MMWR. 1998;47:1-5 1 table omitted ON OCTOBER 17 and October 23, 1997, a man in Texas and a man in New Jersey, respectively, died from rabies. This report summarizes the clinical features of these cases and the epidemiologic investigations by the Texas Department of Health and the New Jersey State Department of Health and Senior Services, which indicated that a bat-associated variant of the rabies virus was responsible for infection in both cases.

From the Centers for Disease Control and Prevention

Objective. —Effective Haemophilus influenzae type b (Hib) conjugate vaccines were first licensed for use in US children at least 18 months old in December 1987 and for infants at least 2 months old in October 1990. We evaluated trends in Hib disease associated with licensure of Hib conjugate vaccines. Design. —Data from two sources, an intensive laboratory-based active surveillance system and the National Bacterial Meningitis Reporting System (NBMRS), were used separately to evaluate disease incidence. Data from vaccine manufacturers on Hib vaccine doses distributed in the United States were compared with trends in Hib disease incidence. Results. —The age-specific incidence of Hib disease among children less than 5 years old decreased by 71% from 37 per 100 000 persons in 1989 to 11 per 100 000 persons in 1991 (active surveillance data). Haemophilus influenzae meningitis incidence decreased by 82% between 1985 and 1991 (NBMRS data). Increases in doses of Hib vaccine distributed in the United States coincided with steep declines in Hib disease. Both surveillance systems showed decreased rates of Hib disease in infants less than 1 year old before vaccine was licensed for use in this age group. Haemophilus influenzae type b disease incidence in persons at least 12 years old and pneumococcal meningitis incidence in children less than 5 years old did not change substantially during the same period; therefore, decreased Hib disease in children less than 5 years old is not likely to be explained solely by changes in surveillance sensitivity or decreases in bacterial disease due to changes in medical practice. Conclusion. —Our data suggest that conjugate vaccines have already had a marked impact on the incidence of Hib disease in the United States, preventing an estimated 10 000 to 16 000 cases of Hib disease in 1991. The decline of disease in infants less than 1 year old before licensure for this age group warrants further investigation. ( JAMA . 1993;269:221-226)

Decline of Childhood Haemophilus influenzae Type b (Hib) Disease in the Hib Vaccine Era

Immune responses to polysaccharide antigens are thymus-independent (TI). Conversion of a polysaccharide antigen to a thymus-dependent (TD) antigen by covalent coupling to an immunogenic protein carrier alters the response to the polysaccharide in several important ways. Of primary importance for the prevention of invasive diseases in infants caused by encapsulated bacteria is the shift of the peak antibody response to a much younger age. Another important change is the development of memory B cells primed and ready to respond to either the polysaccharide, as would be encountered during an infection, or to a second dose of the same antigen. Additional immunoglobulin isotypes not seen or seen as a minor component in response to the polysaccharide are also a feature of the TD response. Finally, the diversity of the antibody population is increased after immunization with a TD vaccine compared with that seen after immunization with a TI vaccine.

Thymus-independent and thymus-dependent responses to polysaccharide antigens.

Serological criteria for evaluation and licensure of new pneumococcal conjugate vaccine formulations for use in infants.

and Examples.- Overview of Vaccine Effects and Study Designs.- Immunology and Early Phase Trials.- Binomial and Stochastic Transmission Models.- and Deterministic Models.- Evaluating Protective Effects of Vaccination.- Modes of Action and Time-Varying VE.- Further Evaluation of Protective Effects.- Vaccine Effects on Post-Infection Outcomes.- Household-Based Studies.- Analysis of Households in Communities.- Analysis of Independent Households.- Assessing Indirect, Total, and Overall Effects.- Randomization and Baseline Transmission.- Surrogates of Protection.

Design and Analysis of Vaccine Studies

Background and Methods. Several conjugate vaccines against Haemophilus influenzae type b have been developed in the search for one that induces protection even in young infants. We evaluated the safety and efficacy of a conjugate vaccine that links the H. influenzae type b capsular polysaccharide to the outer-membrane protein complex (OMPC) of Neisseria meningitidis serogroup B. We conducted a double-blind, placebo-controlled trial in Navajo infants, who are at high risk for systemic infections caused by H. influenzae type b. The infants were randomly assigned to receive the first dose of vaccine or placebo at 42 to 90 days of age and the second at 70 to 146 days of age. Results. Of the infants in the trial, 2588 were assigned to receive the vaccine and 2602 to receive placebo. The mean follow-up was 269 days in the vaccine group and 267 days in the placebo group. Before the age of 18 months, there was 1 systemic H. influenzae type b infection in the vaccine group, as compared with 22 in the placebo group...

https://www.nejm.org/doi/pdf/10.1056/NEJM199106203242503

The efficacy in Navajo infants of a conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex.

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The efficacy in Navajo infants of a conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex.