Disseminated intravascular coagulation and purpura fulminans in a patient with Candida sepsis. Biopsy of purpura fulminans as an aid to diagnosis of systemic Candida infection.

Disseminated intravascular coagulation and purpura fulminans developed in association with septicemia and meningitis due to Candida tropicalis in an 18-year-old female immunosuppressed renal allograft recipient. Although systemic Candida infection was initially suspected, blood cultures showed no growth of this organism until after its identification in the dermis of a skin biopsy specimen obtained from the site of purpura fulminans. This case illustrates the association between Candida sepsis and purpura fulminans, and demonstrates the usefulness of skin biopsy of purpura fulminans in the early diagnosis of Candida sepsis.

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.

Immunogenicity of subcutaneous versus intramuscular Oka/Merck varicella vaccination in healthy children.

To compare the immunogenicity and safety of varicella vaccine by either subcutaneous or intramuscular injection, 166 healthy children aged 12 months to 10 years old who had no prior history of varicella were enrolled from two pediatric practices and randomly assigned to receive 0.5 mL of a single lot of varicella vaccine. Sera from the day of and 6 weeks postvaccination were tested for varicella antibody by gpELISA. Parents recorded clinical events occurring in the 6 weeks following vaccination. In the 132 evaluable children, the mean prevaccination titer was 0.3 gpELISA units for both groups. Sixty-three (97%) of the 65 receiving varicella vaccine by the subcutaneous route seroconverted compared with 67 (100%) of 67 immunized intramuscularly. Postvaccination geometric mean titer in the subcutaneous group was 6.9 +/- 7.0 gpELISA units and did not differ significantly from the geometric mean titer of 10.5 +/- 4.4 in the intramuscular group. Varicella vaccine was generally well tolerated by either route; 21% of both groups complained of reactions at the injection site and 7% had a varicella-like rash. Although varicella vaccine is recommended to be given subcutaneously, the results of this study indicate that inadvertent intramuscular administration of varicella vaccine is not reason for revaccination.

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.

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.

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.

Lack of impact of rapid identification of rotavirus-infected patients on nosocomial rotavirus infections.

The efficacy of rapid identification of rotavirus-infected patients in the control of nosocomial rotavirus infections on an infant and young toddler ward by use of a rotavirus antigen detection test on stool from patients with diarrhea was evaluated by comparing the rate of nosocomial rotavirus infection in children during two separate 5-week periods in the winters of 1984 and 1986. In contrast to 1984 rapid rotavirus antigen testing by latex agglutination of stool from patients with diarrhea was instituted in 1986, in addition to testing for rotavirus by enzyme immunoassay, to determine whether use of rapid antigen testing resulted in an increased incidence of appropriate isolation and a decrease in nosocomial infections. In 1986 rapid identification of rotavirus resulted in an increase in hospitalization of rotavirus-infected patients in single bed rooms from 68% to 100% (P = 0.02, chi square test) but no significant increase in the use of enteric precautions for these patients. The total number of cases of nosocomial rotavirus infection in the two periods did not differ. In both periods 11 cases occurred; the nosocomial infection rate in 1984 was 18.9 cases/1000 days of exposure whereas in 1986 it was 20.2 cases/1000 days. These findings indicate that the use of rapid rotavirus antigen testing of patients with diarrhea is not of appreciable benefit in preventing the nosocomial spread of rotavirus to infants on the ward.

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.

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.

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.

Evaluation of a new enzyme immunoassay (TESTPACK rotavirus) for the detection of rotavirus in fecal specimens.

One hundred and forty fecal specimens were tested for rotavirus using two immunoassays, TESTPACK Rotavirus and Pathfinder Rotavirus. Five discordant specimens were evaluated by a blocking assay. The sensitivity, specificity, positive predictive value, and negative predictive value were 98, 100, 100, and 99% for TESTPACK and 92, 100, 100, and 96% for Pathfinder, respectively.

Respiratory infections in the newborn.

Respiratory infections, especially pneumonia, are common in the first four weeks of life and are the cause of significant morbidity and mortality. Infants may be infected in utero, during labor and delivery, or postnatally. The etiology of neonatal respiratory infections varies widely and spans the spectrum from bacteria to protozoa. The exposure of the infant to maternal flora, the nursery environment, or household members plays an important role in determining the infecting pathogen. Diagnostic testing includes the chest film, CBC and routine bacterial cultures, but newer techniques such as latex agglutination tests for bacterial antigens or viral antigen detection or culture may be indicated in the appropriate clinical setting. This article reviews all of these aspects of respiratory infections and posits certain steps in their treatment.

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.

New tests for the rapid diagnosis of infection in children.

The development of new and more rapid methods by which to diagnose infectious diseases has just begun. Although many assays for the rapid detection of important pediatric pathogens are widely available now, new and improved assays continue to be created and marketed. It is clear that rapid diagnosis will become increasingly available to pediatricians and will assist in the diagnosis and treatment of infections in children.

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.

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.

Risk factors associated with nosocomial rotavirus infection.

A prospective study of hospital-acquired rotavirus infection was undertaken on an infant and young toddler floor to assess the incidence of infection and risk factors associated with nosocomial transmission. During the seven-month study period, gastroenteritis accounted for 60 of 663 admissions, 23 (38%) of which were due to rotavirus. In spite of enteric isolation of 21 (91%) of 23 patients with community-acquired cases, 36 infants developed nosocomial rotavirus infections. The attack rate of hospital-acquired infection was 12.8%, ranging each month from 2% to 21%. Approximately three fourths of both community-acquired cases (17/23) and nosocomial cases (27/36) occurred during the late winter and early spring. Prolonged stays in the hospital were associated with an increased attack rate of rotavirus infection. The risk of nosocomial rotavirus infection was not significantly enhanced by room contact with a rotavirus-infected patient or by the sharing of staff. However, only 47% (17/36) of patients with nosocomial infections were appropriately isolated, despite symptoms of gastroenteritis in all cases. These findings indicate that hospital acquisition of rotavirus is common, and indicate that failure to isolate patients with nosocomial rotavirus infections could be an important factor in hospital transmission.