Prevention of group B meningococcal disease by vaccination: a difficult task

New Zealand has embarked on an immunisation program to reduce the incidence of disease caused by serogroup B Neisseria meningitidis. Similar immunisation programs in Norway and South America have shown good efficacy in older vaccinees (ie, persons receiving vaccinations), but variable efficacy in younger vaccinees. Protective efficacy correlates well with the ability of the vaccine to stimulate a fourfold rise in serum bactericidal antibodies. Unfortunately, second and third doses of serogroup B N. meningitidis vaccines do not boost serum bactericidal antibody titres to very high levels; consequently protective efficacy wanes within a few years of immunisation. The overall outcome of the immunisation program will reflect both the immunogenicity of the vaccine and the uptake of the vaccine by the target population. The especially high incidence of meningococcal disease in Pacific and Maori children means that particular efforts will need to be made to reach these groups.     

Prospects offered by genome studies for combating meningococcal disease by vaccination

Meningococcal disease was first recognised and Neisseria meningitidis isolated as the causative agent over 100 years ago, but despite more than a century of research, attempts to eliminate this distressing illness have so far been thwarted. The main problem lies in the fact that N. meningitidis usually exists as a harmless commensal inhabitant of the human nasopharynx, the pathogenic state being the exception rather than the norm. As man is its only host, the meningococcus is uniquely adapted to this ecological niche and has evolved an array of mechanisms for evading clearance by the human immune response. Progress has been made in combating the disease by developing vaccines that target specific pathogenic serogroups of meningococci. However, a fully comprehensive vaccine that protects against all pathogenic strains is still just beyond reach. The publication of the genome sequences of two meningococcal strains, one each from serogroups A and B and the imminent completion of a third illustrates the extent of the problems to be overcome, namely the vast array of genetic mechanisms for the generation of meningococcal diversity. Fortunately, genome studies also provide new hope for solutions to these problems in the potential for a greater understanding of meningococcal pathogenesis and possibilities for the identification of new vaccine candidates. This review describes some of the approaches that are currently being used to exploit the information from meningococcal genome sequences and seeks to identify future prospects for combating meningococcal disease.     

Prevention of otitis media by vaccination

Otitis media (OM) is one of the commonest infections in childhood and a frequent reason for prescribing antibacterials in infancy. However, the increase in prevalence of antibacterial-resistant respiratory bacterial pathogens has not been matched by the development of new antibacterial agents. Bacterial vaccine strategies aim to prevent OM directly and to reduce nasopharyngeal carriage of pneumococci, thereby reducing the likelihood of developing acute OM. Complete protection against OM would require an approach targeting both bacterial and viral agents. Immunisation with a pneumococcal conjugate vaccine provides protection against acute OM caused by pneumococcal serotypes included in the vaccine, reduces serotype-specific pneumococcal carriage, and reduces carriage of penicillin-resistant pneumococci. However, an increase in non-vaccine serotype OM has been observed in vaccinated children, which may limit the overall effectiveness of this vaccine. New vaccines targeting non-typable Haemophilus influenzae and Mycoplasma catarrhalis are in the early stages of development. Efficacy studies with influenza vaccine have shown the most promising results to date in terms of overall reduction in OM episodes. A more substantial reduction in the burden of OM in childhood would require a combination of vaccines that are effective against the bacterial and viral pathogens involved and that can be administered early in infancy.     

Prevention of Lyme disease.

Lyme disease and the use of tick repellents and physical protective measures to prevent the disease are discussed. Lyme disease is a multiple-organ-system, immune-mediated inflammatory disorder transmitted by the bites of ixodid ticks infected with Borrelia burgdorferi. An individual is at greatest risk for infection when a tick has been attached to the skin for more than 24 hours. Lyme disease occurs in three stages and may affect the skin, nervous system, cardiac system, and joints. Antimicrobials used in management consist primarily of penicillins, cephalosporins, tetracyclines, and erythromycin. Tick repellents are divided into those applied to the skin and those applied to clothing. Skin repellents include N,N-diethyl-meta-toluamide (DEET), 2-ethyl-1,3-hexanediol, and dimethyl phthalate. Permethrin is by far the most effective clothing repellent. DEET plus a permethrin-containing clothing repellent offers the best overall protection. The adverse effects of repellents are minimal, but cases of hypersensitivity have been reported, especially in children. Physical measures to prevent tick bites include avoiding tick-infested areas, wearing light-colored clothing for easy identification of crawling ticks, regularly checking the body and pets for ticks, wearing protective garments and closed-toed shoes, and removing attached ticks promptly by using tweezers or forceps to apply a steady upward pull. A vaccine for the active immunization of humans against Lyme disease remains to be developed. Although antimicrobial therapy is available for persons with Lyme disease, the best approach for those who may be exposed to infected ticks is to apply topical skin or clothing repellents and to practice common-sense measures of physical protection.     

Group A antibody persistence five years after meningococcal polysaccharide vaccination in the Sudan

Large meningococcal group A epidemics occur periodically in the Sudan, a country within the "meningitis belt" of Sub-Saharan Africa. Immunization with meningococcal polysaccharide vaccine induces protective serum bactericidal titers but little information is available on the duration of protection. Serum samples were obtained from 20 subjects, aged 11-47 years, who resided in the Sudan, and who had participated in a meningococcal polysaccharide immunogenicity study five years earlier. Persistence of serum group A bactericidal titers (measured with human complement) was compared to that of 12 immunized adults in North America with no known exposure to group A organisms. One month after vaccination, there were no significant differences in the serum bactericidal titers of the two groups. By five years the respective reciprocal geometric mean bactericidal titers had declined in both groups (82 to 34 in Sudanese, and 69-11 in North Americans, p < or = 0.03). However, the proportion of sera with protective bactericidal titers (> or =1:4) at five years was higher in the Sudanese than North Americans (80% vs. 42%, p < or = 0.05). Recommendations for periodic meningococcal polysaccharide vaccination every 3-5 years to maintain group A immunity may be more appropriate for persons living outside of endemic areas than for persons residing in endemic regions since immunity in endemic areas can be maintained by periodic exposure to group A organisms, even during periods between epidemics.