Serologic and Molecular Characteristics of Hepatitis B Virus among School Children in East Java,Indonesia

Universal childhood hepatitis B vaccination was introduced in Indonesia in 1997; by 2008, coverage was estimated to be 78%. This study aimed to investigate the serologic status and virologic characteristics of hepatitis B virus (HBV) among the children in East Java. A total of 229 healthy children born during 1994–1999 were enrolled in this study. Overall, 3.1% were positive for hepatitis B surface antigen (HBsAg) and 23.6% were positive for antibody to HBsAg (anti-HBs). HBV DNA was detected in 5 of 222 HBsAg-negative carriers, which were suggested to be cases of occult HBV infection. A single amino substitution (T126I) in the S region was frequently found. HBV infection remains endemic, and the prevalence of anti-HBs remains insufficient among children in East Java, Indonesia.     

Epidemiology of hepatitis d

Hepatitis D occurs worldwide. The major victims of the hepatitis D virus (HDV) are individuals carrying the hepatitis B surface antigen (HBsAg); around 5% of the HBsAg carriers in the world are infected also by HDV. With the implementation of a hepatitis B virus (HBV) vaccination since the 1990s, the incidence of hepatitis D has consistently declined in the developed world, particularly in Southern Europe; however, immigrants from areas where HDV remains endemic are reintroducing the infection.Hepatitis D continues to ravage populations of developing and poor countries where HBV remains unchecked; action is needed to enforce HBV vaccination as effective prophylaxis not only against HBV, but against HDV as well.     

Hepatitis D outbreak among children in a hepatitis B hyper‐endemic settlement in Greenland

Summary. Hepatitis B virus (HBV) infection is endemic in Greenland with 5–10% of the population being HBsAg‐positive (chronic carriers). Surprisingly, despite of the high prevalence of HBV infection, acute and chronic hepatitis B, liver cirrhosis and primary hepatocellular carcinoma appear much less frequently than expected. The reasons for the low frequencies are unknown, but as a consequence implementation of a childhood HBV vaccination programme, though debated for years, has never been instituted. We describe an outbreak of hepatitis D (HDV) infection among children in a hepatitis B hyper‐endemic settlement of 133 inhabitants on the west coast of Greenland. In 2006 a total of 27% of the inhabitants were HBsAg‐positive (chronic carriers) and 83% were HBcAb‐positive (previously exposed). Forty‐six percent of the HBsAg‐positive persons were below 20 years of age. On follow‐up 1 year later a total of 68% of the HBsAg‐positive persons were HDV‐IgG positive. Five children, who were HBsAg‐positive in 2006, had HDV‐seroconverted from 2006 to 2007, indicating a HDV‐super‐infection. Most of the HDV‐IgG positive children had markedly elevated liver enzymes. In the multivariate analysis, among the HBV and HDV markers, presence of HDV‐IgG was most strongly associated with elevation of liver enzymes. In conclusion, the HBV‐HDV super‐infection and presumed HDV outbreak in this settlement challenges the notion that HBV infection may not be as harmless in Greenland as previously anticipated. The findings strongly suggest that HBV vaccination should be included in the child‐immunization program in Greenland.     

Secular trend of the viral genotype distribution in children with chronic hepatitis B virus infection after universal infant immunization

Genotypes B and C are the major hepatitis B virus (HBV) genotypes in Taiwan, and genotype C is associated with more severe liver disease than genotype B. Whether the implementation of the hepatitis B immunization program has affected the secular trend of the HBV genotype distribution remains unknown. We thus investigated the HBV genotypes in hepatitis B surface antigen (HBsAg)-carrier children born before the implementation of the universal infant immunization program and in those born afterward. One hundred seven children who were infected with HBV despite appropriate immunization were enrolled as immunized cases with HBV breakthrough infection. Each case was matched with two unimmunized HBsAg carriers according to the age at enrollment. HBV genotypes were determined with molecular methods. Compared with unimmunized HBsAg carriers, more immunized children had HBsAg-positive mothers (65.9% versus 100%, P < 0.001) and were infected with genotype C (16.4% versus 42.1%, P < 0.001). Among the children born to HBsAg-positive mothers, the mothers' and children's HBV genotypes were highly concordant in both unimmunized [κ = 0.97, 95% confidence interval (CI) = 0.90-1.00] and immunized children (κ = 0.97, 95% CI = 0.92-1.00). After adjustments for gender, maternal age, and delivery mode, immunized HBsAg-carrier children born to HBsAg-positive mothers had a higher likelihood of genotype C infection than unimmunized children (odds ratio = 3.03, 95% CI = 1.62-5.65, P = 0.001). However, the increased genotype C to genotype B ratio was not seen in the HBsAg-carrier mother pool in the postimmunization era. CONCLUSION: In the postimmunization era, most HBV breakthrough infections are due to maternal transmission, and immunized children born to genotype C mothers may have a higher rate of breakthrough infection than those born to genotype B mothers.     

Changing epidemiology of HBV infection in Danish children

Hepatitis B continues to be a worldwide threat to human health, especially if infection occurs in childhood. Universal vaccination is recommended by WHO, but has not been implemented in the Scandinavian countries, Holland and UK, because of a low incidence rate. However, clinically overt infections are rare in childhood. We therefore performed a nation wide serosurvey for HBV markers in 2428 children aged primarily 6-16 years from 16 primary schools in Denmark. Anti-HBc was found in altogether 20 children (0.8%), 12 of whom were among 144 immigrant children (8.3%) compared to 8 (0.4%) in those born in Denmark. Three of the children, all immigrants, were HBsAg positive indicating chronic infection. At school level no relation of anti-HBc in Danish born children was found to schools with high number of immigrant children or schools with HBsAg positive children indicating a low risk of Hepatitis B transmission in this setting. The results do not support implementation of general vaccination, but stress the need for HBV screening in immigrants as it provides a mean for immunization of close contacts at risk and information on prevention.     

Impact of the implementation of a vaccination strategy on hepatitis B virus infections in China over a 20-year period

Hepatitis B virus (HBV) vaccination has been recommended for all neonates in China since 1992. This article reviews the impact of HBV vaccination throughout the past 20 years in China. Before the introduction of the HBV vaccination program, approximately 9.8% of the general Chinese population tested positive for hepatitis B virus surface antigen (HBsAg). Since 1992, vaccination coverage has increased each year. In 1999, a National Expanded Programme on Immunization (EPI) review showed that the immunization coverage with three doses of HBV vaccine was 70.7%, and reached 99.0% in Beijing. The HBsAg carrier rate in the general population decreased to 7.2% in 2006. In particular, the prevalence of HBsAg decreased to 2.3% among children aged 5-14 years and to 1.0% among children younger than 5 years. In addition, the administration of the HBV vaccine may have reduced the risk of hepatocellular carcinoma among adults. Despite the administration of hepatitis B immunoglobulin and the HBV vaccine to children with HBsAg-positive mothers, the failure rate of HBV immunoprophylaxis was 5-10%. In China, vaccine failure was related to HBV S gene mutation and inadequate administration of HBV vaccine. The prevalence of HBV carriers in China was markedly reduced after the introduction of the universal HBV vaccination program. If we immunize all susceptible individuals with the hepatitis B vaccine (especially children), interrupt transmission, and provide antiviral treatment for existing HBV carriers, the number of new cases may be reduced to close to zero in the future and this may eventually result in the eradication of HBV.     

Hepatitis B virus vaccination and antenatal transmission of HBV markers to neonates

The high prevalence of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in pregnant women is considered to be the most important factor contributing to the high carrier rate of HBsAg in some populations. Several factors, including the age at which infection occurs, predispose to the acquisition and frequency of the carrier state. The proportion of infected people who become chronic carriers ranges from about 80 to 95% for babies born to HBsAg/HBeAg-positive mothers. In this study of Indonesian infants receiving only active immunization against HBV, we measured the HBV markers passively acquired from their HBsAg-positive mothers. The relationship of these markers with vaccination response and with HBV infection status was studied longitudinally in the infants. In the exposed neonates from the HBsAg-positive mothers (n=61), the seroconversion rate to hepatitis B surface antibody (HBsAb) positivity was 95% after the first booster vaccination, with a geometric mean titre (GMT) of 2017 IUl-1. After 60 months, the GMT in this group decreased to 50 IUl-1. Four newborns in this group became HBsAg carriers. Of the four vaccination failures, three newborns were HBsAg/HBeAg positive at birth, suggesting that they had been infected in utero. No vaccination strategy (active alone, or passive/active) can prevent this transmission from occurring. One carrier was HBsAg negative at birth and up to month 4 but was HBsAg positive at month 12 and subsequently, suggesting a postnatal infection. Vaccination early in life can, to a large extent, prevent perinatal transmission and hepatitis B virus (HBV) infection later in infancy and childhood. In this study, the protective efficacy of the vaccination was 85% in the subcohort of neonates from HBeAg-positive mothers and 100% in the subcohort of neonates from HBeAg-negative mothers. Lack of maternal antibodies to hepatitis B core antigen (HBcAb) correlated strongly with transmission of HBV infection.     

Immunoprophylaxis of infection with hepatitis B virus in infants born to hepatitis B surface antigen-positive carrier mothers

Infants born to carrier mothers positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) received 5 micrograms of hepatitis B virus (HBV) vaccine on four occasions. Group 1 received vaccine only, group 2 received vaccine plus hepatitis B immune globulin (HBIG) at birth, and group 3 received vaccine plus HBIG at birth and at one month. Infants born to HBeAg-positive mothers (group 4) received a reduced dose of vaccine (2.5 micrograms) on three occasions as well as HBIG at birth. As compared with 78.4% of the control group (infants whose parents refused vaccination) who became chronic HBV carriers at the age of 14 months, the protective efficacy rate of vaccination was 75.3% in group 1,85.5% in group 2,89.7% in group 3, and 87.2% in group 4. HBV vaccine (5 micrograms) was also given to infants born to HBsAg-positive, HBeAg-negative mothers on four on four occasions. The antibody response to HBsAg in vaccine recipients was 12% after the first dose, 44% after the second dose, and 75% and 100% at six months and 1.5 years of age, respectively.     

Difference in prevalence of hepatitis B markers in children born either in Sweden or in Turkey of Assyrian immigrants

Sera from 95 children below 20 years of age born to Assyrian immigrants were tested for markers for hepatitis B virus (HBV). HBV markers were found in 26% of the study population. However, no markers were demonstrated in children born in Sweden. Of the 62 children born in Turkey or the Middle East 39% had HBV markers and 4 (6.5%) had HBsAg. Three of the 4 HBsAg+ children had anti-HBe and 1 HBeAg. These results suggest that the transmission of HB in Assyrians may be mainly horizontal rather than vertical. Children of Assyrian immigrants born in Sweden do not seem to constitute a risk group for transmission of HB, whereas those born in Turkey or the Middle East constitute the same risk as reported in a general population of Turks.     

Hepatitis B Surface Antigen Seroprevalence among Children in Papua New Guinea, 2012–2013

Approximately 8% of the population in Papua New Guinea (PNG) has chronic hepatitis B virus (HBV) infection. To decrease the burden of chronic HBV infection, a national 3-dose infant hepatitis B vaccination program was implemented starting in 1989, with a birth dose (BD) added to the schedule in 1992. To assess the impact of the hepatitis B vaccination program, we conducted a serosurvey among children born after vaccine introduction. During 2012–2013, a cross-sectional stratified four-stage cluster survey was conducted to estimate hepatitis B surface antigen (HBsAg) prevalence among children 4–6 years of age. We collected demographic data, vaccination history, and tested children for HBsAg. Of 2,133 participants, 2,130 children had vaccination data by either card or recall: 28% received a BD; 81% received ≥ 3 vaccine doses. Of 2,109 children providing a blood sample, 60 (2.3%) tested positive for HBsAg. This is the largest, most geographically diverse survey of hepatitis B vaccination and HBsAg seroprevalence done in PNG. Progress has been made in PNG toward the Western Pacific Regional goal to reduce the prevalence of chronic HBV infection to < 1% by 2017 among 5-year-old children. Vaccination efforts should be strengthened, including increasing BD coverage and completing the 3-dose series.     

Elimination of new chronic hepatitis B virus infections: results of the Alaska immunization program

An immunization assessment and a serologic survey were conducted to evaluate the effectiveness of a hepatitis B immunization program in eliminating hepatitis B virus (HBV) transmission among Alaska Natives in a region in which HBV infection is endemic. Hepatitis B vaccine coverage was 93% among 567 children 相似文献   

Effectiveness of hepatitis B vaccination in babies born to hepatitis B surface antigen-positive mothers in Italy

This study examined 522 children born to hepatitis B surface antigen (HBsAg)-positive mothers from 1985 through 1994 and evaluated the protection provided by anti-hepatitis B virus (HBV) immunization at birth. Babies were given hepatitis B immunoglobulin and hepatitis B vaccine at birth. At 5-14 years after immunization, 17 children (3.3%) were anti-HB core antigen positive, and 3 also were HBsAg positive. One carrier child had a double mutation, with substitution of proline-->serine at codons 120 (P120S) and 127 (P127S) within the a determinant of HBsAg. Of the 522 children, 400 (79.2%) of 505 still had protective anti-HBsAg titers > or =10 mIU/mL. Thus, HBV vaccination of children born to HBsAg-positive mothers is effective and confers long-term immunity. There is no evidence that the emergence of HBV escape mutants secondary to the immune pressure against wild-type HBV is of concern.     

Combined passive and active immunization for interruption of perinatal transmission of hepatitis B virus in Taiwan

We attempted a clinical trial to interrupt transmission of hepatitis B virus (HBV) infection from hepatitis B surface antigen (HBsAg) positive and hepatitis Be antigen (HBsAg) positive mothers to their infants in Taiwan. Screening of 5,595 pregnant women revealed that 856 (15.3%) were HBsAg positive. Three hundred and sixty-one (42.2%) of the HBsAg positive pregnant women were HBeAg positive. Infants born to HBsAg and HBeAg positive mothers were randomized into 3 groups to receive the HBV vaccine alone or combined with hepatitis B immune globulin (HBIG). HGV vaccine was given at 2, 6, and 10 weeks after birth. Group I received HBV vaccine alone while Group II received HBV vaccine in combination with HBIG at birth and group III received HBV vaccine plus HBIG at birth and again at one month old. Group IV constituted the control group when their parents refused vaccination. At 6 months of age, the HBV carrier rate was 23.7% (9/38) in Group I, 11.1% (4/36) in Group II, and 5.3% (2/38) in Group III infants. Compared with 90% of infants who became HBV carriers in the control group (Group IV), the efficacy of HBV vaccination in preventing HBV infection among these high risk infants at the 6th month was 73.7% in Group I, 87.7% in Group II, and 94.1% in Group III. The antibody to HBsAg (anti-HBs) positivity rate in sera of Group I, II, III infants at 6 months of age was 79.0%, 88.9% and 94.7%, respectively. These initial results indicate that combined passive and active immunization is efficacious in interrupting perinatal transmission of HBV infection.     

Persistent and transient hepatitis B virus (HBV) infections in children born to HBV‐infected mothers despite active and passive vaccination

Summary. Combined passive and active immunization for newborns very effectively prevents perinatal hepatitis B virus (HBV) infections. In the Netherlands, babies born to hepatitis B surface antigen (HBsAg)‐positive women receive passive immunization with hepatitis B and at least three active HBsAg vaccinations. Serological testing for the presence of HBV markers was offered for all infants born to HBsAg‐positive mothers between January 2003 and July 2007, after completion of their vaccination schedule. About 75% of the infants (n = 1743) completed their HB‐vaccination schedule and participated in the serologic evaluation. Twelve of them (0.7%) were found to be HBV infected. Furthermore, we identified three older children with high levels of anti‐HBc, anti‐HBs and anti‐HBe, while they were HBsAg and HBV DNA negative. This serologic profile is evidence for a resolved HBV infection. In the group of older children (1.5–5 years of age, n = 728), about half of the HBV‐infected children (3 of 7) had already cleared their infection at the time of sampling. For a proper evaluation of the efficacy of a new intervention programme to prevent vertical HBV transmission, it is also important to analyse the HBV markers in serum collected when the children are older than 1.5 years. In a programmatic setting, all children born to HBV‐infected mothers should be tested not only for the level of anti‐HBs but also for the absence of HBsAg, because 2 of the 12 HBV‐infected children (17%) had a high level of anti‐HBs.     

Impact of hepatitis B virus infection on women and children.

HBV infection acquired during infancy and early childhood has a high likelihood of progressing to chronic infection, which can lead to chronic hepatitis, cirrhosis, and primary hepatocellular carcinoma. In areas of the world where HBV infection occurs predominantly in infants and young children, routine infant immunization with hepatitis B vaccine is the most appropriate vaccination strategy. In the United States, the majority of HBV infections occur in adults with behaviors or occupations that put them at risk for HBV infection. Nevertheless, infection acquired during infancy and early childhood contributes significantly to the burden of chronic liver disease in the United States. Until recently, the vaccination strategy in the United States has included HBsAg screening of pregnant women and vaccination of infants born to infected women and vaccination of people in groups at high risk for HBV infection. Because of the difficulties in accessing and vaccinating persons from high-risk groups and the recent findings that HBV infection occurs more commonly among children in some groups in the United States than previously appreciated, the Immunization Practices Advisory Committee of the US Public Health Service and the American Academy of Pediatrics in 1991 endorsed a strategy of universal immunization of infants for hepatitis B. This strategy has the advantages of accessing infants in the United States through preexisting vaccine delivery systems and vaccinating individuals prior to their engaging in high-risk behavior. Continued screening of pregnant women for HBsAg is necessary to prevent perinatal HBV transmission and to identify for vaccination those household and sexual contacts of HBV carriers, a group that is also at high risk of HBV infection.     

Natural history of hepatitis B virus infection in children

Hepatitis B virus (HBV) infection during childhood can cause acute, fulminant or chronic hepatitis, liver cirrhosis, and liver cancer. Approximately 90% of the infants of hepatitis B e antigen (HBeAg) seropositive mothers become hepatitis B surface antigen (HBsAg) carriers. Children chronically infected are mostly asymptomatic. Although liver damage is usually mild during childhood, severe liver disease, including cirrhosis and hepatocellular carcinoma, may develop insidiously for 2–7 years. Spontaneous HBeAg seroconversion occurs gradually as the age of the child increases. Viral replication is reduced during this process, which is usually preceded by an elevation of aminotransferases. In a long‐term follow‐up study, the annual HBeAg seroconversion rate was 4–5% in children older than 3 years of age and less than 2% in children under 3 years. The annual seroconversion rate of HBsAg was very low (0.56%). Age at infection, maternal HBsAg and HBeAg status, host immune status, and possibly the HBV strain are the main factors determining the course of HBV infection in children.     

Hepatitis B virus markers in Japanese immigrants and their descendants in Bolivia and native Bolivians

A survey of hepatitis B virus (HBV) markers of Japanese immigrants, their descendants and native Bolivians was performed in two agricultural settlements in Bolivia. The prevalence of HBV markers in sera, either hepatitis B surface antigen (HBsAg) or its antibody (HBsAb), was higher in the Japanese (46.4%) than in the native Bolivian (12.9%) adult generations of both colonies. There was no significant difference between Japanese (4.3%) and Bolivian (0.9%) school children in one colony, but a high percentage (32.6%) was recognized among Japanese children in the other colony. The numbers of adw subtypes were unexpectedly high among these HBsAg positive Japanese children, compared to those in Japan. Antibody to hepatitis delta virus (HDV) was detected in one case. These data suggested that although horizontal transmission of adw HBV had occurred within the Japanese population, HBV and HDV were not endemic to this geographic area.     

Severe liver disease is caused by HBV rather than HCV in children with hematological malignancies

Patients receiving chemotherapy experience exacerbations of chronic hepatitis B (HBV) or hepatitis C (HCV) viral infections. We examined the pattern of liver disease induced by these infections in 92 children and adolescents with elevated transaminases (median age: 9 years). This included 76 with hematological malignancies (55 ALL, 15 NHL and six Hodgkin's disease) and 16 with thalassemia major. Liver disease was graded: A--occasional hypertransaminemia, B--persistent hypertransaminemia, C--severe hepatitis without encephalopathy, D--fulminant hepatic failure (FHF) and death. Screening included HBsAg, anti-HCV antibody, HBV-DNA and HCV-RNA: 26 had liver biopsies. A total of 60 (79%) patients with malignancies were HBsAg and/or HBV-DNA(+)(genotype D-E) and 47 (62%) were anti-HCV and/or HCV-RNA(+); 33 were coinfected with HBV and HCV. Grade A (n=24) included 16 with HCV and 12 with HBV (six coinfected); 18 with HBV and 11 with HCV (10 coinfected) were graded B (n=22). All grade C (n=25) had HBV with 16 HCV coinfected. FHF and death occurred in five HBV-DNA(+) patients, in four within a month of i.v. methotrexate. Patterns C and D were associated with HBsAg and HBV-DNA (P=0.001 and P<0.001, respectively). In all, 70% of HBV-infected children suffered chemotherapy-associated flares. None of the thalassemics had severe hepatitis exacerbations; 94% had HCV markers with none HBV-DNA(+). One died of progressive cirrhosis. CONCLUSIONS: Children with hematological malignancies have worse liver disease when associated with chronic HBV. FHF occurred in HBsAg/HBV-DNA(+) children following i.v. methotrexate. Early recognition of hepatic dysfunction in HBV carriers is essential in order to reduce incidence of life-threatening complications.     

Source of transmission in children with chronic hepatitis B infection after the implementation of a strategy for prevention in those at high risk

Aim: In order to clarify the sources of chronic HBV (hepatitis B virus) infection in children after the implementation of an “at‐risk” strategy in Japan, chronically infected children were assessed. In addition, chronically infected children born to HBsAg‐negative mothers and their family members were assessed to identify the sources of HBV transmission. Methods: Fifty‐seven children who tested HBsAg‐positive after the initiation of a mother‐to‐child transmission prevention program were enrolled in this study. The full‐genome HBV DNA sequence was analyzed to confirm the transmission sources. Results: Of the 57 patients, 37 (65%) were born to HBV carrier mothers. The remaining 20 (35%) patients were born to HBsAg‐negative mothers. Fourteen of these patients had HBV carrier fathers, and 2 patients, who were siblings, did not have an HBV carrier father. The remaining 4 patients had no family members with HBV infection. Phylogenetic tree analysis confirmed that father‐to‐child transmission and sibling‐to‐sibling transmission occurred in 3 families and 1 family, respectively. Conclusion: Although vaccine failure of mother‐to‐child transmission was the major cause of chronic HBV infection in children, father‐to‐child transmission was the second most common mode of transmission. In addition, sibling‐to‐sibling transmission was found. Unless at‐risk individuals and groups can be accurately identified to prevent horizontal transmission, the introduction of universal vaccination is essential for achieving the elimination of HBV infection in Japan.