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The c protein (Ibc) of group B streptococci (GBS) is associated with at least four antigens (alpha, beta, gamma, delta). To assess the virulence potential of these antigens, 255 GBS isolates recovered from septic neonates, healthy neonates, and pregnant women were serotyped and surveyed for reactivity with sera to c protein and the four associated antigens. A radioimmunoassay using intact bacteria was used to detect the GBS antigens. In contrast to earlier reports, most (66%) of the type III strains expressed the c protein. Except for the gamma antigen, none of the other c protein-associated antigens showed an increased association with pathogenic strains independent of the polysaccharide antigens. The gamma antigen was expressed by 15 of 41 c protein-positive early-onset strains and by 4 of 38 c protein-positive late-onset strains (P = .007). This association was independent of the type-specific antigen, suggesting a potential role for the gamma antigen as a virulence factor in GBS strains causing early-onset sepsis.

A group of 1031 parturient women at high risk for intraamniotic infection were studied. Women in whom group B streptococci grew from cultures of the amniotic fluid did not differ in clinical risk factors when compared with similar parturient women without group B streptococcal colonization of amniotic fluid. Patients who had perinatal group B streptococcal disease (maternal or neonatal bacteremia) did not differ from those without disease, by maternal or neonatal acute antibody levels or antibody response, inoculum size, or serotype of the colonizing strain.

The adherence to human epithelial cells, biotype and capsular type of 175 Haemophilus influenzae cultured from the upper respiratory tract were studied in a prospective study of children with recurrent otitis media. Forty-three children who had greater than 2 episodes of acute otitis media (AOM) during the first year of life were followed for at least 1 year. Cultures of the oropharynx were done periodically, and the middle ear fluid (MEF) was cultured at the time of AOM. H. influenzae was recovered from MEF in 44% of the 136 AOM episodes recorded. Thirty-one children had at least one episode of AOM caused by H. influenzae; the remaining 12 children, designated as "controls," had no otitis or had AOM caused by other organisms. The possible differences between carriage and infection strains were evaluated by comparison of MEF and oropharyngeal isolates, by pairwise comparison of MEF and oropharyngeal isolates and by pairwise comparison of multiple isolates from each host recovered at the time of AOM and during infection-free intervals. No significant differences in patterns of adherence, capsular type or biotype were found. The lack of correlation between these characteristics and infection suggests either that H. influenzae organisms have determinants of virulence yet to be defined or that variations in host susceptibility permit infection by the strain colonizing the upper respiratory tract. Adherence per se may be less important in the development of infection than in establishing and maintaining colonization within the host.

Problems encountered with currently recommended selective media for group B streptococci (GBS) (selective broth medium and CNA agar) prompted a searach for alternative culture methods in ongoing epidemiological studies. Previously recommended inhibitory agents were tested in vitro. Gentamicin, alone or in combination with nalidixic acid, proved inhibitory for many GBS strains. Among other agents tested, polymyxin was most complementary to the gram-negative spectrum of nalidixic acid, without compromising GBS growth. Crystal violet provided the simplest, most economical staphylococcal inhibitor. Broth and agar media, constituted with these three agents and designated NPC, were evaluated in vitro and in field studies. This investigation represents the first direct comparison of broth media containing inhibitory agents for the preferential isolation of GBS. In maternal colonization studies, NPC broth proved superior to Todd-Hewitt broth containing nalidixic acid and gentamicin at concentrations employed in the previously described selective broth medium (95% versus 59% recovery). Our comparisons were done without added sheep blood since GBS grow well in Todd-Hewitt broth. NPC broth proved more sensitive than NPC agar for detecting GBS colonization in newborns. The NPC agar medium was useful for further purification of broth cultures and quantitative culture techniques.

The group B streptococci (GBS) are known to have type-specific polysaccharides rich in N -acetylneuraminic aci acid end groups, which are thought to be important immunological determinants. Wheat germ agglutinin (WGA) has affinity for N -acetylneuraminic acid as well as N -acetylglucosamine, and readily precipitates the type but not the group polysaccharide. A WGA-Sepharose affinity column was used to isolate complete type polysaccharides of representative strains of the 4 major GBS types. WGA, other lectins, and rabbit antisera were then used to characterize the products of various extraction procedures and chemical degradations, including mild acid hydrolysis and treatment with neuraminidase. Results of lectin binding studies were consistent with proposed chemical structures of types Ia, Ib and II. Differences were noted, however, between the cross-reactive antigens of pneumococcus type 14 and the desialated GBS type III polysaccharide. Although structurally similar, indirect evidence from lectin binding studies suggest that these antigens may not be identical.

Bacteriuria in pregnancy was prospectively studied in 569 women, with specific reference to group B streptococcal infection. Forty-six patients (8%) had bacteriuria, including 14 with group B streptococcal infection; group B streptococci (GBS) were exceeded in frequency only by Escherichia coli. Two thirds of the bacteriuric patients remained asymptomatic. The outcome of pregnancy was studied in 41/46 bacteriuric patients, including all those with group B streptococcal infection. Two pregnancies ended in intrauterine fetal death, and one neonate developed group B streptococcal sepsis; all three complications occurred in the 14 women with group B streptococcal bacteriuria. Diabetes mellitus appeared to increase the risk of group B streptococcal bacteriuria. This study revealed that group B streptococcal bacteriuria is more common in pregnancy than was previously suspected and suggests that culture methods to detect GBS should be used in bacteriuria screening programs done in pregnancy. In terms of perinatal infection risk, screening for group B streptococcal bacteriuria at or near the time of delivery may be more meaningful than other group B streptococcal surveillance culture studies.

In a study of the natural history of pneumococcal carriage and infection in infants enrolled at birth in Birmingham, Alabama from November 1974 to December 1975, the authors observed patterns of acquisition and carriage that appeared to be influenced by age and the season of the year. To describe more precisely these effects, the original data were used to construct multiple regression models for acquisition, carriage rates, and duration of carriage of pneumococci during the first 24 months of life. The acquisition rate was strongly seasonal, with a marked winter peak and summer low. Seasonal rate increased with age, while the duration of carriage decreased; these combined effects were reflected in the carriage rate, which increased sharply up to the age of nine months, then leveled off. While age and season accounted for a relatively small part of the variation in acquisition and carriage rates, the models were found to fit the data very well. The authors were able to analyze the data in a precise fashion, confirm earlier observations, and relate them to the work of other investigators over the past 50 years.

Streptococcal pharyngitis remains a common problem in children and adolescents. However, the incidence of acute rheumatic fever is now quite low except in developing countries. Proper management of streptococcal pharyngitis has contributed significantly to the decline in ARF. Penicillin treatment has clearly altered the natural history of streptococcal infection; the acute illness is shortened, risk of spread of infection is reduced, suppurative complications are prevented and ARF is prevented. Some cases of acute glomerulonephritis may be prevented. The decline in rheumatic fever has probably contributed to a greater interest in clinical benefits of therapy. Antigen detection tests appear promising for providing a more rapid bacteriologic diagnosis of streptococcal infection, which in turn permits prompt treatment. While penicillin has been the treatment of choice for four decades, a disturbing trend of increasing numbers of clinical relapses or recurrent infections has been noted in recent years. Alternative antibiotics, such as the oral cephalosporins, may now be superior to oral penicillin in terms of lessening the risk of relapse. This advantage must be weighed against other factors including cost effectiveness. The most pressing dilemma for the clinician is management of the patient with repeated episodes of acute streptococcal pharyngitis. Certain of these problem patients may benefit from a period of penicillin prophylaxis during the seasons when streptococcal infections are most prevalent. There is now agreement that posttreatment throat cultures need not be done in the child who remains asymptomatic following therapy. However, it is incumbent on the clinician to make certain that appropriate therapy is prescribed and that compliance with oral regimens of therapy is satisfactory in the management of the patient with acute streptococcal pharyngitis.

Twenty-one patients were seen with puerperal sepsis owing to group B streptococci (GBS), resulting in an attack rate of 2/1,000 deliveries. Most were young primiparous black women from a population with a known high incidence of GBS carriage. The asscciation among abdominal delivery, endometritis, and puerperal sepsis was striking. Cultures of the birth canal or lochia were commonly positive for the same serotype recovered from the blood. Forty-seven patients with nonbacteremic GBS infections were seen; 27 had endometritis or amnionitis. Twenty patients had GBS urinary tract infection: Eight infections occurred prenatally, seven at delivery, and five post partum. Seven neonates developed serious GBS infections; intrauterine exposure occurred in at least four cases. Fetal exposure to GBS also occurred in three of four cases in which parturients with GBS bacteremia were delivered of their infants by cesarean section. Because of the high incidence of puerperal and perinatal GBS infections in this population, antibiotic prophylaxis regimens may be beneficial.

Type-specific antibodies against group B streptococcal and pneumococcal capsular antigens were measured in 68 amniotic fluid samples from healthy women between 16 and 20 weeks of pregnancy. Mean antibody levels ranged from 0.13 to 0.61 microgram/ml, with few samples having greater than 1 microgram/ml against any antigen. The role of antibodies in protection against intrauterine infection is discussed.

Mouse hybridoma antibodies of several major classes against group B streptococcus type III have been produced. Mice were immunized with either whole heat-killed or acid-treated organisms to obtain antibodies against both the complete (sialated) or incomplete (nonsialated) forms of the type III polysaccharide. Resulting monoclonal antibodies showed exclusive specificity for either the complete or incomplete antigen. The ability of these antibodies to protect mice from a lethal challenge of live type III organisms was tested with a mucin model that permitted use of very small inocula given intraperitoneally with antibody and mucin. Antibodies specific for the nonsialated antigen were not protective, whether of IgM, IgG2a, or IgG3 isotypes. Antibodies specific for the complete antigen were, however, highly protective, including monoclonals of IgM, IgG2a, and IgA isotypes. These mouse monoclonal antibodies against group B streptococci that are directed against either complete or incomplete antigenic determinants, and include isotypes other than IgM, should be particularly useful for studying the mechanism of protection against experimental infection.

Mouse monoclonal antibodies were used in the immunochemical characterization of the polysaccharide antigens of group B streptococci (GBS). Monoclonal antibodies specific for the sialylated form of the GBS type III polysaccharide were highly protective in a mouse model of GBS type III infection, whether of IgM, IgG2a, or IgA isotypes, but monoclonal antibodies specific for the nonsialylated form of the type III antigen were not protective, regardless of isotype. Monoclonal antibodies reacting with the type II polysaccharide antigen could be divided into two general antigen binding groups on the basis of the ability of beta-methylgalactopyranoside to inhibit their binding to purified type II antigen. Various proportions of antibodies with the two specificities were observed in rabbit and human sera. Although it was previously reported that rabbit antisera could not distinguish between the sialylated and nonsialylated forms of the type Ib polysaccharide, mouse monoclonal antibodies were found to exhibit exclusive specificity for one or the other form of the antigen. Only monoclonal antibodies specific for the sialylated Ib polysaccharide were protective in a mouse model.

The group-specific polysaccharide of the group B Streptococcus was isolated by nitrous acid extraction followed by gel filtration on Sepharose 6B and chromatography on DEAE-Bio-Gel A. It was composed of rhamnose, galactose, N -acetylglucosamine, and glucitol phosphate. Mild periodate oxidation of the polysaccharide resulted in a rapid reduction in molecular weight, indicating that the glucitol was located in the backbone of the polymer. High-resolution 31 P NMR showed the presence of a single type of phosphodiester bond in the molecule. Methylation analysis and several specific chemical degradations were done to determine sugar linkages. The basic structure of the group B polysaccharide consists of a backbone of 2-linked rhamnose, 2,4-linked rhamnose, and glucitol phosphate, and side chains of rhamnose(1 → 3)galactose(1 → 3) N -acetylglucosamine linked to the 4-position of a rhamnose in the backbone.

A prospective study of group B streptococcal (GBS) carriage and disease was conducted over 6 years. Carriage rates at delivery for mothers and infants were 20% and 12%, respectively. Forty-five cases of GBS disease occurred in infants, 24 "early-onset" disease and 21 "late-onset" disease. The combined attack rate for early and late disease was 3.3 per 1000 live births over the 6 years. The rate of early-onset disease was highest in infants found to be heavily colonized at birth: 50 per 1000 live births. Twenty-three of 24 had evidence of intrauterine-acquired infection. All GBS serotypes were represented. Preterm delivery, prolonged labor, premature rupture of membranes, and maternal infection enhanced the risk of early disease. Septicemia was the predominant form of late-onset disease (15 of 21 cases); GBS type III accounted for 19 of 21 cases. Ten of 21 infants with late infections were colonized at birth with the GBS type that subsequently caused disease. Thus a maternal source of infection was identified in 34 of the 45 infants. These data reveal consistent year-to-year carriage and disease rates in the study population.

The incidence of GBS colonization at birth was determined prospectively among 96% of 2,407 infants born over a 12-month period in an urban community hospital. GBS were recovered from one or more of the four sites cultured in 290 (12.5%) of these newborn infants, 91 of whom were heavily colonized (3 to 4 sites positive). Sepsis or meningitis occurred in 13 infants, an attack rate of 5.4/1,000 live births. Attack rates for early and late onset disease, respectively, were 3.7 and 1.7 per 1,000 live births. All serotypes were found to cause disease. The incidence of early sepsis was strikingly high (8%) in heavily colonized infants. Those colonized at 1 to 2 sites were at no greater risk than noncolonized infants. The maternal vaginal colonization rate at delivery was 19%, with acquisition from the mother documented as the primary source of the organism in early onset infections. Perinatal events, including maternal complications and signs of illness at or immediately after birth, suggested ascending infection with exposure in utero to be likely in six infants. Passive acquisition of GBS (intrapartum exposure) probably occurred in the three remaining early onset cases. This mechanism was also likely responsible for five nonbacteremic infections. The four infants with late onset sepsis or meningitis were not colonized at birth or when discharged from the nursery (day 3); a possible maternal source for infection was found in only one of these infants.

The relationship between nasopharyngeal carriage of Streptococcus pneumoniae types 3, 19, and 23 and the development of homotypic serum antibody was examined in 17 infants followed prospectively from birth. Serially drawn sera from these children and single serum samples from 18 normal adolescents were assayed for opsonizing antibody using reduction of nitroblue tetrazolium to measure phagocytosis of killed whole pneumococci. Selected sera were also tested for quantitative antibody level by a radioimmunoassay, which correlated quite well with the nitroblue tetrazolium assay. All but one of the adolescents had antibody to type 19, and all 18 had antibody to type 23. None of the 12 infants tested for antibody to type 19 pneumococci showed evidence of an antibody response. Two of 10 infants responded to type 23 pneumococci, as did two of three infants tested to type 3 pneumococci.

Theoretically, rheumatic fever and acute glomerulonephritis can be prevented; perhaps enough attention has not been paid to the latter as a complication of streptococcal pyoderma. In warm climates particularly, streptococcal impetigo may sometimes reach epidemic proportions. Alertness to the appearance of specific nephritogenic serotypes and adequate treatment of sibling contacts as well as index cases can do much to reduce the incidence of AGN.

In studies involving 531 children with streptococcal skin lesions, with or without penicillin-resistant staphylococci also present, intramuscular benzathine penicillin G provided the most effective treatment. Streptococci, when present in the respiratory tract, were also eradicated. Neither topical bacitracin nor a single injection of penicillin in oil gave satisfactory results. Six of 54 siblings of children with nephritis, all of whom were infected with nephritogenic streptococci, developed acute glomerulonephritis within one week after initiation of therapy, suggesting that treatment came too late to prevent this complication. It is uncertain how often benzathine penicillin G therapy prevented nephritis in other patients. Such therapy does provide a means for prompt eradication of streptococci, effective clearing of clinical infection, and limiting the spread of organisms to others. Significant untoward reactions to penicillin were not observed.

Rheumatic fever is a recurrent disease which frequently can be prevented. Infection with group A streptococci precipitates both initial and recurrent attacks; therefore, prevention of rheumatic fever and rheumatic heart disease depends upon the control of streptococcal infections. This may be accomplished by (1) prevention of streptococcal injections in rheumatic subjects, and (2) early and adequate treatment of streptococcal infections in all individuals. Bacterial endocarditis may result from dental and other surgical procedures in patients with rheumatic or congenital heart disease. When such procedures are undertaken, these patients should be protected by administration of antibiotics in therapeutic doses.

One of the largest food-borne epidemics of streptococcal infection on record occurred among cadets at the U.S. Air Force Academy in the spring of 1968. Over 1,200 cadets (38.996 of the population) developed symptoms of streptococcal pharyngitis. In the manner characteristic of a common-source epidemic, the majority of cases fell ill in a short period of time. Many were acutely toxic. Of the patients interviewed, over 8096 reported abrupt onset of chills, fever, sore throat, and headache. Epidemiological studies in

Erythromycin, phenoxymethyl penicillin, and intramuscularly administered benzathine penicillin G were compared in the treatment of 708 patients with bacteriologically proved streptococcal skin infection. All forms of therapy were highly effective in eradicating skin streptococci. However, benzathine penicillin G proved more effective than the oral preparations in preventing early recurrences or new cases of impetigo and in reducing streptococcal respiratory carrier rates. Acute nephritis developed in 5 of 91 children known to be infected with nephritogenic streptococci.

Fourteen infants with erythroblastosis fetalis were studied with particular reference to bone marrow activity and its relation to anemia in the infants. Serial studies of the marrow were done in 12 of the 14 infants, and single specimens were examined in two infants. No attempt is made to define the etiology or pathogenesis of the anemia of erythroblastosis fetalis. The purpose of this study was to determine the relationship between degree of anemia and normoblastic activity of bone marrow, as ascertained by morphologic techniques. On the basis of a review of the literature and the experience with this series of infants, true "aregenerative anemia" appears to be a rare occurrence. Indeed, to suggest that the anemia of erythroblastosis is commonly due to a cessation of erythropoiesis seems totally unjustified, because these infants show hyperplasia of the marrow which is analogous to that seen in other compensated hemolytic anemias. Human and Sturgeon have stated, and the authors agree, that a relative hypoplasia may occur as cell destruction exceeds cell production. This does not necessarily imply marrow failure or an "aregenerative state," but it may indicate that the balance can be in favor of blood destruction and an anemia of some degree is the result. In a previous report, infants after exchange transfusion did show excessive destruction of donor erythrocytes. The rate of destruction of Rh-negative cells in erythroblastosis fetalis was twice that of normal. Some of the cases reported in the literature as "aregenerative anemia" lack adequate marrow studies and cannot be accepted as well-documented. It should be emphasized that it may be unwise to conjecture about activity of the bone marrow from reticulocyte studies of the peripheral blood alone. In this series, the percentage of normoblats in the bone marrow was increased in proportion to the degree of anemia.

Twin PREGNANCIES, responsible for 1% of births, account for 4 to 10% of all perinatal deaths?. 2 Premature birth appears to be the greatest hazard. Complications of delivery, intrauterine growth retardation, and hemodynamic abnormalities represent additional risks to the twin. 2 Naeye et aP have suggested that the amniotic fluid infection syndrome may be the most common identifiable cause of perinatal death in twins, being implicated in 16 to 38% of twin deaths, depending upon the population studied. Beta hemolytic streptococci, including members of serologic group B, are among tile causes of the syndrome. 4 Group B streptococcal infection in twins has been described, 5-7 but prospective data are lacking. Our prospective studies of GBS infections in infants have been in progress for several years. Data from the first year of investigation, recently reported, ~ included one set of twins who died with fulminant GBS sepsis. Additional cases, septicemia in a mother and one of her twin infants, prompted this analysis of the outcome of twin pregnancies in this population. An increased risk of GBS !nfection in twin pregnancies was strikingly evident.

Immunity to group B streptococcal (GBS) disease is thought to be conferred by the presence of antibodies to the capsular polysaccharides, and protection of the fetus and newborn probably depends on antibodies of the IgG class, which are readily transferred across the placenta before birth. It has been clearly established that the risk for infection is correlated with the degree of exposure to GBS during the perinatal period [1]. Although it has been suggested that a deficiency of antibody is also a major risk factor in the development of GBS type III disease [2], the prevalence of antibodies to this type has not been studied in a large normal population in which the colonization status of mothers and infants was defined by culture at the time of delivery. We measured IgG antibody to both the complete (sialylated) and incomplete (nonsialylated) capsular antigens of GBS type III in 401 pairs of maternal and cord sera, from healthy patients of defined colonization status. From this we estimated the prevalence of antibody ^ pg/mL for all 8,928 deliveries that occurred during the 4-y study period. The low overall antibody prevalence suggests that antibody deficiency was widespread, even among type III carriers. As we have recently observed in seroepidemiologic studies of GBS type II in the same population [3], the presence or absence of type-specific antibody may not by itself be a useful determinant of risk for GBS disease.

Antibodies to pneumococcal types 3, 6, 14, and 23 were measured in sera from 78 infants prospectively studied from birth. Mean levels of antibodies to capsular antigens were 2-4 micrograms/mL, with no overall differences between carriers and noncarriers of given types. Serial serum samples were studied in selected infants to more precisely define the antibody response in relation to specific pneumococcal colonization and infection. Although some infants had little antibody, and made little in response to exposure, others had demonstrable antibody at the onset of acute otitis media. The highest levels were seen following repeated exposure. After an initial or secondary response, levels declined with or without continued nasopharyngeal carriage.

Detailed comparisons were drawn between similar numbers of patients with acute glomerulonephritis (101), their infected siblings (97) and patients with uncomplicated impetigo (107), all of whom had Streptococcal pyoderma. Hyperimmune antiDNAse B responses in patients with acute glomerulonephritis were most impressive, and were greater in frequency and magnitude than were antistreptolysin O responses among all patients with pyoderma. AntiDNAse B titers were elevated in over 90 per cent of patients with acute glomerulonephritis. In contrast, only half of those patients with acute glomerulonephritis had an elevated antistreptolysin O. Mean antiDNAse B titers in all patient groups were significantly higher than those in uninfected controls. These data are the first unequivocal evidence that the Streptococcal immune response in patients with acute glomerulonephritis is significantly greater than that in comparable groups of infected patients. Serial tests in convalescent patients with pyoderma and acute glomerulonephritis revealed that antiDNAse B titers rose more often and persisted longer than did antistreptolysin O titers. The nature of the Streptococcal immune response is related to the site of infection. Neither antistreptolysin O nor antiDNAse B responses in patients with skin infection and acute glomerulonephritis were influenced by Streptococcal carriage in the throat, which likely represented colonization secondary to pyoderma. The superiority of the antiDNAse B test for serologic study of pyoderma is evident. A general unresponsiveness on the part of the host cannot be invoked to explain the antistreptolysin O findings. Neither do our data support the hypothesis that the antistreptolysin O response is a function of infecting serotype. Local inhibition of the antigenicity of streptolysin O at the site of the skin infection, or other more general mechanisms of inhibition of streptolysin O antigenicity, remain attractive hypotheses to be explored. As a result of our observations, the role of a hyperimmune mechanism in the pathogenesis of acute glomerulonephritis as well as rheumatic fever should be considered. The strikingly high antibody titers in acute glomerulonephritis, particularly in young children, suggest that attack rates are related to the magnitude of the immune response.

In the course of prospective epidemiological studies of group B streptococcal (GBS) colonization and infection, we surveyed 401 paired maternal and cord sera (obtained at delivery) and 23 sera from patients with systemic type II infection for IgG antibody to GBS type II. Type II carriers were more likely to have antibody (greater than 2 micrograms/ml) than were those carrying other GBS types, whereas noncolonized patients were the least likely to have antibody. The overall prevalence of levels of antibody greater than 2 micrograms/ml was estimated to be approximately 6%, on the basis of assay results of the 401 maternal-cord pairs and adjusted for known-colonization status for the entire population of 8,928 deliveries that occurred during the study period. The majority of patients with infection had antibody levels less than 2 micrograms/ml. Five patients, however, had antibody present at levels ranging from 2.7 to 5.8 micrograms/ml. These findings suggest that "antibody deficiency" was widespread and was not by itself a useful determinant of risk for disease caused by GBS type II.

A longitudinal prospective study of carriage of group B streptococci during pregnancy was conducted in 2,540 women over a three-year period. Carriage was documented in 18% of the women by anorectal culture, in 4% by vaginal culture, and in 13% by simultaneously obtained anorectal and vaginal cultures (overall carriage rate, 35%). The rate and pattern of carriage were nearly identical from year to year. In sequential cultures in the second and third trimesters of 754 women, carriage rates were 31% and 28%, respectively; only 17% of the women were carriers in both trimesters. (1) Persistence of carriage was most common when the initial anorectal swabs were positive, (2) spread from the intestinal tract to the vagina occurred, and (3) the intestinal tract was commonly the primary site of acquisition in patients with previously negative cultures. The intestinal tract appears to be a primary reservoir for group B streptococci and the likely source of vaginal or urogenital colonization in pregnant women.

Serotypes of Streptococcus pneumoniae from 525 infected children were examined over a four-year period. Type distribution was similar among 84 cases of bacteremia and 30 cases of meningitis, with types 6, 14, and 18 accounting for half of the illnesses. In contrast, half of 396 episodes of otitis media were caused by three other types, 19, 23, and 3. Four of eight fatalities were due to type 6. Carrier strains isolated from children had a distribution of types similar to that of the otitis media collection. Adult patients had fewer of the types that caused disease in children. Most childhood infections (80%) occurred in children less than or equal to 24 months of age; no relationship between age and infecting serotype was noted. There were no seasonal trends in type distribution.

We examined ampicillin-resistant strains of Haemophilus influenzae to compare the percentage of resistant organisms in each strain with the susceptibility to ampicillin by an agar dilution method. Using an inoculum of 10 4 colony-forming units, the minimal inhibitory concentration (MIC) increased with the percentage of resistant organisms in the strain. Laboratory-manipulated strains composed of different proportions of a susceptible and a resistant strain behaved similarly. The survival of isolated colony-forming units (colony MIC) was then determined by spreading inocula over the surface of a set of MIC plates, resulting in separation of individual colonies. This modification of the susceptibility test to the colony level gave end points that were clear and reproducible and that did not vary with changes in incubation time or temperature. True differences in susceptibility among strains were demonstrated by this method, whereas results of the conventional MIC test may reflect only the number of resistant organisms present in the inoculum.

Three new streptococcal M serotypes, types 59, 60, and 61; have been described. They were first isolated from patients with pyoderma and acute glomerulonephritis (AGN), seen during epidemiological studies in Alabama. A possible antigenic relationship between types 59 and 61 was suggested by their T-agglutination reactions; a more specific T antiserum prepared for type 59 was useful in separating these two types, as well as other strains known to share T antigens 11, 12, and 5/27/44. On the basis of precipitin tests, a common antigenic determinant among types 59, 61, and 49 was suggested. This is of interest in view of the relation between these types and AGN. Type 59 has been relatively more widespread in distribution than type 61, but neither have been related to epidemic AGN. Type 60, first identified as “T-4,” thus being related to previously described M types which share this antigen, is of great interest in terms of the epidemiology of AGN. Most strains in our collection were recovered from patients with pyoderma and AGN or from their infected siblings. Recently, the type was found to be prevalent among patients with pyoderma and AGN seen in Trinidad. Data reported in relation to these new types further illustrate the dichotomy in M serotypes common to pyoderma and AGN on the one hand and those types found in collections of patients with pharyngitis on the other hand. The high rate of non-M-typable streptococci among pyoderma collections, encountered earlier, is best explained by lack of suitable reference antisera available for prevalent pyoderma serotypes.

Investigators from Kenya, Canada, and Belgium have collaborated on several studies of ophthalmia neonatorum in Nairobi, Kenya.1 2 3 In this issue of the Journal, they report on the efficacy of ceft...

The pneumococci possess, in addition to type-specific capsular polysaccharides, a number of antigens common to the species. Antibodies to phosphocholine (PC), a major determinant of the C-carbohydrate, have been shown to protect mice from experimental pneumococcal infection, but little is known of the role of anti-PC antibodies in humans or the extent to which anti-PC levels are affected by carriage or infection. We examined 115 sera from 30 infants, who were followed prospectively from birth through 4 years of age, for the presence of immunoglobulin M antibody to PC, using a solid-phase radioimmunoassay method. Infants were found to develop antibody to PC in response to pneumococcal carriage and infection, and nearly all infants developed some antibody. Antibody levels increased with age. By using a regression model including both age and nasopharyngeal carriage of pneumococci, anti-PC levels were found to be highest after exposure to two or three different types of pneumococci; levels were highest soon after acquisition of pneumococci and declined thereafter.

During a six-month period 69 infants in a newborn nursery were colonized with group A streptococci. Fifty-one had omphalitis, two infected circumcision wounds, and one each had meningitis, primary peritonitis, and conjunctivitis. Thirteen infants were asymptomatically colonized. Control of the epidemic was difficult. Benzathine penicillin prophylaxis to all infants suppressed active infection but did not eradicate asymptomatic colonization of the umbilical cord. Triple dye treatment of the umbilical cord plus benzathine penicillin prophylaxis eradicated the infection from the nursery. The epidemic streptococcus was a newly recognized ""skin strain,'' provisional type strain 5656-S, not previously known to cause epidemic disease or serious systemic infections.

Streptococcus pneumoniae was isolated from 1310 children in a 5-year period from 1979 through 1984. There were 44 cases of meningitis, 172 bacteremic infections, 787 cases of otitis media and 307 respiratory and miscellaneous isolates. The majority of infections could be accounted for by a small number of serotypes, with types 3, 6, 14, 19 and 23 predominating. Most infections (70%) occurred in infants younger than 2 years of age. However, nearly one-fourth of those suffering systemic illness had some underlying condition which may have contributed to their risk for infection, even beyond 2 years of age. Ten of the 12 deaths occurred in patients with altered host defenses. Characteristics of pneumococcal disease and the distribution of serotypes are discussed in relation to the work of other investigators over the past 50 years.

SUMMARYThe specificity of human antibodies for the two major sidechain determinants of the type II group B streptococcal (GBS) polysaccharide was examined in 90 pairs of maternal and cord sera. Using an ELISA system, total antibody was measured against the complete (sialylated) type II antigen and the proportion of antibody against the galactose determinant was estimated by inhibition with free β–methylgalactopyranosided. Mothers colonized by type II or by other GBS types had higher levels of total specific antibody (means, 33 and 4–7 µg/ml, respectively) than those not colonized (mean, 2–2 µg/ml). Cord sera averaged 1–2 µg/ml lower than maternal sera. Colonization with GBS was also associated with higher levels against the galactose determinant (mean, 1.5&µg/ml, compared to 0–7µg/ml for those not colonized). The distribution of specificities favoured antibodies against the sialic acid determinant in maternal but not cord sera. Specificity as well as antibody level may play a role in the epidemiology of GBS type II.

Cephalexin, given twice daily, and dicloxacillin, given four times daily, were compared in a randomly controlled study for the treatment of staphylococcal skin and skin structure infections. Among 70 evaluable patients, 57 had staphylococcal bullous impetigo. The remaining 13 patients had bullous impetigo with streptococcal or mixed streptococcal-staphylococcal cultures (6 patients), abscess (4 patients), or cellulitis with pyoderma (3 patients). Staphylococci were recovered from lesions of 64 of the 70 evaluable patients; all strains were sensitive to both cephalexin and dicloxacillin, but only 2 of the 64 strains were susceptible to penicillin G. Cephalexin and dicloxacillin proved equally effective, Treatment failures were uncommon (1 patient in each group), and recurrences (3 patients in each group) were limited to patients with bullous impetigo. In general, patients with staphylococcal bullous impetigo responded promptly, with clearing of lesions evident within the first week, but delayed healing with persistence of staphylococci in lesions was more common in the group receiving dicloxacillin. Twice-daily dosing with oral antibiotics is obviously convenient and may enhance compliance. Twice-daily therapy with cephalexin for staphylococcal skin and skin structure infections can be recommended with confidence.

An investigation on the natural history of streptococcal skin infection was done in fifty-nine children in a rural day care setting. A double-blind study for prevention of streptococcal pyoderma was done during the peak season for skin infection. Triple antibiotic ointment, containing bacitracin, polysporin, and neomycin, was compared to placebo ointment. Ointments were applied thrice daily for minor skin trauma; mosquito bites and abrasions were predominant. Cultures of normal skin surfaces were taken for group A streptococci each week of the 15-week study period. Skin lesions were cultured whenever present. Eighty-one percent of the fifty-nine patients had positive normal skin cultures on one or more occasions. Nineteen children (32%) developed streptococcal pyoderma. Infection occurred significantly more often in children using placebo ointment than in those using topical antibiotic (47% vs 15%; p = 0.01). The infecting strain was first recovered from normal skin surfaces in 67% of placebo patients and in two of the four patients using antibiotic ointment. This study further confirms the importance of skin carriage of group A streptococci as a precursor to pyoderma and demonstrates the importance of minor skin trauma as a predisposing factor. Topical antibiotics may be useful in preventing streptococcal pyoderma, especially in children known to be at increased risk for such infection.

Studies of the epidemiology of acute glomerulonephritis (AGN) following pyoderma reported over the past 15 years have been reviewed. Investigations in Alabama, at Red Lake in Minnesota, and in Trinidad proved of special interest because they contribute new information concerning the natural history of streptococcal skin infections and the role of such infections in AGN. Interesting contrasts between streptococcal infections of the skin and those of the throat are now apparent. Compared with pharyngeal infections, skin infections are more common in young preschool children, are caused by different serotypes, and differ in the nature of the streptococcal antibody response. A number of new M-serotypes of group A streptococci, including several of importance in AGN, were found in studies of pyoderma. In contrast to M-types 1 and 12 (those of major importance in AGN followng pharyngitis), M-types 2, 49, 55, 57, and 60 are now recognized to be of major importance in AGN following pyoderma. Although streptococcal skin infections are quire important in AGN, they do not result in acute rheumatic fever.

In vitro susceptibility tests of 201 strains of Staphylococcus aureus by agar dilution revealed 90% to be susceptible to 8 μg or less of cefaclor per ml. Strains from hospitalized children and adults were more often resistant than those from patients with bullous impetigo. Cephalothin was more active than cefaclor against all strains tested. Results with disk tests, including those strains examined from the clinical investigation, revealed some discrepancies in identifying strains more resistant to cefaclor. In clinical studies, cefaclor proved quite effective for the treatment of bullous impetigo. Of 73 patients, 90% were cured and 7% improved after completing 5 or more days of treatment. Prompt improvement was noted among most patients seen 3 to 5 days after treatment was begun. One patient experienced mild diarrhea. There were no other adverse or toxic manifestations attributable to therapy.

During the three-year period from 1981 to 1984, all clinical isolates of Streptococcus pneumoniae were screened for resistance to penicillin in the clinical bacteriology laboratory at The Children's Hospital of Alabama, Birmingham. Twenty-eight of 828 isolates were presumed resistant by disk diffusion testing with 1-microgram oxacillin disks (zone diameter, less than 20 mm). Seventeen of the 28 (61%) were found to be intermediately sensitive to penicillin by a conventional agar dilution method. Penicillin-intermediate strains had a minimal inhibitory concentration of 0.125 to 0.5 mg/L; no penicillin-resistant (minimal inhibitory concentration, greater than 1 mg/L) strains were encountered. The prevalence of penicillin-intermediate strains was thus 17 of 828 isolates, or 2.1%. These strains were also examined for susceptibility to ampicillin, vancomycin, cefotaxime, and chloramphenicol. We present the clinical features of 17 patients with disease due to penicillin-intermediate pneumococci.

OUR PRESENT knowledge of impetigo contagiosa extends from descriptions now over 100 years old.1,2The defining of "streptococcal" and "staphylococcal" forms of impetigo has been principally the work of dermatologists,3-5while others, including bacteriologists and epidemiologists, have described the characteristics of infecting organisms.6-10Fewer examples of studies of impetigo are found in the pediatric literature and the above mentioned studies may not be widely appreciated by physicians caring for children. Interest in streptococcal impetigo or pyoderma as an important predisposing infection of acute glomerulonephritis has appeared to be greater among physicians and investigators in the southern and southeastern section of the US reflecting perhaps a higher incidence of impetigo in warmer climates, and its relatively more important role in nephritis.11-16The reports of pyoderma and nephritis among Indians at Red Lake, Minn, indicate however that skin infection is by no means limited to the south.17,18

Two strains of Group A streptococci have been shown to produce streptokinases with different physical and immunologic characteristics. These streptokinases have been designated SK-A and SK-B. Examination of additional strains of Group A streptococci has indicated that SK-A is the more commonly encountered streptokinase. Studies comparing the two Group A streptokinases with streptokinase of Group C origin have indicated that the latter streptokinase is intermediate between SK-A and SK-B in regard to its electrophoretic mobility. Immunological data suggest that the Group C streptokinase differs from SK-B but is closely related to SK-A.