The effect of exposure to wood smoke on outcomes of childhood pneumonia in Botswana.

SETTING: Tertiary hospital in Gaborone, Botswana. OBJECTIVE: To examine whether exposure to wood smoke worsens outcomes of childhood pneumonia. DESIGN: Prospective cohort study of children aged 1-23 months meeting clinical criteria for pneumonia. Household use of wood as a cooking fuel was assessed during a face-to-face questionnaire with care givers. We estimated crude and adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for treatment failure at 48 h by household use of wood as a cooking fuel. We assessed for effect modification by age (1-5 vs. 6-23 months) and malnutrition (none vs. moderate vs. severe). RESULTS: The median age of the 284 enrolled children was 5.9 months; 17% had moderate or severe malnutrition. Ninety-nine (35%) children failed treatment at 48 h and 17 (6%) died. In multivariable analyses, household use of wood as a cooking fuel increased the risk of treatment failure at 48 h (RR 1.44, 95%CI 1.09-1.92, P = 0.01). This association differed by child nutritional status (P = 0.02), with a detrimental effect observed only among children with no or moderate malnutrition. CONCLUSIONS: Exposure to wood smoke worsens outcomes for childhood pneumonia. Efforts to prevent exposure to smoke from unprocessed fuels may improve pneumonia outcomes among children.

Safety of 2 recombinant human immunodeficiency virus type 1 (HIV-1) envelope vaccines in neonates born to HIV-1-infected women.

To determine the safety of 2 candidate vaccines against human immunodeficiency virus type 1 (HIV-1), a randomized, placebo-controlled, multicenter trial compared low, medium, and high doses of the vaccines or an adjuvant among infants born to HIV-infected women. No local or systemic reactions of grade 2 or greater were reported 48 h after the subjects underwent immunization. Grade 3 or 4 chemistry toxicities occurred in 5 (3%) and grade 3 or 4 hematologic toxicities in 17 (11%) of 154 vaccinated subjects (not significantly different from 29 adjuvant recipients). CD4(+) cell percentages of < or = 20% occurred at least once in 9 vaccinated subjects and 1 control subject. Sustained CD4(+) cell percentages of < or = 20% occurred in 4 HIV-infected children. Fourteen infants (8%) were confirmed to be HIV-infected; median CD4(+) cell counts among these children were 2074, 1674, 1584, and 821 cells/mm(3) at birth and weeks 24, 52, and 104, respectively. Thus, both vaccines were safe and well tolerated in neonates, and there was no evidence of accelerated immunologic decline in HIV-infected infants.

Risk factors for sternal wound and other infections in pediatric cardiac surgery patients.

BACKGROUND: This study was undertaken to determine the incidence, pathogens and risk factors associated with development of sternal wound and other infections in children undergoing cardiac surgery. METHODS: Retrospective chart review was performed for all cardiac surgeries performed on children <18 years of age at Upstate Medical University at Syracuse between January, 1996, and June, 1998. For evaluation of risk factors for sternal wound infection, only patients undergoing sternotomy are included in the analysis: those with infection are compared with those without for preoperative, intraoperative and postoperative risk factors. RESULTS: Sternal wound infection developed in 10 of 202 (5%) children after median sternotomy. Superficial sternal wound infection developed in 6 (3%) children, and 4 (2%) had deep infection. Children with sternal wound infection had lower age, higher American Society of Anesthesiologist score, longer preoperative stay, longer period of ventilation and inotropic support, longer intensive care unit and total postoperative hospital stays and increased leukocyte band cell counts preoperatively and on Postoperative Day 1 than those without sternal infection. Causative agents for sternal wound infection were Staphylococcus aureus (6), Pseudomonas aeruginosa (1) and Haemophilus influenzae non-type b (1). In addition 32 bacterial infections occurred at nonsurgical sites after 28 procedures. Infections included pneumonia, urinary tract infection and bacteremia. Longer bypass time and longer operation time were two additional risk factors for nonwound infection. CONCLUSION: Infections continue to be a significant cause of morbidity in cardiac surgery patients. Knowledge of risk factors for infection could be useful in preventive and treatment strategies for these high-risk groups.

Pharmacokinetics of dapsone administered daily and weekly in human immunodeficiency virus-infected children.

Although dapsone is a commonly used alternative agent for prophylaxis against Pneumocystis carinii pneumonia in children intolerant to trimethoprim-sulfamethoxazole, there are few data that describe dapsone pharmacokinetics in children. We studied dapsone pharmacokinetics in 30 children (median age, 2.8 years; age range, 0. 3 to 12 years) receiving a new proprietary liquid preparation by three dosing regimens (1 mg/kg of body weight daily, 2 mg/kg daily, or 4 mg/kg weekly). Dosing of children with 2 mg/kg daily or 4 mg/kg weekly resulted in peak concentrations equivalent to those reached in adults receiving 100-mg tablets daily. For the entire population, the median half-life was 22.2 h (range, 7.1 to 40.3 h), the median oral clearance was 0.0365 liter/kg/h (range, 0.0104 to 0.1021 liter/kg/h), and the median oral apparent volume of distribution was 1.13 liters/kg (range, 0.50 to 2.32 liters/kg). The median dapsone oral clearance was significantly increased in those infants less than 2 years of age compared to the oral clearance in those over 2 years of age (0.0484 versus 0.0278 liter/kg/h; P = 0.011). These data suggest that absorption of this liquid preparation is adequate and that the concentrations in the sera of children receiving 2 mg/kg daily or 4 mg/kg weekly are equivalent to those seen in adults receiving standard dapsone dosing. Dapsone oral clearance appears to be increased in children under 2 years of age.

Enteroviral meningoencephalitis as a complication of X-linked hyper IgM syndrome.

We describe 5 children from 2 families with mutations in the CD40 ligand (CD40L) gene leading to absent expression of CD40L on activated CD4 cells. All subjects presented with interstitial pneumonia with low serum IgG and normal serum IgM. One child had normal and one child had elevated serum IgA. Four had confirmed Pneumocystis carinii pneumonia. In spite of intravenous immunoglobulin treatment yielding therapeutic serum immunoglobulin levels, 3 children had enteroviral encephalitis. When assessed by flow cytometry, the 3 surviving affected male children had absent CD40L expression on activated CD4(+) T cells. The affected children from both families were shown to have the same single nucleotide insertion (codon 131) resulting in frameshift and early termination within exon 4 (extracellular domain). This observation demonstrates that persistent enteroviral infection is not only observed in X-linked agammaglobulinemia but may also occur in patients with X-linked hyper IgM syndrome.

Comparison of human immunodeficiency virus 1 DNA polymerase chain reaction and qualitative and quantitative RNA polymerase chain reaction in human immunodeficiency virus 1-exposed infants.

BACKGROUND: HIV-1 RNA PCR is a widely available and sensitive assay but has not been studied for use in early diagnosis of HIV-1 infection in infants. METHODS: Research HIV-1 DNA PCR and HIV-1 RNA PCR were performed on peripheral blood mononuclear cells and plasma, respectively, from 284 blood samples from 204 infants. A commercially available HIV-1 quantitative RNA PCR was also performed on plasma from the 132 samples from HIV-1-infected infants and 22 of the samples from HIV-1-uninfected infants. RESULTS: Sensitivities of all assays varied with infant age. HIV-1 DNA PCR had a sensitivity of 27% in the < or = 3-week age group (n = 11) whereas qualitative and quantitative RNA PCR had sensitivities of 64 and 55%, respectively (P not significant). Each assay had a sensitivity of 96.2% at 4 to 6 weeks (n = 26) and 100% at > or = 7 weeks of age (n = 95). Specificity of HIV-1 DNA PCR for all age groups was 100%, whereas specificities of qualitative and quantitative RNA PCR assay were 96.1 and 95.5%, respectively. CONCLUSIONS: HIV-1 RNA PCR may offer a slight advantage in sensitivity over DNA PCR in the diagnosis of HIV infection in young infants. Positive RNA results can be found in a small number of infants who are not HIV-1-infected. HIV-1 RNA detection should not be routinely used alone for the diagnosis of HIV infection in young infants.

Early language development in children exposed to or infected with human immunodeficiency virus.

OBJECTIVES: To compare language development in infants and young children with human immunodeficiency virus (HIV) infection to language development in children who had been exposed to HIV but were uninfected, and (among subjects with HIV infection) to compare language development with cognitive and neurologic status. DESIGN: Prospective evaluation of language development in infected and in exposed but uninfected infants and young children. SETTING: Pediatric Infectious Disease Clinic, State University of New York-Health Science Center at Syracuse. SUBJECTS: Nine infants and young children infected with HIV and 69 seropositive but uninfected infants and children, age 6 weeks to 45 months. RESULTS: Mean Early Language Milestone Scale, 2nd edition (ELM-2) Global Language scores were significantly lower for subjects with HIV infection, compared with uninfected subjects (89.3 vs 96.2, Mann-Whitney U test). The proportion of subjects scoring >2 SD below the mean on the ELM-2 on at least one occasion also was significantly greater for subjects with HIV infection, compared with uninfected subjects (4 of 9 infected subjects, but only 5 of 69 uninfected subjects; Fisher's exact test). Seven of the 9 subjects with HIV infection manifested deterioration of language function. Four manifested unremitting deterioration; only 1 of these 4 demonstrated unequivocal abnormality on neurologic examination. Three subjects with HIV infection and language deterioration showed improvement in language almost immediately after the initiation of antiretroviral drug treatment. Magnetic resonance imaging or computed tomography of the brain were performed in 6 of 7 infected subjects with language deterioration, and findings were normal in all 6. ELM-2 Global Language scaled scores showed good agreement with the Bayley Mental Developmental Index or the McCarthy Global Cognitive Index (r = 0. 70). Language deterioration, or improvement in language after initiation of drug therapy, coincided with or preceded changes in global cognitive function, at times by intervals of up to 12 months. CONCLUSIONS: Language deterioration occurs commonly in infants and young children with HIV infection, is seen frequently in the absence of abnormalities on neurologic examination or central nervous system imaging, and may precede evidence of deterioration in global cognitive ability. Periodic assessment of language development should be added to the developmental monitoring of infants and young children with HIV infection as a means of monitoring disease progression and the efficacy of drug treatment.

Influenza surveillance in community-dwelling elderly compared with children.

BACKGROUND: Acute respiratory illnesses (ARIs) are the leading cause of medical visits for community-dwelling patients of all ages, but virologic and clinical descriptions of these illnesses in older adults are infrequent. OBJECTIVES: To determine the feasibility of influenza surveillance in a population of community-dwelling elderly, to compare the patterns of influenza infection in elderly persons with that observed in young populations in which surveillance is usually conducted, and to describe the clinical presentation of influenza infection in elderly outpatients who seek medical attention for ARI. DESIGN: Prospective clinical and viral surveillance of ARIs among ambulatory patients during 3 consecutive winter seasons. SETTING: Nine internal medicine and 3 pediatric practices in Upstate New York in cooperation with the Medicare Influenza Vaccine Demonstration Project. PATIENTS: Elderly (n=808) and pediatric (n=2080) outpatients with ARI office visits. MEASUREMENTS: Frequency of influenza and other respiratory virus isolates and clinical profile of influenza among older adults and children with ARIs. RESULTS: Influenza virus was the viral agent recovered most often from specimens obtained from patients in both age groups with ARI symptoms, especially those with fever. Influenza accounted for 11% of ARIs in adults (87 isolates) and 20% in children (408 isolates). At the initial illness visit, influenza infection was equally common in elderly individuals with or without underlying cardiopulmonary conditions. Lower respiratory tract signs occurred in 13% of the adults and in 7% of the children with influenza documented by laboratory studies. Other respiratory viruses were recovered from specimens obtained from 20 adults and from 259 children. CONCLUSIONS: Viruses are important agents of ARIs in elderly outpatients. Children and older adults experience similar patterns of influenza infection and other epidemic respiratory pathogens, such as parainfluenza and respiratory syncytial viruses. Viral identification is feasible in older adults seen in physicians' offices and may contribute to improved measures of effects of influenza and other respiratory viruses on ARIs.

Acute manifestations and neurologic sequelae of Epstein-Barr virus encephalitis in children.

BACKGROUND: Complications of Epstein-Barr virus (EBV) infection are diverse and include a number of neurologic manifestations such as meningitis, meningoencephalitis, cerebellitis, cranial neuritis and others. In general encephalitis caused by EBV in pediatric patients has been considered a self-limited illness with few or no sequelae. METHODS: Charts were reviewed from all patients < 18 years of age admitted to or discharged from the State University of New York Health Science Center at Syracuse between 1982 and 1992 with a diagnosis of encephalitis or meningo-encephalitis. Eleven cases of EBV encephalitis diagnosed during a 10-year period were reviewed to characterize the clinical and laboratory findings in the acute setting and the extent of neurologic sequelae on follow-up. RESULTS: Acute neurologic manifestations were diverse and included combative behavior (55%), seizures (36%), headache (36%) and evidence of focal involvement (27%). Classic findings of infectious mononucleosis were noted infrequently; 18% each had pharyngitis, adenopathy, positive heterophile antibody tests or atypical lymphocytosis. Two patients (18%) had abnormal neuroimaging studies, one in the acute stage and the other at the time of follow-up. Seven patients (64%) had abnormal electroencephalograms (EEGs) in the acute setting; of these three had persistent abnormalities on follow-up. Forty percent developed persistent neurologic abnormalities including global impairment, perseverative autistic-like behavior and persistent left upper extremity paresis. CONCLUSIONS: Classic signs, symptoms and laboratory findings in infectious mononucleosis may be absent in Epstein-Barr virus encephalitis. Neurologic sequelae occur in a substantial number of patients.

Immunoblot analysis of anti-Ureaplasma urealyticum antibody in pregnant women and newborn infants.

The purpose of the present study was to determine the frequency in which antibody reactive to Ureaplasma urealyticum could be detected in a population of pregnant women and newborn infants. Serum samples from a prospective cohort of 80 healthy, U. urealyticum culture-positive and culture-negative pregnant women and a retrospective cohort of 522 infants born at between 25 and 42 weeks of gestation were studied by immunoblot analysis. Cultures of specimens from the lower genital tract were positive for U. urealyticum for 83% of the pregnant women, and serum immunoglobulin G (IgG) antibody which reacted to U. urealyticum was detectable in 93% of the pregnant women. Samples from five women (8%) had increases in the number of anti-U. urealyticum IgG bands over the course of the pregnancy. Samples from four of these five women had corresponding increases in the number of antibody bands present in IgA immunoblots. Six of the 522 samples from newborns or cord blood (1.1%) were positive for anti-U. urealyticum IgA; 5 of these 6 samples were also positive for IgM. The six anti-U. urealyticum IgA-positive infants were distributed as follows; 3 of 67 (4.5%) infants were delivered at 25 to 30 weeks of gestation, 3 of 176 (1.7%) infants were delivered at 31 to 34 weeks of gestation, and 0 of 279 infants were delivered at > or = 35 weeks of gestation. An antibody response to U. urealyticum can be detected in pregnant women and preterm infants and may serve as a marker of infection.

Failure to identify human immunodeficiency virus-seropositive newborns: epidemiology and enrollment patterns in a predominantly white, nonurban setting.

OBJECTIVE: To describe the epidemiology of newborn seroprevalence for human immunodeficiency virus (HIV) in a predominantly white, nonurban population, and to determine the factors associated with enrollment at a regional pediatric acquired immunodeficiency syndrome (AIDS) center serving that population. DESIGN: Retrospective case series of children enrolled at a regional pediatric AIDS center during a 6-year period and comparison with universal blind newborn screening data collected by the state of New York during the same time interval. SETTING: The Pediatric AIDS Center at State University of New York-Health Science Center at Syracuse, which serves as the only source of HIV-related pediatric care for children in a 16-country region of upstate New York totaling 1.8 million population. RESULTS: One hundred thirty-nine HIV-seropositive infants were born in the region during the 6-year study period; complete blind screening data were available for 138. Sixty-five (47%) of these infants were white. Thirty-nine (28%) of 138 had been enrolled at the Pediatric AIDS Center within the first 90 days of life. An additional 22 (16%) were enrolled at older than 90 days of life. The remaining 77 (56%) have never been seen at the center and are presumed to be unidentified. County enrollment rates varied from 0% to 100% and correlated with percent nonwhite births (r = .58; 95% confidence interval, 0.04-0.86). Children in outlying counties were at greater risk for nonenrollment than children from Onondaga County (site of the Pediatric AIDS Center) (adjusted relative risk, 1.38; 95% confidence interval, 1.05-1.85). White infants residing outside of Onondaga County were at the greatest risk of nonenrollment; of 50 seropositive white infants residing outside of Onondaga County, only 7 (14%) were enrolled at the center within the first 90 days of life. CONCLUSIONS: Local demographic factors can skew the racial distribution of HIV-seropositive infants dramatically compared with the national experience. White race and residence in counties away from the medical center each constituted risk factors for nonenrollment at the Pediatric AIDS Center. The epidemiology of HIV in this predominantly white, rural population, coupled with physician practices, probably contributed to low identification and enrollment rates. As the AIDS epidemic spreads into similar populations elsewhere, HIV infection in pregnant women or newborn infants is likely to become progressively harder to detect, unless universal screening is adopted.

Oropharyngeal candidiasis in immunocompromised children: a randomized, multicenter study of orally administered fluconazole suspension versus nystatin. The Multicenter Fluconazole Study Group.

OBJECTIVE: To compare the efficacy, safety, and tolerance of fluconazole suspension versus nystatin in the treatment of oropharyngeal thrush in immunocompromised children. DESIGN: Multicenter, randomized, observer-masked trial. SETTING: Thirty-two centers participated, including hospitals and ambulatory care clinics. PATIENTS: We enrolled 182 immunocompromised infants and children, ages 5 months to 14 years, with signs of oral thrush and presence of yeasts on potassium hydroxide- or gram-stained preparations. Subjects were randomly assigned to receive a single daily dose of fluconazole suspension, 2 to 3 mg/kg per day, or nystatin, 400,000 units four times daily for 14 days; 159 patients, who had culture confirmation of thrush and received at least 7 days of study drug, were evaluated for efficacy; all patients were evaluated for safety. RESULTS: Clinical cure was demonstrated in 91% of the subjects in the fluconazole group and 51% of the subjects in the nystatin group (p < 0.001), and eradication of the organism cultured at entry occurred in 76% and 11% (p < 0.001), respectively. Gastrointestinal conditions developed in six patients who received fluconazole and in three who received nystatin; two fluconazole recipients were subsequently withdrawn from the study. Laboratory abnormalities occurred with equal frequency in both groups. Clinical relapse rates were similar in both groups at 2 weeks (18% and 24% for fluconazole and nystatin, respectively) and 1 month (28% and 27%, respectively) after the completion of study drug. CONCLUSIONS: Fluconazole suspension is more effective than nystatin in the treatment of thrush in immunocompromised children. Both regimens were well tolerated.

Respiratory syncytial virus and influenza A infections in the hospitalized elderly.

Respiratory syncytial virus (RSV) infections in the institutionalized elderly have been described; however, there is little information on the impact of RSV infection on community-dwelling elderly. The purpose of this study was to determine the relative numbers of hospitalizations associated with RSV infection and compare the clinical manifestations with influenza A infection. Between November and April during 1989-1992, persons > or = 65 years old hospitalized with acute cardiopulmonary conditions or influenza-like illnesses were evaluated. Evaluation included viral culture, RSV antigen detection, and serologic analysis; 159 (10%) of 1580 had RSV infection and 221 (11%) of 2091 had influenza A. RSV and influenza A cases occurred simultaneously throughout the 3 years. Clinical manifestations were similar; however, patients with RSV infection were more likely to receive therapy for bronchospasm. Death rates were 10% and 6% for RSV infection and influenza A, respectively. RSV infection is the cause of serious disease in community-dwelling older persons.

Diagnosis and management of Baylisascaris procyonis infection in an infant with nonfatal meningoencephalitis.

Baylisacaris procyonis, the common raccoon ascarid, is known to cause life-threatening visceral, neural, and ocular larva migrans in mammals and birds. Two human fatalities have been previously described; however, little is known about the spectrum of human disease caused by B. procyonis. In this report, the case of a 13-month-old child who had nonfatal meningoencephalitis secondary to B. procyonis infection is presented. The suspected diagnosis was confirmed with use of newly developed enzyme immunoassay and immunoblot techniques. The diagnosis, management, and prevention of B. procyonis infection in humans is discussed. Clinical, serological, and epidemiological evaluations established B. procyonis as the etiologic agent. The child survived his infection but continued to have severe neurological sequelae. The potential for human contact and infection with B. procyonis is great. There is no effective therapy; therefore, prevention is paramount.

Rehospitalization for respiratory illness in infants of less than 32 weeks' gestation.

All 133 surviving infants of gestational age less than or equal to 32 weeks born July 1, 1985, to June 30, 1986, as well as a socioeconomically matched full-term control group were observed prospectively for 2 years to determine the incidence of rehospitalization for respiratory illness. Perinatal and seasonal factors associated with increased risk for such hospitalizations were also examined. Forty-seven (36%) preterm infants were rehospitalized compared with 3 (2.5%) of 121 term infants (P less than .001). Preterm infants with and without rehospitalization were similar for mean birth weight (1104 +/- 329 g and 1188 +/- 360 g, respectively) and gestational age (28 +/- 2 weeks for both groups); however, infants who were subsequently rehospitalized had required more days of mechanical ventilation, supplemental oxygen therapy, and neonatal intensive care. While a history of bronchopulmonary dysplasia was a risk factor for rehospitalization (45% compared with 25% of those without bronchopulmonary dysplasia, P less than .05), preterm infants with no history of bronchopulmonary dysplasia still showed a 10-fold increase compared with control infants. Among the 43 infants who required no mechanical ventilation beyond the day of birth, 10 (23%) required rehospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of the 4 S polycyclic aromatic hydrocarbon-binding protein with the cytochrome P-450c gene.

The induction of cytochrome P-450c, the isozyme most closely associated with aryl hydrocarbon hydroxylase activity in the rat, is mediated through a cytosolic polycyclic aromatic hydrocarbon (PAH)-binding protein(s). We have reported on the purification and characterization of a 4 S protein that interacts in a specific and saturable manner with [3H]benzo[a]pyrene and other PAHs. (W. H. Houser et al. (1985) Biochemistry 24, 7839-7845). We have also reported on the specific and saturable interaction of the 4 S protein with a plasmid containing 1.9 kbp of cloned rat P-450c sequence including exon 1, the 5' half of intron 1, and approximately 882 bp upstream information. Our investigations now show that incubation of this protein with a portion of the rat P-450c gene, followed by digestion with either lambda exonuclease or exonuclease III, tentatively identified two protected regions at -225 and -455 bp 5' from exon 1. To further study the significance of these protected regions, a 3.4-kbp fragment containing cytochrome P-450c promoter and 5'-upstream sequences (-882 to +2545) was fused to the chloramphenicol acetyl transferase (CAT) reporter gene and transfected into either rat epithelial RL-PR-C cells or rat hepatoma H-4-II-E cells. Both cell lines expressed CAT activity in response to induction by 3-methylcholanthrene (3MC), indicating that important regulatory regions responsive to 3MC are present in these constructs. However, neither cell line expressed CAT activity in response to 3MC when transfected with plasmids containing deletions (-95 to -724 or -240 to -720) in the regions shown to be protected by our footprinting studies. These results corroborate previous studies which indicated that the 4 S PAH-binding protein interacts in a specific manner with regions of the rat cytochrome P-450c gene. We conclude that the 4 S protein may play an important role in the regulation of expression of cytochrome P-450c in the rat.