INTRODUCTION
A mass gathering has been defined by the WHO as an occasion, either organized or spontaneous where the ‘number of people attending is sufficient to strain the planning and response resources of the community, city, or nation hosting the event’ [1]. The WHO guidelines list diseases to be included in enhanced surveillance that: ‘Have modes of transmission likely to be enhanced in a mass gathering situation (e.g. meningitis, gastrointestinal and respiratory diseases)’.
Some of the largest mass gathering events are religious. The Hajj is an annual Islamic pilgrimage to Mecca, Kingdom of Saudi Arabia (KSA). This event follows the lunar calendar with pilgrims coming from both northern and southern hemispheres gathering in Mecca bringing to the locally circulating infections a group imported from a mixed seasonality and diseases epidemiology. In 2019, the number of pilgrims coming from inside and outside KSA to perform Hajj was 2 489 406 [2]. The Kumbh mela is the largest religious mass gathering in the world attracting over a 100 million Hindu pilgrims from all over India over 3 months every 12 years. The Arbaeen, Iraq, is the largest annual religious gathering in Iraq for Shia Muslims lasting for 14 days and attracting an estimated 15 million pilgrims in 2018. Other mass gathering event are the world Olympic games, football cups and other sports events.
Mass gathering events are bringing people close together from different areas, regions and countries, which increases the risk of spreading aerosol transmissible diseases, including transmission of multidrug resistant bacteria [3▪▪]. A study of upper respiratory samples taken before and after the 2013 Hajj found that the prevalence of viruses and bacteria increased, from 7.4 and 15.4% before the Hajj to 45.4 and 31% after the Hajj, respectively, because of the acquisition of rhinovirus, coronaviruses (229E, HKU1, OC43), influenza A H1N1, Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus[4]. Surveillance systems need to be in place and should be tailored to target selective diseases/events of public health significance, as no surveillance system can cover every possible event [5▪▪].
In this review, we discuss recent literature on influenza, pertussis, measles, tuberculosis and Middle East Respiratory Coronavirus Syndrome (MERS-CoV) at the annual Hajj pilgrimage.Â
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Box 1: no caption available
GENERIC STUDIES ON RESPIRATORY TRACT INFECTIONS
A study of French Hajj pilgrims between 2014 and 2017 showed that 82.1% presented with respiratory tract infections (RTIs) [6▪▪]. Respiratory chronic diseases were associated with cough, influenza-like illness (ILI) and the acquisition of H. influenzae. Vaccination against invasive pneumococcal diseases (IPD) and influenza was associated with a decrease in the acquisition of Strep. pneumoniae and prevalence of ILI and Relative Risk (aRR) = 0.69, 95% confidence interval (CI 0.52–0.92). Individuals carrying rhinovirus and H. influenzae--Strep. pneumonia together were, respectively, twice and five times more likely to have respiratory symptoms. Individual with H. influenza--Klebsiella pneumoniae carriage were twice (P = 0.04) as likely to develop a cough [7,8]. The use of disposable handkerchiefs was associated with a decrease in the acquisition of Staph. aureus [aRR = 0.75, 95% CI (0.57–0.97)]. The study confirmed the effectiveness of influenza and IPD vaccinations in reducing ILI symptoms and acquisition of Strep. pneumoniae carriage, respectively.
A study of ill travelers returning from mass gathering events based on the GeoSentinel database found that respiratory diseases accounted for almost 80% of all diagnoses, with vaccine preventable illnesses, such as influenza and pneumonia accounting for 26 and 20% of all diagnoses, respectively [9▪▪]. A study of 9350 pilgrims from United Kingdom, Australia, Saudi Arabia and Qatar voluntarily taking influenza and pneumococcal vaccines prior to Hajj found no observed benefit of combined vaccination (RR = 1.1; 95% CI 0.8–1.4) [10].
PNEUMOCOCCAL INFECTIONS
A review of studies on the prevalence of Strep. pneumoniae carriage among Hajj pilgrims before and after participating in the Hajj activities showed a significant increase in nasopharyngeal carriage of pneumococci including antibiotic resistant strains following the pilgrimage, with acquisition rates ranging from 18 to 36% [10]. There was no significant difference observed in the prevalence ratio of pneumococcal carriage between vaccinated and unvaccinated pilgrims. Another study found that the Hajj may increase pneumococcal carriage – particularly, conjugate vaccine serotypes and antibiotic nonsusceptible strains, although the exact mechanism remains unknown. The Hajj may, therefore, provide a mechanism for the global distribution of pneumococci [11]. However, the efficacy and effectiveness of the current vaccines in the context of Hajj and Umrah have not been studied [12].
INFLUENZA
A review of studies of influenza in Hajj pilgrims found influenza vaccination to be significantly associated with a reduced prevalence of ILI [RR 0.5 (95% CI 0.4--0.6), P < 0.01] [13]. The vaccine benefits extend beyond protecting the individual during their ritual to prevention of outbreaks in home countries secondary to different strains of influenza. A study of the uptake of influenza vaccines among Hajj pilgrims found the vaccine uptake was 2% and the attack rate of influenza was 8.2% [14].
MIDDLE EAST RESPIRATORY SYNDROME CORONA VIRUS
The MERS-CoV was first described from Saudi Arabia in 2012 [15]. It had a mortality rate of 59.8% in one study from Riyadh in people with comorbidities like chronic lung diseases and renal failure [16▪▪,17]. A study of 132 Hajj pilgrims found that influenza A, followed by non-MERS human coronaviruses, rhinoviruses and influenza B was the most common virus acquired during the Hajj [18]. Regulations for screening all camels participating in racing and beauty competitions in KSA had limited spread of MERS-CoV during such gatherings and also from slaughtered camels at Hajj ritual. No cases of MERS-CoV have yet been identified in pilgrims during Hajj or upon return to their home countries. Other coronaviruses identified at the Hajj include alpha-coronavirus and beta-coronavirus, of which the 229E strain is the most common cause of upper respiratory tract illnesses. A study from France evaluated the level of knowledge of MERS-CoV among Hajj pilgrims before and after an education health programme during international vaccine consultations in France [19]. Less than 25% were aware of the routes of transmission, symptoms and preventive behaviours and remained less than 50% after the Hajj.
TUBERCULOSIS
Tuberculosis remains the commonest cause of death from an infectious disease worldwide. Many people attending the Hajj and other religious mass gathering come from tuberculosis (TB)-high endemic counties defined as an annual incidence of 150/100 000 population [20]. TB is a slowly evolving disease and it is not unusual for persons to have symptoms like cough for months before they are diagnosed with active, pulmonary TB. Thus, people with pulmonary TB will participate in mass gatherings and with the close contact with others, the risk of transmission is high. No predeparture screening for active TB, for instance with a chest X-ray (CXR), is currently practised for pilgrims attending the Hajj as most likely it will not be cost effective.
The incidence of tuberculosis in travelers has been reported. A study of peace corps volunteers from USA. found 0.02 cases of active TB (95% CI 0.01–0.03) per 1000 volunteer-months, which is 24/100 000 persons per year [21]. An earlier study including travellers from The Netherlands to high endemic countries found that 1.8% converted from a negative to a positive skin test [22].
These two studies cannot directly be extrapolated to mass gathering events, but mass gathering in TB-high endemic countries or involved people from high endemic countries like the Hajj, must be assumed to have a higher risk.
One study including 352 pilgrims to the Hajj found that out of 149 with a negative interferon-gamma release assay (IGRA), pre-Hajj 10.4% had positive IGRA post-Hajj [23▪▪].
This indicate that 10% of the Hajj pilgrims are exposed to TB during the Hajj, which is an extraordinarily high number. However, 90% of exposed people never develop active TB and it may take years before a latent TB infection develops into active TB. It is, therefore, difficult to assess the real risk. In addition, issues relating to the standarization of the cut-off positive results for IGRA among pilgrims coming from over 180 countries need to be taken into consideration. However, there in an urgent need for repeating this study using tuberculin skin test and IGRA test pre-Hajj and post-Hajj to determine the risk and perhaps take steps to perform pre-Hajj screening for active TB for instance with a CXR.
VACCINATIONS
Every year the Saudi Arabian Ministry of Health issues updated guidelines on travel immunization recommendations for pilgrims (Table 1) [24]. Apart from three mandatory vaccines are the quadrivalent meningococcal vaccine for all pilgrims and the Yellow fever and Polio vaccines for pilgrims coming from countries with active polio transmission, recommended vaccines include influenza vaccine and pneumococcal vaccine. Owing to the high incidence of pertussis seen among Hajj pilgrims in 2003, Bordetella pertussis is considered a risk in pilgrims, especially those who have not completed their immunization schedule.
Table 1: Vaccination requirements for the 2019 Hajj
The KSA Ministry of Health recommends that all pilgrims attending the Hajj be up to date with their adult immunizations, inclusive of all vaccine preventable diseases. But no studies have been conducted in KSA to check compliance of pilgrims with pertussis immunization or the percentage of pilgrims who demonstrate pertussis acute infection or immunity.
NONINFLUENZA VACCINE PREVENTABLE DISEASES
Pertussis
Pertussis (whooping cough), is an infectious disease of the respiratory tract caused by B. pertussis, and is endemic in all countries. In 2014, the WHO reported an estimated 24.1 million pertussis cases and 160 700 deaths from pertussis in children less than 5 years of age globally. Increase of pertussis attack rates have been observed during community outbreaks, even in populations with a high rate of immunization because of the waning of immunity conferred by childhood vaccination [25].
In a prospective seroepidemiological study among 358 adult Malay pilgrims from Singapore to determine the incidence of pertussis, 5 (1.4%) were found to have acquired pertussis during the Hajj [21]. Of the 40 pilgrims who had no pre-Hajj immunity to pertussis, 3 (7.5%) acquired pertussis [26]. The vaccination coverage for pertussis, for example, was found to be 30% among Australian pilgrims who attended pretravel clinics [27]. This is a public health concern as returning pilgrims may present a reservoir transmitting infection to susceptible infants in their home countries who are prone to the most severe forms of infection [28].
Extrapolating from the reported high incidence in travellers to the Hajj, the risk may be more substantial than thought. There are no universal recommendations for pertussis vaccination for adult travellers, and studies are needed to develop evidence-based guidelines.
Measles
Measles is an airborne viral infection that can rapidly spread resulting in serious disease in nonimmune individuals, especially infants. The infection had re-emerged at global level because of fall in vaccination coverage in many countries and there had been reports of outbreaks in different settings including mass gathering events. Measles outbreaks have occurred among unvaccinated participants in 2005 at a church gathering in the USA [29], international youth sporting event in Pennsylvania in 2007, in France during the Taizé festival in 2010, during the international dog show in Slovenia in 2014 and at the Disney theme parks in California [30–32]. Most of these outbreaks involved secondary cases through the participants spreading the illness upon return to their country of origin.
The re-emergence of measles became a major public health issue, which had ignited the concerns about travel-related spread of measles and special concerns were raised about mass gathering events. For Hajj 2019, we reviewed measles vaccine coverage, measles incidence and number of pilgrims attending Hajj from each of the countries. On the basis of the expected age of pilgrims, we assumed that 70% of pilgrims were measles-immune (born before 1957) and calculated the number of susceptible pilgrims based on the vaccine coverage based on 2018 Hajj data. An estimated 110 measles importations were predicted to occur during the Hajj 2019 but KSA Ministry of Health did neither report any cases nor were there any reported cases or outbreaks outside KSA from returning pilgrims [22].
The unintentional ‘mass gatherings’, such as refugees sheltering in very crowded camps with poor hygiene and vaccines coverage (e.g. Syrian camps post displacement from civil war) are not usually regarded as mass gathering events, but nevertheless they pose great risk of aerosol transmissible diseases transmission like tuberculosis, measles and polio [33]. Mumps outbreaks had been rarely reported following mass gathering events like the one that happened after Easter festival in Austria in 2006 and resulted in 214 individuals been affected [34].
The recommendations from WHO and centers for disease control and prevention (CDC) for health consultation prior to travelling to a mass gathering had been associated with a two-fold increase in vaccinations among Hajj pilgrims who seek such advice compared with those who do not [23▪▪].
Multidrug-resistant bacterial infections
The potential spread of drug-resistant bacterial infections between participants in mass gathering event – whether symptomatic or not – is a concern where many of the nations now experiencing an upsurge in the prevalence of such superbugs, allow unrestricted access to antibiotics from private pharmacies. A recent study in hospitalized Hajj pilgrims in Mecca found that Escherichia coli (28%), followed by K. pneumoniae and Pseudomonas spp. were the most commonly encountered antibiotic resistant bacteria. Methicillin-resistant Staph. aureus (MRSA) was found in 9.6% [35]. Nasal swabs were taken from 979 Umrah visitors before and after events to evaluate the transmission of Staph. aureus and showed an increase in the carriage rate from 15.8 to 24% [36].
Prevention and management of respiratory infection in participants at mass gathering activities
A cross-sectional study of 225 Malaysian Hajj and Umrah pilgrims assessed the knowledge, attitude and practice towards prevention of RTIs during the 2018 Hajj [37▪▪]. Using a validated self-administered questionnaire showed good knowledge of RTIs among Malaysian pilgrims. However, a poor attitude was reflected in their preventive practice behaviours and the study highlighted the need for an educational health campaign to raise pilgrims the awareness of RTIs.
Proper planning and preparation for the participation in mass gathering event is the most important step in minimizing risk of contracting infections. Each individual should consider his vulnerability and discuss ahead of time with his physician possible strategies in mitigating the risks based also on understanding the geographical epidemiology and season of the event. The participants’ need for vaccines like influenza, meningococcal, measles, pertussis among others should be assessed and given at least 2 weeks prior to the event. Routine infection prevention and control (IPC) measures like practicing hand and respiratory hygiene are important tools in reducing the transmission of infections and it should be in educational and advocacy materials for the event.
Returning participants should seek medical attention if they develop acute respiratory illness with fever and cough during the 2 weeks after their return, or cough persisting more than 3 weeks especially if symptoms are severe enough to interfere with their daily activity. They need to be reminded about respiratory hygiene practice when ill (covering mouth and nose when coughing or sneezing; washing hands and or cleaning it with alcohol-based hand rubs after contact with respiratory secretions; and keeping a distance of 1 m from other persons) to prevent spreading infection. The management of a mass gathering participants with severe respiratory infection should consider investigation and empirical coverage for most likely cause based on syndromic surveillance data from hosting country and/or other relevant exposure history during events.
CONCLUSION
Respiratory infections are common among Hajj pilgrims with viral cause identified in most of them but bacterial infections are also possible. The management of severe respiratory infections should consider investigation and empirical coverage for most likely cause based on syndromic surveillance data from hosting country and/or other relevant exposure history during events. Pneumococcal and pertussis vaccines should be recommended for Hajj pilgrims. The SARS-CoV-2 outbreak started after the contribution to the special issue was closed. However, it is important to highlight that the Kingdom of Saudi Arabia has closed the borders for pilgrims, several countries world wide have cancelled mass gatherings and even the Olympics in Japan in the 24th August to the 9th August this year, is being discussed.
Acknowledgements
Sir Alimuddin Zumla is a co-PI of the Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-IDNET;https://www.pandora-id.net/) funded by the European and Developing Countries Clinical Trials Partnership the EU Horizon 2020 Framework Programme for Research and Innovation. Sir Zumla is also in receipt of an National Institutes of Health Research senior investigator award.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
â–ª of special interest
▪▪ of outstanding interest
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