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.

Ocular manifestations in pediatric patients with acquired immunodeficiency syndrome.

Forty pediatric patients seropositive for human immunodeficiency virus antibody and conforming to Centers for Disease Control, Atlanta, Ga, case definition of acquired immunodeficiency syndrome underwent ophthalmic examinations to evaluate prospectively the incidence, type, and natural history of ocular involvement in pediatric acquired immunodeficiency syndrome. A total of 87 examinations were performed on the patient population throughout the course of the study. Twenty percent had ocular findings, including two cases of cytomegalovirus retinitis, one case of isolated retinal cotton-wool spots, one case of toxoplasmosis retinochoroiditis, and three cases of external infections of adnexal structures. One patient had unusual peripheral retinal findings. The incidence of ocular manifestations in pediatric acquired immunodeficiency syndrome is considerably less than reported in several adult series. However, we recommend ophthalmic screening in all pediatric patients with acquired immunodeficiency syndrome with encephalopathy or disseminated opportunistic infections, or when symptoms suggest ophthalmic involvement.

The changing epidemiology of astrovirus-associated gastroenteritis: a review.

Our understanding of the epidemiology of astrovirus-associated gastroenteritis has changed markedly with each improvement in detection method. In early surveys based on electronmicroscopy (EM), astroviruses appeared to be a rare cause of gastroenteritis, being found in fewer than 1% of children with diarrhea, usually in small outbreaks of disease and primarily during the winter season. The development and use of monoclonal antibodies and enzyme immunoassays (EIA) to detect astroviruses led to reports of a higher prevalence (2.5%-9%) of astrovirus infection among patients hospitalized with diarrhea. Astroviruses appeared second only to rotaviruses as a cause of hospitalization for childhood viral gastroenteritis. Studies based on EIA detection of astroviruses indicate that astroviruses are common causes of diarrhea in children worldwide, and that most children are infected during their first two years of life. The elderly and the immunocompromised represent high-risk groups as well. The observations that newborns monitored prospectively rarely have repeat disease and that the rate of detection decreases with increasing age suggest that immunity to astroviruses, as immunity to rotaviruses, may develop early in life. The cloning and sequencing of astroviruses have led to more sensitive assays to detect the viruses by reverse transcription, polymerase chain reaction (RT-PCR). Application of RT-PCR for detection of astroviruses in children in day-care centers showed a marked increase in the detected prevalence of astrovirus-associated diarrhea, the rate of asymptomatic infection, and the duration of shedding of virus among those infected, when compared with studies that used other methods. As with rotaviruses, neither the mode of transmission nor the reservoir of astrovirus infection has been identified. Both immune and molecular-based assays to detect astrovirus serotypes indicate that serotype 1 is most common worldwide, although the predominant serotypes may vary by region and time. In the absence of obvious strategies to prevent astrovirus-associated diarrhea, vaccines might be considered if further studies establish that the disease burden would render such a vaccine cost-effective.

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.

Relationship of familial prominent corneal nerves and lesions of the tongue resembling neuromas to multiple endocrine neoplasia type 2B.

PURPOSE: We studied a two-generation family with an inherited syndrome of prominent corneal nerves and lesions of the tongue resembling neuromas without the characteristic neoplasms of the multiple endocrine neoplasia type 2B syndrome. Several different point mutations in the RET proto-oncogene on chromosome 10 have been associated with the multiple endocrine neoplasia type 2 syndromes. Molecular genetic studies of families with partial phenotypic expression of these syndromes may aid in further understanding the origin of the variety of clinical manifestations observed in multiple endocrine neoplasia type 2. METHODS: A family consisting of an 8-year-old male proband, his 10-year-old sister, and 40-year-old mother was identified as having prominent corneal nerves and lesions of the tongue resembling neuromas. Pentagastrin-stimulated serum calcitonin levels were measured in the mother and sister. Molecular genetic studies were performed on all three affected members, to look for the specific point mutation seen in over 95% of patients with multiple endocrine neoplasia type 2B. RESULTS: Serum calcitonin levels were normal, indicating no C-cell hyperplasia or medullary thyroid carcinoma. Molecular genetic studies on these individuals did not disclose the specific point mutation seen in multiple endocrine neoplasia type 2B. CONCLUSIONS: This family demonstrates some of the phenotypic features of the multiple endocrine neoplasia type 2B syndrome without the characteristic neoplasms or the mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B. Their physical findings may be caused by genetic alterations within the RET proto-oncogene on chromosome 10 at yet undetermined sites.

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.

Synergistic divergence and jaw-winking phenomenon.

Synergistic divergence is a congenital syndrome of monocular adduction deficit, with simultaneous abduction of both eyes on attempted gaze into the field of action of the paretic medial rectus muscle. Based on electromyographic data, it has been speculated that it is a neural miswiring disorder related to Duane's retraction syndrome. The association between Duane's retraction syndrome and the Marcus Gunn jaw-winking phenomenon, another neural miswiring disorder, has been previously reported. The authors describe a patient with both bilateral synergistic divergence and Marcus Gunn jaw-winking phenomenon.

Vitrectomy and juvenile epiretinal membrane.

The cases of two children who had idiopathic epiretinal membranes are reported. Causes for juvenile epiretinal membranes, including trauma, pars planitis, toxocariasis, Coats' disease, or combined hamartomas, were not present. Both patients previously had documented normal vision in the affected eye. Observation revealed deterioration of vision, and a pars plana vitrectomy and a membranectomy were performed. The 5-year -old girl's vision improved from counting fingers at 5 feet to 20/80. The 12-year-old boy's vision improved from 20/200 to 20/80. Selected cases of juvenile epiretinal membranes may benefit from surgical excision.

Diabetes and hypertension quality measurement in four safety-net sites: lessons learned after implementation of the same commercial electronic health record.

BACKGROUND: In this new era after the Health Information Technology for Economic and Clinical Health (HITECH) Act of 2009, the literature on lessons learned with electronic health record (EHR) implementation needs to be revisited. OBJECTIVES: Our objective was to describe what implementation of a commercially available EHR with built-in quality query algorithms showed us about our care for diabetes and hypertension populations in four safety net clinics, specifically feasibility of data retrieval, measurements over time, quality of data, and how our teams used this data. METHODS: A cross-sectional study was conducted from October 2008 to October 2012 in four safety-net clinics located in the Midwest and Western United States. A data warehouse that stores data from across the U.S was utilized for data extraction from patients with diabetes or hypertension diagnoses and at least two office visits per year. Standard quality measures were collected over a period of two to four years. All sites were engaged in a partnership model with the IT staff and a shared learning process to enhance the use of the quality metrics. RESULTS: While use of the algorithms was feasible across sites, challenges occurred when attempting to use the query results for research purposes. There was wide variation of both process and outcome results by individual centers. Composite calculations balanced out the differences seen in the individual measures. Despite using consistent quality definitions, the differences across centers had an impact on numerators and denominators. All sites agreed to a partnership model of EHR implementation, and each center utilized the available resources of the partnership for Center-specific quality initiatives. CONCLUSIONS: Utilizing a shared EHR, a Regional Extension Center-like partnership model, and similar quality query algorithms allowed safety-net clinics to benchmark and improve the quality of care across differing patient populations and health care delivery models.