One concern is to what extent the subset of NHANES participants evaluated for HCV infection and diabetes was representative of the entire NHANES population sample. This is a significant question because the overall NHANES sample is considered the best representation of the general population of the United States, a collection of subjects free of the bias usually present in clinic-based investigations. Thus, it was reassuring that the subset of NHANES that could be evaluated for HCV infection and diabetes was both large (9,841 persons) and similar to other NHANES members with respect to many factors, including all recognized correlates of both HCV infection and diabetes. 1 This representation essentially eliminates the potential for selection bias. Another strength of the NHANES analysis is the careful testing for HCV infection performed by the Hepatitis Branch at the Centers for Disease Control and Prevention. Because HCV infection was assessed by second-generation enzyme immunoassay and confirmed by supplemental antibody testing, there is no doubt that most positive results reflect true HCV exposure. Indeed, in the subset tested for both HCV antibody and RNA, HCV RNA was detected in all but 26%, the percent one would expect to have cleared infection if all antibody-positive subjects had been previously infected. 3 Dr. Everhart raised the question of whether the antibody testing should be the main determinant of HCV or if the analysis should be restricted to persons with both HCV antibody and RNA. 2 If one were convinced that the association exists exclusively because ongoing HCV infection caused diabetes, it would have been appropriate to restrict the analysis to persons whose blood contained both HCV antibodies and RNA. Because too little is known about the pathogenesis and temporal sequence of HCV infection and diabetes to make these assumptions, the analysis initially was presented using antibody testing as the marker of HCV exposure. Nonetheless, Dr. Nainan and coworkers at the Centers for Disease Control and Prevention generously provided the HCV RNA data. For the subset for whom there is HCV RNA testing, the age-adjusted odds of type 2 diabetes in persons with HCV RNA and antibody was 2.48 (95% CI 1.23-5.01) compared with 0.98 for persons with HCV antibody but not RNA. If confirmed , these data are not consistent with the conjecture that diabetes leads to HCV infection, but instead favor hypotheses suggesting that persistent HCV infection is associated with the subsequent development of diabetes. Another important discovery in the analysis of HCV infection and type 2 diabetes in NHANES was the difference in the magnitude and direction of the association in persons of relatively young ages. Type 2 diabetes is a clinically heterogeneous syndrome that, according to the Cecil Textbook of Medicine, "typically appears after the age of 40 years." 4 In NHANES III, type 2 diabetes was not associated with HCV infection in persons less than 40 years of age. 1 Type 2 diabetes may be a different condition when it mani...

A pairwise comparison of the nucleic acid sequence of 168 bases from 152 wild-type or unique cell cultureadapted strains of hepatitis A virus (HAV) revealed that HAV strains can be differentiated genetically into seven unique genotypes (I to VII). In general, the nucleotide sequence of viruses in different genotypes differs at 15 to 25 % of positions within this segment of the genome. Viruses from four of the genotypes (I, II, III and VII) were recovered from cases of hepatitis A in humans, whereas viruses from the other three genotypes (IV, V and VI) were isolated only from simian species developing a hepatitis A-like illness during captivity. Among non-epidemiologically related human HAV strains, 81 were characterized as genotype I, and 19 as genotype III. Within each of these major genotypes, there were two distinct groups (subgenotypes), which differed in sequence at approximately 7-5 % of base positions. Each genotype and subgenotype has a characteristic amino acid sequence in this region of the polyprotein, with the most divergent genotypes differing at 10 of 56 residues. Strains recovered from some geographical regions belonged to a common (endemic) genotype, whereas strains from other regions belonged to several, probably imported, genotypes. Thus, HAV strains recovered in North America were for the most part closely related at the nucleotide sequence level, whereas in other regions, such as Japan and Western Europe, HAV strains were derived from multiple genotypes or sub-genotypes. These data indicate that patterns of endemic transmission can be differentiated from situations in which infections are imported due to travel.

No abstract

If duration of membrane rupture and internal fetal monitoring are confirmed to be associated with transmission, interventions may be possible to decrease the risk of transmission.

SUMMARY Current serologic tests provide the foundation for diagnosis of hepatitis A and hepatitis A virus (HAV) infection. Recent advances in methods to identify and characterize nucleic acid markers of viral infections have provided the foundation for the field of molecular epidemiology and increased our knowledge of the molecular biology and epidemiology of HAV. Although HAV is primarily shed in feces, there is a strong viremic phase during infection which has allowed easy access to virus isolates and the use of molecular markers to determine their genetic relatedness. Molecular epidemiologic studies have provided new information on the types and extent of HAV infection and transmission in the United States. In addition, these new diagnostic methods have provided tools for the rapid detection of food-borne HAV transmission and identification of the potential source of the food contamination.