Cause Of Invasive Bacterial Infections Research Articles

Invasive bacterial infections in a paediatric emergency department in the era of the heptavalent pneumococcal conjugate vaccine

To describe the characteristics of patients diagnosed with invasive bacterial infections (IBIs) in a Paediatric Emergency Department (PED) following the introduction of the heptavalent pneumococcal conjugated vaccine (PCV7). Descriptive retrospective study of children under 14 years of age diagnosed with IBIs in a PED of a tertiary hospital between January 2008 and December 2009. In this period we registered 123 396 episodes and 59 patients who were diagnosed with IBIs (22 patients under 1 year of age, 37.2%). Of these, 11 (18.6%) had some severe underlying condition and 38 (64.4%) were stable on arrival. The most common diagnoses were sepsis with/without meningitis (23, 38.9%) and bacteraemia (14, 23.7%), while the pathogens most frequently isolated were Streptococcus pneumoniae (23, 38.9%) and Neisseria meningitidis (18, 30.5%). Pathogens were isolated from blood in 57 patients and from the cerebrospinal fluid in eight (in these, the same bacterial species was isolated in the blood, except for two cases with S. pneumoniae). Of the pneumococci isolated, 80% corresponded to serotypes included in the 13-valent PCV13. In seven cases, pathogens were detected using only PCR analysis (N. meningitidis, four; S. pneumoniae, three). Twenty-five patients were admitted to the Paediatric Intensive Care Unit. No patient died but two had sequelae. In the era of PCV7, pneumococcus is the leading cause of IBI in PED. The introduction of PCV13 may lead to a very significant decrease in the IBI rate and meningococcus may become the leading cause of IBI.

Colonization and Transmission of <i>Haemophilus influenzae </i>Type b(Hib)

Haemophilus influenzae type b (Hib) remains the leading cause of invasive bacterial infection in Japanese children. More than 110 countries that have included Hib conjugate vaccines in their routine vaccination programs have seen dramatical decrease in the incidence of Hib infections. In Japan, the vaccine has been introduced for voluntary immunization since December 2008 and has been provided free of charge only since January 2011. This review reports the prevalence of Hib and its clones among healthy children and pediatric patients diagnosed with invasive or non-invasive Hib infections in Sado Island, Japan. Of 25 Hib isolates collected in this surveillance, 4 genotypic patterns (ST54-gBLPACR-III, ST54-gBLNAR-I/II, ST190-gBLNAS, and ST95-gBLPACR-I/II) were detected. These STs were double or triple-locus variants of each other. Under the same antimicrobial selective pressure, high prevalence of gBLPACR strain (76.0%) was confirmed in Hib isolates, while gBLPACR prevalence in nontypeable H. influenzae was very low (5.2%). These data suggested that each ST strain may be brought into Sado Island by different routes. We note that surveillance of healthy subjects to identify Hib carriers is important to understand their role in transmission of Hib.

Peptides complementary to the active loop of porin P2 from Haemophilus influenzae modulate its activity

Haemophilus influenzae type b (Hib) is one of the leading causes of invasive bacterial infection in young children. It is characterized by inflammation that is mainly mediated by cytokines and chemokines. One of the most abundant components of the Hib outer membrane is the P2 porin, which has been shown to induce the release of several inflammatory cytokines. A synthetic peptide corresponding to loop L7 of the porin activates JNK and p38 mitogen-activated protein kinase (MAPK) pathways. We report a novel use of the complementary peptide approach to design a peptide that is able to bind selectively to the protein P2, thereby reducing its activity. This work provides insights into essential molecular details of P2 that may affect the pathogenesis of Hib infections where interruption of the signaling cascade could represent an attractive therapeutic strategy.

Transmission probabilities and durations of immunity for three pathogenic group B Streptococcus serotypes

Group B Streptococcus (GBS) remains a major cause of neonatal sepsis and is an emerging cause of invasive bacterial infections. The 9 known serotypes vary in virulence, and there is little cross-immunity. Key parameters for planning an effective vaccination strategy, such as average length of immunity and transmission probabilities by serotype, are unknown. We simulated GBS spread in a population using a computational model with parameters derived from studies of GBS sexual transmission in a college dormitory. Here we provide estimates of the duration of immunity relative to the transmission probabilities for the 3 GBS serotypes most associated with invasive disease: Ia, III, and V. We also place upper limits on the durations of immunity for serotype Ia (570 days), III (1125 days) and V (260 days). Better transmission estimates are required to establish the epidemiological parameters of GBS infection and determine the best vaccination strategies to prevent GBS disease.

Long-term protection after immunization with protein–polysaccharide conjugate vaccines in infancy

The polysaccharide-encapsulated bacteria, Haemophilus influenzae type b, Neisseria meningitidis and Streptococcus pneumoniae are important causes of invasive bacterial infection in childhood, accounting for most of the cases of bacterial pneumonia and meningitis worldwide. Protein–polysaccharide conjugate vaccines have been developed over the last 20 years and have proven very effective in controlling these infections. Although studies have consistently shown that herd immunity is critical for population protection, long-term individual protection against polysaccharide-encapsulated bacteria appears to depend on persisting antibody and, perhaps to a lesser extent, immunological memory. However, some studies have reported that the concentration of serum antibody and vaccine effectiveness are not sustained after infant immunization, despite persistence of immunological memory. In this article, we detail the mechanisms of protection against invasion by encapsulated bacteria, describe the age-dependent B-cell and antibody responses to protein–polysaccharide conjugate vaccines and propose strategies to guarantee protection during periods of increased disease burden.

Immunogenicity of a Single Dose of Tetravalent Meningococcal Serogroups A, C, W-135, and Y Conjugate Vaccine Administered to 2- to 10-year-olds Is Noninferior to a Licensed-ACWY Polysaccharide Vaccine With an Acceptable Safety Profile

Meningococcal disease remains an important cause of invasive bacterial infections in children less than 5 years of age. Immunogenicity and safety of the investigational ACWY vaccine conjugated with tetanus toxoid (ACWY-TT, GlaxoSmithKline Biologicals) were evaluated in 1501 healthy 2- to 10-year-old children in the Philippines, India, Lebanon, and Saudi Arabia. Children were randomized (3:1) to receive ACWY-TT or licensed tetravalent meningococcal polysaccharide vaccine (Mencevax, GlaxoSmithKline, Men-PS). Diary cards were used to collect solicited symptoms for 4 days after vaccination. Serious adverse events were reported for 6 months. Serum bactericidal activity (rSBA, rabbit complement) was measured before and 1 month after vaccination in the first 75% of subjects enrolled in each country. The statistical criteria for noninferiority in terms of rSBA vaccine responses were reached. Exploratory analyses showed that postvaccination rSBA titers ≥ 1:8 and ≥ 1:128 were significantly higher after ACWY-TT than Men-PS for serogroups C, W-135, and Y, and rSBA vaccine responses and geometric mean antibody titers were significantly higher for all 4 serogroups after administration of ACWY-TT. Noninferiority in terms of incidences of grade 3 general symptoms was not demonstrated. ACWY-TT was well tolerated with grade 3 events reported in <1% of subjects per group. No serious adverse events were considered related to vaccination. ACWY-TT was immunogenic in children between 2 to 10 years of age with a clinically acceptable safety profile that resembled licensed Men-PS. These data support a positive benefit/risk ratio for the ACWY-TT vaccine.

Haemophilus influenzae Type b Carriage and Novel Bacterial Population Structure among Children in Urban Kathmandu, Nepal

Haemophilus influenzae type b (Hib) is a major cause of invasive bacterial infection in children that can be prevented by a vaccine, but there is still uncertainty about its relative importance in Asia. This study investigated the age-specific prevalence of Hib carriage and its molecular epidemiology in carriage and disease in Nepal. Oropharyngeal swabs were collected from children in Kathmandu, Nepal, from 3 different settings: a hospital outpatient department (OPD), schools, and children's homes. Hib was isolated using Hib antiserum agar plates, and serotyping was performed with latex agglutination. Hib isolates from children with invasive disease were obtained during active microbiological surveillance at Patan Hospital, Kathmandu, Nepal. Genotyping of disease and carriage isolates was undertaken using multilocus sequence typing (MLST). Swabs were taken from 2,195 children, including 1,311 children at an OPD, 647 children attending schools, and 237 children in homes. Overall, Hib was identified in 5.0% (110/2,195; 95% confidence interval [95% CI], 3.9% to 6.4%). MLST was performed on 108 Hib isolates from children carrying Hib isolates and 15 isolates from children with invasive disease. Thirty-one sequence types (STs) were identified, and 20 of these were novel STs. The most common ST isolates were sequence type 6 (ST6) and the novel ST722. There was marked heterogeneity among the STs from children with disease and children carrying Hib. STs identified from invasive infections were those commonly identified in carriage. This study provides evidence of Hib carriage among children in urban Nepal with genetically diverse strains prior to introduction of universal vaccination. The Hib carriage rate in Nepal was similar to the rates observed in other populations with documented high disease rates prior to vaccination, supporting implementation of Hib vaccine in Nepal in 2009.

Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5

Group B Streptococcus (GBS) is a leading cause of invasive bacterial infections in human newborns. A key GBS virulence factor is its capsular polysaccharide (CPS), displaying terminal sialic acid (Sia) residues which block deposition and activation of complement on the bacterial surface. We recently demonstrated that GBS Sia can bind human CD33-related Sia-recognizing immunoglobulin (Ig) superfamily lectins (hCD33rSiglecs), a family of inhibitory receptors expressed on the surface of leukocytes. We report the unexpected discovery that certain GBS strains may bind one such receptor, hSiglec-5, in a Sia-independent manner, via the cell wall–anchored β protein, resulting in recruitment of SHP protein tyrosine phosphatases. Using a panel of WT and mutant GBS strains together with Siglec-expressing cells and soluble Siglec-Fc chimeras, we show that GBS β protein binding to Siglec-5 functions to impair human leukocyte phagocytosis, oxidative burst, and extracellular trap production, promoting bacterial survival. We conclude that protein-mediated functional engagement of an inhibitory host lectin receptor promotes bacterial innate immune evasion.

Phase III Comparison of an Investigational Quadrivalent Meningococcal Conjugate Vaccine with the Licensed Meningococcal ACWY Conjugate Vaccine in Adolescents

Neisseria meningitidis is an important cause of invasive bacterial infection in the United States, and disease rates are higher for adolescents than for the general population. Quadrivalent meningococcal conjugate vaccine is recommended for routine vaccination of adolescents and high-risk groups. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, with the licensed meningococcal conjugate vaccine, Menactra. In this multicenter phase III study, 2180 adolescents 11-18 years of age were randomly assigned to 4 groups (1:1:1:1) to receive a single dose of 1 of 3 lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained before vaccination and 1 month after vaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers after vaccination with MenACWY-CRM or Menactra were compared in noninferiority and superiority analyses. The hSBA geometric mean titers after MenACWY-CRM vaccination were higher than the hSBA geometric mean titers after Menactra vaccination, and criteria for superiority were met for this end point for all 4 serogroups. Also, the criteria for superiority of MenACWY-CRM, compared with Menactra, were met for the end points of proportion of subjects with postvaccination hSBA titers 1:8 and proportion of seroresponders for serogroups A, W-135, and Y. MenACWY-CRM was noninferior to Menactra for serogroup C for these end points. Reactogenicity was similar, with 64% of the MenACWY-CRM recipients and 70% of the Menactra recipients reporting mild and/or moderate solicited reactions. Neither vaccine was associated with a serious adverse event. MenACWY-CRM vaccine is well tolerated in adolescents and generates a stronger immune response than Menactra for all 4 serogroups. Clinicaltrials.gov identifier: NCT00450437 .

Invasive infections caused by Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae among children in St Petersburg, Russia

This study investigated the causes of invasive bacterial infections in children aged <15 years in St Petersburg, Russia, during 2001-2003, using culture and antigen detection methods (rapid antigen latex agglutination (RAL)) for normally sterile body fluids. A pathogen was detected in 90 cases (culture 50, RAL 40). Neisseria meningitidis was the most common pathogen (66%), followed by Haemophilus influenzae (19%) and Streptococcus pneumoniae (16%). Meningitis was the main clinical diagnosis (68/90, 76%), with N. meningitidis serogroup B, H. influenzae type b (Hib), and S. pneumoniae serogroup 1 being the most common isolates. Hib was less prevalent in St Petersburg than it was in industrialised countries before the introduction of Hib vaccinations.

Haemophilus influenzae type-b and non-b-type invasive diseases in urban children (

To prospectively study the epidemiology and antibiotic resistance of Haemophilus infuenzae isolates from invasive infections in children. Children (<5years) with pneumonia, meningitis and septicemia from three hospitals in Dhaka, Bangladesh were enrolled (1999-2003); clinical and laboratory data, and blood for cultures were collected. Cerebrospinal fluid (CSF) of meningitis cases was analyzed (Gram stain, culture and biochemical tests). Hib antigen was detected by latex agglutination (LA) in culture-negative pyogenic CSF and PCR was done for bexA gene in culture- and LA-negative pyogenic CSF. Antibiotic susceptibility was determined by E-Tests and beta-lactamase by nitrocefin stick. Seventy-three cases of H. influenzae infections (46 of 293 meningitis cases, 25 of 1493 pneumonia cases, 2 of 48 septicemia cases) were detected; 63%, 34% and 3% of them had meningitis, pneumonia and septicemia respectively. H. influenzae type b (Hib) caused infections in 80.8% of cases (60.3% meningitis, 20.5% pneumonia). Most (86%) infections clustered in 4-12month infants. The case-fatality in pneumonia was 8% compared to 19% in meningitis. H. influenzae isolates from pneumonia and meningitis children were equally resistant to antibiotics (46% vs 43%). Of 10 drugs tested, isolates were resistant to ampicillin (31%), chloramphenicol (42%), trimethoprim-sulfamethoxazole (44%) and azithromycin (1.4%). Multidrug-resistant (MDR) strains were equally prevalent in Hib (31%) and non-b-type (29%) isolates, and in pneumonia (31%) and meningitis (34%) cases. None was resistant to amoxicillin-clavulanate, ceftriaxone, ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin. Of all H. influenzae infections, 40%, 4.4% and 100% of pneumonia, meningitis and septicemia cases were caused by other serotypes or non-typeable strains. All ampicillin-resistant-strains produced beta-lactamase without detection of beta-lactamase-negative-ampicillin-resistant (BLNAR) strains. Hib is a leading cause of invasive bacterial infections in infants. Multidrug-resistant H. influenzae is common and requires amoxicillin-clavulanate, ceftriaxone or azithromycin as empirical therapy with specific recommendation for use of ceftriaxone for treatment of meningitis particularly MDR cases. New fluoroquinolines has potential utility. An effective national Hib vaccination programme is essential in Bangladesh although non-Hib infections will remain an issue.

A group B streptococcal pilus protein promotes phagocyte resistance and systemic virulence

Group B Streptococcus (GBS) is a major cause of invasive bacterial infections in newborns and certain adult populations. Surface filamentous appendages known as pili have been recently identified in GBS. However, little is known about the role of these structures in disease pathogenesis. In this study we sought to probe potential functional role(s) of PilB, the major GBS pilus protein subunit, by coupling analysis of an isogenic GBS pilB knockout strain with heterologous expression of the pilB gene in the nonpathogenic bacterium Lactococcus lactis. We found the knockout GBS strain that lacked PilB was more susceptible than wild-type (WT) GBS to killing by isolated macrophages and neutrophils. Survival was linked to the ability of PilB to mediate GBS resistance to cathelicidin antimicrobial peptides. Furthermore, the PilB-deficient GBS mutant was more readily cleared from the mouse bloodstream and less-virulent in vivo compared to the WT parent strain. Strikingly, overexpression of the pilB gene alone in L. lactis enhanced resistance to phagocyte killing, increased bloodstream survival, and conferred virulence in a mouse challenge model. Together these data demonstrate that the pilus backbone subunit, PilB, plays an integral role in GBS virulence and suggests a novel role for gram-positive pili in thwarting the innate defenses of phagocyte killing.

Akutes Fieber beim Kleinkind

The body temperature is influenced among other things by time of day or age and exhibits a Gaussian inter-individual distribution. If measured orally, normal values vary between 35.6 degrees C and 38.2 degrees C. Temperature exceeding the 99th percentile (> 37.7 degrees C) can therefore be interpreted as fever. Nevertheless, an universally accepted definition of fever does not exist. Viral infection is the most frequent cause of acute fever in infants, even in the absence of a source. Bacterial infections are by far a rarer reason. Nevertheless, below the age of 3 years, acute fever is a ticklish issue because of the higher risk for rapidly evolving life-threatening invasive bacterial infections. Following introduction of vaccination against Haemophilus influenzae type b (Hib), Streptococcus pneumoniae has advanced to the most frequent cause of invasive bacterial infections in infants. Fever is rarely seen in newborns (age 1-28 days), but when present, it is more frequently serious. Around 12% of these newborns show an invasive bacterial infection. Therefore, a full workup for sepsis is strongly indicated. This includes cultures of blood,urine and cerebrospinal fluid plus a chest radiography. In addition, immediate start of an empirical intravenous antibiotic therapy and monitoring in a hospital setting are necessary. Apart from this exception, primary antibiotic therapy is rarely necessary in fever without a detectable focus and source. Also, routine prescription of antipyretics is not indicated. Though paracetamol may improve well-being and drinking behavior of infants, it does neither shorten the duration of fever duration, nor prevent febrile seizures.

Epidemiologic and Clinical Characteristics of Community-Acquired Invasive Bacterial Infections in Children Aged 2???29 Months in The Gambia

The incidence of community-acquired bacteremia (CAB) in Africa is several-fold higher than in industrialized countries. We report here the incidence of invasive bacterial infections in rural Gambia and compare the clinical characteristics of children with pneumococcal infection with those of children with extraintestinal nontyphoidal salmonella infection (NTS) or other bacterial infections. As part of a pneumococcal conjugate vaccine trial, we investigated children aged 2-29 months who presented with signs suggestive of invasive bacterial infections. The incidence of invasive bacterial infections in all subjects was 1009 (95% CI, 903-1124) cases per 100,000 person-years. It was 1108 (95% CI, 953-1282) among children who had not received pneumococcal conjugate vaccine. Incidence decreased with increasing age but remained relatively high in 24- to 29-month-olds for pneumococcal infections. Pneumococcal infection was more frequent than NTS infections in the hot dry season. Respiratory symptoms and signs, consolidation on chest radiograph, and a primary diagnosis of pneumonia were more frequent in children with pneumococcal infection than in those with NTS or other infections. Diarrhea, laboratory evidence of malaria infection, and a primary diagnosis of malaria were more common in children with NTS infections. Bacterial infections continue to cause significant morbidity in rural Africa. Although vaccines could greatly reduce the pneumococcal burden, a high index of suspicion and appropriate use of antimicrobials are needed to manage other causes of invasive bacterial infections.

Structural Requirements for Proinflammatory Activity of Porin P2 Loop 7 from Haemophilus influenzae

Haemophilus influenzae type b (Hib) is one of the leading causes of invasive bacterial infection in young children, characterized by inflammation mainly mediated by cytokines and chemokines. One of the most abundant components of the Hib outer membrane is the P2 porin, which has been shown to induce the release of several inflammatory cytokines. Synthetic peptides corresponding to loops L5, L6, and L7 activate JNK and p38 mitogen-activated protein kinase (MAPK) pathways, L7 being the most active peptide. Therefore, sequence-activity relationships and key residues were identified by elongating sequence to different extents, designing cyclic peptides, and performing an alanine scan of L7. The ability of mutant peptides to induce activation of signal transduction pathways and release of TNF-alpha and IL-6 has been determined, and, in conjunction with CD spectra, bioinformatics analysis, and molecular dynamics data, showed that 6 out of 8 amino acids contribute significantly to the overall activity. Molecular dynamics showed that L7 modifications increased loop rigidity and helicity after Gly6 mutation, thus, providing a possible structural explanation for observed loss of bioactivity. This work provides insights into essential molecular details of P2 that may impact on the pathogenesis of Hib infections where interruption of the signaling cascade could represent an attractive therapeutic strategy.

Haemophilus influenzae type b conjugate vaccines.

Haemophilus influenzae type b (Hib) is one of the leading causes of invasive bacterial infection in young children worldwide. During childhood, acquisition of antibody directed against the polysaccharide capsule of the organism, presumably as a result of asymptomatic carriage, confers protection and disease is much less common after the age of 4 years. Like other polysaccharides, the polyribosyl ribitol phosphate (PRP) of the Hib capsule is a T-independent antigen and not immunogenic when administered as a vaccine in infancy. Because the highest rates of disease occur in the first 2 years of life, efficacious Hib vaccines have been designed by covalently linking the PRP capsule to a carrier protein that recruits T-cell help for the polysaccharide immune response and induces anti-PRP antibody production even in the first 6 months of life. Introduction of Hib protein-polysaccharide conjugate vaccines into many industrialized countries over the past 15 years has resulted in the virtual elimination of invasive Hib disease. However, despite the success of the vaccine programme several factors may interfere with the effectiveness of the vaccine in the routine programme, as observed in the UK recently. Such factors may include interference with other concomitant vaccines, waning immunity in the absence of booster doses of vaccine, and reduced natural boosting as a result of decreased transmission of the organism. However, the burden of disease remains highest in resource-poor countries and urgent efforts are needed to provide the benefits of this vaccine for children living in regions where it cannot be used for economic and logistical reasons.

Pneumococcal vaccination of children

Streptococcus pneumoniae is the most frequent cause of invasive bacterial infection in children younger than 2 years of age, reaching a peak incidence at 6 to 12 months of age. Pneumococci also cause many cases of pneumonia, sinusitis, and otitis media. Incidence rates of invasive infection in children with sickle cell disease, acquired or congenital splenectomy, or human immunodeficiency virus infection are 20- to 100-fold higher than are those of healthy children during the first 5 years of life. Other healthy children, such as those of American Indian, Native Alaskan, or African American descent, also have high rates of invasive infection, and those children enrolled in out-of-home care may have modestly increased risks. Pneumococcal polysaccharide polyvalent vaccines have been available for more than 2 decades but are limited in their usefulness for children because of their inability to induce protective antibody responses in children younger than 2 years of age and lack of immunologic memory. In contrast, pneumococcal protein conjugate vaccines induce presumptive protective responses in infants younger than 6 months, and immunologic memory further enhances responses after booster doses are given. Currently, a single heptavalent pneumococcal protein conjugate vaccine is licensed for use in the United States and is recommended for routine administration to all children, beginning at 2 months of age. It also is recommended for children between 24 and 59 months of age who are at high risk of acquiring invasive disease. Copyright 2002, Elsevier Science (USA). All rights reserved.

Pneumococcal vaccine: an update.

* Abbreviation: HIV = : human immunodeficiency virus Streptococcus pneumoniae is the most common cause of invasive bacterial infection in children. In addition, the organism causes 30% to 50% of cases of acute otitis media; 24 million visits to pediatricians per year in the United States are referable to this diagnosis.1 It is also responsible for a significant amount of morbidity and mortality in children and adults in the United States and in other countries. A majority of cases of invasive disease caused by S pneumoniae occur in children <2 years of age and adults 65 years of age and older.1 The current 23-valent pneumococcal vaccine has been shown to be ineffective in children <2 years old.2In addition, resistance of S pneumoniae to penicillin, cephalosporins, and other antibiotics has become a serious problem.3 These factors prompted investigations that have culminated in the development of conjugated polysaccharide-protein vaccines. These new vaccines are similar in design to the already licensed Haemophilus influenzae, type b conjugate vaccine. Widespread deployment of the conjugate H influenzae vaccine in 1987 has been followed by a major decrease in morbidity and mortality of H influenzae infection.4 In this commentary, we will review briefly pneumococcal infection and discuss the roles of current and future vaccines in the prevention of pneumococcal disease. Nasopharyngeal colonization with S pneumoniae occurs in a majority of children and is most common in children <4 years of age.2 Colonization may be followed by acute otitis media and other upper respiratory infections, as well as by pneumonia. Severe infection, including bacteremia and meningitis, also may occur with significant attendant morbidity and mortality.1 Children 6 to …

Vaccination with highly purified cell surface proteins confers protection against experimental group B streptococcal infection.

Group B Streptococcus (GBS) is the major cause of invasive bacterial infections among neonates. Although the polysaccharide capsule of GBS has attracted the most attention with regard to vaccine development, there is evidence that bacterial surface proteins may also confer protective immunity.3 Previous work has shown that ≈90% of all GBS strains causing invasive infections express either protein Rib or protein α on the cell surface.3 The Rib and α proteins are structurally related and define a novel family of streptococcal proteins, which in vitro show little or no cross-reactivity immunologically.2, 3, 4 To analyze whether these proteins can be used for vaccination against GBS disease, we developed a method for isolation of these proteins in a highly purified form, free of polysaccharides. Here we summarize data from our experiments which demonstrate that active immunization with each of these purified proteins protects mice from lethal infection with GBS strains expressing the corresponding protein.2

Haemophilus influenzae type b conjugate vaccines.

In summary, all of the Hib conjugate vaccines are highly immunogenic and efficacious in children older than 12-15 months of age, and HbOC, PRP-OMPC, and PRP-T are highly immunogenic and demonstrated to be efficacious in infants as young as 2 months old. HbOC, PRP-OMPC, and PRP-T have been licensed in numerous countries for infants and are recommended for infant immunization. However, perhaps the greatest tribute one can pay to all four Hib vaccines described in this review is to note the dramatic decrease in the incidence of Hib disease that has occurred since their introduction. In fact, according to the Morbidity and Mortality Weekly Report (March 4, 1994), the incidence of Hib disease in children less than 5 years old has declined by 95% from 41 cases per 100,000 in 1987 to 2 cases per 100,000 in 1993, timing that coincides with the availability and use of the Hib conjugate vaccines (Anderson, 1994). As universal administration is achieved and the apparent vaccine-induced reduction in carriage of Hib by the population continues, Hib vaccines may follow the lead of past vaccines (such as smallpox, measles, mumps, rubella, and polio) toward eradication of disease or at least a high degree of medical control, thereby virtually eliminating the mortality and insidious morbidity associated with invasive Hib diseases.