Haemophilus influenzae is a gram-negative coccobacillus that exists as encapsulated and non-encapsulated strains. Based on the chemical composition of the polysaccharide capsule, the encapsulated strains may be further classified into 6 serotypes (a, b, c, d, e, and f). Non-encapsulated strains are non-typeable. Both encapsulated and non-encapsulated strains are pathogenic to humans.
Among the strains, H. influenzae type b (Hib) is the most virulent strain and responsible for more than 95% of invasive diseases in children. The gram negative bacteria first colonises the host’s nasopharynx, and subsequently either (a) invades the blood stream which results in bacteraemia and secondary spread can lead to meningitis, epiglottitis, pneumonia, arthritis, osteomyelitis and cellulitis [which are collectively known as invasive disease], or (b) spreads contiguously to adjacent sinuses or middle ear and results in sinusitis or otitis media, respectively.
Prior to the widespread use of Hib vaccine in resource-limited countries, Hib was estimated to have resulted in 371,000 deaths and >8 million serious infections in children aged <5 years old in 2000 alone. The number of deaths caused by Hib had reduced significantly to 203,000 in children aged <5 years old in 2008; the year when the total number of WHO member states that had introduced Hib vaccine into their national immunisation programmes rose to 136 from 62 in 2000.
The other encapsulated strains of H. influenzae occasionally cause invasive disease similar to that of Hib while the non-encapsulated strains cause mucosal infections, including otitis media, conjunctivitis, sinusitis, bronchitis and pneumonia. These strains rarely cause invasive disease in children. In adults, non-encapsulated strains account for nearly 50% of invasive infections.
The Hib vaccine is derived from the polyribosylribitol phosphate (PRP) capsule of the bacteria. The PRP capsule is a key virulence determinant of the organism. It enables the bacterium to evade phagocytosis of leucocytes and therefore facilitates systemic dissemination through the blood stream. The specific antibody to PRP is the primary contributor to immunity, and increasing levels of antibody are associated with decreasing risk of invasive Hib disease. Like other bacteria-derived polysaccharides, the immune response to PRP is a T-cell independent antigen response, where B lymphocytes provide the primary response without a contribution from T-helper cells. As a result, the antibody response to pure polysaccharide antigen is poor in children less than 18 months. In order to improve the immunogenicity of PRP, the polysaccharide antigen is conjugated with a T-cell dependent protein antigen, like diphtheria toxoid – hence the term, conjugate vaccine.
Vaccines Available in Malaysia
- Hiberix® (H. infleunzae type b)
GlaxoSmithKline Pharmaceutical (M) Sdn Bhd/GlaxoSmithKline Biologicals S.A., Belgium
Mode of Administration
Hib vaccines are administered by intramuscular injection into the anterolateral aspect of the deltoid or thigh. It should not be administered intravenously, intradermally, or subcutaneously.
In children, primary immunisation comprises 3 doses that are given during the first 6 months of age. In Malaysia, under the National Immunisation Programme (NIP), the immunisation is given at 2, 3 and 5 months. A booster dose is given at 18 months.
In adults the dosing regimen would depend on the circumstances for vaccination.
Co-administration with Other Vaccines
Hib vaccine can be co-administered with other injectable vaccines, but should not be mixed with any other vaccine in the same syringe or vial. Hib vaccine should be given in separate syringes and at different injection sites.
Contraindications and Adverse Effects
- The vaccine should not be administered to individuals with:
- Confirmed anaphylactic reaction to Hib-containing vaccine.
- Confirmed anaphylactic reaction to neomycin, streptomycin or
polymyxin B, as they may be present in small amounts.
- Acute illness with systemic upset and fever.
- Evolving or undiagnosed, deteriorating neurological abnormalities.
- Severe adverse events following administration of Hib vaccine are
uncommon, making it one of the safest vaccines currently available. In a study of >4,000 infants, there were no differences in the type and frequency of severe adverse events occurring among those receiving Hib conjugate vaccine and those receiving a placebo. Mild adverse effects are reaction at the site of injection (10%) and fever (2%).
- To date, the most frequently reported adverse events for Hib vaccines received by the National Pharmaceutical Regulatory Agency (NPRA) include local site reactions such as injection site inflammation, swelling, fever and rash.
Target Groups in Malaysia
Hib vaccine is primarily a vaccine for children. However, Hib vaccination should be given to the following adults:
- Anatomical or functional asplenia: For those who have not received or completed Hib immunisation in childhood – 1 dose 2 weeks before elective splenectomy or as soon as possible after an emergency splenectomy.
- Recipients of bone marrow transplants – 3 doses at 12, 14 and 24 months after successful transplantation regardless of Hib vaccination history.
Evidence for Effectiveness
The introduction of Hib vaccine has considerably reduced the reported incidents of Hib diseases in all settings regardless of their level of socioeconomic status and development. In addition the nasopharyngeal colonisation rate of Hib in the population has also declined with the widespread use of Hib vaccine, which has contributed to a reduction in disease incidence of Hib through the establishment of herd immunity. Countries which have introduced mass immunisation have witnessed near elimination of invasive Hib infections. There is however less evidence of efficacy in adults.
- Greenberg, D. P., Doemland, M., Bettinger, J. A., Scheifele, D. W., Halperin, S. A., Waters, V., Kandola, K. (2009). Epidemiology of Pertussis and Haemophilus influenzae type b Disease in Canada With Exclusive Use of a Diphtheria-Tetanus-Acellular Pertussis-Inactivated Poliovirus-Haemophilus influenzae type b Pediatric Combination Vaccine and an Adolescent-Adult Tetanus-Diphtheria-Acellular Pertussis Vaccine. The Pediatric Infectious Disease Journal, 28(6), 521-528. doi:10.1097/inf.0b013e318199d2fc
- Haemophilus b Conjugate Vaccines for Prevention of Haemophilus influenzae Type b Disease Among Infants and Children Two Months of Age and Older Recommendations of the ACIP. (1991). PsycEXTRA Dataset. doi:10.1037/e546452006-001
- Haemophilus influenzae type b (Hib). (2014, January 24). Retrieved from https://www.who.int/immunization/diseases/hib/en/
- The Malaysian National Centre for Adverse Drug Reactions Database. Accessed: October 10, 2019.
- National Pharmaceutical Regulatory Agency (NPRA), Ministry of Health Malaysia. Senarai Produk Vaksin Berdaftar Dengan Pihak Berkuasa Kawalan Dadah. Received September 5, 2019.
- Observed Rate of Vaccine Reactions Global Vaccine Safety (2002). Retrieved December 1, 2013, from https://www.who.int/vaccine_safety/initiative/tools/Influenza_Vaccine_rates_information_sheet.pdf?ua=1
- WHO. (2013, October 21). Haemophilus influenzae type b (Hib) Vaccination WHO position paper: July 2013 Recommendations. Retrieved from https://www.sciencedirect.com/science/article/pii/S0264410X13014217?via=ihub