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Monoclonal antibodies (mAbs) to cell surface molecules have been proven as a key tool for phenotypic and functional characterization of the cellular immune response. One of the major difficulties in studying camel cellular immunity consists in the lack of mAbs that dtect their leukocyte differentiation antigens. In the present study two-parameter flow cytometry was used to screen existing commercially available mAbs to human leukocyte antigens and major histocompatibility molecules (MHC) for their reactivity with camel leukocytes. The comparison of patterns of reactivity obtained after labelling human and camel leukocytes have shown that mAbs specific to human cluster of differentiation (CD) 18, CD11a, CD11b and CD14 are predicted to be cross-reactive with homologous camel antigens.Keywords: Antibodies, Cross-reactivity, Dromedary camel, Flow cytometry

Objective This study assessed the risk of venous thromboembolism (VTE) among privately insured adults in the U.S. with one or more of the following autoimmune diseases: autoimmune hemolytic anemia (AIHA), immune thrombocytopenic purpura (ITP), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Materials and Methods Using the Truven Health MarketScan® Databases, patients 18–64 years of age with a diagnosis of AIHA, ITP, RA, or SLE in 2007 and a sex and age-group matched comparison group of enrollees were followed up through 2010 to identify VTE events. Survival curve and Cox proportional hazards analyses were conducted to assess differences between groups. Results Among patients with AIHA, ITP, RA, or SLE, or > 1 of these diseases, the risk of at least one VTE event was 19.74, 7.72, 4.90, 9.89, and 13.35 per 1,000 person-years, respectively; among the comparison group, the risk was 1.91 per 1,000 person-years. The adjusted hazard ratios (aHRs) for VTE among patients with AIHA, ITP, RA, or SLE, or > 1 of these diseases (when compared with the comparison group) tended to decline over follow-up time; at 1 year, the aHRs were 6.30 (95% confidence interval [CI]: 4.44–8.94), 2.95 (95% CI: 2.18–4.00), 2.13 (95% CI: 1.89–2.40), 4.68 (95% CI: 4.10–5.33), and 5.11 (95% CI: 4.26–6.14), respectively. Conclusion Having AIHA, ITP, RA, or SLE, or > 1 of these diseases was associated with an increased likelihood of a VTE event. More research is necessary to develop better understanding of VTE occurrence among people with autoimmune diseases.

Previous research has suggested autoimmune diseases are risk factors for developing venous thromboembolism (VTE). We assessed whether having diagnoses of selected autoimmune diseases associated with anti-phospholipid antibodies—autoimmune hemolytic anemia (AIHA), immune thrombocytopenic purpura (ITP), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE)—were associated with having a VTE diagnosis among US adult hospitalizations. A cross-sectional study was conducted using the 2010 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. VTE and autoimmune diseases were identified using International Classification of Diseases, Ninth Revision, Clinical Modification coded diagnoses information. The percentages of hospitalizations with a VTE diagnosis among all non-maternal adult hospitalizations without any of the four autoimmune diseases of interest and among those with AIHA, ITP, RA, and SLE diagnoses were 2.28, 4.46, 3.35, 2.65 and 2.77 %, respectively. The adjusted odds ratios (OR) for having a diagnosis of VTE among non-maternal adult hospitalizations with diagnoses of AIHA, ITP, RA, and SLE were 1.25 [95 % confidence interval (CI) 1.05–1.49], 1.20 (95 % CI 1.07–1.34), 1.17 (95 % CI 1.13–1.21), and 1.23 (95 % CI 1.15–1.32), respectively, when compared to those without the corresponding conditions. The adjusted OR for a diagnosis of VTE associated with a diagnosis of any of the four autoimmune diseases was 1.20 (95 % CI 1.16–1.24). The presence of a diagnosis of AIHA, ITP, RA, and SLE was associated with an increased likelihood of having a VTE diagnosis among the group of all non-maternal adult hospitalizations.

Objective. In 1995, the Advisory Committee on Immunization Practices (ACIP) recommended routine hepatitis B (HB) vaccination of all unvaccinated 11- to 12-year-old adolescents. Little is known about the implementation of these recommendations in a managed care setting. The objective of this study was to determine the impact of ACIP recommendations on HB vaccination among adolescents in 3 managed care settings. Methods. We assessed HB vaccination coverage among adolescents who were enrolled in 3 large health maintenance organizations (HMOs) and who turned 13 years old after the 1995 ACIP recommendations. Children who were 8 to 10 years of age during May 1993 and were continuously enrolled through December 1998 were eligible. We used the HMOs’ computerized immunization tracking system to collect HB vaccination dates. The percentage of adolescents who received 3 doses of HB vaccine was determined. Results. In HMOs A, B, and C, coverage levels for 3 doses of HB vaccine were 43.4%, 65.5%, and 25.7%, respectively, among 13-year-olds in 1998 compared with 26.1%, 50.4%, and 5.5% among 13-year-olds in 1996. Between the ages of 11 and 13 years, coverage rates among adolescents aged 13 in 1998 rose more than the coverage among adolescents aged 13 in 1996. The proportion of 13-year-olds in 1998 who received the first dose of HB vaccine by December 1998 was much higher at 89.6%, 65.2%, and 56.6% in HMOs A, B, and C, respectively, compared with the proportion who completed the 3-dose series (43.4%, 65.5%, and 25.7%, respectively). Conclusions. After the 1995 ACIP recommendations, HB vaccination coverage levels among 13-year-olds increased in each of the HMOs, suggesting adherence with national recommendations. Differences among the 3 HMOs may reflect differences in internal policies. More effective strategies may be needed to achieve the Healthy People 2010 goal of 90% vaccination coverage rates among adolescents.

To evaluate the economic impact of the current 2-dose measles-mumps-rubella (MMR) vaccination program in the United States, a decision tree-based analysis was conducted with population-based vaccination coverage and disease incidence data. All costs were estimated for a hypothetical US birth cohort of 3803295 infants born in 2001. The 2-dose MMR vaccination program was cost-saving from both the direct cost and societal perspectives compared with the absence of MMR vaccination, with net savings (net present value) from the direct cost and societal perspectives of US dollars 3.5 billion and US dollars 7.6 billion, respectively. The direct and societal benefit-cost ratios for the MMR vaccination program were 14.2 and 26.0. Analysis of the incremental benefit-cost of the second dose showed that direct and societal benefit-cost ratios were 0.31 and 0.49, respectively. Varying the proportion of vaccines purchased and administered in the public versus the private sector had little effect on the results. From both perspectives under even the most conservative assumptions, the national 2-dose MMR vaccination program is highly cost-beneficial and results in substantial cost savings.

Objective. To determine hepatitis A vaccination coverage and factors associated with not receiving hepatitis A vaccine among children.Methods. A random cluster sample survey was conducted of parents of children who attended kindergarten in Butte County, California, in 2000. Because of a history of recurrent epidemics, an aggressive hepatitis A vaccination program was ongoing during the time this study was conducted. Receipt of 1 or 2 doses of hepatitis A vaccine was studied.Results. Of 896 surveys sent, 648 (72%) were completed. The vaccination coverage for at least 1 dose of hepatitis A vaccine was 398 (62%) and for 2 doses was 272 (42%). Factors associated with not receiving the vaccine included lack of provider recommendation (vs having recommendation; odds ratio [OR]: 7.8; 95% confidence interval [CI]: 4.9–12.2), not having heard of the vaccine (OR: 2.4; 95% CI: 1.2–4.9), and parent’s not perceiving child is likely to get hepatitis A (vs perceiving child might get disease; OR: 2.1; CI: 1.6–2.9).Conclusions. Vaccination coverage among kindergartners did not reach high levels (ie, >90%), despite aggressive vaccination efforts in this community. Lack of provider recommendation and lack of parental awareness of hepatitis A vaccine were the 2 most significant factors associated with failure to receive vaccine. These findings will facilitate the development of vaccination strategies for communities in which hepatitis A vaccination is recommended.

Economic studies of vaccines, including vaccine development and delivery issues, are increasingly needed to inform policy recommendations and programmatic decisions in the USA. This need arises from the increasing costs of vaccines, the complexity of the US healthcare system and the limited number of vaccine manufacturers in the market. We have developed a national research agenda in domestic and global vaccine economics by conducting key informant interviews with 42 experts and inviting ideas from an additional 128 experts. To assess priorities among the 129 ideas that were generated, we asked 15 experts representing a broad range of perspectives to rank the ideas and we analyzed their votes. The highest-ranking domestic research ideas included evaluating: the costs of vaccine shortages, the cost-effectiveness of potential human papillomavirus vaccination and adult and adolescent pertussis vaccination programs and the cost-effectiveness of universal vaccine purchase programs for adults as well as children. The highest-ranking globally-oriented ideas included developing a resource allocation model to support the best vaccination program decisions with limited funds and assessing the cost-effectiveness of HIV, rotavirus, meningococcal and malaria vaccines in developing countries. To optimize the usefulness of vaccine economics research, conceptual issues, such as how to set values for the prevention of illness and how to maximize social equity through investments in vaccines, must be addressed.

Objective. To evaluate the economic impact of universal Haemophilus influenzae type b (Hib) vaccination starting at 2 months of age.Methods. Decision-tree-based analysis was conducted of a hypothetical US birth cohort of 3 815 469 infants using population-based vaccination coverage and disease incidence data. All costs were estimated from both the direct cost (medical and nonmedical) and societal perspectives. Net present value, cost-effectiveness ratios, and benefit-cost ratios of the US Hib vaccination program were evaluated.Results. The results of these analyses showed that the universal vaccination program using the Hib conjugate vaccines in the United States in 2000 was cost-saving from both the direct and societal perspectives, with the benefit of the Hib vaccination program (net present value) from the direct cost and societal perspectives of $0.95 billion and $2.09 billion, respectively. Without a Hib vaccination program, the direct and societal costs of Hib invasive cases would be $1.35 billion and $2.58 billion, respectively. The direct and societal costs of the Hib vaccination program were estimated at $0.39 billion and $0.48 billion, respectively. The direct and societal benefit-cost ratios for the Hib vaccination program were 3.4 and 5.4, respectively. Varying the proportion of vaccines purchased and administered in the public versus the private sector and the proportion of combination vaccine versus monovalent vaccine administered did not have much effect on the results.Conclusions. Regardless of the perspective (direct cost or societal) and the assumptions used, the benefit-cost ratios of the US vaccination program are >1.0. Potential changes in the program, including use of more or less Hib combination vaccines, would not significantly alter the benefit-cost ratio. The national Hib vaccination program is highly cost beneficial and results in substantial cost savings.

Background. In 1991 the Advisory Committee on Immunization Practices recommended vaccination of all infants with three doses of hepatitis B virus vaccine (HepB) by 18 months of age as a key component of a comprehensive strategy to eliminate hepatitis B virus transmission in the United States. The American Academy of Pediatrics and the American Academy of Family Physicians published similar recommendations soon afterward. Methods. Data were obtained from the National Immunization Survey, a survey that began in 1994 and is conducted quarterly by the Centers for Disease Control and Prevention to estimate vaccination coverage among noninstitutionalized US children 19 to 35 months of age. Results. The 1999 National Immunization Survey data indicate that 88.1% (95% confidence interval, 87.4, 88.8) of children 19 to 35 months of age had received at least three doses of HepB (HepB3). There has been a consistent increase in HepB3 coverage since 1994. However, the rate of increase has slowed in recent years and HepB3 coverage remains lower than coverage attained with three doses of diphtheria-tetanus-pertussis and Haemophilus influenzae vaccines. HepB3 coverage varied slightly by racelethnicity and was highest among white and Asian children (89%). Coverage also varied by state; 26 states had levels of at least 90%. Conclusions. Since the 1991 recommendations for universal hepatitis B vaccination, there has been a dramatic increase in coverage levels among children 19 to 35 months of age. However, the Childhood Immunization Initiative goal of 90% coverage has not been reached. Therefore continued efforts are needed to protect US children against this serious but preventable infection.

The use of thromboprophylaxis among at-risk groups of inpatients to prevent hospital-associated venous thromboembolism (HA-VTE) has long been considered suboptimal. Little is known, though, whether utilization of anticoagulants in inpatient settings has increased in recent years. The objective of this study was to assess trends in the administration of anticoagulants to inpatients in a sample of US hospitals from 2006 through 2010 and to further evaluate how trends in utilization vary by type of patient group. A comprehensive national database of all-payer billing records from more than 600 US acute care hospitals, the Truven Health MarketScan® Hospital Drugs Database, was accessed for the years 2006 through 2010. Uniquely, this national hospital database contains records on prescription medications administered in the inpatient setting. Data were analyzed for a subset of hospitals for which an indicator of potential record error was zero. Data for this analysis were contributed by 394 hospitals in 2006 and 333 hospitals in 2010. The analysis was restricted to inpatient admissions of longer than 1 day for adult (age ≥ 18 years) patients who were neither admitted from nor discharged to another acute care hospital (i.e., no hospital transfers). Records were excluded for admissions with a diagnosis that could require anticoagulation for treatment, i.e., deep vein thrombosis, pulmonary embolism, atrial fibrillation, stroke, or myocardial infarct. Total admissions included were 3,188,966 in 2006 and 2,554,806 in 2010. For the purposes of this study, records with one or more prescriptions for the following anticoagulants--enoxaparin, dalteparin, fondaparinux, or warfarin--were classified as presumed thromboprophylaxis since conditions for which anticoagulants are prescribed as treatment had been excluded. In addition, administration of unfractionated heparin of 1,000 U or more was considered prophylactic; low-dose heparin prescriptions (< 1000 U) were assumed to be used as a heparin flush. Anticoagulation prophylaxis rates were assessed for all inpatients and for 5 selected at-risk patient groups based on ICD-9-CM codes used for the same patient groups in Amin A, et al. (2011; 2012): hip/knee surgery, cancer, congestive heart failure (CHF), severe lung disease (including chronic obstructive pulmonary disease), and infectious disease. The associated numbers of admissions in 2010 and the percentages of all admissions for the five at-risk groups are: 52,517 (2.1%) knee/hip, 127,407 (5.0%) cancer, 33,212 (1.3%) severe lung disease, 28,514 (1.1%) CHF, and 27,541 (1.1%) infection. Provisional results indicate that the frequency of administration of thromboprophylaxis in a sample of US inpatient hospitalizations increased over time, from 34.0% in 2006 to 41.40% in 2010, a relative increase of 21.5% in a 4-year period. The use of anticoagulation was highest among major orthopedic surgical patients at each point, 85.97% in 2006 and 87.40% in 2010. The second highest use was observed in hospitalizations for patients with severe lung disease, increasing from 65.33% in 2006 to 69.63% in 2010. Use of anticoagulants for hospitalizations with CHF diagnoses increased from 60.61% in 2006 to 67.99% in 2010. Increases in use of anticoagulation were larger in both absolute and relative terms for two other groups of at-risk hospitalizations. For hospitalizations associated with infectious disease diagnoses, the frequency of use increased from 46.03% in 2006 to 57.71% in 2010, a relative increase of 25.4%. Finally, the largest relative increase in thromboprophylaxis use in at-risk patient groups was observed for hospitalizations associated with cancer diagnoses, among which use increased from 40.52% in 2006 to 52.53% in 2010, a relative increase of 29.6%. These data suggest that substantial increases have occurred in recent years in the frequency with which anticoagulants are prescribed to US inpatients for the prevention of HA-VTE. Additional analyses are being conducted to assess whether increased use of anticoagulants for thromboprophylaxis has been associated with outcomes such as changes in the frequency of in-hospital bleeding events that require treatment. Disclosures: Amin: Johnson & Johnson: Research Funding, Speakers Bureau; BMS/Pfizer: Research Funding, Speakers Bureau.

Objectives To identify parental perceptions regarding vaccine safety and assess their relationship with the immunization status of children. Design, Setting, and Participants Case-control study based on a survey of a sample of households participating in the 2000-2001 National Immunization Survey, a quarterly random-digit-dialing sample of US children aged 19 to 35 months. Three groups of case children not up-to-date for 3 vaccines were compared with control children who were up-to-date for each respective vaccine. Main Outcome Measure Measles-containing or measles-mumps-rubella, diphtheria and tetanus toxoids and pertussis or diphtheria and tetanus toxoids with acellular pertussis, and hepatitis B vaccination coverage. Results Among those sampled from the 2000-2001 National Immunization Survey, the household response rate was 2315 (52.1%) of 4440. Most respondents (>90%) in all groups believed vaccinations are important. In each case-control group, there was no significant difference between the percentage of case and control parents expressing general vaccine safety (range, 53.5%-64.1%). However, case parents were more likely to have asked that their child not be vaccinated for reasons other than illness (range, 10.2%-13.7% vs range, 2.9%-5.3%, respectively) and to believe their children received too many vaccinations (range, 3.4%-7.6% vs range, 0.8%-1.0%, respectively). Among the case-control group receiving a measles-containing or measles-mumps-rubella vaccination, only a small percentage of parents knew about the alleged association between autism and measles-mumps-rubella vaccinations (8.2%), and case parents were more likely to believe it than control parents (4.4% vs 1.5%, respectively; χ 2 P = .04). Conclusions Despite belief in the importance of immunization by a vast majority of parents, the majority of parents had concerns regarding vaccine safety. Strategies to address important misperceptions about vaccine safety as well as additional research assessing vaccine safety are needed to ensure public confidence.

ContextThe association between infant age at initiation of hepatitis B vaccination and completion of the 3-dose hepatitis B vaccination series is unclear.ObjectiveTo assess the association between administration of the first dose of hepatitis B vaccine within 7 days of birth and completion of the hepatitis B vaccine series and the 4:3:1:3 vaccine series (4 doses of diphtheria-tetanus-pertussis vaccine, 3 doses of polio vaccine, 1 dose of measles-containing vaccine, and 3 doses of Haemophilus influenzae type b vaccine).Design, Setting, and ParticipantsAnalysis of data from the 1998 National Immunization Survey, a random-digit-dialing telephone survey (n = 34,480 completed interviews) of parents of children aged 19 to 35 months from 50 states and 28 selected urban areas in the United States that included a provider record check mail survey.Main Outcome MeasuresPercentage of infants who received at least 3 doses of hepatitis B vaccine and percentage who received the 4:3:1:3 vaccine series, by age at receipt of the first dose of hepatitis B vaccine.ResultsOverall, 86.9% of children 19 to 35 months of age in 1998 received 3 or more doses of hepatitis B vaccine, and 79.9% completed the 4:3:1:3 vaccine series. Multivariate analysis indicated that, compared with children who received the first hepatitis B vaccine dose within 7 days of birth, odds ratios (ORs) for not completing the 3-dose hepatitis B vaccine series among children who received the first dose at 8 to 41 days, 42 to 91 days, 92 to 182 days, 183 to 273 days, and 274 or more days of age were 2.4 (95% confidence interval [CI], 2.0-3.0), 7.8 (95% CI, 6.5-9.3), 9.6 (95% CI, 7.0-13.3), 18.3 (95% CI, 12.0-28.0), and 46.6 (95% CI, 33.7-64.5), respectively; ORs for not completing the 4:3:1:3 vaccine series among these same groups were 1.0 (95% CI, 0.8-1.1), 1.0 (95% CI, 0.8-1.1), 1.7 (95% CI, 1.3-2.3), 3.8 (95% CI, 2.6-5.6), and 4.0 (95% CI, 2.9-5.5), respectively.ConclusionAdministration of the first dose of hepatitis B vaccine at birth is associated with increased likelihood of completion of the hepatitis B vaccination series.