Humoral immunity to commensal oral bacteria in human infants: salivary secretory immunoglobulin A antibodies reactive with Streptococcus mitis biovar 1, Streptococcus oralis, Streptococcus mutans, and Enterococcus faecalis during the first two years of life.

Secretory immunoglobulin A (SIgA) antibodies reactive with the pioneer oral streptococci Streptococcus mitis biovar 1 and Streptococcus oralis, the late oral colonizer Streptococcus mutans, and the pioneer enteric bacterium Enterococcus faecalis in saliva samples from 10 human infants from birth to age 2 years were analyzed. Low levels of salivary SIgA1 and SIgA2 antibodies reactive with whole cells of all four species were detected within the first month after birth, even though S. mutans and E. faecalis were not recovered from the mouths of the infants during the study period. Although there was a fivefold increase in the concentration of SIgA between birth and age 2 years, there were no differences between the concentrations of SIgA1 and SIgA2 antibodies reactive with the four species over this time period. When the concentrations of SIgA1 and SIgA2 antibodies reactive with all four species were normalized to the concentrations of SIgA1 and SIgA2 in saliva, SIgA1 and SIgA2 antibodies reactive with these bacteria showed a significant decrease from birth to 2 years of age. Adsorption of each infant's saliva with cells of one species produced a dramatic reduction of antibodies recognizing the other three species. Sequential adsorption of saliva samples removed all SIgA antibody to the bacteria, indicating that the SIgA antibodies were directed to antigens shared by all four species. The induction by the host of a limited immune response to common antigens that are likely not involved in adherence may be among the mechanisms that commensal streptococci employ to persist in the oral cavity.

Humoral immunity to commensal oral bacteria in human infants: salivary antibodies reactive with Actinomyces naeslundii genospecies 1 and 2 during colonization.

The secretory immune response in saliva to colonization by Actinomyces naeslundii genospecies 1 and 2 was studied in 10 human infants from birth to 2 years of age. Actinomyces species were not recovered from the mouths of the infants until approximately 4 months after the eruption of teeth. However, low levels of secretory immunoglobulin A1 (SIgA1) and SIgA2 antibodies reactive with whole cells of A. naeslundii genospecies 1 and 2 were detected within the first month after birth. Although there was a fivefold increase in the concentration of SIgA between birth and age 2 years, there were no differences between the concentrations of SIgA1 and SIgA2 antibodies reactive with A. naeslundii genospecies 1 and 2 over this period. When the concentrations of SIgA1 and SIgA2 antibodies reactive with whole cells of A. naeslundii genospecies 1 and 2 were normalized to the concentrations of SIgA1 and SIgA2 in saliva, the A. naeslundii genospecies 1- and 2-reactive SIgA1 and SIgA2 antibodies showed a significant decrease from birth to 2 years of age. The fine specificities of A. naeslundii genospecies 1- and 2-reactive SIgA1 and SIgA2 antibodies were examined by Western blotting of envelope proteins. Similarities in the molecular masses of proteins recognized by SIgA1 and SIgA2 antibodies, both within and between subjects over time, were examined by cluster analysis and showed considerable variability. Taken overall, our data suggest that among the mechanisms Actinomyces species employ to persist in the oral cavity are the induction of a limited immune response and clonal replacement with strains differing in their antigen profiles.

Viral studies of mothers with human immunodeficiency virus infection at delivery and their infants in the first 3 days of life.

OBJECTIVE: We studied 49 mother-infant pairs for human immunodeficiency virus (HIV) (a) to assess the virological and immunological status of HIV-infected mothers at delivery and their infants within the first 3 days of the infant's life, and (b) to correlate these findings with eventual infection outcome in the infant. METHOD: Maternal blood from women in labor and infant's blood within 3 days of life were tested for the titer of HIV immunoglobulin G (IgG) antibody, for presence of HIV by culture, for p24 antigen, for HIV DNA by polymerase chain reaction (PCR), and for absolute T-helper cell count (CD4). RESULTS: Eight infants were in the confirmed infected (CI) group, with a transmission rate of 21%. Thirty infants were in the confirmed uninfected (CU) group. In the mother, mean anti-HIV IgG titer was 1:2600 (CI group) and 1:3350 (CU group); in the infant, the mean titer was 1:3250 (CI group) and 1:2710 (CU group). Eighty-seven percent of the mothers were culture-positive in the CI group compared to 33% in the CU group (p = 0.005). Eighty-seven percent of CI infants were PCR-positive at birth; none was PCR-positive in the CU group (sensitivity = 87%; specificity = 100%). Sixty-two percent of CI infants were culture-positive at birth, whereas none was positive in the CU group (sensitivity = 62%; specificity = 100%). Of the uninfected infants, 23% were positive for p24 antigen at birth. CONCLUSIONS: HIV IgG antibody titers in mothers and their infants at birth were markedly elevated in both CI and CU groups but were not protective against infection. However, the high titers explain the long duration of this antibody in the blood of infants born to infected mothers. Culture positivity in the mother at delivery correlated highly with eventual infection in the infant (p = 0.005). HIV antigen, specifically p24 antigen, was detectable in uninfected infants when tested at birth.

Clonal diversity of Streptococcus mitis biovar 1 isolates from the oral cavity of human neonates.

The clonal diversity of 101 isolates of the pioneer bacterium Streptococcus mitis biovar 1 obtained from the oral cavities of 40 human neonates 1 to 3 days, 2 weeks, and 1 month postpartum was examined by using rRNA gene restriction patterns. There was a high degree of genetic diversity, with the 101 isolates comprising 93 unique PvuII ribotypes. There were eight identical pairs of ribotype patterns, and seven of the eight pairs were obtained from individual neonates. Only one identical pair comprised isolates obtained from different neonates. In all but two cases, isolates with matching ribotypes were obtained at one visit. Two pairs of isolates with matching ribotype patterns were obtained from neonates on successive visits. The ribotype patterns of the isolates were examined by cluster analysis. The isolates forming each cluster were very similar, yet each cluster was well separated from its neighbors. When several isolates were obtained from individual neonates at a particular visit, in some instances they were contained in a single cluster, whereas in other cases each isolate was contained in a separate cluster. Isolates obtained from individual neonates on successive visits tended to be contained in different clusters. This high degree of diversity, which has been observed in other mucosal commensal bacteria, may serve as a mechanism for avoiding immune elimination of these bacteria.

Identification of pioneer viridans streptococci in the oral cavity of human neonates.

Three hundred and sixty-seven strains of pioneer streptococci isolated from the mouths of 40 healthy, full-term infants during the first month of life were examined by two taxonomic schemes that incorporated biochemical and physiological characteristics, IgA1 protease production and glycosidase activities. Streptococcus mitis biovar 1 and S. oralis comprised 55.0% of the pioneer streptococci isolated from neonates. S. salivarius constituted 25.3% of the isolates, while S. anginosus, S. mitis biovar 2, S. sanguis and S. gordonii accounted collectively for 11.4%. Difficulties in identifying streptococci were encountered and 8.4% of the 367 isolates could not be assigned to a recognised species.

Pioneer oral streptococci produce immunoglobulin A1 protease.

As part of a longitudinal study of the relationship between bacterial colonization and the secretory immune response, 367 isolates of pioneer viridans streptococci collected from 40 breast- and bottle-fed neonates within the first month postpartum were tested for the production of immunoglobulin A1 (IgA1) protease and glycosidases. Fifty percent of the streptococci isolated produced IgA1 protease, including all isolates of Streptococcus oralis and S. sanguis, 60.7% of S. mitis biovar 1 isolates, and some isolates that could not be identified. Three cleavage patterns of alpha 1 heavy chains were observed. Six isolates of S. mitis biovar 1 that did not produce IgA1 protease attacked the alpha 1 chain. Incubation of IgA1 protease-negative S. mitis biovar 1 isolates with IgA1, either prior to or together with S. sanguis, rendered the IgA1 paraprotein resistant to cleavage by the IgA1 protease of S. sanguis. The ability of some pioneer streptococci in the human oral cavity to produce IgA1 protease and of others to modify the susceptibility of IgA1 to cleavage by IgA1 protease perhaps enhances their ability to survive in this habitat.

Immunoglobulin A subclasses in infants' saliva and in saliva and milk from their mothers.

We sought to determine (1) the ontogeny of secretory IgA subclasses in saliva of breast- and formula-fed infants and (2) the influence of breast-feeding on the maturation of secretory salivary IgA subclasses. Secretory IgA and subclasses 1 and 2 concentrations were determined in saliva from 40 healthy, term infants from birth to age 18 months, and in parallel milk samples from the infants' mothers who were breast-feeding during the first 6 months after birth. Secretory IgA was detected in the neonates' saliva as early as 3 days after birth, increased rapidly during the next 6 months, but then stabilized at a level approximately one-sixth that of the mothers' salivary secretory IgA. Secretory IgA2 represented less than 15% of secretory IgA in saliva collected 2 weeks after birth but by 6 months represented 24.4% of secretory IgA, a value approaching that of the mothers' salivary secretory IgA2 (30.4%). This increase in the proportion of secretory IgA2 was temporally related to a reduction in the proportion of secretory IgA2 in milk throughout lactation. The secretory IgA concentration increased more rapidly during the first 6 months after birth in infants exclusively breast fed than in those exclusively bottle fed. We conclude that although secretory immunity is immature in infants, breast-feeding may aid in protection against pathogenic microorganisms by increasing the rate of mucosal IgA maturation.

Comparison of an immunochromatographic method for rapid identification of group A streptococcal antigen with culture method.

OBJECTIVES: To compare the sensitivity and specificity of Concise Strep A (Hybritech, San Diego, Calif), an immunochromatographic group A streptococcal rapid antigen detection system, with a two-plate culture method for the diagnosis of streptococcal pharyngitis, and to evaluate the need for routine back-up culture when this rapid test is used. DESIGN: Throat cultures were obtained from 351 children with acute pharyngitis by duplicate rayon-tipped swabs held in parallel and vigorously rubbed against both tonsils and the posterior pharyngeal wall. One swab was tested for group A streptococcal antigen by a registered licensed laboratory technologist in the pediatrician's office. The other swab was streaked over each of two sheep blood agar plates, one of which was enhanced with trimethoprim in combination with sulfamethoxazole. The plain sheep blood agar plate was then incubated in a candle-extinguish jar. The enhanced agar plate was placed in a gas-pack anaerobic jar. Both plates were incubated for up to 48 hours at 35 degrees C. SETTING: A six-person group pediatric practice. PARTICIPANTS: Three hundred fifty-one children. RESULTS: The Concise Strep A antigen detection test produced 129 positive results. Only six of the 129 were not confirmed by culture method. There were four false-negative rapid streptococcal antigen detection test results, all of which were found after a single overnight incubation. The sensitivity for the Concise Strep A test was 96.9% and the specificity was 97.4%. The plain 5% sheep blood agar plate (without trimethoprim and sulfamethoxazole), which was incubated in a candle-extinguish jar, identified 123 (97%) of the 127 positive throat cultures. The second 24-hour incubation and use of trimethoprim and sulfamethoxazole agar were not rewarding for this study. CONCLUSIONS: Concise Strep A, a polyclonal antibody test, in conjunction with a color immunochromatographic assay for soluble streptococcal carbohydrate antigen A appears to be accurate, sensitive, and specific when throat swabs are carefully obtained and when qualified, licensed laboratory technologists perform the procedure. Further studies should be done to confirm our findings, especially when nurses or office staff perform the rapid test procedure in the office setting. If our findings are confirmed, the use of back-up cultures for negative rapid test results obtained using Concise Strep A would be unnecessary.

Factors influencing pseudomonas colonization in cystic fibrosis.

In order to assess the relationship between various factors influencing Pseudomonas (Ps) colonization of the respiratory tract of patients with cystic fibrosis (CF) and the appearance of various strains of Ps, two groups of CF patients were studied during a 5-year period. Group A consisted of 24 Ps-negative patients, and Group B consisted of 32 Ps-positive patients, including eight patients who expired. Several clinical and laboratory parameters were evaluated. Although the precise mechanism causing the appearance of Ps in the respiratory tract of CF patients remains elusive, we analyzed several biologic characteristics of both host and organism. This study indicates that frequent use of antibiotics combined with the eradication of Staphylococcus aureus from the respiratory tract heralds the onset of persistent Ps colonization and a subsequent downhill course for CF patients.

Children less than three-years-old with pharyngitis. Are group A streptococci really that uncommon?

During a 15-month period, 148 infants and children less than 3-years-old who presented with signs and/or symptoms of pharyngitis were monitored in a private pediatric practice. Clinical signs included fever (95 or 64%), tonsillar exudate (16 or 11%), and cervical adenopathy (5 or 3%). Beta-hemolytic streptococci (BHS) from group A were isolated from throat swabs in 37 (25%) instances. These isolations were more common among children 25-35 months old than among children less than 2 years old (35% vs. 19%, p less than 0.05), and were significantly more likely when overnight anaerobic culture techniques were used rather than conventional aerobic methods (23% vs. 11%, p less than 0.01). Group A BHS may be isolated relatively frequently from symptomatic children under 3-years-old. Whether these isolations reflect invasive infection or asymptomatic carriage is uncertain.

Sore throats in adolescents.

The approach to the adolescent with sore throat requires few diagnostic tools: an accurate history, a good physical examination and the ability to perform simple laboratory tests such as complete blood count, a test for heterophile antibody and a throat culture. The majority of adolescent patients with a sore throat require only symptomatic relief for what is probably a short lived viral infection of the upper respiratory tract.

Occult bacteremia in toxic-appearing, febrile infants. A prospective clinical study in an office setting.

The prevalence of occult bacteremia was evaluated prospectively in two groups of infants: those with a toxic appearance and temperature greater than 38.8 C and a comparison group with similar fever but without a toxic appearance. All patients were diagnosed by one physician employed in a suburban, middle-class, private ambulatory pediatric practice. Toxicity scores were assigned based on the results of history and physical examination. Peripheral white blood cell (WBC) counts and blood cultures were obtained for every child. Of 52 toxic infants involved in the study, an infectious source, commonly otitis media, was found in 26 (50%). Eighteen patients (35%) had WBC counts above 15,000. Bacteremia was documented in six patients (12%), due to Streptococcus pneumoniae in five and to group C Streptococcus in one. Five bacteremic infants had toxic, febrile illnesses for which no overt focus could be identified. None of 31 febrile infants without a toxic appearance had bacteremia. We conclude that highly febrile, toxic-appearing infants are at risk for occult bacteremia even when they are seen in the pediatrician's office. Toxicity diagnosed on the basis of clinical findings in a febrile infant warrants obtaining a white blood cell count and a blood culture.