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Clinical Microbiology Reviews Jun 2021Haemophilus influenzae serotype b (Hib) was previously the most common cause of bacterial meningitis and an important etiologic agent of pneumonia in children aged... (Review)
Review
Haemophilus influenzae serotype b (Hib) was previously the most common cause of bacterial meningitis and an important etiologic agent of pneumonia in children aged <5 years. Its major virulence factor is the polyribosyl ribitol phosphate (PRP) polysaccharide capsule. In the 1980s, PRP-protein conjugate Hib vaccines were developed and are now included in almost all national immunization programs, achieving a sustained decline in invasive Hib infections. However, invasive Hib disease has not yet been eliminated in countries with low vaccine coverage, and sporadic outbreaks of Hib infection still occur occasionally in countries with high vaccine coverage. Over the past 2 decades, other capsulated serotypes have been recognized increasingly as causing invasive infections. H. influenzae serotype a (Hia) is now a major cause of invasive infection in Indigenous communities of North America, prompting a possible requirement for an Hia conjugate vaccine. H. influenzae serotypes e and f are now more common than serotype b in Europe. Significant year-to-year increases in nontypeable H. influenzae invasive infections have occurred in many regions of the world. Invasive H. influenzae infections are now seen predominantly in patients at the extremes of life and those with underlying comorbidities. This review provides a comprehensive and critical overview of the current global epidemiology of invasive H. influenzae infections in different geographic regions of the world. It discusses those now at risk of invasive Hib disease, describes the emergence of other severe invasive H. influenzae infections, and emphasizes the importance of long-term, comprehensive, clinical and microbiologic surveillance to monitor a vaccine's impact.
Topics: Child; Haemophilus Infections; Haemophilus Vaccines; Haemophilus influenzae type b; Humans; Infant; Serogroup; Vaccines, Conjugate
PubMed: 34076491
DOI: 10.1128/CMR.00028-21 -
Hematology. American Society of... Dec 2020An estimated 1 million people in the United States have functional or anatomic asplenia or hyposplenia. Infectious complications due to encapsulated organisms such as...
An estimated 1 million people in the United States have functional or anatomic asplenia or hyposplenia. Infectious complications due to encapsulated organisms such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae can lead to fulminant sepsis and death, particularly in young children, in the period shortly after splenectomy, and in immunocompromised patients. Patients with asplenia are also at risk for less common infections due to Capnocytophaga, Babesia, and malaria. Antibiotic prophylaxis, vaccines, and patient and family education are the mainstays of prevention in these at-risk patients. Recommendations for antibiotic prophylaxis typically target high-risk periods, such as 1 to 3 years after splenectomy, children ≤5 years of age, or patients with concomitant immunocompromise. However, the risk for sepsis is lifelong, with infections occurring as late as 40 years after splenectomy. Currently available vaccines recommended for patients with asplenia include pneumococcal vaccines (13-valent pneumococcal conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine), meningococcal vaccines (meningococcal conjugate vaccines for serogroups A, C, Y and W-135 and serogroup B meningococcal vaccines), H. influenzae type b vaccines, and inactivated influenza vaccines. Ongoing booster doses are also recommended for pneumococcal and meningococcal vaccines to maintain protection. Despite the availability of prevention tools, adherence is often a challenge. Dedicated teams or clinics focused on patient education and monitoring have demonstrated substantial improvements in vaccine coverage rates for individuals with asplenia and reduced risk of infection. Future efforts to monitor the quality of care in patients with asplenia may be important to bridge the know-do gap in this high-risk population.
Topics: Adult; Anti-Bacterial Agents; Bacterial Capsules; Bacterial Infections; Child; Haemophilus Vaccines; Humans; Infection Control; Infections; Meningococcal Vaccines; Pneumococcal Vaccines; Primary Immunodeficiency Diseases; Spleen; Splenectomy; Vaccination
PubMed: 33275684
DOI: 10.1182/hematology.2020000117 -
Pediatrics May 2022The majority of children are prescribed antibiotics in the first 2 years of life while vaccine-induced immunity develops. Researchers have suggested a negative...
BACKGROUND
The majority of children are prescribed antibiotics in the first 2 years of life while vaccine-induced immunity develops. Researchers have suggested a negative association of antibiotic use with vaccine-induced immunity in adults, but data are lacking in children.
METHODS
From 2006 to 2016, children aged 6 to 24 months were observed in a cohort study. A retrospective, unplanned secondary analysis of the medical record regarding antibiotic prescriptions and vaccine antibody measurements was undertaken concurrently. Antibody measurements relative to diphtheria-tetanus-acellular pertussis (DTaP), inactivated polio (IPV), Haemophilus influenzae type b (Hib), and pneumococcal conjugate (PCV) vaccines were made.
RESULTS
In total, 560 children were compared (342 with and 218 without antibiotic prescriptions). Vaccine-induced antibody levels to several DTaP and PCV antigens were lower (P < .05) in children given antibiotics. A higher frequency of vaccine-induced antibodies below protective levels in children given antibiotics occurred at 9 and 12 months of age (P < .05). Antibiotic courses over time was negatively associated with vaccine-induced antibody levels. For each antibiotic course the child received, prebooster antibody levels to DTaP antigens were reduced by 5.8%, Hib by 6.8%, IPV by 11.3%, and PCV by 10.4% (all P ≤ .05), and postbooster antibody levels to DTaP antigens were reduced by 18.1%, Hib by 21.3%, IPV by 18.9%, and PCV by 12.2% (all P < .05).
CONCLUSIONS
Antibiotic use in children <2 years of age is associated with lower vaccine-induced antibody levels to several vaccines.
Topics: Anti-Bacterial Agents; Antibodies, Viral; Child; Child, Preschool; Cohort Studies; Diphtheria-Tetanus-acellular Pertussis Vaccines; Haemophilus Vaccines; Humans; Poliovirus Vaccine, Inactivated; Retrospective Studies; Vaccines, Combined
PubMed: 35474546
DOI: 10.1542/peds.2021-052061 -
Frontiers in Immunology 2021The humoral response to vaccinations varies widely between individuals. There is no data available on the correlation between responses to different vaccines. In this...
INTRODUCTION
The humoral response to vaccinations varies widely between individuals. There is no data available on the correlation between responses to different vaccines. In this study, we investigated the correlation of antibody responses between routine vaccine antigens in infants.
METHODS
One and seven months after the 6-month vaccinations and one month after the 12-month vaccinations, antibody concentrations to diphtheria, tetanus, pertussis, polio (serotypes 1-3), type b (Hib), pneumococcus (13 serotypes), meningococcus C, measles, mumps and rubella were measured using fluorescent bead-based multiplex immune-assays. For the correlation of antibody responses, Spearman's rank correlation coefficients (ρ) with 95% confidence intervals (CI) were calculated between responses to each vaccine antigen.
RESULTS
The correlation between concentrations of antibodies to the vaccinations ending at 6 months of age was higher one month compared to seven months after vaccination. The strongest correlations at both time points were observed between antibody responses to different polio serotypes, certain pneumococcal serotypes and between responses to diphtheria and pneumococcal (conjugated to a diphtheria toxoid) vaccine antigens. Correlation between responses to tetanus, Hib, pertussis, polio and other vaccine antigens were weak. The correlation between antibody responses to the 12-month vaccine antigens was weaker than to the 6-month vaccine antigens and there was a negative correlation between responses to measles, mumps, rubella vaccine and non-live vaccine antigens (meningococcus C, tetanus and Hib). There was only weak correlation between antibody responses to vaccines of the same type (e.g. conjugated polysaccharide or toxoid vaccines).
CONCLUSION
Correlation between antibody responses to similar antigens in the same vaccine (such as different serotypes of a bacteria or virus), as well as responses to antigens conjugated to similar carrier proteins, are strong. In contrast, correlation between responses to other vaccines are weak. Measuring antibody responses to one or a few vaccine antigens therefore does not offer a reliable surrogate marker of responses to unrelated vaccines.
Topics: Antibodies, Bacterial; Antibodies, Viral; Antibody Formation; Bacterial Vaccines; Diphtheria-Tetanus-acellular Pertussis Vaccines; Female; Haemophilus Vaccines; Hepatitis B Vaccines; Humans; Immunoassay; Infant; Male; Pertussis Vaccine; Pneumococcal Vaccines; Reproducibility of Results; Vaccination; Viral Vaccines
PubMed: 33868282
DOI: 10.3389/fimmu.2021.646677 -
Human Vaccines & Immunotherapeutics Nov 2022Given increased global concern about vaccine hesitancy, this study estimates coverage of mandatory vs non-mandatory vaccines in children, and assesses whether vaccine...
Given increased global concern about vaccine hesitancy, this study estimates coverage of mandatory vs non-mandatory vaccines in children, and assesses whether vaccine hesitancy among young parents relates to their child's eventual vaccination status in Shanghai, China. In a cohort study within Shanghai, China, we ascertained vaccine hesitancy among parents of young infants, and later abstracted their child's electronic immunization records. We measure full coverage of vaccines on the mandatory, and publicly funded Expanded Program on Immunization (EPI). Non-EPI vaccines included pneumococcal conjugate vaccine, type b vaccine, and rotavirus vaccine. Vaccine hesitancy was linked to vaccine uptake through mixed effects logistic regression models. Among 972 children, full coverage of all EPI vaccines by 15 months was 95%, compared to dose 1 coverage of pneumococcal conjugate vaccine at 13%, type b vaccine at 68%, and rotavirus vaccine at 52%. Vaccine hesitancy was not significantly linked with full coverage of all EPI vaccines (OR: 1.55, 95% CI: .89, 2.72), but coverage in the vaccine hesitant was lower for pneumococcal conjugate vaccine dose 1 (OR: .70, 95% CI: .53, .91), and rotavirus vaccine dose 1 (OR: .69, 95% CI: .56, .86). Disparities by education level were not significant for EPI vaccines, but were for dose 1 of pneumococcal conjugate vaccine rotavirus vaccine. Overall, vaccine hesitancy was related to lower uptake of non-EPI, but not EPI vaccines. Shanghai has a robust system for insurance equitable access to EPI vaccines, but if vaccine hesitancy grows, it could reduce coverage of non-EPI vaccines.
Topics: Child; China; Cohort Studies; Haemophilus Vaccines; Humans; Infant; Pneumococcal Vaccines; Rotavirus Vaccines; Vaccination; Vaccination Hesitancy; Vaccines, Conjugate
PubMed: 35321621
DOI: 10.1080/21645515.2022.2043025 -
Expert Review of Vaccines 2023Hexaxim is a hexavalent vaccine approved as primary and booster vaccination in infants 6 weeks and older, protecting against diphtheria, tetanus, pertussis,... (Review)
Review
INTRODUCTION
Hexaxim is a hexavalent vaccine approved as primary and booster vaccination in infants 6 weeks and older, protecting against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B and Haemophilus influenzae type b.
AREAS COVERED
To evaluate the immunogenicity and reactogenicity (safety) of Hexaxim (Hexyon, Hexacima) in primary and booster vaccine schedules; long-term antibody persistence; concomitant use with other childhood vaccines and use in immunocompromised infants. Hexaxim was found to be noninferior to other licensed hexavalent vaccines, being highly immunogenic for all toxoids/antigens and with an acceptable safety profile. It can be administered concomitantly with other childhood vaccines. Hexaxim can be given as a booster for infants primed with Infanrix Hexa and given in a pentavalent-hexavalent-pentavalent series. Hexaxim elicits a similar immune response and safety profile in human immunodeficiency virus (HIV) positive infants. It has the benefit of being a ready-to-use liquid formulation, minimizing dosage errors and preparation time.
EXPERT OPINION
Hexaxim has an acceptable safety profile and provides immunity against all six targeted diseases. It is an acceptable alternative to other hexavalent vaccines on the market. Further studies are required on the use of immunocompromised patients as well as the antibody persistence of each of the vaccine components.
Topics: Infant; Humans; Child; Immunization, Secondary; Immunization Schedule; Diphtheria-Tetanus-Pertussis Vaccine; Haemophilus Vaccines; Poliovirus Vaccine, Inactivated; Hepatitis B Vaccines; Vaccines, Combined; Antibodies, Bacterial
PubMed: 36545777
DOI: 10.1080/14760584.2023.2161519 -
Human Vaccines & Immunotherapeutics Dec 2022The DTacP-sIPV-Hib combination vaccine can replace the single-component acellular pertussis, diphtheria, tetanus, polio, and Haemophilus influenzae type B vaccines. In...
The DTacP-sIPV-Hib combination vaccine can replace the single-component acellular pertussis, diphtheria, tetanus, polio, and Haemophilus influenzae type B vaccines. In this study, we evaluated the safety and immunogenicity of a newly developed DTacP-sIPV-Hib combination vaccine in animal models. We used 40 mice and 46 cynomolgus monkeys to evaluate acute and long-term toxicity. Thirty-six guinea pigs were used for sensitization assessment. For immunogenicity assessment, 50 NIH mice and 50 rats were equally randomized to receive 3 doses of 3 different batches of the tested vaccine at an interval of 21 d, or physiological saline solution (0.5 mL). Orbital blood was collected at an interval of 21 d post inoculation to detect related antibody titers or neutralizing antibody titers against poliovirus. Gross autopsy and histopathological examination revealed no abnormal toxicity or irritation in mice and cynomolgus monkeys. Sensitization assessment in guinea pigs indicated the lack of evident allergic symptoms in the high- and low-dose vaccine groups within 30 min after repeated stimulation. The DTacP-sIPV-Hib combination vaccine induced significant immune responses in mice, rats, and cynomolgus monkeys, with 100% seroconversion rates after 3 doses. The DTacP-sIPV-Hib combination vaccine is safe and immunogenic in animal models. Three doses of the vaccine elicited satisfactory antibody responses in mice, rats, and cynomolgus monkeys.
Topics: Animals; Guinea Pigs; Mice; Rats; Antibodies, Bacterial; Haemophilus influenzae type b; Haemophilus Vaccines; Hepatitis B Vaccines; Macaca fascicularis; Models, Animal; Poliovirus Vaccine, Inactivated; Vaccines, Combined; Diphtheria-Tetanus-acellular Pertussis Vaccines
PubMed: 36576263
DOI: 10.1080/21645515.2022.2160158 -
Journal of Medical Economics Oct 2017The World Health Organization (WHO) recommends the use of Haemophilus influenzae type b (Hib) conjugate vaccines, but China and Thailand have not used Hib vaccination in... (Review)
Review
AIMS
The World Health Organization (WHO) recommends the use of Haemophilus influenzae type b (Hib) conjugate vaccines, but China and Thailand have not used Hib vaccination in their national immunization programs. This systematic review aimed to update published economic evaluations of Hib vaccinations and to determine factors that potentially affected their cost-effectiveness.
METHODS
Searches were performed from the inception until December 2015 using 13 databases: CAB direct; CEA registry; EconLit; EMBASE; E-library; NHSEED; PAHO; POPLINE; PubMed; Redalyc project; RePEc; SciELO; and WHOLIS. Reference lists of relevant studies and grey literature were also searched. Full economic evaluations of Hib vaccination with results of costs and outcomes were included. The WHO checklist was used to evaluate the quality of the included studies. Data from eligible studies were extracted using a standardized data collection form.
RESULTS
Out of 830 articles, 27 were included. Almost half of the studies (12/27) were conducted in high-income countries. Twelve studies (12/27) investigated the Hib vaccine as an addition to the existing vaccination program. Most studies (17/27) examined a 3-dose schedule of Hib vaccine. Nineteen studies (19/27) reported the model used, where all were decision tree models. Most of the studies (23/27) demonstrated an economic value of Hib vaccination programs, key influential parameters being incidence rates of Hib disease and vaccine price.
CONCLUSIONS
Hib vaccination programs are mostly found to be cost-effective across geographic regions and country income levels, and Hib vaccination is recommended for inclusion into all national immunization programs. The findings are expected to support policy-makers for making decisions on allocating limited resources of the Hib vaccination program effectively.
Topics: Child, Preschool; Cost of Illness; Cost-Benefit Analysis; Developed Countries; Developing Countries; Haemophilus Infections; Haemophilus Vaccines; Health Expenditures; Humans; Infant
PubMed: 28737468
DOI: 10.1080/13696998.2017.1359181 -
Journal of Immunology Research 2016Haemophilus influenzae type b (Hib) causes many severe diseases, including epiglottitis, pneumonia, sepsis, and meningitis. In developed countries, the annual incidence... (Review)
Review
Haemophilus influenzae type b (Hib) causes many severe diseases, including epiglottitis, pneumonia, sepsis, and meningitis. In developed countries, the annual incidence of meningitis caused by bacteria is approximately 5-10 cases per population of 100,000. The Hib conjugate vaccine is considered protective and safe. Adjuvants, molecules that can enhance and/or regulate the fundamental immunogenicity of an antigen, comprise a wide range of diverse compounds. While earlier developments of adjuvants created effective products, there is still a need to create new generations, rationally designed based on recent discoveries in immunology, mainly in innate immunity. Many factors may play a role in the immunogenicity of Hib conjugate vaccines, such as the polysaccharides and proteins carrier used in vaccine construction, as well as the method of conjugation. A Hib conjugate vaccine has been constructed via chemical synthesis of a Hib saccharide antigen. Two models of carbohydrate-protein conjugate have been established, the single ended model (terminal amination-single method) and cross-linked lattice matrix (dual amination method). Increased knowledge in the fields of immunology, molecular biology, glycobiology, glycoimmunology, and the biology of infectious microorganisms has led to a dramatic increase in vaccine efficacy.
Topics: Adjuvants, Immunologic; Antigens, Bacterial; Bacterial Capsules; Drug Design; Haemophilus Vaccines; Haemophilus influenzae type b; Humans; Immunity, Innate; Immunoconjugates; Meningitis, Haemophilus; Polysaccharides, Bacterial; Vaccination; Vaccines, Conjugate
PubMed: 26904695
DOI: 10.1155/2016/7203587 -
Clinical and Experimental Immunology Jan 2000
Review
Topics: Bacterial Vaccines; Child; Glycoconjugates; Haemophilus Vaccines; Humans; Immunologic Memory; Infant; Pneumococcal Vaccines; Polysaccharides, Bacterial; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 10671089
DOI: 10.1046/j.1365-2249.2000.01109.x