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Clin Infect Dis 2002 Aug 15;35(4):465-74
 

New vaccines for the prevention of tuberculosis.

Von Reyn CF, Vuola JM

Infectious Disease Section, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA; and Vaccine Development Laboratory, National Public Health Institute, Helsinki, Finland. c.fordham.von.reyn@hitchcock.org

[Medline record in process]
 

Mycobacterium bovis, bacille Calmette-Guerin (BCG) is administered widely to newborns throughout the world and has been shown to be effective in preventing childhood tuberculosis but not reactivation pulmonary disease or human immunodeficiency virus-associated tuberculosis. Development of a more effective, better standardized, affordable vaccine with durable activity and fewer side effects is a major priority. Contemporary molecular techniques have identified promising immunodominant antigens and novel immunization strategies. Vaccine development has also been informed by an improved understanding of the role of nontuberculous mycobacteria in the efficacy of BCG and in the prevention of tuberculosis. Vaccines under investigation include attenuated or enhanced whole-cell live, whole-cell inactivated, subunit, DNA, and prime-boost vaccines. Several candidate vaccines have demonstrated activity in animal models that is equal to or superior to that of BCG, and human trials are under way. Because there is no identified surrogate marker for protection, identification of an improved vaccine will require long-term efficacy trials in humans.

PMID: 12145732, UI: 22139848

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Clin Infect Dis 2002 Aug 15;35(4):370-7
 

Influence of High-Risk Medical Conditions on the Effectiveness of Influenza Vaccination among Elderly Members of 3 Large Managed-Care Organizations.

Hak E, Nordin J, Wei F, Mullooly J, Poblete S, Strikas R, Nichol KL

HealthPartners Research Foundation, Bloomington, IN, USA.

[Medline record in process]
 

This serial cohort study assessed the risk of hospitalization or death associated with influenza and the effectiveness of influenza vaccination among subgroups of elderly members of 3 managed-care organizations in the United States. Data on baseline characteristics and outcomes were obtained from computerized databases. A total of 122,974 (1996-1997 season) and 158,454 (1997-1998 season) persons were included in the cohorts. Among unvaccinated persons, hospitalizations for pneumonia/influenza or death occurred in 8.2 of 1000 healthy and 38.4 of 1000 high-risk persons in year 1, and in 8.2 of 1000 healthy and 29.3 of 1000 high-risk persons in year 2. After adjustments, vaccination was associated with a 48% reduction in the incidence of hospitalization or death (95% confidence interval [CI], 42-52) in year 1 and 31% (95% CI, 26-37) in year 2. Effectiveness estimates were statistically significant and generally consistent across the healthy and high-risk subgroups. The absolute risk reduction, however, was 2.4- to 4.7-fold higher among high-risk than among healthy elderly persons. All elderly individuals may substantially benefit from vaccination. However, the impact of influenza is greater in persons with high-risk medical conditions.

PMID: 12145718, UI: 22139834

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Indian Pediatr 2002 Jul;39(7):625-31
 

Hepatitis B Vaccination in Premature and Low Birth Weight (LBW) Babies.

Bhave S, Bhise S, Chavan SC, Naik SS, Pusapati RV, Bavdekar A, Pandit A

Department of Pediatrics, KEM Hospital, Pune 411 011,*Department of Biochemistry & Endocrinology, KEM Hospital, Pune 411 011 and +Shantha Biotechnics Pvt. Limited, Hyderabad 500 034, India. kemhrc@vsnl.com

[Medline record in process]
 

OBJECTIVE: To assess the immune response of preterm and low birth weight babies (LBW) to hepatitis B (HB) vaccine. SETTING: Neonatal Intensive Care Unit (NICU), postnatal ward and follow up clinics of KEM Hospital, Pune. DESIGN: Open trial. METHODS: 100 babies were enrolled in four study groups. Group I - preterm, gestational age (GA) &LT 34 weeks; Group II - GA 34 to 36 weeks; Group III full term &LT2.5 kg (LBW babies); and Group IV full term &GT2.5 kg (controls). A recombinant DNA HB vaccine was given at 0, 1, 2 and 12 month schedule. The first injection was administered as soon as the neonate was stabilized. Immune response in terms of anti HBs titres (AUSAB EIA Diagnostic kit) was measured one month after each of the first three injections and at the time of one year booster. Adverse events were monitored. RESULTS: 88 and 62 babies completed the study till the third dose and one year booster dose respectively. Immune response of HB vaccine was uniformly good in all the study groups with 100 &PERCNT sero-conversion after the second dose itself. By one year (i.e. before the booster dose), very high titres were recorded in all 100&PERCNT, with 85&PERCNT demonstrating titres &GT1000 mIU/ml. Preterm and LBW babies had higher GMT as compared to full term babies till one month after third dose. By one year (before booster), full term babies had higher GMT than preterm and LBW babies. However, these differences were not statistically significant. The vaccine was well tolerated and safe and there were no adverse reactions. CONCLUSION: Immune response of preterm, LBW and full term babies to the new generation recombinant DNA HB vaccine was uniformly good. High and long term seroprotective levels were achieved after the second dose itself.

PMID: 12147887, UI: 22142472

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Infect Immun 2002 Jul;70(7):3707-13
 

Effect of O acetylation of Neisseria meningitidis serogroup A capsular polysaccharide on development of functional immune responses.

Berry DS, Lynn F, Lee CH, Frasch CE, Bash MC

Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland 20892, USA.

The importance of O-acetyl groups to the immunogenicity of Neisseria meningitidis serogroup A polysaccharide (PS) was examined in studies using human sera and mouse immunization. In 17 of 18 postimmunization human sera, inhibition enzyme-linked immunosorbent assay indicated that the majority of antibodies binding to serogroup A PS were specific for epitopes involving O-acetyl groups. Studies with mice also showed an essential role for O-acetyl groups, where serum bactericidal titers following immunization with de-O-acetylated (de-O-Ac) conjugate vaccine were at least 32-fold lower than those following immunization with O-Ac PS-conjugate vaccine and 4-fold lower than those following immunization with native capsular PS. Inhibition studies using native and de-O-Ac PS confirmed the specificity of murine antibodies to native PS. The dramatic reduction in immunogenicity associated with removal of O-acetyl groups indicates that O acetylation is essential to the immunogenic epitopes of serogroup A PS. Since levels of bactericidal antibodies are correlated with protection against disease, O-acetyl groups appear to be important in protection.

PMID: 12065513, UI: 22060689

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Infect Immun 2002 Jul;70(7):3557-65
 

Mechanisms of monophosphoryl lipid A augmentation of host responses to recombinant HagB from Porphyromonas gingivalis.

Yang QB, Martin M, Michalek SM, Katz J

Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Porphyromonas gingivalis, a gram-negative, black-pigmented anaerobe, is among the microorganisms implicated in the etiology of adult periodontal disease. This bacterium possesses a number of factors, including hemagglutinins, of potential importance in virulence. Our laboratory has shown the induction of protection to P. gingivalis infection after subcutaneous immunization with recombinant hemagglutinin B (rHagB). The purpose of this study was to determine if humoral antibody responses are induced after intranasal (i.n.) immunization of rHagB and if monophosphoryl lipid A (MPL), a nontoxic derivative of the lipid A region of lipopolysaccharide, acts as a mucosal adjuvant and potentiates responses to rHagB. Further, the effects of MPL on the nature of the response to HagB and on the costimulatory molecules B7-1 and B7-2 on different antigen-presenting cells (APC) were evaluated. Groups of BALB/c mice were immunized three times (2-week intervals) by the i.n. route with HagB (20 microg) alone or with MPL (25 microg). A group of nonimmunized mice served as control. Serum and saliva samples were collected prior to immunization and at approximately 2-week intervals and evaluated for serum immunoglobulin G (IgG) and IgG subclass and for salivary IgA antibody activity by enzyme-linked immunosorbent assay. Mice immunized with rHagB plus MPL had significantly higher salivary IgA (P < 0.05) and serum IgG (P < 0.05) anti-HagB responses than mice immunized with rHagB alone. The IgG1 and IgG2a subclass responses seen in mice immunized with rHagB plus MPL were significantly higher (P < 0.05) than those seen in mice immunized with rHagB only. Further, the IgG2a/IgG1 ratio in the latter group was approximately 1, whereas in mice immunized with rHagB plus MPL the ratio was <1. These results provide evidence for the participation of T helper (Th) 1 and Th2 cells in responses to rHagB and that MPL potentiates a type 2 response to HagB. MPL was also shown to preferentially up-regulate B7-2 expression on B cells, whereas a preferential increase in B7-1 costimulatory molecule was seen on macrophages and dendritic cells. These results provide evidence that MPL exerts a differential regulation in the expression of costimulatory molecules on APC.

PMID: 12065496, UI: 22060672

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Infect Immun 2002 Jul;70(7):3355-62
 

Protective immunity conferred by attenuated aroA derivatives of Pasteurella multocida B:2 strains in a mouse model of hemorrhagic septicemia.

Tabatabaei M, Liu Z, Finucane A, Parton R, Coote J

Infection and Immunity Division, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

Hemorrhagic septicemia (HS) is a fatal systemic disease of cattle and buffaloes. In South Asia HS is caused by infection with Pasteurella multocida serotype B:2. Some control is achieved with alum-precipitated or oil-adjuvanted killed whole-cell vaccines injected subcutaneously, but these vaccines provide only short-term immunity and require annual administration for effective use. Live attenuated vaccines have the advantage of a natural route of entry into the host, but for live strains to be used as vaccines, the mode of attenuation should be well defined. We constructed aroA attenuated derivatives of two P. multocida serotype B:2 strains by allelic exchange of the native aroA sequence with aroA sequences disrupted with a kanamycin resistance cassette or with marker-free aroA sequences containing an internal deletion. These strains were confirmed to be aroA mutants by PCR and Southern blot analysis, enzyme assay, and lack of growth on minimal medium. The aroA derivatives were highly attenuated for virulence in a mouse model of HS. Mouse challenge experiments showed that intraperitoneal or intranasal vaccination of an aroA strain completely protected mice against challenge with a high dose (>1,000 50% lethal doses) of either the parent strain or the other wild-type B:2 strain. The spread of the parent and the aroA derivatives to different organs was compared when the organisms were inoculated by different routes.

PMID: 12065473, UI: 22060649

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J Infect Dis 2002 Jun 15;185(12):1697-703
 

Dengue-specific T cell responses in peripheral blood mononuclear cells obtained prior to secondary dengue virus infections in Thai schoolchildren.

Mangada MM, Endy TP, Nisalak A, Chunsuttiwat S, Vaughn DW, Libraty DH, Green S, Ennis FA, Rothman AL

Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.

Children who experience secondary dengue virus (DV) infections are at increased risk for dengue hemorrhagic fever. To study the effect of preexisting T cell responses to DV on the severity of secondary virus infection, peripheral blood mononuclear cells (PBMC) from 10 subsequently hospitalized and 12 nonhospitalized Thai schoolchildren were stimulated with inactivated dengue antigens, and proliferation of interferon (IFN)-gamma or tumor necrosis factor (TNF)-alpha responses of the preinfection PBMC were measured. Proliferation responses were observed in 11 subjects, and IFN-gamma responses were seen in 12 subjects, 6 of whom showed broad serotype cross-reactive IFN-gamma responses. TNF-alpha responses were detected exclusively in 4 hospitalized subjects. Four PBMC samples that showed neither proliferation nor cytokine responses to any dengue antigen were from nonhospitalized subjects. This study, thought to be the first to investigate T cell responses to DV in preinfection PBMC, suggests that the pattern of preexisting T cell responses influences the risk for severe disease.

PMID: 12085313, UI: 22079867

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MMWR Morb Mortal Wkly Rep 2002 Jul 12;51(27):598-9
 

Resumption of routine schedule for diphtheria and tetanus toxoids and acellular pertussis vaccine and for measles, mumps, and rubella vaccine.

PMID: 12143834, UI: 22138551

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Pediatr Infect Dis J 2002 May;21(5):482-7
 

Future directions in vaccine prevention of respiratory syncytial virus.

Piedra PA

Department of Molecular Virology, Baylor College of Medicine, Houston, TX 77030, USA. ppiedra@bcm.tmc.edu

[Medline record in process]
 

PMID: 12150197, UI: 22144740

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Pediatr Infect Dis J 2002 May;21(5):399-405
 

Use of lidocaine-prilocaine patch to decrease intramuscular injection pain does not adversely affect the antibody response to diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b conjugate and hepatitis B vaccines in infants from birth to six months of age.

Halperin BA, Halperin SA, McGrath P, Smith B, Houston T

Department of Pediatrics, Dalhousie University and the IWK Health Centre, Halifax, Nova Scotia, Canada.

[Medline record in process]
 

BACKGROUND: Topical lidocaine-prilocaine (EMLA) effectively decreases the pain associated with minor procedures including immunization, although the effect on the antibody response to diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b conjugate (DTaP-IPV-Hib) and hepatitis B vaccines has not been assessed. OBJECTIVE: To measure the antibody response to DTaP-IPV-Hib and hepatitis B vaccines; to measure pain reduction associated with the use of the lidocaine-prilocaine (EMLA) patch; and to assess safety by comparing adverse reactions. PARTICIPANTS AND SETTING: One hundred nine healthy 6-month-old infants (Part A of study) and 56 healthy infants birth to 2 months of age (Part B of study) undergoing primary immunization with DTaP-IPV-Hib and hepatitis B vaccines in an ambulatory setting. DESIGN AND INTERVENTIONS: Two center, randomized, double blind, controlled trial of EMLA patch or placebo before DTaP-IPV-Hib and hepatitis B immunization. Antibody titers measured at 0 to 2, 6 and 7 months. OUTCOME MEASURES: The primary outcome measure was the antibody response to diphtheria, tetanus, pertussis antigens, Haemophilus influenzae type b and hepatitis B by enzyme immunoassay; and poliovirus 1, 2 and 3 by neutralization. The secondary outcomes were pain scores by the Modified Behavioral Pain Scale and drug- and vaccine-associated adverse events collected with a parent diary and structured questionnaire. RESULTS: There was no difference in the antibody response between the EMLA- and placebo-treated groups as assessed by geometric mean antibody titers, rates of seroconversion or the proportion of participants achieving protective or positive antibody titers postimmunization. At the 6-month visit, EMLA recipients had less pain after immunization (total pain score, 6.75 vs. 7.35; P = 0.005; pain score increase, 3.99 vs. 4.74; P = 0.004) than did placebo recipients. Skin pallor and erythema at the patch application site were more frequently reported after EMLA use. Rates of vaccine-associated adverse events were similar in the two groups. CONCLUSIONS: The EMLA patch has no adverse effect on the antibody response to the vaccine antigens, is effective in reducing pain associated with DTaP-IPV-Hib and hepatitis B immunizations and does not result in any significant or unexpected adverse reactions.

PMID: 12150176, UI: 22144719

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Pediatr Infect Dis J 2002 May;21(5):393-9
 

Defining the potential impact of conjugate bacterial polysaccharide-protein vaccines in reducing the burden of pneumonia in human immunodeficiency virus type 1-infected and -uninfected children.

Madhi SA, Cumin E, Klugman KP

SAIMR/University of the Witwatersrand/Medical Research Council Pneumococcal Diseases Research Unit.

[Medline record in process]
 

BACKGROUND: The evaluation of bacterial conjugate vaccines in preventing pneumonia requires the definition of suitable outcome measures against which their use can be evaluated. One such possible outcome measure is alveolar consolidation confirmed by chest radiograph (CXR). OBJECTIVE: To define the CXR presentation in relation to identified bacterial and respiratory viral pathogens among HIV-1-infected and -uninfected children. METHODS: The CXRs of 1186 of 1434 children hospitalized with severe lower respiratory tract infection were evaluated for the presence of alveolar consolidation (homogenous airspace infiltrate), bronchopneumonia (patchy airspace consolidation) or other CXR findings. Children were also investigated for bacterial infection by blood culture in 1364 of 1434 episodes and for respiratory viruses in 990 of 1434 episodes by immunofluorescein monoclonal antibody assays. RESULTS: The prevalence of HIV-1 infection among children who had CXRs in the study was 527 (46.2%) of 1142. Alveolar consolidation was more common in HIV-1-infected (63.7%) than in HIV-uninfected children (42.4%, P < 10(-5)) whereas bronchopneumonic changes (29.0% vs. 38.0%, P = 0.001) or a normal CXR occurred in 7.0 vs. 18.2% (P < 10(-5)) of HIV-1-infected and -uninfected children, respectively. Alveolar consolidation was the main CXR presentation in HIV-1-infected (78.6%) and HIV-uninfected children (64.9%, P = 0.14) with all-cause bacteremic pneumonia as well as those with bacteremic Streptococcus pneumoniae pneumonia (76.9% vs. 83.3%, respectively; P = 0.99). Respiratory virus-associated lower respiratory tract infection, however, was more likely to present with alveolar consolidation in HIV-1-infected (55.8%) than in HIV-uninfected (36.1%, P = 0.02) children. CONCLUSION: Although alveolar consolidation may be a useful tool in defining both the efficacy and burden of bacterial pneumonia in HIV-1-uninfected children, this may not be so for HIV-1-infected children. The higher occurrence of respiratory virus-associated alveolar consolidation, possibly coupled with Pneumocystis carinii pneumonia, may be significant confounders in the interpretation of CXR in HIV-1-infected children, limiting the use of alveolar consolidation as an outcome measure when evaluating the efficacy of bacterial conjugate vaccines in HIV-1-infected children.

PMID: 12150175, UI: 22144718

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Pediatr Infect Dis J 2002 May;21(5):361-5
 

Observed costs and health care use of children in a randomized controlled trial of pneumococcal conjugate vaccine.

Ray GT, Butler JC, Black SB, Shinefield HR, Fireman BH, Lieu TA

Division of Research, Kaiser Permanente Medical Care Program, Oakland, CA 94611, USA. gtr@dor.kaiser.org

[Medline record in process]
 

BACKGROUND: Pneumococcal conjugate vaccine for infants has recently been found to be effective for prevention of meningitis, bacteremia, pneumonia and otitis media, but it is more costly than previously introduced vaccines. AIM: We sought to determine the savings in medical costs through 36 months of life attributable to the use of the vaccine in healthy infants in a large randomized trial. METHODS: We analyzed the actual medical costs of 36 471 children involved in a randomized trial of heptavalent pneumococcal conjugate vaccine conducted in the Northern California Kaiser Permanente Medical Care Program. The costs of the vaccine and vaccine administration were excluded. RESULTS: Compared with the control group, the vaccinated group experienced a 2% reduction in clinic related costs [$48; 95% confidence interval (CI), $10 to $83] and a nearly significant 14% reduction in outpatient hospitalization costs ($32; CI -$1 to $66). The savings in total medical costs were 1.2%, but this difference was not significant ($41; CI -$204 to $270). Inpatient hospital costs were highly variable and were responsible for the lack of precision in the difference in total cost. In a post hoc analysis that excluded hospital costs not believed to be potentially pneumococcal related, savings in medical costs were $78 and significant (CI $5 to $158). CONCLUSIONS: The pneumococcal conjugate vaccine reduced ambulatory care costs in children in the first 36 months of life, but without a larger trial, the magnitude of the savings in total medical costs is uncertain. These results indicate, however, that any medical cost savings that are associated with the vaccine are unlikely to be high enough to offset the cost of the vaccine at its current price.

PMID: 12150168, UI: 22144711

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Science 2002 Jul 12;297(5579):201-2
 

Microbiology. A binding contract for anthrax.

Bull JJ, Parrish CR

Section of Integrative Biology and Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712, USA. bull@bull.biosci.utexas.edu

PMID: 12114612, UI: 22111263

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Wkly Epidemiol Rec 2002 Jul 12;77(28):230-9
 

Influenza vaccines.

[Medline record in process]
 

PMID: 12143096, UI: 22139060

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