In the study reported here, chronic hepatitis B (positive result for hepatitis B surface antigen) and C (positive enzyme-linked immunosorbent assay result for hepatitis C virus) were exclusion criteria, and no hepatitis B or C cases were diagnosed

In the study reported here, chronic hepatitis B (positive result for hepatitis B surface antigen) and C (positive enzyme-linked immunosorbent assay result for hepatitis C virus) were exclusion criteria, and no hepatitis B or C cases were diagnosed. Viral hepatitis is a well-known cause of elevated levels of liver enzymes and should be ruled out in any clinical trial participant with this laboratory abnormality. the University of Bamako since 1988. Healthy children 23 years of age were screened and 36 children were enrolled and received up to two doses of study vaccine or control vaccine (Hiberix,Haemophilus influenzaB) in a dose-escalating design. The study was conducted under a protocol reviewed and approved by the Institutional Review Board of the National Institute of Allergy and Infectious Disease and by the Ethics Committee of the Faculty of Medicine, Pharmacy and Dentistry, University of Bamako. Community and individual informed consent was obtained from all participants. Screening occurred in February 2006; eligibility criteria are described in detail elsewhere. 1Two dose cohorts of 18 subjects each were enrolled and vaccinated at 0 and 1 months. The low-dose cohort received first vaccinations on March 16 and the high-dose cohort received first vaccinations on March 31. A local medical monitor reviewed safety data prior to dose escalation, and a data safety and 3-Methoxytyramine monitoring board (DSMB) reviewed safety data prior to enrollment of a larger cohort for a Phase 2 study. Serum levels of alanine aminotransferase (ALT) were checked at screening, at each vaccination day, and on days 3 and 14 after each vaccination (a total of seven times for each child enrolled during the first six weeks of participation). If other inclusion/exclusion criteria were met, children were eligible 3-Methoxytyramine for enrollment if the ALT level was < 62 U/L (1.25 3-Methoxytyramine times the upper limit of normal [ULN], 49.6 U/L). The protocol defined an ALT level > 10 times the ULN (496 U/L) as a serious adverse event (SAE). Seventy-seven children were screened, among whom three were excluded for an ALT level above the specified 3-Methoxytyramine limit (Figure 1). One of these three children also had jaundice, pallor, swelling in the lower extremities, hepatomegaly, and a clinical history of diarrhea. He was subsequently diagnosed with hepatitis A by detection of IgM antibody to hepatitis A virus (HAV); he had a negative result for hepatitis B surface antigen, and no antibodies to hepatitis C. This child lived in a large family compound with other children who were also eligible for participation, and a sibling living in the same compound was enrolled in the study. No other case of elevated ALT levels and icterus was found although six and two subjects had positive serologic results for hepatitis B or C, respectively, at screening. == FIGURE 1. == Flow chart for screening and vaccinations. The 36 children enrolled and vaccinated had ALT levels below the protocol-specified limit at screening and had no acute illness on the day of enrollment. During the period of enrollment and initial follow-up (to day 50), eight children were found to have elevated ALT levels, and seven of them were diagnosed with acute hepatitis A on the basis of presence of antibody to HAV. Three subjects did not receive second vaccinations because of hepatitis A diagnosed after first vaccination and three were diagnosed soon after the second vaccination (Figure 1). One additional case of hepatitis A was diagnosed in the later, less-intensive phase of follow-up, for a total MADH3 of 8 cases. One child had persistent mild elevation of the ALT level with repeated 3-Methoxytyramine negative serologic results for hepatitis; for that child the elevated ALT level was graded possibly related to vaccination. The hepatitis A cases were equally distributed in.