Impact of conjugate versus polysaccharide quadrivalent ACWY vaccine on meningococcal carriage among Hajj pilgrims

Intense congestion, including shared accommodation and compromised hygiene, during mass events such as Hajj pilgrimage amplify the risk of invasive meningococcal disease. Intercontinental spread of serogroup A meningococcal disease in 1987 and serogroup W135 disease in 2000 and 2001 affected thousands of Hajj pilgrims globally. Quadrivalent meningococcal polysaccharide (serogroups A, C, W135 and Y) vaccine was able to bring these epidemics under control, but the vaccine is not effective at reducing pharyngeal carriage of meningococci. A conjugate vaccine can reduce long term meningococcal carriage; for example, the quadrivalent conjugate vaccine has been shown to reduce carriage over 12 months from vaccination in adults aged 18-24 years old. However, the impact of conjugate meningococcal vaccines on meningococcal carriage status among Hajj pilgrims, most of whom are older than 24 years, is not known. We, therefore, believe that a well-powered carriage study in Hajj pilgrims is an urgent need. During the Hajj 2017, we plan to conduct a single-blinded, randomised, controlled trial of quadrivalent meningococcal conjugate vaccine for head-to-head comparison with quadrivalent polysaccharide among pilgrims from Australia, Qatar and Saudi Arabia. Pilgrims from participating countries, planning to attend Hajj in Makkah in 2017 will be randomised to receive either a ‘conjugate vaccine’ or a ‘polysaccharide vaccine’. Following informed consent, pharyngeal swabs will be collected from pilgrims in both arms a few months before their travel to Hajj. The participants will then receive their respective vaccines (observers will remain blind to this selection), a second set of pharyngeal swabs will be collected within sixty days after completion Hajj, preferably within 7 days and a third set of pharyngeal swabs will be collected at 6 to 11 months. Pharyngeal swabs will be processed by standard culture methods to detect meningococcal carriage; isolates will be characterised by serogroup, subtype, serosubtype, and sequence type. The pharyngeal swabs will also be tested for any antimicrobial resistance elements present. Data will be anonymised and analysed for the following end points: a) comparison between the study arms with respect to pharyngeal carriage rates of meningococci after return from Hajj, b) change in pharyngeal carriage rates of meningococci from before to a few months after vaccination, and c) comparison of long term carriage rates at 6 to 11 months after vaccination between study arms, and d) comparison of adverse events related to vaccination between study arms. This research could inform renewed policy on meningococcal vaccination for Hajj pilgrims as well as for attendees of other large events.