Economic impact of an infection control education program in a specialized preschool setting.

OBJECTIVE: To assess the economic impact, from a societal perspective, of a multidimensional infection control education program (ICEP) in a preschool for children with Down syndrome. METHODS: Krilov et al implemented a comprehensive ICEP in a specialized preschool setting and reported a significant decrease in medical resource utilization and days absent from school. Clinical and economic data from Krilov et al and other sources were incorporated into a health-state transition (Markov) decision analysis model that estimated annual expected costs for the baseline and intervention years. Procedure and diagnosis codes were assigned to all physician office visits, emergency department visits, hospitalizations, and laboratory and diagnostic tests. Cost estimates then were derived using 1999 national reimbursement schedules and other sources. Productivity losses for parents were estimated using national wage rates. The costs of the ICEP were compared with the reduction in the costs of illness (direct medical costs plus costs associated with lost parental working time). The outcomes measured were mean annual costs of illness per child, total annual ICEP costs, and net annual costs or savings. RESULTS: With a comprehensive ICEP, the mean costs of illness in the baseline year was $1235 per child, of which 68% and 14% were for productivity losses and physician visits, respectively. In the intervention year, the mean costs of illness per child was $615, of which 71% and 20% were for productivity losses and physician visits, respectively. The cost of the preexisting infection control (IC) practices in place at the onset of the study (baseline year) was $716. The comprehensive ICEP cost (intervention year) was $75 627, 92% of which was spent to hire a cleaning service to decontaminate toys 3 times per week. When a secondary analysis was performed to reflect a less intensive ICEP in a nonspecialized preschool setting, the mean costs of illness in the baseline and intervention years were $962 and $614 per child, respectively, representing a total annual cost-of-illness savings of $13 224 for the 38 children who participated in the study by Krilov et al. The annual incremental cost of the less intensive ICEP was $2371; therefore, the estimated net annual savings of the less intensive ICEP in a nonspecialized preschool was $10 853. CONCLUSIONS: This study suggests that the reduction in the costs of illness could more than offset the cost of implementing a multidimensional ICEP in a preschool setting.

Active immunization in the United States: developments over the past decade.

The Centers for Disease Control and Prevention has identified immunization as the most important public health advance of the 20th century. The purpose of this article is to review the changes that have taken place in active immunization in the United States over the past decade. Since 1990, new vaccines have become available to prevent five infectious diseases: varicella, rotavirus, hepatitis A, Lyme disease, and Japanese encephalitis virus infection. Improved vaccines have been developed to prevent Haemophilus influenzae type b, pneumococcus, pertussis, rabies, and typhoid infections. Immunization strategies for the prevention of hepatitis B, measles, meningococcal infections, and poliomyelitis have changed as a result of the changing epidemiology of these diseases. Combination vaccines are being developed to facilitate the delivery of multiple antigens, and improved vaccines are under development for cholera, influenza, and meningococcal disease. Major advances in molecular biology have enabled scientists to devise new approaches to the development of vaccines against diseases ranging from respiratory viral to enteric bacterial infections that continue to plague the world's population.

A prospective case-control study of the role of astrovirus in acute diarrhea among hospitalized young children.

This study examines the importance of astroviruses as a cause of acute diarrhea in hospitalized children <10 years old during a 5-year period. Stools were screened by electron microscopy and were tested for astrovirus, rotavirus, and enteric adenovirus by EIA. During the study, 14.6% of hospitalized children had diarrhea. Astroviruses were second only to rotaviruses as etiologic agents of both community-acquired and nosocomial diarrhea. Community-acquired astrovirus infection occurred in 6.8% of patients, and nosocomial disease occurred in 16.2%. Most cases occurred from March through June, and astrovirus type 1 was the most common. The symptoms of astrovirus-infected children were similar to those of children with rotavirus infection. However, astrovirus-infected children had a lower median age, less dehydration, and lower symptom severity scores and were less likely to have been admitted for gastroenteritis than were children with rotavirus. Astrovirus, for which only rehydration therapy is required, should be considered as another common diarrheal pathogen in children <2 years old.

Rotavirus vaccine and intussusception. Where do we go from here?

Since the discovery of rotavirus in 1973, vaccine technology has moved from the use of monovalent attenuated animal rotavirus strains to the development of multivalent human-animal reassortment vaccines. The first licensed vaccine, a rhesus-human tetravalent vaccine, was licensed in 1998. This vaccine was withdrawn from the market a year later when it was noted that administration of vaccine was associated with an increased risk of intussusception. The future of rotavirus vaccine is dependent on the reasons for this association that have yet to be discovered.

Transmission of rotavirus and other enteric pathogens in the home.

Rotavirus is the most common gastrointestinal pathogen present in day-care settings. Control and prevention of rotavirus infection are difficult because of the lack of a licensed vaccine, the absence of any effective treatment other than palliative measures and the presence of asymptomatic children shedding virus. Rotavirus is transmitted by fecal-oral contact and possibly by contaminated surfaces and hands and respiratory spread. Other gastrointestinal pathogens are also transmitted primarily by the fecal oral route, although contaminated surfaces, hands or food may also serve to transmit infection in some cases. Control and prevention measures for all enteric pathogens include isolating infected children from others, thoroughly cleaning and disinfecting environmental surfaces with effective agents and strictly following handwashing procedures before and after contact with infected persons and/or potentially contaminated surfaces.

Enzyme-linked immunosorbent assay to assess respiratory syncytial virus concentration and correlate results with inflammatory mediators in tracheal secretions.

OBJECTIVE: We developed an enzyme-linked immunosorbent assay (ELISA) for the quantitation of respiratory syncytial virus (RSV) in respiratory secretions in intubated patients infected with RSV. METHODS: We compared the quantitative ELISA and a standardized plaque assay in intubated children <2 years of age who were mechanically ventilated for severe RSV disease and enrolled in a randomized double blind placebo-controlled treatment trial of a monoclonal antibody to the F protein of RSV (palivizumab; Synagis). We also examined the relationship between the concentrations of virus as measured by ELISA and of three inflammatory indices in respiratory secretions (white blood cell count, myeloperoxidase and eosinophilic cationic protein). RESULTS: Quantitative ELISA and plaque assay were highly correlated for both tracheal aspirates (r = 0.67, P = 0.001) and nasal wash specimens (r = 0.75, P = 0.001). Treatment with palivizumab significantly neutralized RSV in tracheal aspirates as measured by plaque assay. In contrast quantitation of RSV by ELISA was not affected by palivizumab treatment. This finding is consistent with results that were obtained in preliminary studies of RSV-containing media treated with monoclonal antibody, where we found that the ELISA measured virus whether antibody-bound or not. The inflammatory indices were not correlated with RSV concentration measured by ELISA or plaque assay. CONCLUSIONS: We conclude that this quantitative ELISA is a potentially useful tool for measurement of RSV concentration in respiratory secretions that may help elucidate the pathophysiology of acute RSV infection. Specific antiviral strategies for the treatment of RSV disease could be evaluated by this method.

Evaluation of the ImmunoCardSTAT! rotavirus assay for detection of group A rotavirus in fecal specimens.

Rapid detection of group A rotavirus was performed by using ImmunoCardStat! Rotavirus (ICS-RV) (which uses immunogold-based, horizontal-flow membrane technology), two commercial enzyme immunoassays (Premier Rotaclone and TestPack Rotavirus), and electron microscopy. A total of 249 stool specimens collected from children with gastroenteritis between February and April 1997 were tested. After resolution of 19 of the 22 discordant results by reverse transcription-PCR for group A rotavirus, ICS-RV detected 125 positives while Rotaclone and TestPack detected 127 and 129 positives, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value were 94.0, 100, 100, and 93.4% for ICS-RV; 95.5, 100, 100, and 95.0% for Rotaclone; and 97.0, 96.5, 97.0, and 96.5% for TestPack. ICS-RV was sensitive and specific and was relatively simple to perform and interpret.

Reduction of respiratory syncytial virus (RSV) in tracheal aspirates in intubated infants by use of humanized monoclonal antibody to RSV F protein.

Thirty-five children <2 years of age mechanically ventilated for respiratory syncytial virus (RSV) infection were randomized to receive an intravenous infusion of 15 mg/kg MEDI-493 or placebo. RSV concentration was measured in tracheal secretions by plaque assay before and at 24-h intervals after treatment. The reduction in tracheal RSV concentration from day 0 to day 1 (-1.7+/-0.28 vs. -0. 6+/-0.21 log10 pfu/mL; P=.004) and from day 0 to day 2 (-2.5+/-0.26 vs. -1.0+/-0.41 log10 pfu/mL; P=.012) was significantly greater in the MEDI-493 group than in the placebo group. RSV concentration in nasal aspirates did not differ significantly between the groups. No significant differences were observed in the tracheal aspirate white blood cell count, or myeloperoxidase or eosinophilic cationic protein concentration, or in measures of disease severity between the groups. Thus, treatment with 15 mg/kg MEDI-493 intravenously was well-tolerated and significantly reduced RSV concentration in tracheal aspirates of children with respiratory failure due to RSV.

Serologic responses by immunoblot following natural infection with rotavirus serotypes G1 and G4 in children.

Serologic responses to proteins of rotavirus serotypes G1, P1A[8]; G2, P1B[4]; G3, P1A[8]; and G4, P2A[6] were evaluated by immunoblotting paired sera from 17 children with primary rotavirus infection. Ten children were infected with G1, P1A[8]; five with G4, P1A[8]; and two with G4, P2A[6] viruses. Anti-VP6 and anti-VP2 were seen in most responses. Homotypic anti-VP7 developed following G1 and G4 infections in 8 (80%) and 6 (86%) cases, respectively. Homotypic anti-VP4 developed in 9 (60%) cases following P1A[8] infection and in 0 of 2 cases following P2A[6] infection. Heterotypic anti-VP7 appeared against G4 (20%) and G3 (20%) following the 10 G1 infections, and against G3 (86%) and G1 (57%) following the 7 G4 infections. Heterotypic anti-VP4 occurred in only 3 (18%) children. The data show the antigenic predominance of internal proteins VP6 and VP2. Homotypic antibodies developed against VP7 but not against VP4 in most cases, while heterotypic antibodies were infrequent.

Outbreak and control of a rotaviral infection in a nursery.

Neonatal rotaviral infection generally causes an asymptomatic or mild illness. Once introduced into a nursery, it is very difficult to eradicate. We prospectively studied an outbreak of rotavirus infection in a normal newborn nursery from October 1994 through May 1995. Stool samples from infants more than 24 hours old were tested for rotaviral infection, either weekly, biweekly, or monthly. Rotavirus was identified in 164 (16%) of 1,037 tested neonates. Ninety-four (57%) rotavirus-positive neonates became symptomatic: 56 had diarrhea, 26 developed fever (rectal temperature > 38 degrees C), 25 experienced vomiting, 17 showed poor feeding, and 14 had an elevated core temperature. In total, 24 neonates were evaluated for suspected sepsis. RNA electropherotyping of samples from 91 neonates revealed infection by the same rotavirus strain in all cases. This strain differed from that isolated from 64 rotavirus-infected infants and toddlers in the pediatric ward during the same period. Infection control procedures (hand washing, isolation of infected neonates, and careful management of diapers) and early discharge of uninfected neonates were instituted, and the outbreak was eradicated 8 months after the onset. Our findings indicate that many rotavirus-infected term neonates become symptomatic and have signs suggestive of sepsis. Extended hospital stay may be an important factor in promoting rotaviral transmission. Thus, early discharge may be an additional effective method of controlling rotavirus outbreaks in a nursery.

Standardization of gastric aspirate technique improves yield in the diagnosis of tuberculosis in children.

BACKGROUND: The diagnosis of tuberculous disease in children remains a difficult one, based on epidemiologic investigation, Mantoux skin testing and suggestive radiologic findings. Because children with pulmonary tuberculosis are unable to produce sputum, gastric aspirates remain the procedure of choice for microbiologic confirmation of tuberculous disease; however, yield is frequently low. OBJECTIVES: To evaluate the effect of a standardized gastric aspirate collection protocol on diagnostic culture yield. METHODS: The gastric aspirate culture yield for Mycobacterium tuberculosis in 13 historical control children with clinically confirmed tuberculosis from 1979 to 1994 was compared with the yield in 8 children with tuberculous disease after institution of a standardized gastric aspirate collection protocol involving physician education, strict timing of collection, base neutralization of aspirate specimens and expedited processing. RESULTS: Retrospective survey of gastric aspirate results in Rhode Island from 1979 to 1994 revealed that only 1 of 13 cases (8%) of pediatric pulmonary tuberculosis were confirmed in this manner. During a 12-month period after institution of a protocol, gastric aspirates yielded positive cultures in 4 of 8 children (50%) with pulmonary tuberculosis, a yield that compares favorably with the sensitivities of 20 to 52% published in the literature. CONCLUSIONS: Attention to the technique of gastric aspirate collection, and expedited processing in particular, appears to improve the yield of this diagnostic procedure for pediatric tuberculosis.

Comparative evaluation of reactogenicity and immunogenicity of two dosages of oral tetravalent rhesus rotavirus vaccine. US Rhesus Rotavirus Vaccine Study Group.

OBJECTIVE: To compare the safety and immunogenicity of two dosages of tetravalent rhesus rotavirus vaccine (RRV-TV) and the effect of age at dosing. METHODS: A total of 195 infants were stratified by age into 2 groups, 6 to 12 weeks and 16 to 24 weeks, and randomly assigned to receive a single dose of placebo or RRV-TV containing either 4 x 10(5) or 4 x 10(6) plaque-forming units (pfu). Symptoms were recorded for 5 days after vaccination. Anti-rotavirus IgA and neutralizing antibody to human rotavirus serotypes G1 to G4 and RRV were measured in serum obtained pre- and postvaccination. RESULTS: Rates of fever > 38 degrees C (9%), diarrhea (6%) and vomiting (8%) were similar in all groups. IgA (69% vs. 49%, P = 0.02) and RRV (85% vs. 66%, P = 0.004) seroconversion rates were significantly higher in the 4 x 10(6) pfu vaccine group as were antibody titers to RRV (440.2 vs. 263.7, P = 0.04). Older infants demonstrated significantly higher seroconversion rates and antibody titers for IgA (71% vs. 52%, P = 0.03; and 110.6 vs. 54.8, P = 0.004) and RRV (92% vs. 66%, P = 0.05 and 498.3 vs. 205.6, P = 0.01) at either dose level than did the younger infants. There were no significant differences in seroconversion rates or antibody titers to human rotavirus types G1 to G4 between the two vaccination groups. CONCLUSIONS: RRV-TV at a dose of 4 x 10(6) pfu can be safely administered to infants 6 to 24 weeks of age. A single dose of 4 x 10(6) pfu of RRV-TV was significantly more immunogenic than a single dose of 4 x 10(5) pfu but did not improve responses to the human serotypes. Older vaccine recipients demonstrated significantly higher IgA and neutralizing antibody seroconversion rates and antibody titers than younger infants independent of dosage.

Safety and efficacy of high-dose rhesus-human reassortant rotavirus vaccines--report of the National Multicenter Trial. United States Rotavirus Vaccine Efficacy Group.

OBJECTIVE: Rotavirus is a leading cause of morbidity and mortality from dehydrating gastroenteritis in infants and young children worldwide. Virtually every child is infected by age 4 years, justifying universal childhood immunization when a safe and effective vaccine is available. We report the results of a multicenter, placebo-controlled field trial in the United States of monovalent serotype 1 and tetravalent (TV) rhesus-human reassortant rotavirus vaccines (RRVs). DESIGN: In this randomized, double-blind trial, 1278 healthy infants ages 5 to 25 weeks received three oral doses of RRV serotype 1, RRV-TV, or a placebo at approximately 2, 4, and 6 months of age. Vaccines contained 4 x 10(5) plaque-forming units of virus. Gastroenteritis episodes were monitored, and severity was graded throughout one rotavirus season. Two stool specimens per episode were tested for rotavirus. RESULTS: The incidence of reactions did not differ among treatment groups during the 5-day, postvaccination safety surveillance period for any of the three doses. Both vaccines significantly reduced the incidence of rotavirus gastroenteritis. Vaccination was most protective against serious rotavirus illness; RRV-TV prevented 49% of rotavirus episodes, 80% of very severe episodes, and 100% of dehydrating rotavirus illness. Reduction of rotavirus disease by RRV-TV resulted in significantly fewer total episodes of gastroenteritis of all causes and an 82% reduction in all cases of dehydrating diarrhea. CONCLUSION: RRV-TV is highly protective against very severe, dehydrating rotavirus gastroenteritis.

Sequence conservation and expression of the gene encoding the outer capsid glycoprotein among human group C rotaviruses of global distribution.

Group C rotaviruses have been identified recently from fecal samples of children with diarrhea in the United States. Using reverse transcriptasepolymerase chain reaction and sequence analysis, we sequenced gene 8s encoding VP7 from two U.S. strains (RI-1 and RI-2), and eight other strains isolated from patients on four continents, and compared these with the sequences of four published strains. The gene 8s of the 14 strains were remarkably conserved in size and in predicted primary and secondary structures. When the sequences of the human VP7s were compared with that of the prototype porcine Cowden strain, six regions were found variable in both deduced primary and predicted secondary structures, four of which were predicted to be hydrophilic and might determine serotype specificity. Gene 8 of the human S-1 strain was further characterized by expression in recombinant baculoviruses. The expressed product was immunogenic but failed to elicit neutralizing antibodies. Our sequence analysis indicates that all the human strains characterized to date belong to a single G genotype, which may constitute a single G serotype, pending further antigenic analysis. Whether the human strains and the Cowden strain are the same serotype remains to be determined.

First detection of group C rotavirus in fecal specimens of children with diarrhea in the United States.

Group C rotaviruses cause sporadic cases and outbreaks of acute diarrhea in children and adults in many countries but have never been identified from patients in the United States. Fecal specimens from children with diarrhea who were hospitalized in Providence, Rhode Island, were screened for group C rotaviruses if rotavirus was detected by electron microscopy but the specimens were negative for group A rotavirus by ELISA. Of 16 specimens examined, 3 were positive for group C rotavirus by ELISA using reagents specific to the Cowden strain of porcine group C rotavirus and all 16 were positive using a more sensitive assay: reverse transcriptase-polymerase chain reaction. Group C rotavirus infections occurred primarily among infants in winter in 4 of the 5 years examined and were acquired both in community and nosocomial settings. Future clinical and epidemiologic studies with group C rotavirus will require development of assays that are more sensitive and simpler to perform.

Varicella vaccine for prevention of chickenpox.

Release of varicella vaccine is anticipated in early 1995. The vaccine has proved to be safe and effective in clinical trials over the past 12 years. Proposed recommendations for use include a single dose for routine vaccination of 12 to 18-month-old infants and for catch-up immunization of children from 18 months to 12 years of age and a two dose schedule to immunize susceptible adolescents and adults.

Seroconversion rates to combined measles-mumps-rubella-varicella vaccine of children with upper respiratory tract infection.

OBJECTIVE: To determine if upper respiratory tract infection (URI) affects the seroconversion rate or quantitative response to each component of a combined measles-mumps-rubella-varicella vaccine. SUBJECTS AND METHODS: One hundred forty-nine children between 15 and 18 months of age were prospectively divided into two groups according to the presence of URI or recent history of URI symptoms within the 4 weeks before vaccination. Once stratified, 74 children in the healthy group and 75 children in the URI group were randomly assigned to receive one of three lots of measles-mumps-rubella varicella vaccine by subcutaneous injection into the deltoid area. Serum was obtained from each child just before vaccination and 4 to 6 weeks later for measuring antibody levels against each virus. RESULTS: Prevaccination antibody levels against each virus in the URI and healthy groups did not differ. Nine children had pre-existing antibodies to varicella and six to mumps; no child had positive serologies for measles or rubella before vaccination. Children with pre-existing antibody were excluded from analysis of seroconversion for that virus. Seroconversion to measles, mumps, and rubella occurred in 100% of children in both groups. Mean antibody levels did not differ between the healthy and URI groups for measles (111 vs 122), mumps (97 vs 108), or rubella (96 vs 102). Three (4%) of 70 children with URIs in whom varicella serologies were available failed to seroconvert to varicella vaccine although none of the 69 healthy children had vaccine failure (P = .24). The mean varicella antibody level was 11.3 +/- 1.4 in the healthy children, which did not differ significantly from the level of 9.5 +/- 0.9 in the URI group. CONCLUSIONS: Seroconversion to measles, mumps, rubella, and varicella was not significantly affected by the presence of a concurrent or recent URI in 15- to 18-month-old children.

A prospective study of Shiga-like toxin-associated diarrhea in a pediatric population.

Although population-based studies have shown that children have the highest age-specific incidence of infection with the Shiga-like toxin-producing E. coli (SLTEC), these sporadic case series were not focused specifically on the pediatric age group. We undertook a prospective study to determine the frequency of detection of SLT in an exclusively pediatric population. The study design minimized ascertainment and referral bias by systematically defining the population by the presence of diarrheal symptoms rather than by specific diagnosis, previous submission of stool for culture, or referral to a diarrhea study. All children < 10 years of age hospitalized at a tertiary care pediatric hospital, irrespective of admission diagnosis, were surveyed prospectively at admission and for 2 days thereafter for the presence of defined diarrheal symptoms. From May 1, 1991, to April 30, 1992, 227 patients and 92 age- and season-matched controls were enrolled. Fecal SLT was detected in six (2.6%) patients, three of whom had E. coli O157:H7 organisms were isolated; SLT was not found in any of the controls. SLT was more commonly detected in children 2-10 years of age and in bloody stools. Salmonella was isolated in six (2.6%) cases, Shigella in five (2.2%), and Yersinia in three (1.3%); rotavirus was detected in 46 (20.3%). Two patients with SLT-associated diarrhea had hemolytic uremic syndrome (HUS), and four had hemorrhagic colitis. SLT-associated diarrhea occurred in the summer and fall months in contradistinction to that with rotavirus, which occurred in the winter and spring.(ABSTRACT TRUNCATED AT 250 WORDS)