Respiratory syncytial virus infections in malnourished children.

The prevalence of respiratory syncytial virus (RSV) infection among severely malnourished children was studied at the University of Benin Teaching Hospital, Benin City, Nigeria at a time when the infection was known to be prevalent in the community. Nasopharyngeal washings were obtained from subjects on admission and thereafter every 4 days until discharge. RSV was detected by ELISA technique. Of 20 well nourished children who served as controls, 11 were ELISA-positive for RSV (55%). Eight (16%) of the 51 patients who were malnourished were ELISA-positive, four of whom (8%) had nosocomial infection. Fever and rhinitis were the most common presenting features in the RSV-infected malnourished children. None of the children showed any clinical or radiological signs of lower respiratory tract infection. Malnourished children appear not to be at increased risk of RSV infection, and those who contract the infection usually do not manifest severe disease.

Effect of extracorporeal membrane oxygenation on neutrophil function in neonates.

OBJECTIVE: To study the effect of long-term extracorporeal membrane oxygenation (ECMO) support on neutrophil function. DESIGN: A prospective, clinical investigation. SETTING: A pediatric intensive care unit. PATIENTS: Four groups of patients: ECMO group 1, newborns after 1 day of ECMO support (n = 10); ECMO group 2, newborns after 5 days of ECMO support (n = 6); group 3, normal newborns (n = 20); group 4, normal adults (n = 30). INTERVENTIONS: Two mL of heparinized blood was obtained from patients in each group. A modification of the Smith and Rommel technique was used to measure neutrophil phagocytosis and killing utilizing live Candida tropicalis as the test organism. Neutrophils were incubated for 90 mins in normal adult serum with live Candida. Viability of Candida after phagocytosis was tested by vital fluorochrome staining. Phagocytic index (the number of neutrophils with intracytoplasmic Candida divided by the total neutrophils) and candidicidal ratio (neutrophils with dead Candida divided by total neutrophils with Candida) were determined daily. MEASUREMENTS AND MAIN RESULTS: Neutrophils from ECMO group 1 (day 1) and ECMO group 2 (day 5) patients had significantly higher phagocytosis indices (72.8 +/- 20 and 76 +/- 18) and candidicidal ratios (0.15 +/- 0.1 and 0.16 +/- 0.09) compared with neutrophils from group 3 patients (normal neonates) (64 +/- 7 and 0.06 +/- 0.04). The phagocytosis indices were significantly lower in neutrophils from ECMO group 1 (day 1) and ECMO group 2 (day 5) patients compared with group 4 (adults) patients (86 +/- 9). However, the candidicidal ratios in neutrophils from ECMO groups 1 and 2 (ECMO day 1 and day 5) patients were equal to that value in group 4 (adults) (0.10 +/- 0.04). ECMO support for 5 days (ECMO group 2 vs. group 1) did not significantly change either the phagocytosis index or candidicidal ratio. CONCLUSIONS: Phagocytosis and intracellular killing by neutrophils of ECMO-supported neonates were significantly greater than those values found in normal newborns. ECMO support for 5 days produced no significant changes in neutrophil phagocytosis or killing.

Nosocomial respiratory syncytial virus infection in a newborn nursery.

The nosocomial spread of respiratory syncytial virus (RSV) was studied in a newborn nursery in Benin City, Nigeria at a time the virus was known to be highly prevalent in the community. Nasopharyngeal washings were obtained from babies on admission and, thereafter, every 4 days until discharged. Questionnaires were administered to medical personnel with upper respiratory tract infection (URTI). RSV was detected by an ELISA technique. A total of 56 babies were studied, made up of 33 preterm and 23 full term babies. Fourteen of the 56 babies (25%) developed RSV infection. Eleven babies (20.8%) acquired the infection nosocomially. The infected babies were all symptomatic and some had significant morbidity. One preterm baby died following acquisition of RSV. The study demonstrated that medical personnel working in our newborn nursery were a major contributor to the spread of nosocomial RSV infection. Babies hospitalized for more than 4 weeks were more likely to acquire RSV infection. Control measures are outlined for the reduction of nosocomial spread of RSV infection in our newborn nursery.

Seasonal variation in respiratory syncytial virus infections in children in Benin-City, Nigeria.

The seasonal variation in respiratory syncytial virus (RSV) infections in children was examined in Benin City. Nasopharyngeal washes were obtained from children under 3 years hospitalised for acute lower respiratory infections during two seasons - rainy season (June-August) and dry season (December-February). RSV surface antigen was identified by ELISA. 54% of patients in the rainy season were ELISA positive for RSV compared to 8.8% during the dry season. Clinical features in the RSV infected patients were not different between the two seasons and were similar to that reported from temperate climates. It is concluded that RSV infections occur all year round with a peak during the rainy season.

Chronic granulomatous disease with cranial fungal osteomyelitis and epidural abscess. Case report.

A patient is described with osteomyelitis of the cranium and epidural abscess due to Aspergillus fumigatus as the presenting manifestations of chronic granulomatous disease. The diagnosis was suggested by the unusual nature of the organism isolated and confirmed by appropriate laboratory studies. The details of diagnostic assessment and therapeutic management are discussed, and the central nervous system manifestations of chronic granulomatous disease are reviewed.

Effects of maternal protein deprivation on the nutritional status and neutrophil function of suckling neonatal rats.

An animal model of neonatal protein deprivation was developed to examine the effects of maternal malnutrition on growth and development and on the host defense system of the suckling offspring. Adult rats were fed either a protein-deficient (3% casein) or normal (25% casein) diet beginning one day after parturition. Offspring of the protein-deprived animals showed biochemical signs of nutritional imbalance such as changes in serum acid hydrolase levels as early as the second day of life; growth retardation and hypoproteinemia developed by day 4. When malnourished and control sucklings were infected at 12 days of age with Staphylococcus aureus, it was noted that protein deprivation did not influence neutrophil mobilization. However, malnourished animals responded to infection with larger perturbations in neutrophil counts than did the controls, were unable to control the infection, and ultimately showed neutrophil depletion. These studies suggest that protein deprivation affects the quantity and quality of milk and that the offspring of a protein-deficient animal are not only growth retarded but are also compromised in their ability to deal with infection.

Inefficient in vivo neutrophil migration in neonatal rats.

While neutrophils from neonates respond less efficiently in vitro to a chemotactic stimulus than do adult cells, the in vivo recruitment of phagocytic cells to focal sites of inflammation in some situations appears to be similar in adults and neonates. To resolve this apparent discrepancy between the in vitro and in vivo observations, neonatal and adult rats were inoculated intraperitoneally with a variety of chemotactic agents. The neutrophil response was far more intense in adults than in neonates, strengthening the hypothesis that chemotaxis is less efficient in neonates than in adults. This relative deficiency may play an important role in the inability of the newborn to deal with infection effectively.

Effect of fetal protein malnutrition on the postnatal structure and function of alveolar macrophages.

To test the hypothesis that intrauterine malnutrition may alter ontogeny of the host defense system, an animal model of fetal protein deprivation was developed. Young adult female rats were fed either a deficient (8% protein) diet or a normal (25% protein) diet for 10 days before insemination and throughout gestation. Offspring of the malnourished animals showed significant growth retardation and were hypoproteinemic. Lavageable pulmonary cells from both groups of neonates were similar with respect to number (2.05 x 10(5) cells per animal), type (95% macrophages), size (approximately 10-micrometer diameter), ultrastructure, and presence of surface receptors for IgG. Despite these similarities, alveolar macrophages from malnourished neonates were significantly impaired in their ability both to ingest and to kill Candida tropicalis. Nutritional supplementation of nursing females reversed these functional macrophage defects in their offspring by the time that weaning occurred. These data indicate that fetal protein malnutrition affects macrophage function but that with postnatal nutritional supplementation these defects are rapidly reversed.

Depressed blood neutrophil response to lithium stimulation in newborn rats.

The blood neutrophil response to lithium chloride challenge was determined in one-day-old and young adult rats to test the hypothesis that granulocytopoiesis is less efficient in neonates than in adults. Adult animals responded rapidly to lithium chloride treatment, showing a 134% increase in blood neutrophils on the second day of exposure and ultimately increasing by 260% by the tenth day. Newborn rats on the other hand, showed a 25% decrease in blood neutrophils after one day of treatment with lithium, then remained at that or at pretreatment levels throughout the subsequent 10 days. These observations suggest that hematopoietic tissue in the newborn is less responsive than is that of adults.

Pharmacokinetics of cefaclor in chronic middle ear effusions.

Fifty children aged 1 to 13 years with chronic or recurrent otitis media with effusion received a single dose of cefaclor (15 mg/kg body weight) by the oral route 30 minutes to seven hours before the removal of middle ear effusion and insertion of tympanostomy tubes. Serum and middle ear aspirate concentrations of the antibiotic were determined employing a microbiological assay technique by a disk diffusion method. Middle ear specimens were also cultured for aerobic bacteria. The mean peak serum concentration level (8.49 +/- 7.89 micrograms/ml) was observed after 30 minutes, whereas the middle ear peak level (0.47 +/- 0.78 micrograms/ml) occurred after one hour. Of the 87 middle ear specimens, 37 had cefaclor concentrations which were detectable within the resolution of the bioassay method (greater than 0.16 micrograms/ml). There was no correlation between the type of middle ear effusion (mucoid or serous) and the concentration of cefaclor in the middle ear. Only 18% of the middle ear cultures were positive for aerobic bacteria; Hemophilus influenzae was the most common organism.

Indolent neutrophil response to endotoxin in newborn rats.

The blood neutrophil response to endotoxin challenge was determined in one-day-old and young adult rats to test the hypothesis that the neonate is unable to mobilize neutrophils from bone marrow to the peripheral circulation at a rate similar to adults. Adult animals responded to endotoxin with a brief neutropenia followed rapidly by marked neutrophilia. The maximum adult neutrophil count occurred at 11 hr after challenge and returned to baseline values by 28 hr. In contrast, one-day-old rats showed a prolonged neutropenia after a comparable injection. Peak neutrophil counts in neonates occurred later than those seen in adults (16 versus 11 hr) and were also lower. However, neutrophilia, once established in the neonates, persisted considerably longer than in adults. The age at which the adult response to endotoxin is achieved was assessed by bleeding animals of increasing ages 7 hr after endotoxin challenge. A gradual progression toward the adult neutrophil response began at 2 wk of age. The mose rapid change in endotoxin responsiveness occurred after 6 wk of age.

Kinetics of phagocyte response to group B streptococcal infections in newborn rats.

To test the hypothesis that inadequate in vivo mobilization of leukocytes may contribute to the unique susceptibility of neonates to infection, we studied the kinetics of phagocyte response to neonatal and adult rats to intraperitoneal infection with group B streptococcus, type Ia. The 50% lethal dose was considerably greater for adults than for neonates (1.1 x 10(7) colony-forming units per g versus 2.7 x 10(2) colony-forming units per g). After challenge with group B streptococcus, type Ia, the number of neonatal peritoneal leukocytes increased more slowly than did those of adult rats. For example, at 4 h, the adult neutrophil count was 41 times greater than that of the neonate, but at 24 h, neonatal peritoneal neutrophils had not yet reached the adult 4-h level. Peritoneal macrophages also increased more rapidly in adults than in neonates. After intraperitoneal infection, both adults and neonates developed bacteremia, but adults cleared the bacteria with greater efficiency. Adult blood neutrophils increased 247% by 12 h and then decreased; neonatal neutrophils steadily decreased to a 57% reduction by 24 h. These data suggest that the neonatal neutrophil response to group B streptococcus, type Ia, infection is inadequate and may contribute to the high mortality associated with this infection.

Phagocytic dysfunction in monocytes of normal newborn infants.

The kinetics of phagocytosis by monocytes isolated from cord blood and from the blood of adult volunteers was studied. Monocytes attached to glass coverslips were incubated with polystyrene spheres (1.1 mu diameter) for up to 120 minutes. In this system, the rate of phagocytosis was considerably slower in newborn monocytes than in those from adults. By the time phagocytosis had occurred in virtually all of the adult cells, only 38% of the neonatal monocytes had engulfed particles. However, this defect was not absolute, since ultimately all of the newborn cells contained engulfed spheres. Levamisole had no effect on normal adult monocytes but accelerated phagocytosis of newborn cells to a rate identical with that of adult cells. These data demonstrate that newborn monocytes are less efficient in the early stages of phagocytosis than are comparable cells from adults, raising the question of the impact of phagocytic kinetics in the development of neonatal sepsis. The correction of this defect by levamisole suggests that the differences in neonatal and adult monocytes may be evaluated more thoroughly by similar pharmacologic probes.

Phagocytosis and intracellular killing of pathogenic yeasts by human monocytes and neutrophils.

The kinetics of phagocytosis and killing of four fungal forms with varying virulence by two types of phagocytic cells was examined. Human monocytes ingested Saccharomyces cerevisiae, Candida tropicalis, and the blastospores of Candida albicans more rapidly than did human neutrophils. There was no difference in the rate of phagocytosis of C. albicans pseudohyphae by these two cell types. Intracellular killing of each of the four fungal forms was consistently and significantly more rapid by monocytes than by neutrophils. Neutrophils were unable to destroy ingested C. albicans pseudohyphae. These experiments suggest that the monocyte plays an important role in host defenses against fungal diseases and that the relative virulence of the pathogenic yeasts in human disease may be related to the ability of these organisms to survival after being ingested by circulating phagocytes.