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Economic evaluations of Haemophilus influenzae type b (Hib) vaccine: a systematic review

Chongmelaxme B, Hammanee M, Phooaphirak W, Kotirum S, Hutubessy R, Chaiyakunapruk N

J Med Econ, 2017 Oct;20(10):1094-1106.
PMID: 28737468 DOI: 10.1080/13696998.2017.1359181

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.

Matched MeSH terms: Haemophilus Vaccines/administration & dosage*; Haemophilus Vaccines/economics*
Carriage of Haemophilus influenzae among children attending childcare centres in Kuala Lumpur, Malaysia in the post vaccination era: A cross-sectional study

Palaniappan PA, Mohamed Sukur S, Liow YL, Maniam S, Sherina F, Ahmad N

Vaccine, 2020 12 03;38(51):8232-8237.
PMID: 33139134 DOI: 10.1016/j.vaccine.2020.09.066

BACKGROUND: Haemophilus influenzae (H. influenzae) is a human upper respiratory tract colonizer which causes wide range of disease especially in children<5 years old and in the elderly. Although worldwide incidence in industrialised countries where Hib vaccination is commonly used has dropped sharply since implementation of H. influenzae type b (Hib) vaccination, there is limited data on the disease burden caused by H. influenzae in Malaysia post vaccination era. A change in predominant serotype from type b to non-b serotypes of H. influenzae in invasive diseases was reported worldwide. We investigated the carriage of H. influenzae post vaccination era among 2-4 years old.
METHODOLOGY: Randomly, we collected 436 oropharyngeal swabs from healthy children aged 2-4 years in 30 registered childcare centres in Kuala Lumpur (August 2018-May 2019). Informed consent and written questionnaires were obtained from parents. H. influenzae was identified by standard microbiological methods. Univariable analysis was carried out to describe variables associated with colonization. All variables with p 

Matched MeSH terms: Haemophilus Vaccines*
A review of Hib epidemiology in Asia

Lolekha S, Cooksley G, Chan V, Isahak I, Ismael S, John J, et al.

Southeast Asian J Trop Med Public Health, 2000 Dec;31(4):650-7.
PMID: 11414406

Meningitis due to an invasive Haemophilus influenzae type b (Hib) infection, has been previously perceived to be relatively uncommon in Asia. However, the incidence of disease and its impact may have been underestimated. In addition to a lack of microbiological facilities in some hospitals, difficulties in culturing the organism and the widespread use of antibiotics may have hidden the true incidence of the disease in some countries. Furthermore, the reported disease burden probably underestimates the incidence of Hib pneumonia. The epidemiology of invasive Hib disease for various Asian nations is reviewed in this paper. Hospital-based studies show that Hib is a major cause of bacterial meningitis and/or pneumonia in the Philippines, India, Thailand, Malaysia, Indonesia and Vietnam. Singapore and Hong Kong have a low incidence of infection compared with Western and other Asian nations. This low incidence is not due to a higher level of natural protective antibodies, but may be related to an interaction between environmental and genetic factors. Therefore the widespread belief that Hib infection is unimportant in Asia does not refer to Asia as a whole and possibly to Chinese patients only, and failure to recognize this has serious implications. The inclusion of Hib vaccine in the routine infant immunization schedule in many industrialized nations has significantly reduced the incidence of invasive disease. Recent studies have shown Hib vaccination is also effective in preventing invasive disease in children in developing countries. While population-based data may be required to confirm the need for public-funded infant Hib immunization in Asia, its introduction in countries with a high incidence of Hib meningitis and/or pneumonia has the potential to significantly improve pediatric health and survival.

Matched MeSH terms: Haemophilus Vaccines/administration & dosage
Fulltext Economic impact of switching from partially combined vaccine "Pentaxim® and hepatitis B" to fully combined vaccine "Hexaxim®" in the Malaysian National Immunization Program

Aljunid SM, Al Bashir L, Ismail AB, Aizuddin AN, Rashid SAZA, Nur AM

BMC Health Serv Res, 2022 Jan 05;22(1):34.
PMID: 34986870 DOI: 10.1186/s12913-021-07428-7

BACKGROUND: The decision to implement new vaccines should be supported by public health and economic evaluations. Therefore, this study was primarily designed to evaluate the economic impact of switching from partially combined vaccine (Pentaxim® plus hepatitis B) to fully combined vaccine (Hexaxim®) in the Malaysian National Immunization Program (NIP) and to investigate healthcare professionals (HCPs)' and parents'/caregivers' perceptions.
METHODS: In this economic evaluation study, 22 primary healthcare centers were randomly selected in Malaysia between December 2019 and July 2020. The baseline immunization schedule includes switching from Pentaxim® (four doses) and hepatitis B (three doses) to Hexaxim® (four doses), whereas the alternative scheme includes switching from Pentaxim® (four doses) and hepatitis B (three doses) to Hexaxim® (four doses) and hepatitis B (one dose) administered at birth. Direct medical costs were extracted using a costing questionnaire and an observational time and motion chart. Direct non-medical (cost for transportation) and indirect costs (loss of productivity) were derived from parents'/caregivers' questionnaire. Also, HCPs' and parent's/caregivers' perceptions were investigated using structured questionnaires.
RESULTS: The cost per dose of Pentaxim® plus hepatitis B vs. Hexaxim® for the baseline scheme was Malaysian ringgit (RM) 31.90 (7.7 United States dollar [USD]) vs. 17.10 (4.1 USD) for direct medical cost, RM 54.40 (13.1 USD) vs. RM 27.20 (6.6 USD) for direct non-medical cost, RM 221.33 (53.3 USD) vs. RM 110.66 (26.7 USD) for indirect cost, and RM 307.63 (74.2 USD) vs. RM 155.00 (37.4 USD) for societal (total) cost. A similar trend was observed for the alternative scheme. Compared with Pentaxim® plus hepatitis B, total cost savings per dose of Hexaxim® were RM 137.20 (33.1 USD) and RM 104.70 (25.2 USD) in the baseline and alternative scheme, respectively. Eighty-four percent of physicians and 95% of nurses supported the use of Hexaxim® in the NIP. The majority of parents/caregivers had a positive perception regarding Hexaxim® vaccine in various aspects.
CONCLUSIONS: Incorporation of Hexaxim® within Malaysian NIP is highly recommended because the use of Hexaxim® has demonstrated substantial direct and indirect cost savings for healthcare providers and parents/caregivers with a high percentage of positive perceptions, compared with Pentaxim® plus hepatitis B.
TRIAL REGISTRATION: Not applicable.

Matched MeSH terms: Haemophilus Vaccines
Four is better than nine. a combined diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine for routine immunization in Malaysia

Wong SL, Soosai P, Teoh YL, Han HH, Lefevre I, Bock HL

Southeast Asian J Trop Med Public Health, 2008 May;39(3):474-83.
PMID: 18564687

Malaysian infants would have to receive nine injections during the first few months of life in order to be protected against disease caused by hepatitis B (HBV), diphtheria, tetanus, pertussis and Haemophilus influenzae type b (Hib) if single HBV and Hib vaccines were used. We evaluated a combined DTPw-HBV/Hib vaccine administered at 1.5, 3 and 5 months after a birth dose of hepatitis B vaccine (HBV). One month after completion of the primary vaccination, 99% of subjects had seroprotective anti-HBV antibody levels, and at least 98% had seroprotective antibodies against diphtheria, tetanus, and Hib, and were seropositive for pertussis antibodies. The immune response to the combined vaccine was comparable to that induced by separate injections with DTPw, HBV and Hib vaccines. Overall, the DTPw-HBV/Hib vaccine was as well tolerated as separate administration of DTPw, HBV and Hib vaccines. The combined DTPw-HBV/Hib vaccine induces protection against five diseases as recommended in the Malaysian routine vaccination schedule. Use of the combined DTPw-HBV/Hib vaccine can reduce the required number of injections from nine to four in the first few months of life.

Matched MeSH terms: Haemophilus Vaccines/administration & dosage*; Haemophilus Vaccines/adverse effects; Haemophilus Vaccines/immunology
Vaccination in Southeast Asia--reducing meningitis, sepsis and pneumonia with new and existing vaccines

Richardson A, Morris DE, Clarke SC

Vaccine, 2014 Jul 16;32(33):4119-23.
PMID: 24907487 DOI: 10.1016/j.vaccine.2014.05.062

Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis are leading causes of vaccine-preventable diseases such as meningitis, sepsis and pneumonia. Although there has been much progress in the introduction of vaccines against these pathogens, access to vaccines remains elusive in some countries. This review highlights the current S. pneumoniae, H. influenzae type b, and N. meningitidis immunization schedules in the 10 countries belonging to the Association of Southeast Asian Nations (ASEAN). Epidemiologic studies may be useful for informing vaccine policy in these countries, particularly when determining the cost-effectiveness of introducing new vaccines.

Matched MeSH terms: Haemophilus Vaccines*
Vaccine preventable meningitis in Malaysia: epidemiology and management

McNeil HC, Jefferies JM, Clarke SC

Expert Rev Anti Infect Ther, 2015 06;13(6):705-14.
PMID: 25962101 DOI: 10.1586/14787210.2015.1033401

Worldwide bacterial meningitis accounts for more than one million cases and 135,000 deaths annually. Profound, lasting neurological complications occur in 9-25% of cases. This review confirms the greatest risk from bacterial meningitis is in early life in Malaysia. Much of the disease burden can be avoided by immunization, particularly against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae. Despite inclusion of the Hib vaccine in the National Immunisation Programme and the licensure of pneumococcal vaccines, these two species are the main contributors to bacterial meningitis in Malaysia, with Neisseria meningitidis and Mycobacterium tuberculosis, causing a smaller proportion of disease. The high Hib prevalence may partly be due to dated, small-scale studies limiting the understanding of the current epidemiological situation. This highlights the need for larger, better quality surveillance from Malaysia to evaluate the success of Hib immunization and to help guide immunization policy for vaccines against S. pneumoniae and N. meningitidis.

Matched MeSH terms: Haemophilus Vaccines/therapeutic use*
Vaccine-induced immune thrombocytopaenia purpura in autologous haematopoietic stem cell transplantation

Wan Jamaludin WF, Kok WH, Loong L, Palaniappan SK, Zakaria MZ, Ong TC, et al.

Med J Malaysia, 2018 12;73(6):430-432.
PMID: 30647224

Immune Thrombocytopenia Purpura (ITP) secondary to vaccinations is rare, especially after autologous hematopoietic stem cell transplantation (HSCT). A 31-yearold female received autologous HSCT for relapsed Hodgkin Disease, with platelet engraftment at Day+14. One week after receiving second scheduled vaccinations, she developed severe thrombocytopenia (3x109/L) associated with pharyngeal hematoma. Bone marrow (BM) examinations were consistent with ITP, possibly secondary to Influenza vaccine. Platelet increment was poor despite high dose corticosteroids, intravenous immunoglobulin (IVIG), Danazol and Eltrombopag. A repeated BM biopsy was in agreement with ITP. Re-treatment with tapering doses of prednisolone resulted in stable platelet counts at 120x109/L a year later.

Matched MeSH terms: Haemophilus Vaccines/adverse effects