Delayed immunologic maturation--among other things based on a selective lack of antibodies against some acute purulent otitis media (AOM)-associated pneumococcal types--has been proposed in children with recurrent AOM (rAOM). To further elucidate the immunologic response in these children, we compared the antibody responses to diphtheria, tetanus, and rubella vaccinations in 13 children with rAOM and 29 children without AOM. The children took part in a prospective study from birth to the age of 3 years. The antibody response to the rubella vaccine was significantly lower in the children with rAOM. The responses to tetanus and to diphtheria did not differ between children with and without rAOM. Thus, the results indicate that in addition to the known lack of antibodies against pneumococcal polysaccharide antigens, a lower antibody response against at least one protein antigen may exist in otitis-prone children.
Replication of hepadnaviruses involves a viral DNA polymerase containing both a DNA-dependent and an RNA dependent activity. This polymerase is a potential target for chemotherapy against hepatitis B. We have used human hepatitis B virus DNA-dependent DNA polymerase from human serum and duck hepatitis B virus DNA-dependent DNA polymerase from duck serum as well as RNA-dependent DNA polymerase activity from duck hepatitis B-infected duck liver. Triphosphates of thymidine analogs have been synthesized and tested for their inhibitory activities against these enzymes with the intention both to explore differences between these enzymes and structural requirements for inhibitors. The results showed that with the inhibitors tested, hepatitis B virus DNA-dependent DNA polymerase was the most sensitive enzyme and the triphosphate of 5-propenyl-2'-deoxyuridine was the most active inhibitor. In addition, the 5'-triphosphate of 5-propenyl-arabinofuranosyluracil also inhibited the hepadnavirus DNA-dependent DNA polymerases, and was a competitive inhibitor with respect to 2'-deoxythymidine triphosphate as showed by kinetic studies with duck hepatitis B virus DNA-dependent DNA polymerase from serum. Pharmacokinetic analysis showed 5-propenyl-2'-deoxyuridine to be well absorbed orally, but rapidly cleared from plasma. The arabinofuranosyl analog was also well absorbed but cleared less rapidly. Hence, these results indicate the potential of 5-propenyl-2'-deoxyuridine and 5-propenyl-arabinofuransyluracil for chemotherapy of hepatitis B.
Acute otitis media (AOM) has been epidemiologically related to viral respiratory tract infections, and viral antigens have also been detected in middle ear secretion in some AOM episodes. Successive serum samples from children followed prospectively for three years from birth were analysed for IgG antibodies against respiratory syncytial virus (RSV), adenoviruses and influenza A virus. Values from serum antibody activity gradually decreased during the first six months of life, followed by a gradual increase. Various relationships were found to obtain between age and the increases of antibody activity against the different viruses. Thus, three quarters of those tested had manifested increased antibody activity against RSV by 18 months of age, and against adenoviruses by 30 months of age. No increase of antibody activity against influenza A was noted before 12 months of age, and then only seen in two thirds of those tested during the entire three-year observation period. With regard to age, however, the proportion of children with increased antibody activity to RSV, adenoviruses or influenza A virus did not differ between otitis-prone and non-otitis-prone children. Thus, as compared to non-otitis-prone children, development of the ability to produce antibodies against these viruses was not found to be delayed in otitis-prone children.
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