Immunization against Bacteria Associated with Meningitis

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Chapter: Pharmaceutical Microbiology : Vaccination And Immunization

Meningococcus (Neisseria meningitidis) is a bacterium that exclusively colonizes and/or infects humans; there is no animal reservoir.


IMMUNIZATION AGAINST BACTERIA ASSOCIATED WITH MENINGITIS

 

1)  Meningococcal Immunization

Meningococcus (Neisseria meningitidis) is a bacterium that exclusively colonizes and/or infects humans; there is no animal reservoir. It is present as part of the normal microbiota of the pharynx in approximately 10% of individuals but can rarely spread through the bloodstream and to the brain through poorly understood mechanisms, causing meningitis and septicaemia. These are life-threatening, systemic infections; overall mortality from meningococcal disease is approximately 10%, assuming symptoms are recognized and treatment is commenced without delay, but rises considerably if there are delays. Diagnosis is therefore considered a medical emergency. At least 12 subtypes or serogroups of meningococcus have been identified, but groups B and C account for the majority of cases in Europe and the Americas. In the UK, group B accounts for approximately two-thirds of reported cases with group C accounting for the remaining third. Neisseria meningitidis group A does not normally cause disease in the UK but is an endemic cause of meningitis in other parts of the world, particularly sub-Saharan Africa in an area between Senegal (West Africa) to Ethiopia (East) that has been termed the ‘meningitis belt’. It is believed that reasons for the hyperendemic incidence of group A meningococcal meningitis in this part of the world include high incidence of upper respiratory tract infections during the dry (dusty) season, combined with overcrowding, migration and pilgrimages.

 

Whilst group C meningitis is most common in the under 1-year-old group in the UK, mortality is highest in adolescents. Although meningitis accounts for the majority of invasive meningococcal disease, in 15-20% of cases septicaemia predominates and is associated with significantly higher mortality. There is currently no vaccine available for group B meningococcus but vaccines are available for groups A and C. As with the Hib vaccine (see below), the preparations are intended to invoke protective immunity towards the polysaccharide component of the bacterium. Early vaccines, composed of purified polysaccharide, worked in adults but had poor efficacy in infants —the most at-risk group. The new MenC conjugate vaccine comprises capsular polysaccharide components conjugated to a carrier protein (usually diphtheria or tetanus toxoid). This vaccine is effective in the very young and is therefore suitable for protecting infants. The vaccine is normally administered along with DTaP and Hib at 3, 4 and 12 months and a single dose is sufficient to immunize individuals over 12 months of age; it has also been used to provide prophylaxis for teenagers, adolescents and young adults. Group A vaccine is available for those travelling to areas of the world where the infection is epidemic.

 

2)  Haemophilus Influenzae Type B (Hib) Immunization

Haemophilus influenzae can cause infections ranging from bronchitis and otitis media to life-threatening, invasive disease (meningitis and bacteraemia). Invasive infections, which are most common in young children, are normally caused by encapsulated strains of the bacterium that can be serologically differentiated into six typeable capsular serotypes (a-f). Before the introduction of vaccination, H. influenzae type b (Hib) was the most prevalent of these in invasive disease. Non-invasive haemophilus disease is most often caused by non-encapsulated strains that are not amenable to typing based on capsular serology. Although the most common form of invasive Hib disease is meningitis, accounting for 60% of cases, Hib can also cause other infections, including pneumonia and pericarditis.

 

The fatality rate for treated Hib meningitis infections is approximately 5% and complications include deafness and intellectual impairment (in c. 10% of cases). Hib often forms part of the normal microbiota of the nasopharynx in healthy individuals and the frequency of carriage before the Hib vaccine was introduced was approximately 4 in every 100 for preschool children. Carriage of this bacterium is now rare because of the effectiveness of the Hib vaccination. Hib meningitis is rare in children under 3 months and peaks in its incidence at around 10-11 months of age; infection is uncommon after 4 years of age. Before the introduction of Hib vaccination the incidence of the disease in the UK was estimated at 34 per 100 000.

 

The vaccine utilizes purified preparations of the polysaccharide capsule of the major serotypes of the bacterium associated with disease. Polysaccharides are poorly immunogenic and must be conjugated onto a protein carrier (diphtheria or tetanus toxoids) to enhance their efficacy. The Hib vaccine is given as part of a combined product of H. influenzae type b, diphtheria, tetanus, acellular pertussis and inactivated polio vaccine (DTaP/IPV/ Hib), or as the Hib/MenC conjugate vaccine.

 

3)  Pneumococcal Vaccination

Streptococcus pneumoniae (pneumococcus) is an encapsulated Gram-positive coccus. As with meningococcus and Hib, the capsule is an important virulence factor for this bacterium (non-capsulated strains are normally avirulent). Many different capsular types have been characterized but approximately 66% of the serious infections in adults and 80% of invasive pneumococcal infections in children are caused by about 10 capsular types. Pneumococci are often part of the normal microbiota of the nasal cavity and associated tissues but commensal strains are often avirulent. Conversely, invasive infections (i.e. meningitis and septicaemia) are often caused by strains not considered to be normal commensals. S. pneumoniae is a versatile pathogen which can cause sinusitis or otitis media (infections of the sinuses or middle ear). The bacterium may also cause deep lung infections (pneumonia), which accounts for its species name, and is also capable of causing systemic infections including bacteraemic pneumonia, bacteraemia and meningitis. The incidence of infection by pneumococci is highest in the winter, and transmission by aerosols or direct contact with respiratory secretions is believed to require either frequent or prolonged close contact. Two distinct vaccines have been developed to provide protection against this bacterium: the pneumococcal polysaccharide vaccine (PPV) which contains purified capsular polysaccharide from 23 capsular types of bacterium and the pneumococcal conjugate vaccine (PCV) which comprises capsular polysaccharides from 7 common capsular types. Importantly, PCV is conjugated to protein in a manner similar to the Haemophilus influenzae type b (Hib) and MenC vaccines. While PPV is an effective vaccine in adults, the effectiveness of pneumococcal prophylaxis is considerably improved in children by protein conjugation; PCV is immunogenic in children and the childhood vaccination schedule recommends that doses be given at 2 and 4 months of age with a booster at 13 months. The PPV vaccine is recommended for adults over 65 years and at-risk groups aged 2 years or over. It will provide additional prophylaxis to individuals who have already received the PCV vaccine because it protects from additional serotypes.


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