CD5+ B cells in normal newborns and infants, and in those with HIV and intrauterine infections.
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Biomedical subjects
Publications and source records attributed to B J Stoll.
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OBJECTIVE: To assess the outcome of infants born to hepatitis B surface antigen (HBsAg)-positive mothers who received prenatal and infant care in a large, public health care system. DESIGN: Follow-up of a cohort of infants born to HBsAg-positive mothers. SETTING: Large, urban hospital providing prenatal care and obstetric services to county health departments. PARTICIPANTS: Forty-two infants born to HBsAg-positive women. INTERVENTIONS: Prenatal testing of women and immunoprophylaxis of infants with hepatitis B immune globulin at birth and hepatitis B vaccine at birth and ages 1 and 6 months. RESULTS: All 42 infants received hepatitis B immune globulin and the first dose of vaccine. Of forty-one infants (98%) who received the second dose of vaccine, 37 received it by age 4 months. Thirty-two infants (76%) completed the three-dose vaccine series by age 12 months, and 34 infants (81%) completed the series by age 18 months. The rate of completion of the hepatitis B vaccine series was comparable to that of infants receiving the third dose of diphtheria-pertussis-tetanus vaccine. Of 26 infants who completed the hepatitis B vaccine series and had follow-up serologic testing, 24 (92%) had adequate levels of antibody to HBsAg. Only one infant who did not complete the vaccine series had serologic evidence of hepatitis B virus infection. No infant was HBsAg-positive. CONCLUSIONS: Public programs serving urban populations can effectively deliver hepatitis B immunoprophylaxis to infants born to HBsAg-positive mothers.
Group B streptococcus (GBS) is a common cause of early-onset sepsis in neonates. The most recent reviews describing incidence, diagnosis, treatment, and outcome evaluated data on patients from the early 1980s. To obtain current information about this disease, we retrospectively evaluated data on neonates with GBS early-onset sepsis from nine hospitals in the United States between Jan. 1, 1987, and Dec. 31, 1989. There were 245 infants with GBS bacteremia identified among 61,809 live births, resulting in an incidence of 0.32%. Ninety-six infants (39%) were preterm (less than 38 weeks of gestational age). Maternal risk factors for infected preterm and term infants were similar. Antibiotics were administered during parturition in 10% of infants with bacteremia. Mothers of preterm infants received antibiotics up to 48 hours before delivery; mothers of term infants received antibiotics less than 4 hours before delivery. All preterm infants with bacteremia had symptoms; 22% of term infants with bacteremia had no symptoms. Group B streptococcal meningitis was confirmed in 6.3% of infants. Although 86% survived, GBS sepsis increased the birth weight-specific mortality rate up to eightfold in preterm infants and more than 40-fold in term infants. Although the incidence of GBS early-onset sepsis is not changing, we speculate that the improved birth weight-specific survival rate and the changing clinical presentation are due to improved intrapartum and neonatal management.
Newborn infants may have IgG deficiencies that increase their susceptibility to bacterial infection. To determine whether intravenous immune globulin (IVIG) therapy improves survival rates in early-onset sepsis, we prospectively entered 753 neonates (birth weight 500 to 2000 gm, gestation less than or equal to 34 weeks, age less than or equal to 12 hours) into a multicenter, double-blind, controlled trial. Blood culture specimens were obtained and infants randomly assigned to receive 10 ml (per kilogram) intravenously of a selected IVIG (500 mg/kg) or albumin (5 mg/kg) preparation. Maternal and neonatal risk factors were not different between groups. Thirty-one babies (4.2%) had early-onset sepsis; the causative organisms were group B streptococcus (12 babies), Escherichia coli (6), and others (13). Of these 31 neonates, 7 (23%) died. Total serum IgG was higher for 7 days after IVIG therapy than after albumin treatment (p less than 0.05). During these 7 days, 5 (30%) of 17 albumin-treated and none of 14 IVIG-treated patients died (p less than 0.05). The survival rate at 56 days of age, however, was not significantly improved. Group B streptococcus type-specific IgG antibody was significantly increased after IVIG treatment and appeared to be related to the amount of IVIG specific antibody. Infusion-related adverse reactions were less frequent in patients receiving IVIG therapy (0.5%) than in those receiving albumin. The IVIG therapy in neonates with early-onset sepsis, while reducing the early mortality rate, did not significantly affect the overall survival rate. Further studies are necessary to confirm these findings and to determine more effective therapeutic regimens.
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Intrapartum antibiotics are frequently administered to parturient women for suspected chorioamnionitis to treat infection in the mother and to prevent or treat infection in the baby. We sent a questionnaire to the 150 United States fellowship program directors in neonatology and pediatric infectious disease, focusing on recommendations for evaluation and therapy of apparently healthy, pretreated, term gestation infants. Eighty-three (55%) of the completed responses were analyzed. Sixteen (19%) respondents do no initial laboratory evaluation but simply observe the baby, 65 (78%) take a complete blood count as well as a platelet count, 59 (71%) obtain blood cultures, 41 (49%) check urine antigen for Group B Streptococcus (GBS) and 23 (28%) perform a lumbar puncture. Only 39% of respondents would begin antibiotic therapy for all pretreated infants. If the evaluation were unremarkable 65 directors would treat for less than or equal to 3 days. If only the urine GBS antigen were positive 47 would treat for greater than or equal to 7 days, while if an elevated immature neutrophil:total neutrophil ratio were the sole abnormality 19 would treat for greater than or equal to 7 days. Forty-four respondents thought that a combination of an elevated immature neutrophil:total neutrophil ratio and a positive urine GBS antigen should always be considered indicative of bacteremia. Given a different scenario, that of a mother treated with intrapartum antibiotics because of a positive cervical culture for GBS and a risk factor (e.g. temperature greater than or equal to 38 degrees C), 58 respondents would begin antibiotics. There is no consensus regarding management of pretreated, healthy appearing, term gestation neonates.
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The blood culture results of all samples obtained from newborns at Grady Memorial Hospital, Atlanta, Ga., during a 6-month period were analyzed to determine the time required for a blood culture to become positive, the time at which a culture could safely be considered negative, and the spectrum of isolated organisms. During the study period, 1,248 samples were submitted from all nurseries and processed by an automated detection instrument (BACTEC NR660). Of the 1,248 samples, 98 (7.8%) were positive by the end of a 7-day processing period; 29 of the 98 were classified as definite bacterial pathogens, 52 were classified as possible bacterial pathogens, 9 were classified as yeasts, and 8 were classified as contaminants. Virtually all organisms (28 of 29) categorized as definite pathogens were identified by day 2 of processing, and all were identified by day 4. All isolates of group B streptococcus, Escherichia coli, Klebsiella species, and Staphylococcus aureus were identified by day 2. Of all positive blood cultures, 79% were identified by day 2, 88% were identified by day 3, and 94% were identified by day 4. Of the 21 isolates identified after day 2, the only definite pathogen was from a sick baby in the intensive care unit. From among the 870 term low-risk newborns cultured because of maternal risk factors, only four possible pathogens were identified after day 2. The positive and negative predictive values of blood culture at days 2 and 4 were 92 and 99%, respectively. We conclude that, in our institution, (i) a 2-day processing period is sufficient to detect positive blood cultures in the asymptomatic term infant, (ii) a 4-day processing period will detect virtually all clinically important infections, and (iii) clinical yield from continuing blood culture processing beyond 4 days does not justify the time and cost involved.
The association between undernutrition and the risk of colonization and disease with Vibrio cholerae O1, concentrations of salivary IgA and the serologic response to infection and to orally administered cholera B subunit were examined prospectively in a family study in Bangladesh. Children ages 1 to 8 years who were family contacts of patients hospitalized with culture-confirmed cholera were visited within 24 hours of the hospitalization and daily for 10 days, queried for the presence of diarrhea and cultured for V. cholerae O1. On Day 1 each child was weighed and saliva was collected to measure total IgA. On Days 1 and 21 blood was taken to assess vibriocidal and antitoxin titers, and on Days 1 and 2 B subunit or placebo was given orally as part of a trial to look for a toxin-blocking effect. Of 412 children enrolled in the study 35% (143) became infected with V. cholerae O1 and 49% (70) of these developed diarrhea. Undernutrition, defined in a child as weight less than 70% of the Harvard reference weight-for-age, was not associated with colonization, disease or the duration or severity of cholera. Moreover well-nourished children did not differ from undernourished children in their concentrations of salivary total IgA, initial serum antitoxin or vibriocidal antibodies or in their serologic response to colonization, disease or B subunit. The immune system in its response to cholera appears to be quite resistant to nutritional insults. The good antitoxin response to B subunit among undernourished children is of particular importance in considering the use of future oral cholera vaccines in areas where such undernutrition is common.
Entamoeba histolytica was studied in 33 lactating women and their infants in a periurban village in Bangladesh. Infant-mother pairs were followed for a period of 10-15 months: 67% of mothers excreted E. histolytica during the observation period, the majority for 3 months or more. Only one mother was symptomatic, with a mild, non-dysenteric diarrhoea. 58% of mothers were seropositive, several of them continuously and with a high titre, indicating past invasive infection. 67% had detectable antibodies in breast milk and 36% in saliva. Despite the high prevalence of E. histolytica in these mothers, infants were mostly uninfected: E. histolytica cysts in small numbers were found in only 2 of 1200 samples from infants aged 6 and 10 months. Several of the children were infected with Giardia lamblia. Although lower exposure to E. histolytica than to Giardia may account for the difference in infant infection rates with these parasites, defence mechanisms possibly exist which protect against E. histolytica but are ineffective against Giardia.
Fifteen patients hospitalized with acute, watery diarrhea and with enterotoxigenic Escherichia coli (ETEC) detected from stool samples were studied to evaluate the extent to which natural ETEC diarrhea induces local and systemic antibody responses to E. coli heat-labile toxin (LT), homologous lipopolysaccharide (LPS), and colonization factors (CFA/I and CFA/II). Specific IgA and IgG antibodies to LT, CFA I and II, and each patient's homologous LPS were determined by ELISA in serum, saliva, breastmilk, and intestinal lavage fluid. The majority of patients had greater than a twofold rise in local levels of IgA antibodies in the intestine: 80% of LT+ patients responded to LT, 63% of CFA+ patients responded to CFA, and 78% of all toxin-positive patients responded to the LPS of their infecting strain. Local antibody responses in the intestine were associated with responses in breastmilk and saliva, but relationships were not clear-cut, and the usefulness of these secretions as proxy measures of local intestinal antibody production remains unclear. Antibody responses in serum also occurred in most patients and were significantly more frequent in cases than in controls. This study demonstrates that natural ETEC disease results in local IgA responses to LT, CFA, and LPS in the gut and also in immune responses in breastmilk, saliva, and serum.
To investigate whether breast-feeding protects children against rotavirus diarrhea (RVD), we compared rates of breast-feeding by age and enteric pathogens among 2,276 children with diarrhea 0-4 years of age who attended a diarrhea hospital in Bangladesh. Infants 0-5 months were less likely to be breast-fed than children 6-11 months of age suggesting that some protection against diarrhea with all agents was associated with early breast-feeding. In every age group studied, breast-feeding was more common among children with RVD than among children with non-RVD whereas it was less common among children with cholera and shigellosis. Twenty percent of breast milks consumed by infants less than 1 year of age had high levels of neutralizing activity (greater than or equal to 320) to the Wa strain of rotavirus but this activity did not appear to be protective since the 30 infants with RVD consumed milk which had titers that did not differ significantly from those consumed by 44 infants with diarrhea of other cause. Despite the prolonged breast-feeding which is common in Bangladesh, the mean age of hospitalization with RVD is approximately the same as in countries where the duration of breast-feeding is quite short. None of these 3 independent observations support a protective role for breast-feeding against rotavirus diarrhea after the first months of life.
A murine monoclonal antibody (MAb) was prepared against Pseudomonas aeruginosa immunotype-1 (It-1) lipopolysaccharide (LPS). The MAb bound It-1 LPS in the enzyme-linked immunosorbent assay and in the immunodiffusion and immunoblotting assays, agglutinated and opsonized It-1 bacteria, and protected against challenge with live It-1 organisms in a murine burn infection model. All of these activities were immunotype specific. Correlation of the opsonic and protective properties of the MAb with its recognition site on the LPS O side chain confirmed that such immunotype-specific determinants are important targets for protective antibodies in Pseudomonas disease. The functional equivalence of this MAb and polyclonal antibodies from hyperimmune plasma underscores the therapeutic potential of single MAbs which recognize critical determinants in the LPS O side chain.
Fecal Escherichia coli isolates from 196 patients with watery diarrhea and 68 healthy individuals (controls) were analyzed in Bangladesh immediately after isolation for the presence of colonization factor antigen (CFA) I or II (CFA/I or CFA/II, respectively) by a mannose-resistant hemagglutination (MRHA) test with six species of erythrocytes and by a slide agglutination test with absorbed CFA/I or CFA/II antisera. The presence of CFAs was confirmed by immunodiffusion analyses done in Sweden. By these methods, it was found that 49 of 69 enterotoxin-producing E. coli strains isolated from patients carried CFA/I or CFA/II, whereas none of the nonenterotoxigenic E. coli isolates or the three toxin-positive strains isolated from healthy individuals carried these adhesins. All E. coli strains retained their MRHA ability after transportation to Sweden followed by one subculture and after storage at -70 degrees C (but not at room temperature) for 1 to 2 years without further subculturing. After 5 to 10 subcultures of the fresh isolates, however, 70% of the initially CFA/I- and 80% of the initially CFA/II-carrying strains analyzed did not hemagglutinate. The efficacy of different methods for detecting CFAs on the fresh isolates was compared with that of immunodiffusion. The sensitivity of MRHA with human blood group A erythrocytes for the detection of CFA/I was high (97%), but the specificity was only 69%. The sensitivity of MRHA with bovine erythrocytes for the detection of CFA/II in Bangladesh was very low but increased considerably when chicken erythrocytes were also used. Whereas both false-positive and false-negative reactions were obtained when absorbed CFA antisera were used for agglutination, antisera against purified CFAs were equally effective as immunodiffusion in identifying CFA/I and CFA/II-carrying strains.
Anti-chlamydial antibodies were detected in 25 of 93 patients with diarrhoea in Bangladesh. This first report of evidence for chlamydial infection in this country should stimulate a search for a causal relationship between chlamydiae and prevalent diseases of Bangladesh.
To study the pathogenesis of diarrhea occurring with typhoid fever, we selected 42 patients with diarrhea and blood cultures positive for Salmonella typhi or Salmonella paratyphi A, but without diarrheal copathogens, for measurement of stool output and examination of fecal composition. The mean duration of fever before hospitalization was 9.5 days, and the mean duration of diarrhea was 5.8 days. All patients passed liquid stool on their first day in the hospital, ranging in volume from 4 to 172 ml/kg with a mean of 45 ml/kg. Red blood cells were in the stools of 57% of the patients. All patients had fecal leukocytes with a mean of 4,950 leukocytes/mm3, predominantly polymorphonuclear leukocytes. In the stools, the mean protein concentration was 9.3 g/liter; the mean pH was 6.1, and the mean concentration of electrolytes was as follows: sodium, 47 mEq/liter; potassium, 48 mEq/liter; and chloride, 43 mEq/liter. The mean total CO2 was 24 mmol/liter. During treatment with chloramphenicol, this group of patients showed daily improvement with a drop in both fever and stool output. The results indicate that patients with diarrhea during typhoid fever have a wide range of rates of purging, and the diarrhea is characterized by liquid stool containing large quantities of leukocytes and protein and is resolved by treatment with chloramphenicol.
At the Matlab Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, the authors examined the blood groups of patients hospitalized between January and September 1979 for diarrheal disease due to a variety of bacterial and viral agents. A significant association was identified only for cholera, in which cholera patients were twice as likely to have blood group O and one-ninth as likely to have blood group AB as community controls. A follow-up study of family contacts of cholera patients, carried out between September 1980 and July 1982, indicated that blood group did not affect an individual's risk of having a culture-proven infection with V. cholerae 01 but was directly related to the severity of disease. Individuals with the most severe diarrhea compared with those with asymptomatic infection were more often of blood group O (68% versus 36%, p less than 0.01) and less often of AB (0% versus 7%, p less than 0.01). It was not possible to identify the molecular basis for this genetically related protection using biologic models of cholera that are currently available. The constant selective pressure of cholera against people of O blood group may account in part for the extremely low prevalence of O group genes and the high prevalence of B group genes found among the people living in the Gangetic Delta.
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