Noroviruses as a Cause of Diarrhea in Immunocompromised Pediatric Hematopoietic Stem Cell and Solid Organ Transplant Recipients.

Case reports describe significant norovirus gastroenteritis morbidity in immunocompromised patients. We evaluated norovirus pathogenesis in prospectively enrolled solid organ (SOT) and hematopoietic stem cell transplant (HSCT) patients with diarrhea who presented to Texas Children's Hospital and submitted stool for enteric testing. Noroviruses were detected by real-time reverse transcription polymerase chain reaction. Clinical outcomes of norovirus diarrhea and non-norovirus diarrhea patients, matched by transplanted organ type, were compared. Norovirus infection was identified in 25 (22%) of 116 patients, more frequently than other enteropathogens. Fifty percent of norovirus patients experienced diarrhea lasting ≥14 days, with median duration of 12.5 days (range 1-324 days); 29% developed diarrhea recurrence. Fifty-five percent of norovirus patients were hospitalized for diarrhea, with 27% requiring intensive care unit (ICU) admission. One HSCT recipient developed pneumatosis intestinalis. Three HSCT patients expired ≤6 months of norovirus diarrhea onset. Compared to non-norovirus diarrhea patients, norovirus patients experienced significantly more frequent ICU admission (27% vs. 0%, p = 0.02), greater serum creatinine rise (median 0.3 vs. 0.2 mg/dL, p = 0.01), and more weight loss (median 1.6 vs. 0.6 kg, p < 0.01). Noroviruses are an important cause of diarrhea in pediatric transplant patients and are associated with significant clinical complications.

A randomized controlled trial of a video module to increase U.S. poison center use by low-income parents.

CONTEXT: U.S. poison centers decrease medical visits by providing telephone advice for home management of potential poisonings, but are underutilized by low-income African-American and Latino parents, and those with limited English proficiency, due to lack of knowledge and misconceptions about poison centers. OBJECTIVES: To assess the effectiveness of a poison prevention video module in improving knowledge, behavior, and behavioral intention concerning use of poison centers in a population of low-income, language-diverse adults attending parenting courses offered by a community organization. METHODS: A randomized, blinded, controlled trial was conducted at 16 parenting course sites of a community organization and included 297 participants. The organization's instructors presented the video module (intervention) or the usual class curriculum (control). Participants completed questionnaires at baseline and a telephone interview 2-4 weeks later. Changes from baseline to follow-up were compared between the intervention and control groups using analysis of variance and Chi-square tests. Intervention group participants were stratified by English proficiency and compared to assess baseline and follow-up responses by language. RESULTS: After the intervention, participants in the intervention group had a significantly greater increase in knowledge about the poison center, were more likely to have the correct poison center phone number at home, and had greater behavioral intention to use the poison center compared to control group participants. At baseline, Spanish-primary-language participants with limited English proficiency had less knowledge about the poison center, were less likely to have the poison center number at home, and had lower behavioral intention to use the poison center than English proficient participants, but significantly improved after the intervention. CONCLUSIONS: This video module, when presented by a community organization's instructors, was highly effective in improving knowledge, behavior, and behavioral intention concerning use of poison centers within a low-income, language-diverse population.

Placental release of distinct DNA-associated micro-particles into maternal circulation: reflective of gestation time and preeclampsia.

BACKGROUND: The aim of this study was to determine whether DNA-associated micro-particles (MPs) in maternal plasma express fetal-derived human leukocyte antigen-G (HLA-G) or placental alkaline phosphatase (PLAP) and whether the levels differ between women with normotensive pregnancies and preeclampsia. METHODS: DNA-associated MPs expressing HLA-G or PLAP were examined in the plasma of normal pregnant women and preeclamptic patients using flow cytometric analysis. RESULTS: DNA-associated HLA-G(+) MPs were significantly increased in maternal plasma compared to plasma from non-pregnant controls (p<0.005), with highest levels found in the first and second trimesters. DNA-associated PLAP(+) MPs were also increased in maternal plasma compared to plasma from non-pregnant controls (p<0.006), with highest levels in the second and third trimesters. Term preeclamptic women had higher levels of DNA-associated MPs than control pregnant women. HLA-G(+) MPs from the plasma of preeclamptic women had more DNA per MP than HLA-G(+) MPs from the plasma of normal pregnant women (p<0.03). CONCLUSIONS: HLA-G(+) and PLAP(+) MPs increase in maternal circulation at different times during gestation. DNA amounts per HLA-G(+) MP increase in preeclamptic women which might indicate dysfunctional extravillous cytotrophoblasts.

New sexual partners and readiness to seek screening for chlamydia and gonorrhoea: predictors among minority young women.

OBJECTIVES: To determine (1) level of readiness and (2) demographic and behavioural predictors of readiness to seek chlamydia (CT) and gonorrhoea (NGC) screening in the absence of symptoms after sex with a "new" partner. METHODS: Baseline data, obtained as part of a larger randomised controlled clinical trial in young women, were analysed. Readiness to seek screening for CT and NGC after sex with a "new" partner was assessed using the stages of change framework from the transtheoretical model of change-precontemplation, contemplation, preparation, and action. Ordinal logistic regression, using the proportional odds model, was used to determine predictors of being in action for or having already been screened for CT and NGC after sex with a "new" partner. RESULTS: The sample consisted of 376 predominantly African American (67%) young women (mean age 18.5 (SD 1.4) years). The distribution of readiness to seek CT and NGC screening was 4% precontemplation, 11% contemplation, 28% preparation, and 57% action. The best fitting logistic model that predicted being in action for seeking screening after sex with a "new" partner included high perceived seriousness of acquiring a sexually transmitted infection (OR = 2.02, 95% CI 1.05 to 3.89), and having "other" (not steady) partners in the last 6 months (OR = 0.50, 95% C.I. 0.32 to 0.78) CONCLUSIONS: Many young women report that they were not getting screened for CT and NGC after sex with a "new" partner and therefore may be at increased risk of an untreated STI. Enhancing level of perceived seriousness of acquiring an STI from a "new" partner may increase a young woman's readiness to seek screening after initiating a new sexual relationship.

Maternal immunization with pneumococcal polysaccharide vaccine in the third trimester of gestation.

In a randomized, double blinded study, 23-valent pneumococcal polysaccharide vaccine (PSV) or conjugate Haemophilus influenzae type b (HbOC) vaccine was administered to 60 healthy women in the third trimester of gestation. Total IgG, IgG1, and IgG2 antibodies to pneumococcal serotypes 6B, 14, 19F and 23F were measured by ELISA in mothers prior to immunization, at delivery and 7 months after delivery, and in infants at birth (cord blood), 2 and 7 months after delivery. IgA was evaluated in breast milk at 2 and 7 months, and opsonophagocytic activity in cord blood. PSV was safe and immunogenic in pregnant women. Transplacental transmission of vaccine-specific antibodies was efficient. Maternal immunization with PSV resulted in significantly higher concentrations of pneumococcal antibodies in infants at birth and at 2 months of age, and greater functional opsonophagocytic activity of passively acquired IgG antibody.

Production of interferons and beta-chemokines by placental trophoblasts of HIV-1-infected women.

OBJECTIVE: The mechanism whereby the placental cells of a human immunodeficiency virus (HIV)-1-infected mother protect the fetus from HIV-1 infection is unclear. Interferons (IFNs) inhibit the replication of viruses by acting at various stages of the life cycle and may play a role in protecting against vertical transmission of HIV-1. In addition the beta-chemokines RANTES (regulated on activation T cell expressed and secreted), macrophage inflammatory protein-1-alpha (MIP-1alpha), and MIP-1beta can block HIV-1 entry into cells by preventing the binding of the macrophage-trophic HIV-1 strains to the coreceptor CCR5. In this study the production of IFNs and beta-chemokines by placental trophoblasts of HIV-1-infected women who were HIV-1 non-transmitters was examined. METHODS: Placental trophoblastic cells were isolated from 29 HIV-1-infected and 10 control subjects. Supernatants of trophoblast cultures were tested for the production of IFNs and beta-chemokines by enzyme linked immunosorbent assay (ELISA). Additionally, HIV-1-gag and IFN-beta transcripts were determined by a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) assay. RESULTS: All placental trophoblasts of HIV-1-infected women contained HIV-1-gag transcripts. There were no statistical differences in the median constitutive levels of IFN-alpha and IFN-gamma produced by trophoblasts of HIV-1 infected and control subjects. In contrast, trophoblasts of HIV-1-infected women constitutively produced significantly higher levels of IFN-beta protein than trophoblasts of control subjects. Furthermore, the median levels of beta-chemokines produced by trophoblasts of HIV-infected and control women were similar. CONCLUSIONS: Since there was no correlation between the placental HIV load and the production of interferons or beta-chemokines, the role of trophoblast-derived IFNs and beta-chemokines in protecting the fetus from infection with HIV-1 is not clear.

The burden of pediatric HIV/AIDS in Constanta, Romania: a cross-sectional study.

BACKGROUND: By 1990, 94 percent of the acquired immunodeficiency syndrome (AIDS) cases in Romania were in children less than 13 years of age. The majority of the cases were identified in the city of Constanta. The purpose of this paper was to describe the current burden of pediatric human immunodeficiency virus (HIV) infection in the Constanta county. METHODS: A cross-sectional study was designed to address the primary objective. Between April 1999 and March 2000, all living cases of pediatric HIV infection in the Constanta county were identified from records at the HIV hospital clinic which serves the Constanta county. Standard demographic, social, clinical, treatment and hospitalization data were collected for each study subject. Data were analyzed according to cross-sectional study design methodology. RESULTS: Of the 762 subjects, the majority were seven to 11 years of age, lived with their parents and attended school. Only 70% of the fathers and 13% of the mothers were employed. Horizontal transmission accounted for 90% of the cases. Most of the children had moderate to severe disease as indicated by their AIDS-defining signs; 40% had AIDS. Less than half of the children were receiving antiretroviral therapy (ART). ART and children of mothers with a high school or greater education were independent predictors of long-term non-progression of HIV disease. CONCLUSIONS: This cross-sectional study demonstrated that ten years after the HIV epidemic was identified in Romania, it remains a health and economic burden. The infected children are very ill, but ART is not available for all. The proportion with vertical transmission has increased from an estimated four % to nine %. Our findings support the need to get HIV therapy to economically challenged countries such as Romania.

Comparison of CD8(+) T-cell subsets in HIV-infected rapid progressor children versus non--rapid progressor children.

BACKGROUND: CD8(+) T-cell subsets have not been adequately described in HIV-infected (HIV(+)) children classified with respect to disease progression as rapid-progressors (RPs) and non-rapid progressors (non-RPs). OBJECTIVE: The purpose of this investigation was to determine the distribution of CD8(+) T-cell subsets in HIV(+) children and correlate the findings with degree of immunosuppression and HIV viral burden. METHODS: By means of 3-color flow cytometry, percentages of CD38(+)DR(+), CD28(+), and CD57(+) CD8(+) T-cell subsets were examined in RP (n = 15) and non-RP (n = 36) HIV(+) children and in HIV-exposed but uninfected (n = 11) and HIVunexposed (n = 8) children. The CD8(+) T-cell subsets were correlated with mean CD4(+) T-cell percentages and HIV RNA levels. Analysis of covariance was used for group comparisons for the control of the covariate of age. RESULTS: The HIV-exposed and HIV-unexposed controls were not different from each other in CD8(+) T-cell subset percentages, except that the DR(-)CD38(+)CD8(+) T-cell percentages were higher in the exposed controls than in the unexposed controls. RPs had a higher mean percentage of DR(+)CD38(+)CD8(+) T cells than non-RPs and both control groups, and RPs had higher viremia than non-RPs. CD38(+)CD8(+) T-cell percentages did not correlate with viral burden as it has been seen to do in HIV(+) adults. Percentages of CD28(+)CD8(+) T cells were lower in HIV-infected children than in controls. There was a positive correlation of percentage of CD28(+)CD57(-)CD8(+) T cells with CD4(+) T-cell percentages in each HIV-infected group. CONCLUSION: CD8(+) T cells become activated (dual expression of DR and CD38) and lose CD28, some acquiring CD57, in relation to rapidity of disease progression in pediatric HIV infection.

The effect of late doses on the achievement of seroprotection and antibody titer levels with hepatitis b immunization among adolescents.

OBJECTIVE: To determine the effect of varying dosing schedules and predictor variables on the seroprotection rates and geometric mean titer levels resulting from the hepatitis B vaccination series among adolescents. METHODS: Adolescents received the hepatitis B vaccination series at varying schedules according to their natural adherence patterns. Data collected included participants' medication use; chronic illness; use of cigarettes, alcohol, and marijuana; age; race/ethnicity; and body mass index. Participants' dates of vaccinations were recorded and titer levels for hepatitis B surface antibody were drawn ~12 and 24 months after study enrollment. The data for 498 participants were analyzed using chi(2) tests, Student t tests, logistic regression models, and analysis of variance. RESULTS: Seroprotection rates among adolescents were not affected by late vaccinations. The only factors affecting the achievement of seroprotection ~12 and 24 months after the first vaccination were body mass index and the number of immunizations received. Increased time between doses 1 and 2 and doses 2 and 3 showed a trend toward correlating with increasing titer levels. CONCLUSIONS: Although adolescents at risk of acquiring hepatitis B should receive the hepatitis B vaccination series in a timely fashion, late doses are not detrimental, and may be beneficial, to achieving high antibody levels against the hepatitis B virus.

Comparison of intravenous midazolam with pentobarbital for sedation for head computed tomography imaging.

OBJECTIVE: To compare the efficacy of intravenous (IV) midazolam with that of IV pentobarbital when used for sedation for head computed tomography (CT) imaging in emergency department (ED) pediatric patients. METHODS: Prospective, randomized clinical trial in an urban children's hospital. During a two-and-a-half-year period, 55 patients were enrolled: 34 males and 21 females. Measurements included induction time, recovery time, efficacy, side effects, complications, and failure with each drug. Success of sedation was graded as good (GS), adequate (AS), poor (PS), or unsuccessful (US). RESULTS: Sedation for CT was used for patients with the following problems: head trauma (21/55), central nervous system pathology (17/55), ventriculoperitoneal shunt evaluation (6/55), periorbital cellulitis (6/55), and retropharyngeal abscess (5/55). Twenty-nine (53%) patients received pentobarbital (mean +/- SD dose 3.75 +/- 1. 10 mg/kg) and 26 (47%) patients received midazolam (mean +/- SD dose 0.2 +/- 0.03 mg/kg). In the pentobarbital group, 28 (97%) patients were scanned and successfully sedated. Pentobarbital's mean induction time was 6 minutes and duration of sedation averaged 86 minutes. In the midazolam group, only five (19%) patients were successfully scanned with midazolam alone. Of the 21 (81%) patients given midazolam who were unsuccessfully sedated, 12 (61%) were subsequently sedated with the addition of pentobarbital for completion of CT imaging. Mild oxygen desaturation, O(2) sat >90% yet <94%, was seen in only four patients. All four patients responded to blow-by oxygen and required no other intervention. CONCLUSION: Intravenous pentobarbital is more effective than IV midazolam for sedation of children requiring CT imaging.

The changing epidemic of pediatric hiv infection in romania.

PURPOSE: By the late 1980s, over 100,000 infants and children were living in public institutions in Romania. It was not uncommon for children in these facilities to receive one or more 'micro-transfusions' of blood, unscreened for HIV, as therapy for anemia or malnutrition. To assess the impact of pediatric HIV infection in Romania, the European country with the most pediatric cases, cross-sectional and cohort studies were implemented in Constanta (the epi-center of pediatric HIV in Romania) in April 1999.METHODS: Demographic, clinical and social data are collected once for all cross-sectional subjects. Similar data are collected every 11-13 months for subjects in the cohort. The cross-sectional study population was defined as all living HIV-infected infants and children, 0-18 years, known to the investigators from April to September 1999. The cohort consists of subjects diagnosed with HIV between 1995 and 1999.RESULTS: Enrolled are 791 subjects, of which 357 are in the cohort study. The majority (83%) are Romanian, vs Gypsy or Turkish/Hun and their mean age is 11 years (SD = 1.3). Biologic parents are the primary caretakers of 77% and 86% attend school. Mode of transmission was perinatal for 8%; blood transfusion/parental therapy modes account for 89% of the transmission and the presumed timing was between 1-12 months of age. Mean age at HIV confirmation was 5 years (SD = 3.2). AIDS has been diagnosed in 40% and 52% are receiving antiretroviral therapy.CONCLUSIONS: The Romanian pediatric HIV epidemic differs vastly from that in the US. Fewer children are with their biologic parent(s) and attending school. Early diagnosis of infection is rare, as therapy did not become available until the late 1990's. Perinatal transmission is increasing, however, which supports the need for HIV education and intervention in Eastern Europe.

Cost-effectiveness of childhood immunization reminder/recall systems in urban private practices.

OBJECTIVE: To assess cost and cost-effectiveness of immunization reminder/recall systems in the private sector. METHODS: A manual postcard system (mail) was compared with a computer-based telephone system (autodialer) and control. Costs included time costs and the cost of equipment and supplies. The cost per child and the incremental cost of the intervention relative to control were computed. Cost-effectiveness ratios were computed for return visits and for immunizations delivered. RESULTS: The average cost per child was $2.28 for the mail group and $1.47 for the autodialer group. The incremental visit cost relative to the control was higher for the mail group ($9.52) than for the autodialer group ($3.48). The autodialer was more cost-effective in delivering immunizations: $4. 06 per extra immunization (autodialer) versus $12.82 (mail). CONCLUSIONS: Excluding start-up costs, the autodialer system was most cost-effective. Including autodialer equipment costs, the autodialer system is more cost-effective only for larger practices.

Understanding partner notification (Patient self-referral method) by young women.

STUDY OBJECTIVE: To understand the communication process involved in the patient-self referral method among adolescent females with chlamydia and gonococcal infection. DESIGN: A cross-sectional descriptive study using a convenience sample was conducted in 54 predominantly African-American females, 13 to 20 years-old, with gonococcal and/or chlamydia cervicitis at an urban hospital based reproductive health clinic. Subjects interviewed at their treatment visit were asked what method of notification they used to tell their partner(s). Subjects who had not notified their partner were asked about their intended communication method and what they envisioned they would say to their partner. Coding methodology was used to analyze the information. In addition to qualitative information, outcome measures were the proportion of subjects who notified their partner(s), their communication method, style, and barriers to communication. RESULTS: According to the treatment visit, 57% (31/54) of subjects reported notifying their partner. Most had notified their partner by phone or face-to-face, stated basic facts about the infection, and used a "direct" and "sensitive" communication style. Of the subjects who had not notified their partner (23/54), several barriers to notification were reported, but 82% said they intend to notify their partner(s). CONCLUSIONS: Strategies to promote the patient-self referral method among young women who do not notify their partner(s) need further assessment.

Oral manifestations of pediatric vertical HIV infection.

To assess the prevalence and prognostic significance of the history of oral manifestations in children with human immunodeficiency virus infection (HIV), a cohort study of 73 children with vertical HIV infection was conducted. The study subjects were examined every 6 months for oral manifestations. The period prevalence of oral manifestations ranged from a low of 1% for submandibular enlargement and 3% for hairy leukoplakia to a high of 36% for xerostomia and 51% for cervical lymphadenopathy. The occurrence of oral manifestations did not change significantly over time from 1995 to 1998. Finally, the odds of occurrence of cervical lymphadenopathy, xerostomia, and oral candidiasis were greater among children in whom these manifestations had been diagnosed in the preceding 6-18 months than in children without prior diagnosis. Oral manifestations are significant clinical outcomes in pediatric vertical HIV infection, particularly for children diagnosed previously with an oral manifestation.

Assessment of oral contraceptive pill continuation in young women.

STUDY OBJECTIVE: To assess oral contraceptive pill (OCP) continuation rates and factors associated with OCP continuation in young women. DESIGN: A 12-month retrospective cohort study by chart review of 226 young women seen for an initial clinic visit. SETTING: Urban hospital-based family planning clinic. PARTICIPANTS: Predominantly African-American, sexually active young women, 12 to 21 years of age (median age, 17.2 years). MAIN OUTCOME MEASURES: Scheduled OCP-appointment-keeping rates, pregnancy rates, and associated factors were compared between OCP-compliant and -noncompliant groups. RESULTS: The OCP-appointment-keeping rate declined dramatically over 1 year, from 29% at the 3-month visit to 9% at the 12-month visit. Almost half seeking a postpartum visit checkup (PPVup) did not return after the initial clinic visit. Overall, a higher OCP-appointment-keeping rate was noted in those seeking OCPs vs. PPVup at the initial visit; P < .05 for 12-month visit. There was no difference in the pregnancy rates between OCP-compliant and -noncompliant groups. School enrollment and nulliparity was significantly associated with OCP compliance until the 6-month visit (P < .05). CONCLUSION: In an urban hospital based clinic, the OCP continuation rate after the initial visit was poor. Continuation of OCPs may be anticipated by type of services sought at an initial visit. Methods to improve OCP continuation in this setting should be implemented.

Health status of children with special health care needs: measurement issues and instruments.

The methods for measuring health care outcomes and monitoring the health status of the child with a chronic health condition must be available, accessible, and meaningful. This review was evoked by this need to identify reliable and valid instruments for measuring the health status of children with special health care needs. The objectives are as follows: (1) to review the methodologic and substantive issues related to the selection of instruments and (2) to identify those instruments available currently for collecting data regarding health status of children with special health care needs. A Medline search of the literature published since 1966 through 1998 and restricted to human subjects and the English language was conducted. Indexing terms included health status, quality of life, outcome assessment, functional status, and patient satisfaction. Multiple reviewers selected instruments based on their usefulness in clinical settings as generic, disease nonspecific, child health status instruments. Few instruments were identified that can be used by pediatricians for tracking and monitoring the health status of children with special health care needs. In conclusion, to progress in the field of outcomes measurement of children with special health care needs, it will be necessary to develop new measurement tools. These instruments must (1) provide valid and reliable information on health status; (2) be useful in guiding the management of patients; and (3) not be a burden for physicians, patients, or patient's families.

Effects of viral lower respiratory tract infection on lung function in infants with cystic fibrosis.

OBJECTIVE: To determine the effect of respiratory viral infections on pulmonary function in infants with cystic fibrosis (CF) after the respiratory virus season (October through March). METHODS: Recruitment was for one respiratory virus season during a 3-year span, 1988 to 1991, with reenrollment allowed; 22 infants <2 years of age with CF (30 patient-seasons) and 27 age-matched controls (28 patient-seasons) participated. Primary outcome variables were preseason and postseason pulmonary function tests and serology for viral antibodies. Twice-weekly telephone calls screened for respiratory symptoms. The presence of respiratory symptoms triggered a home visit and an evaluation for upper or lower (LRTI) respiratory tract infection. A nasopharyngeal sample for viral culture was performed with each visit. RESULTS: Controls and CF infants each had a mean of 5.3 acute respiratory illnesses; CF infants were four times more likely to develop an LRTI compared with controls (odds ratio, 4.6; 95% confidence interval, 1.3 and 16.5). Three of 7 (43%) CF infants with respiratory syncytial virus infection (documented by culture) required hospitalization. Controls had no association between respiratory illness and postseason pulmonary function. For CF infants, reduced postseason maximal flow at functional residual capacity (V'maxFRC) was associated with two interactions, ie, respiratory syncytial virus infection and LRTI, and male sex and LRTI; increased gas trapping (FRC) was associated with an interaction between respiratory syncytial virus and LRTI and day care. Postseason pulmonary function tests were obtained a mean of 3. 2 months after final LRTI. CONCLUSIONS: Infants with CF incurring respiratory virus infection are at significant risk for LRTI, for hospitalization, and for deterioration in lung function that persists months after the acute illness.