Antibody persistence and immune memory in adults, 15 years after a three-dose schedule of a combined hepatitis A and B vaccine

A combined hepatitis A and B vaccine is available since 1996. Two separate open‐label primary studies evaluated the immunogenicity and safety of this hepatitis A and B vaccine (720 EI.U of HAV and 20 µg of HBsAg) in 306 healthy subjects aged 17–43 years who received three doses of the vaccine following a 0, 1, and 6 months schedule. These subjects were followed up annually for the next 15 years to evaluate long‐term persistence of anti‐HAV and anti‐HBs antibodies. The subjects whose antibody concentrations fell below the cut‐offs between Year 11 and Year 15 (anti‐HAV: <15 mIU/ml; anti‐HBs: <10 mIU/ml) were offered an additional dose of the appropriate monovalent hepatitis A and/or B vaccine. In subjects who received the additional vaccine dose, a blood sample was collected 1 month after vaccination. At the Year 15 time point, all subjects in Study A and Study B were seropositive for anti‐HAV antibodies and 89.3% and 92.9% of subjects in the respective studies had anti‐HBs antibody concentrations ≥10 mIU/ml. Four subjects (two in each study) received an additional dose of monovalent hepatitis B vaccine and mounted anamnestic responses to vaccination. No vaccine‐related serious adverse events were reported. This study confirms the long‐term immunogenicity of the three‐dose regimen of the combined hepatitis A and B vaccine, as eliciting long‐term persistence of antibodies and immune memory against hepatitis A and B for up to at least 15 years after a primary vaccination. J. Med. Virol. 84:11–17, 2011. © 2011 Wiley Periodicals, Inc.     

Predicted 30‐year protection after vaccination with an aluminum‐free virosomal hepatitis A vaccine

Few studies have examined the duration of protection following vaccination against hepatitis A virus (HAV) with currently licensed HAV vaccines. This study explored the long‐term immunogenicity in individuals vaccinated with the virosomal hepatitis A virus, Epaxal®. Adult volunteers (N = 130) previously enrolled into four different studies between 1992 and 1994 and who had completed a 0/12‐month immunization regimen (primary and booster dose) were asked to participate in this follow‐up study. Yearly anti‐HAV titers up to 6 years following booster vaccination, and then once 9–11 years after booster were measured using two assays, Enzygnost® and AxSYM® HAVAB 2.0. Based on the Enzygnost® assay, the seroprotection rate 9–11 years after booster was 100%, with a geometric mean concentration (GMC) of anti‐HAV antibodies of 526 mIU/ml. Females had markedly higher GMCs than males (741 mIU/ml vs. 332 mIU/ml). Using an anti‐HAV cut‐off titer of ≥10 mIU/ml, a linear mixed mathematical model predicted a median duration of protection of 52.1 years. A duration of protection ≥35.7 years was predicted for 95% of subjects. A more stringent cut‐off of ≥20 mIU/ml shortened the median predicted duration of protection to 45.0 years. In conclusion, a two‐dose Epaxal® vaccination regimen confers in healthy adults a real‐time protection of at least 9–11 years; this protection is predicted to last at least 30 years in over 95% of individuals. Further studies are necessary to assess the real duration of seroprotection and whether an additional booster is necessary later. J. Med. Virol. 82:1629–1634, 2010. 2010 Wiley‐Liss, Inc.     

新生儿单纯乙型肝炎血源疫苗的免疫持久性和远期保护效果

目的 掌握我国新生儿单纯接种乙型肝炎血源疫苗后的免疫持久性和远期预防效果；观察新生儿免疫较长时间后是否需加强免疫。方法 在湖南湘潭市等4个乙型肝炎疫苗试点区间，对1986－1988年出生并接种乙型肝炎血源疫苗的新生儿，连续14－15年按免疫儿年龄分层随机抽样采血随访，累计随访21680人次，观察免疫儿HBsAg、抗－HBs和抗－HBc的动态变化。结果 新生儿单纯乙型肝炎血源疫苗全程基因免疫后，在15年随访中没有加强免疫，各试点区免疫儿童HBsAg携带率低于1．66％，携带率没有随免疫后的延长而增加；阻断HBV慢性感染的效果持续在90％左右（95％可信限为：83．1％－97．2％）；免疫后不同年限间HBsAg携带率、HBV感染率和保护效果差异均无显著性（P＞0．05）。免疫儿抗－HBs阳性率随免疫后年限延长而逐年明显下降，至第9－10年下降为40％－50％，之后数年内下降幅度不大，至免疫后13－14年抗－HBs阳性率维持在30％－42％；抗－HBs滴度下降了90％。结论 新生儿单纯乙型肝炎疫苗接种后抗－HBs阳性率与滴度的下降不影响其远期预防效果；就群体而言，新生儿及时完成全程免疫后，无需加强免疫可有效阻断HBV感染后成为HBsAg慢性携带者，而很有可能终生受益。     

Vaccination against hepatitis B virus at the Lyon Pasteur Institute. A seven-year evaluation]

Results of immunization against hepatitis B among Pasteur Institute staff members are reported. Prior to immunization, 439 subjects were tested for hepatitis B virus (HBV) markers, including HBs antigen, anti-HBs antibody, and anti-HBc antibody (Ausria, Ausab, Corab assays; Abbott). Forty-seven subjects tested positive for anti-HBs antibody. 317 subjects negative for all the HBs markers studied were given three intramuscular doses of Hevac B (Pasteur vaccins) at one-month intervals. Anti-HBs antibodies were assayed after the third injection with the following results: mean titer, 1,454 mIU/ml, standard deviation, 5,349 mIU/ml, and range, 4 to 41,100 mIU/ml. Anti-HBs titers above 10 mIU/ml were found in 879.4% of subjects. Non-responders and weak responders (anti-HBs titer under 10 mIU/ml) were given a fourth dose of vaccine. Ultimately, after the last (third of fourth) injection 97.6% of subjects had protective antibody titers. No case of HBV infection was seen during the seven-year follow-up period.     

Antibody persistence and immune memory in healthy adults following vaccination with a two-dose inactivated hepatitis A vaccine: long-term follow-up at 15 years

Long‐term persistence of vaccine‐induced immune response in adults was assessed annually for 15 years following primary immunization with a two‐dose inactivated hepatitis A vaccine. In 1992, 119 and 194 subjects aged 17–40 years and naïve for hepatitis A virus (HAV) were enrolled in two studies to receive 1,440 ELISA units (El.U) of inactivated hepatitis A vaccine (Havrix?, GlaxoSmithKline Biologicals, Belgium) according to a standard 0, 6 or an extended 0, 12 months schedule, respectively. Serum samples were taken 1 month after the second vaccine dose and every consecutive year up to 15 years after primary vaccination for measurement of anti‐HAV antibody concentrations (NCT00291876 and NCT00289757). At year 15, 100% (48/48) and 97.3% (108/111) of subjects vaccinated at 0, 6 or 0, 12 months remained seropositive for anti‐HAV antibodies, with geometric mean concentrations (GMCs) of 289.2 and 367.4 mIU/ml, respectively. An additional dose of HAV vaccine (1,440 El.U) was administered to the six subjects who had become seronegative for anti‐HAV antibodies since year 11. All subjects mounted a humoral immune response to the additional HAV challenge dose, although post‐challenge anti‐HAV antibody levels remained low in one subject. These studies represent the longest annual follow‐up of hepatitis A vaccine in healthy adults. The immune response induced by two doses of this inactivated HAV vaccine was shown to persist for at least 15 years. No difference in long‐term antibody persistence was observed between the two primary vaccination schedules, reinforcing the potential for flexibility in the timing of the second primary vaccine dose. J. Med. Virol. 83:1885–1891, 2011. © 2011 Wiley‐Liss, Inc.     

Association between polymorphisms of the cytokine and cytokine receptor genes and immune response to hepatitis B vaccination in a Chinese Han population

The immune response to hepatitis B vaccination varies among individuals. It has been reported that polymorphisms in cytokine and cytokine receptor genes are associated with these individual differences. The aim of the current study was to investigate the association between polymorphisms of the Th1/Th2 cytokine and cytokine receptor genes and the response to hepatitis B vaccination in a Chinese Han population. A total of 10 single nucleotide polymorphisms distributed in 6 genes (TNFRSF1A, IL12A, IL12B, IFNG, IL4, and IL10) were genotyped in 214 high‐responders [hepatitis B surface antibody (anti‐HBs) ≥1,000 mIU/ml] and 107 low‐responders (anti‐HBs: 10–99 mIU/ml). The minor CTCTAA allele of rs17860508 in the IL12B gene was associated with a low response to hepatitis B vaccination (P = 0.039, odds ratio = 1.41, 95% confidence interval = 1.00–1.99). In addition, a significant gene–gene interaction was found: the frequency of the combined genotypes IL12A rs2243115 TT and IL12B rs17860508 CTCTAA/CTCTAA was significantly higher in the low‐response group than in the high‐response group (P = 0.008, odds ratio = 2.19, 95% confidence interval = 1.23–3.93). These findings suggest that polymorphisms in the IL12A and IL12B genes might play an important role jointly in determining the response to hepatitis B vaccination. J. Med. Virol. 84:26–33, 2011. © 2011 Wiley Periodicals, Inc.     

国产甲型肝炎灭活疫苗的安全性和免疫原性研究

目的 评价一种国产甲型肝炎（甲肝）灭活疫苗对人体的安全性和免疫原性。方法 为Ⅰ期临床试验。31名对甲肝易感的成年人被随机分为两组，实验组16个，接种国产甲肝灭活疫苗，对照组15人，接种史克必成公司生产的甲肝灭活疫苗。按0、3程序进行接种。国产疫苗剂量为每针1000U／0．5ml，史克疫苗剂量为每针720ELISAU／1ml。观察并比较两种接种后的局部和全身反应以及接种后1、3、4个月血清抗体阳转率和滴率。结果 两组初免和加强接种后个别接种对象表现轻微局部或全身反应，未发现肝功能损害。初次免疫后1个月、3个月和加强后1个月，国产疫苗的抗体阳转率分别为94％，100％和100％；史克疫苗为73％，80％和100％。国产疫苗抗体几何平均滴度分别为139．2mIU/ml、137．7mIU/ml和1066．7mIU/ml；史克必成疫苗分别为104．3mIU/ml、111．3mIU／ml和760．7mIU／ml。结论 国产甲肝灭活疫苗具有良好的安全性和免疫原性。     

Hepatitis B Virus Antibody Levels 7 to 9 Years after Booster Vaccination in Alaska Native Persons

Hepatitis B antibody persistence was assessed in individuals who had previously received a vaccine booster. We measured hepatitis B surface antigen antibody (anti-HBs) levels 7 to 9 years post-hepatitis B booster in individuals with primary vaccination at birth. While 95 (91.3%) of 104 participants had detectable anti-HBs (minimum, 0.1 mIU/ml; maximum, 1,029 mIU/ml), only 43 (41%) had protective levels of ≥10 mIU/ml. Pre- and week 4 postbooster anti-HBs levels were significant predictors of hepatitis B immunity at follow-up (P < 0.001). Almost all participants had detectable anti-HBs 7 to 9 years after the hepatitis B vaccine booster, but less than half had levels ≥10 mIU/ml.     

Randomized trial of the immunogenicity and safety of the Hepatitis B vaccine given in an accelerated schedule coadministered with the human papillomavirus type 16/18 AS04-adjuvanted cervical cancer vaccine

The human papillomavirus type 16/18 (HPV-16/18) AS04-adjuvanted cervical cancer vaccine is licensed for females aged 10 years and above and is therefore likely to be coadministered with other licensed vaccines, such as hepatitis B. In this randomized, open-label study, we compared the immunogenicity of the hepatitis B vaccine administered alone (HepB group) or with the HPV-16/18 AS04-adjuvanted vaccine (HepB+HPV group) in healthy women aged 20 to 25 years (clinical trial NCT00637195). The hepatitis B vaccine was given at 0, 1, 2, and 12 months (an accelerated schedule which may be required by women at high risk), and the HPV-16/18 vaccine was given at 0, 1, and 6 months. One month after the third dose of hepatitis B vaccine, in the according-to-protocol cohort (n = 72 HepB+HPV; n = 76 HepB), hepatitis B seroprotection rates (titer of ≥10 mIU/ml) were 96.4% (95% confidence interval [CI], 87.5 to 99.6) and 96.9% (CI, 89.2 to 99.6) in the HepB+HPV and HepB groups, respectively, in women initially seronegative for anti-hepatitis B surface antigen (HBs) and anti-hepatitis B core antigen (HBc). Corresponding geometric mean titers of anti-HBs antibodies were 60.2 mIU/ml (CI, 40.0 to 90.5) and 71.3 mIU/ml (CI, 53.9 to 94.3). Anti-HBs antibody titers rose substantially after the fourth dose of hepatitis B vaccine. All women initially seronegative for anti-HPV-16 and anti-HPV-18 antibodies seroconverted after the second HPV-16/18 vaccine dose and remained seropositive up to 1 month after the third dose. Both vaccines were generally well tolerated, with no difference in reactogenicity between groups. In conclusion, coadministration of the HPV-16/18 AS04-adjuvanted vaccine did not affect the immunogenicity or safety of the hepatitis B vaccine administered in an accelerated schedule in young women.     

Hepatitis B vaccination in patients with chronic hepatitis C.

The aim of the study was to evaluate the safety, immunogenicity, and possible therapeutic effect of hepatitis B vaccine in patients with chronic hepatitis C. The subjects studied included three groups: group I, 26 patients with chronic hepatitis C who were susceptible to hepatitis B virus infection; group II, 35 healthy subjects who were susceptible to both hepatitis B and hepatitis C virus infection; and group III, 30 patients with chronic hepatitis C receiving no hepatitis B vaccination as controls. Three 20 microg/dose of recombinant hepatitis B vaccines were given to subjects of groups I and II in months 0, 1, and 6. Blood samples from the subjects were collected before and 1 month after each dose of vaccination for serological testing. The subjects of groups I and II had similar antibody to hepatitis B surface antigen (anti-HBs) response rates after the first (30.8% vs. 17.1%), second (61.5% vs. 60.0%), and third (88.5% vs. 91.4%) doses of vaccination. Also, their geometric mean titers of anti-HBs did not differ much when vaccination completed in 7 months (360 vs. 581 mIU/ml). During vaccination period, patients with chronic hepatitis C demonstrated no significant change of serum cytokines and HCV RNA levels, but significantly lowered ALT levels after three doses of vaccination. Hepatitis B vaccination is safe and immunogenic in patients with chronic hepatitis C. It did not significantly affect their levels of HCV RNA, but tended to lower ALT levels.     

Clinical safety and efficacy of first indigenous recombinant hepatitis B vaccine

A pilot study was conducted to assess the clinical safety and immunogenicity of an indigenously developed recombinant hepatitis B vaccine (Shanvac B) in 18 healthy adults. 20 microg of vaccine was administered at 0, 1 and 2 months. Protective anti HBs titres developed in 22%, 77% and 100% one month after 1st, 2nd and 3rd dose of vaccination, respectively. The geometric mean titre after the 3rd dose was 1015.29 mIu/ml. The vaccine was well tolerated with minor local and systemic side effects in 28% and 22%, respectively. The indigenously developed recombinant hepatitis B vaccine is safe, well tolerated and highly immunogenic.     

Reactivity and immunogenicity of Engerix B, the recombinant DNA vaccine against hepatitis B

A group of 67 health workers with no markers indicating previous hepatitis B infection were vaccinated against hepatitis B with a new DNA recombinant vaccine, Engerix B (commercially manufactured by Smith-Kline-RIT, Belgium). Three injections were given according to the 0-1-6 schedule. One month after the last injection the vaccinees were tested for anti-HBs antibodies by the enzyme-linked assay. Antibody titers equal or less than 10 mIU/ml were found only in three subjects or in 4.5% of them. Titers ranging from 11 to 99 mIU/ml were found in 7 subjects (10.4%), from 100 to 999 mIU/ml in 28 (41.8%) and those equal or more than 1000 mIU/ml in 29 subjects (43.3%). It is inferred that the seroconversion rate is 95.5%. Only one subject did not develop detectable antibodies but three subjects had titers over 10000 mIU/ml. No one developed overt hepatitis B during the trial nor did the high responders experienced inapparent infections. They were tested for anti HBc with negative results. Postvaccinal reactions were mild and almost exclusively local. There were no complications. For its high immunogenicity and acceptable reactogenicity the Engerix B vaccine has a promising future.     

HBsAg阳性儿童和健康儿童对国产甲型肝炎灭活疫苗免疫原性和安全性的观察

目的：观察HBsAg阳性儿童对国产甲型肝炎灭活疫苗的免疫原性和安全性。方法：随机选取121名1－10岁健康儿童和10名同龄的HBsAg阳性儿童，抗－HAV均阴性，接种唐山怡安生物工程有限公司研制的甲型肝炎灭活疫苗。接种剂量为500U／剂和1000U／剂两组，免疫程序为0和6个月，并在初免后30d，第二针后30和180d用ELISA方法检测抗－HAV。结果：HBsAg阳性儿童和健康儿童接种500U／剂和1000U／剂甲型肝炎灭活疫苗后抗体阳转率均为100％。第二针免疫后30d抗体平均几何滴度500U／剂组分别为4684．9mIU和4535．6mIU；1000U／剂组分别为5399．8mIU和7347．1mIU。二者比较差异无显著性，免疫后亦未见异常反应，初免后1年抗体水平仍然很高。结论：HBsAg阳性儿童接种国产甲型肝炎灭活疫苗具有良好的免疫应答，同时也是安全的。     

Humoral and Cellular Responses to a Single Dose of Fendrix in Renal Transplant Recipients with Non‐response to Previous Hepatitis B Vaccination

Approximately 70% of kidney transplant recipients are non‐responders to conventional hepatitis B virus (HBV) vaccines. We examined whether Fendrix™, an HBV vaccine containing 3‐O‐desacyl‐4′‐monophosphoryl lipid A (MPL) as adjuvant, could induce HBV immunity in these patients and compared their vaccination efficacy with healthy controls tested previously by the same assays. We selected 35 kidney transplant recipients who had been vaccinated at least thrice against HBV but had never displayed anti‐HBs antibodies. We re‐assessed their anti‐HBs antibody titres and further determined cellular HBV immunity by proliferation assay and interferon (IFN)‐γ ELISpot. Seventeen recipients did neither display humoral nor cellular immunity and could be tested prior to and at month 1 after vaccination. Of note, HLA antigens associated with non‐response to HBV vaccination (HLA‐DRB1*03 and HLA‐DQB1*02) were over‐represented in these 17 recipients. At month 1 after a single vaccination with Fendrix™, we observed a significant increase in anti‐HBs antibodies (P = 0.02). In seven of 17 recipients, we detected anti‐HBs antibodies ≥10 IU/l (10–264), in four HBV‐specific lymphocyte proliferation (stimulation index of 2.6–8.7) and in one specific IFN‐γ responses (12 spots increment). The vaccination response to Fendrix™ was significantly higher (P = 0.035) than the response to HBVaxPro™ in young healthy controls. In summary, the results show that a single vaccination with Fendrix^™ could already induce HBV‐specific humoral and/or cellular responses in ten of 17 kidney transplant patients. Thus, Fendrix™ appears as an efficient vaccine in this patient cohort.     

Persistence and immune memory to hepatitis B vaccine 20 years after primary vaccination of Thai infants, born to HBsAg and HBeAg positive mothers

This study assessed antibody persistence and immune memory to hepatitis B vaccine 20 y after priming with a recombinant hepatitis B virus (HBV) vaccine during infancy. Infants were vaccinated according to a 0, 1, 6 mo schedule with or without simultaneous administration of hepatitis B immunoglobulin (HBIg). Half of the subjects enrolled received an interim booster dose at year 5 (boosted) group, whereas the other half of the subjects enrolled did not (unboosted group). Antibody persistence was assessed until year 20. Immune memory was assessed by administration of a final HBV vaccine challenge dose at year 20 in a second study. At year 20, anti-HBs antibody concentration ≥ 10 mIU/ml rates and GMCs were higher among subjects in the boosted group (84.2% [16/19]; 95%CI: 60.4-96.6) when compared with those in the unboosted group [44.0% (11/25)]; 95% CI: 24.4-65.1). After the HBV vaccine challenge dose at year 20, anti-HBs anamnestic response for subjects in the unboosted and boosted groups was observed in 93.1% (95% CI: 77.2-99.2) and 100% (95% CI: 76.8-100) of subjects, respectively. The mean anti-HBs antibody concentration (GMC) was 562.0 mIU/ml (292.5-1079.7 mIU/ml) post administration of the challenge dose; this is a 28.5 fold increase from the pre- to post-challenge dose administration at year 20. This study demonstrates persistence of anti-HBs antibodies and presence of immune memory following hepatitis B vaccination for up to at least 20 y in Thailand. Immune memory was demonstrated for virtually all subjects, regardless whether they received they had received the additional HBV dose or not. The challenge dose at year 20 was well tolerated and a robust response was demonstrated. ClinicalTrials.gov Identifier: NCT00240526, NCT00774995.     

Prevalence of viral hepatitis B and C in riverside communities of the Tucuruí Dam,Pará, Brazil

Epidemiologically, the relevance of infection caused by hepatitis viruses is related mainly to their wide geographic distribution and the large number of infected individuals in all parts of the world. In this study, 668 residents from the islands around the Tucuruí Dam were selected. Blood samples were collected for investigation of serological markers (HBsAg, total anti‐HBc, anti‐HBS, and anti‐HCV) by enzyme immunoassays. HCV‐positive subjects were tested using RT‐PCR and RFLP for the identification of viral genotypes. Among the 668 subjects studied, 1.9% were HBsAg positive, 28% were total anti‐HBc positive, and 41.9% were anti‐HBs positive. The anti‐HBs marker alone (vaccine response) was detected in 25.7% of the volunteers. Anti‐HCV antibody was detected in 2.2% of the subjects and genotype 1 was the predominant genotype (70%). The results indicate an intermediate level of HBV and HCV endemicity in the region studied, as well as low HBV vaccination coverage. J. Med. Virol. 84:1907–1912, 2012. © 2012 Wiley Periodicals, Inc.     

抗—HBs基因水平的研究

本研究应用ＲＴ－ＰＣＲ、ＤＮＡ－ＰＣＲ及Ｓｏｕｔｈｅｒｎｂｌｏｔ等分子生物学技术检测不同人群中针对一株抗－ＨＢｓ优势克隆的基因水平。发现慢性乙肝（ＨＢｓＡｇ阳性）患者中检出率为２０．６９％（６／２９），明显低于乙肝疫苗注射后人群的６２．９６％（１７／２７），Ｐ＜０．０１；而与未接种过乙肝疫苗组的检出率相比则无明显差异（Ｐ＞０．０５），后者阳性率为２１．４２％。这一结果提示：慢性乙肝患者与乙肝疫苗注射后相比，在抗－ＨＢｓ基因水平上存在差异，可能有抗－ＨＢｓ克隆的缺失或转录、ｍＲＮＡ翻译合成抗－ＨＢｓ的异常。本工作中对人群中抗－ＨＢｓ基因研究的尝试，为乙肝免疫耐受的研究提供了新的线索，同时也为乙肝的基因治疗提供了一定依据。     

High rate of seroconversion following administration of a single supplementary dose of recombinant hepatitis B vaccine in Iranian healthy nonresponder neonates

Forty-nine Iranian neonates who failed to develop a protective anti hepatitis B surface antigen (HBs) response following primary vaccination with triple doses of recombinant hepatitis B vaccine, were classified as hypo-responders (anti-HBs > 1 < 10 IU/l) or non-responders (anti-HBs < 1 IU/l) and subsequently challenged with a single supplementary vaccine dose. A protective and anamnestic type of response was observed in 90% (44/49) of the neonates. The mean titer of anti-HBs antibody was significantly higher following supplementary vaccination, compared to that achieved after primary vaccination. This was more evident in the primary hypo-responder neonates (P < 0.00001) than the non-responder group (P < 0.002). The results indicate that a significant proportion of the non-responder neonates to HBs antigen can be induced to develop a protective and long-lasting antibody response by administration of a single additional vaccine dose. Received: 24 September 1996     

Seroprevalence of hepatitis B virus infection among children and adolescents in Singapore, 2008–2010

A national pediatric survey was undertaken to determine the prevalence of hepatitis B virus markers in Singapore. The aim was to assess the impact of the national childhood immunization program against hepatitis B implemented for all newborns since 1987. The survey involved prospective collection of residual sera from Singapore residents aged 1–17 years attending inpatient services or day surgery in two public hospitals between August 2008 and July 2010. A total of 1,200 sera were collected comprising 400 in each of the three age groups of 1–6, 7–12, and 13–17 years. The sera were tested for hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti‐HBs). Four of the 1,200 samples tested positive for HBsAg, giving an overall prevalence of 0.3%. One and three in the 7–12 years and 13–17 years age groups, respectively, were positive for HBsAg. About 40% possessed anti‐HBs (≥10 mIU/ml); the antibody prevalence decreased significantly from 63.8% in children aged 1–6 years to 32.8% in 7–12 year olds, and 23.5% in 13–17 year olds (P < 0.0005). The successful implementation of the national childhood hepatitis B immunization program over the last two decades has resulted in a low prevalence of HBsAg among children and adolescents. Singapore has achieved the World Health Organization Western Pacific Region's goal in reducing the prevalence of chronic HBV infection to below 2% among children aged 5 years and older by 2012 and to below 1% by 2017. J. Med. Virol. 85:583–588, 2013. © 2013 Wiley Periodicals, Inc.     

Reactivation of occult hepatitis B virus infection following cytotoxic lymphoma therapy in an anti‐HBc negative patient

Screening hepatitis B virus (HBV) surface antigen (HBsAg) and HBV core antibody (anti‐HBc) is recommended prior to cytotoxic or immunosuppressive therapy. This case describes an anti‐HBc negative, DNA positive occult HBV infection in a 71‐year‐old Caucasian male following rituximab‐based treatment for follicular lymphoma. Pre‐screening serology indicated negative HBsAg and anti‐HBc. However, following sequential treatment cycles the patient developed weak HBsAg with a low HBV DNA load (<1,000 IU/ml), but remained anti‐HBc negative. The DNA load peaked 5 months later (>1 × 10⁶ IU/ml) and he was subsequently treated with Tenofovir. Currently the patient remains anti‐HBc negative, and is anti‐HBe negative, anti‐HBs negative, HBeAg positive. No clinical or biochemical evidence of hepatitis has occurred. Sequencing and phylogenetic analysis identified the HBV genosubtype as D4, most probably acquired some years ago during a stay in Papua New Guinea, in spite of prior hepatitis B vaccination. Four amino acid substitutions were detected within the HBsAg loop yet none in the core protein. This case questions the dependability of anti‐HBc testing and highlights the role of HBV DNA testing prior to and throughout cytotoxic or immunosuppressive regimes. As this case exemplifies, vaccination protects against clinical infection but may not exclude seronegative occult infection with the possibility of reactivation. J. Med. Virol. 85:597–601, 2013. © 2013 Wiley Periodicals, Inc.