Haemophilus influenzae is an important cause of severe bacterial infections in children younger than 5 years. It was first identified by Koch in 1883 but it was not until the influenza pandemic in 1918 that H. influenzae was recognized as a cause for secondary infection and not the primary cause of influenza [ 1 ]. In 1931, Pittman [ 2 ] demonstrated two categories of H. influenzae - encapsulated and nonencapsulated forms and further designated six serotypes (a–f) [ 2 ] on the basis of capsular properties. H. influenzae type b (Hib) was responsible for 95 % [ 3 ] serious invasive bacterial infections in the prevaccine era.

Haemophilus influenzae is an aerobic, non-spore-forming gram-negative coccobacillus. It requires two factors “X” (hemin) and “V” (nicotinamide adenine dinucleotide) [ 4 ] for in vitro growth, a property that distinguishes it from other Haemophilus species. The polyribosyl-ribitol-phosphate polysaccharide capsule is responsible for virulence and immunity. Hib colonizes nasopharynx (asymptomatic carriers) and is spread through respiratory droplets. Antecedent viral infections may play a role in invasive disease. Common invasive presentations include meningitis, pneumonia, otitis media, epiglottitis, septicemia, cellulitis, and osteoarticular infections. Non-type-b-encapsulated H. influenzae rarely causes invasive disease. A positive culture of H. influenzae from infected sterile body fluid or detection of Hib polysaccharide anti gen in CSF is diagnostic. Serotyping is extremely important as type b isolated in children younger than 15 years is a potentially vaccine - preventable disease.

The first-generation pure polysaccharide vaccine (HbPV) was introduced in the early 1980s in the USA but was not immunogenic in children younger than 18 months and had variable efficiency in older children (age-dependent vaccine response). It was used until 1988 and is no longer available in the USA. The conjugation of the polysaccharide to the “carrier” protein results in a T-dependent antigen and increases immunogenicity and boosts response. The annual incidence of invasive Hib disease before the use of conjugate vaccine was 20–88 cases per 100,000 cases in the USA and has dramatically reduced ever since its introduction. Four conjugate Hib vaccines have been developed [ 5 ]. The first H. influenzae type b polysaccharide protein conjugate vaccine (PRP- diphtheria toxoid conjugate) was licensed in 1987 and is no longer available. The Haemophilus b oligosaccharide conjugate (HbOC) licensed in 1990 contains oligo saccharides from purified PRP from Hib Eagan strain coupled with nontoxic variant of diphtheria toxin isolated by Corynebacterium diphtheriae . The PRP-OMP vaccine was also licensed in 1990 and is a purified PRP from Hib Ross strain covalently bonded to an outer membrane protein complex of Neisseria meningitides strain B11. PRP-T is covalently bound PRP to tetanus toxoid and was licensed in 1993. The three HiB conjugate vaccines licensed for use are inter changeable. The Advisory Committee on Immunization Practices (ACIP) recommends start of immunization as early as 6 weeks of age with total of three doses of any combination HiB vaccines before the first birthday and a booster dose at 12–15 months of age. The only contraindication is hypersensitivity to vaccine components. HiB is not routinely recommended for persons 5 years and older; it can be considered in special situations such as asplenia, sickle cell anemia, or HIV infection (Fig. 1 ).

Fig. 1 Incidence of invasive Hib disease 1990–2009 (rate per 100,000 children less than 5 years of age). Graph from CDC/vaccines/pinkbook/hib

The routine use of HiB conjugate vaccine has dramatically decreased disease in developed countries and shown to be highly effective in reducing the incidence of disease in developing countries. Efforts are under way by the WHO to increase awareness and global availability of this effective vaccine especially in resource- limited countries.

References
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[1] Tognotti E (2003) Scientifi c triumphalism and learning from facts: bacteriology and the “Spanish flu” challenge of 1918. Soc Hist Med 16:97–110

[1] Pittman M (1931) Variation and type specificity in bacterial species Hemophilus influenzae. J Exp Med 53:471–492

[3]Dajani AS, Asmar BI, Thirumoorthi MC (1979) Systemic Haemophilus influenzae disease: an overview. J Pediatr 94:355–364

[4]Tebbutt GM (1983) Evaluation of some methods for the laboratory identification of Heamophilus influenzae. J Clin Pathol 36:991

[5]Centers for Disease Control and Prevention. www.cdc.gov/vaccines/hib

مواضيع ذات صلة

Pertussis Vaccines

Hepatitis A Vaccines

Cholera Vaccines

Viral Vaccines

Monitoring the immune response in vaccine research

Antigen selection for new vaccines

Reverse vaccinology (RV) and other applications

RNA vaccines

Immunisation

DNA vaccines

Subunit vaccines

Inactivated vaccines