First Dose Of Hepatitis Research Articles

Reprint of: Factors associated with effectiveness of the first dose of hepatitis B vaccine in China: 1992–2005

BackgroundIn China, the prevalence of chronic hepatitis B infection was high because of perinatal and early childhood transmission. A three-dose hepatitis B vaccine schedule with a first dose as soon as possible after birth was introduced in 1992 and generalized in 2002 in the Expanded Programme of Immunization (EPI). In 2006, a serological survey evaluated the effectiveness of vaccination. MethodsWe conducted a restricted analysis of the national serological survey that sampled children and collected information on demographic characteristics, birth history, hepatitis B vaccination and hepatitis B surface antigen (HBsAg) status as determined by ELISA testing. We compared children who received the first dose in a timely way (i.e., within 24h of birth) with others in terms of HBsAg status, stratified by birth cohort and place of birth. ResultsThree-dose hepatitis B vaccine coverage increased from 60.8% for children born in 1992–1997 to 93.2% for children born in 2002–2005. Meanwhile, timely birth dose coverage increased from 38.7% to 74.4%. Among 29,410 children born in 1992–2005 who had received three vaccine doses and no hepatitis B immune globulin, factors associated with being HBsAg-negative in multivariate analysis included receiving a timely birth dose (p=0.04), birth after 1998 (p<0.001), living in an urban setting (p=0.008) and hospital birth (p=0.001). The relative prevalence of HBsAg among children receiving the timely birth dose was lower for children born in county or larger hospitals (0.39), intermediate in township hospitals (0.73) and highest at home (0.87). ConclusionsHospital birth and receiving a timely birth dose are the main determinants of the field effectiveness of the first dose of hepatitis B vaccine. Efforts to increase the proportion of hospital deliveries are key to increasing timely birth dose coverage and its effectiveness.

The risk of perinatal hepatitis B virus transmission: hepatitis B e antigen (HBeAg) prevalence estimates for all world regions

BackgroundHBeAg presence in childbearing-age women is a major determinant of perinatal hepatitis B virus (HBV) transmission. The risk of developing chronic HBV infection and liver disease is highest at young age. Our aim was to assess perinatal HBV transmission risk by means of estimating age- and region-specific HBeAg prevalence.MethodsBased on observed HBeAg seroprevalence data obtained from a systematic literature review, we modeled HBeAg prevalence using an empirical Bayesian hierarchical model. Age- and region-specific estimates were generated for 1990 and 2005.ResultsGlobally, highest HBeAg prevalence of over 50 % was found in 0–9 years old girls. At reproductive age, HBeAg prevalence was 20-50 %. Prevalence was highest in young females in East Asia in 1990 (78 %), the infection was less common in Sub-Saharan and North Africa. Regional differences in prevalence were smaller in 2005. There was an overall decrease in HBeAg between 1990 and 2005, which was strongest among girls in Oceania (23.3 % decline), South and South-East Asia (14 % decline). However, in these regions, prevalence remained high at 67 % among young females in 2005. Smaller decreases were observed in women at reproductive age, at which 24-32 % of all HBsAg-positive women were HBeAg-positive in 2005, with lowest prevalence in Southern Sub-Saharan Africa and highest prevalence in Oceania and South-East Asia.ConclusionsHBeAg estimates are crucial for understanding the epidemiology of HBV and for prioritizing implementation of WHO`s prevention recommendations for all infants to receive the first dose of hepatitis B vaccine within 24 hours of birth. Results will have importance as access to treatment for chronic HBV infection is expanded.

The Association of Hepatitis B Vaccine Supply Policy with Timing of Receipt of the First Dose of Hepatitis B Vaccination

An estimated 800,000 - 1.4 million persons in the US have chronic hepatitis B virus (HBV) infection. The risk for chronic infection is greatest among young children; approximately 90% of infants will remain chronically infected with HBV. Approximately 25% of those who become chronically infected during childhood die prematurely from cirrhosis or liver cancer. Hepatitis B vaccination is the most effective measure to prevent HBV infection and its consequences. In 2006, 29 US states had Hepatitis B Vaccine Supply (HBVS) policy which either supplies hepatitis B vaccine at no cost to all providers for all children or provides hepatitis B vaccine to delivery hospitals-only free of charge for all infants; other 21 US states and the District of Columbia did not have. 17,636 infants born in 2006 obtained from 2007-2009 National Immunization Survey (NIS) were analyzed with survival analysis procedures of Kaplan-Meier estimate and Cox proportional hazards model for complex sample survey to evaluate the association between state HBVS policy and the timing of infant age in days to receipt of hepatitis B vaccination. State HBVS policy is associated with infant age in days from birth to receipt of the first dose of hepatitis B vaccine (P < 0.01), and to completion of the 3-dose hepatitis B vaccine series (P < 0.01). Receipt of the first dose of hepatitis B vaccine occurred 31% earlier among infants residing in states with HBVS policy than among infants residing in states without (adjusted hazards ratio 1.31, 95%CI (1.23, 1.39)). Completion of the 3-dose hepatitis B vaccine series were 12% sooner among infants living in states with HBVS policy than among infants living in states without (adjusted hazards ratio 1.12, 95%CI (1.06, 1.18)). State HBVS policy may help overcome barriers to timely delivery of hepatitis B vaccines to infants.

Prevention of perinatal hepatitis B virus transmission in the Netherlands, 2003–2007: Children of Chinese mothers are at increased risk of breakthrough infection

In the Netherlands, different hepatitis B vaccination schedules have been used for children born to HBV-infected mothers. All schedules included a birth dose of hepatitis B immunoglobuline (HBIg). We assessed determinants of perinatal HBV transmission and determinants of anti-HBs titers in infants born to HBsAg positive mothers. We included infants born to HBV infected mothers between 1.1.2003 and 30.6.2007, using national databases and a separate database for Amsterdam. Risk factors for perinatal transmission and determinants of the anti-HBs titer were studied using logistic and linear regression, respectively. Of 2657 infants registered in the national database, 91% were registered to have received HBIg and at least three hepatitis B vaccinations. In Amsterdam, this coverage among 413 children at risk was higher (96%, p<0.01). Serological test results for 2121 infants (80%) indicated that 13 (0.6%) were HBsAg positive. A mother of Chinese descent was the only risk factor for perinatal HBV infection identified (RR 9.1, 95% CI 3.1-26.8). Receiving a birth dose of hepatitis B vaccine later than in the first week of life was not associated with an increased risk of perinatal HBV infection. A shorter period between last vaccination and testing, and having received more doses of hepatitis B vaccine were independently associated with a higher anti-HBs titer. Infants born to Chinese mothers were at increased risk of perinatal HBV infection. All HBsAg positive pregnant women of Chinese origin should be assessed to determine whether there is an indication for anti-viral treatment during pregnancy. Among infants who received HBIg at birth, we did not detect an increased risk of perinatal HBV infection when the first dose of hepatitis B vaccine was administered after the first week of life.

Progress in newborn hepatitis B vaccination by birth year cohorts—1998–2007, USA

In 1999, the American Academy of Pediatrics (AAP) and the U.S. Public Health Service (USPHS) issued a joint statement on thimerosal in vaccines, which advised clinicians to temporarily postpone the first dose of hepatitis B vaccine for infants born to hepatitis B surface antigen (HBsAg)-negative women. In 2005, the Advisory Committee on Immunization Practices (ACIP) updated the strategy to improve prevention of perinatal and early childhood hepatitis B virus (HBV) transmission. To evaluate the progress in hepatitis B birth dose vaccination coverage in birth year cohort from 1998 to 2007 and assess the impact of changes in ACIP recommendations on the birth dose coverage. Birth year cohort study of hepatitis B birth dose vaccination status of 200,865 children aged 19-35 months in the United States and by selected socio-demographic factors; percentage increases of hepatitis B birth dose vaccination coverage between two consecutive birth year cohorts from 1998 to 2007. From 1998 to 1999, hepatitis B birth dose vaccination coverage declined overall in the United States and among selected socio-demographic groups (P<0.001). Conversely, from 1999 to 2007 hepatitis B birth dose vaccination coverage increased significantly by birth year cohort (P<0.001), from approximately 30% in the 1999 birth year cohort to approximately 60% in the 2007 birth year cohort. The first significant increase in hepatitis B birth dose vaccination coverage occurred from 2000 to 2001 birth year cohort. Coverage increases ranged from 8.4% to 11.9% (P<0.001) in the U.S. and across all socio-demographic strata. The second largest increase in hepatitis B birth dose vaccination coverage occurred from 2005 to 2006 birth year cohort in the U.S. and among almost all socio-demographic strata, ranging from 5.6% to 8.7% (P<0.001). Forty-one of the 50 states and the District of Columbia (80%) in the U.S. had increases in hepatitis B birth dose vaccination coverage from 2005 to 2006 birth year cohort. The United States has made substantial progress in increasing hepatitis B birth dose vaccination and recovered from coverage declines associated with temporary postponement of the birth dose in 1999. The hepatitis B birth dose coverage in the U.S. remains substantially below the Healthy People 2020 target of 85%.

Routine Newborn Hepatitis B Immunization

Abstract This article reviews the arguments for a hepatitis B vaccination schedule at birth and at 1 month and 6 months of age. Vertical transmission is a major route of hepatitis B infection and in 2009 the World Health Organization stated that All infants should receive their first dose of hepatitis B vaccine as soon as possible after birth, preferably within 24 hours. Administering the second dose 1 month after the birth dose counters risk of infection and minimizes risk of chronic carriage. The risk of developing chronic hepatitis B infection is almost four times higher in infants with an interval of more than 10 weeks between the first 2 doses than in infants with intervals of less than 10 weeks. Administering the second dose at age 1 month also promotes the achievement of protective antibodies at an early age. The interval between the second and third doses impacts on hepatitis B antibody concentrations after the third dose: shorter intervals (eg, third dose at 2 months of age) results in linear response kinetics, whereas administration at 6 months of age results in an anamnestic response. The World Health Organization considers the birth dose mandatory regardless of hepatitis B endemicity, and the second dose given 1 month later reduces the risk of chronic carriage in high-risk newborns. Finally, at least 4 months between the last 2 doses is important to ensure longer-term protection.

Hepatitis A Virus: Seroepidemiological Study in Fars Province

Dear Editor, I read the article on Seroprevalence study of hepatitis A virus in Fars province, southern Iran that published in one of previous issues of Hepatitis Monthly by Taghavi SA et al. in which authors recommended hepatitis A vaccination in five year old children [1]. In developed countries the first dose of hepatitis A vaccination injects in one year old children while some other researchers recommend second dose after 9-15 months. There are Two main methods to prevent hepatitis A infection: 1) passive immunoprophylaxis; 2) active immunoprophylaxis through vaccination [2]. In developing countries that almost all adults carry HAV antibody, general vaccination isn't cost benefit but due to reduction in HAV infection in children, it seems that vaccination may be requirement, on the other hand, prevalence of HAV differs in developed and developing countries, therefore, the best age for vaccination against HAV may be different. Iran is an endemic area for hepatitis A infection but the prevalence varies in different provinces [3]. Recently, improvement on both environment sanitation and healthy water and food has decreased clinical HAV infection in childhood that is why this life threating infection seems more common among adults. Passive immunoprophylaxis also may be one other strategy of HAV prevention in mini epidemic or family outbreak in developing countries. In endemic area human serum immunoglobulin can be used in persons within two weeks after exposure [4]. Immunoglobulin is as effective as vaccination and it should be used in countries that HAV vaccination is not available such as Iran, but it isn't approved for general prevention. In developed countries children receive HAV vaccination at the age of one; however, it may be different in developing countries in which HAV and mother immunity transmitted is endemic and it causes neonatal immunity for long time [5]. It seems that suggestion of vaccination in five year old children in the mentioned article needs to be evaluated more practically. In conclusion, more studies on seroepidemology of hepatitis A virus are required to evaluate the most appropriate age of HAV vaccination among vhildren in developing countries.

Immunogenicity of two different hepatitis B vaccine schedules

Dear Sir, A letter by Rashmi Ranjan Das et al. was recently published in Infection in which the authors commented on our article entitled “Immunogenicity of recombinant hepatitis B vaccine: comparison of two different vaccination schedules” [1]. We would like to take the opportunity provided by this letter to discuss our findings in particular and hepatitis B epidemiology in Turkey in general. The study performed by Das et al. [2] is one of the few published to date that compares different vaccination schedules of hepatitis B immunization in children [2–4]. These authors performed a randomized clinical trial on the immunogenicity of two different hepatitis B vaccine schedules, i.e., birth, 6 weeks, and 14 weeks (Group A) or 6, 10, and 14 weeks (Group B), and found that seroconversion rates for hepatitis B vaccine were comparable in the two groups. In contrast, two other studies [3, 4], similar to our study, revealed lesser seroconversion in infants whose vaccination started immediately after birth. Such data will contribute to the generation of recommendations on the optimal timing of the initial dose of hepatitis B immunization in infants. In addition to seroprotection, other factors, such as the feasibility of screening for hepatitis B virus surface antigen (HBsAg) in pregnancy and changing epidemiology of the disease in vaccinated populations will also have an effect on these recommendations. With respect to hepatitis B epidemiology in Turkey, we agree with the conclusions of Das et al. [2]. It is likely that vaccinated children born to HBsAg-positive mothers or living in areas where hepatitis B infection is endemic are exposed to hepatitis B throughout childhood. Such children can obtain natural booster doses, which is also an approach to be considered in countries with moderate endemicity. Turkey is known to have moderate hepatitis B endemicity, but in the previous decade the prevalence of HBsAg positivity declined from 4.19 to 2.10 [5–8]. Although hepatitis B infection seroprevalances are accepted to have increased in the more eastern regions in Turkey relative to the western ones, a recent study found that the incidence of hepatitis B carriers in pregnancy was 2.1% in southeastern regions of Turkey [9]. This decrease is the result of the implementation of hepatitis B vaccination programs for infants in 1998 and catch-up vaccination programs for school-age children. According to Turkish Ministry of Health data, the hepatitis B coverage rate for infants <1 year of age in 2010 was 95%, and incidences of HBsAg positivity for children <5 years of age were 3/100,000 and 0.5/100,000 in 2005 and 2010, respectively [10]. Turkey is shifting from moderate to low endemicity and, consequently, the possibility of repeated sub-clinical exposure and natural boosters is also decreasing. These facts support the comment made in our study “as children need long-term protectivity and if immunological memory may later decline or become undetectable, the risk of breakthrough infection may occur”. Infants born to HBsAg-positive mothers should receive the first dose of hepatitis B vaccine at birth, but the first dose may be given at a later age for other children. However, screening is costly and not usually feasible in Turkey. In countries where screening programs for pregnancy are not available, vaccination at birth for hepatitis B perinatal infections is still a necessity. We agree with Das et al. [2] on the necessity of post-vaccination follow-up of different schedules, including birth dose of vaccination with sero-epidemiological studies. As we emphasized previously, our study is a preliminary report and we plan to follow up these infants until puberty and evaluate their immunological status.

Outcomes of passive-active immunoprophylaxis given to infants of mothers infected with hepatitis B virus in Babol, Iran

Background Infants born to chronic hepatitis B virus (HBV) infected mothers may be infected in spite of receiving passive-active immunoprophylaxis. Objectives The purpose of this study was to assess the outcome of infants born to women actively infected by HBV. Study design From April 2004 to September 2009, infants born to women actively infected by HBV received hepatitis B immune globulin (HBIG) and the first dose of hepatitis B vaccine at birth. The second and third doses of HBV vaccine were administered at 1 and 6 months of age. Post-vaccination tests to detect HBsAg and anti-HBs were assessed between 12 and 15 months of age. Those who had anti-HBs titers < 10 mIU/ml received the second series of HBV vaccine. Results Thirty-four and 201 infants were born to HBeAg-seropositive and anti-HBe-seropositive mothers, respectively. HBsAg was detected in 6 (17.6%) infants born to HBeAg-seropositive mothers and in 3 (1.5%) to anti-HBe-seropositive mothers ( p = 0.0001). Anti-HBs ≥ 10 mIU/ml were achieved in 26 (76.5%) and 178 (88.6%) infants of HBeAg-seropositive and anti-HBe-seropositive mothers, respectively ( p > 0.05). Twenty-two (9.4%) infants were non-responders and 11(50%) of them responded to the second series of HBV vaccine. Conclusions The results show that infants of HBeAg-seropositive mothers have higher risk of developing of HBV infection. Some HBsAg-seronegative infants may not respond to passive-active immunoprophylaxis and may remain at risk of HBV infection.

Factors associated with effectiveness of the first dose of hepatitis B vaccine in China: 1992–2005

Background In China, the prevalence of chronic hepatitis B infection was high because of perinatal and early childhood transmission. A three-dose hepatitis B vaccine schedule with a first dose as soon as possible after birth was introduced in 1992 and generalized in 2002 in the Expanded Programme of Immunization (EPI). In 2006, a serological survey evaluated the effectiveness of vaccination. Methods We conducted a restricted analysis of the national serological survey that sampled children and collected information on demographic characteristics, birth history, hepatitis B vaccination and hepatitis B surface antigen (HBsAg) status as determined by ELISA testing. We compared children who received the first dose in a timely way (i.e., within 24 h of birth) with others in terms of HBsAg status, stratified by birth cohort and place of birth. Results Three-dose hepatitis B vaccine coverage increased from 60.8% for children born in 1992–1997 to 93.2% for children born in 2002–2005. Meanwhile, timely birth dose coverage increased from 38.7% to 74.4%. Among 29,410 children born in 1992–2005 who had received three vaccine doses and no hepatitis B immune globulin, factors associated with being HBsAg-negative in multivariate analysis included receiving a timely birth dose ( p = 0.04), birth after 1998 ( p < 0.001), living in an urban setting ( p = 0.008) and hospital birth ( p = 0.001). The relative prevalence of HBsAg among children receiving the timely birth dose was lower for children born in county or larger hospitals (0.39), intermediate in township hospitals (0.73) and highest at home (0.87). Conclusions Hospital birth and receiving a timely birth dose are the main determinants of the field effectiveness of the first dose of hepatitis B vaccine. Efforts to increase the proportion of hospital deliveries are key to increasing timely birth dose coverage and its effectiveness.

Improved immunization practices reduce childhood hepatitis B infection in Tonga

Background Hepatitis B infection is hyper-endemic in Tonga and 19% of pregnant women test positive for hepatitis B surface antigen (HBsAg). Routine childhood immunization against hepatitis B was introduced in 1989 and the target for elimination was set at <1% HBsAg prevalence in children. A study conducted in 1998, a decade after the introduction of hepatitis B immunization, found the HBsAg prevalence to be 3.8% in pre-school children. The finding resulted in the strengthening of the delivery of hepatitis B vaccine with emphasis on providing the first dose within 24 h after birth. The aim of this study was to measure the impact of improved immunization practices on the prevalence of hepatitis B infection in pre-school children, and to assess the progress towards hepatitis B elimination in Tonga. Measured outcome Prevalence of HBsAg antigen. Type of study Cross-sectional study. Methods Children aged 6–59 months who were admitted to Vaiola Hospital, Nuku’alofa, Tonga, and had blood collected for clinical investigation, were tested for HBsAg with a rapid serological test (Abbott Determine ®). A total of 449 children were recruited and interviewed and 375 (84%) were tested for HBsAg. Convenience testing was chosen, as it was likely to be a relatively unbiased method in this situation where all children on the island have good and equitable access to hospital services. Immunization status was checked against the children's immunization cards and cross-checked against the records kept by the public health nurses. Information about socio-economic status, parent education, blood transfusion, breast-feeding, mode of delivery, and place of birth was collected through interviews with mothers using a standardized questionnaire. Results Three children tested positive for HBsAg resulting in a prevalence of 0.8% (CI 0.2–2.5%). Hepatitis B 1 (Hep B 1) immunization coverage was found to be high, 99.1% (CI97.7–99.7) and 91.9% (CI 88.9–94.2) of children received the first dose of hepatitis B vaccine within 24 h after birth. Coverage for the third dose of hepatitis B vaccine was 97.6% (CI 95.5–98.7) and of the children with complete immunization 84.7% (CI 80.9–87.9) had received all three doses by 6 months of age. Conclusions The results show that the instituted changes in the delivery of hepatitis B vaccine have been effective in reducing the transmission of hepatitis B to children and indicate that Tonga appears to have achieved the elimination target of less than 1% HBsAg prevalence in children. This convenience survey used a simple, cost effective and reproducible study design. Convenience testing can be recommended for surveillance of the effectiveness of immunization programmes in settings where the population has good access to health services.

Increased Work of Breathing in a 16-day-old Newborn

A 16-day-old term Caucasian boy presents with increased work of breathing and “head-bobbing” since birth.He was born full term via induced vaginal delivery with Oxytocin to a 28-year-old G2P2002 mother without any complications. He weighed 8lbs at birth. He has since had no other medical problems, and has received the first dose of hepatitis B vaccine.The pertinent family history includes asthma in the father, and obstructive sleep apnea in the mother. His sibling is healthy. There is no substance (tobacco, alcohol, illicit drugs) abuse in the family. He currently takes no medications.His parents took him to his primary care physician who after a brief examination stated that “everything was okay” and that the infant was doing well. His parents deny any episodes of cyanosis, apnea or breath holding. According to the mother, the patient moves his entire body when breathing, along with “head-bobbing.” She also states that his breathing sounds exactly like a suction-bulb syringe. He has decreased oral intake for one day and is experiencing “constipation” for two days. There are no sick contacts, no URI symptoms, no emesis and no change in number of wet diapers. Usually he drinks cow’s milk formula (4 ounces every 3 hours).Physical examination revealed heart rate of 138 beats/min and respiratory rate of 38 breaths/min. All other Vital Signs were within normal limits. Significant examination findings include subcostal retractions and decreased breath sounds in all fields of the right lung. The rest of the examination was unremarkable.Laboratory results are as follows: WBC count 10,900/mcL (30% Neutrophils, 3% Bands, 58% Lymphocytes, 6% Monocytes, 2% Eosinophils), Hgb 11.9 gm/dL, Hct 33.8%, and Platelets 500,000/mcL. Capillary Blood Gas showed pH 7.39, PCO2 57, PO2 58, HCO3 31, SPO2 98%.The infant underwent surgery (Figure 2) and was discharged in healthy condition (Figure 3) The infant was seen in follow-up a month later (Figure 4) and was doing well.The incidence of congenital lobar emphysema (CLE) is approximately 1/ 20,000 – 30,000 live births, predominantly affecting males. It most commonly affects the left upper lobe or right middle lobe for unknown reasons. However, in some infants both lungs may be affected. The age of presentation can be from the newborn period to one year of age. Young infants usually present with severe disease. Most (95%) of patients are symptomatic before the age of 5 months.The pathogenesis of CLE is currently unknown. Some of the theories which explain the pathogenesis of CLE are: inadequate cartilaginous support of the bronchus; poly-alveolar lobe leading to a drastic increase in the number alveoli present in a single lobe of the lung and external compression of the bronchus by aberrant vessels.Common presenting symptoms of CLE are generally non-specific respiratory findings such as difficulty breathing, increased work of breathing, feeding difficulty, and fatigue. Signs that may be associated with CLE include wheezing, stridor, cyanosis and asymmetric breath sounds. The physical examination of the infant with CLE may or may not include all of these signs and symptoms. Thus the symptoms and signs are non-specific and suggestive of CLE but not diagnostic for it. The next step in diagnosing CLE would be chest radiographs.Chest Radiographs in CLE show a hyperlucent area surrounded by minimal bronchovascular markings. Possible mediastinal shift may occur depending on the severity and progression of the disorder.Initial management of the disease depends on the severity of symptoms. These patients may need to have CT of chest, bronchoscopy and V/Q scan performed to evaluate the extent and severity of the disease. Patients with mild to moderate symptoms may be treated conservatively with close follow-up. Patients with severe symptoms require immediate surgery. The definitive treatment of the lesions is lobectomy.JoDee M. Anderson, MD, Division of Neonatal Medicine, Oregon Health & Science University, Portland, OR.Dr. Deepak Kamat MD, PhD†‡

Compliance with hepatitis B immunisation commenced in hospital

Introduction: The UK implements a selective immunisation programme for hepatitis B virus (HBV), screening all pregnant women antenatally and targeting high-risk groups. At the time of this audit, babies considered to be at environmental risk of HBV were scheduled to be immunised at birth, 2 and 4 months. This included all babies of women booked to deliver within the Women’s Reproductive Health Service at the Princess Royal Maternity (PRM). The objective was to audit, through retrospective cohort analysis, compliance with the hepatitis B immunisation schedule in this group of babies. Methods: The study cohort included all babies who had received their first dose of hepatitis B vaccine at the PRM during the period 01/02/2005–01/03/2006. Infants considered to be at high risk of perinatal transmission were excluded. Sources of information were a database of infants notified directly to public health from the PRM, the Scottish Immunisation Recall System (SIRS), a database of infants born to drug misusing women at PRM and pharmacy records at PRM. Databases were compared to identify infants given one or more doses of hepatitis B vaccine. Results: A total of 203 infants were given a first dose of hepatitis B vaccine in the PRM and notified directly to public health. A further 36 infants were notified to SIRS by their GP. During the same study period, 274 doses of vaccine were dispensed by the pharmacy at PRM. One hundred and fifty-four (67%) infants were born to mothers who were known to be drug misusers. Only 52.8% of infants given their first dose of hepatitis B vaccination at the PRM completed the course (defined as more than three doses) and are therefore fully protected against HBV. In the drug-misusing population, the results were no better, with only 54.5% of infants completing the course. Conclusions: There are both clinical and practical reasons for poor compliance with hepatitis B vaccination, which include communication problems (including notification to public health), the mobility of the population, poor parental understanding, the increasing complexity of the childhood immunisation programme and problems with implementing selective rather than universal immunisation. An improved notification system, standardised consent form and parental information leaflet have been introduced. The cycle of audit will be completed after the changes have been implemented. The relationship between angiotensin-converting enzyme (ACE) genotype, serum ACE concentration and markers of asymmetrical growth restriction in premature infants

Hepatitis B vaccination of newborn infants in rural China: evaluation of a village-based, out-of-cold-chain delivery strategy

To prevent perinatal transmission of hepatitis B virus (HBV), WHO recommends that the first dose of hepatitis B (HepB) vaccine be given within 24 hours after birth. This presents a challenge in remote areas with limited cold-chain infrastructure and where many children are born at home. Rural townships in three counties in China's Hunan Province were randomized into three groups with different strategies for delivery of the first dose of HepB vaccine. In group 1, vaccine was stored within the cold chain and administered in township hospitals. In group 2, vaccine was stored out of the cold chain in villages and administered by village-based health workers to infants at home. Group 3 used the same strategy as group 2, but vaccine was packaged in a prefilled injection device. Training of immunization providers and public communication conveying the importance of the birth dose was performed for all groups. Among children born at home, timely administration (within 24 hours after birth) of the first dose of HepB vaccine increased in all groups after the study: group 1, from 2.4% to 25.2%; group 2, from 2.6% to 51.8%; and group 3, from 0.6% to 66.7%; P < 0.001 in each case. No significant difference in antibody response to vaccine was observed between the groups. Timely administration of the first dose of HepB vaccine was improved by communication and training activities, and by out-of-cold-chain storage of vaccine and administration at the village level, especially among children born at home.

Differences in Response to a Hepatitis B Vaccine Booster Dose Among Alaskan Children and Adolescents Vaccinated During Infancy

The duration of protection provided by hepatitis B vaccination is unknown, but the presence of immune memory can be evaluated indirectly by measuring the immune response to a booster dose of vaccine. Participants included 74 adolescents (aged 11.7-14.9 years) who had received a plasma-derived 3-dose primary vaccine series and 138 adolescents (aged 10.0-14.7 years) and 166 children (aged 5.0-7.0 years) who received a recombinant 3-dose primary vaccine series. All were born to hepatitis B surface antigen-negative mothers and had received the first dose of hepatitis B vaccine within 7 days of birth. The proportion of participants with serologic evidence of protective immunity (antibody to hepatitis B surface antigen > or = 10 mIU/mL) at baseline (prebooster), the proportion who developed an anamnestic response (increase to > or = 10 mIU/mL or at or more than fourfold increase in antibody to hepatitis B surface antigen to > 10 mIU/mL), and the geometric mean concentration by 1, 2, and 4 weeks after a 5-microg recombinant vaccine booster dose were determined. No participant had evidence of chronic hepatitis B virus infection. Overall, 99% of the group of children who received recombinant hepatitis B vaccine, 83% of the group of adolescents who received recombinant hepatitis B vaccine, and 69% of the group of adolescents who received the plasma-derived vaccine had an anamnestic response to a booster dose; among responders, the geometric mean concentration at 2 weeks postbooster was 3360 and 128 mIU/mL among adolescents who received plasma-derived vaccine with antibodies to hepatitis B surface antigen > or = 10 and < 10 mIU/mL at baseline, respectively, compared with 1283 and 369 mIU/mL among adolescents who received recombinant hepatitis B vaccine and 5091 and 696 mIU/mL for children who received recombinant hepatitis B vaccine. The anamnestic response rate at 2 weeks postbooster among participants with antibodies to hepatitis B surface antigen < 10 mIU/mL at baseline was inversely associated with age; 97% of 5-year-olds responded compared with 60% of 14-year-olds. Although most participants responded to a booster dose of hepatitis B vaccine, the significance of the increased proportion of nonresponses among older adolescents might indicate waning immune memory.

Perinatal Hepatitis B Transmission and Vaccination Timing in a Managed Care Cohort

From July to September 1999, due to a concern of toxicity from exposure to thimerosal-containing vaccines, the American Academy of Pediatrics and U.S. Public Health Service temporarily recommended delaying the administration of first dose of hepatitis B vaccine until the age of 2-6 months for infants born to hepatitis B surface antigen negative mothers. Our objectives were to determine whether the recommendation affected the rate of perinatal hepatitis B infection in a multistate managed care population; to describe neonatal and early childhood cases of hepatitis B infection and to evaluate a possible role of the recommendation; and to assess the timeliness, with respect to the U.S. childhood immunization schedule, of vaccinations during the first 2 years of life. We identified 3 cohorts of infants born before (July 1998 to June 1999), during (July 1999 to September 1999) and after (October 1999 to September 2000) the recommendation period. We used automated claims data to identify possible neonatal and early childhood hepatitis B cases using specific ICD-9 diagnosis and CPT procedure codes and validated cases through medical record review. Using Health Plan Employer Data and Information Set (HEDIS) data, we calculated vaccination coverage for the first dose of hepatitis B vaccine at 3-month intervals from January 1999 to September 2000. The eligible populations in the "before," "during" and "after" cohorts were 29,347, 7791 and 29,215 infants, respectively. Of 41 possible hepatitis B cases identified in the 3 cohorts, we confirmed 1 case in the after cohort with medical record review. Despite receiving the first dose of hepatitis B vaccine and hepatitis B immunoglobulin within 12-24 hours of birth, the infant was diagnosed with laboratory-confirmed chronic hepatitis B at age of 9 months. An analysis of HEDIS data showed that vaccination coverage for the first dose of hepatitis B vaccine was 98% (January to March 1999) and 96% (April to June 1999) for the "before" cohort and 66% for the "during" cohort. For the "after" cohort the coverage was 72% (October to December 1999), 83% (January to March 2000), 91% (April to June 2000) and 95% (July to September 2000). This study did not identify any perinatal hepatitis B transmission among health plan enrollees associated with the 1999 recommendation. The recommendation did result in a delay of hepatitis B birth dose in the "during" cohort as intended for infants born to hepatitis B surface antigen negative mothers. Six months after the recommendation was rescinded there was still a delay in the timing of first dose of hepatitis B vaccine, but the timing had returned to the prerecommendation level after 9-12 months.

Simultaneous sudden infant death syndrome

The simultaneous sudden deaths of twins rarely occur and therefore it has received limited attention in the medical literature. When the deaths of the twins meet the defined criteria for sudden infant death syndrome (SIDS) independently and take place within the same 24 h range it can be called as simultaneous SIDS (SSIDS). The case(s): Twin girls (3.5-month-old) were found dead by their mother in their crib, both in supine position. The infants were identical twins and delivered at a hospital by cesarean section. Both infants were healthy and did not have any serious medical history. Two days prior to the incident, the twins had received the second dose of oral polio, DPT and the first dose of hepatitis B vaccines and they had fever on the first day of the vaccination and been given teaspoonful of acetaminophen. Death scene investigation, judicial investigation, parental assessment, macroscopic and microscopic autopsy findings and the toxicological analysis did not yield any specific cause of death. The case(s) were referred to a supreme board composed of multidisciplinary medical professionals at the Institute of Forensic Medicine, Ministry of Justice, in Istanbul. The Board decided that the available data was consistent with SIDS. These SIDS case(s) are presented because twin SIDS are rare and this is the first time that a simultaneous twin SIDS have been reported in Turkey. Simultaneous SIDS cases have many implications regarding definition, diagnosis and medico-legal approach.

Anti-phospholipid antibodies following vaccination with recombinant hepatitis B vaccine

This study was undertaken to evaluate the possible role of hepatitis B recombinant vaccine inducing the synthesis of IgG and IgM anti-cardiolipin antibodies (aCL), antibodies against beta(2)GPI (anti-beta(2)GPI), lupus anti-coagulant (LA), anti-nuclear antibodies and antibodies against extractable nuclear antigens (anti-ENA). The study population consisted of 85 healthy students (63 female, 22 male; mean age 20.8 years), vaccinated with three doses of recombinant DNA hepatitis B vaccine. One month after vaccination with the first dose of hepatitis B vaccine a minority of vaccinated individuals showed changes in IgG or IgM aCL or anti-beta(2)GPI or LA activity (P < 0.001). Among subjects in whom changes of IgG anti-beta(2)GPI were observed, a significantly higher number of increased (8/85) than decreased (2/85) values were found (P < 0.01). Analyses of paired data showed that differences in aCL or anti-beta(2)GPI levels before vaccination or 1 month later did not reach statistical significance. In two people aCL transitorily reached medium positivity after the first dose of hepatitis B vaccine with a drop 5 months later. Similar evident anti-beta(2)GPI fluctuation was also observed in one person. Another participant was initially low positive for IgG anti-beta2GPI and the levels were increasing after vaccination. Two participants became positive for anti-nuclear antibodies during 6 months' follow-up. There were no sex-dependent differences in tested antibodies observed and no associations between levels of aPL and levels of anti-HBV antibodies. We conclude that HBV can induce aPL, although rarely. In genetically susceptible individuals or together with some other triggers such combination might confer the risk of developing a continuous autoimmune response in an individual.

Hepatitis B vaccine in the EPI schedule

This study was carried out to evaluate the adequacy of seroconversion when Hepatitis B vaccine is given along with other vaccines at 0, 6 weeks (along with DPT and OPV) and at 9 months (along with measles). 725 infants born to apparently healthy mothers were enrolled to receive the hepatitis B vaccine at 0, 6 weeks and 9 months (Group A) or at 0, 1 and 6 months as per WHO schedule--(Group B). Baseline HbsAg testing was carried out and the babies were immunized with the first dose of hepatitis B vaccine within 48 hours of birth. BCG and the other EPI vaccines were given as per schedule. Serum samples were collected 4 weeks after the second and the third immunizations. 604 infants (83.3%) completed the study. The testing for HbsAg and Anti Hbs titers were conducted in the Department of Microbiology, Maulana Azad Medical College, New Delhi utilizing standard ELISA kits. The seroconversion rates 4 weeks after the second dose of the vaccine were 90.89% (GMT = 48.23) and 91.82% (GMT = 43.95) (P=0.8) in Group A and Group B respectively. After 4 weeks of the third dose the seroconversion rates were 98.99 (GMT = 161.12) and 98.45 (GMT = 150.12) (p=0.17) in Group A and Group B respectively. The two schedules were comparable on using the Kruskal-Wallis H method for analysis. The schedule of hepatitis B vaccination at 0, 6 weeks and 9 months has the same seroefficacy as the currently recommended schedule of 0, 1 and 6 months.

Screening of pregnant Saudi women for hepatitis B surface antigen.

BackgroundThe high prevalence of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in pregnant women is considered the most important factor contributing to the higher carrier rate of HBsAg in some populations, including Saudi Arabia. Universal hepatitis B vaccination in infancy was implemented in Saudi Arabia in 1990 to avoid early acquisition of infection. At the same time, another program was launched to vaccinate all school children at school entry as a second target group. The aim of this study was to evaluate the HBsAg prevalence rate in Saudi pregnant women 12 years after launching the program and to assess regional variation, if any.MethodsIn a cross-sectional study, 2664 pregnant Saudi women were recruited from the five main regions in Saudi Arabia. Blood samples were tested for HBsAg. Positive samples were tested also for HBeAg.ResultsOf 2664 pregnant Saudi women, 65 were positive for HBsAg (2.46%, 95% Cl=2.11 %– 2.69%). Four were positive for HBeAg (0.15%). The HBsAg prevalence rate was higher in Gizan (4.2%) and lower in Tabuk (1.4%) (P=0.035). Only one case was positive for HBsAg in women under the age of 20 years (1/186), a 0.5% positivity rate in this age group compared with 2.6% in the older age group (P=0.049 for the one-sided test). A history of surgical procedures was associated with a higher (3%), but not significantly higher rate of HBsAg positivity. No significant association was found between HBsAg positivity and a history of dental procedures or blood transfusion.ConclusionAlthough the HBsAg prevalence rate among Saudi pregnant women was lower than previously published data, the full impact of the hepatitis B vaccination program in infancy and childhood will take more years to decrease the prevalence rate in pregnant women. The MOH should continue to give the first dose of hepatitis B vaccine at birth to prevent early acquisition, but in the meantime a regional policy can be adopted to deal with the high prevalence rate of HBsAg among pregnant Saudi women.