Hib Vaccine Research Articles

Lot-to-lot consistency, safety and immunogenicity of 3 lots of Haemophilus influenzae type b conjugate vaccine: results from a phase III randomized, multicenter study in infants

BackgroundVaccination against Haemophilus influenzae type b (Hib) is included in routine pediatric immunization schedule in the United States. Previous vaccine shortages have created the need for additional options for Hib vaccination. MethodsThis phase III, randomized, multi-centered study (NCT01000974) evaluated the safety and immunogenicity of a monovalent tetanus toxoid-conjugate Hib vaccine (Hib-TT) compared to a monovalent (Hib-TT control) and a combination Hib-TT vaccine. We hierarchically assessed lot-to-lot consistency of 3 Hib-TT lots and non-inferiority of Hib-TT to Hib-TT control. We co-administered routine pediatric vaccines with Hib-TT vaccines at 2, 4, 6months (primary vaccination) and 15–18months of age (booster vaccination). We recorded adverse events (AEs) for 4 (solicited) and 31days (unsolicited) post-vaccination and serious AEs (SAEs) throughout the study. ResultsOf 4009 enrolled children, 3086 completed booster phase. Lot-to-lot consistency was not demonstrated. The study met statistical criteria for non-inferiority of Hib-TT to Hib-TT control in terms of immune responses to Hib and co-administered vaccines’ antigens, but not in terms of participants achieving post-primary vaccination anti-PRP levels ≥1µg/mL. Because of the hierarchical nature of the objectives, non-inferiority could not be established. In all groups, 92.5–96.7% and 99.6–100% of participants achieved anti-PRP levels ≥0.15µg/mL, while 78.3–89.8% and 97.9–99.1% had anti-PRP levels ≥1µg/mL, post-primary and post-booster vaccination, respectively. Immune responses to co-administered vaccines and reported incidence of AEs were comparable among groups. We recorded SAEs for 107/2963 (3.6%), 24/520 (4.6%), and 21/520 (4.0%) children post-primary vaccination, and 29/2337 (1.2%), 4/435 (0.9%), and 2/400 (0.5%) children post-booster vaccination with Hib-TT, Hib-TT control and combination Hib-TT vaccine, respectively; 6/5330 (0.1%) SAEs in the Hib-TT groups were considered vaccine-related. ConclusionHib-TT induced seroprotective antibody concentrations in the majority of participants and was well-tolerated when co-administered with routine pediatric vaccines according to a 3+1 schedule.

Overview of the Immunization Situation in Albania

Vaccination coverage is one of the most important components which describe the immunization situation in a country. Now days more and more combined vaccines are being used which help the immunization programs to achieve high coverage for more than one antigen. Another reason for coverage improvement is the use of one or two-dose vials for the administration of DTP-HepB–Hib or MMR vaccine, enabling the vaccination of children at any time. In the last three years vaccination coverage with two doses of MMR and three doses of DTP containing vaccines is more than 95% or sometimes even 98% at national level. The coverage of Hepatitis B vaccine is also high due to its use on 5 in 1 combination. The use of one dose vials has played an important role on sustaining and increasing vaccination coverage. Another component affecting the immunization situation in the country is the influence of parental knowledge for vaccines and vaccination in Albania. Collected data through the use of a questionnaire showed that 6% of respondents have had fear and consequently refused vaccination of their children. While 92% of parents had the opinion that information about the health benefits or risks of vaccines would be absolutely useful and given to them prior to vaccination from health care workers. 72% of the subjects were concerned about the side-effects but this concern hasn’t stopped them to vaccinate their children. 35% of the interviewed mothers were still concerned that their child would contract a disease even though he/she had been already vaccinated.

The Asplenic Patient: Post-Insult Immunocompetence, Infection, and Vaccination.

Splenic injury can occur through multiple mechanisms and may result in various degrees of residual immunocompetence. Functionally or anatomically asplenic patients are at higher risk for infection, particularly with encapsulated bacteria. Vaccination is recommended to prevent infection with these organisms; however, the recommendations are routinely updated, and vaccine selection and timing are complex. Review of the pertinent English-language literature, including the recommendations of the U.S. Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. Overwhelming post-splenectomy infection is associated with high morbidity and mortality rates. Patients requiring splenectomy for trauma-related injury appear to be at lower risk for infection than those undergoing splenectomy for a hematologic or oncologic indication. Initial vaccination is dependent on immunization history but generally should consist of the 13-valent pneumococcal conjugate, quadrivalent meningococcal conjugate, meningococcal serogroup B, and Haemophilus influenzae serotype b (Hib) vaccines. Antimicrobial prophylaxis for certain asplenic patients, such as children under the age of five y, may be indicated. Immunization remains a key measure to prevent overwhelming post-splenectomy infection. Consideration of new recommendations and indications, possible interactions, and timing remains important to including optimal response to the vaccines.

Pediatric bacterial meningitis in Japan, 2013-2015 - 3-5 years after the wide use of Haemophilus influenzae type b and Streptococcus pneumoniae conjugated vaccines.

Haemophilus influenzae type b (Hib) vaccine and pneumococcal conjugated vaccine (PCV) have been widely used since 2010 in Japan when both vaccines were supported by the regional governments, and they were covered as routine recommended vaccines in 2013. The incidence of bacterial meningitis due to these organisms decreased in 2011 and 2012, but meningitis due to Streptococcus agalactiae and Escherichia coli remained unchanged. We planned to confirm whether the incidence also decreased in subsequent years. We analyzed the epidemiological and clinical data for 2013-2015, and compared the information obtained in the previous nationwide survey database and our previous reports. We also investigated the risk factors for disease outcome. In the 2013-2015 surveys, 407 patients from 366 hospitals from all prefectures were evaluated. S.agalactiae (33%), Streptococcus pneumoniae (25%), and E.coli (10%) were the main organisms. The total number of patients hospitalized with bacterial meningitis per 1000 admissions decreased from 1.19 in 2009-2010 to 0.37 in 2013-2015 (p<0.001). The incidence of H.influenzae and S.pneumoniae meningitis significantly decreased from 0.66 in 2009-2010 to 0.01 in 2013-2015, and from 0.30 to 0.09, respectively (p<0.001). Only 0-2 cases with Neisseria meningitidis were reported each year throughout 2001-2015. The fatality rates for H.influenzae, S. pneumoniae, S. agalactiae, and E.coli in 2013-2015 were 0.0, 4.1, 3.1, and 2.6%, respectively. Risk factors for death and sequelae were consciousness disturbance, convulsion, low CSF glucose, and Staphylococcus sp. as a causative organism (p<0.01). Hib vaccine and PCV have decreased the rate of bacterial meningitis. S.agalactiae has subsequently become the most common cause of bacterial meningitis in Japan.

Invasive Haemophilus influenzae infections in children in Kamikawa subprefecture, Hokkaido, Japan, 2006-2015: The effectiveness of H.influenzae type b vaccine.

We evaluated 24 children with invasive Haemophilus influenzae infections between 2006 and 2015 in Kamikawa subprefecture of Hokkaido, Japan. The most frequent disease was pneumonia in 12 cases (50.0%), followed by meningitis in 7 (29.2%) and bacteremia in 5 (20.8%). Patients ranged in age from 3 months to 12 years of age. Seventeen (70.8%) of the total were less than 2 years old. The incidence rate of H.influenzae infection varied from 15.1 to 36.3 per 100,000 population in the Kamikawa area during the period from 2006 through 2011. The corresponding rate decreased to 10.4 per 100,000 population in 2012, and there were no cases after 2013. Meningitis occurred in 1-2 patients annually from 2006 to 2011, showing an incidence rate of 4-10 per 100,000 population per year, while no cases were reported during or after 2012. No patients with invasive H.influenzae infection died, but sequelae were seen at discharge in 1 patient with meningitis, that had hydrocephalus and developmental delay. In Japan, introduction of the H.influenzae type b (Hib) vaccine was in November 2008. Initially, this vaccination was voluntary, resulting in a low vaccination rate. According to the national policy, and the self-pay burden for vaccination was decreased in December 2010, and the vaccination rate increased markedly to over 90%. This report provides a meaningful demonstration that introduction of the Hib vaccine markedly reduced invasive H.influenzae infections, exerting a beneficial effect in Japan, as it has in the world.

The immunogenicity and safety of a Hib-MenAC vaccine: a non-inferiority randomized, observer-blind trial in infants aged 3-5 months

ABSTRACTBackground: The objective of this study was to evaluate the immunogenicity and safety of the novel combined Haemophilus influenzae type b–Neisseria meningitidis serogroup A and C–tetanus toxoid conjugate vaccine (Hib-MenAC).Methods: We conducted a non-inferiority, randomized, observer-blind, positive control clinical trial in 900 healthy infants aged between 3–5 months in Funing County, Jiangsu Province, China. Participants were randomly allocated, in a ratio of 2:1 (block = 6), to receive experimental combined Hib-MenAC vaccines co-administrated with placebo or the co-administration of licensed Hib vaccine and MenAC vaccine, according to a three-dose immunization schedule. The seroconversion of antibody titer against meningococcal serogroups A, C and Hib was the primary endpoint.Results: The experimental vaccines was non-inferior to the licensed two control vaccines. Participants receiving experimental Hib-MenAC vaccines showed a seroconversion rate of 99.0%, 96.1% and 97.7% for rSBA-MenA, rSBA-MenC and anti-PRP antibodies, respectively. The Hib-MenAC vaccine did not result in an increase in adverse reaction, and no serious adverse event was judged to be related to the vaccination.Conclusions: The novel combined Hib-MenAC conjugate vaccine was safe and highly immunogenic in infants aged between 3 to 5 months.

A randomized study of fever prophylaxis and the immunogenicity of routine pediatric vaccinations

ObjectiveProphylactic antipyretic use during pediatric vaccination is common. This study assessed whether paracetamol or ibuprofen prophylaxis interfere with immune responses to the 13-valent pneumococcal conjugate vaccine (PCV13) given concomitantly with the combined DTaP/HBV/IPV/Hib vaccine. MethodsSubjects received prophylactic paracetamol or ibuprofen at 0, 6–8, and 12–16 h after vaccination, or 6–8 and 12–16 h after vaccination at 2, 3, 4, and 12months of age. At 5 and 13months, immune responses were evaluated versus responses in controls who received no prophylaxis. ResultsAfter the infant series, paracetamol recipients had lower levels of circulating serotype-specific pneumococcal anticapsular immunoglobulin G than controls, reaching significance (P<0.0125) for 5 serotypes (serotypes 3, 4, 5, 6B, and 23F) when paracetamol was started at vaccination. Opsonophagocytic activity assay (OPA) results were similar between groups. Ibuprofen did not affect pneumococcal responses, but significantly (P<0.0125) reduced antibody responses to pertussis filamentous hemagglutinin and tetanus antigens after the infant series when started at vaccination. No differences were observed for any group after the toddler dose. ConclusionsProphylactic antipyretics affect immune responses to vaccines; these effects vary depending on the vaccine, antipyretic agent, and time of administration. In infants, paracetamol may interfere with immune responses to pneumococcal antigens, and ibuprofen may reduce responses to pertussis and tetanus antigens. The use of antipyretics for fever prophylaxis during infant vaccination merits careful consideration.ClinicalTrials.gov identifier: NCT01392378https://clinicaltrials.gov/ct2/show/NCT01392378?term=NCT01392378&rank=1

Effect of stepwise perinatal immunization education: A cluster-randomized controlled trial

BackgroundPerinatal immunization education is important for improving the immunization outcomes of infants; however, the content of educational materials used at each perinatal period has not been carefully evaluated. We hypothesized that stepwise education offered at different perinatal periods would improve infant immunization status and enhance maternal immunization knowledge. MethodsIn this cluster-randomized controlled trial, pregnant women were recruited from nine obstetric sites in Niigata, Japan. The intervention group received a stepwise, interactive education intervention (prenatally, postnatally, and 1month after birth). The control group received a leaflet containing general information on immunization. Infant immunization status was evaluated at 6months of age, and maternal immunization knowledge was evaluated by a written survey after each intervention. ResultsAmong 188 study participants, 151 (80.3%) replied to the final post-intervention survey. At 6months of age, the percentage of children who completed three doses of inactivated polio, diphtheria, tetanus toxoid, and acellular pertussis (DTaP-IPV) vaccine was higher in the intervention group than in the control (p=0.04); however, no differences between groups were observed for the Haemophilus influenzae type b (Hib) (p=0.67) or 13-valent pneumococcal conjugate (PCV13) vaccines (p=0.20). The duration to the completion of the third dose of the DTaP-IPV, Hib, and PCV13 vaccines was shorter in the intervention group than in the control (p=0.03, p<0.01, and p<0.01, respectively). Furthermore, maternal knowledge scores exhibited significantly greater improvement in the intervention group over time compared with those of the control group (p=0.02). ConclusionsStepwise perinatal immunization education improved immunization schedule adherence for required vaccines and improved maternal immunization knowledge.

Modeling the Potential for Vaccination to Diminish the Burden of Invasive Non-typhoidal Salmonella Disease in Young Children in Mali, West Africa.

BackgroundIn sub-Saharan Africa, systematic surveillance of young children with suspected invasive bacterial disease (e.g., septicemia, meningitis) has revealed non-typhoidal Salmonella (NTS) to be a major pathogen exhibiting high case fatality (~20%). Where infant vaccination against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae has been introduced to prevent invasive disease caused by these pathogens, as in Bamako, Mali, their burden has decreased markedly. In parallel, NTS has become the predominant invasive bacterial pathogen in children aged <5 years. While NTS is believed to be acquired orally via contaminated food/water, epidemiologic studies have failed to identify the reservoir of infection or vehicles of transmission. This has precluded targeting food chain interventions to diminish disease transmission but conversely has fostered the development of vaccines to prevent invasive NTS (iNTS) disease. We developed a mathematical model to estimate the potential impact of NTS vaccination programs in Bamako.Methodology/Principal FindingsA Markov chain transmission model was developed utilizing age-specific Bamako demographic data and hospital surveillance data for iNTS disease in children aged <5 years and assuming vaccine coverage and efficacy similar to the existing, successfully implemented, Hib vaccine. Annual iNTS hospitalizations and deaths in children <5 years, with and without a Salmonella Enteritidis/Salmonella Typhimurium vaccine, were the model’s outcomes of interest. Per the model, high coverage/high efficacy iNTS vaccination programs would drastically diminish iNTS disease except among infants age <8 weeks.Conclusions/SignificanceThe public health impact of NTS vaccination shifts as disease burden, vaccine coverage, and serovar distribution vary. Our model shows that implementing an iNTS vaccine through an analogous strategy to the Hib vaccination program in Bamako would markedly reduce cases and deaths due to iNTS among the pediatric population. The model can be adjusted for use elsewhere in Africa where NTS epidemiologic patterns, serovar prevalence, and immunization schedules differ from Bamako.

High pneumonia lifetime-ever incidence in Beijing children compared with locations in other countries, and implications for national PCV and Hib vaccination.

ObjectivesTo compare the proportion of Beijing children who have ever had pneumonia (%Pneumonia) to those in other locations, and to estimate by how much national vaccine coverage with Pneumococcal Conjugate Vaccine (PCV) and Haemophilus Influenzae Type b (Hib) could reduce Beijing %Pneumonia.Methods%Pneumonia was obtained for each age group from 1 to 8 years inclusive from 5,876 responses to a cross-sectional questionnaire. Literature searches were conducted for world-wide reports of %Pneumonia. Previous vaccine trials conducted worldwide were used to estimate the pneumococcal (S. pneumoniae) and Hib (H. influenzae) burdens and %Pneumonia as well as the potential for PCV and Hib vaccines to reduce Beijing children’s %Pneumonia.FindingsThe majority of pneumonia cases occurred by the age of three. The cumulative %Pneumonia for 3–8 year-old Beijing children, 26.9%, was only slightly higher than the 25.4% for the discrete 3 year-old age group, similar to trends for Tianjin (China) and Texas (USA). Beijing’s %Pneumonia is disproportionally high relative to its Gross National Income (GNI) per capita, and markedly higher than %Pneumonia in the US and other high GNI per capita countries. Chinese diagnostic guidelines recommend chest X-ray confirmation while most other countries discourage it in favor of clinical diagnosis. Literature review shows that chest X-ray confirmation returns far fewer pneumonia diagnoses than clinical diagnosis. Accordingly, Beijing’s %Pneumonia is likely higher than indicated by raw numbers. Vaccine trials suggest that national PCV and Hib vaccination could reduce Beijing’s %Pneumonia from 26.9% to 19.7% and 24.9% respectively.ConclusionNational PCV and Hib vaccination programs would substantially reduce Beijing children’s pneumonia incidence.

Potentially Preventable Number of Cases and Deaths Associated with Pneumococcal Diseases and Haemophilus Influenzae in Iran during (2010-2013)

Background: Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) is a leading cause of bacterial pneumonia, meningitis, and sepsis in children under 5-year of age. This study aims to estimate potentially preventable number of cases and deaths caused by Hib and pneumococcal in Iran.Materials and Methods:We used the burden of diseases model estimates of the World Health Organization (WHO) to calculate the number of cases and deaths caused by Streptococcus pneumoniae and Haemophilus influenzae in children less than 5 years old. Efficacy of Hib and pneumococcal vaccine was obtained from literature. Vaccine coverage was cited of published report from Ministry of Health and Medical Education Iran (National Committee on Immunization). Hib and Streptococcus pneumoniae diseases burden was obtained from the WHO global burden of disease project.Results: We found that the number of potentially preventable cases and deaths from meningitis caused by Hib among under five years old children in 2013 were 5,414 (95% confidence intervals [CI]: 2838, 11630), and 61 (95% CI: 31, 93), respectively. Estimated number of Streptococcus pneumoniae related pneumonia cases in 2010 and 2013 were 37,732 (95% CI: 22,183, 58,334), and 30,728 (95% CI: 17,023, 50,412), respectively. The corresponding values for pneumonia related deaths from Streptococcus pneumonia were 438 (95% CI: 257, 677), in 2010 and 356 (95% CI: 197, 586), in 2013.Conclusions: Findings favor the effects of both Hib and Pneumococcal conjugate vaccine (PCV) in reducing the burden of disease and death in Iran. Policy makers are advised to introduce PCV to National immunization program.

Impact of the Pneumococcal Heptavalent Conjugated Vaccine on &amp;lt;i&amp;gt;Streptococcus pneumoniae&amp;lt;/i&amp;gt; Nasopharyngeal Carriage and Antimicrobial Susceptibility in Children 2-5-Year-Old in Beijing, China

Streptococcus pneumoniae is a primary cause of illness and death among children younger than 5 years in China. The heptavalent pneumococcal conjugate vaccine (PCV7) was the only conjugated vaccine (PCV) available in China from 2008 to 2013. This randomized, controlled, open-label study conducted at 46 Beijing clinics involved 3281 healthy 2-5-year-old Chinese children, randomized 1:1 to receive one dose of the S. pneumoniae heptavalent conjugated vaccine (PCV7) (n = 1643) or Haemophilus influenzae type b conjugate vaccine (Hib) (n = 1638). The main objective of this study was to investigate the impact of PCV7 against that of Hib vaccination in the nasopharyngeal S. pneumoniae colonization in healthy Chinese children. Nasopharyngeal (NP) samples for culture, serotyping and antimicrobial susceptibility testing were collected before vaccination and at Day 60 and 180 post-vaccination. A total 3281 children were enrolled in the study. Demographic characteristics were similar among both study groups: 1641 children received PCV7. Before immunization, S. pneumoniae was isolated in 338 and 360 children in the PCV7 (144 PCV7 isolates) and Hib groups (145 PCV7 isolates), respectively. At Day 180, PCV7 vaccination was more effective than Hib vaccination in reduction NP carriage (20.2% [P = 0.052]) and new acquisition (19.0% [P = 0.066]). When reductions in NP carriage and new acquisition of PCV7 VT plus 6A was analyzed, reduction in the PCV7 vaccinated group achieved statistical significance (P = 0.034 and P = 0.042 versus Hib, respectively). NP carriage of NVT increased in both groups (P = 0.305 between study groups at Day 180). PCV7 decreased NP carriage of non-susceptible VT to amoxicillin (P = 0.000), ceftriaxone (P = 0.047) and MDR (P = 0.024) versus Hib. PCV7 vaccination in Chinese children 2 to 5 years of age was more effective than vaccination with Hib in the reduction of S. pneumoniae nasopharyngeal carriage, new acquisition and non-susceptible isolates.

Evaluation of the immunogenic property of NT H. influenzae protein D with Neisseria meningitidis OMV in BALB/c.

Identifying ideal non typeable Haemophilus influenzae (NTHi) vaccine candidates has not been easy due to extensive sequence and antigenic variation among gene products interacting with the immune system. Protein D (PD) is a highly conserved 42 kDa surface lipoprotein available in all H. influenzae, including NTHi. In this study, the gene encoding PD was cloned from H. influenzae and expressed in Escheriachia coli TOPO10 cell in pBAD vector. Arabinose was used to express recombinant protein. In order to purify the protein, Ni-NTA agarose was used to perform affinity chromatography. Purified PD and PD mixed with outer membrane vesicle (OMV) and alum adjuvant were used for subcutaneous immunization in BALB/c mice. After vaccination, IgG responses to PD-OMV, PD-alum, and PD alone were determined by enzyme-linked immunosorbent assay (ELISA). The recombinant PD containing His6 residues showed a molecular weight of 42 kDa. Anti-PD IgG was detected after first immunization in all groups of mice compared to the negative control group, and it increased after first vaccination, but results showed that the addition of OMV to PD led to a remarkable increase in IgG responses. Our results suggest an important role for OMV as an adjuvant and show how it could potentially be used when conjugated to H. influenzae PD or other safe subunit vaccine candidates.

Feasibility Trial for Primary Stroke Prevention in Children with Sickle Cell Anemia in Nigeria (SPIN Trial)

Background: In children with sickle cell anemia (SCA), the routine use of transcranial Doppler (TCD) measurements and regular blood transfusion therapy for those with elevated velocities > 200 cm/sec, has dramatically decreased the rate of strokes. However, blood transfusion therapy for primary stroke prevention is not an option for most children in Africa. In preparation for a phase III trial of hydroxyurea therapy (20 mg/kg/day vs 10 mg/kg/day) for primary prevention of strokesin children with SCA in Africa, we conducted a single site, single-arm feasibility trial of hydroxyurea therapy for primary stroke prevention in children with SCA. Participants were between 5 and 12 years of age, attending the pediatric sickle cell disease clinic of Aminu Kano Teaching Hospital, in Kano, Nigeria. The main objectives of the feasibility trial were to determine the acceptability rate of a hydroxyurea therapy trial to families, and to obtain preliminary evidence of hydroxyurea safety in Africa.Methods:All eligible participants were screened with TCD, non-imaging technique, to determine increased stroke risk; defined as time-averaged maximum velocity (TAMV) greater than or equal to 200cm/sec in the middle cerebral artery (MCA). Families were offered moderate fixed dose hydroxyurea (~20mg/kg/day) for initially 2 years. Primary outcome measures of acceptability were based on three key components required for phase II randomized controlled trial: recruitment rate, retention rate and adherence to the study medication. To determine the expected background rate of adverse events and serious adverse events in this population, children with TCD velocities less than 200cm/sec who were not on hydroxyurea therapy were enrolled.Results: A total of 375 families were approached to be screened for elevated TCD measurements, of which 90% (330 of 375) enrolled; 8% (27 of 330) had two consecutive elevated TCD measurements; and 92% (25 of 27) participated in the trial. A total of 210 participants were identified with TCD velocities less than 200 cm, signed informed consents, and agreed to be followed prospectively in a comparison group. The median age for the trial participants and comparison group were 8 and 6.8 years, respectively. No statistically significant difference was observed in age, sex, ethnicity, height and weight of the treatment and comparison groups. The median time on therapy was 2.1 years (range: 0 to 2.8 years), and the average mean cell volume increased from 85 fl at baseline to 101.3 fl at 2 years. As per protocol, all patients were expected to attend monthly research visits and none were missed (n=total 603 visits). No participant in the treatment group dropped voluntarily from the trial, though one participant was withdrawn due to development of progressive renal failure. After follow up visits, participants in the comparison group with subsequent TCD measurements, were given the option to receive hydroxyurea therapy, and the only 2 with elevated TCD values elected to do so. No stroke occurred in the treatment group and 1 stroke occurred in the comparison group. Hospitalization rates in treatment and comparison groups were 35.1 and 48.0 per 100 patient years respectively, (p=0.06). A total of 9 deaths occurred, 1 death in the treatment group, but after participant withdrew from the trial because of progressive renal disease (1.76 per 100 patient-years) and 8 deaths in the comparison group (1·88 per 100 patient-years) p = 0.94. No participants that died received any PCV-13 vaccinations and only 2 received Hib vaccinations. At the time of death, all participants were prescribed malaria prophylaxis, and 8 of 9 participants were prescribed penicillin prophylaxis.Conclusion:In Nigeria, participants in SPIN Trial with elevated TCD measurements treated with moderate dose of hydroxyurea, showed high rates of successful recruitment, retention and adherence rates to trial medication. Importantly hydroxyurea therapy did not reveal any evidence of excessive toxicity when compared to those not treated with hydroxyurea. Our results provide strong preliminary evidence supporting the current multi-center randomized controlled trial comparing hydroxyurea therapy (20 mg/kg/day vs 10 mg/kg/day) for preventing primary strokes in children with SCA living in Nigeria (1R01NS094041-01;clinical trials.gov NCT 02560935). DisclosuresNo relevant conflicts of interest to declare.

Invasive bacterial infections in Gambians with sickle cell anemia in an era of widespread pneumococcal and hemophilus influenzae type b vaccination.

There is relatively little data on the etiology of bacterial infections in patients with sickle cell anemia (SCA) in West Africa, and no data from countries that have implemented conjugate vaccines against both Streptococcus pneumoniae and Haemophilus influenzae type b (Hib).We conducted a retrospective analysis of SCA patients admitted to the Medical Research Council Unit, The Gambia, during a 5-year period when there was high coverage of Hib and Pneumococcal conjugate vaccination. We evaluated 161 admissions of 126 patients between April 2010 and April 2015.Pathogenic bacteria were identified in blood cultures from 11 of the 131 admissions that had cultures taken (8.4%, 95% CI 4.5–14.1%). The most frequent isolate was Salmonella Typhimurium (6/11; 54.5%), followed by Staphylococcus aureus (2/11; 18.2%) and other enteric Gram-negative pathogens (2/11; 18.2%) and there was 1 case of H influenzae non-type b bacteremia (1/11; 9.1%). There were no episodes of bacteremia caused by S pneumoniae or Hib.The low prevalence of S pneumoniae and Hib and the predominance of nontyphoidal Salmonella as a cause of bacteremia suggest the need to reconsider optimal antimicrobial prophylaxis and the empirical treatment regimens for patients with SCA.

Global Routine Vaccination Coverage, 2015.

In 1974, the World Health Organization (WHO) established the Expanded Program on Immunization* to provide protection against six vaccine-preventable diseases through routine infant immunization (1). Based on 2015 WHO and United Nations Children's Fund (UNICEF) estimates, global coverage with the third dose of diphtheria-tetanus-pertussis vaccine (DTP3), the first dose of measles-containing vaccine (MCV1) and the third dose of polio vaccine (Pol3) has remained stable (84%-86%) since 2010. From 2014 to 2015, estimated global coverage with the second MCV dose (MCV2) increased from 39% to 43% by the end of the second year of life and from 58% to 61% when older age groups were included. Global coverage was higher in 2015 than 2010 for newer or underused vaccines, including rotavirus vaccine, pneumococcal conjugate vaccine (PCV), rubella vaccine, Haemophilus influenzae type b (Hib) vaccine, and 3 doses of hepatitis B (HepB3) vaccine. Coverage estimates varied widely by WHO Region, country, and district; in addition, for the vaccines evaluated (MCV, DTP3, Pol3, HepB3, Hib3), wide disparities were found in coverage by country income classification. Improvements in equity of access are necessary to reach and sustain higher coverage and increase protection from vaccine-preventable diseases for all persons.

Status of New Vaccine Introduction - Worldwide, September 2016.

Since the global Expanded Program on Immunization (EPI) was launched in 1974, vaccination against six diseases (tuberculosis, polio, diphtheria, tetanus, pertussis, and measles) has prevented millions of deaths and disabilities (1). Significant advances have been made in the development and introduction of vaccines, and licensed vaccines are now available to prevent 25 diseases (2,3). Historically, new vaccines only became available in low-income and middle-income countries decades after being introduced in high-income countries. However, with the support of global partners, including the World Health Organization (WHO) and the United Nations Children's Fund, which assist with vaccine prequalification and procurement, as well as Gavi, the Vaccine Alliance (Gavi) (4), which provides funding and shapes vaccine markets through forecasting and assurances of demand in low-income countries in exchange for lower vaccine prices, vaccines are now introduced more rapidly. Based on data compiled in the WHO Immunization Vaccines and Biologicals Database* (5), this report describes the current status of introduction of Haemophilus influenzae type b (Hib), hepatitis B, pneumococcal conjugate, rotavirus, human papillomavirus, and rubella vaccines, and the second dose of measles vaccine. As of September 2016, a total of 191 (99%) of 194 WHO member countries had introduced Hib vaccine, 190 (98%) had introduced hepatitis B vaccine, 132 (68%) had introduced pneumococcal conjugate vaccine (PCV), and 86 (44%) had introduced rotavirus vaccine into infant vaccination schedules. Human papillomavirus vaccine (HPV) had been introduced in 67 (35%) countries, primarily targeted for routine use in adolescent girls. A second dose of measles-containing vaccine (MCV2) had been introduced in 161 (83%) countries, and rubella vaccine had been introduced in 149 (77%). These efforts support the commitment outlined in the Global Vaccine Action Plan (GVAP), 2011-2020 (2), endorsed by the World Health Assembly in 2012, to extend the full benefits of immunization to all persons.

Knowledge and practice of healthcare providers as regards routine children vaccination in primary healthcare facilities of Quewisna District, Menoufia Governorate

Objectives The aim of this study was to assess the knowledge and practice of healthcare providers (HCPs) as regards the safe practice during routine children vaccination in primary healthcare facilities. Background Primary vaccine failures can occur after high immunization coverage has been achieved. Healthcare workers' knowledge and practices are influential factors in preventing vaccine failures. Adequate knowledge and practices in the cold chain system, as well as handling and administration of different vaccines, are important to maintain the potency of vaccines and effectiveness of immunization. Participants and methods This cross-sectional study included 140 HCPs and 14 primary healthcare units and one center in Quewisna District, Menoufia, Egypt. A self-administered questionnaire and observational checklist were applied to collect data. The questionnaire assessed the knowledge of HCPs about the storage, handling, administration, scheduling, doses, routes, and contraindications of the different vaccines routinely used for children under 5 years of age in primary healthcare facilities. The checklist assessed the practice of HCPs as regards cold chain, room layout, preparation for vaccination session, and general and specific practice related to each vaccine. Results The total knowledge score was higher among high nurses (nurses with nursing bachelor degree) and HCPs who received training courses. The postvaccination practice was poor compared with prevaccination and during-vaccination practice. Conclusion According to these findings, the knowledge of HCPs as regards all vaccines is satisfactory, except for Hib vaccine. A regular training course to improve the HCPs' knowledge about immunization is highly recommended.

Bactericidal assay with autologous serum demonstrates increased bactericidal activity after Hib vaccination in C2 deficiency

Bactericidal assay with autologous serum demonstrates increased bactericidal activity after Hib vaccination in C2 deficiency

Vaccination Coverage Disparities Between Foreign-Born and U.S.-Born Children Aged 19-35Months, United States, 2010-2012.

Healthy People 2020 targets high vaccination coverage among children. Although reductions in coverage disparities by race/ethnicity have been described, data by nativity are limited. The National Immunization Survey is a random-digit-dialed telephone survey that estimates vaccination coverage among U.S. children aged 19-35months. We assessed coverage among 52,441 children from pooled 2010-2012 data for individual vaccines and the combined 4:3:1:3*:3:1:4 series (which includes ≥4 doses of diphtheria, tetanus, and acellular pertussis vaccine/diphtheria and tetanus toxoids vaccine/diphtheria, tetanus toxoids, and pertussis vaccine, ≥3 doses of poliovirus vaccine, ≥1 dose of measles-containing vaccine, ≥3 or ≥4 doses of Haemophilus influenzae type b vaccine (depending on product type of vaccine; denoted as 3* in the series name), ≥3 doses of hepatitis B vaccine, ≥1 dose of varicella vaccine, and ≥4 doses of pneumococcal conjugate vaccine). Coverage estimates controlling for sociodemographic factors and multivariable logistic regression modeling for 4:3:1:3*:3:1:4 series completion are presented. Significantly lower coverage among foreign-born children was detected for DTaP, hepatitis A, hepatitis B, Hib, pneumococcal conjugate, and rotavirus vaccines, and for the combined series. Series completion disparities persisted after control for demographic, access-to-care, poverty, and language effects. Substantial and potentially widening disparities in vaccination coverage exist among foreign-born children. Improved immunization strategies targeting this population and continued vaccination coverage monitoring by nativity are needed.