Pandemic influenza: mass gatherings and mass infection
Authors: Harunor Rashid, Elizabeth Haworth, Shuja Shafi, Ziad A Memish, Robert Booy
Journal: The Lancet Infectious Diseases (2008)

Mass gatherings, such as this year's Beijing Olympic Games, typically involve travel and extended close contact among participants and spectators. Influenza is one of the most frequently identified respiratory viruses in travellers,1Camps M Vilella A Marcos MA et al.Incidence of respiratory viruses among travelers with a febrile syndrome returning from tropical and subtropical areas.J Med Virol. 2008; 80: 711-715Crossref PubMed Scopus (24) Google Scholar and the high density of people at mass events further increases the risk of transmission. Despite this, the epidemiology of influenza outbreaks in large congregations is poorly understood. Variability of venues and the infrequency of mass events may have been barriers for systematic study of communicable diseases in these situations. However, because the venue does not change and the event occurs every year, the Islamic Hajj pilgrimage to Mecca, Saudi Arabia, does provide an excellent opportunity to research infectious diseases that not only affect a mass event but also have the potential for pandemic spread. Infectious diseases at the Hajj have been reported for centuries. During the first Hajj in 632AD, the pilgrims had febrile illness known locally as "Yethrib fever", which is now believed to be malaria.2Farid MA Implications of the Mecca pilgrimage for a regional malaria eradication programme.Bull World Health Organ. 1956; 15: 828-833PubMed Google Scholar Subsequently, major epidemics such as plague and cholera have been reported. Over the past decades there have been several intercontinental outbreaks of meningococcal disease, first caused by serogroup A and later by W135.3Ahmed QA Yaseen MA Memish ZA Health risks at the Hajj.Lancet. 2006; 367: 1008-1015Summary Full Text Full Text PDF PubMed Scopus (328) Google Scholar Currently, respiratory infections are the commonest illnesses encountered at the Hajj and include, among others, influenza, pertussis, and tuberculosis.3Ahmed QA Yaseen MA Memish ZA Health risks at the Hajj.Lancet. 2006; 367: 1008-1015Summary Full Text Full Text PDF PubMed Scopus (328) Google Scholar Depending on study design, the occurence of seasonal influenza at the Hajj ranges from 6% to 38%, affecting both domestic and overseas pilgrims.4Balkhy HH Memish ZA Bafaqeer S Almuneef MA Influenza a common viral infection among Hajj pilgrims: time for routine surveillance and vaccination.J Travel Med. 2004; 11: 82-86Crossref PubMed Scopus (137) Google Scholar, 5Rashid H Shafi S Haworth E et al.Viral respiratory infections at the Hajj: comparison between UK and Saudi pilgrims.Clin Microbiol Infect. 2008; 14: 569-574Summary Full Text Full Text PDF PubMed Scopus (91) Google Scholar, 6El Bashir H Haworth E Zambon M Shafi S Zuckerman J Booy R Influenza among UK pilgrims to Hajj, 2003.Emerg Infect Dis. 2004; 10: 1882-1883Crossref PubMed Scopus (50) Google Scholar So far, no human case of avian influenza A (H5N1) has been reported at the Hajj or in Saudi Arabia, but cases of H5N1 in human beings (table) have been reported in Indonesia, Pakistan, and Turkey, countries from which many people make the annual pilgrimage to Mecca. Counting Bangladesh, Iraq, Egypt, Azerbaijan, Nigeria, and Djibouti, a total of nine countries with predominantly Muslim populations have already been affected by the virus. As of July 25, 2008, over half (214/385) of the reported number of H5N1 influenza cases have been in Muslims.7WHOCumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. Geneva: World Health Organization.http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_06_19/en/index.htmlGoogle Scholar Furthermore, there was an outbreak of H5N1 influenza in Saudi poultry earlier last year.TableMuslim countries with H5N1 influenza that send pilgrims on HajjPopulation (millions)Proportion of population who are MuslimNumber of pilgrims per yearNumber of cases of H5N1 influenza7WHOCumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. Geneva: World Health Organization.http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_06_19/en/index.htmlGoogle ScholarH5N1 case fatality (%)7WHOCumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. Geneva: World Health Organization.http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_06_19/en/index.htmlGoogle ScholarIndonesia237·586·1%200 000135110 (81%)Pakistan167·897%150 00031 (33%)Turkey71·999·8%120 000124 (33%)Nigeria138·350%90 00011 (100%)Egypt81·790%75 0005022 (44%)Bangladesh153·683%65 00010 (0%)Iraq28·297%30 00032 (67%)Azerbaijan8·293·4%400085 (63%)Djibouti0·594%200010 (0%)Total....736 000214145 (68%) Open table in a new tab The recent account of likely human-to-human transmission of H5N1 influenza in China, reported by Wang and colleagues,8Wang H Feng Z Shu Y et al.Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China.Lancet. 2008; 371: 1427-1434Summary Full Text Full Text PDF PubMed Scopus (248) Google Scholar alerts us to the possibility of a pandemic arising from mass events such as the Hajj pilgrimage. In Wang and colleagues' report the index case was a young salesman whose source of exposure could not be ascertained; for the second case, which concerned his retired father, the infected son was the only apparent source of exposure. Genomic sequencing showed that the viruses from both patients were essentially homologous. This is the third example of potential person-to-person transmission of H5N1 influenza after the Thai and Indonesian family clusters.8Wang H Feng Z Shu Y et al.Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China.Lancet. 2008; 371: 1427-1434Summary Full Text Full Text PDF PubMed Scopus (248) Google Scholar What can be done to prevent an influenza outbreak during the Hajj? An awareness campaign and better surveillance can have an important role. Severe acute respiratory syndrome (SARS) is a good example of the success of this approach. During the 2003 episode, of 8000 cases of SARS reported worldwide at least 142 were travel-associated.9Gushulak B Funk M Steffen R Global changes related to travelers' health.J Trav Med. 2007; 14: 205-208Crossref PubMed Scopus (8) Google Scholar However, tight measures taken by Saudi authorities, which included applying a ban on visitors from SARS-hit countries, home quarantine for domestic travellers, installation of thermal cameras in major airports, and ensuring facilities for rapid detection of SARS virus, prevented establishment of the virus in the country.10Memish ZA Wilder-Smith A Global impact of severe acute respiratory syndrome: measures to prevent importation into Saudi Arabia.J Travel Med. 2004; 11: 127-129Crossref PubMed Scopus (9) Google Scholar Initial results from studies of prototype vaccines against H5N1 influenza were disappointing, with two or more doses, of high antigenic content, being necessary to induce protective immunity.11Booy R Brown LE Grohmann GS MacIntyre CR Pandemic vaccines: promises and pitfalls.Med J Aust. 2006; 185: S62-S65PubMed Google Scholar Also, from our experience with seasonal influenza, we can assume that the H5N1 vaccine could be ineffective despite good immunogenicity if the pandemic strain does not match with the vaccine strain(s). Three studies from Pakistan, Malaysia, and Iran have so far assessed the effectiveness of seasonal influenza vaccine against influenza-like illness among Hajj pilgrims. The Pakistani and Malaysian studies reported the vaccine to be effective; however, the Iranian study, which was done over two consecutive influenza seasons, reported that the vaccine was effective during the 2003 Hajj but not during the 2004 Hajj.12Qureshi H Gessner BD Leboulleux D Hasan H Alam SE Moulton LH The incidence of vaccine preventable influenza-like illness and medication use among Pakistani pilgrims to the Haj in Saudi Arabia.Vaccine. 2000; 18: 2956-2962Crossref PubMed Scopus (62) Google Scholar, 13Mustafa AN Gessener BD Ismail R et al.A case-control study of influenza vaccine effectiveness among Malaysian pilgrims attending the Haj in Saudi Arabia.Int J Infect Dis. 2003; 7: 210-214Summary Full Text PDF PubMed Scopus (34) Google Scholar, 14Razavi M Sadeghi-Hasanabadi M Salamati P The comparison of influenza vaccine efficacy on respiratory disease among Iranian pilgrims in the 2003 and 2004 seasons.Acta Med Iran. 2005; 43: 279-281Google Scholar Virological surveillance reports suggest that the rate of influenza in vaccinated pilgrims might not significantly differ from that in unvaccinated pilgrims.5Rashid H Shafi S Haworth E et al.Viral respiratory infections at the Hajj: comparison between UK and Saudi pilgrims.Clin Microbiol Infect. 2008; 14: 569-574Summary Full Text Full Text PDF PubMed Scopus (91) Google Scholar, 6El Bashir H Haworth E Zambon M Shafi S Zuckerman J Booy R Influenza among UK pilgrims to Hajj, 2003.Emerg Infect Dis. 2004; 10: 1882-1883Crossref PubMed Scopus (50) Google Scholar Stockpiling antiviral drugs is another important control strategy but resistance can be a problem. Therefore, a multi-pronged approach will be required to prevent pandemic influenza at mass gatherings such as the Hajj. Key elements of this approach include education and awareness, improved surveillance, rapid diagnosis, and containment with antiviral treatment of cases and close contacts, non-pharmacological interventions including surgical masks, and, above all, coordinated global research with viral typing in countries of origin and sharing of these data. Because the recent report of probable inter-human transmission of H5N1 occurred in China,8Wang H Feng Z Shu Y et al.Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China.Lancet. 2008; 371: 1427-1434Summary Full Text Full Text PDF PubMed Scopus (248) Google Scholar the host of this year's Olympic Games, we believe that pandemic influenza should be an important consideration in public-health planning for the event. With data from other mass sporting events, we can postulate that respiratory and gastrointestinal infections will predominate during this year's Olympic season. Respiratory illnesses were the leading medical encounters during the 2002 Winter Olympics in Salt Lake City, USA; a hospital electronic medical record-based public-health surveillance system deployed during the event suggested a substantial increase in influenza during the games.15Gundlapalli AV Olson J Smith SP et al.Hospital electronic medical record-based public health surveillance system deployed during the 2002 Winter Olympic Games.Am J Infect Control. 2007; 35: 163-171Summary Full Text Full Text PDF PubMed Scopus (30) Google Scholar For the past few years the Hajj has been a winter event. At this time of year, there is increased risk of human influenza and also the possibility of dual infection with human and avian viruses, potentially leading to a genetically altered influenza virus of high virulence and transmissibility. The latest report of likely inter-human transmission of H5N1 influenza suggests that the virus is slowly becoming more adapted to human beings.8Wang H Feng Z Shu Y et al.Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China.Lancet. 2008; 371: 1427-1434Summary Full Text Full Text PDF PubMed Scopus (248) Google Scholar If the transmission among human beings becomes sustained, mass gatherings could help spread the virus all over the world at a very rapid pace. Therefore, coordinated global response and research is a high priority. RB has received financial support from pharmaceutical companies, including CSL, Sanofi, GSK, Roche, and Wyeth, to attend or present at scientific meetings; if fees were offered, these were placed in a university research/education account. All other authors declare that they have no conflicts of interest.