Humoral and cellular immune memory response 12 years following single dose vaccination against hepatitis A in Argentinian children.

Infants' universal hepatitis A virus (HAV) single-dose vaccination has been highly effective for controlling HAV infection in Argentina, and in other Latin-American countries that adopted that strategy. Although antibodies wane over time, this has not been associated with HAV outbreaks or breakthrough infections, suggesting a relevant role for memory immunity. This study assessed long term humoral and cellular immune memory response after an average of 12 years follow-up of HAV single-dose vaccination. We selected 81 HAV-single dose vaccinated individuals from a 2015 study, including 54 with unprotective (UAL) and 27 with protective antibody levels (PAL) against HAV. Humoral memory response was assessed by measuring anti-HAV antibody titers at admission in both groups, and 30 days after a booster dose in the UAL group. Flow cytometry analysis of peripheral blood mononuclear cell samples stimulated with HAV antigen was performed in 47/81 individuals (21 with PAL, 26 with UAL) to identify activated CD4 + memory T cells or CD8 + memory T cells. The results showed that 48/52 (92%) individuals from UAL group who completed follow up reached protective levels after booster dose. In the PAL group, anti-HAV Abs waned in 2/27 (7%) individuals lacking seroprotection, while in 25/27 (93%) Abs remained >10 mUI/mL. HAV-specific memory CD4 + T cells were detected in 25/47 (53.2%) subjects while HAV-specific memory CD8 + T cells were observed in 16/47 (34.04%) individuals. HAV-specific memory CD4+ and CD8+ T cell responses were detected in 11/21 (52.4%) and in 9/21 (42.9%) subjects with PAL and in 14/26 (53.8%) and in 7/26 (26.9%) individuals with UAL, showing that the presence of memory T-cells was independent of the level or presence of anti-HAV antibodies. Long-term immunity demonstrated in the present work, including or not antibody persistence, suggests that individuals with waned Ab titers may still be protected and supports the single-dose HAV strategy.

Economic analysis of the single-dose immunization strategy against hepatitis A in Argentina.

BACKGROUND: Vaccination against hepatitis A (HA) was carried out only as part of a limited outbreak control strategy in Argentina until June 2005, when universal immunization in infants was introduced into the national immunization calendar. A single-dose strategy was chosen instead of the standard two-dose schedule used elsewhere. This study aimed to estimate preventive, medical, and non-medical costs related to HA and to compare these costs in the periods before and after mass vaccination. METHODS: A retrospective analysis estimated treatment costs of HA and unspecified hepatitis cases reported to the National Health Surveillance System from 2000 to 2010. Costs related to immunization, fulminant hepatitis (FH), liver transplantation, and death were projected as well. Using a social perspective and a healthcare system perspective, costs in two 5-year periods were compared: 2000-2004 versus 2006-2010. Finally, we evaluated the impact of different discount rates, FH risk, and exclusion of unspecified hepatitis cases in the sensitivity analysis. RESULTS: Total HA and unspecified hepatitis cases decreased from 157,871 in 2000-2004 to 17,784 in 2006-2010. Medical and non-medical costs decreased from US$11,811,600 and US$30,118,222 to US$1,252,694 and US$4,995,895 in those periods, respectively. Immunization costs increased from US$6,506,711 to US$40,912,132. Total preventive, medical, and non-medical costs decreased from US$48,436,534 to US$47,160,721, representing a 2.6% reduction in total costs between the two periods. When a healthcare system perspective was considered or unspecified hepatitis cases were excluded, total costs were 130.2% and 30.8% higher in 2006-2010 than in the previous period, respectively. CONCLUSION: After implementation of the universal single-dose vaccination against HA in infants in Argentina, an impressive decline was observed in HA cases, with a decrease in medical and non-medical costs in the first 5 years. The single-dose strategy, which is simpler and less expensive than the standard two-dose scheme, can be a good alternative for future vaccination policies in other countries where HA is endemic.

Liver infiltrating mononuclear cells in children with type 1 autoimmune hepatitis.

OBJECTIVE: To investigate infiltrating cells in the liver of children with type 1 autoimmune hepatitis (AH-1). METHODS: liver biopsies from 24 untreated AH-1 patients (14 children, 10 adults), five patients with hepatitis C virus related chronic hepatitis (HCV), and 10 control liver specimens (CL) were processed for immunohistochemical cell characterisation. RESULTS: Two different cell distribution patterns were detected in the liver of patients with AH-1: (1) CD4(+) and CD20(+) cells were found in the central areas of the portal tracts (portal distribution); (2) CD8(+) cells were observed at the periphery of the portal space (periportal distribution). Some cell subsets, like CD56, CD57, Fas-L, and Bak, showed a non-defined distribution pattern. The presence of two well defined patterns of cell distribution was not observed in HCV and CL (CD4(+), CD20(+), and CD8(+) cells were uniformly distributed in the portal space). In AH-1 and CL, the NK markers CD56 and CD57 were found scattered throughout the liver parenchyma. However, in HCV biopsies, CD56(+) cells were also clearly increased in both the portal and the periportal areas. Biopsies of AH-1 and HCV patients showed a uniform distribution of Fas-L and Bak in the portal and periportal areas, with Bak staining also detected in the hepatic parenchyma. CONCLUSIONS: Despite clinical and genetic differences, there was a similar distribution of liver infiltrating mononuclear cells in children and adults with AH-1. These results raise the possibility of reclassifying cryptogenic chronic hepatitis by immunohistochemical analysis of infiltrating liver cells.

Protracted, but not acute, hepatitis A virus infection is strongly associated with HLA-DRB*1301, a marker for pediatric autoimmune hepatitis.

HLA alleles are known to be associated with susceptibility to develop autoimmune hepatitis (AH), and hepatitis A virus (HAV) infection is postulated as a putative trigger for AH. We investigated whether HLA may influence the outcome of the HAV infection by studying 67 children with self-limited and 39 children with protracted forms of this infection. HLA typing of the uncomplicated forms showed no significant increase of any HLA class I or II alleles. In contrast, DRB1*1301 was present in 46.1% of the children with protracted forms (vs. 9.8% in healthy controls; relative risk [RR]: 7.6; chi(2) = 33.3; P = 2 x 10(-9)). In uncomplicated hepatitis, 45% developed anti-smooth muscle antibody (SMA)/actin antibodies, but only 1 child had detectable antibodies after 3 months of infection onset. In contrast, after 1 year, 69% of the patients suffering protracted forms had titers of anti-SMA/actin antibodies that ranged between 1:40 and 1:160. Within their follow-up, 2 patients developed a Hashimoto's thyroiditis, but the remaining patients showed no signs of developing autoimmune hepatitis. We conclude that the DRB1*1301 haplotype is strongly associated with the protracted forms of HAV infection and suggest that the infection allows a sustained release of liver self-antigens. However, other still-unknown susceptibility genes are required for the full development of pediatric AH.

[HCV and HBV prevalence in hemodialyzed pediatric patients. Multicenter study]. / Prevalencia de HCV y HBV en pacientes pediátricos hemodializados. Estudio multicéntrico.

Hemodialized pediatric patients are a risk population for the hepatitis B and C virus infection. The aim of this paper was to study the serum prevalence of HBV and HCV infection in hemodialized children. We study 61 pediatric patients at hemodialisis, 12 on renal transplant, range between 2 and 20 years old (mean: 12.9 years), 23 male and 38 female. The specific anti-HCV IgC were measured by enzyme immunoassay (ELISA Abbott) and confirmed by LIA-TEK (Organon). The anti-HBV were measured by ELISA Abbott and transaminases by cinetic method (ASAT: 29 UI/L and ALT: 33 UI/L). The 19.7% of studied children were HCV (+) and 29.5% were HBV (+), 38.9% of them were HbsAg (+) and 50% anti-HBs (+). The HCV and HBV infection was more elevated in relation to the transfusion number and the hemodilisis time. The elevation of ALT/ASAT activity isn't a right infection index for HCV and HBV in this children.

[Hepatitis A virus infection in children in Argentina: a pilot study]. / Infección por virus de hepatitis A (HAV) en niños en Argentina. Ensáyo piloto.

UNLABELLED: The severity and/or the prognostic of infections with the hepatitis A virus (HAV) is related to the age at which the infection occurs. Since transmission of the virus occurs by the fecal-oral route, the prevalence and age-relate incidence of infection is determined by the adequacy of sanitation hygienic measures and the socio economic level of exposed populations. Thus, the disease is having an increasing impact in developing countries with improving sanitary standards whereas inhabitants of industrialized countries are particularly at risk while visiting under-developed countries. We have established a cooperative group for the serologic study of children range between six months to ten years old, without sintomatology of acute hepatitis. The patients live in Buenos Aires, San Justo, Trelew, Rosario and Tucumán cities. We studied 3699 children. The specific Ab-antiHAV IgG were measured by enzyme immunoassay with commercial available kits (Organon and-or Abbott). The variable of study were age, sex and water quality. RESULTS: 45.19% were of San Justo, 26.15% of Rosario, 13% of Buenos Aires, 8.37% of Trelew and 7.29% of Tucumán. We observed the highest of possibility percentage (%POS) in Tucumán (81.4%), followed by San Justo (57.8%), Rosario (46.5%), Trelew (41.99%) and Buenos Aires (29.4%). In all the cities the lowest %POS was found in children under three years old. Between three and six years old the results were variable and an increase in %POS was observed related to the growth. The global %POS was 51.56%. CONCLUSIONS: This study confirms Argentina as a high endemic country for HAV infection. A global vaccination program is the only strategy that has the potential to prevent recurrent epidemics of hepatitis A and its erradication.