婴幼儿轮状病毒无症状感染的研究

目的     

A prospective study of rotavirus infection in infants and young children

Diarrhea in neonates, followed as a cohort, and their families was studied prospectively. The families were followed for an average of 16.3 months. Stool and serum specimens were obtained at least every three months. Stool specimens were examined for viruses by electron microscopy and cultured for enteropathogens, and serum specimens were tested for antibodies to rotavirus and Norwalk virus. During the study, 237 episodes of gastroenteritis were observed in 104 infants and their 62 siblings. Rotavirus, detected 82 times in 72 children, was by far the most common enteropathogen. It was associated with gastrointestinal symptoms in 72% (with diarrhea in 65%). Rotavirus diarrhea occurred mostly in winter months and was significantly more frequently associated with respiratory symptoms than were diarrheas with other etiologies. Rotavirus infection was uncommon in the first six months of life, but by two years of age, 62% of the infants had had at least one infection. Neither breast feeding nor the presence of antibody to rotavirus in cord blood appeared to be protective.     

A comparative trial of rhesus monkey (RRV-1) and bovine (RIT 4237) oral rotavirus vaccines in young children

Heterologous live, oral rotavirus vaccines of rhesus monkey (RRV-1) and bovine (RIT 4237) origin were tested for immunogenicity, excretion of virus, and clinical reactions in six- to eight-month-old infants. Antibody response, indicating infection with the vaccine virus, was detected in 21 (88%) of 24 children receiving the RRV-1 vaccine and in 18 (75%) of 24 receiving the RIT 4237 vaccine. Excretion of virus in the stools within one week after vaccination was demonstrable in 84% of the RRV-1 and in 21% of the RIT 4237 vaccinees. RRV-1 vaccination was associated with a febrile response (over 38 C) that clustered on days 3 or 4 postvaccination in 64% of the recipient children. In addition, 20% of the RRV-1 vaccinees had watery stools on days 4 or 5. Fever on days 3 and 4 and loose stools were not seen in the RIT 4237 vaccinees. We concluded that in young children the RRV-1 (rhesus monkey) rotavirus vaccine is more immunogenic than the RIT 4237 (bovine) rotavirus vaccine, but vaccination with RRV-1 is associated with significant adverse reactions.     

上海地区婴幼儿院内感染轮状病毒致腹泻病的分子流行病学调查

目的 了解上海地区婴幼儿院内感染轮状病毒(RV)致腹泻病的分子流行病学特征.方法 采用胶体金法和套式PCR,对2006年11月至2008年1月复旦大学附属儿科医院收集的226例院内感染性腹泻患儿的粪便标本进行RV病原检测,并对阳性标本进行分型,调查患儿的临床特征.数据分析分别以构成比、阳性榆出率表示,均值采用t检验.结果 胶体会法RV阳性率为47.8%.院内感染RV腹泻以1岁以内的年龄段最高,新生儿占RV腹泻患儿的32.4%.发病高峰在10、11月份.采用套式-PCR对除新生儿外的67份RV阳性标本进行分型,G3为主要流行的血清型,占46.3%,其次为G1占23.9%、G2占3.0%、G9占1.5%,7份为混合感染,均为G1、G3混合,10份未能分型.从P分型来看,主要流行株为P[8]型,占90.0%,其次为P[4]型占6.0%,3份标本未能分型.未发现P[6]、PE9]和P[10]型.G3P[8]为主要分离株,占61.2%,其次为G1P[8],占17.9%,G1、G3P[8]混合感染占9.5%,G2P[4]、G8P[9]各1例.新生儿32份RV阳件标本中10份成功分型,均为G1P[8].院内感染RV腹泻延长住院天数、增加住院费用.结论 RV是上海地区院内感染性腹泻病的主要病原,其流行的主要血清型为G3P[8]型,但仍需加强监测G1流行株的暴发流行.     

Evaluation of RIT 4237 bovine rotavirus vaccine in newborn infants: correlation of vaccine efficacy to season of birth in relation to rotavirus epidemic period

A single oral dose of bovine rotavirus vaccine RIT 4237 or placebo was given to 2 groups of 5-day-old infants, born in October 1984 (n = 244) and June 1985 (n = 245), who remained in follow-up for 2.8 and 2.0 years, respectively. The vaccine had no effect on the total number of detectable episodes of rotavirus diarrhoea: there were 22 cases in the vaccinees and 24 in the placebo recipients in the October group and 18 and 16 respectively in the June group. However, vaccination decreased significantly the clinical severity of rotavirus diarrhoea, as assessed by a numerical score 0-20; this vaccine effect was much greater in the infants born in October. The mean severity scores for vaccine and placebo recipients were 4.55 and 10.75 respectively in the October group (p less than 0.0001, t-test) and 8.2 and 11.6 respectively in the June group (p = 0.010, t-test). Vaccine-induced clinical protection against rotavirus diarrhoea did not correlate well with serological response after vaccination, but showed good correlation to the presence of rotavirus antibodies before the rotavirus epidemic season. It is concluded that bovine rotavirus vaccine is more efficacious when given immediately before the rotavirus epidemic season: the vaccine effect may be amplified by exposure to wild rotaviruses during the season.     

Evaluation of a new highly purified pertussis vaccine in infants and children

Purified acellular pertussis vaccine (12.5 micrograms of lymphocytosis promoting factor [LPF] and 12.5 micrograms of filamentous hemagglutinin [FHA]) was compared with conventional pertussis vaccine in a randomized double-blind study involving 40 children aged 4-6 y, 40 children aged 18-24 mo, and 50 infants. Increases in antibody were significantly greater among recipients of acellular vaccine than among recipients of conventional vaccine for antibodies to LPF in all age groups and for antibodies to FHA in infants and children aged 4-6 y; the increase in FHA antibody was also greater with acellular vaccine among children aged 18-24 mo but not significantly so. Compared with conventional vaccine, acellular vaccine was significantly associated with reduced frequency of leg pain and fretfulness at all ages and less frequent fever and anorexia at some ages. The reduced reaction rates and comparable or enhanced immunogenicity of the acellular vaccine make it an attractive candidate for larger field trials, particularly among infants.     

Safety and immunogenicity of human rotavirus vaccine strain M37 in adults, children, and infants.

Rotavirus vaccine strain M37 (serotype 1), recovered from the stool of an asymptomatic newborn infant and serially passaged in cell culture, was given orally to adults, children, and infants. Serologic responses were detected by neutralization assay or EIA in 59% of 17 adults (10(5)-pfu dose), 55%-60% of 21 infants and children (10(4)-pfu dose), and 70% of 10 infants (10(5)-pfu dose), vaccine virus was shed by 24%, 20%-36%, and 70%, respectively. In adults, neutralizing antibody rises to strain M37 and the related serotype 1 strain Wa occurred with equal frequency (41% vs. 47%). In pediatric subjects, the former were more frequent (36%-40%) than the latter (10%-18%). This was also true of 8 infants who received two doses of vaccine. Mild gastrointestinal illnesses occurred with equal frequency in pediatric subjects who received vaccine or placebo. Thus, strain M37 was well tolerated and immunogenic in young infants, but elicited primarily vaccine-strain-specific rather than serotype-specific neutralizing antibody responses.     

Diarrhea associated with rotavirus in rural Guatemala: a longitudinal study of 24 infants and young children.

A population of 24 infants and young children followed prospectively during the first 3 years of life was studied for the occurrence of rotavirus infection by using enzyme-linked immunosorbent assay to detect virus in stools. Infection with rotavirus was associated with 26 (14.2%) of 183 selected diarrheal episodes. Twenty of the 24 infants and young children had diarrhea associated with rotavirus on at least one occasion and six had two such episodes. Rotavirus infection was documented in over 50% of the dehydrating episodes studied, thus further indicating the importance of rotavirus in this population.     

Effect of breast-feeding on oral rhesus rotavirus vaccine seroconversion: a metaanalysis

The effect of concomitant breast-feeding on seroconversion following oral administration of rhesus rotavirus vaccine (RRV, serotype 3, strain MMU 18006) at 10(4) pfu was analyzed. Three studies were included, all randomized, double-blind trials involving a single dose of RRV to infants aged 2-5 months. None received concomitant oral polio vaccine. Seroconversion was measured by microneutralization or tube neutralization assay. The results show that 42 (48%) of 88 (95% confidence interval, 37%-58%) breast-fed babies seroconverted compared with 62 (70%) of 88 (95% confidence interval, 61%-80%) bottle-fed babies (chi 2 = 9.35, P less than .005). Thus, there was a significant adverse effect of breast-feeding with respect to RRV vaccine seroconversion.     

Psychomotor seizures in infants and young children

off authors analyzed the ictal clinical symptoms (in 6 cases with videotape monitoring) of 12 infants and young children, who had focal epileptic discharges in the temporal regions (fig. 3, 4, 5). The average age was 1 9/12 years with a range of 3 months to 5 years. In 6 cases the seizures were typical "psychomotor" with oral automatisms, aimless movements of the upper extremities and/or tonic versive motor manifestations (fig. 2). In 5 cases the seizures consisted of staring and arrest of any movement. In another case, automatisms of the upper extremities were accompanied by a psychomotor arrest reaction. It is probable that in this age group seizures with sudden arrest of activity ("temporal pseudoabsences") are more frequently the main expression of partial complex seizures than in older children and in adults.     

Whole-gut irrigation in infants and young children

In the search for a superior alternative to conventional bowel preparation which often gives unsatisfactory results in children, we have introduced whole-gut irrigation for pediatric use. After a pilot study on 15 children during which adjustments on the technique were made, we settled on an intensive regimen with some notable modifications from conventional adult practice: the use of warm Hartmann's solution, a relatively large fluid load (mean volume 5.3 l/kg body weight, range 3.0–12.0 l/kg) and a rapid infusion rate (1.5 ml/kg/min). We then evaluated its safety, effectiveness, and acceptability prospectively on 45 patients undergoing colonoscopy or colorectal surgery, age ranging from 4 months to 11 years, with a mean of 3.9 years. Subjective complaints were mild and included nausea/vomiting, 12 cases (26.7 percent); abdominal colic, two (4.4 percent); and distending discomfort, three (6.7 percent). There was a mean weight gain of 4.0 percent but no gross electrolyte disturbances. Results of bowel preparation were satisfactory in 33 (73.3 percent), adequate in ten (22.2 percent) and poor in two (4.4 percent). Compared with our previous method, in which inadequate preparation occurred in 4/20 patients, (20 percent) by conventional measures, whole-gut irrigation represents a statistically significant improvement (P<0.05). In addition, whole-gut irrigation shortened hospital stay and obviated the traditional need of two to three days' dietary restrictions.     

Rotavirus gastroenteritis in infants and young children

Summary The electronmicroscopic examination of stool samples from 18 infants and young children with gastroenteritis, hospitalized at the Clinic of Infectious Diseases in Prague, was carried out. In ten children rotavirus was found in the faeces and the bacteriological findings were negative. Rotavirus particles were aggregated by convalescent child sera and by normal human gamma globulin. The clinical picture was characterized by the sudden onset of vomiting and fever, in one case with febrile convulsions. Diarrhoea was watery and yellow-green, and usually persisted for four to five days. The condition of the children improved rapidly after rehydratation and a special diet. Older siblings, and in one family also adult members, were frequently affected.

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Rotaviren-Gastroenteritis bei Säuglingen und Kleinkindern

Zusammenfassung Während des Frühjahres 1977 wurden in der Infektionsklinik in Prag elektronenoptische Untersuchungen von Stuhlsuspensionen bei 18 Säuglingen und Kleinkindern durchgeführt. Die epidemiologischen Angaben wiesen keinen Verdacht auf Salmonellosen, Shigellosen oder Coli-Infektionen auf. In zehn Fällen wurden Rotaviren nachgewiesen. Die bakteriologischen Befunde waren bei allen Kindern negativ. Rotavirus-Partikel wurden mit Kinder-Rekonvaleszentenserum und auch mit normalem humanem Gammaglobulin aggregiert. Für das klinische Bild waren plötzlicher Ausbruch mit Erbrechen und Fieber, in einem Fall mit febrilen Krämpfen charakteristisch. Die Diarrhöe war wässerig, gelbgrün und dauerte meistens 4 bis 5 Tage. Nach Rehydratation und Diät-Maßnahmen erholten sich die Kinder rasch. Oft erkrankten auch die älteren Geschwister der Kinder und in einem Fall auch die erwachsenen Familienmitglieder.

     

Field trial of rhesus rotavirus or human-rhesus rotavirus reassortant vaccine of VP7 serotype 3 or 1 specificity in infants. The Elmwood, Panorama, and Westfall Pediatric Groups.

Orally administered live rhesus monkey rotavirus vaccine (RRV, VP7 serotype 3) and human-rhesus reassortant rotavirus vaccine (DxRRV, VP7 serotype 1) were evaluated in a placebo-controlled field trial of 223 infants 2-4 months old. Both vaccines were mildly reactogenic but were generally well tolerated in the 10 days after vaccination. RRV and DxRRV were immunogenic, inducing serum antibody responses in 78% and 71% of the vaccines, respectively. Efficacy of RRV vaccine was 66% (P = .01) and of DxRRV vaccine 77% (P = .002) against rotavirus-associated illness in the first season after vaccination. Efficacy of RRV vaccine against rotavirus-associated illness over three rotavirus seasons was 51.2% (P = .045) and of DxRRV vaccine was 67.3% (P = .006). RRV vaccine provided heterotypic protection of 58.5% (P = .041) and DxRRV vaccine provided homotypic protection of 72.8% (P = .005) over three seasons against the predominant serotype 1 rotavirus.     

Protective effect of WC3 vaccine against rotavirus diarrhea in infants during a predominantly serotype 1 rotavirus season

We used a double-blind, placebo-controlled trial to study the efficacy of WC3 rotavirus vaccine administered to 104 infants (ages, three to 12 months) before the rotavirus season. Forty-nine infants received vaccine; 55 received placebo. Rotavirus disease during this season was predominantly caused by a serotype 1 strain. In placebo recipients there were 14 cases of rotavirus diarrhea (attack rate, 25%); 11 were moderate to severe (attack rate, 20%). Vaccinees experienced only three cases of rotavirus disease (attack rate, 6.1%), all mild. When all cases (whether associated with rotavirus or not) of clinically significant diarrhea (CSD) were evaluated, WC3 vaccine provided statistically significant (P less than .01) protection against the total number of episodes of CSD and reduced the number of days of CSD-associated diarrhea, vomiting, fever, or illness. Seventy-one percent of the WC3-vaccinated infants had serum antibody responses to the vaccine. The 14 placebo recipients who experienced natural disease predominantly had antibody responses to serotype 1. Sera taken after the rotavirus season revealed a nearly identical rate (40%) of natural rotavirus infection in the vaccinated and placebo groups.     

Bronchodilator responsiveness in normal infants and young children

Several studies have demonstrated that normal infants exhibit bronchoconstriction after inhalation of nonspecific agonists and that the induced airway narrowing can be reversed by the inhalation of a beta-agonist. However, there are very limited data on baseline airway tone and the airway response to a beta-agonist in this subject population. The purpose of our study was to evaluate in normal infants baseline airway responsiveness to the inhaled beta-agonist, albuterol, using changes in maximal expiratory flows. Forty-one healthy infant volunteers with no history of respiratory disease or recurrent wheezing (ages 5.4 to 141.4 wk) were studied. Maximal expiratory flow- volume curves were obtained at baseline and 10 min after inhalation of albuterol (n = 28) or placebo (n = 13) using a metered-dose inhaler with a spacer. The mean percent change was significantly greater (p < 0.05) in the albuterol versus placebo group for FEV(0.5) (2.2% versus -1.5%), FEF(75%) (10.6% versus -3.1%), and FEF(85%) (12.9% versus 0.5%). Six of 28 albuterol-treated infants demonstrated increases in FEF(75%) greater than two standard deviations from the mean change in FEF(75%) seen in the placebo group. These infants were younger and more frequently exposed to maternal smoking during pregnancy. We conclude that normal healthy infants have overall levels of baseline airway tone that are similar to that reported in adults and older children; however, among the infants we evaluated the response to an inhaled bronchodilator was greatest in the youngest infants and in those exposed to tobacco smoking. Keywords: airway responsiveness; asthma; tobacco smoke; infant pulmonary function; bronchodilator     

Efficacy of the human rotavirus vaccine RIX4414 in malnourished children

The effect of nutritional status on protective efficacy of a live attenuated human rotavirus vaccine (RIX4414) was studied. Vaccine protection was evaluated through a secondary analysis of data from an efficacy study conducted in Brazil, Mexico, and Venezuela. Vaccine efficacy against rotavirus gastroenteritis (RVGE) was similar in well-nourished and malnourished infants: 74.1% (95% confidence interval [CI], 52.2%-86.2%) and 73% (95% CI, 11.2%-92.3%) for severe RVGE and 60.9% (95% CI, 37.4%-75.4%) and 61.2% (95% CI, 10.4%-83.1%) for RVGE of any severity, respectively. RIX4414 significantly decreased the rate of RVGE regardless of nutritional status, which suggests that this patient group can also benefit from rotavirus vaccination. CLINICAL TRIALS REGISTRY: e-Track 444563-006, NCT00385320 (http://www.clinicaltrials.gov).