Emergence of Invasive Meningococcal Disease During Hajj Pilgrimage – Vigilance and Preparedness, in the Post-Pandemic Year

Worldwide, meningococcal disease is a leading cause of morbidity and mortality [1]. In countries where there are epidemics, the rate of meningococcal disease can rise to 1,000 cases per 100,000 people. There are 12 serogroups of Neisseria meningitidis (N. meningitidis), only 6 of which — A, B, C, W, Y, and X — are accountable for the majority of invasive infections. The most prevalent form of invasive infection is meningitis and septicemia, which is associated with high case fatality rate (10%) and lifelong, disabling sequelae in 10‒20% of survivors [2,3]. N. meningitidis and other respiratory infection outbreaks often erupt during mass gatherings [4–8] (Table 1). N. meningitidis has historically been linked to large-scale events like the Hajj, when and where the possibility of respiratory and droplet-transmitted infections is high [9]. The Hajj pilgrimage may increase the acquisition of N. meningitidis because of the crowding and the gathering of millions in a small place [7,8,10]. The first global outbreak of N. meningitidis serogroup A disease after the Hajj happened in 1987, and W135 was the causative serogroup in the 2000-2001 Hajj seasons [5,11,12] .Table 1Serogroups of Neisseria meningitidis and previous Hajj-associated outbreaksSerogroupGeographyHajj-associated outbreaksSubsequent Hajj-required vaccineACommon in Africa1987MenA vaccineBMany countries, including the United States, Europe--CEurope, Americas, Western Pacific--WWorldwide, associated with outbreaks2000-2001quadrivalent MenACWY vaccineYCommon cause in the United States--XBurkina Faso-- Open table in a new tab N. meningitidis is normally carried in the nasopharynx of 10-15% of the adolescent population. In previous Hajj outbreaks, carriage rates as high as 80% had been reported leading to outbreaks during the Hajj in 1987 and 2000-2001 [5,11,12]. Owing to these outbreaks, the Saudi Ministry of Health implemented mandatory vaccination with conjugated quadrivalent meningococcal vaccine (ACYW135) for all Hajj travelers, yearly immunization drives for locals living in the vicinity of the pilgrimage site, and requirements for oral ciprofloxacin prophylaxis for travelers from meningitis-belt countries in sub-Saharan Africa [1,13–15]. Recent data on the N. meningitidis pre- and post-Hajj carriage rate showed an overall low rate of 0.74%, with significantly higher rates in the post- compared to pre-Hajj samples (0.38% vs 1.10%, p = 0.0004) [16]. In another study, 36 (3.4%) arriving unpaired pilgrim tested positive for nasopharyngeal N. meningitidis, 66.7% of which were serogroup B while the remainder were non-groupable [17]. The serogroup distribution of meningococcal carriage/infection during Hajj seasons has evidently changed overtime (Table 1). In the African meningitis belt, N. meningitidis serogroup A accounted for more than 80% of seasonal meningitis epidemics before the introduction of meningococcal serogroup A conjugate vaccine (MenACV) in December 2010 [18] with no confirmed cases of serogroup A diseases in these countries since 2017. The decline of N. meningitidis serogroup A carriage in both vaccinated and unvaccinated populations suggests that the vaccine has successfully generated herd immunity [19,20]. While dramatic impact of MenACV programs has been witnessed, the risk of resurgence must not be ignored. Community burden of N. meningitidis infection remains high as N. meningitidis serogroup W (ST-11 clonal complex) and X (ST-181 clonal complex), along with C (ST-10217 clonal complex), have been the major causes of invasive meningococcal disease in the meningitis belt since 2011 [18]. Overall, there was very limited genetic diversity, but local evolution of hyper-virulent lineages was noted [18]. Thus, meningococcal meningitis epidemics remain unpredictable. In the American region, recent data indicated a surge in invasive meningococcal disease caused by N. meningitidis serogroup Y, prompting the Centers for Disease Control and Prevention (CDC) in Atlanta to issue a Health Alert Network (HAN) Health Advisory [21]. Disturbingly, as of March 25, 2024, the number of reported cases for the current calendar year has already surpassed the figure recorded by this date in 2023 [21]. The invasive meningococcal disease caused by serogroup Y, particularly the ST-1466 strain, exhibited distinctive clinical presentation. Most cases presented with bacteremia rather than typical meningitis symptoms. Additionally, the case-fatality rate of 18% for diseases caused by the ST-1466 strain has exceeded the historical rate (11%) reported for serogroup Y cases in 2017–2021 [21]. The American upsurge raises concerns, when considering the history of meningococcal outbreaks during the Hajj pilgrimage [8]. The surge of serogroup Y cases disproportionately affected certain population segments, including individuals aged 30 to 60 years and Black or African American individuals [21], who could be among the pilgrims. The Hajj has drawn millions of pilgrims from around the world [8,22], a situation that would be even bigger this year – the post-COVID-19 pandemic year. The recognition of the recent upsurge in the cases of N. meningitidis serogroup Y in this context highlights the need for enhanced surveillance, intensified vaccination campaigns in the Hajj premises cities Makkah and Madinah, and monitoring compliance with Saudi's mandatory vaccination requirements targeting Hajj pilgrims. The Hajj season lasts two weeks and will be in the middle of June 2024, but the pilgrims could spend additional two weeks prior to or following the event. In 2022, the number of Hajj pilgrims was 926,062 and this doubled to 1,845,045 in 2023 (Figure 1), with 90% of them being external pilgrims. For 2024, the number of pilgrims is expected to exceed the pre-COVID-19 pandemic numbers. It is important to prepare pilgrims with intensive education about the risk of communicable diseases during the Hajj and the importance of following the comprehensive infection prevention and control guidance of Saudi Ministry of Health. Given the diverse backgrounds of Hajj participants, tailored interventions and targeted outreach efforts to ensure the safety and well-being of all pilgrims are crucial. The epidemiological changes in serogroup distribution of meningococcal carriage and diseases in the world, especially in countries sending most pilgrims to Saudi Arabia, need to be closely monitored, which will facilitate vaccination requirement adjustment depending on the predominant serogroups circulating in those countries with special focus on serogroup B and X which are not currently covered with the mandated meningococcal vaccine [14]. An affordable multivalent meningococcal conjugate vaccine offers the opportunity to eliminate meningococcal meningitis epidemics [18]. On the other hand, emergence of ciprofloxacin resistance puts into question the value of continuing its use as a decolonizing agent for African meningitis belts pilgrims [13]. In the context of the Hajj pilgrimage, syndromic surveillance plays a crucial role in the early detection of meningococcal disease. By monitoring symptoms and syndromes associated with meningococcal infection, such as fever, severe headache, neck stiffness, and rash, healthcare providers can identify potential cases promptly. Syndromic surveillance systems enable real-time data collection and analysis, allowing for rapid responses and targeted interventions [15,23]. Healthcare providers worldwide should maintain a vigilant approach towards meningococcal disease, not only when dealing with individuals planning to go on the Hajj pilgrimage but also with those who have returned from the Hajj. This includes maintaining a high index of suspicion, promoting vaccination, and ensuring adherence to robust infection control measures. To enable early detection and response, surveillance systems for N. meningitidis cases must be strengthened so as to track their incidence and distribution. Research on the emergence and transmission dynamics of N. meningitidis, as well as the effects of travel-related factors, should be conducted. It is important to encourage cooperation between public health organizations, medical professionals, and international partners. Community engagement is crucial in a variety of ways, for example, launching community-based awareness campaigns to inform pilgrims about the importance of getting vaccinated against meningococcal disease. Those who intend to perform the Hajj should be aware of the latest guidelines and directives issued by the Saudi Ministry of Health. It is also important to deliver accurate and updated information on health risks related to travel, including the Hajj pilgrimage, and suggest suitable precautions. [1] Memish ZA. Meningococcal Disease and Travel. Clin Infect Dis 2002;34:84-90. 10.1086/323403.[2] [No authors listed]. Meningococcal vaccines: WHO position paper, November 2011. 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