 presented higher binding affinity for RVA particles than 3B2. Neither prophylactic nor therapeutic administration of the VHH interfered with the host's humoral immune response against RVA. When 2KD1 (200 µg) was administered after diarrhea development, it also significantly reduced RVA intestinal infection and fecal shedding. Host antibody responses against the oral VHH treatment were not detected, nor did viral escape mutants. Our findings show that oral administration of anti-VP6 VHH constitute, not only an effective prophylactic treatment against RVA-associated diarrhea, but also a safe therapeutic tool against RVA infection, even once diarrhea is present. Anti-VP6 VHH could be used complementary to ongoing vaccination, especially in populations that have shown lower immunization efficacy. These VHH could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea.
Assuntos
Cadeias Pesadas de Imunoglobulinas/uso terapêutico , Região Variável de Imunoglobulina/uso terapêutico , Infecções por Rotavirus/tratamento farmacológico , Infecções por Rotavirus/virologia , Rotavirus/fisiologia , Animais , Animais Recém-Nascidos , Camelídeos Americanos , Diarreia/tratamento farmacológico , Diarreia/virologia , Fezes/virologia , Concentração de Íons de Hidrogênio , Imunidade Humoral/imunologia , Cadeias Pesadas de Imunoglobulinas/administração & dosagem , Região Variável de Imunoglobulina/administração & dosagem , Intestinos/patologia , Intestinos/virologia , Camundongos Endogâmicos BALB C , Mutação/genética , Filogenia , Proteólise , Infecções por Rotavirus/imunologia , Vírion/metabolismo , Eliminação de Partículas ViraisRESUMO
AIMS: The aim of this study was to determine the antiviral activity of four probiotic metabolites (Lactobacillus and Bifidobacetrium species) against rotavirus in vitro infection monitored by the NSP4 protein production and Ca(2+) release. METHODS AND RESULTS: The antiviral effect of the metabolites was performed due a comparison between a blocking model and an intracelullar model on MA104 cells, with the response of NSP4 production and Ca(2+) liberation measured by flow cytometry. Significant results were obtained with the metabolites of Lactobacillus casei, and Bifidobacterium adolescentis in the reduction of the protein production (P = 0·04 and P = 0·014) and Ca(2+) liberation (P = 0·094 and P = 0·020) in the intracellular model, which suggests a successful antiviral activity against RV infection. CONCLUSIONS: This study demonstrates that probiotic metabolites were able to interfere with the final amount of intracellular NSP4 protein and a successful Ca(2+) regulation, which suggests a new approach to the mechanism exerted by probiotics against the rotavirus infection. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel anti-rotaviral effect exerted by probiotic metabolites monitored by the NSP4 protein during the RV in vitro infection and the effect on the Ca(2+) release is reported; suggesting a reduction on the impact of the infection by decreasing the damage of the cells preventing the electrolyte loss.
Assuntos
Antivirais/farmacologia , Bifidobacterium adolescentis/metabolismo , Glicoproteínas/metabolismo , Lacticaseibacillus casei/metabolismo , Probióticos/farmacologia , Rotavirus/efeitos dos fármacos , Toxinas Biológicas/metabolismo , Proteínas não Estruturais Virais/metabolismo , Animais , Antivirais/uso terapêutico , Linhagem Celular , Macaca mulatta , Probióticos/uso terapêutico , Rotavirus/metabolismo , Infecções por Rotavirus/tratamento farmacológico , Infecções por Rotavirus/virologiaRESUMO
Group A Rotavirus (RVA) remains a leading cause of severe diarrhea and child mortality. The variable domain of camelid heavy chain antibodies (VHH) display potent antigen-binding capacity, have low production costs and are suitable for oral therapies. Two sets of anti-RVA VHHs have been developed: ARP1-ARP3; 2KD1-3B2. Here, we explore the potential of both sets as a prevention strategy complementary to vaccination and a treatment option against RVA-associated diarrhea in endangered populations. Both sets have been expressed in multiple production systems, showing extensive neutralizing capacity against strains of RVA in vitro. They were also tested in the neonatal mouse model with various degrees of success in preventing or treating RVA-induced diarrhea. Interestingly, mitigation of the symptoms was also achieved with freeze-dried ARP1, so that it could be applied in areas where cold chains are difficult to maintain. 3B2 was tested in a pre-clinical trial involving gnotobiotic piglets where it conferred complete protection against RVA-induced diarrhea. ARP1 was used in the first clinical trial for anti-RVA VHHs, successfully reducing stool output in infants with RVA diarrhea, with no detected side effects.
Assuntos
Diarreia/tratamento farmacológico , Diarreia/virologia , Fragmentos de Imunoglobulinas/uso terapêutico , Infecções por Rotavirus/tratamento farmacológico , Animais , Animais Recém-Nascidos , Bangladesh , Criança , Diarreia/prevenção & controle , Humanos , Camundongos , Plantas Geneticamente Modificadas , Probióticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções por Rotavirus/prevenção & controle , SuínosRESUMO
Rotaviruses are the leading cause of severe, acute, and dehydrating diarrhea affecting children under 5 years of age worldwide. Despite an important reduction in rotavirus-caused deaths as a consequence of the rotavirus vaccine, alternative or complementary strategies for preventing or treating rotavirus-associated diarrhea are needed mainly in the poorest countries. We describe the cases of four rotavirus-unvaccinated 12-13-month-old girls and a 5-year-old boy who developed rotavirus-associated diarrhea confirmed by enzyme-linked immunosorbent assay, Western blotting, and immunochemistry analyses. After the first day of diarrheal episodes, three of the five patients were immediately administered oral N-acetylcysteine (NAC) 60 mg/kg daily, divided into three equal doses every 8 hours. The other two patients did not receive NAC and served as controls. Administration of NAC resulted in a decreased number of diarrheal episodes, excretion of fecal rotavirus antigen, and resolution of symptoms after 2 days of treatment. Our results suggest that NAC treatment after the first diarrheal episode could be an efficient strategy for treating rotavirus-affected children and preventing the associated severe life-threatening accompanying dehydration.
Assuntos
Acetilcisteína/uso terapêutico , Antivirais/uso terapêutico , Diarreia Infantil/prevenção & controle , Diarreia/prevenção & controle , Gastroenterite/tratamento farmacológico , Infecções por Rotavirus/tratamento farmacológico , Acetilcisteína/administração & dosagem , Administração Oral , Antivirais/administração & dosagem , Pré-Escolar , Colômbia , Desidratação/etiologia , Desidratação/prevenção & controle , Diarreia/etiologia , Diarreia/fisiopatologia , Diarreia Infantil/etiologia , Diarreia Infantil/fisiopatologia , Feminino , Gastroenterite/fisiopatologia , Gastroenterite/virologia , Humanos , Lactente , Masculino , Recidiva , Infecções por Rotavirus/fisiopatologia , Infecções por Rotavirus/virologia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Live attenuated vaccines have recently been introduced for preventing rotavirus disease in children. However, alternative strategies for prevention and treatment of rotavirus infection are needed mainly in developing countries where low vaccine coverage occurs. In the present work, N-acetylcysteine (NAC), ascorbic acid (AA), some nonsteroidal anti-inflammatory drugs (NSAIDs) and peroxisome proliferator-activated receptor gamma (PPARγ) agonists were tested for their ability to interfere with rotavirus ECwt infectivity as detected by the percentage of viral antigen-positive cells of small intestinal villi isolated from ECwt-infected ICR mice. Administration of 6 mg NAC/kg every 8 h for three days following the first diarrhoeal episode reduced viral infectivity by about 90%. Administration of AA, ibuprofen, diclofenac, pioglitazone or rosiglitazone decreased viral infectivity by about 55%, 90%, 35%, 32% and 25%, respectively. ECwt infection of mice increased expression of cyclooxygenase-2, ERp57, Hsc70, NF-κB, Hsp70, protein disulphide isomerase (PDI) and PPARγ in intestinal villus cells. NAC treatment of ECwt-infected mice reduced Hsc70 and PDI expression to levels similar to those observed in villi from uninfected control mice. The present results suggest that the drugs tested in the present work could be assayed in preventing or treating rotaviral diarrhoea in children and young animals.
Assuntos
Acetilcisteína/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Diarreia/tratamento farmacológico , PPAR gama/agonistas , Infecções por Rotavirus/tratamento farmacológico , Rotavirus , Animais , Antioxidantes/uso terapêutico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Diarreia/virologia , Proteínas de Choque Térmico HSC70/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Intestinos/virologia , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismoRESUMO
Live attenuated vaccines have recently been introduced for preventing rotavirus disease in children. However, alternative strategies for prevention and treatment of rotavirus infection are needed mainly in developing countries where low vaccine coverage occurs. In the present work, N-acetylcysteine (NAC), ascorbic acid (AA), some nonsteroidal anti-inflammatory drugs (NSAIDs) and peroxisome proliferator-activated receptor gamma (PPARγ) agonists were tested for their ability to interfere with rotavirus ECwt infectivity as detected by the percentage of viral antigen-positive cells of small intestinal villi isolated from ECwt-infected ICR mice. Administration of 6 mg NAC/kg every 8 h for three days following the first diarrhoeal episode reduced viral infectivity by about 90%. Administration of AA, ibuprofen, diclofenac, pioglitazone or rosiglitazone decreased viral infectivity by about 55%, 90%, 35%, 32% and 25%, respectively. ECwt infection of mice increased expression of cyclooxygenase-2, ERp57, Hsc70, NF-κB, Hsp70, protein disulphide isomerase (PDI) and PPARγ in intestinal villus cells. NAC treatment of ECwt-infected mice reduced Hsc70 and PDI expression to levels similar to those observed in villi from uninfected control mice. The present results suggest that the drugs tested in the present work could be assayed in preventing or treating rotaviral diarrhoea in children and young animals.