A case-control study of risk factors for Haemophilus influenzae type B disease in Navajo children.
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To understand the potential risk factors and protective factors for invasive Haemophilus influenzae type b (Hib) disease, we conducted a case-control study among Navajo children less than two years of age resident on the Navajo Nation. We analyzed household interview data for 60 cases that occurred between August 1988 and February 1991, and for 116 controls matched by age, gender, and geographic location. The Hib vaccine recipients were excluded from the analyses. Conditional logistic regression models were fit to examine many variables relating to social and environmental conditions. Risk factors determined to be important were never breast fed (odds ratio [OR] = 3.55, 95% confidence interval [CI] = 1.52, 8.26), shared care with more than one child less than two years of age (OR = 2.32, 95% CI = 0.91, 5.96); wood heating (OR = 2.14, 95% CI = 0.91, 5.05); rodents in the home (OR = 8.18, 95% CI = 0.83, 80.7); and any livestock near the home (OR = 2.18, 95% CI = 0.94, 5.04). (+info)
Altered helper T lymphocyte function associated with chronic hepatitis B virus infection and its role in response to therapeutic vaccination in humans.
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Theradigm-hepatitis B virus (HBV) is an experimental lipopeptide vaccine designed to stimulate induction of HBV-specific CTL responses in HLA-A2 individuals. Previous studies had demonstrated high immunogenicity in healthy volunteers, but comparatively weak CTL responses in chronically infected HBV patients. Herein, we examined helper T lymphocyte (HTL) responses in chronically infected patients. Despite normal proliferation and IL-2 secretion, IL-12 and IFN-gamma secretion in vitro in response to the vaccine was reduced compared with healthy volunteers. A similar pattern of cytokine secretion was observed following mitogen stimulation, suggesting a general altered balance of Th1/Th2 responses. Further analysis indicated that HTL recall responses to whole tetanus toxoid protein were reduced in chronically infected subjects, and reduced responsiveness correlated with the outcome of Theradigm-HBV immunization. Finally, experiments in HBV transgenic mice indicated that the nonnatural Pan DR HTL epitope, PADRE, is capable of inducing high levels of IFN-gamma secretion and that its inclusion in a lipopeptide incorporating an immunodominant Ld-restricted CTL epitope resulted in breaking tolerance at the CTL level. Overall, our results demonstrate an alteration in the quality of HTL responses induced in chronically infected HBV patients and suggest that use of a potent HTL epitope may be important to overcome CTL tolerance against specific HBV Ags. (+info)
Home delivery of heat-stable vaccines in Indonesia: outreach immunization with a prefilled, single-use injection device.
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Extending immunization coverage to underserved populations will require innovative immunization strategies. This study evaluated one such strategy: the use of a prefilled, single-use injection device for outreach immunization by village midwives. The device, UniJect, is designed to prevent refilling or reuse. Stored at ambient temperatures for up to 1 month in midwives' homes, vaccine-filled UniJect devices were immediately available for outreach. Between July 1995 and April 1996, 110 midwives on the Indonesia islands of Lombok and Bali visited the homes of newborn infants to deliver hepatitis B vaccine to the infants and tetanus toxoid to their mothers. Observations and interviews showed that the midwives used the device properly and safely to administer approximately 10,000 sterile injections in home settings. There were no problems with excessive heat exposure during the storage or delivery of vaccine. Injection recipients and midwives expressed a strong preference for the UniJect device over a standard syringe. Use of the prefilled device outside the cold chain simplified the logistics and facilitated the speed and efficiency of home visits, while the single-dose format minimized vaccine wastage. (+info)
Update on diagnosis, management, and prevention of hepatitis B virus infection.
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Acute and chronic hepatitis B virus (HBV) infection is a leading cause of liver disease worldwide. It is estimated that approximately 350 million people worldwide have chronic HBV infection and that 1 million persons die each year from HBV-related chronic liver disease. In the past decade, significant progress in the understanding of the molecular virology and pathogenesis of HBV infection has been made. In addition, effective treatment modalities have been developed for persons with chronic infection. Worldwide, prevention of HBV transmission has become a high priority. In 1992, the Global Advisory Group to the World Health Organization recommended that all countries integrate hepatitis B vaccine into national immunization programs by 1997. Currently, 80 countries have done so and several others are planning to. Many countries have reported dramatic reductions in the prevalence of chronic HBV infection among children born since the hepatitis B vaccine was introduced into infant immunization schedules. Recent reports from Taiwan indicate a reduction in the incidence of liver cancer among children as a result of widespread hepatitis B vaccination programs. (+info)
Immunogenicity of hepatitis B vaccine in preterm infants.
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AIM: To assess the immunogenicity of hepatitis B vaccine in preterm and term infants, given in a sequence of three doses beginning soon after birth. METHOD: The immunogenicity of hepatitis B vaccine was assessed in 176 preterm infants (< 35 weeks of gestation), immunised soon after birth, and compared with that in 46 term infants. Titres of hepatitis B antibodies were determined one to two months after the third vaccine. The significance of the differences between the term and preterm groups was determined using Student's t test. RESULTS: A similar proportion of infants in both preterm and term groups attained protective titres of hepatitis B antibodies (88.7% vs 93.4%, respectively; p = NS). However, the term infants had a higher geometric mean titre of antibodies after the third vaccine than did the preterm infants (701.2 (745.0) vs 469.1 (486.2) mU/ml, respectively; p < 0.03). CONCLUSION: Hepatitis B vaccine is effective in most preterm infants when given soon after birth. It may be advisable to determine the immune response at 12-24 months of age to booster the non-responders. (+info)
Intracellular retention of hepatitis B virus surface proteins reduces interleukin-2 augmentation after genetic immunizations.
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We have previously shown that hepatitis B virus (HBV) surface antigens (HBsAgs) are highly immunogenic after genetic immunization. Compared to the secreted middle HBV surface proteins (MHBs) or small HBV surface proteins (SHBs), the nonsecreted large HBV surface protein (LHBs), however, induced significantly weaker humoral and cellular immune responses that could not be augmented by genetic coimmunizations with cytokine expression plasmids. In order to understand the mechanisms underlying this phenomenon, we examined the effect of coimmunizations with an interleukin-2 (IL-2) DNA expression plasmid on the immunogenicity at the B- and T-cell level of nonsecreted wild-type LHBs, a secreted mutant LHBs, wild-type SHBs, and a nonsecreted mutant SHBs. Coimmunizations of mice with plasmids encoding wild-type SHBs or the secreted mutant LHBs and IL-2 increased anti-HBs responses, helper T-cell proliferative activity and cytotoxic T-lymphocyte killing. By contrast, coimmunizations of plasmids encoding wild-type LHBs or nonsecreted mutant SHBs and IL-2 had no significant effects on immune responses. Interestingly, mice immunized with cytokine expression plasmids 14 days after the injection of the wild-type LHBs plasmid showed augmented immune responses compared to animals simultaneously injected with both expression constructs. Anti-HBs responses in mice injected with plasmids encoding secreted forms of HBsAgs were detectable about 10 days earlier than those in mice immunized with plasmids encoding nonsecreted forms of HBsAgs. Based on these observations, we conclude that cytokines produced by DNA plasmids at the initial site of antigen presentation cannot augment LHBs specific immune responses because LHBs is not produced at high enough levels or is not accessible for uptake by antigen-presenting cells. (+info)
A mathematical model predicting anti-hepatitis B virus surface antigen (HBs) decay after vaccination against hepatitis B.
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The determination of serum levels of antibodies against hepatitis B virus surface antigen (anti-HBs) after hepatitis B vaccination is currently the only simple test available to predict the decay of protection and to plan the administration of booster doses. A total of 3085 vaccine recipients of plasma-derived and recombinant vaccine have been followed for 10 years to determine the kinetics of anti-HBs production and to construct a mathematical model which could efficiently predict the anti-HBs level decline. The anti-HBs peak level was reached 68 days after the last dose of recombinant vaccine and 138 days after the last dose of plasma-derived vaccines. The age of vaccinees negatively influenced the anti-HBs levels and also the time necessary to reach the anti-HBs peak. A bilogarithmic mathematical model (log10 level, log10 time) of anti-HBs decay has been constructed on a sample of recombinant vaccine recipients and subsequently validated on different samples of recombinant or plasma-derived vaccine recipients. Age, gender, type of vaccine (recombinant or plasma-derived), number of vaccine doses (three or four) did not influence the mathematical model of antibody decay. The program can be downloaded at the site: http:@www2.stat.unibo.it/palareti/vaccine.htm . Introducing an anti-HBs determination obtained after the peak, the program calculates a prediction of individual anti-HBs decline and allows planning of an efficient booster policy. (+info)
Hepatitis B vaccination in high-risk infants: 10-year follow-up.
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The long-term efficacy of hepatitis B vaccination among high-risk infants was determined in 805 vaccine responders, immunized at birth in Taiwan during 1981-1984 and followed to age 10 years, via life table survival and Cox multivariate analyses. At 10 years, cumulative persistence of antibody to hepatitis B surface antigen (anti-HBs) was 85%, and cumulative incidence of hepatitis B virus (HBV) infection was 15%. Three children became carriers. Twelve-month anti-HBs titer was the strongest predictor of efficacy. The higher the initial titer, the lower the risk of anti-HBs loss (relative risk [RR], 0.26 for titer of 100-999 mIU/mL; RR, 0.08 for titer >1000 mIU/mL; P<.001) and HBV infection (RR, 0.55 and 0.27; P<.05). Maternal hepatitis B e antigen positivity but not hepatitis B immunoglobulin dose or gender predicted greater antibody persistence to age 10 years. Because the level of antibody persistence remained high and few became carriers, booster revaccination within 10 years seems unnecessary. (+info)