Haemophilus influenzae Prevention
Vaccines against Haemophilus influenzae type b (Hib) are the most effective means of preventing Hib related diseases. The introduction of Hib vaccines dramatically changed the epidemiology of Hib disease, such that the disease is considered as being rare in developed countries where the vaccines were first introduced in the late 1980s and early 1990s.
DTwP – HepB – Hib vaccine
Biological E. Limited, India – Photo credit: Benild Moiane
Who
As Hib disease mainly affects infants aged between 4 months to 18 months, it is important that children get vaccinated early. Hib vaccines provides 98% protection against Hib diseases especially in children below 5 years.
When and How
The World Health Organisation (WHO) recommends that the Hib vaccine is given in 3 to 4 doses depending on the vaccine formulation and age when first doe is administered, however it is recommended that the first dose is given as early once 6 weeks of age is reached and not before.
Several different Hib vaccines have been developed and licensed as monovalent formulations where the Hib polysaccharide/capsule antigen is conjugated to a carrier protein.
There are four types of monovalent conjugate vaccines available:
- diphtheria toxoid conjugate (PRP-D; ProHIBiT)
- diphtheria toxin conjugate (PRP-CRM or HbOC; HibTITER)
- meningococcal outer membrane protein conjugate (PRP-OMP; PedvaxHIB)
- Tetanus toxoid conjugate (PRP-T; ActHIB, OmniHIB, or Hiberix
Polyvalent formulations are also available where the Hib antigen is administered in combination with other vaccine antigens such as DTP, HBV & IPV eg Infanrix-Hib, Infanrix Hexa, Pentacel, MenHibrix
Vaccine Impact
Conjugate Hib vaccines have proven to be the most effective public health prevention strategy against Hib disease as studies have demonstrated high efficacy of over 90% in the first months of life following receipt of a primary series of 2 or 3 doses. Furthermore, Hib disease in a fully vaccinated infant or child is rare.
As such conjugate vaccines have resulted in an unprecedented decline in Hib disease. For instance, the introduction of the vaccine in Kenya in 2000/1 resulted in the drastic decline of Hib disease from 62.6 to 4.5 per 100 000 population in 2004.
The introduction of Hib vaccines has led to the dramatic decline of Hib leading to the near elimination of the disease in most countries with routine vaccination programmes and high levels of coverage. Vaccination is highly effective in eradicating asymptomatic Hib carriage and, in countries that routinely immunise against Hib in infancy that have high vaccine uptake, vaccinated children rarely carry Hib, thereby providing reduced opportunities for transmission and therefore disease, leading to herd immunity. This ultimately benefits not only the children who have received the vaccine but also older people.
What next?
Despite the resounding success of the Hib vaccine, not all countries have introduced this vaccine into their programmes and the WHO notes that Hib disease continues to claim the lives of approximately 350 000 to 700 000 unvaccinated children per year. The Hib vaccine had been introduced in 192 countries by the end of 2019, and global coverage with 3 doses of Hib vaccine was estimated at 72%. There is great variation between regions. the WHO region of South-East Asia is estimated to have 89% coverage, while it is only 24% in the WHO Western Pacific Region (WHO website, Slack M et al 2021).
Although there is a global decline in cases of meningitis caused by Hib, it is important for Ministries of Health to maintain surveillance systems to provide evidence for ongoing protection and early detection of resurgences in all age groups. In addition, potentially increased disease numbers as a consequence of the decline in childhood vaccination coverage, including the Hib vaccine, in some countries due to the COVID-19 pandemic, is also worthy of monitoring. Furthermore, other encapsulated (particularly serotypes a, e and f) and non-encapsulated H. influenzae strains also have the potential to cause invasive disease, although seen at much lower incidence rates than that experienced with Hib in pre-vaccination era.
Parents and caregivers need to know the signs and symptoms of invasive disease caused by H. influenzae and ensure that children are vaccinated as early as possible.
References
WHO. (2001). Estimating the local burden of Haemophilus influenzae type b (Hib) disease preventable by vaccination A rapid assessment tool. www.who.int/vaccines-documents/
Shapiro, E. D. (1993). Infections Caused by Haemophilus influenzae Type b: The Beginning of the End? JAMA: The Journal of the American Medical Association, 269(2), 264–266. https://doi.org/10.1001/jama.1993.03500020098040
Carreras-Abad, C., Ramkhelawon, L., Heath, P. T., & Doare, K. Le. (2020). A vaccine against group b streptococcus: Recent advances. In Infection and Drug Resistance (Vol. 13, pp. 1263–1272). Dove Medical Press Ltd. https://doi.org/10.2147/IDR.S203454
Hammitt, L. L., Crane, R. J., Karani, A., Mutuku, A., Morpeth, S. C., Burbidge, P., Goldblatt, D., Kamau, T., Sharif, S., Mturi, N., & Scott, J. A. G. (2016). Effect of Haemophilus influenzae type b vaccination without a booster dose on invasive H influenzae type b disease, nasopharyngeal carriage, and population immunity in Kilifi, Kenya: A 15-year regional surveillance study. The Lancet Global Health, 4(3), e185–e194. https://doi.org/10.1016/S2214-109X(15)00316-2
Soeters, H. M., Diallo, A. O., Bicaba, B. W., Kadadé, G., Dembélé, A. Y., Acyl, M. A., Nikiema, C., Sadji, A. Y., Poy, A. N., Lingani, C., Tall, H., Sakandé, S., Tarbangdo, F., Aké, F., Mbaeyi, S. A., Moïsi, J., Paye, M. F., Sanogo, Y. O., Vuong, J. T., … Novak, R. T. (2019). Bacterial Meningitis Epidemiology in Five Countries in the Meningitis Belt of Sub-Saharan Africa, 2015-2017. In Journal of Infectious Diseases (Vol. 220, pp. S165–S174). Oxford University Press. https://doi.org/10.1093/infdis/jiz358
Shapiro, E. D., & Ward, J. I. (1991). The epidemiology and prevention of disease caused by Haemophilus influenzae type b. Epidemiologic Reviews, 13(1), 113–142. https://doi.org/10.1093/oxfordjournals.epirev.a036066
Knoll, M., DeloriaO’Brien, L., K., Henkle, Emily Lee, E., Watt, J. P., McCall, N., & Mangtani, P. (2009). Global literature review of Haemophilus influenzae type b and Streptococcus pneumoniae invasive disease among children less than five years of age 1980–2005. https://apps.who.int/iris/bitstream/handle/10665/69991/WHO_IVB_09.02_eng.pdf?sequence=1
WHO. (2019). Defeating Meningitis By 2030-baseline situational analysis. https://www.who.int/immunization/sage/meetings/2019/april/2_
DEFEATING_MENINGITIS_BY_2030_baseline_situation_analysis.pdf?ua=1
Jin, Z., Romero-Steiner, S., Carlone, G. M., Robbins, J. B., & Schneerson, R. (2007). Haemophilus influenzae type a infection and its prevention. In Infection and Immunity (Vol. 75, Issue 6, pp. 2650–2654). American Society for Microbiology (ASM). https://doi.org/10.1128/IAI.01774-06
Peltola, H. (2000). Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: Global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates. In Clinical Microbiology Reviews (Vol. 13, Issue 2, pp. 302–317). American Society for Microbiology (ASM). https://doi.org/10.1128/CMR.13.2.302-317.2000
Tsang, R. S. W., & Ulanova, M. (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. Vaccine, 35(33), 4270–4275. https://doi.org/10.1016/j.vaccine.2017.06.001
Tsang, R. S. W., & Ulanova, M. (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. Vaccine, 35(33), 4270–4275. https://doi.org/10.1016/j.vaccine.2017.06.001
Paulina, M., & Slack, E. (2021). Long Term Impact of Conjugate Vaccines on Haemophilus influenzae Meningitis: Narrative Review. Microorganisms. https://doi.org/10.3390/microorganisms9050886
WHO. (2013). Weekly epidemiological record| Relevé épidémiologique hebdomadaire. https://www.who.int/wer/2013/wer8839.pdf?ua=1
Khattak, Z. E., & Anjum, F. (2021). Haemophilus Influenzae. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/pubmed/32965847
Watt, J. P., Wolfson, L. J., O’brien, K. L., Henkle, E., Deloria-Knoll, M., Mccall, N., Lee, E., Levine, O. S., Hajjeh, R., Mulholland, K., & Cherian, T. (2009). Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates. In The Lancet (Vol. 374). https://doi.org/10.1016/S0140-6736(09)61203-4
