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.

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.

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.

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.

Costimulatory pathways mediate monocyte-dependent lymphocyte apoptosis in HIV.

Examination of annexin V binding, an indicator of early apoptosis, on lymphocytes from HIV+ people immediately after isolation showed that both CD4(+) and CD8(+) T cells were apoptotic, whereas B cell apoptosis was induced mainly after incubation. CD8(+) T cell apoptosis correlated with fewer CD4(+) T cells, but not the level of viremia. To determine potential mechanisms for apoptosis, we examined FasL expression, which was dramatically elevated on CD14(+) monocytes; however, antibody to FasL did not reproducibly inhibit apoptosis. Rather, CD8(+) T cell apoptosis was caused by antigen-presenting cells because removal of monocytes or addition of antibodies to CD80 and CD86 reduced apoptosis. B cell apoptosis also involved costimulatory signals delivered by T cells but not monocytes. A unique CD8(bright)CD28(dim) T cell population died after costimulation by monocytes. Because this population was increased in patients with undetectable viremia, abnormal antigen-presenting cells may contribute to continued CD8(+) T cell exhaustion by inducing apoptosis.

Evaluation of a diagnostic approach to pediatric interstitial lung disease.

OBJECTIVE: To evaluate the value of a systematic approach to the diagnosis of pediatric interstitial lung disease (ILD). METHODS: In this descriptive, observational, prospective study, we evaluated 51 children presenting with ILD of unknown etiology during a 3-year period. Specific clinical information regarding history, physical examination, diagnostic evaluation, and final diagnosis was recorded on each patient. RESULTS: A specific diagnosis was established by history and physical examination alone in 1 patient, noninvasive tests alone in 8 others, and invasive tests, including lung biopsy, in another 26. Of the remaining patients, 8 had a suggestive diagnosis, and 8 had no specific diagnosis. CONCLUSIONS: A systematic approach to the diagnosis of pediatric ILD is useful, and not all patients need lung biopsy for diagnosis.

Meta-analysis of the risk of metachronous hernia in infants and children.

BACKGROUND: Inguinal herniorrhaphy is the most common general surgical procedure performed in children. The presence of a contralateral patent processus vaginalis forms the basis of the recommendation for contralateral exploration in patients undergoing unilateral herniorrhaphy. However, a patent processus vaginalis does not necessarily go on to become a clinically apparent inguinal hernia. METHODS: All published pediatric series, in which patients underwent unilateral inguinal hernia repair and were evaluated for the development of a metachronous hernia, were included. The incidence of and risk factors associated with development a metachronous hernia were evaluated with meta-analysis. RESULTS: There were 15,310 patients ranging in age from birth to 16 years, including premature infants. Of these, 1,062 patients (7%) developed a metachronous hernia. Gender and age were not risk factors. There was an 11% risk of metachronous hernia if the original hernia was on the left side, a risk that was 50% greater than if the original hernia was on the right. Of patients who developed a metachronous hernia, 90% did so within 5 years. The complication rate of metachronous hernia was 0.5%. CONCLUSION: There is no role for routine contralateral groin exploration. High-risk infants and children, especially those who undergo left inguinal herniorrhaphy, may benefit from contralateral groin exploration. If a patent processus vaginalis is found, it should be ligated. Patients who do not undergo contralateral groin exploration should be followed up for 5 years.

Diagnostic value of transbronchial, thoracoscopic, and open lung biopsy in immunocompetent children with chronic interstitial lung disease.

OBJECTIVES: To evaluate the diagnostic value of transbronchial biopsy (TBB), video-assisted thoracoscopy (VAT), and open lung biopsy (OLB) in immunocompetent children with chronic, diffuse infiltrates; to identify factors that may predict diagnosis in children requiring biopsy; to determine whether age, number of biopsies, or type of procedure are associated with diagnostic yield in children undergoing transthoracic biopsy; and to compare morbidity of VAT with that of OLB. STUDY DESIGN: As part of a prospective, descriptive study to define the clinical spectrum of pediatric interstitial lung disease, 30 immunocompetent children required TBB, VAT, and/or OLB for diagnosis of diffuse infiltrates. We reviewed and analyzed the following clinical variables: age; preoperative diagnosis; type of procedure; number of lobes undergoing biopsies; durations of surgery, chest tube insertion, and hospitalization; tissue diagnosis; and complications. RESULTS: Specific diagnoses were made in 50%, 60%, and 53% of patients undergoing TBB, VAT, and OLB, respectively. A variety of rare disorders was found, and tissue diagnosis confirmed the preoperative diagnosis in 25% of all procedures. For patients who underwent transthoracic biopsy, patient age of greater than 24 months was significantly associated with increased diagnostic yield, but the number of lobes biopsied and type of procedure were not. VAT was associated with shorter operating time, chest tube placement, and hospitalization when compared with OLB. The complications of VAT and OLB were comparable. CONCLUSION: Lung biopsy is an important tool for the diagnosis of interstitial lung disease in immunocompetent children, but the diagnosis of many children, particularly those aged 2 years or younger, remains uncertain.

Inflammatory cytokine expression is correlated with the level of human immunodeficiency virus (HIV) transcripts in HIV-infected placental trophoblastic cells.

The inflammatory cytokines interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) have been associated with increased human immunodeficiency virus (HIV) expression and enhanced lymphocyte adhesion to trophoblastic cells in experimental systems. To determine if there is a correlation between the expression of these cytokines and the levels of HIV transcripts in trophoblasts of term placentas from HIV-infected women, we studied the placentae of 30 HIV-positive and 13 control gravidae. Twenty-three of the HIV-positive women received zidovudine (ZDV) as prophylaxis against HIV vertical transmission; only one of the seven women who did not receive ZDV was a transmitter, for an overall vertical transmission rate of 3.8%. Cytokine production was measured by enzyme-linked immunosorbent assay in the supernatants of trophoblastic cell cultures. Additionally, cytokine transcripts and HIV gag sequences were determined by a quantitative reverse transcription-PCR assay. In general, trophoblastic cells of HIV-positive placentas expressed significantly higher levels of IL-1beta, IL-6, and TNF-alpha than those of control placentas. All placentas from HIV-positive women expressed HIV gag transcripts at either a low (<156 copies per microg of total RNA) or a high (>156 copies per microg of total RNA) level. There was a statistically significant positive association between the basal level of TNF-alpha production and the level of HIV gag transcripts of HIV-positive placental trophoblastic cells. Nevertheless, these data, coupled with a low transmission rate, would indicate that some other factors, perhaps working in concert with cytokines, are necessary for vertical transmission of HIV from mother to infant.

Leukocyte esterase dipstick as a rapid screening test for vaginitis and cervicitis.

STUDY OBJECTIVE: To assess the ability of vaginal and cervical leukocyte esterase (LE) dipstick to detect vaginitis and cervicitis. DESIGN: A prospective, cross-sectional study to assess the ability of the LE dipstick of vaginal secretions to detect trichomonads, candida, and bacterial vaginosis and the LE dipstick of vaginal and cervical secretions to detect gonococcal and chlamydia infection and polymorphonuclear cells (PMNs). SETTING: An inner-city shelter facility clinic. PARTICIPANTS: 183 sexually active, nonmenstruating females aged 13-21 years (Mean = 17.7, SD = 1.98 years): 47% black, 40% white, and 11% Hispanic. OUTCOME MEASURES: Sensitivity (SN), specificity (SP), positive and negative predictive values (PVP, PVN), with 95% confidence intervals, of vaginal and cervical LE dipstick > or = trace in detecting vaginal and cervical infections. RESULTS: A positive vaginal LE had a moderately high SN and PVN but poor SP and PVP in detecting trichomonas and candida vaginitis and bacterial vaginosis. A positive vaginal and cervical LE had a high SN and PVN but poor SP and PVP in detecting gonorrhea and chlamydia infection. A positive cervical LE had a moderate SN and low SP in detecting PMNs on Gram stain. CONCLUSIONS: The LE dipstick of vaginal and cervical secretions was only a moderately good screening test for vaginal infection but a good screening test for cervical infection.

Antenatal steroids are associated with less need for blood pressure support in extremely premature infants.

OBJECTIVE: To determine if antenatal steroids decrease the amount of blood pressure support required by extremely premature infants between 23 and 27 weeks' gestation. DESIGN: Retrospective cohort study. SETTING: Texas Children's Hospital neonatal intensive care unit from January 1986 to December 1991. PARTICIPANTS: Two hundred forty premature infants between 23 and 27 weeks' gestation who survived at least 48 hours. MAIN OUTCOME MEASURES: The amount of blood pressure support received in the form of dopamine and colloid. Secondary analysis investigated differences in mortality, respiratory support requirements, the incidence of intraventricular hemorrhage, necrotizing enterocolitis, infection, retinopathy of prematurity requiring surgery, and the length of hospitalization. RESULTS: During the first 48 hours of life, premature newborns exposed to antenatal corticosteroids were less likely to receive dopamine for blood pressure support (47% vs 67%), and if they did, the amount of dopamine expressed as a dopamine score was less than that received by those infants not exposed to antenatal corticosteroids (281 +/- 240 vs 407 +/- 281). Those exposed to antenatal corticosteroids also had a lower mortality rate (8% vs 24%) and lower respiratory support requirements. The incidence of grade 3 or 4 intraventricular hemorrhage was 8% in infants exposed to antenatal corticosteroids and 17% in infants not exposed. No difference was found in the incidence of necrotizing enterocolitis, infection, or retinopathy of prematurity requiring surgery, or length of hospitalization. CONCLUSION: Receipt of antenatal corticosteroids is associated with less need for blood pressure support during the first 48 hours after birth in premature infants between 23 and 27 weeks' gestation.

A comparative study of human immunodeficiency virus culture, polymerase chain reaction and anti-human immunodeficiency virus immunoglobulin A antibody detection in the diagnosis during early infancy of vertically acquired human immunodeficiency virus infection.

The infection status of 91 infants born to mothers with human immunodeficiency virus (HIV) infection was determined. Twenty-eight (31%) infants had confirmed HIV infection and 63 (69%) had seroreverted to HIV and lack evidence of infection. During the first 6 months of life HIV culture had a sensitivity and specificity for diagnosis of HIV infection of 80 and 100%, respectively. False negative HIV cultures were observed in only 7 of 35 specimens, 6 from among the 12 infected infants tested at birth. The sensitivity and specificity of polymerase chain reaction (PCR) detection of HIV were 95 and 93% respectively. A single false negative PCR test result was observed among the 19 tests performed on specimens from HIV-infected infants. False positive PCR test results were observed occasionally throughout the first 6 months of life. Detection of HIV-specific IgA antibody lacked diagnostic sensitivity; positive test results were observed in only 53% of specimens obtained from infected infants. Culture and PCR detection offer excellent sensitivity and specificity for diagnosis of HIV infection during the first 6 months of life; however, false-negative HIV cultures sometimes are observed, particularly during the newborn period, and either false negative or false positive PCR test results may be noted occasionally. For purposes of clinical decision-making, any positive test result should be confirmed with a second HIV culture or PCR test performed on a separate blood specimen.

Sensitivity, specificity and predictive value of physical examination, culture and other laboratory studies in the diagnosis during early infancy of vertically acquired human immunodeficiency virus infection.

The medical records of 142 infants referred for evaluation solely because they were born to human immunodeficiency virus (HIV)-infected mothers (i.e. not because of signs or symptoms suggesting HIV infection), were reviewed. The infection status of 85 of these infants has been determined; 17 (20%) have confirmed HIV infection and 68 have seroreverted to HIV and lack evidence of infection. During the first 6 months of life HIV culture had better sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of HIV infection than did physical examination, serum immunoglobulin determination or HIV p24 antigen determination. Of the 16 HIV-infected infants who were available for evaluation during the first 6 months of life, all had at least one culture from blood positive for HIV. Two of 4 and 10 of 11 infants were culture-positive at birth and during the first 3 months of life, respectively. A positive HIV culture results was the earliest finding of infection in 15 infants; 10 of these infants concomitantly were found to have hyperimmunoglobulinemia (8 cases) and/or an abnormal physical examination (4 cases). One HIV-infected infant developed hyperimmunoglobulinemia G and A at age 3 months without other evidence of HIV infection until age 5 months when a positive HIV culture was noted. All HIV-infected infants had abnormal findings by physical examination, a positive HIV culture, and/or hyperimmunoglobulinemia by 3 months of age. Infants with normal physical examination and laboratory test results at 3 and/or 6 months of age invariably were HIV-uninfected.

Formaldehyde complaint investigations in mobile homes by the Texas Department of Health.

The Texas Department of Health sampled for formaldehyde (HCHO) in 443 mobile homes between April, 1979, and May, 1982, at the request of the occupants. Colorimetric detector tubes were used most frequently for sample acquisition. HCHO concentrations ranged from below detectable limits (less than 0.5 ppm) to 8.0 ppm. Twenty-seven percent of homes one year of age or less had mean concentrations equal to or greater than 2.0 ppm while 11.5% of older homes had concentrations of 2.0 ppm or more. An inverse relationship is demonstrated between home age and HCHO level. The primary health complaints reported were headaches, respiratory discomfort, and ocular irritation. Evidence of a dose-response relationship was not present.