Neonatal Gastroenteritis Research Articles

Effects of milk extracellular vesicles from bovine, human, and caprine origin on rotavirus infectivity in cultured human intestinal cells

Rotavirus is the leading cause of severe gastroenteritis in neonates representing a global health burden. Milk-derived extracellular vesicles [EVs] have emerged as potential antivirals, offering a promising avenue for intervention. The present study evaluated the antiviral activity of EVs sourced from bovine, human, and caprine milk against the infection of the human Wa and bovine WC3 rotavirus strains. EVs induced an endogenous effect in Caco-2 cells, resulting in a significant reduction of rotaviral infection. The antiviral properties of the milk EVs, were found to be associated with synergistic interactions at pre- and post-attachment stages of the infection. Finally, the effect of milk processing on bovine milk EVs efficacy was assessed. It was found that after high-temperature short-time pasteurization EVs retained their activity, while homogenization resulted in no antiviral effect at all. Overall, our findings demonstrate a significant reduction in rotavirus infection in cultured Caco-2 cells when treated with milk EVs.

Tinjauan Ketepatan Kode Diagnosa Gastroenteritis pada Pasien Rawat Inap di Rumah Sakit Umum Daerah Budhi Asih

The results of early observations at the Budhi Asih Hospital, on the medical record files of inpatients with a diagnosis of gastroenteritis, found that there were still coding errors. The Gastroenteric Code is divided into two, namely infectious gastroenteritis and non-infectious gastroenteritis. Infectious gastroenteritis can be coded A09.0 (acute infectious gastroenteritis) or A09.9 (unspecified infectious gastroenteritis). Meanwhile, non-infectious gastroenteritis can be coded K52.- and non-infectious gastroenteritis in neonates is coded P78.3.
 The completeness and accuracy of gastroenteritis coding comes from doctors and nurses who record information on the patient's condition, as well as coding officers providing coding. The purpose of this study was to determine the completeness and accuracy of coding in cases of gastroenteritis in hospitalized patients based on ICD-10.
 Keywords: Diagnostic code accuracy, Gastroenteritis, Discharge Summary.

The prevalence and factors contributing to the incidence of neonatal gastroenteritis in newborn calves

The results of monitoring the situation of neonatal gastroenteritis of calves are presented for four farms in the north-western districts of the Saratov region, during the period of mass calving. The incidence of neonatal gastroenteritis of calves was 11.92 - 16.36%. Factors contributing to the morbidity of newborn calves with neonatal gastroenteritis - complications of pregnancy, depending on the gestational period, subclinical ketosis (27.65%), osteodystrophy (15.71%), liver and kidney diseases (10.59%) have been established. In 30.23% of calves with NG, a large number of under-oxidized metabolic products and impaired liver and kidney function were observed. In patients with severe neonatal gastroenteritis, the following indicators were at a low level: alkaline reserve (40.8 ± 1.3 vol% CO2), glucose content (2.86± 0.12 mmol/L). In the central part of the liver, large-drop granular dystrophy is observed with the preservation of the structure of hepatocytes.

Modern aspects of pathogenetic therapy of newborn calves in neonatal gastroenteritis

The article presents the results of experimental studies of the effectiveness of the use of combined drugs of domestic production in the complex therapy of acute gastrointestinal pathology in newborn calves of the colostrum period. The therapeutic efficacy of various drug regimens used in mild and severe forms of neonatal gastroenteritis was evaluated. Hematological and biochemical parameters are presented before treatment and during therapy of experimental and control groups of calves with neonatal gastroenteritis. The most effective scheme of complex treatment of newborn calves with neonatal gastroenteritis has been established.

Site-specific integration of rotavirus VP6 gene in rabbit β-casein locus by CRISPR/Cas9 system.

Rotavirus (RV) is the leading cause of viral gastroenteritis in neonates and VP6 protein has been discussed as a potential candidate vaccine. CRISPR/Cas9 was the latest generation of gene editing tools that can mediate the site-specific knock-in of exogenous genes, providing strong support for the expression of recombinant proteins. Here, seeking to design a rotavirus vaccine that would be suitable for both mammary-gland-based production and milk-based administration, rabbit β-casein (CSN2) locus was chosen as the target site to integrate the VP6 gene. The efficiency of inducing mutations in different target sites of rabbit CSN2 locus was analyzed and g4 site seems to be the best one to generate mutations (g4 72.76 ± 0.32% vs g1 30.14 ± 1.93%, g2 38.53 ± 0.75%, g3 52.26 ± 1.16%, P < 0.05). We further compared the knock-in efficiency through cytoplasmic injection of two group mixtures (containing 100ng/μL Cas9 mRNA or Cas9 protein, 20ng/μL sgRNA4, and 100ng/μL donor vector) in rabbit zygotes, though the Cas9 mRNA group induced an HDR efficiency as high as 20.0% ± 2.6% than Cas9 protein group (10.3% ± 3.1%), 37.5% of the knock-in events were partial integration in the target site, when Cas9 protein used in the CRISPR/Cas9 system, all of the positive blastocysts showed completely integrated, results showed that the use of Cas9 protein is better than Cas9 mRNA to integrate the correct exogenous gene into the target site. Moreover, the transgenic rabbit that harbored correct integration of VP6 gene was obtained using Cas9 protein group and was used to produce an experimental milk-based rotavirus vaccine. Our research provides a novel strategy to produce rotavirus subunit vaccine and make a foundation for building broader milk-based vaccine protection against other pathogens.

Changes in the heart of neonatal rats after cryptosporidial gastroenteritis of different degrees of severity

Disturbances at the childhood age increase risk of the appearance of cardiovascular diseases decades later. The nature of this interconnection called ontogenetic programming is not completely understood. Valuable sources of knowledge about mechanisms of ontogenetic programming are data of interspecies study of biology of the body life cycles and of heart physiological capabilities. Taken into account the interspecies differences, these data allow finding the correct direction of experimental investigations. Results of studies of almost 100 homoiothermal species have shown the slow growth and a high loading on the heart at postnatal development to decrease its aerobic capability in adults. Basing on these data, we suggested that the neonatal gastroenteritis causing tachyarrhythmia, malabsorption, and the growth deceleration might lead to pathological changes in the heart. Our task was to evaluate the effect of cryptosporidial gastroenteritis of different degrees of severity on heart of the neonatal rats. By using methods of Real-Time PCR, immunocytochemistry, image analysis, and study of interatrial septum, we have established that a gradual increase of intensity of infestation with Cryptosporidium parvum oocytes causes sharp changes corresponding to the "all or nothing" response. At a weak infestation the interatrial septum was close (like in control), while significant changes in expression of isoforms of heavy chains of alpha- and beta-myosin were absent. At the intermediate and severe infestation, in the interatrial septum the foramen ovale was visualized and there were observed cardiac atrophy and a strong shift of ration of expression of myosin heavy chains toward the low-velocity beta chain. Thus, by disturbing the frequency-strength ratios and causing outflow of resources from the formed heart, the neonatal gastroenteritis produces pathological changes of the organ molecular and anatomical structures. Our results can be interest to evolutionary biologists and physicians, as they show importance of knowledge of evolutionary-comparative investigations for the search for novel risk factors of heart diseases and demonstrate interconnection between gastroenteritis, pathology of interatrial septum, and a change of composition of the main contractile proteins in cardiomyocytes.

Remodeling of rat cardiomyocytes after neonatal cryptosporidiosis. I. Change of ratio of isoforms of myosin heavy chains

Diseases of the human cardiovascular system are the main cause of death in developed countries. Therefore, searching for new risk factors thereof is of particular interest. Upon comparing epidemiological data with data of transcriptome of cardiomyocytes and comparative physiology of vertebrate ontogenesis, we have come to the conclusion that one such factor may be gastroenteritis. This disease includes at once several stimuli able to cause functional and metabolic alterations in the heart: tachycardia, hormonal and ionic misbalance, and outflow of resources from the cardiovascular system. Using the model of rat neonatal gastroenteritis caused by the widespread human and animal enteropathogen Cryptosporidium parvum (Apicomplexa, Sporozoa), we studied the change of expression of α- and β-myosin heavy chains after the developed cryptosporidiosis. Online data obtained by methods of immunocytochemistry, quantitative morphometry, and polymerase chain reaction not only have confirmed our suggestion, but also have shown that moderate 4-day-long cryptosporidiosis is sufficient for producing a significant (1.7- to 4.5-fold) shift in the ratio of myosin isoforms toward the β-isoform beta at the level of mRNA and at the level of protein (2.5–6 times). The reciprocity of the changes, as well as their clear similarity at the level of mRNA and of protein, indicates that the cryptosporidial gastroenteritis involves all the main chains of a complex network of regulation of expression of the myosin heavy chains. A shift of the ratio of myosin isoforms toward the β-isoform that has an ATPase activity several times lower than the α-isoform is the commonly accepted indicator of human heart failure; therefore, the cryptosporidial gastroenteritis can be considered a novel risk factor for decrease of the heart’s contractile ability. Our data may be of interest for clinical and preventive medicine.

Outbreak of Neonatal Gastroenteritis Associated with Astrovirus Serotype 1 at a Hospital in Inner Mongolia, China

This report describes for the first time an outbreak of acute gastroenteritis among neonates associated with human astrovirus (HAstV) serotype 1b at a maternity hospital in Inner Mongolia, China. Of 40 specimens, 28 were astrovirus positive and rotavirus, calicivirus, and adenovirus negative. Poor hygiene likely contributed to the spread and persistence of HAstV in the neonatal care room.

L'observatoire de la grande douve : Évaluation des mesures à mettre en place dans les élevages pour maîtriser la fasciolose et premiers résultats

Les premiers résultats de l’ «Observatoire de la grande douve » offrent une plateforme intéressante aux vétérinaires praticiens pour l’élaboration de plans de lutte formalisés contre des maladies endémiques (parasitisme, mammites, gastro-entérites néonatales…). En effet, les éleveurs acceptent de plus en plus l’idée de rémunérer un conseil, sous réserve qu’il soit pertinent et rentable. Ces protocoles de traitement et de prévention, conformes à la méthode HACCP, laissent percevoir l’organisation de la politique sanitaire des années à venir. L’exemple de la maîtrise de la fasciolose illustre les actions à promouvoir : dépister, identifier les facteurs de risque, prescrire des mesures thérapeutiques et agronomiques, et enfin, contrôler l’efficacité du plan d’action. Les premiers résultats obtenus en élevage confirment l’intérêt majeur de cette démarche.

Pharmacokinetics of marbofloxacin, after one bolus oral administration in buffaloes calves: Preliminary study.

Buffalo breeding system has a great economic importance in South-America, principally in marginal or sub-tropical lands. The therapeutic recommendations applied to a single ruminant species are extrapolated to others but important differences among those were recognized. Marbofloxacin bolus is indicated in the treatment of neonatal gastroenteritis caused by Escherichia coli, in calves (25-50kg). The aim of this study was determined the pharmacokinetic behaviour of marbofloxacin after oral administration, as bolus, following the label approved recommendations to cattle. One bolus (50 mg) was administered in two clinically healthy buffaloes (two days-old, 48-50kg). Plasma concentrations of the marbofloxacin were determined by a HPLC/u.v. method. After oral administration, the values obtained were: tmax=0.5-6h, Cmax= 1.19-0.04μg/mL, AUCt=1.57-0.38μg·h/mL and MRTt= 3.34-6.92h, for calves 1 and 2 respectively. Fluoroquinolones act by concentration dependant killing mechanism, so high plasma concentration initially is important. For this reason, the recommended dose of 1mg/kg is inadequate in buffaloes.

Extended Spectrum ??-Lactamase-Positive Escherichia coli Bacteremia Complicating Rotavirus Gastroenteritis

To the Editors: In a recent publication in the Journal, Carneiro et al1 described a case of acute rotavirus gastroenteritis complicated by extended spectrum β-lactamase-positive Escherichia coli septicemia, presenting as fever, lethargy and hypotension 4 days after the initial symptoms of viral gastrointestinal disease. We present here an additional case and highlight the clinical messages concluded from this experience. A 16-month-old girl was transferred from a local hospital to the Pediatric Intensive Care Unit at the Schneider Children's Medical Centre of Israel, for the correction of a tracheobronchial congenital anomaly consisting of severe tracheal stenosis, abnormal origin of the right upper lobe bronchus and a pulmonary sling. Because of this anomaly, she had been hospitalized for most of her life and required multiple courses of antibiotic therapy for recurrent episodes of respiratory infections. Twenty-six days after surgery, severe diarrhea and a low grade fever ensued. Enzyme immunoassay of a stool specimen was positive for rotavirus. Intravenous fluids were administered, and her condition rapidly improved. Five days after the first gastroenteritis symptoms, the child developed a fever of 39.8°C. Laboratory examinations showed a white blood cell count of 28,000/mm3, absolute neutrophil count of 20,000/mm3 with a normal platelet count (172,000/mm3) and hemoglobin concentration (11 mg/dL). Coagulation studies were normal. Blood and urine cultures were obtained. Because of her good general condition, antibiotic treatment was not started initially. Upon receiving the initial blood culture result of Gram-negative bacteria, treatment with ceftriaxone was initiated. However, the blood culture isolate was identified as an extended spectrum β-lactamase-producing E. coli resistant to cephalosprins. Antimicrobial treatment was then changed to a 7-day course of ertapenem with a subsequent event-free course. Urine culture was negative. The child was transferred back to her local hospital for further follow-up. It has been recently reported that rotavirus gastroenteritis in neonates and young infants may be complicated by enteric Gram-negative rod bacteremia.2,3 Although the precise pathogenesis remains to be ascertained, it is conceivable that the damaged intestinal mucosa caused by rotavirus enabled translocation of bacteria from normal intestinal flora, causing secondary bacteremia. The typical course of this complication is a second peak of fever.2,3 A similar sequence has been reported in other causes of acute gastroenteritis.4–6 In the case presented here, the patient had previously received numerous courses of antibiotics, enabling the growth of a multiply resistant strain. Eran Mel, MD Elhanan Nahum, MD Unit of Pediatric Intensive Care Alexer Lowenthal, MD, MSc Unit of Pediatric Infectious Diseases Shai Ashkenazi, MD, MSc Department of Pediatrics A Schneider Children's Medical Center Petah Tikva, Israel Second affiliation for Drs Nahum and Ashkenazi Sackler School of Medicine Tel Aviv University Tel Aviv, Israel

Factors associated with time to neonatal diarrhoea in French beef calves

A prospective study was carried out on 92 randomly selected beef herds in the Midi-Pyrénées region in France. The objective was to determine factors associated with time to neonatal gastroenteritis. By taking into account the “intra-herd” correlation in failure time (in the semiparametric Cox model), we identified 12 management risk factors associated with hazard of diarrhoea. Some previously have been identified, but “new” risk factors were feeding of corn silage and the incidence of diarrhoea in the last season. We used the two main approaches which are often reviewed: marginal and frailty Cox models. Our results show that these two models give different parameter estimates, so the choice of the model remains crucial.

Characterization of G10P[11] rotaviruses causing acute gastroenteritis in neonates and infants in Vellore, India.

Rotavirus G10P[11] strains, which are commonly found in cattle, have frequently been associated with asymptomatic neonatal infections in India. We report the finding of G10P[11] strains associated with severe disease in neonates in Vellore, southern India. Rotavirus strains from 43 fecal samples collected from neonates with or without gastrointestinal symptoms between 1999 and 2000 were genotyped by reverse transcription-PCR. Forty-one neonates (95%) were infected with G10P[11] rotavirus strains, and 63% of the infections were in children who had gastrointestinal symptoms, including acute watery diarrhea. G10P[11] strains were also seen infecting older children with dehydrating gastroenteritis in Vellore. Characterization of the genes encoding VP7, VP4, VP6, and NSP4 of these strains revealed high sequence homology with the corresponding genes of the asymptomatic neonatal strain I321, which in turn is very closely related to bovine G10P[11] strains circulating in India. No significant differences were seen in the sequences obtained from strains infecting symptomatic neonates or children and asymptomatic neonates.

Immunogens of rotaviruses

Rotaviruses cause gastroenteritis in neonates of many animal species including cattle, swine, horses, dogs, cats, chickens and turkeys. Rotavirions are nonenveloped, are about 75 nm in diameter, have a double capsid, and contain 11 double-stranded RNA segments as their genome. Several antigenically distinct groups of rotaviruses have been identified and have been alphabetically designated as A through G. Group A rotaviruses were the first group of rotaviruses isolated and are the most commonly detected rotaviruses in diarrheic animals. Group A rotaviruses have two surface proteins, VP4 and VP7, both of which are important in serotype determination and in inducing neutralizing antibodies and protective immunity. Multiple serotypes of group A rotavirus based on glycoprotein VP7 (designated as G types) and based on VP4 (P types) have been identified. The immune response to rotaviruses is essentially serotype specific, however, cross-reactive or heterotypic epitopes have also been identified. Currently acceptable methods for immunogen quantitation include the induction of neutralizing antibody in host or laboratory animals. The in vivo efficacy of vaccines against rotavirus-associated gastroenteritis remains the standard method against which in vitro methods must be compared. Several animal models have been developed which could potentially be used in evaluating the efficacy of candidate vaccines. Monoclonal antibodies to rotavirus immunogens are also currently available and serve as valuable reagents for in vitro quantitation of rotaviral immunogens.

Nosocomial outbreak of neonatal gastroenteritis caused by a new serotype 4, subtype 4B human rotavirus

A nosocomial outbreak of rotavirus gastroenteritis involving 52 newborns occurred between June and September 1988 at the University Children's Hospital of Freiburg, Federal Republic of Germany. Stools from 27 representative patients were examined for rotavirus serotypes, using a monoclonal antibody-based enzyme-linked immunosorbent assay. The electropherotype was also examined by polyacrylamide gel electrophoresis of genomic RNA. As many as 18 patients were found to be infected by serotype 4, subtype 4B strain, and in all of them the same electropherotype was detected. Although rotavirus from the remaining nine patients could not be typed, the electropherotype in four was identical to that of the serotype 4, subtype 4B strain. Thus, most of the patients in the outbreak were infected by the same rotavirus strain. Retrospective epidemiological studies showed that the 4B strain began to circulate at the hospital in January 1988, whereas only rotavirus serotypes 1, 3, and 4A were detected in 1985-1987. The primary case of the outbreak was presumably a newborn with acute gastroenteritis, admitted to the hospital from a small maternity unit in the same urban area. During the outbreak, 12 of 44 healthy newborns in the nurseries of the Children's Hospital and other maternity hospitals were found to be asymptomatic rotavirus carriers, and in three of the newborns the same 4B strain was detected. This is the first reported outbreak caused by a serotype 4, subtype 4B strain.

A comparison of three rapid diagnostic methods for the detection of rotavirus infection in calves

Three techniques for the detection of rotavirus in faecal samples from calves with neonatal gastroenteritis were compared. A preliminary study indicated that reverse passive haemagglutination (RPHA) was at least as sensitive as the enzyme-linked immunosorbent assay (ELISA). These two immunoassays were compared with the detection of viral RNA by polyacrylamide gel electrophoresis (PAGE) on 209 field samples. Of the 77 samples in which at least one test gave a positive result, 69 were positive by both RPHA and PAGE, but only 49 were also positive by ELISA, indicating a lower sensitivity for the latter test. The overall agreement between RPHA and PAGE was 96%. The reasons for the discrepancies between the tests are discussed.