Disease transmission and mass gatherings: a case study on meningococcal infection during Hajj

Mass gatherings (MGs) are defined by the World Health Organization as concentrations of people at a specific location for a specific purpose, over a set period of time with the potential to strain local resources [1]. MGs come in many different forms but can be grouped into three main categories: social events (concerts, festivals, etc.), sport events (FIFA World Cup, Olympic Games, etc.) and religious events (Kumbh Mela, Hajj, etc.). Because of increased global mobility, MGs have become both more frequent and more attended.

MGs put a strain on the resources of the location hosting these events, from transporting and housing gatherers to crowd control and policing. From the perspective of health, MGs pose a variety of significant public health threats, so much so that in 2011, the Jeddah declaration on Mass Gatherings Health laid out principles organising the field of mass gathering medicine [2]. Health issues stemming from MGs typically involve increased risks of injuries and spread of communicable diseases between participants and the local population [3‐5]. While the initial focus of the medical community was on dealing with issues arising in the host location, the problem evolved in recent years to include global health aspects [6, 7]. Two issues are of particular concern in this context. First, participants to MGs often originate from a variety of locations with different health systems, varying susceptibility, and immunity to pathogens. Therefore, one can ask what is the risk of infectious disease outbreak due to the MG event and how can this risk be mitigated? Second, if an outbreak occurs at the MG site, what is the risk that participants returning to their homes spread the infection to a previously unaffected region?

Here, we focus on the first of these questions and take transmission of invasive meningococcal disease (IMD) during Hajj as a case study. Hosted by the Kingdom of Saudi Arabia (KSA), Hajj is one of the largest mass gathering events globally. Muslim pilgrims perform the annual Hajj in the city of Mecca in KSA from 8th to 12th of Dhul-Hijja, the 12th month of the Islamic lunar calendar. Although pilgrims stay together during the 5-day period to follow the rituals, most of them spend three to six weeks in Mecca and Medina before and/or after the event. Medina is another holy place for Muslims, 450km away from Mecca. Over two million pilgrims attend Hajj every year. Their movement within Mecca and to Medina is regulated, yet all pilgrims gather in Mecca for the 5-day ritual. The overcrowding and intense congestion in Hajj has indeed caused outbreaks among pilgrims and the local population. During the 2000 and 2001 Hajj pilgrimages, outbreaks of IMD had occurred and led to global spread of the responsible strain [6, 8].

IMD is caused by Neisseria meningitidis leading to severe disease, complication and long term sequelae or even death. N. meningitidis carriage and transmission are particularly high in crowded conditions and close contacts [9]. The demographics of pilgrims is also an important factor for disease transmission [8]. Many Hajj pilgrims originate from the meningitis belt, a region in central Africa where major outbreaks of IMD are occurring [10]. A majority of these pilgrims are elderly potentially impacted by immunosenescence [11].

Following the 2000–2001 outbreak, the Hajj Monitoring Authority (HMA) initiated several measures including mandatory vaccination with a quadrivalent vaccine against serogroups A, C, W and Y, prophylactic treatments, masks, counseling, real-time surveillance and sharing of data [12, 13]. These preventive measures were successful to contain many outbreaks. However, the risk of a major transmission or outbreak still remains due to various unpredictable factors e.g. introduction of novel pathogens or new strains, reduction of vaccine coverage for vaccine-preventable diseases, deterioration in the other preventive measures. Indeed, COVID-19 pandemic led KSA to cancel Hajj pilgrimage of 2020 [14, 15].

In this paper, we aim to provide better understanding of the transmission mechanisms during Hajj and insights regarding the effectiveness of vaccination both for local and pilgrim population.

The analysis performed is based on a compartmental, meta-population, and age-structured model representing the transmission dynamics of meningococcal infection. This model was specifically designed for assessing the impact of Hajj pilgrimage on disease transmission and calibrated with historical IMD data in Saudi Arabia.

Our analysis first highlighted the very significant role of Hajj on meningitis transmission. The calibration process identified a 78-fold larger transmission rate during Hajj (Table 2). This magnified transmission rate could be translated to nearly 78-fold new cases compared to the transmission in a regular population with no added density (Fig. 4). The density has a nonlinear effect on the transmission rate and new cases. The cases can be increased by 15–20% if the density increases by 10% from its base value. While this result may not be verified without further data, other studies suggest that mass gathering could magnify an outbreak significantly [21, 22].

Following model validation, we evaluated the impact of the quadrivalent ACWY meningococcal vaccine on the transmission among the pilgrims and non-pilgrims. It suggests that in the absence of vaccination the risk of large outbreak is significant (17% probability to observe more than 100 IMD cases). However, under current vaccine policy (100% coverage) our analysis predict that hardly 10 IMD cases may occur. In addition, we assessed the possibility of vaccine supply shortage and attendance of unvaccinated pilgrims from one cluster. In this scenario, the outbreak seems to be less significant unless the unvaccinated pilgrims are traveling from the medium endemicity cluster which may result in about 25 cases. A possible reason for this could be the number of participants in the Hajj from this cluster that represent about half of all pilgrims.

The results also suggest that pilgrim vaccination may significantly affect the residents of Mecca due to their close proximity with the pilgrims (Fig. 2). Every outbreak in the Hajj has an immediate consequence in Mecca. IMD outbreaks in Hajj would spread to Mecca residents and may not affect the entire region of KSA. These results are consistent with the previous outbreaks [23]. To protect the local residents, a routine quadrivalent ACWY meningococcal vaccination has been implemented in Mecca and KSA since 2002 and the drastic reduction in IMD cases observed the following years provide a direct indication of the important role of vaccination. Our simulation indicates that routine vaccine in the hosting country is crucial to prevent any local outbreaks. Stopping the routine vaccination program may not have a severe impact immediately, but in its absence, the IMD cases may rise gradually and the number can be quadrupled in 40 years, Table 3. Overall, these results highlight the importance of continuing the current vaccination policy for the pilgrims and local residents. However, the risk of a major transmission or outbreak still remains due to various unpredictable factors including the introduction of novel pathogens or new strains, and reduction of vaccine coverage.

Our study has several limitations. First, we simplified N. meningitidis transmission by aggregating all serogroups to focus more specifically on the consequences for Hajj. Our representation of Hajj also does not capture fully the complexity of transmission mechanisms at play : only 5 clusters where considered in our model whereas pilgrims originate from more than 100 countries, we used a standard duration for Hajj pilgrimage (20 days) whereas this duration vary significantly among pilgrims, pilgrims also tends to have more close contact with other pilgrims with the same country of origin. The vaccine characteristics considered in our analysis correspond to a conjugate vaccine whereas either polysaccharide or conjugate vaccines can be used for Hajj pilgrimage [24]. Polysaccharide vaccines are associated with a shorter duration of protection and have no significant impact on carriage [25]. They might therefore have a more limiting ability to prevent outbreaks. However, to meet vaccine requirements, polysaccharide vaccine needs to be administered less than 3 years before Hajj and there is also evidence that such vaccines can reduce transmission [26, 27]. Data used also derive from a variety of sources which raises some consistency and quality issues. Information on meningitis prevalence for instance remains limited. We used a limited period of time for model calibration (7 years) and did not account for vaccination effect during this period whereas some pilgrims had received at that time bivalent vaccination.