Meningococcal Carriage, Disease and Vaccination

Invasive meningococcal disease (IMD) is caused by Neisseria meningitidis; a Gram-negative, aerobic encapsulated diplococcus that can cause large scale meningitis outbreaks. The risk of meningococcal carriage and disease is higher among particular age groups, certain community settings and travellers. The prevalence of invasive meningococcal disease peaks during infancy due to lack of immunity and again, to a lesser extent, in late adolescence/early adulthood due to increased social mixing. Closed and semi-closed community settings are also associated with high rates of meningococcal transmission and carriage acquisition and have experienced recurrent outbreaks of IMD. Travelling, including pilgrimage to Hajj, is yet another vulnerable circumstance. Despite advanced intensive care support, about 20% of survivors are left with long-term sequelae following IMD, thus prevention by vaccination is the most practical and effective measure of reducing the morbidity and mortality associated with IMD. The use of polysaccharide and then conjugate vaccines against specific meningococcal serogroups causing outbreaks led to a dramatic decline in IMD incidence. However, the observation of waning of immune responses over time following early childhood vaccination remains a concern for resurgence of disease in adolescence. Additionally, issues such as quantifying the effect of various meningococcal vaccines on carriage and the immune interaction between the carrier protein components of meningococcal conjugate vaccines and other vaccines containing the same proteins as antigens remain outstanding. To this end, the purpose of this thesis is to explore ways to better protect vulnerable populations, focusing on vaccination coverage in settings where a mandatory vaccination policy is in place, understanding the effect of vaccination on meningococcal carriage, and interpretation of the immune interactions between vaccines and changes to the immune response over time following vaccination. This thesis considers the annual Hajj pilgrimage as an exceptional context to achieve its aims as it comprises two groups of at-risk individuals: travellers and those within a closed population, and pilgrims often receive multiple vaccines during their preparation to the Hajj journey including meningococcal vaccine. Meningococcal vaccination is mandatory for domestic Hajj pilgrims and healthcare workers; however, their uptake has not been thoughtfully assessed. Hence, we evaluated the meningococcal vaccine coverage among these two groups and explored possible influencing factors. The uptake was suboptimal among both groups; gender, education, employment, receiving pre-Hajj health advice and distance of travel were important influencing factors and lack of awareness was the main barrier. One possible way to compensate for the suboptimal vaccination coverage is to assess and, if possible, limit meningococcal carriage. Therefore, a randomised controlled trial was conducted primarily to explore if meningococcal conjugate vaccines are better than their polysaccharide counterparts in reducing nasopharyngeal carriage among Hajj pilgrims. Actually, among the 1146 participants, the carriage of meningococci was almost non-existent. This may be suggestive of a successful vaccination policy or, more likely, a low season of meningococcal carriage. Hajj pilgrims, as travellers, are often required to receive multiple vaccinations within a short time period. These vaccines may include conjugate vaccines that could interact with other diphtheria-tetanus containing vaccines. Thus, the immune response of Neisseria meningitidis serogroup W (MenW) to the quadrivalent meningococcal conjugate vaccine (conjugated to cross-reacting material 197 (CRM197)) one month after being administered concurrently with, or 3-4 weeks prior to, or following combination tetanus, diphtheria and acellular pertussis vaccine (Tdap) was evaluated in a randomised controlled trial among Hajj pilgrims. The trial found that concurrent or sequential administration of Tdap and Neisseria meningitidis serogroups A, C, W and Y (MenACWY) CRM197 conjugate vaccine did not have a significant effect on the MenW immune response. While gradual waning of immune response, particularly following early childhood immunisations have been observed extensively and investigated, however, an exceptional phenomenon of a natural rise in immune responses has also been noted but not previously investigated. Thus, a secondary analysis of available data on changes over several years to the immune response to meningococcal serogroup C conjugate vaccines among children vaccinated in early childhood was undertaken. This analysis found that a substantial minority (~15%) of children had a rise in their bactericidal antibody titers in the absence of a booster dose of vaccine. This may be attributed to a potential carriage-induced booster response and hence raises concerns that herd immunity is not as well-maintained as previously thought