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Clin Infect Dis 2002 Sep 1;35(5):547-55
 

Historical changes in pneumococcal serogroup distribution: implications for the era of pneumococcal conjugate vaccines.

Feikin DR, Klugman KP

Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA. drf0@cdc.gov

[Medline record in process]
 

Of the 90 pneumococcal serotypes, the 7 in the licensed pneumococcal conjugate vaccine (Prevnar) currently account for >80% of invasive pneumococcal infections among children in the United States. Our objective was to document and explain the changes in pneumococcal serogroup distribution in the United States during the last century. We evaluated temporal trends in the serogroup distribution, using linear regression. Between 1928 and 1998, the proportion of pneumococcal infections caused by the 7 serogroups in the conjugate vaccine increased significantly, from 15% to 59%, in 13 adult studies, and from 53% to 87%, in 19 pediatric studies. The proportion of infections caused by the "epidemic" serogroups (1-3 and 5) decreased significantly, from 71% to 7%, in the adult studies, and from 18% to 2%, in the studies of children. These historical trends in serogroup distribution may be explained by changes in antibiotic use, socioeconomic conditions, the immunocompromised status of populations, and blood-culturing practices.

PMID: 12173128, UI: 22161913

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Infect Immun 2002 Sep;70(9):5107-5114
 

Immunogenicity in a Mouse Model of a Conjugate Vaccine Made with a Synthetic Single Repeating Unit of Type 14 Pneumococcal Polysaccharide Coupled to CRM197.

Mawas F, Niggemann J, Jones C, Corbel MJ, Kamerling JP, Vliegenthart JF

Division of Bacteriology. Laboratory for Molecular Structure, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Herts EN6 3QG, United Kingdom. Bijvoet Center, Department of Bio-Organic Chemistry, Utrecht University, NL-3508 TB Utrecht, The Netherlands.

[Record supplied by publisher]
 

Oligosaccharides (OSs) related to the pneumococcal type 14 capsular polysaccharide (Pn14PS) were studied for their ability to inhibit the binding between anti-PS14 antisera and native PS14. A synthetic tetrasaccharide corresponding to the repeating unit of the Pn14PS, a hexasaccharide mimic, and an octasaccharide fragment obtained by Pn14PS depolymerization were good inhibitors. CRM197 conjugates of the tetrasaccharide and an octasaccharide mimic were prepared by using either adipic acid diester or diethyl squarate linkers. The conjugate with the tetrasaccharide chains induced anti-Pn14PS antibodies when injected subcutaneously into mice, as determined by an enzyme-linked immunosorbent assay, and antibody titers increased with oligosaccharide loading. The adipic acid-linked tetrasaccharide conjugates elicited higher antibody titers than those prepared with a squarate spacer. The lower anti-Pn14PS antibody response of the octasaccharide mimic conjugate indicates the importance of the backbone galactose residue for an appropriate antibody response. The OS-CRM197 conjugate prepared from a single repeat unit of the Pn14PS is a potential vaccine candidate.

PMID: 12183560

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Infect Immun 2002 Sep;70(9):5096-106
 

Attenuated Salmonella enterica Serovar Typhi Expressing Urease Effectively Immunizes Mice against Helicobacter pylori Challenge as Part of a Heterologous Mucosal Priming-Parenteral Boosting Vaccination Regimen.

Londono-Arcila P, Freeman D, Kleanthous H, O'Dowd AM, Lewis S, Turner AK, Rees EL, Tibbitts TJ, Greenwood J, Monath TP, Darsley MJ

Acambis Ltd., Cambridge, United Kingdom. Acambis Inc., Cambridge, Massachusetts.

[Medline record in process]
 

Recombinant vaccine strains of Salmonella enterica serovar Typhi capable of expressing Helicobacter pylori urease were generated by transforming strains CVD908 and CVD908-htrA with a plasmid harboring the ureAB genes under the control of an in vivo-inducible promoter. The plasmid did not interfere with the ability of either strain to replicate and persist in human monocytic cells or with their transient colonization of mouse lungs. When administered to mice intranasally, both recombinant strains elicited antiurease immune responses skewed towards a Th1 phenotype. Vaccinated mice exhibited strong immunoglobulin G2a (IgG2a)-biased antiurease antibody responses as well as splenocyte populations capable of proliferation and gamma interferon (IFNgamma) secretion in response to urease stimulation. Boosting of mice with subcutaneous injection of urease plus alum enhanced immune responses and led them to a more balanced Th1/Th2 phenotype. Following parenteral boost, IgG1 and IgG2a antiurease antibody titers were raised significantly, and strong urease-specific splenocyte proliferative responses, accompanied by IFNgamma as well as interleukin-4 (IL-4), IL-5, and IL-10 secretion, were detected. Neither immunization with urease-expressing S. enterica serovar Typhi alone nor immunization with urease plus alum alone conferred protection against challenge with a mouse-adapted strain of H. pylori; however, a vaccination protocol combining both immunization regimens was protective. This is the first report of effective vaccination against H. pylori with a combined mucosal prime-parenteral boost regimen in which serovar Typhi vaccine strains are used as antigen carriers. The significance of these findings with regard to development of a human vaccine against H. pylori and modulation of immune responses by heterologous prime-boost immunization regimens is discussed.

PMID: 12183559, UI: 22170756

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Infect Immun 2002 Sep;70(9):5086-90
 

Analysis of Serum Cross-Reactivity and Cross-Protection Elicited by Immunization with DNA Vaccines against Streptococcus pneumoniae Expressing PspA Fragments from Different Clades.

Miyaji EN, Ferreira DM, Lopes AP, Brandileone MC, Dias WO, Leite LC

Centro de Biotecnologia, Instituto Butantan. Secao de Bacteriologia, Instituto Adolfo Lutz, Sao Paulo, Brazil.

[Medline record in process]
 

Streptococcus pneumoniae is a major cause of disease, especially in developing countries, and cost-effective alternatives to the currently licensed vaccines are needed. We constructed DNA vaccines based on pneumococcal surface protein A (PspA), an antigen shown to induce protection against pneumococcal bacteremia. PspA fragments can be divided into three families, which can be subdivided into six clades, on the basis of PspA amino acid sequence divergence (S. K. Hollingshead, R. Becker, and D. E. Briles, Infect. Immun. 68:5889-5900, 2000). Since most clinical isolates belong to family 1 or family 2, PspA fragments from members of both of these families were analyzed. Vectors encoding the complete N-terminal regions of PspAs elicited significant humoral responses, and cross-reactivity was mainly restricted to the same family. DNA vaccines encoding fusions between PspA fragments from family 1 and family 2 were also constructed and were able to broaden the cross-reactivity, with induction of antibodies that showed reactions with members of both families. At least for the pneumococcal strains tested, the cross-reactivity of antibodies was not reflected in cross-protection. Animals immunized with DNA vaccines expressing the complete N-terminal regions of PspA fragments were protected only against intraperitoneal challenge with a strain expressing PspA from the same clade.

PMID: 12183557, UI: 22170754

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Infect Immun 2002 Sep;70(9):4946-4954
 

Effect of Vaccination with Carrier Protein on Response to Meningococcal C Conjugate Vaccines and Value of Different Immunoassays as Predictors of Protection.

Burrage M, Robinson A, Borrow R, Andrews N, Southern J, Findlow J, Martin S, Thornton C, Goldblatt D, Corbel M, Sesardic D, Cartwight K, Richmond P, Miller E

Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wiltshire. PHLS Meningococcal Reference Unit, Withington Hospital, Manchester. Immunisation Division, Communicable Disease Surveillance Centre, Public Health Laboratory Service. Immunobiology Unit, Institute of Child Health, London. National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire. Gloucester Vaccine Evaluation Unit, Public Health Laboratory, Gloucestershire Royal Hospital, Gloucester, United Kingdom.

[Record supplied by publisher]
 

In order to plan for the wide-scale introduction of meningococcal C conjugate (MCC) vaccine for United Kingdom children up to 18 years old, phase II trials were undertaken to investigate whether there was any interaction between MCC vaccines conjugated to tetanus toxoid (TT) or a derivative of diphtheria toxin (CRM(197)) and diphtheria-tetanus vaccines given for boosting at school entry or leaving. Children (n = 1,766) received a diphtheria-tetanus booster either 1 month before, 1 month after, or concurrently with one of three MCC vaccines conjugated to CRM(197) or TT. All of the MCC vaccines induced high antibody responses to the serogroup C polysaccharide that were indicative of protection. The immune response to the MCC-TT vaccine was reduced as a result of prior immunization with a tetanus-containing vaccine, but antibody levels were still well above the lower threshold for protection. Prior or simultaneous administration of a diphtheria-containing vaccine did not affect the response to MCC-CRM(197) vaccines. The immune responses to the carrier proteins were similar to those induced by a comparable dose of diphtheria or tetanus vaccine. The results also demonstrate that, for these conjugate vaccines in these age groups, both standard enzyme-linked immunosorbent assays and those that measure high-avidity antibodies to meningococcal C polysaccharide correlated equally well with assays that measure serum bactericidal antibodies, the established serological correlate of protection for MCC vaccines.

PMID: 12183540

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Infect Immun 2002 Sep;70(9):4833-4840
 

Coadministration of an Interleukin-12 Gene and a Trypanosoma cruzi Gene Improves Vaccine Efficacy.

Katae M, Miyahira Y, Takeda K, Matsuda H, Yagita H, Okumura K, Takeuchi T, Kamiyama T, Ohwada A, Fukuchi Y, Aoki T

Department of Respiratory Medicine. Department of Molecular and Cellular Parasitology. Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421. Department of Tropical Medicine and Parasitology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582. Department of Veterinary Sciences, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.

[Record supplied by publisher]
 

We tested the immunogenicity of two Trypanosoma cruzi antigens injected into mice in the form of DNA vaccine. Immunization with DNA encoding dihydroorotate dehydrogenase did not confer protective immunity in all mouse strains tested. Immunization with DNA encoding trans-sialidase surface antigen (TSSA) protected C57BL/6 (H-2(b)) mice but not BALB/c (H-2(d)) or C3H/Hej (H-2(k)) mice against lethal T. cruzi infection. In vivo depletion of CD4(+) or CD8(+) T cells abolished the protective immunity elicited by TSSA gene in C57BL/6 mice. Enzyme-linked immunospot assay with splenocytes from T. cruzi-infected mice or TSSA gene-vaccinated mice identified an H-2K(b)-restricted antigenic peptide, ANYNFTLV. The CD8(+)-T-cell line specific for this peptide could recognize T. cruzi-infected cells in vitro and could protect naive mice from lethal infection when adoptively transferred. Coadministration of the interleukin-12 (IL-12) gene with the TSSA gene facilitated the induction of ANYNFTLV-specific CD8(+) T cells and improved the vaccine efficacy against lethal T. cruzi infection. These results reinforced the utility of immunomodulatory adjuvants such as IL-12 gene for eliciting protective immunity against intracellular parasites by DNA vaccination.

PMID: 12183527

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Infect Immun 2002 Sep;70(9):4785-90
 

Enhancement of Protective Efficacy following Intranasal Immunization with Vaccine Plus a Nontoxic LTK63 Mutant Delivered with Nanoparticles.

Baudner BC, Balland O, Giuliani MM, Von Hoegen P, Rappuoli R, Betbeder D, Del Giudice G

IRIS Research Center, Chiron SpA, 53100 Siena, Italy. Biovector Therapeutics, Chemin du Chene Vert, 31676 Labege, France.

[Medline record in process]
 

Most vaccines are still given parenterally. Mucosal vaccination would offer different advantages over parenteral immunization, including blocking of the pathogens at the portal of entry. In this paper, nontoxic Escherichia coli heat-labile enterotoxin (LT) mutants and Supramolecular Biovector systems (SMBV) were evaluated in mice as mucosal adjuvants and delivery systems, respectively, for intranasal immunization with the conjugated group C meningococcal vaccine. The conjugated vaccine formulated together with the LT mutants and the SMBV induced very high titers of serum and mucosal antibodies specific for the group C meningococcal polysaccharide. This vaccination strategy also induced high titers of antibodies with bactericidal activity, which is known to correlate with efficacy. Importantly, the mucosal vaccination, but not the conventional parenteral vaccination, induced bactericidal antibodies at the mucosal level. These data strongly support the feasibility of development of intranasal vaccines with an enhanced protective efficacy against meningococci and possibly against other encapsulated bacteria.

PMID: 12183520, UI: 22170717

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J Immunol 2002 Aug 1;169(3):1492-9
 

Long-term protective and antigen-specific effect of heat-killed Mycobacterium vaccae in a murine model of allergic pulmonary inflammation.

Zuany-Amorim C, Manlius C, Trifilieff A, Brunet LR, Rook G, Bowen G, Pay G, Walker C

Novartis Horsham Research Center, Novartis Pharmaceutical Ltd., Horsham, United Kingdom. claudia.zuany_amorim_fromond@pharma.novartis.com

This report examines the effect of heat-killed Mycobacterium vaccae in a mouse model of allergic pulmonary inflammation. The s.c. administration of M. vaccae 3 wk before the immunization significantly reduced Ag-induced airway hyperreactivity and the increase in the numbers of eosinophils observed in the bronchoalveolar lavage fluid, blood, and bone marrow, even though no detectable changes in either cytokine (IL-4, IL-13, IL-5, and IFN-gamma) or total IgE levels were observed. Furthermore, transfer of splenocytes from OVA-immunized and M. vaccae-treated mice into recipient, OVA-immunized mice significantly reduced the allergen-induced eosinophilia by an IFN-gamma-independent mechanism, clearly indicating that the mechanism by which M. vaccae induces its inhibitory effect is not due to a redirection from a predominantly Th2 to a Th1-dominated immune response. The protective effect of M. vaccae on the allergen-induced eosinophilia lasted for at least 12 wk after its administration, and the treatment was also effective in presensitized mice. Moreover, the allergen specificity of the inhibitory effect could be demonstrated using a double-immunization protocol, where M. vaccae treatment before OVA immunization had no effect on the eosinophilic inflammation induced by later immunization and challenge with cockroach extract Ag. Taken together, these results clearly demonstrate that M. vaccae is effective in blocking allergic inflammation by a mechanism independent of IFN-gamma, induces long term and Ag-specific protection, and therefore has both prophylactic and therapeutic potential for the treatment of allergic diseases.

PMID: 12133976, UI: 22129057

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J Immunol 2002 Jul 1;169(1):566-74
 

Differential induction of mucosal and systemic antibody responses in women after nasal, rectal, or vaginal immunization: influence of the menstrual cycle.

Kozlowski PA, Williams SB, Lynch RM, Flanigan TP, Patterson RR, Cu-Uvin S, Neutra MR

GI Cell Biology Research Laboratory, Children's Hospital, and Department of Pediatrics, Harvard University, Boston, MA 02115, USA. pamela.kozlowski@tch.harvard.edu

A cholera vaccine containing killed vibrios and cholera toxin B subunit (CTB) was used to compare mucosal immunization routes for induction of systemic and mucosal Ab. Four groups of women were given three monthly immunizations by the rectal immunization (R(imm)) route, nasal immunization (N(imm)) route, or vaginal immunization route during either the follicular (V-FP(imm)) or luteal (V-LP(imm)) menstrual cycle phase. N(imm) was performed with 10-fold less vaccine to determine if administration of less Ag by this route can, as in rodents, produce mucosal Ab responses comparable to those induced by higher dose R(imm) or vaginal immunization. Concentrations of Ab induced in sera and secretions were measured by ELISA. None of these routes produced durable salivary Ab responses. N(imm) induced greatest levels of CTB-specific IgG in sera. R(imm) failed to generate CTB-specific IgA in genital tract secretions. N(imm), V-FP(imm), and V-LP(imm) all produced cervical CTB-specific IgA responses comparable in magnitude and frequency. However, only V-FP(imm) induced cervical IgA2-restricted Ab to the bacterial LPS vaccine component. V-FP(imm), but not V-LP(imm), also induced CTB-specific IgA in rectal secretions. N(imm) was superior to V-FP(imm) for producing rectal CTB-specific IgA, but the greatest amounts of CTB-specific IgA and LPS-specific IgA, IgG, and IgM Ab were found in rectal secretions of R(imm) women. These data suggest that in women, N(imm) alone could induce specific Ab in serum, the genital tract, and rectum. However, induction of genital tract and rectal Ab responses of the magnitude generated by local V-FP(imm) or R(imm) will likely require administration of comparably high nasal vaccine dosages.

PMID: 12077289, UI: 22072233

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J Immunol 2002 Jul 1;169(1):63-7
 

IL-12 administration leads to a transient depletion of T cells, B cells, and APCs and concomitant abrogation of the HLA-A2.1-restricted CTL response in transgenic mice.

Peter K, Brunda MJ, Corradin G

Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.

The injection of a mixture of bona fide T cell epitopes can lead to the occurrence of immunodominance, meaning that the immune response is focused on the recognition of a single epitope or a small portion of the epitopes injected. We have previously demonstrated that the administration of rIL-12 can counteract immunodominance in BALB/c mice. In this study, we show that the administration of rIL-12 to HLA-A2.1 transgenic mice (A2k(b) mice) abrogates specifically the immune response against HLA-A2.1-restricted HIV epitopes in the spleen. This lack of immune response is most probably due to a transient depletion of B cells, T cells, macrophages, and dendritic cells in this organ. Therefore, our study explains the mechanism of immunosuppression by rIL-12 in vivo.

PMID: 12077229, UI: 22072173

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J Immunol 2002 Jul 1;169(1):5-9
 

Cutting edge: molecular portrait of human autoimmune disease.

Maas K, Chan S, Parker J, Slater A, Moore J, Olsen N, Aune TM

Division of Rheumatology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

Autoimmune diseases affect 3-5% of the population, are mediated by the immune response to self-Ags, and are characterized by the site of tissue destruction. We compared expression levels of >4,000 genes in PBMC of control individuals before and after immunization to those of individuals with four distinct autoimmune diseases. The gene expression profile of the normal immune response exhibits coordinate changes in expression of genes with related functions over time. In contrast, each individual from all autoimmune diseases displays a similar gene expression profile unrelated to the pattern of the immunized group. To our surprise, genes with a distinct expression pattern in autoimmunity are not necessarily "immune response" genes, but are genes that encode proteins involved in apoptosis, cell cycle progression, cell differentiation, and cell migration.

PMID: 12077221, UI: 22072165

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J Infect Dis 2002 Jul 15;186(2):290-4
 

Role of upper and lower respiratory tract immunity in resistance to Mycoplasma respiratory disease.

Hodge LM, Simecka JW

Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. drlisahodge@hotmail.com

This study determined whether respiratory tract immunization protects against mycoplasma infection and compared preferential immunization of the upper respiratory tract (nasal) with upper and lower respiratory tract (nasal-pulmonary) immunization. Small volumes of inoculum preferentially deposited antigen and induced IgA responses in nasal passages. Larger inoculums deposited antigen in both the upper and lower respiratory tracts, generating corresponding IgA responses. Mice were given nasal or nasal-pulmonary immunizations with Mycoplasma pulmonis antigen alone or with cholera toxin (CT), and resistance to infection was determined. Generation of upper respiratory tract immunity reduced mycoplasma infection at this site, but CT was needed to elicit protective responses. In the lower respiratory tract, nasal-pulmonary immunization was most effective, but nasal immunization did confer some protection from pulmonary infection. In contrast, intraperitoneal immunization resulted in little protection. Thus, respiratory tract immunity plays a major role in resisting mycoplasma infection, and it should be considered during vaccine development.

PMID: 12134269, UI: 22129119

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J Pediatr 2002 Aug;141(2):287-93
 

Prevention of otitis media: Role of pneumococcal conjugate vaccines in reducing incidence and antibiotic resistance.

Jacobs MR

Case Western Reserve University, and the Department of Pathology, University Hospitals of Cleveland, Cleveland, Ohio.

[Medline record in process]
 

PMID: 12183732, UI: 22171018

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Pediatr Infect Dis J 2002 Jun;21(6):599-604; discussion 613-4
 

Acute otitis media in an era of increasing antimicrobial resistance and universal administration of pneumococcal conjugate vaccine.

Pelton SI

Boston University School of Medicine, and Department of Pediatrics, Boston Medical Center, MA 02118, USA. spelton@bu.edu

[Medline record in process]
 

The last decade has witnessed a shift in the epidemiology of acute otitis media (AOM) with an earlier onset of disease and a greater proportion of children with recurrent episodes before 1 year of age. In addition antimicrobial resistance to beta-lactams, macrolides and trimethoprim-sulfamethoxazole among otopathogens has increased significantly. Most recently universal administration of a seven valent pneumococcal conjugate vaccine has been endorsed by the American Academy of Pediatrics and the Advisory Committee on Immunization Practices. Earlier onset of disease and the decrease in antimicrobial susceptibility among pediatric respiratory bacterial pathogens is likely to increase the risk of failure among young children with AOM. A seven valent pneumococcal conjugate vaccine (PCV7) has demonstrated efficacy for prevention of serotype-specific pneumococcal otitis; however, increase in disease caused by nonvaccine serotypes and Haemophilus influenzae has been reported. With these events as the background, I have reviewed the strategies most likely to be successful for the treatment of AOM in 2002.

PMID: 12182397, UI: 22169764

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Pediatr Infect Dis J 2002 Jun;21(6):592-8; discussion 613-4
 

Management of community-acquired pediatric pneumonia in an era of increasing antibiotic resistance and conjugate vaccines.

Bradley JS

Division of Infectious Diseases, Children's Hospital, San Diego, CA, USA.

[Medline record in process]
 

The antibiotic management of infants and children with pneumonia is based on the clinician's assessment of the most likely infecting pathogens, the susceptibilities of the infecting pathogens and the seriousness of the illness. The bacterial etiology of pneumonia changed significantly following the universal use of protein-conjugated vaccines for Haemophilus influenzae type b. Similar significant changes are likely to occur with universal use of protein-conjugated vaccines for Streptococcus pneumoniae, requiring the clinician to alter assumptions of the risk of invasive bacterial infection in the child who presents with pneumonia. New strategies are likely to require fewer ancillary tests (e.g. white blood cell count, C-reactive protein and blood culture) and suggest a decreased need for empiric antibiotic therapy. Although the majority of lower respiratory tract infections in children have a viral etiology and are not amenable to antibiotic therapy, for the seriously ill child who is thought to be likely to have pneumonia caused by a bacterial pathogen, recent changes in the susceptibility patterns of both common organisms such as S. pneumoniae and more unusual pulmonary pathogens such as Staphylococcus aureus have forced changes in the selection of both empiric and definitive antibiotic therapy. Third generation cephalosporins ceftriaxone and cefotaxime appear to be effective therapy for pneumonia caused by virtually all current isolates of S. pneumoniae. In contrast antibiotic regimens for life-threatening pulmonary infections in which Staphylococcus aureus is a suspected pathogen should include vancomycin.

PMID: 12182396, UI: 22169763

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Pediatr Infect Dis J 2002 Jun;21(6):576-7
 

The need for immunoglobulin for travelers who receive hepatitis A vaccine.

Halsey NA

Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

[Medline record in process]
 

PMID: 12182391, UI: 22169758

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Pediatr Infect Dis J 2002 Jun;21(6):568-9
 

Lack of association between receipt of conjugate haemophilus influenzae type B vaccine (HbOC) in infancy and risk of type 1 (juvenile onset) diabetes: long term follow-up of the HbOC efficacy trial cohort.

Black SB, Lewis E, Shinefield HR, Fireman B, Ray P, DeStefano F, Chen R

Kaiser Permanente Vaccine Study Center, Oakland, CA 94612, USA. Steve.Black@kp.org

[Medline record in process]
 

We evaluated the effect of infant vaccination with HbOC Haemophilus influenzae type b (Hib) conjugate vaccine on the risk of onset of type 1 juvenile diabetes later in life by examining data from a large controlled prospective Phase III clinical efficacy trial conducted within Northern California Kaiser Permanente between 1988 and 1990. The overall study population included children who were offered the Hib conjugate vaccine (acceptors and refusers) as well as a cohort of children who were systemically excluded from the trial on the basis of their birth date. These children are now 10 to 12 years of age. We found no evidence that vaccination with Hib conjugate vaccine in infancy is associated with risk of diabetes later in life.

PMID: 12182385, UI: 22169752

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Pediatr Infect Dis J 2002 Jun;21(6):555-61
 

Vaccination with measles, mumps and rubella vaccine and varicella vaccine: safety, tolerability, immunogenicity, persistence of antibody and duration of protection against varicella in healthy children.

Shinefield HR, Black SB, Staehle BO, Matthews H, Adelman T, Ensor K, Li S, Chan I, Heyse J, Waters M, Chan CY, Vessey SJ, Kaplan KM, Kuter BJ

Kaiser Permanente Vaccine Study Group, Oakland, CA 94612, USA. Henry.Shinefield@kp.org

[Medline record in process]
 

BACKGROUND: Administration of M-M-R II (Measles, Mumps and Rubella Virus Vaccine, Live) and VARIVAX [Varicella Virus Vaccine Live (Oka/Merck)] given concomitantly at separate injection sites during the same office visit could increase vaccine compliance by reducing the number of health care visits for immunizations. We compared the safety and immunogenicity of M-M-R II and VARIVAX given concomitantly at separate sites (Group A) with administration of the two vaccines 6 weeks apart (Group B) as well as the persistence of varicella antibody and the duration of protection afforded by varicella vaccine. METHODS: A total of 603 healthy children, ages 12 months to 6 years, with no history of measles, mumps, rubella, varicella and zoster or vaccination against these diseases, were randomized to either Group A or B and were followed for clinical reactions and serologic responses to all four viral components. Children were enrolled from August through December, 1993. Subjects were followed for 5 years to evaluate persistence of varicella antibody and breakthrough varicella rates. We compared breakthrough rates to expected attack rates in unvaccinated children to produce estimates of vaccine efficacy. RESULTS: Both vaccine regimens were generally well-tolerated. There were no significant differences between the groups in the rates of fever, injection site reactions or rashes after vaccination. Seroconversion rates and geometric mean titers for measles, mumps and rubella were not significantly different between groups. The varicella seroconversion rate and percentage with glycoprotein-based ELISA titers > or = 5.0 units were similar between the two groups (99.5 and 92.5% vs. 100 and 94.8% for Groups A and B, respectively), but the geometric mean titers were statistically significantly different (13.2 for Group A and 17.9 for Group B). Varicella antibody persistence rates were >98 to 100% during 6 years of follow-up in both groups. Compared with historical rates, varicella vaccine efficacy during 5 years was estimated to be 90.5% (95% confidence interval, 86.2%, 95.0%) and 88.9% (95% confidence interval, 83.7%, 93.7%) in Groups A and B, respectively. CONCLUSIONS: Administration of M-M-R II and VARIVAX concomitantly at separate injection sites or 6 weeks apart was generally well-tolerated and immunogenic in healthy children 12 months to 6 years of age. VARIVAX administered with M-M-R II induced persistent immunity and long-term protection against breakthrough varicella infection.

PMID: 12182381, UI: 22169748

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Pediatr Infect Dis J 2002 Jun;21(6):548-54
 

Immune response to octavalent diphtheria- and tetanus-conjugated pneumococcal vaccines is serotype- and carrier-specific: the choice for a mixed carrier vaccine.

Sigurdardottir ST, Ingolfsdottir G, Davidsdottir K, Gudnason T, Kjartansson S, Kristinsson KG, Bailleux F, Leroy O, Jonsdottir I

Department of Immunology, Landspitali-University Hospital, Reykjavik Iceland. veiga@landspitali.is

[Medline record in process]
 

BACKGROUND: Development of protein-conjugated pneumococcal vaccines for infants has led to formulations that are immunogenic in the age group at highest risk for pneumococcal diseases. This study focuses on the search for an optimal formulation. METHODS: In a randomized trial Icelandic infants (n = 160) were immunized at age 3, 4 and 6 months with one of two octavalent pneumococcal conjugate vaccines (serotypes 3, 4, 6B, 9V, 14, 18C, 19F and 23F conjugated to diphtheria toxoid (PncD) or tetanus protein (PncT) followed with a booster of either the same conjugate or 23-valent polysaccharide vaccine at 13 months. Safety data were collected after each vaccination, and IgG responses (enzyme-linked immunosorbent assay) were measured at 3, 4, 6, 7, 13 and 14 months. RESULTS: Both conjugates were safe and caused fewer local reactions than the routine vaccines (P < 0.0001). At 7 months both groups had significant IgG response to all serotypes. The geometric mean concentration range was 0.35 to 4.09 and 0.65 to 3.38 microg/ml for PncD and PncT, respectively, with 88.2 to 100% and 92.4 to 100% of subjects reaching > or = 0.15 microg/ml. The PncD gave better primary responses to serotypes 3, 9V and 18C, whereas PncT gave better response to serotype 4. Similar responses were induced to the other serotypes. Good booster IgG responses were obtained in all vaccine groups; 97.5 to 100% of subjects reached > or = 1 microg/ml. CCONCLUSIONS: Both octavalent pneumococcal conjugates were safe and immunogenic in infants. Based on the results from this and similar trials, a mixed diphtheria and tetanus pneumococcal conjugate vaccine was designed to provide the optimal immune response to each serotype.

PMID: 12182380, UI: 22169747

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Pediatr Infect Dis J 2002 Jun;21(6):542-7
 

Instituting a routine varicella vaccination program in Canada: an economic evaluation.

Getsios D, Caro JJ, Caro G, De Wals P, Law BJ, Robert Y, Lance JM

Caro Research, Montreal, Canada.

[Medline record in process]
 

BACKGROUND: After licensing of a varicella vaccine in Canada in 1998, Health Canada commissioned a study to evaluate options for a vaccination program. The evaluation of a program of vaccination of 12-month-old children, with and without a catch-up program for susceptible 12-year-olds, is presented here. METHODS: An economic model was developed simulating the expected experience, with and without vaccination, of cohorts of children susceptible to varicella. The cohorts were simulated for 70 years, and infection and complication rates were calculated along with the attendant costs, with an assumed vaccine cost of $60. RESULTS: With an 85% coverage rate vaccination is expected to reduce the number of chickenpox cases by approximately two-thirds and varicella-related complications by up to 75%. The overall costs of varicella are expected to drop by >$4 million (1998 Canadian dollars) per 100,000 eligible vaccinees, but costs to the health care system are expected to increase by >$2 million. From the health care system perspective, vaccination would cost approximately $42 per discounted case avoided. INTERPRETATION: Routine varicella vaccination would likely substantially reduce the overall costs of managing chickenpox but would result in an increase in health care expenditures. These findings are consistent with evaluations in other countries.

PMID: 12182379, UI: 22169746

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Pediatr Infect Dis J 2002 Jun;21(6):535-41
 

Antibody persistence in five-year-old children who received a pentavalent combination vaccine in infancy.

Carlsson RM, Claesson BA, Fagerlund E, Knutsson N, Lundin C

Department of Infectious Diseases, Sahlgrenska University Hospital/Ostra, Goteborg, Sweden. rose-marie.carlsson@infect.gu.se

[Medline record in process]
 

BACKGROUND: Antibody persistence was studied in 5.5-year-old Swedish children who in infancy completed a vaccine trial of a combined diphtheria toxoid, tetanus toxoid, acellular pertussis, inactivated polio and Haemophilus influenzae type b conjugate vaccine. Three priming doses at ages 2-4-6 months induced higher geometric mean concentrations of antibodies for all antigens than did two doses at 3-5 months, but there were no differences in proportions with protective antibody concentrations. After the booster dose administered at 13 or 12 months of age, respectively, there were no differences in concentrations or proportions between the groups. METHODS: In the present follow-up serum samples from 180 of the 228 vaccinees, 88 from the 4-dose and 92 from the 3-dose group, were 4.5 years later again tested for antibodies. RESULTS: The two groups did not differ significantly in antibody concentrations or proportions with antibodies above protective or other defined levels, with the exception of poliovirus type 3 (P < or = 0.01). In all 89% had > or = 0.01 IU/ml antibodies against diphtheria by enzyme-linked immunosorbent assay and 76% by the Vero cell neutralization test, 93% had > or = 0.01 IU/ml antibodies against tetanus, 96 to 99% had detectable antibodies against the polioviruses and 97% had > or = 0.15 microg/ml H. influenzae type b antibodies. As for pertussis only 44% had detectable antibodies against pertussis toxoid by enzyme-linked immunosorbent assay but 99% by Chinese hamster ovary cell neutralization test, and 94% had detectable antibodies against filamentous hemagglutinin. CONCLUSION: We found the persistence of antibodies satisfactory, with no clinically relevant differences in antibody concentrations demonstrated between children vaccinated according to a three dose or a four dose schedule in infancy.

PMID: 12182378, UI: 22169745

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Pediatr Infect Dis J 2002 Jun;21(6):498-504
 

Childhood vaccinations and risk of asthma.

DeStefano F, Gu D, Kramarz P, Truman BI, Iademarco MF, Mullooly JP, Jackson LA, Davis RL, Black SB, Shinefield HR, Marcy SM, Ward JI, Chen RT

Centers for Disease Control and Prevention, Atlanta, GA, USA.

[Medline record in process]
 

BACKGROUND: A few previous studies have suggested that childhood vaccines, particularly whole cell pertussis vaccine, may increase the risk of asthma. We evaluated the suggested association between childhood vaccinations and risk of asthma. METHODS: Cohort study involving 167,240 children who were enrolled in 4 large health maintenance organizations during 1991 to 1997, with follow-up from birth until at least 18 months to a maximum of 6 years of age. Vaccinations were ascertained through computerized immunization tracking systems, and onset of asthma was identified through computerized data on medical care encounters and medication dispensings. RESULTS: In the study 18,407 children (11.0%) developed asthma, with a median age at onset of 11 months. The relative risks (95% confidence intervals) of asthma were: 0.92 (0.83 to 1.02) for diphtheria, tetanus and whole cell pertussis vaccine; 1.09 (0.9 to 1.23) for oral polio vaccine; 0.97 (0.91 to 1.04) for measles, mumps and rubella (MMR) vaccine; 1.18 (1.02 to 1.36) for Haemophilus influenzae type b (Hib); and 1.20 (1.13 to 1.27) for hepatitis B vaccine. The Hib result was not consistent across health maintenance organizations. In a subanalysis restricted to children who had at least 2 medical care encounters during their first year, the relative risks decreased to 1.07 (0.71 to 1.60) for Hib and 1.09 (0.88 to 1.34) for hepatitis B vaccine. CONCLUSION: There is no association between diphtheria, tetanus and whole cell pertussis vaccine, oral polio vaccine or measles, mumps and rubella vaccine and the risk of asthma. The weak associations for Hib and hepatitis B vaccines seem to be at least partially accounted for by health care utilization or information bias.

PMID: 12182372, UI: 22169739

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Science 2002 Jul 19;297(5580):312-3
 

HIV/AIDS meeting. Tough challenges ahead on political and scientific fronts.

Cohen J

Publication Types:
 

• Congresses
• News

PMID: 12130753, UI: 22127078

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