This review analyses the cumulated data from a number of long-term follow-up studies among infants, children and adults vaccinated against hepatitis B in industrialised and developing countries. Despite low or undetectable antibody responses years after vaccination, the development of HBsAg was a rarity and, if present, only transient. Some vaccinees developed anti-HBc responses but none developed an HB carrier state or clinical manifestations of disease. Studies demonstrating anamnestic responses among those with low or undetectable anti-HBs levels following challenge with HB vaccine, together with the production of anti-HBs in circulating B-cells by spot ELISA, confirmed the presence of immune memory among vaccinees. Anamnestic anti-HBs responses all correlate close in kinetics and magnitude with proliferative T-cell responses. The accumulated data from studies assessed in this Review indicate that protection is dependent on immune memory, rather than declining anti-HBs responses and add additional weight to the European Consensus recommendations (12) that following a complete course of vaccination, booster doses are unnecessary in immunocompetent persons. If implemented, this recommendation will have considerable cost benefits world-wide.
Changes in intestinal permeability and lactose hydrolysis have been investigated in three adults and fifteen infants with acute rotaviral gastroenteritis by differential sugar absorption. The method involves chromatographic measurement of urinary lactose, lactulose and L-rhamnose excretion following combined ingestion in an iso-osmolar test solution. All patients had abnormal intestinal permeability indicated by raised urine lactulose/L-rhamnose excretion, ratio of percentages recovered in 5 h, of 0.462 (0.100-1.227) mean and range, compared with 0.027 (0.008-0.052) for healthy controls (P less than 0.001). Ten patients also had urinary lactose/lactulose excretion ratios raised above the normal range (0.014-0.41, mean 0.258) during their acute illness, indicating impaired intestinal lactose hydrolysis. Both indices had become normal 4 weeks after the acute illness, serial investigation of five patients showing that improvement was complete much earlier. Except for the short duration these changes are similar to those associated with villous atrophy in coeliac disease. The test procedure was verified with respect to intestinal lactose hydrolysis by demonstrating a linear relationship between lactose/lactulose excretion and log jejunal mucosal lactase activity by in vitro assay (R2 = 0.95) in a further group of subjects. Differential lactose/lactulose/L-rhamnose absorption provides a non-invasive and sensitive index of small intestinal integrity of value for the interpretation of prolonged or otherwise complicated enteritis and the distinction of primary secondary intestinal lactase deficiency.
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