HIB / H. Flu Type B
Haemophilus influenzae type b (Hib) has been commonly associated with otitis media, sinusitis, bronchitis and other respiratory tract disorders. Prior to the development of the HiB vaccine, this bacteria caused meningitis in children under 2 years of age. The case-fatality rate of meningitis is about 5%.
Haemophilus influenzae type b - Epidemiology and Prevention of Vaccine-Preventable Diseases The Pink Book: Course Textbook - 12th Edition
Package Inserts:
Act-Hib Sanofi Pasteur, package insert (pdf)
ActHIB is also marketed as OmniHIB by SmithKline Beecham Pharmaceuticals
Comvax Merck, package insert (pdf) Haemophilus b Conjugate Vaccine & Hepatitis B Vaccine
Hiberix GSK, package insert (pdf)
Hibtiter - Wyeth, package insert
PedVaxHIB Haemophilus B Conjugate Vaccine (Meningococcal Protein Conjugate) PRP-OMP Merck Sharp & Dohme Corp.
Pentacel Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Sanofi Pasteur Limited
Polysaccharide HiB vaccine 1985
ProHibIt (PRP-D) Connaught Laboratories Inc. package insert as of July 1992
Tetramune Wyeth (DTP-HbOC) - package insert
March 31, 2018 - Immunogenicity and Reactogenicity of DTPa-HBV-IPV/Hib and PHiD-CV When Co-Administered with MenACWY-TT in Infants: Results of an Open, Randomized Trial
- Conflict of Interest and Source of Funding: GlaxoSmithKline Biologicals SA was the funding source and was involved in all stages of the study conduct and analysis. GlaxoSmithKline Biologicals SA also funded all costs associated with the development and the publishing of the present manuscript.
- ACM received financial support from the “Fundación Médica Alfonso Carmona”. JMMA received non-financial support and fees for consulting, lectures and expert testimony from the GSK group of companies and has received fees from Pfizer SA and Mundipharma outside the submitted work.
- XMPP was a speaker, researcher and consultant for the GSK group of companies.
- JMB served on the Board of Sanofi Pasteur MSD and has received fees from Sanofi Pasteur MSD (for lectures including service on speakers’ bureaus), from the GSK group of companies (for lectures including service on speakers’ bureaus, and as a principal investigator in clinical trials), and from Pfizer (as a principal investigator in clinical trials and for lectures including service on speakers’ bureaus).
- MW is an employees of the GSK group of companies.
- YB and DK were employees of the GSK group of companies at the time of the study.
YB and MW declared stock ownership in the GSK group of companies.
March 7, 2018 - The National Vaccine Advisory Committee at 30: Impact and opportunity "Notably, in 1988 ACIP recommended vaccination of all children against 8 diseases (i.e., diphtheria, tetanus, pertussis, polio, measles, mumps, rubella, and Haemophilus influenzae type b), and 30 years later the recommendations cover 16 diseases (i.e., the 8 above plus hepatitis B, hepatitis A, rotavirus, pneumococcal disease, influenza, meningococcal disease, HPV, and varicella). ... Further, despite substantial progress in reducing vaccine-preventable diseases of childhood (due to very high coverage with highly effective vaccines), significant effort remains to achieve the same for adults. NVAC will most likely need to focus on overcoming barriers and facilitating vaccine uptake of recommended vaccines for adults. In addition, vaccine hesitancy and vaccine confidence will likely continue to represent priorities, for which NVAC will likely play a continued role in addressing public and professional concerns."
December 4, 2017 - Hib antibody responses in infants following diphtheria, tetanus, acellular pertussis, and conjugated Haemophilus influenzae type b (Hib) combination vaccines with decreasing amounts of tetanus toxoid "DTaP vaccine manufactured by Connaught Laboratories (now known as Sanofi Pasteur) given with mHib and with Wyeth Hib-CRM197 (HbOC) as separate injections. Vaccines were administered to 240 healthy infants at 2, 4, and 6 months of age, and blood specimens for antibody determination were obtained before each immunization and one month after the third immunization. ... Reducing tetanus toxoid amounts did not produce comparable immunogenicity for Hib. The nature of the interaction between immune responses to DTaPH components should be explored further to enable the development of better Hib-containing combination vaccines."
July 24, 2017 - The changing epidemiology of invasive Haemophilus influenzae disease: Emergence and global presence of serotype a strains that may require a new vaccine for control "Although invasive Hia disease can be found globally, the current epidemiological data suggest that this infection predominantly affects Indigenous communities in North America. The clinical disease of Hia and the clonal nature of the bacteria resemble that of Hib. The high incidence of invasive Hia disease in Indigenous communities, along with potential fatality and severe sequelae causing long-term disability in survivors, may support the development of a new Hia conjugate vaccine for protection against this infection similar in design to the one introduced in the 1990s to control invasive Hib disease."
June 16, 2017 - 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 (full text) "Post-primary vaccination, 107/2963 (3.6%) infants receiving Hib-TT, 24/520 (4.6%) receiving Hib-TT control, and 21/520(4.0%) receiving DTaP-IPV/Hib-TT (Table S5) experienced a total of 233 SAEs. We assessed 6 SAEs as being causally related to vaccination: 5 in the Hib-TT group (2 normal sleep myoclonus events occurring in the same infant on days 3 and 38 post-dose 3, 1 Kawasaki’s disease with onset on the day of dose 3, 1 convulsion occurring on day 14 post-dose 1, and 1 involuntary muscle contractions of leg reported 63 days post-dose 1) and 1 in the Hib-TT control group (convulsion occurring on the day of the first vaccination). All related SAEs resolved by the end of the post-primary phase. Post-booster vaccination, we recorded 35 SAEs in 29/2337 (1.2%) toddlers in the Hib-TT group, 4/435 (0.9%) in the Hib-TT control and 2/400 (0.5%) in the DTaP-IPV/Hib-TT group (Table S5). We assessed 1 SAE (febrile seizure 1 day post-booster dose, resolved by the end of the study) in the Hib-TT group as being related to vaccination. There were no deaths during the study."
- Funding GlaxoSmithKline Biologicals SA was the funding source and was involved in all stages of the study conduct and analysis. GlaxoSmithKline Biologicals SA also took responsibility for all costs associated with the development and publishing of the present manuscript.
- Conflict of interest LBW, MLL, MV, and NPK declare receipt of research grants from GSK group of companies.
- LBW also received research grants from Merck and Novartis and speaker fees from Sanofi.
- MV received research grants from Merck, Sanofi, Novartis, Regeneron, Pfizer, MedImmune, and speaker fees from Pfizer and Sanofi.
- NPK declares receipt of grants from Merck, Pfizer, Sanofi Pasteur, MedImmune, Novartis and Protein Science.
- SEG is speaker for Sanofi and speaker and consultant for Pfizer.
- BC, JMM, NM, RAE and SRG hold shares in the GSK group of companies as part of their employee remunerations.
- ML and YB were employees of GSK group of companies during the study and report receipt of company restricted shares.
June 2017 - Immunogenicity and Safety of a Booster Injection of DTap-IPV//Hib (Pentaxim) Administered Concomitantly With Tetravalent Dengue Vaccine in Healthy Toddlers 15–18 Months of Age in Mexico: A Randomized Trial "Two nonrelated deaths were reported during the study: complex congenital cyanogen cardiopathy and postoperative complications in a participant not randomized at month 6, and myelomonocytic leukemia in a participant in group 2. One participant in group 1 experienced an SAE of special interest that was considered significant (hemorrhagic dengue requiring hospitalization, nonsevere). Five participants reported non-SAEs of special interest: 2 participants (0.6%) in group 1 and 3 participants (1.0%) in group 2. Only 1 episode, urticaria, was considered related to the study vaccines."
- This study was funded by Sanofi Pasteur.
- E.R., C.V. and F.N. are employees of Sanofi Pasteur.
- Address for correspondence: Enrique Rivas, MD, Clinical Sciences, Sanofi Pasteur, Avenida Universidad 1738, Coyoacán, 04000 Mexico City, Mexico. E-mail: enrique.rivas@sanofipasteur.
com. - Editorial assistance with the preparation of the manuscript was provided by professional medical writer, Lorraine Ralph of inScience Communications, Springer Healthcare, funded by Sanofi Pasteur.
May 19, 2017 - Effect of prophylactic or therapeutic administration of paracetamol on immune response to DTwP-HepB-Hib combination vaccine in Indian infants (full text) "The study found no evidence that paracetamol usage either as prophylactic or for treatment impact immunological responses to DTwP-HepB-Hib combination vaccine."
- Conflict of interests The site investigators have no financial interest in the vaccine or the manufacturer but received research grants from Shantha Biotechnics Private Limited –a sanofi Company; for conducting the study at their respective sites.
- AS, BNP, MSD, SPR, MVJ, NA, SM, SR and JE were all employees of the manufacturer of the investigational vaccine (Shantha Biotechnics Private Limited – a Sanofi Company) and MD is an employee of Sanofi Pasteur, France involved during the planning, analysis and interpretation of the study.
- Financial disclosure The study was fully funded by Shantha Biotechnics Private Limited –a Sanofi Company.
February 2017 - A Phase III Randomized, Double-blind, Clinical Trial of an Investigational Hexavalent Vaccine Given at Two, Three, Four and Twelve Months (full text) "A hexavalent vaccine [diphtheria–tetanus toxoids–pertussis, hepatitis B vaccine, inactivated poliovirus vaccine and H. influenzae type b (DTPa3–HBV–IPV/Hib); Infanrix-hexa (GlaxoSmithKline Inc., Mississauga, Ontario, Canada); Control] has been licensed in Europe for over a decade (the only hexavalent vaccine available at the time of the study), a period during which improvement in immunization timeliness and stable effectiveness in disease prevention has been observed." . . . "The fully liquid investigational hexavalent vaccine [diphtheria–tetanus toxoids–acellular pertussis 5, hepatitis B, inactivated poliovirus vaccine and H. influenzae type b (DTaP5–HB–IPV–Hib)] reported here contains a 5-antigen pertussis component and has a different carrier protein conjugated to the Hib antigen. This report presents results from a pivotal European Union Phase III study (NCT01341639), assessing the safety, tolerability and immunogenicity of DTaP5–HB–IPV–Hib compared with Control, when administered at 2, 3, 4 and 12 months, concomitantly with Prevenar 13 (PCV13) (Pfizer, Philadelphia, PA), RotaTeq (RV5) (Merck & Co., Inc., Kenilworth, NJ) and ProQuad (MMRV) (Merck & Co., Inc., Kenilworth, NJ). Another study of DTaP5–HB–IPV–Hib and Control when administered in the 2-month, 4-month, and 11-month to 12-month schedule has also been completed and is described in a separate manuscript.
- Funding for this research was provided by Merck & Co., Inc., Sanofi Pasteur, Inc. and Sanofi Pasteur MSD. Although the funding companies formally reviewed a penultimate draft, the opinions expressed are those of the authors and may not necessarily reflect those of the sponsors. All coauthors approved the final version of the manuscript.
- T.V., T.B., A.F.V. and K.P. were investigators for the sponsor supported by research grants.
- M.F.P., S.A.F., J.X., G.F.L., J.E.S. and A.W.L. are employees of Merck & Co., Inc. and may hold company stock and/or stock options.
- F.B., S.T. and E.Z. are employees of Sanofi Pasteur MSD
COMMENT: I believe this was perhaps one of the most despicable studies I have ever seen…using a FULL complement of vaccines and nearly the SAME VACCINE as the placebo/control. Nearly 100% of babies in both groups had side effects, which were only followed for a dismal 15 days (remember, if they develop seizures or SIDS on day 16 or after, it’s not due to the vaccine, according to the study design.) Prevnar 13 and ProQuad (MMRV) are two of the most neurotoxic vaccines on the market. Thirty children had serious adverse events (SAEs) within the first 30 days, but the types of side effects were not included in the discussion.
Arghhh!! 'All that matters to these poisoners who have been deemed to be “investigators” is that EACH vaccine antigen induces an antibody, the generalized marker of contamination. This “research” should be labeled medical assault, maybe assault with a potentially deadly weapon. I wonder what was offered to coerce parents into sacrificing their children to the Pharma gods? I wonder how many of these '''''children remained “healthy” after at the endpoint of this trial?
December 7, 2016 - Simultaneous vaccination with MMR and DTaP-IPV-Hib and rate of hospital admissions with any infections: A nationwide register based cohort study "By 2 years of age, 4965 children had simultaneous MMR and DTaP-IPV-Hib as their most recent vaccination. Compared with MMR alone, simultaneous administration was associated with a higher rate of lower respiratory tract infections (adjusted incidence rate ratio (IRR), 1.27; 95% confidence interval (CI), 1.13–1.42). There was no effect on other infections. Overall, simultaneous administration was associated with a 7% (95% CI, 0–15%) increase in infectious disease admissions."
August 31, 2016 - Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study (full text) "The overall proportion of adverse reactions for the PRP-CRM197 group (82.4%, 229/278) was higher than that for the PRP-T group (62.0%, 85/137 subjects), owing to the higher proportion of injection site
July 29, 2016 - Safety of DTaP-IPV/Hib vaccine administered routinely to infants and toddlers (full text) "Poisoning by other medications and drugs - There were a total of 11 cases combined after the 3rd and 4th doses. Of these, one that was after the 4th dose of DTaP-IPV/Hib was determined by the study investigator (Klein) possibly to be related to receipt of DTaP-IPV/Hib. It consisted of an approximate 3×4cm flat area of erythema near the injection site that was diagnosed as “Vaccines adverse reaction”. "..."The largest two categories of non-fever events were “Nausea with vomiting” and “Vomiting alone” of which there were 16 total cases. The range of days was from the day 1 to day 18. The mean days for medical attention were 11 and 6, respectively, or 8.6 when the two categories are combined. Additionally, one sub-category was allergic reactions of which there were four cases, two of which were determined by the investigator to be related to receipt of DTaP-IPV/Hib (both being cases of urticaria beginning on the day of vaccination).
July 19, 2016 - A Phase III randomized, double-blind, clinical trial of an investigational hexavalent vaccine given at 2, 4, and 11–12 months "A Phase III randomized, double-blind, clinical trial of an investigational hexavalent vaccine given at 2, 4, and 11–12 months "The DTaP5-HB-IPV-Hib Group received the investigational hexavalent vaccine (DTaP5-HB-IPV-Hib) and the Control Group received Infanrix-hexa (DTPa3-HBV-IPV/Hib) at 2, 4 and 11–12 months of age. Both groups received concomitantly Prevnar 13 (PCV13) and Rotateq (RV5) or Rotarix (RV1) at 2, 4 months of age and PCV13 at 11–12 months. Subjects administered RV5 received a 3rd dose at 5 months of age." Comment: This is not a true control group.
May 18, 2015 -Review of Epidemiological Studies on Hib & Hepatitis B Vaccines and Autism (pdf) "Studies referenced by the CDC website as well as other potentially relevant studies were reviewed. The review concluded that there are zero studies meeting these criteria which resulted in a finding of ‘no association’. The review identified one independent study which found a 3x increased risk of autism associated with the HBV vaccine. In summary, there were no studies on the Hib Conjugate Vaccine and the only study which was performed found a link between the Hepatitis B vaccine and autism. The details of the review are included in the following tables."
March 6, 2015 - Update on Vaccination Guidelines for Older Adults "The number of infections covered and the types of vaccines available has grown significantly in recent years. Although this represents tremendous progress, it can also result in confusion and missed opportunities to provided recommended vaccinations. This review summarizes the current guidelines for vaccination of older adults and highlights the latest innovations."..."Generalizing vaccine guidelines for adults and implementing them in practice is more complicated than for childhood vaccines. A range of c'o-morbidities may affect vaccine recommendations; for instance, there are no age-specific recommendations for Haemophilus influenzae or meningococcus vaccination, although they are recommended in all asplenic adults.There is the practical hurdle of understanding payer responsibility and reimbursement, and there is the challenge of understanding the potential benefits and limitations of a vaccine.
February 2015 - Immunological effect of administration of sequential doses of Haemophilus influenzae type b and pneumococcal conjugate vaccines in the same versus alternating limbs in the routine infant immunisation schedule: an open-label randomised controlled trial "In this open-label, randomised, controlled study, eligible healthy infants 6–12 weeks of age recruited through five clinical trials units (four in the UK and one in Malta) were randomly assigned in a 1:1 ratio to two vaccination groups: consistent limb or alternating limb."..."Use of different (alternating) limbs for sequential doses of routine infant vaccines does not reduce, and might enhance, immunogenicity. The underlying mechanism for this finding warrants further research."
- Funding NIHR Oxford Biomedical Research Centre and GlaxoSmithKline Biologicals.
January 15, 2015 - Adverse Events following Haemophilus influenzae Type b Vaccines in the Vaccine Adverse Event Reporting System, 1990-2013 "VAERS received 29 747 reports after Hib vaccines; 5179 (17%) were serious, including 896 reports of deaths. Median age was 6 months (range 0-1022 months). Sudden infant death syndrome was the stated cause of death in 384 (51%) of 749 death reports with autopsy/death certificate records. The most common nondeath serious AE categories were 'neurologic (80; 37%)', other noninfectious (46; 22%) (comprising mainly constitutional signs and symptoms); and gastrointestinal (39; 18%) conditions. No new safety concerns were identified after clinical review of reports of AEs that exceeded the data mining statistical threshold."
November 2014 - A Case-Control Study Evaluating the Relationship Between Thimerosal-Containing Haemophilus influenzae Type b Vaccine Administration and the Risk for a Pervasive Developmental Disorder Diagnosis in the United States "The present study revealed cases diagnosed with PDD were overall, among both male and female cases analyzed separately, and on a dose-dependent basis, significantly more likely than controls to receive increased organic Hg exposure from Thimerosal in Hib-containing vaccines administered at specific intervals within the first 15 months of life."
October 2, 2014 - A randomised trial to evaluate the immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines in Singapore and Malaysia (full text) "One Grade 3 unsolicited AE considered causally related to vaccination (urticaria) was reported in the ComCom group. Four toddlers in the ComCom group reported SAEs; none were considered causally related to vaccination and none were fatal."
- Competing interests: CYC declared having received grants from GlaxoSmithKline Biologicals SA for research coordination, clinics, and vaccines. CYC received payment for training workshop lectures and for travelling to a conference.
- MTK and FSL declared having received grants for carrying out the reported study and other studies and travel fees for presenting the study results at conferences. MTK received honorarium as speaker at meetings organised by the Malaysian Paediatric Association.
- PCC received payment for giving talks on vaccination to doctors and nurses and for travelling to a conference.
- DB, FS, YLT were employed by GlaxoSmithKline Vaccines during the study period. KS and MH worked as consultant for GlaxoSmithKline Vaccines. DB declared stock options ownership in GlaxoSmithKline Vaccines.
- Role of the funding source: GlaxoSmithKline Biologicals SA was the funding source and was involved in all stages of the study conduct and analysis. GlaxoSmithKline Biologicals SA also took responsibility for all costs associated with the development and publishing of the present manuscript.
August 8, 2014 - Vaccine effectiveness of the pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against clinically suspected invasive pneumococcal disease: a cluster-randomised trial "'The vaccine effectiveness was 50% (95% CI 32—63) in the 30 527 infants with three plus one and two plus one schedules combined and the absolute incidence rate reduction was 207 episodes per 100 000 person-years (95% CI 127—286). The vaccine effectiveness against the patient-file verified non-laboratory-confirmed invasive pneumococcal disease was 71% (95% CI 52—83) in infant three plus one and two plus one schedules combined."..."Funding: GlaxoSm
November 14, 2013 - Motor palsies of cranial nerves (excluding VII) after vaccination: Reports to the US Vaccine Adverse Event Reporting System (full text) Cranial nerve palsies were reported after a wide variety of vaccines (Table 3). Most reports (43; 63%) listed a single vaccine. Among reports listing single vaccines, the most common vaccines were influenza vaccine seasonal trivalent inactivated, human papillomavirus vaccine quadrivalent, influenza H1N1 vaccine inactivated, and zoster vaccine live. Among reports listing multiple vaccines, the most common vaccines included hepatitis A vaccine; measles, mumps, and rubella vaccine live; diphtheria and tetanus toxoids and acellular pertussis vaccine; Hemophilus influenzae type b vaccine; and pneumococcal conjugate vaccine 7-valent. There was no conspicuous clustering of live or inactivated vaccines with palsies of particular cranial nerves.
November 2013 - Nonprotective Responses to Pediatric Vaccines Occur in Children Who Are Otitis Prone "We recently found that children who experience recurrent otitis media 'despite individualized care' (stringently-defined otitis prone [sOP]) 'do not develop an antibody response' to several vaccine candidate protein antigens expressed by Streptococcus pneumonia (Spn) and Haemophilus influenzae. Here we sought to determine if these same children also failed to develop antibody to routine pediatric vaccinations."
November 2013 - Enhancement of Serum and Mucosal Immune Responses to a Haemophilus influenzae Type B Vaccine by Intranasal Delivery "Intranasal (i.n.) vaccination is potentially the most direct method for conveying upper respiratory and mucosal immunity to respiratory pathogens. However, for unclear reasons, vaccines introduced into the nasal sinuses often have lower efficacy than vaccines administered by the more frequently used parenteral routes."
Sepetember 1, 2013 - Effect of breast feeding on immunologic priming in young infants."The proposed research tests the hypothesis that breast feeding accelerates B cell priming and immunoglobulin diversity following immunizations at 2 and 4 months of age by modulating the microbial colonization of the infant gut. Studies will focus on the response to the conjugated vaccines against Haemophilus influenza (HIb) and Streptococcus pneumonia [Prevnar 13(R)]. A major goal of this application is to determine mechanisms by which breast feeding impacts neonatal B cell development and antibody affinity maturation. To test our hypothesis, immune responses and gastrointestinal microbe colonization from birth to one year of age will be examined among infants who are exclusively breast fed for at least the first four months of life versus those who are exclusively formula fed."
June 18, 2013 - Non- Protective Responses to Pediatric Vaccines Occur in Children Who are Otitis Prone "We recently found that children who experience recurrent otitis media despite individualized care (stringently-defined otitis prone, sOP) '''do not develop an antibody response to several vaccine candidate protein antigens expressed by Streptococcus pneumonia (Spn) and Haemophilus influenzae (Hi). Here we sought to determine if these same children also failed to develop antibody to routine pediatric vaccinations."
July 9, 2013 - Effectiveness of Haemophilus influenzae Type b Vaccines Administered According to Various Schedules: Systematic Review and Meta-Analysis of Observational Data "There was some evidence that Hib vaccine was less effective when administered with acellular (rather than whole cell) pertussis vaccine. Weak evidence from two studies suggested that a booster confers some additional protection following full primary vaccination and may compensate for an incomplete primary series."
June 2013 - Septic Arthritis Caused by Noncapsulated Haemophilus influenzae "Since the introduction of type b Haemophilus influenzae vaccination, noncapsulated H. influenzae has become responsible for most cases of invasive H. influenzae diseases. Comment: The particular strain in the vaccine was the most prevalent before use of the Hib vaccine. As more people received the vaccine this strain mentioned above, noncapsulated (meaning not a vaccine type) Haemophilus influenzae became the dominant strain.
April 2013 - Making a case for universal Hib immunization in India: over interpreting the data (pdf) "No justification was provided as to why the data from the next year (when there were only 3 cases of Hib) were not used . In the present study 1 , 62 cases of Hib were found among 2912 children with clinically suspected meningitis and it represents 2.1 per cent of the clinically suspected cases (not 12% as used in the Kerala projection).
November 16, 2012 - Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster randomised trial "3 culture-confirmed vaccine-type cases of invasive pneumococcal disease were detected: none in the PHiD-CV10 3+1 group, one in the PHiD-CV10 2+1 group, and 12 in the control groups. The estimates for vaccine effectiveness were 100% (95% CI 83—100) for PHiD-CV10 3+1 and 92% (58—100) for PHiD-CV10 2+1 groups. Two cases of any culture-confirmed invasive disease irrespective of serotype were detected in combined PHiD-CV10 infant cohorts compared with 14 in the corresponding control cohorts (vaccine effectiveness 93%, 75—99). In catch-up cohorts, seven cases of invasive disease were reported, all in the control group: two cases in the children enrolled at 7—11 months of age; and five cases in children enrolled at 12—18 months of age (vaccine effectiveness 100%, 79—100). Non-fatal serious adverse events suspected to be vaccine-related were reported via routine post-immunisation safety surveillance in 18 children."... Funding'GlaxoSmit'hKline Biologicals SA and National Institute for Health and Welfare, Finland'''.
September 1, 2012 - Haemophilus influenzae Type b Disease and Vaccine Booster Dose Deferral, United States, 1998–2009 "Among Hib cases in both time periods, most were unvaccinated or too young to have received Hib vaccine. During 2001 to 2009, there were <53 Hib cases per year, with an estimated 6 to 12 Hib cases misclassified as unknown serotype."
April 30, 2012 - Recurrent 6th nerve palsy in a child following different live attenuated vaccines: case report (pdf) "There is limited information in the literature regarding the safety of a repeat dose of a live vaccine in this setting. As detailed above, a recurrent case of a nerve palsy has been described post MMR. [5,7] A second and further dose is recommended to increase the likelihood of sero-conversion, but ultimately further immunizations should be considered on an individual basis.
April 16, 2012 - Haemophilus influenzae type b combination vaccines and atopic disorders: A prospective cohort study (full text) "A total of 19,968 children completed the follow-up and participated in the study. AD was noted in 1584 (7.9%) infants while recurrent wheezing was found in 1220 (6.1%) infants. The adjusted odds ratios (ORs) (95% CI) for the development of AD in the DPT-Hib&OPV and DPT-Hib-IPV vaccination groups were given as 1.38 (1.15-1.65) and 1.49 (1.29-1.72), compared to those without Hib vaccination (DTP&OPV vaccination). However, the association between DPT-Hib&OPV and DPT-Hib-IPV vaccinations and recurrent wheezing failed to reach statistical significance. Conclusion There is a potential risk for AD after receiving Hib combination vaccines. Hib vaccination is important to the public health, and therefore the observation requires further investigations."
February 22, 2012 - Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b "DTaP-IPV-Hib vaccination was associated with an increased risk of febrile seizu'res on the day of the first 2 vaccinations given at 3 and 5 months, although the absolute risk was small. Vaccination with DTaP-IPV-Hib was not associated with an increased risk of epilepsy." Comment: It has long been assumed that febrile seizures do not lead to a life time of epilepsy. However, if a vaccine is causing febrile seizures, perhaps the vaccine is doing more the brain than simply causing a fever? The answer is unknown.
February 2012 - Immune response to Haemophilus influenzae type b conjugate vaccine in preterm infants "There is a possibility that perinatal factors and the environment unique to preterm infants are related to their lower antibody positivity rates compared to full-term infants. It may therefore be preferable to modify the proposed immunization schedule." Comment: This seems to be a big push to vaccinate earlier and earlier. Preterm infants are vaccinated on time and with the full dose of the vaccine, even if they were born 8 weeks early. There is no recognition by the medical community of the immaturity of the immune system, the central nervous system, etc. The focus is simply to be sure that the infants are' vaccinated.
November 8, 2011 - Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H. influenzae type b in Brazil. "Following routine childhood vaccination against Haemophilus influenzae type b (Hib) disease in Brazil in 1999, passive laboratory surveillance reported increased numbers of non-b serotypes and nontypeable H. influenzae (NTHi) from meningitis cases." Comment: This study documents that strain selection is starting to occur. Strains of H influenzae have been erotyped into 6 different types (a-f) based on their biochemically different capsules. Some strains have no capsule and are termed nonencapsulated H influenzae or nontypeable H influenzae (NTHi). Widespread use of the vaccine to eliminiate serotype b is allowing other strains to emerge.
September 2011 - Infantile bullous pemphigoid developing after hexavalent, meningococcal and pneumococcal vaccinations "We present a 3-month-old girl with a blistering eruption on her palms and soles, and urticarial plaques on trunk, and face, 3 weeks after vaccine at two months (hepatitis B, diphtheria, tetanus, pertussis, polio, Haemophilus influenzae B, meningococcal C, pneumococcus). The clinical course worsened with vaccinations at 4 and 6 months." Comment: Bullous pemphigoid is a chronic, autoimmune, subepidermal, blistering skin disease. IgG autoantibodies bind to the skin basement membrane, activating complement and other inflammatory mediators. If untreated, the disease can persist for months or years, with periods of spontaneous remissions and exacerbations. In most patients who are treated, bullous pemphigoid remits within 1.5-5 years. Patients with aggressive or widespread disease, those requiring high doses of corticosteroids and immunosuppressive' agents.
September 2011 - Increasing incidence of invasive Haemophilus influenzae disease in adults, Utah, USA. "Despite the virtual elimination of Hib in areas with widespread use of Hib vaccine, invasive disease caused by H. influenzae remains a major source of illness and death. The incidence of invasive H. influenzae in Utah adults appears to be increasing; most of the increase in H. influenzae disease incidence was attributable to an increase in nontypeable and Hi(f) strains. We found that invasive H. influenzae disease was most common in persons >65 years of age and was associated with a high mortality rate." Comment: Another study documenting strain selection is occurring. Strains of H influenzae have been erotyped into 6 different types (a-f) based on their biochemically different' capsules.
May 2011 - Femoral neuropraxia after vaccination in a 3-month-old infant: a case report "We report an incidence of a 3-month-old infant who developed femoral neuropraxia after vaccination (diphtheria, tetanus and acellular pertussis/inactivated poliovirus/haemophilus influenzae type B vaccine) in the thigh." Comment: Neuropraxia is a nerve disorder in which there is a temporary loss of motor and sensory function due to blockage of nerve conduction. Neurapraxia results in temporary damage to the myelin sheath but leaves the nerve' intact.
July 29, 2010 - Dear Health Care Provider Letter: Information Re: Hiberix (Haemophilus B Conjugate Vaccine [Tetanus Toxoid Conjugate) Tip Caps Of The Prefilled Diluent Syringes May Contain Natural Rubber Latex Which May Cause Allergic Reactions In Latex Sensitive Individuals] Comment: Natural rubber latex in vaccine vials has been shown to cause serious allergic reactions. Synthetic rubber for stoppers have been available for more than 60 years, but has only been widely used in vaccine vials since 2010. Many vaccine stoppers still use' latex.
May 28, 2010 - Changing epidemiology of invasive Haemophilus influenzae in Ontario, Canada: evidence for herd effects and strain replacement due to Hib vaccination. "Vaccination against Hib has altered the epidemiology of invasive H. influenzae infections in Ontario. Prevention of invasive Hib disease was observed in both vaccinated and unvaccinated age groups. Invasive H. influenzae infection now commonly presents as sepsis due to non-typeable serotype (h). influenzae in older individuals. However, strain replacement of Hib with serotype f and non-typeable strains in children under 5 years was documented." Comment: More strain selection due to HiB vaccines.
February 2010 - Epiglottitis due to nontypeable Haemophilus influenzae in a vaccinated child. Comment: More strain selection due to HiB vaccines.
August 4, 2009 - Booster may be beneficial for children who experience Hib vaccine failure Comment: When the vaccine doesn't produce an antibody, revaccinating is recommended.
February 2009 - WHO study suggests low incidence of Hib in India is due to natural immunity (pdf)
2008 - Risk of Vaccine Induced Diabetes in Children with a Family History of Type 1 Diabetes (pdf) Dr. Barton Classen. "The rate ratios in children who received at least one dose of a specific vaccine were also elevated in the subgroup and were statistically the same as in the general population. Three doses of the hemophilus vaccine were associated with a rate ratio of 1.23 and an absolute risk in the general population of three cases/100,000 per year compared to 1.58 and an absolute risk of 2885 cases/100,000 per year in the subgroup with a sibling with type 1 diabetes. The hemophilus immunization is associated with a cumulative attributable risk of 2.3/100 (2.3%) of developing insulin-dependent diabetes in the subgroup".
December 17, 2007 - Merck Recalls HIB Vaccine: Contamination Risk - "In what appears to be a pattern involving vaccine quality control production problems, on Dec. 12, 2007 Merck & Co. announced that it was recalling 13 Lots containing 1.2 million doses of HIB vaccine (PedvaxHIB and the combination COMVAX containing HIB and hepatitis B vaccines) for possible contamination with the common bacterium called Bacillus cereus (B. cereus)."
December 11, 2007 - Recall of PedvaxHIB [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) and COMVAX [Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine]-Merck & Co., Inc]. FDA: These lots of PedvaxHIB and COMVAX are being recalled due to lack of assurance of product sterility.
November 21, 2007 - Haemophilus b Conjugate Vaccine Tetanus Toxoid Conjugate (ActHIB) "The professional journal advertisement is misleading because it states that ActHIB is superior to PedvaxHIB [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)] and HibTITER [Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate)], when this has not been demonstrated by substantial evidence or substantial clinical experience."
August 21, 2007 - Re-emergence of Haemophilus influenzae type b (Hib) disease in The Gambia following successful elimination with conjugate Hib vaccine Comment: Vaccination campains were in 1997 but cases of meningitis occurred in 2002-3. Vaccination does not permanently eliminate invasive disease.
July 10, 2007 - Research on Hib vaccine 'dubious' "Where starvation and cholera kill thousands of children each year, international agencies such as the GAVI Alliance, USAID and the WHO are bu'sy spending millions on dubious research to emphasise the harm from a disease that local doctors hardly ever come across. All this so that vaccine manufacturers can fill their coffers. This situation can only be described as scandalous."
September 2005 - Presence of multiple copies of the capsulation b locus in invasive Haemophilus influenzae type b (Hib) strains isolated from children with Hib conjugate vaccine failure "Recently, an increase in the incidence of invasive Hib disease has been observed in the United Kingdom, predominantly in immunized children. Although predisposing host risk factors and the use of less immunogenic vaccines have been considered, the possibility that particular virulent traits of the bacterium may contribute to vaccine failure cannot be ruled out."
May 2005 - Bullous pemphigoid in an infant after vaccination (Spanish full text) "We present a case of BP in a two-month-old infant with bullous pemphigoid lesions on the palms and soles, which appeared one week after receiving the first dose of the hepatitis B, polio, DTP and HiB vaccine."
March 2005 - Vaccination failure: case report of Haemophilus influenzae b meningitis in a 14-month-old child
July 8, 2004 - Anaphylaxis Complicating Routine Childhood Immunization: Hemophilus Influenza b Conjugated Vaccine We report the case of a 4-month-old Caucasian male who developed an urticarial rash within 10 minutes of receiving his 4-month immunizations, diphtheria-tetanus-acellular pertussis (DTaP), inactivated polio (IPV), and the diphtheria mutant protein (CRM197) conjugated Hemophilus influenzae type b (HiB). The child was referred for an allergy-immunology consultation in order to determine the cause of the reaction and a future vaccine management strategy... Skin testing with CRM197 alone (the protein conjugate in HiB) was positive, confirming the source of the reaction. The patient tolerated subsequent Hib immunization with a CRM-free preparation without complications. Our case report suggests that the mutant diphtheria protein CRM197 may be an allergenic protein in some patients who develop anaphylaxis to the HiB vaccine. The new pneumococcal vaccine (Prevnar) contains CRM197.
April 2004 - Endotoxin content in Haemophilus influenzae type b vaccine (pdf) "However, endotoxin that can carry over from Gram-negative H. influenzae with a purified component may contribute to adverse events following Hib vaccination. In the present study, we examined the endotoxin content in Hib conjugate vaccines. The Hib conjugate vaccine batches''', which were produced by a European vaccine manufacturer, were shown to have considerably high endotoxin activity and to vary from' 13.9 to 173.7 endotoxin units/dose'''. These results suggest that it is necessary to monitor the endotoxin content of the vaccine batches to ensure the quality and safety of the vaccines."
February 2004 - Haemophilus influenzae meningitis in a child with complete immunisation
January 2004 - Outbreak of Haemophilus influenzae type b disease among fully vaccinated children in a day-care center
November 2003 - Vaccinations may induce diabetes-related autoantibodies in one-year-old children "Vaccinations have been discussed as one among many environmental candidates contributing to the immune process that later may lead to type 1 diabetes. Furthermore, '''the titers of IA-2A were significantly higher in those children who had got HIB vaccination. When 99th percentile was used as cutoff to identify the children at risk of type 1 diabetes, BCG vaccination was also associated with increased prevalence of IA-2A (p < 0.01). We conclude that HIB vaccination may have an unspecific stimulatory polyclonal effect increasing the production of GADA and IA-2A. This might be of importance under circumstances when the β cell-related immune response is activated by other mechanisms."
May 27, 2003 - Classen Immunotherapies Inc. Release: More Proof Published That Common Childhood Vaccines Are The Cause Of The Diabetes Epidemic, Data Identifies Children Eligible For Compensation "The Journal of Pediatric Endocrinology and Metabolism published a study by Dr. J. Bart Classen, an immunologist at Classen Immunotherapies, and David Carey Classen, an infectious disease specialist at the University of Utah, providing support for a causal relationship between several common pediatric vaccines and the development of insulin dependent diabetes. Their previously published work proved the hemophilus vaccine, a common pediatric vaccine, caused a 25% rise in insulin dependent diabetes in children under the age of 7.
April-May 2003 - Clustering of cases of type 1 diabetes mellitus occurring 2-4 years after vaccination is consistent with clustering after infections and progression to type 1 diabetes mellitus in autoantibody positive individuals. - "Conclusion: The identification of clusters of cases of type 1 diabetes (T1DM) occurring in consistent temporal time periods allowed a link between the hemophilus vaccine and T1DM to be established'''. The current findings indicate the there are also clusters of cases of T1DM occurring 2-4 years post-immunization with the pertussis, MMR, and BCG vaccine. The data are consistent with the occurrence of clusters following mumps infection and the progression to T1DM in patients with antipancreatic autoantibodies."
May 2003 - Haemophilus influenzae type b conjugate vaccine failure
April 2003 - Paediatric acute epiglottitis: not a disappearing entity "Whilst the incidence of Haemophilus type b epiglottitis has significantly diminished, vaccine failure does occur."
July 31, 2002 - Hemophilus meningitis vaccine proven to cause diabetes in clinical trial of over 100,000 children. Many diabetics eligible for compensation. "After 7 years the group receiving 4 doses of the vaccine had an statistically significant 26% elevated rate of diabetes, or an extra 54 cases/100,000 children, compared to children who did not receive the vaccine. By contrast immunization against hemophilus is expected to prevent only 7 deaths and 7 to 26 cases of permanent disability per 100,000 children immunized. The study showed that almost all of the extra cases of diabetes caused by the vaccine occurred between 3-4 years after vaccination."
July 2002 - Clustering of cases of insulin dependent diabetes (IDDM) occurring three years after hemophilus influenza B (HiB) immunization support causal relationship between immunization and IDDM "Conclusion: Exposure to HiB immunization is associated with an increased risk of insulin-dependent diabetes."
July 2002 - Hemophilus Vaccine Study in Finland Proves a Causal Relationship Between Vaccines and Diabetes (published Autoimmunity 35:247-253,2002)
February 2002 - Haemophilus influenzae type b conjugate vaccine diluted tenfold in diphtheria-tetanus-whole cell pertussis vaccine: a randomized trial "Conclusions. The 1/10 dose of vaccine was as immunogenic and safe as the full dose. The technique of diluting a single dose of PRP-T in a 10-dose DTP vial could potentially allow the widespread introduction of Hib vaccine in resource-poor countries currently unable to afford full dose Hib conjugate vaccine." Comment: If using only 1/10 of the normal dose of vaccine can induce an antibody response, why is a full dose needed?
August 2001 - Adverse events following vaccination in premature infants "The aims of this study were to study the frequency, severity and types of adverse reactions following DPT/Hib (diphtheria and tetanus toxoids and pertussis Haemophilus influenzae type B conjugate) immunization in very preterm infants and to identify possible risk factors. ... Apparent adverse events were noted in 17 of 45 babies: 9 had major events, i.e. apnoea, bradycardia or desaturations, and 8 had minor events, i.e. increased oxygen requirements, temperature instability, poor handling and feed intolerance."
May 2000 - Diminution of the anti-polyribosylribitol phosphate response to a combined diphtheria-tetanus-acellular pertussis/Haemophilus influenzae type b vaccine by concurrent inactivated poliovirus vaccination. "Conclusion: In this trial concurrent IPV appeared to interfere with the anti-PRP response to DTaP/Hib vaccine, suggesting that introduction of new vaccines may require evaluation of immune responses to all concurrently administered vaccines." Comment:This study confirms that administering polio vaccines with DTaP and HiB vaccines can cause immunosuppression and inadequate antibody development.
October 23, 1999 - Association between type 1 diabetes and Hib vaccine - Causal relation is likely
July 1999 - Severe apnoeas following immunisation in premature infants. "Four premature infants developed apnoeas severe enough to warrant resuscitation after immunisation with diphtheria, pertussis, and tetanus (DPT), and Haemophilus influenzae B (Hib). One required re-intubation and ventilation. Although apneas after immunization are recognized, they are not well documented. It is time for further research to elucidate the best time to immunise such infants."
May 7, 1999 - Hemophilus vaccine and increased IDDM, causal relationship likely.
November 1999 - Acute epiglottitis despite vaccination with haemophilus influenzae type B vaccine. "We present the case of a 20-month-old child who required admission to the intensive care with a presumptive diagnosis of acute laryngo–tracheo-bronchitis, for the management of acute upper airway obstruction. This child had received a complete course of Haemophilus influenzae type B (Hib) vaccine. Subsequent events showed that the diagnosis was not laryngo–tracheo-bronchitis but acute epiglottitis. We propose that a full course of vaccination is no guarantee against a subsequent illness with Hib and may actually lead to the wrong diagnosis and possibly life-threatening consequences."
September 1998 - Haemophilus influenzae type b vaccines: history, choice and comparisons "The conjugate Haemophilus influenzae type b (Hib) vaccines are safe and far more immunogenic among infants and young children than is the unconjugated H. influenzae type b polysaccharide. The vaccines differ in their immunogenicity when used for primary immunization of infants, and these differences appear to be predictive of efficacy, such that some vaccines might be more suitable than others in certain populations." Comment: Initially, there were two different HiB vaccines on the market; H flu polysaccharide vaccines eventually fell into disuse because they were associated with an increased risk of invasive HiB disease.
March 1998 - Invasive infection with Haemophilus influenzae type b in spite of complete vaccination "Five patients, 4 boys and 1 girl aged 13-41 months, developed invasive Haemophilus influenzae type b (Hib) disease (2 epiglottitis, 3 meningitis) despite full (or at least 3 times) vaccination."
October 1997 - IgA nephropathy in mice following repeated administration of conjugated Haemophilus influenzae type B vaccine (PRP-T) We concluded that conjugated Haemophilus influenzae type b vaccine, given at two-week intervals to a total of six doses, caused secondary IgA nephropathy in mice.
1997 - Post immunization Hib antigen detection in the CSF of a patient with meningococcal meningitis "We report a case of meningococcal meningitis where the cerebrospinal fluid was negative for Neisseria meningitidis but positive for Haemophilus influenzae type b by rapid antigen detection test. We believe that this was due to prior immunization with Haemophilus influenzae type b vaccine."
December 10, 1996 - NICHD Researchers Honored by World Health Organization for Developing Vaccines Against Hemophilus Influenzae "Although effective, the polysaccharide vaccine failed to stimulate protective antibody levels in infants, the age group with the highest incidence of serious disease. In work for which they would later receive their Lasker Award, the two NICHD investigators developed a new 'conjugate' technology to create a vaccine. They linked a "weak" polysaccharide to a protein easily recognized by the immature immune system. The conjugate vaccine was soon found to be effective in infants as well as older children. Since 1987, Hib conjugate vaccines have been licensed and marketed, and have become part of the routine pediatric immunization series given to babies starting at age 2 months."
July 1996 - The Perilous HIB By Hilary Butler "The June 1992 issue of Newsletter from the Journal of Paediatric Infectious Disease (JPID) stated: 'THE PERILOUS PNEUMOCOCCUS. We have great concern for the increasing prevalence of relatively or absolutely penicillin resistant pneumococci coupled with the increased relative frequency of pneumococcal diseases as a result of universal Haemophilus vaccination.'" 'Comment: As the HiB was used more, the bacteria that filled in the gap was pneumoccoccus. After HiB, came the development of Prevnar for pneumococcus with the subsequent rise in the incidence of Nissieria memingitidis (severe meningitis.). After the development of Menactra and Menomune, we are now seeing the rise on MRSA.
June 1996 - Invasive disease due to Haemophilus influenzae serotype f: clinical and epidemiologic characteristics in the H. influenzae serotype b vaccine era. The Haemophilus influenzae Study Group. (pdf) "With the decline in the rate of infections caused by Haemophilus influenzae serotype b, H. influenzae serotype f (Hif) is becoming a relatively important cause of invasive disease due to H. influenzae."
April 1996 - Haemophilus influenzae meningitis following vaccination. Consequence or coincidence? "A 4 month-old infant was admitted for a severe form of Hib meningitis with septicemia whose first manifestations developed 3 hours after the first immunization with a conjugate vaccine against Hib (PRP-T)."
March 1996 - Molecular characteristics of Haemophilus influenzae causing invasive disease during the period of vaccination in Switzerland: analysis of strains isolated between 1986 and 1993 "After the introduction of Haemophilus conjugate vaccines in 1990, there was a relative increase of nontypeable strains from 3 to 6.6% (P = 0.27). Of the type b strains, 281 (75.5%) had the same OMP subtype and ribotype pattern."
January 20, 1996 - Changing patterns of invasive Haemophilus influenzae disease in England and Wales after introduction of the Hib vaccination programme "Non-capsulate H influenzae isolates have shown an increase in annual attack rate (for all ages) from 0.25 cases per 100000 population in 1990-1 (45 cases recorded) to 0.37 in 1993-4 (67 cases). The total number of recorded cases of non-type b infections (non-capsulate and other serotypes: 75 cases) exceeded the number of cases of H influenzae type b (50 cases) in 1993-4.
December 1994 - Combination of DTP and Haemophilus influenzae type b conjugate vaccines can affect laboratory evaluation of potency and immunogenicity. "However, combination with the Hib vaccine comprising polysaccharide conjugated to tetanus toxoid had dramatic effects on tetanus potency and immunogenicity when assayed in mice. This combination resulted in a five-fold potentiation of the tetanus potency and a similarly large increase in the antibody responses to tetanus toxin and toxoid. The level of the antibody response to the Hib polysaccharide in this vaccine was also elevated, more than 20-fold, as a result of the combination. Such phenomena were not evident with combinations involving the other two Hib vaccines. These results have implications for the control testing of combined vaccines containing a whole-cell pertussis component and Hib polysaccharide-tetanus protein conjugate vaccine."
November-December 1994 - Haemophilus influenzae type B epiglottitis after immunization with HbOC conjugate vaccine
October 1994 - Hemophilus influenzae meningitis despite vaccination "An 18-month-old male previously vaccinated with 4 doses of HbOC developed meningitis caused by Hemophilus influenzae type B. Immunological status was normal and antibody titer to Hemophilus influenzae type b was in the normal range for immunized children. Meningitis due to this organism should be considered even in children who are fully vaccinated."
July 1993 - Guillain-Barré syndrome following immunisation with Haemophilus influenzae type b conjugate vaccine "So far, only four cases of GBS have been observed following immunisation with a conjugate vaccine against Haemophilus influenzae type b. We report another patient with GBS after this vaccination. We measured immunoglobulins against the H. influenzae type b polysaccharide (PRP) component of the vaccine. Surprisingly the anti-PRP IgM antibody level was markedly elevated (100 micrograms/ml) in the plasma of this patient. We speculate that an excessive anti-PRP IgM antibody response to the vaccine might be the cause of GBS."
August 1992 - Differences in the immunogenicity of three Haemophilus influenzae type b conjugate vaccines in infants.
June 1992 - The Biology of Haemophilus influenzae Type b Vaccination Failure
April 1, 1991 - Praxis HibTITER History of Misleading Promotional Activities Cited - "The violations occurred both prior to approval of the vaccine in December 1988 and postapproval, the reg letter notes. The Center for Biologics Evaluation and Research sent Praxis four letters, in 1988 and 1989, warning the company that its HibTITER promotions were inappropriate."
December 1991 - Haemophilus b disease after vaccination with Haemophilus b polysaccharide or conjugate vaccine
November 15, 1990 - Limited Efficacy of a Haemophilus influenzae Type b Conjugate Vaccine in Alaska Native Infants
November 15, 1990 - Impaired Antibody Response to Haemophilus influenzae Type b Polysaccharide and Low IgG2 and IgG4 Concentrations in Apache Children
October 1, 1990 - Haemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine in vaccinated children who developed Haemophilus disease
August 4, 1990 - Effect of breast-feeding on antibody response to conjugate vaccine "Infants were immunised at the ages of 2, 4, and 6 months with conjugate Haemophilus influenzae type b vaccine, and their responses to the vaccine were evaluated by feeding method (breast or formula). ... However the antibody levels were significantly higher in the breast-fed (57 infants) than the formula-fed group (24 infants) at 7 months ... These findings are strong evidence that breast-feeding enhances the active immune response in the first year of life, and therefore the feeding method must be taken into account in the evaluation of vaccine studies in infants."
August 1990 - Safety evaluation of PRP-D Haemophilus influenzae type b conjugate vaccine in children immunized at 18 months of age and older: follow-up study of 30,000 children."Hospitalization and seizures (0.15% and 0.09% of vaccinated children, respectively) occurring within 1 month of immunization appeared to be unrelated to vaccination. One 29-month-old child had onset of a fatal episode of Hib sepsis/meningitis within 48 hours of vaccination. Also, a 30-month-old child developed Hib meningitis 10 months after PRP-D vaccination."
September 9, 1988 - Lack of efficacy of Haemophilus b polysaccharide vaccine in Minnesota. "The vaccine's protective efficacy for children with any history of vaccination was -58% (95% confidence interval = -204% to 18%). The vaccine's protective efficacy for children who were most likely to be protected by vaccination was -55% (95% confidence interval = -238% to 29%). Our results indicate that vaccination with Haemophilus b polysaccharide vaccine had no effect in preventing H influenzae type b disease in Minnesota children."
August 1988 - Spectrum of disease due to Haemophilus influenzae type b occurring in vaccinated children "Haemophilus b polysaccharide vaccine was first licensed in the United States in April 1985. Between May 1985 and September 1987, 228 reports of disease due to Haemophilus influenzae in vaccinated children were submitted to the Food and Drug Administration, of which 216 were accepted for analysis. We compared the relative frequencies of the different disease entities caused by H. influenzae type b reported in vaccinated children with those reported in unvaccinated children (>1000 cases that occurred between 1973 and 1984, as reported in the literature). Over 90% of the vaccinated children were >24 mo of age. A higher proportion of cases was reported to have occurred within the first two months after vaccination, with 10 cases occurring within 72 h of vaccination. Vaccination did not alter the expected frequencies of the different clinical entities associated with invasive H. influenzae disease. No estimates of clinical efficacy are possible based on the adverse events submitted to the Food and Drug Administration."
October 1, 1987 - Safety and efficacy of Haemophilus influenzae type b polysaccharide vaccine "Haemophilus influenzae type b vaccine was licensed in the United States in the spring of 1985. Prior to licensure, extensive data had accumulated, indicating that this vaccine was safe and was immunogenic in children >18 to 23 months of age. Furthermore, in a large efficacy trial conducted in Finland, the vaccine also was found to be approximately 80% protective in preventing invasive type b Haemophilus disease in children 24 to 35 months of age (95% confidence interval 8, 95).1,2 Unfortunately, it was ineffective in children <18 months of age, the group most susceptible to Haemophilus disease, and it was of uncertain efficacy in those 18 to 23 months of age."
August 1987 - Adverse reactions reported following receipt of Haemophilus influenzae type b vaccine: an analysis after 1 year of marketing.
February 1987 - Prospective surveillance of Haemophilus influenzae type b disease in Dallas County, Texas, and in Minnesota. "Finally, because only 15% of systemic Haemophilus disease in these regions occurred in children in the age groups recommended for vaccination (24 to 59 months), the new Haemophilus type b polysaccharide vaccine is expected to have a limited impact on the overall incidence of disease."
December 18, 1986 - Hemophilus Influenzae Type B Disease in Children Vaccinated with Type B Polysaccharide Vaccine "We studied 55 cases of invasive Hemophilus influenzae type b disease occurring in children at least three weeks after vaccination with type b polysaccharide vaccine. Their mean age at the time of immunization was 27.8 months (range, 18 to 47). Meningitis developed in 39 patients, of whom 3 died and 6 had neurologic sequelae. We investigated certain host factors that may have contributed to the failure of the vaccine."
April 19, 1985 - Recommendation of the Immunization Practices Advisory Committee (ACIP) Polysaccharide Vaccine for Prevention of Haemophilus influenzae Type b Disease
October 1984 - Bronchial hyperreactivity to histamine induced by Haemophilus influenzae vaccination
April 4, 1980 - The effects of Haemophilus influenzae vaccination on anaphylactic mediator release and isoprenaline-induced inhibition of mediator release.
March 1979 - Comparison of vaccination of mice and rats with Haemophilus influenzae and Bordetella pertussis as models of atopy. "The Haemophilus influenzae vaccinated experimental animal provides a model that is possibly more related to human atopy than the Bordetella pertussis vaccinated animal."
January 1979 - Effects of Haemophilus influenzae vaccination on the (para-)sympathic-cyclic nucleotide-histamine axis in rats. - "Haemophilus influenzae vaccination induced changes in the cholinergic system compatible with higher cyclic GMP levels and enhanced histamine release."