Weight-based policy of hepatitis B vaccination in very low birth weight infants in Taiwan: a retrospective cross-sectional study.

BACKGROUND: The current recommendation of giving the first dose of hepatitis B vaccine to very low birth weight (VLBW) infants at 30 days of chronologic age usually is not practical, because most VLBW infants are not medically stable at that age. We use an alternative body-weight-based protocol, and evaluate its efficacy in an endemic area under a universal immunization program. METHODS: The immunogenicity of the current hepatitis B vaccination strategy in 155 VLBW preterm infants was evaluated at age 2 to 13 years, with parental consent. All of the infants were born between 1995 and 2006, and received their first dose of hepatitis B vaccine when they reached 2,000-2,200 g, irrespective of chronological age. Hepatitis B immunoglobulin (HBIG) was given at birth to infants born to HBsAg(+)/HBeAg(+) mothers. RESULTS: All 155 of the recruited children were HBsAg and anti-HBc negative. The anti-HBs seropositivity rate (geometric mean titer) was 84.1% (146.5 mIU/mL) for children under 3 years, 73.5% (68.8 mIU/mL) for 4- to 7-year-olds, 27.7% (55.4 mIU/mL) for 8- to 11-year-olds and 20% (6.0 mIU/mL) for children ≥12 years of age. More than 90% of these children received the first vaccination after 30 days of age, half (51%) at 60 to 90 days, and 29 children (18.6%) after 90 days of age. Of the 26 infants born to HBsAg(+) mothers, 6/6 infants of HBeAg(+) mothers received HBIG at birth, and 12/20 infants of HBeAg(-) mothers received HBIG. None of the 26 infants became infected. CONCLUSIONS: Delaying hepatitis B vaccinations in VLBW preterm infants until they reach a weight of 2,000 g, with the administration of HBIG at birth for infants of HBsAg(+) mothers provided adequate immunogenicity and protection in a highly endemic area. Weight-based policy of hepatitis B vaccination is an effective and practical alternative strategy for VLBW infants.

Compared effectiveness of the 7-valent pneumococcal conjugate vaccine in children with the 13-valent vaccine in adults.

13-valent-pneumococcal conjugated vaccine was recently approved in the USA and Europe for adults 50 years of age or more. But this approval was followed by recommendations limiting its use to immunocompromised and asplenic patients. The extension of indications to adults was based on the well-demonstrated clinical effectiveness in infants less than 2 years of age, and on a better immune response either quantitatively or qualitatively with conjugated vaccines compared to the immunogenicity of plain polysaccharide vaccines. Nevertheless, the issue was to know whether results observed with the 7-valent pneumococcal conjugate vaccine in children are reproducible in adults with the 13-valent. The answer was given by comparing the epidemiological and physiopathological data, and the immunological response of the two populations. Very few clinical effectiveness studies in adults are available. We had for aim to assess these various issues in infants and adults. A lot of questions remain, such as the unknown impact of serotype replacement with the 13-valent pneumococcal conjugated vaccine on the clinical epidemiology and emergent Streptococcus pneumoniae pathogenicity, while waiting for the CAPITA study results expected in 2014.

Effectiveness of HBV vaccination in infants and prediction of HBV prevalence trend under new vaccination plan: findings of a large-scale investigation.

BACKGROUND: Hepatitis B virus (HBV) infection remains a severe public health problem. Investigating its prevalence and trends is essential to prevention. METHODS: To evaluate the effectiveness of HBV vaccination under the 1992 Intervention Program for infants and predicted HBV prevalence trends under the 2011 Program for all ages. We conducted a community-based investigation of 761,544 residents of 12 counties in Zhejiang Province selected according to their location, population density, and economic development. The HBV prevalence trends were predicted by a time-shifting approach. HBV surface antigen (HBsAg) and alanine amino transferase (ALT) were determined. RESULTS: Of the 761,544 persons screened for HBsAg, 54,132 were positive (adjusted carrier rate 6.13%); 9,455 had both elevated ALT and a positive HBsAg test (standardized rate 1.18%). The standardized HBsAg carrier rate for persons aged ≤20 years was 1.51%. Key factors influencing HBV infection were sex, age, family history, drinking, smoking, employment as a migrant worker, and occupation. With the vaccination program implemented in 2011, we predict that by 2020, the HBsAg carrier rate will be 5.27% and that for individuals aged ≤34 years will reach the 2% upper limit of low prevalence according to the WHO criteria, with a standardized rate of 1.86%. CONCLUSIONS: The national HBV vaccination program for infants implemented in 1992 has greatly reduced the prevalence of HBV infection. The 2011 program is likely to reduce HBV infection in Zhejiang Province to a low moderate prevalence, and perinatal transmission is expected to be controlled by 2020.

Pneumococcal 13-valent conjugate vaccine for the prevention of invasive pneumococcal disease in children and adults.

Pneumococcal disease remains a global problem despite the availability of effective conjugate vaccines. The 13-valent pneumococcal conjugate vaccine (PCV13) extends the valency of PCV7 by including six additional serotypes highly associated with invasive pneumococcal disease (IPD). Comparisons between PCV13 and PCV7 or the pneumococcal polysaccharide vaccine have established noninferiority of PCV13 for both safety and immunogenicity profiles for use in children and adults, respectively. At the end of 2011, PCV13 had been approved and launched in 104 countries worldwide, with 54 including the vaccine in their pediatric national immunization program. Surveillance data from early adopters of PCV13 has indicated reductions are occurring in both overall IPD and IPD caused by the six non-PCV7 serotypes; early reports of serotype replacement in carriage are also emerging. While serotype replacement for PCV7 was observed to varying degrees for both carriage and disease, the extent to which this will occur for PCV13 is yet to be determined.

Assessment of Aspergillus sensitization or persistent carriage as a factor in lung function impairment in cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF) patients presenting with persistent carriage of, or sensitization to, Aspergillus fumigatus are often treated with antifungal therapies because the presence of the fungus is commonly thought to impede lung function, even in the absence of allergic bronchopulmonary aspergillosis (ABPA). The aim of this study was to assess Aspergillus-related status modulating the forced expiratory volume in 1 s (FEV1) of CF patients. METHODS: From 1995 to 2007, 251 patients were evaluated. Demographic data, cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations, body mass index, and FEV(1) were recorded. The presence of A. fumigatus and Pseudomonas aeruginosa in sputum and the levels of A. fumigatus precipitin, total IgE (t-IgE), and specific anti-A. fumigatus IgE (Af-IgE) were determined. Patients were divided into 3 groups: (1) ABPA: A. fumigatus precipitin ≥3 lines, Af-IgE > 0.35 IU/ml, and t-IgE ≥500 IU/ml; (2) sensitization: Af-IgE > 0.35 IU/ml but t-IgE < 500 IU/ml; and (3) persistent carriage: Af-IgE ≤ 0.35 IU/ml with either an A. fumigatus persistent positive culture or an A. fumigatus precipitin ≥3 lines, provided this serological finding had been found associated with at least 1 A. fumigatus-positive culture. The remaining patients represented the control group. A multivariate analysis was carried out with FEV(1) as the outcome variable. RESULTS: ABPA, sensitization, and persistent carriage were significantly associated with a larger decline in FEV1 compared with the control group, with odds ratios of 15.9, 14.9, and 10.7, respectively. This association was independent of other associated factors (P. aeruginosa transient detection, age, being underweight, and low FEV1 at baseline). CONCLUSIONS: In addition to ABPA, sensitization and persistent carriage appear to have an impact on pulmonary function in CF patients.

Hepatitis B virus markers among teenagers in the Araguaia region, Central Brazil: assessment of prevalence and vaccination coverage.

The Brazilian hepatitis B (HBV) vaccination program for neonates was implemented in 1998 and broadened to include young people up to 20 years of age in 2001. However, HBV coverage of teenagers has not been systematically assessed in Brazil. A cross-sectional study was performed to estimate the magnitude of HBV infection and vaccine coverage among adolescent students regularly enrolled in the public schools of Barra do Garças, a city located in the state of Mato Grosso, Brazil. A representative sample was randomly obtained and participants were interviewed and had blood samples collected to test for HBV markers. The sample was composed of 576 subjects, 51% of which were females. The average age was 15, with the group ranging from 12 to 20 years of age. There were 29 anti-HBc reactive participants (5.0%). Four out of 29 were HBsAg positive (0.7%). Anti-HBs alone (vaccinated profile) showed in 323 (56.1%) students and 224 (38.9%) were negative for all HBV markers. Increasing age was associated with HBV exposure in a χ(2) for trend analysis (p=0.004). The prevalence of anti-HBs alone decreased as the subjects' age increased. Multivariate analysis showed independent association between HBV infection and the start of sexual activity. Another associated variable was the fact that the some students were enrolled in two low-income neighborhood schools. Our findings classify this area as low endemic for HBV and suggest that there is a progressive decrease in the spread of HBV in the region due to the introduction of universal vaccination of neonates. Approximately half of the adolescents 15 years or older were not immunized, which raises a concern in terms of the need to increase the vaccination rate for this segment of the population.

Effects of exposure to calves persistently infected with bovine viral diarrhea virus type 1b and subsequent infection with Mannheima haemolytica on clinical signs and immune variables: model for bovine respiratory disease via viral and bacterial interaction.

The objective was to determine effects of an intratracheal Mannheimia haemolytica challenge after 72-h exposure to bovine viral diarrhea virus type 1b (BVDV1b) persistently infected (PI) calves on serum antibody production, white blood cell count (WBC), cytokine concentrations, and blood gases in feedlot steers. Twenty-four steers (initial BW = 314 +/- 31 kg) were randomly allocated to 1 of 4 treatments (6 steers/treatment) arranged as a 2 x 2 factorial. Treatments were 1) steers not exposed to steers PI with BVDV nor challenged with M. haemolytica (control; CON); 2) steers exposed to 2 steers PI with BVDV for 72 h (BVD); 3) steers intratracheally challenged with M. haemolytica (MH); and 4) steers exposed to 2 steers PI with BVDV for 72 h and challenged with M. haemolytica (BVD+MH). There were 12 h between exposure to PI steers and challenge with M. haemolytica. Rectal temperature was increased (P < 0.001) for MH and BVD+MH during the initial 24 h after the M. haemolytica challenge. For MH and BVD+MH, total WBC count was increased (P < 0.01) at 36 h post M. haemolytica challenge compared with CON, whereas in BVD steers, WBC count was decreased (P < 0.01). Total lymphocyte count was increased (P = 0.004) during the initial 72 h post BVDV exposure for the BVD and BVD+MH groups compared with MH and CON, and this difference remained at 96 h post M. haemolytica challenge. An increased (P < 0.001) total neutrophil count was observed during the initial 36 h for the MH group and at 72 h for the BVD+MH challenge group. Interleukin 1beta, IL-6, and tumor necrosis factor alpha (TNFalpha) concentrations were greater (P

Mathematical modeling of the cause of tuberculosis during tumor necrosis factor blockade.

OBJECTIVE: Tumor necrosis factor (TNF) blockade increases the risk of tuberculosis (TB). The purpose of this study was to use Markov modeling to examine the contributions of reactivation of latent tuberculous infection (LTBI) and the progression of new infection with Mycobacterium tuberculosis to active TB due to TNF blockade. These 2 pathogenic mechanisms cannot otherwise be readily distinguished. METHODS: Monte Carlo simulation was used to represent the range of reported values for the incidence of TB associated with infliximab (TNF monoclonal antibody) and etanercept (soluble TNF receptor) therapy. Iterative methods were then used to identify for each pair of incidence rates the Markov model parameters that most accurately represented the distribution of time to onset of TB as reported to the Food and Drug Administration. RESULTS: Modeling revealed an apparent median monthly rate of reactivation of LTBI by infliximab treatment of 20.8%, which was 12.1 times that with etanercept treatment (P<0.001). In contrast, both drugs appeared to pose a high risk of progression of new M tuberculosis infection to active TB. Progression of new infection appeared to cause nearly half of the etanercept-associated cases; it became the predominant cause of infliximab-associated cases only after the first year. CONCLUSION: Despite sharing a common therapeutic target, infliximab and etanercept differ markedly in the rates at which they reactivate LTBI. Confirmation of these findings will require the application of molecular epidemiologic tools to studies of TB in future biologics registries. Hidden Markov modeling and Monte Carlo simulation are powerful tools for revealing otherwise hidden aspects of the pathogenesis of TB.

Modeling future changes to the meningococcal serogroup C conjugate (MCC) vaccine program in England and Wales.

The UK meningococcal serogroup C conjugate (MCC) vaccine program has successfully controlled serogroup C disease, due to high vaccine effectiveness and substantial herd immunity. However, children immunised at 2, 3 and 4 months of age receive only short-term direct protection and may be at risk of disease 15 months after vaccination. To investigate this we applied a mathematical model to predict the future epidemiology of serogroup C disease, with and without changes to the immunization schedule. Only a few cases of serogroup C disease were predicted to occur over the next few years because of persisting herd immunity, even without a change to the vaccine schedule. The inclusion of a booster dose is likely to improve the impact of the MCC program and reducing the number of doses in infancy will improve cost-effectiveness and create space in the schedule for the addition of other vaccines.

Hepatitis B vaccination in a hyper-endemic tribal community from India: assessment after three years.

Hepatitis B infection is highly endemic among the primitive tribes of Andaman and Nicobar Islands, India and it is necessary to initiate hepatitis B vaccination for control of this infection. A pilot project of mass hepatitis B vaccination using indigenously developed vaccine was initiated among Nicobarese tribe of Car Nicobar Island. Sero-protection rates after second and third year were 89% and 85.5%, respectively. The rate of chronic infection in the vaccinated population after three years was 1.86% compared to the pre-vaccination rate of 20.7%. Considering high sero-protection rates and low cost, the indigenous vaccine could be used for vaccination programme in this tribal community.

Conjugated heptavalent pneumococcal vaccine.

OBJECTIVE: To review the immunogenicity, efficacy, and safety of the heptavalent conjugated pneumococcal vaccine (PCV7). DATA SOURCES: A MEDLINE search (1993-August 2001) of research limited to humans published in the English language was conducted. STUDY SELECTION: Findings from randomized, controlled, multicenter trials were reviewed. Literature regarding epidemiology, control, and treatment of invasive pneumococcal diseases in different populations and the Advisory Committee on Immunization Practices recommendations were also reviewed. DATA SYNTHESIS: PCV7 administered to infants aged 2, 4, and 6 months, with a booster dose at 12-15 months, has been shown to be immunogenic. It decreases the incidence of invasive pneumococcal disease; individual data on bacteremia and meningitis are unavailable. Findings from clinical trials showed that invasive pneumococcal disease caused by vaccine serotypes was reduced by 87%, 58%, and 62% for children <1 year, <2 years, and <5 years of age, respectively, after introduction of routine vaccine use. The overall incidence of acute otitis media did not decrease significantly. However, culture-confirmed episodes and episodes due to pneumococcal serotypes included in the vaccine were reduced. The vaccine was immunogenic in children with sickle cell disease, but its efficacy in preventing invasive pneumococcal diseases remains unclear. Although immunogenicity and efficacy trials are lacking, the vaccine is recommended for Alaskan Native or American Indian children between 24 and 59 months of age, and for children with underlying conditions such as HIV infection, AIDS, other immunocompromising conditions, and chronic illnesses. At the manufacturer's list price of 58 dollars/dose, PCV7 is not projected to be cost-effective after 4 doses. Postmarketing analysis evaluating immunogenicity and efficacy in the excluded population may favorably change this. CONCLUSIONS: Based on published efficacy and immunogenicity data, pharmacy formularies should include PCV7.

[HBs antigen carrier state in pregnant women in Bobo Dioulasso (Burkina Faso)]. / Portage de l'antigène HBs chez les femmes enceintes a Bobo-Dioulasso (Burkina Faso).

The aim of this study was to evaluate the prevalence rate and the risk factors for the carriage of hepatitis B markers in pregnant women in Bobo Dioulasso, Burkina Faso. Out of 917 pregnant women recruited during antenatal care, 98 (10.7%) were HBs antigen positive. Among these ones, 18.2% carded HBe antigen, 66.7% antiHBe antibodies and 95.6% antiHBc antibodies. Two risk factors were identified: maternal age of 23 and 28 (RR = 2.33, chi2 =12.21, p = 0.005) and widowage (Fisher test RR = 6.43, p = 0.0016). This high prevalence of HBs antigen calls for systematic screening for hepatitis B during antenatal care along with an immunization policy toward women of reproductive age and newborns.

KEMRI Hep-cell II hepatitis B surface antigen screening kit.

BACKGROUND: Kenya is a high hepatitis B virus (HBV) endemic zone. Prevention of HBV transmission by transfusing safe blood is necessary. Kits for screening hepatitis B surface antigen (HBsAg) are usually imported and are expensive. Hence it has been difficult to screen donated and patient blood samples all over Kenya. OBJECTIVE: To produce a HBsAg screening kit locally in order to be able to screen donated and patient blood samples all over Kenya. DESIGN: A laboratory based study. SETTING: Centre for Virus Research (CVR), Kenya Medical Research Institute (KEMRI), Nairobi. METHOD: Purified HBsAg from plasma of carriers obtained from National Public Health Laboratories Services (NPHLS) was used to minimise guinea pigs to produce antihepatitis B (anti HBs) antibody. The anti HBs was then used to sensitise sheep red blood cells (SRBC). The final product was freeze dried (lyophilised) and its sensitivity and specificity was compared with other commercial kits. RESULTS: The sensitivity and specificity of KEMRI Hep-cell II was found to be 98% and 99%, respectively. The kit was found to be stable and potent for one year whether kept 4 degrees C, 37 degrees C or room temperature. CONCLUSION: KEMRI Hep-cell II was successfully produced locally. The sensitivity and specificity were comparable to other commercial kits. The kit was stable and potent for one year between temperature of 4 degrees C and 37 degrees C. The kit required only simple apparatus to carry out the test hence it can be used anywhere in Kenya. It was also cheap and affordable.

PIP: Kenya is a high hepatitis B virus endemic zone, and prevention of viral transmission by transfusing safe blood is necessary. However, kits for screening hepatitis B surface antigen (HBsAg) are usually imported and are expensive; hence, it has been difficult to screen donated and patient blood samples all over the country. This laboratory-based study, conducted at the Kenya Medical Research Institute (KEMRI), produced a HBsAg screening kit locally in order to be able to screen donated and patient blood samples throughout Kenya. Purified HBsAg from plasma carriers obtained from the National Public Health Laboratories Services was used to induce guinea pigs to produce anti-hepatitis B antibody (anti-HBs). The anti-HBs was then used to sensitize sheep red blood cells. The final product was freeze dried (lyophilized) and its sensitivity and specificity was compared with other commercial kits. The KEMRI Hep-cell II had 98% and 99% sensitivity and specificity, respectively, in comparison with other commercial kits. The kit was found to be stable and potent for 1 year at temperatures of 4 degrees Celsius, 37 degrees Celsius, or at room temperature. The KEMRI Hep-cell II kit is cheap and affordable and requires a simple apparatus to carry out the test; hence, it can be used anywhere in Kenya.

A non-invasive assessment of hepatitis B virus carrier status using saliva samples.

A non-invasive testing method to determine hepatitis B virus (HBV) carrier status in pregnant women was evaluated. Paired serum and saliva samples were collected and assessment of hepatitis B markers were performed. Of the 502 women enrolled, 5.6% (28/502) of their sera were found to be positive for HBV surface antigen (HBsAg). Assessment of 28 HBsAg seroreactive and 200 HBsAg sero-non-reactive paired saliva samples showed that 17 saliva contained HBsAg. Fourteen of the saliva reactive samples were matched to the serum reactive samples (50% sensitivity); and 3 saliva samples were positive for HBsAg among 200 subjects seronegative for HBsAg (98.5% specificity). Seven of the 28 HBsAg positive sera were found to be reactive for HBV envelope antigen (HBeAg) (25%). One of seven HBeAg seroreactive and 16 HBeAg seronegative paired saliva samples tested were non-reactive for HBeAg. This report found a non-invasive saliva testing method to be a possible alternative approach for determining chronic HBV carrier status if the sensitivity of the test can be improved.

Inquérito soro-epidemiológico antilistéria em Uberaba, MG / A seroepidemiological investigation of listerosis in Uberaba, MG

From a total of 445 individuals, 17.1 per cent had antibodies against L. monocytogenes detected by the agglutination tube test. They were separated in seven groups: bloods donnors (n = 50), Hospital visitors (n = 40), frigorific workers (n = 28), aviculture workers (n = 87), herdsman (n = 31), agriculture students (n = 60) and street-sweepers (n = 51). L1/2a serotype was predominant. Individuals from urban areas (19.5 per cent) and those who had less contact with animals (21.7 per cent) had significantly positive serology when compared with individuals from rural areas (9.4 per cent) and those who had close contact with animals (13.2 per cent). The overall picture is individuals of more specialized occupations had more frequently (25.9 per cent) anti listeria antibodies similar to the results observed in developed countries where listeriosis is a public health problem in urban areas.

Impact of immunization on Haemophilus influenzae type b disease.

Epidemiological surveillance programs have shown that before the introduction of effective vaccines, Haemophilus influenzae type b (Hib) was the primary pathogen associated with bacterial meningitis in children. Vaccines composed of the bacterium's polysaccharide conjugated onto protein carriers began to be introduced into routine health care practices for infants as early as 1989 in some European countries. Continued introduction in industrialized nations, including the United States in late 1990, has resulted in the rapid decline in the incidence of reported invasive Hib disease. Follow-up surveillance studies show that (a) the decline in the incidence of Hib disease is temporally related to the introduction of effective vaccines, (b) the decline in Hib epiglottitis preceded the decline in meningitis in the United States, (c) the incidence of disease declined in children under the age of 5 years but remained constant in older children and adults, (d) other bacterial pathogens are now the primary causative agents of infant meningitis and epiglottitis even though the incidence of disease caused by these other pathogens has not changed, and (e) the pharyngeal carriage rate of Hib in children has declined without any evidence of an increase in the carriage of non-type b strains or other pathogens. The introduction of effective conjugate vaccines appears to protect at-risk children from invasive Hib disease as well as reduce the opportunities for interpersonal transmission of this bacterium. In addition, Hib conjugate vaccine utilization has benefited society through economic savings.

[An anti-Listeria seroepidemiological study in Uberaba, MG]. / Inquérito soro-epidemiológico antilistéria em Uberaba, MG.

From a total of 445 individuals, 17.1% had antibodies against L. monocytogenes detected by the agglutination tube test. They were separated in seven groups: bloods donnors (n = 50), Hospital visitors (n = 40), frigorific workers (n = 28), aviculture workers (n = 87), herdsman (n = 31), agriculture students (n = 60) and street-sweepers (n = 51). L1/2a serotype was predominant. Individuals from urban areas (19.5%) and those who had less contact with animals (21.7%) had significantly positive serology when compared with individuals from rural areas (9.4%) and those who had close contact with animals (13.2%). The overall picture is individuals of more specialized occupations had more frequently (25.9%) anti listeria antibodies similar to the results observed in developed countries where listeriosis is a public health problem in urban areas.

Detection of foot-and-mouth disease virus-infected cattle by assessment of antibody response in oropharyngeal fluids.

The detection of foot-and-mouth disease virus (FMDV)-persistent carriers among convalescent ruminants is of paramount importance in the aftermath of a field outbreak. To this purpose, FMDV-specific antibody should be investigated first, since virus isolation procedures from such carriers are seriously constrained. The complexity of the overall picture may be compounded by possible emergency vaccinations in the affected areas at the beginning of the outbreak. In this case, it is suggested that mucosal rather than serum antibody be investigated. In fact, we showed that FMDV-infected cattle regularly mount an antibody response in oropharyngeal fluids, in contrast to vaccinated cattle. Antibody could be revealed by neutralization assays and/or an immunoglobulin A (IgA)-specific kinetic enzyme-linked immunosorbent assay (ELISA). Cattle vaccinated once seldom showed a mucosal antibody response, which could be only detected by a total immunoglobulin-specific kinetic ELISA. Very few, if any, cattle showed a mucosal IgA response after repeated vaccinations. Our kinetic, IgA-specific ELISA generally allowed an early detection of FMDV-infected cattle; in particular, it proved to be more sensitive than the usual indirect, antigen-trapping ELISA in experiments on saliva samples.