Systematic review on the design of randomized controlled trials about therapeutic drugs for rotavirus infection in children / 中国药房

OBJECTIVE To systematically analyze the related clinical research of therapeutic drugs for rotavirus infection in children， and to provide reference for the improvement of scientific and normative implementation in clinical trials. METHODS PubMed， the Cochrane Library and Embase databases were systematically searched， and English literature on randomized controlled trials （RCTs） about therapeutic drugs for pediatric rotavirus infection published between 2000 and 2022 was included. After literature screening and data extraction， the quality of the included literature was evaluated using the bias risk assessment scale recommended by Cochrane Handbook for Systematic Reviews. The research objectives， overall design， subject inclusion and exclusion criteria， interventions， course of treatment， follow-up visits， efficacy and safety evaluations， and results were analyzed descriptively. RESULTS & CONCLUSIONS A total of 17 RCTs were included， involving 1 345 subjects. The purpose included relieving rotavirus infection-induced diarrhea， promoting rotaviral shedding， improving clinical symptoms such as dehydration， fever， vomiting， and shortening hospital stays， etc. All trials were randomized and single-center studies， mostly double-blind （13 trials） and placebo-controlled （16 trials）， and 64.71% had sample size estimation. The inclusion and exclusion criteria included diarrhea attack， virus detection， clinical symptoms， disease types and drugs， etc. The interventions included probiotics （8 trials）， biological agents （3 trials）， anti-infective agents （3 trials）， etc. Most of treatment course was 1-5 days （13 trials）. A total of 58.82% were designed for follow-up. In the validity evaluation， diarrhea attack， microbiology test and fecal culture， clinical symptoms such as dehydration， fever and vomiting， length of hospital stays or duration of symptoms were included. Vesikari scale， WHO criteria and researcher evaluation were the evaluation criteria. In the safety evaluation， 10 trials were designed for adverse events/adverse reaction observation； only one trial listed ethical approval numbers. The information of literature included in the study covers the basic elements for the design of RCTs of drugs for rotavirus infection in children. Nevertheless， all are single- center studies. Partial studies lack the basis for sample size estimation and related contents of drug combination， and the quality needs to be improved. In the future， the high-quality multi-center clinical trials should be further conducted， with objective measurement indexes as the validity results， and the ethical review and safety evaluation should be emphasized.

Interpretation of Rotavirus-positivity Patterns Across India.

bjective: To analyze variation in rotavirus-positivity using simple alternative statistical measures. Methods: Hospital-based rotavirus surveillance among children admitted with acute gastroenteritis between 2005 and 2009. Prevalence, adjusted proportions and symmetrized index were calculated. Results: Rotavirus prevalence was 40% (range 37% - 44%). Adjusted proportion analysis revealed higher level of deviation from annual prevalence in seasons (December – February and September – November); age groups (<12 months and 12-23 months) and regions (East and South). Analysis of symmetrized index revealed higher estimates of variation in all years, except in 2006. Conclusion: Proposed statistical measures are useful as refined measures to study extent of disease spread in surveillance programmes, aiding evaluation of the load and pattern of disease burden in different regions over time.

A Case of Rotavirus Infection Presenting with Direct Hyperbilirubinemia / 대한주산의학회잡지

Rotavirus is the most common cause of infectious gastroenteritis in infants and young children and estimated to cause more than 111 million cases of diarrhea annually. Most patients show no specific symptom or experience mild fever, vomiting, non-bloody diarrhea and symptoms often resolve within several days. However, some of patients suffer from severe complication such as necrotizing enterocolitis, intussusception, seizure, encephalitis, and cholestasis. We report a neonatal case of rotavirus infection presenting with reversible direct hyperbilirubinemia with a brief review of associated literatures.

Clinical analysis of rotavirus enteritis in children in Yueqing city / 中国小儿急救医学

Objeetive To explore the situation of rotavirus infection and extraintestinal organe damage in children in Yueqing city.Methods Two hundred and eighty-seven cases with acute rotavirus gastroenteritis in our hospital were analyzed for prospective study from October 2011 to January 2013 by stool tests.Results Rotavirus infection was found to be more common in autumn and winter.There were 223 cases (17.7％) got extraintestinal organe damage,175 cases (60.80％) got myocardial lesion,and 78 cases (27.18％) got respiratory infection.At the same time,there were 51 cases (17.77％) and 21 cases (7.31％) got liver function lesion and convulsion respectively.Among the metabolic acidosis(48 cases),39 cases were combined with myocardial lesion.While non metabolic acidosis were 239 cases (81.25％),and 136 cases were combined with myocardial lesion.Therefore,the myocardial lesion was significant correlation with metabolic acidosis (P ＜ 0.01).Iron deficiency anemia was 123 cases and combined with 15 cases (12.19％) convulsion,while the convulsion prevalence rates of non iron deficiency anemia was 6 cases (3.65 ％).There was a statistically significant difference between the convulsion prevalence rates of iron deficiency anemia and that of non iron deficiency anemia (P ＜ 0.01).Conclusion Rotavirus diarrhea can lead to extraintestinal organe damage,and the clinical doctors should pay attention to them.

Inhibition of rotavirus ECwt infection in ICR suckling mice by N-acetylcysteine, peroxisome proliferator-activated receptor gamma agonists and cyclooxygenase-2 inhibitors

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.

Rotavirus Nosocomial Infection in Children under 5 years of age: A Preliminary study in Nepal.

Introduction: Rotavirus is one of the most common causes of acute gastroenteritis among infants and young children. The spread of rotavirus infection in pediatric wards can cause acute diarrhoea during hospitalization, and in turn, prolong hospitalization or need, rehospitalization. The aim of the study was to determine the prevalence of nosocomial infection due to rotavirus and other causal organisms among children less than 5 years of age. Methodology: A cross-sectional study between November 2009 and May 2010 was conducted among 96 pediatric patients in children hospital, Nepal. Stool samples were collected during hospitalization and up to 3 days after discharge from the hospital. Rotavirus antigens were detected by EIA and standard microbiological procedure were applied for other enteric pathogens. Results: The prevalence of nosocomial infection due to rotavirus was 30.2% (29/96). Of them, 16 (55.17%) of the 29 children with nosocomial infection during hospitalization and/or up to 72 hours after discharge developed diarrhoea. The prevalence of symptomatic cases of nosocomial infection was 55.17% (16/29), which involved 16.7% (16/96) of the study subjects, showing a prevalence of 44.82% (13/29) for asymptomatic nosocomial infection consisted of 13.54% (13/96) of the total subjects. Eleven of the 16 symptomatic subjects of nosocomial infection were affected by diarrhoea during hospitalization and five subjects after discharge. Bacteria (8.3%) and protozoa (5.2%) agents were also causing nosocomial infection in children. Conclusions: Children attending hospital may asymptomatically carry enteric pathogens and potentially act as source of nosocomial infection. Due to the relatively high frequency of nosocomial infection in the Children Hospital of Nepal, it is necessary to follow strictly hygienic rules such as isolation of patients with diarrhoea and hand-washing before and after the examination of each patient and cleaning the examination instruments after use in each patient.

Progress of rotavirus infection and NF-κB / 国际儿科学杂志

In rotavirus infection, NF-κB plays an important role in regulation of host defense and pathogenic of rotavirus. On the one hand, by the signal regulation mechanism of NF-κ Bmediated, host plays antiviral effect and immune-related role. On the other hand, by blocking NF-κB nuclear accumulation and other reactions, rotavirus evades the host immune response. Consequently, the outcome of rotavirus infection may depend on dominant way of NF-κ Bregulating.

Transient splenial lesion of the corpus callosum in a case of benign convulsion associated with rotaviral gastroenteritis / 소아과

Transient magnetic resonance (MR) signal changes in the splenium of the corpus callosum (SCC) arise from many different conditions, including encephalopathy or encephalitis caused by infection, seizures, metabolic derangements, and asphyxia. Few case reports exist on reversible SCC lesions associated with rotavirus infection. A benign convulsion with mild gastroenteritis (CwG) is frequently associated with rotaviral infections. This entity is characterized by normal laboratory findings, electroencephalogram, neuroimaging, and good prognosis. We report a case of a 2.5-year-old Korean girl with rotavirus-associated CwG demonstrating a reversible SCC lesion on diffusion-weighted MR images. She developed 2 episodes of brief generalized tonic-clonic seizure with mild acute gastroenteritis without any other neurologic abnormality. Stool test for rotavirus antigen was positive. Brain MRI done on the day of admission showed a linear high signal intensity and decreased apparent diffusion coefficient values on the SCC. The lesion completely disappeared on follow-up MRI 6 days later. The patient fully recovered without any sequelae.

Clinical Observation on Treatment of Infantile Diarrhea by Tuina and Medications / 针灸推拿医学（英文版）

Objective: To observe the clinical effect of tuina plus medications on infantile diarrhea induced by rotavirus infection. Methods: After 55 cases of confirmed sick infants were divided into two groups by the order of their visits, 30 cases in the medication group were treated by intravenous infusion of Ribavirin and oral administration of Smecta; 25 cases in the tuina plus medication group were treated by the manual techniques of tonifying Pijing(脾经) and clarifying Dachangjing (大肠经), rubbing the abdomen and kneading the navel clockwise, pushing Shangqijiegu (上七节骨), kneading Guiwei (龟尾), and pinching the skin of the spine, in combination with same medications used as in the medication group. Results: The total effective rate was 96% in the tuina plus medication group, P < 0.01, in comparison with the medication group. Conclusion: tuina has a good therapeutic effect in the treatment of infantile diarrhea induced by rotavirus infection and is importantly significant for shortening the course, enhancing the therapeutic effect and lowering down the medical cost.

Development of rotavirus detection techniques and study of rotavirus subgroup and serotype epidemiology in Sri Lanka

This study included a study of the prevalence of rotavirus subgroups during a six year (1988 - 1993) and the prevalence of serotypes in and around Colombo over a five year period (1988 - 1992), and development of rotavirus detection kits using murine monoclonal antibodies (Mabs) as well as an attempt to detect group C rotaviruses. Subgrouping and detection of group C rotaviruses were performed by RNA gel electrophoresis. Serotyping was performed by reverse transcriptase polymerasse chain reaction (RT-PCR). An attempt was made to develop enzyme immunoassay (EIA) to serotype with serotype 2 specific monoclonal antibodies developed during this study and purchased monoclonal antibodies specific for setrotype 1,3 and 5. Latex agglutination test (LA) and reverse passive haemagglutination tests (RPHA) were developed with serotype 2 monoclonal antibodies. Two stocks (previous and present) of stool sample (1988-1982 and 1993) collection were used in this study. dsRNA from 840 stool samples positive by EIA collected during 1988-1993 were extracted and subgroups were determined by 10 percent continuous sodium dodecyl polyacryalamide gel electrophoresis (SDS PAGE). 20 samples did not give bands in SDS PAGE. Efficacy of determination of subgroups was 97.6 percent. On analysis of the band patterns 303 of 820 (36.9 percent) isolates were subgroup 1 (short pattern: serotype 2) and 517 of 820 (63 percent) were subgroup II (long pattern: serotype 1,3,4,8,9 or 12 during this study period. The difference in the percentage of occurrence of subgroup I and II was statistically significant. Prevalence of subgroup I in consecutive years from 1988 to 1993 was lowest (25 percent) in 1991 and highest 48.2 percent) in 1993. In contrast subgroup II prevalence was highest in 1991 (75 percent) and lowest in 1993 (51.5 percent). The prevalence of subgroup II since 1991 declined steadily with time, while prevalence of subgroup I increased. Both subgroups approached 50 percent prevalence in 1993. This indicates that prevalence of subgroups changed with time and reflects the changes in immunity of the population at risk. Serotyping was performed by reverse transcriptase polymerase chain reaction (RT PCR). Purified dsRNA of representative stool samples (from previous stock) in subgroup II (long pattern viruses from each year (1988-1992) were serotyped by RT PCR. The prevalence of serotype 1,3,8 and 9 changed significantly over the study period. Serotype 2 and 4 did not show sharp changes. There were untypable serotypes in 1988 and 1990. The prevalence of serotype I increased sharply to 25 percent in 1992. The prevalence of serotype 3 was maximum in 1990 and 1991 (28.3 percent and 36 percent respectively) but fell sharply to 2.5 percent in 1992. The prevalence of serotype 8 increased after 1988 to 34.2 percent in 1989, decreased significantly in 1990 (28.3 percent and fell to 6 percent and 5 percent in 1991 and 1992 respectively. The prevalence of serotype 9 was maximum in 1988 (10 percent) and fell gradually in 1991 and 1992 to zero. This reflects the herd immunity of the study population during 1988-1992. In spite of the herd immunity, certain serotypes remained in the community although they varied in their frequency. The appearance of different serotypes at different time periods during this period, indicated the emergence of new strains of rotaviruses. This shows the existence of strain diversity of serotypes. An attempt was made to produce monoclonal antibodies (Mabs) to different serotypes of rotaviruses with the intention of developing rapid, cheap and relaiable detection tests for rotaviruses in stools. Several rotavirus serotypes (1,2,3 and 4) were grown in tissue culture and purified by column chromatography for antigen preparation. Antigens were concentrated by lyophylisation and used to immunize Balb/C mice intraperitoneally and intrasplenically. 25 fusions (splenic cell and myeloma cells) were performed from mice immunized intrasplenically and 17 were performed from intraperitoneally immunized mice. Two fusions performed from mice intrasplenically immunized with serotype 2 yielded Mabs. These Mabs were specific for serotype 2 and belonged to immunoglobulin subclass IgG3. Latex agglutination test (LA-Mab) and reverse passive hemagglutination test (RPHA-Mab) were developed with serotype 2 specific monoclonal antibodies developed during this study. In adition, a reverse passive haemagglutination test (RPHA-B218) using commercially available polyclonal antibodies (B218-Dakopatts), was also developed. Sensitivity and specificity of these three tests were compared with commercially available EIA (Dakopatts) which was considered as the gold standard. Sensitivity and specificity of latex agglutination test was evaluated in two series of tests. In one series 130 of 240 subgrouped rotaviruses were detected by LA-Mab giving a sensitivity of 54.1 percent and a specificity of 88perecent.In the case of subgroup I rotaviruses the LA-Mab detected 98 of 163(60.1 percent) in contrast to 32 of 77 (41.5 percent) subgroup II viruses. In the second series 75 rotavirus positive and 75 negative stools were tested by LA-Mab, RPHA-B218. LA-Mab detected 66 of 75 giving a 88 percent sensitivity and 90.4 percent specificity. RPHA-Mab detected 73 of 75 giving a sensitivity of 97.3 percent and 92.5 percent specificity. RPHA-B218 detected 74 of 75 with 98.6 percent sensitivity and 94.4 percent specificity. RPHA-Mab test developed in this study was more sensitive and specific than LA-Mab. RPHA-B218 was more sensitive and specific than RPHA-Mab. Using EIA (Dakopatts as gold standard, the positive predictive values of three tests developed were compared. Positive predictive value of LA-Mab, RPHA-Mab and RPHA-B218 were 90.4 percent, 92.4 percent, 94.87 percent respectively. Hence, of the three rapid tests developed, RHPAB218 in which polyclonal antibodies were used, was the most promising and easy to perform rapid test for rotavirus detection. For the detection of group C rotaviruses, 400 stool samples which were negative by EIA were analysed by SDS-PAGE. None of the samples contained group C rotaviruses. This was the first attempt to detect group C rotaviruses in Sri Lanka and this indicated that group C rotaviruses were not a significant cause of diarrhea in children in Sri Lanka respectively. Hence, of the three rapid tests developed, RHPAB218 in which polyclonal antibodies were used, was the most promising and easy to perform rapid test for rotavirus detection. For the detection of group C rotaviruses, 400 stool samples which were negative by EIA were analysed by SDS-PAGE. None of the samples contained group C rotaviruses. This was the first attempt to detect group C rotaviruses in Sri Lanka and this indicated that group C rotaviruses were not a significant cause of diarrhea in children in Sri Lanka.

Detecção de roteiros e adenovírus na Grande São Paulo no período 1984-1986: estudo eletroforético do genoma dos rotavírus / Rotavirus and adenovirus detection in the Greater Säo Paulo in 1984-1986: eletrophoretic study of the rotavirus genome

No período de 1984 a 1986, 285 amostras de fezes de crianças com sintomatologia diarreica foram submetidas às provas diagnósticas de ensaio imunoenzimático, eletroforese em gel de poliacrilamida e microscopia eletrônica. Destas amostras, 15,4% foram positivas para rotavírus e 3,2% para adenovírus. Das 44 (15,4%) amostras positivas para rotavírus pelo método imunoenzimático, 37 apresentaram perfil eletroforético do RNA característico dos rotavírus. Destas últimas, 27 foram analisadas segundo o esquema de Lourenço et alii, 1981, tendo sido verificada grande heterogeneidade de perfis e predominância dos rota vírus do subgrupo 1 foi detectada (AU).