Outbreaks at mass gathering events:
What do we know?
---Dr. Philippe Gautret
Institut Hospitalo-Universitaire Méditerranée-Infection,
UMR Vecteurs – Infections Tropicales et Méditerranéennes
VITROME
EuroTravNet
Marseille, France
DIU/DESIU Médecine Tropicale et
Méditerranéenne, Capacité de Médecine
Tropicale, Marseille, May 2018
Mass gathering
what’s that?
WHO definition
• MGs are characterized by the concentration
of people at a specific location for a specific
purpose over a set period of time and which
has the potential to strain the (medical)
planning and response resources of the
country or community.
• Size doesn’t matter!
Sporting events
– Summer Olympics, every twoyears: 7.5 millions attendees in Rio, in 2016, over 16 days
– FIFA World Cup, every four years: 3.4 millions attendees in Brazil, in 2014, over 1 month
– EURO foot-ball cup, every four years: 2.4 millions attendees in 2016, in France
Cultural MGs
– Coachella Valley Music and Arts Festival : 250,000 attendees in 2017, over 4 days, Indio, California, US
– Glastonbury Festival of Contemporary Performing Arts: 120,000 attendees in 2017, over 5 days, UK
– Sziget Festival: 450,000 attendeesin 2017, over 7 days, Obudai-sziget, Hungary
Religious pilgrimages
– Kumbh Mela Hindu pilgrimagealong the river Ganges, every 3 years: 30-100 millions (?) pilgrims in 2013, over 45 days
– Lourdes: French Catholicnational pilgrimage, every year: 250,000 in 2017, over 5 days
– Arbaïn pilgrimage in Karbala, Irak, every year: 17 millions pilgrims in 2014
Political assemblies
– Gay Pride parade, every year: Sao Paulo, Brazil, : 3.0 millions in 2017
– Inauguration of President Elect in the US, Washington: BarackObama 1.8 million in 2009/ Donald Trump 250,000 in 2017
– Departure of President Hosni Mubarak, Cairo, Egypt : 5 millionsin 2011
Potential health risks at MGs
• Accidents and other types of injuries
• Potential for release of chemical, biological, radiological agents and/or bomb/blast events
• Effects of environmental conditions
• Increased risk of disease transmission
Global travel to the Hajj 2017
75% foreign pilgrims from outside
the Kingdom of Saudi Arabia
• Saudis: 9%
• Migrants
living
in KSA: 16%
• Foreign
pilgrims: 75%
Foreign pilgrims in 2017
(international travelers)
• Asia: 1,042,335 (59.5%) Indonesia, Pakistan, India, Bangladesh
• Arab countries: 415,644 (23.7%) Egypt, Iran, Turkey, North Africa
• Sub-Saharan-Africa: 186,873 (10.7%) Nigeria, Sudan, Ethiopia, Mali
• Europe: 84,894 (4.9%)
• America and Australia: 22,268 (1.3%)
European pilgrims 2017 (top 5)
UK : 25,000
France: 22,000
Russia: 20,500
Germany: 8,000
The Netherlands: 4,200
2,352,122 pilgrims gathering for 7
days in Mecca in 2017
The Hajj, step by step
Crowd density of
6–8 people per square meter
50 000 tents
50-100 pilgrims per tent
The Hajj in the time of cholera
1865
• 1831 and 1846 : 15,000 deaths
• 1865: 18,000 deaths
• 1881 : 5000 deaths
(5% of the total number of pilgrims)
• […]
• 1989: 102 cases
• 2011: 150 cases (Nigerian camp at Mina)
Diarrhea at the Hajj, today
Causes of consultation and hospitalization at
secondary and tertiary care hospitals in Saudi Arabia
• Hajj 1986: gastroenteritis = 77%
• Hajj 2002-2010: GID overall = 12% with
gastroenteritis relatively uncommon.
Causes of consultation at Mina primary health
care structure (outpatients)
• Hajj 2008 (4136 patients): GID = 13%,
gastroenteritis = 4%.
Cohort surveys
• 2002-2013 (262,999 pilgrims): diarrhea = 2% (1-23%)
Hajj-related meningitis outbreaks
• Hajj 1987: 1841 reported cases in KSA, subgroup A (III-1 clonal
complex)
• Hajj 2000-2001: > 500 cases (more than 40% serogroup W135
ET-37 clone)
Meningitis B+++ and X are regularly
isolated from asymptomatic pilgrims
next epidemic?
Hajj and respiratory infections
Causes of hospitalization at ICU
• Hajj 2009-2010: 452 patients pneumonia = 67%
Causes of consultation and hospitalization at
secondary and tertiary care hospitals in Saudi Arabia
• Hajj 1986: RTI = 10%, pneumonia = 8%
• Hajj 2002-2010: RTI = 44%, pneumonia = 28%
Causes of consultation at Mina primary health
care structure (outpatients)
• Hajj 2008 (4136 patients): RTI = 61%
Cohort surveys
• Hajj 2005 (75676 Iranian pilgrims): cough = 70%
• Hajj 2007 (394 Malaysian pilgrims): cough = 92%
• Hajj 2012-2014 (382 French pilgrims): cough = 81%
Recent works
2012-2017
IHU Méditerranée Infection
Marseille, France
RTI at the Hajj
Syndromic surveillance
• Sex ratio M/F : 1.41
• Citizenchip : France 34.3%, Algeria 34.1%, Morocco 19.8%, Tunisia 10%
• North African origin : 90.7%
• Living in France since > 20 y : 85.1%
• Median age : 61 y (20-84)
45-64 y : 52.1%
> 64 y : 34.7%
Marseille pilgrim’s characteristics(Gautret et al, 2007 - 2017)
• Currently working (< 65 years) 19.9%
• Education > Baccalaureate: 13.0%
• Social housing tenants: 47.5%
• Chronic diseases (43%)– Diabetes : 22.8%
– Hypertension : 25.3%
– Hypercholesterolaemia : 10.3%
– Chronic respiratory disease : 4.0%
– Walking disability : 26.0%
Marseille pilgrim’s characteristics
Vaccination coverage
(Gautret et al, 2007)
0,0%
10,0%
20,0%
30,0%
40,0%
Allegated 22,6% 16,1% 16,9% 10,6% 11,5% 27,3%
Certified 9,8% 8,9% 9,1% 2,4% 2,4% 6,1%
Tetanus Diphteria Poliomyelitis Pertussis Hepatitis A Influenza
Gautret et al, JTM, 2011Pneumococcal vaccination
Preventive measure Number (%)
Wearing a surgical face maskNeverOccasionallyFrequently
56 (20.4%)106 (38.7%)112 (40.9%)
Hand washingAs usualMore frequently than usual
83 (30.3%)191 (69.7%)
Hand disinfectant 212 (77.4%
Disposable handkerchief 246 (89.8%)
Gautret et al, JTM, 2011
Observance of preventive measures
N = 382
Cough prevalence : 81%
URTI +++
• Persistant symptoms on return to France
in > 50% pilgrims
N = 382
Molecular epidemiology
Before/after
• Questionnaire Questionnaire
• Syst Sampling Syst Sampling
MEDICAL FOLLOW-UP DURING TRAVEL
+/- Sampling at onset of symptoms
– influenza A /H3N2, A/2009/H1N1, Influenza B viruses;
– Coronavirus 229E, HKU1, NL63, OC43;– human metapneumovirus; – human rhinovirus;– human adenovirus ; – human enterovirus
– Human parainfluenzavirus, 1, 2, 3, 4– Respiratory syncitial virus
– Bordetella pertussis;– Chlamydophila pneumoniae;
– Mycoplasma pneumoniae
16 Respiratory viruses and 3 bacteria FilmArray Respiratory Panel BioFire
Hajj 2016, Marseille pilgrims
Nasal carriage (%)
• Hajj 2016 (110/103 French pilgrims)
0
5
10
15
20
25
30
35
40
45
50
Before traveling On return
At least one virus Rhinovirus Enterovirus Coronavirus 229E
Coronavirus HKU1 Coronavirus NL63 Coronavirus OC43 Adenovirus
Influenza virus RSV PIV MPV
Bacteria
Cough: 75%
Fever: 25%
Significant acquisition of respiratory viruses (50%)
0
1
2
3
4
5
6
7
8
9
10
11
12
Total patients with onset of symptoms Patients sampled at onset of symptoms
Rhinovirus/enterovirus positive Coronavirus positive
Influenza virus positive 2 Moy. mobile sur pér. (Total patients with onset of symptoms )
2 Moy. mobile sur pér. (Rhinovirus/enterovirus positive) 2 Moy. mobile sur pér. (Coronavirus positive)
Mecca Mina Medina
High virus carriage at the time of onset (96%)
USA
A: 135
D: 47
Somalia
A: 100
D: 118
France
A: 36
D: 31
Albania
A: 35
D: 45Pakistan
A: 100
D: 110
India
A: 99
D: 111
Bangladesh
A: 99
D: 104
Malaysia
A: 100
D: 111
Indonesia
A: 99
D: 86Tanzania
A: 103
D: 107
Ethiopia
A: 99
D: 80
Nigeria
A: 100
D: 91
Egypt
A: 101
D: 121
Hajj 2013: 1200 pilgrims from 13 countries
– influenza A (FLUA), B (FLUB), C (FLUC), and A/2009/H1N1 viruses;– human respiratory syncytial virus A (VRSA) and B (VRSB); – human metapneumovirus (HMPV A/B); – human rhinovirus (HRV);– human adenovirus (HAdV); – and human enterovirus (HEV)– Human bocavirus– human cytomegalovirus– human parainfluenza virus (1, 2, 3, 4)– human parechovirus– human coronaviruses (non MERS-CoV = 4 coronaviruses)– MERS-CoV– S. pneumoniae , – N. meningitidis, – Bordetella pertussis, – Mycoplasma pneumoniae– Coxiella burnetii– Chlamydophila pneumoniae– Haemophilus influenzae– Klebsiella pneumoniae– Legionella pneumophilla– Salmonella spp.– Staphylococcus aureus– S. pyogenes– Pneumocystis jiroveci
22 Respiratory Viruses12 bacteria
+ PneumocystisqPCR
Not isolated at any time
– influenza (FLUC),
– human metapneumovirus (HMPV A/B); – human cytomegalovirus– MERS-CoV– Bordetella pertussis, – Mycoplasma pneumoniae
– Chlamydophila pneumoniae– Legionella pneumophilla– Salmonella spp.– S. pyogenes– Pnneumocystis jiroveci
Rarely isolated
– influenza B (FLUB),
– human respiratory syncytial virus A (VRSA) and B (VRSB); – human adenovirus (HAdV); – human enterovirus (HEV)– Human bocavirus– human parainfluenza virus (1, 2, 3, 4)
– human parechovirus– N. meningitis (5 cases at departure)– C. burnetii (1 case at departure)
– Influenza A H1N1
– Influenza A H3N2– Rhinovirus
– Coronavirus 229E
– Coronavirus HKU1
– Coronavirus OC43
– Coronavirus 229E– S. pneumoniae
– H. influenzae
– K. pneumoniae
– S. aureus
HAJJ’S ELEVEN
Frequently isolated
N = 382
Cough prevalence : 81%
URTI +++
bla-OXA-51 in 0% pre-Hajj but 23.2% post-Hajj
sample (A. baumannii)
blaOXA-72 in 1 post-Hajj pharyngeal sample (A.
baumannii)
blaOXA-48 in 1 post-Hajj pharyngeal sample
blaOXA-58 in 3 post-Hajj pharyngeal samples
Screening pharynx samples for
carbapenemase encoding genes by PCR
9.2% pre-Hajj / 32.6% post-Hajj
Screening stools for ESBL-encoding genes by PCR
Multivariate
• Shortness of breath
(OR, 2.56; 95% CI, 1.14–5.73; P = .023)
• Diarrhea (OR, 3.35; 95% CI, 1.20–9.36; P = .021)
• Macrolide (OR, 0.15; 95% CI, 0.04–0.57; P = .0005)
Univariate
• Moroccan origin, shortness of breath, diarrhea and use
of β-lactam antibiotics during the Hajj were
demonstrated to be risk factors of CTX-M gene
acquisition.
• Use of macrolide = protective factor
Risk factors for CTX-M gene acquisition
Screening stools for Colistine resistance-encoding
genes by PCR
mcr-1 gene: in 1.4% pre-Hajj but 9.1% post-Hajj
Identification: E. coli (10) and K. pneumoniae (1)
Screening stools for
carbapenemase encoding genes by PCR
blaOXA-51 in 0% pre-Hajj and 38.9% post Hajj (rectum)
blaOXA-58 in 19 post-Hajj rectal samples
blaNDM-5 in 1 post-Hajj rectal sample (E. coli)
blaNDM-1 in 1 post-Hajj rectal sample
Practical consequences
• Vaccination against influenza
• Vaccination against S. pneumoniae
• Face mask and hand hygiene
• Reduction of antibiotic consumption (β-lactam)
http://www.who.int/ith/updates/20170408/en
/
Official recommendations for Hajj pilgrims
http://www.moh.gov.sa/en/Hajj/HealthGuidelines/HealthGuidelinesBeforeHajj/Page
s/default.aspx
http://invs.santepubliquefrance.fr/Publications-et-outils/BEH-
Bulletin-epidemiologique-hebdomadaire/Archives/2018/BEH-
hors-serie-Recommandations-sanitaires-pour-les-voyageurs-
2018
Hajj and vaccinations
recommendations
MeningococcalInfluenzaPolio (< 15 y, endemic countries and re-established transmission countries)YF (endemic countries)Diphtheria, Tetanus, Pertussis Measles and Mumps
• Meningite
• Polio
• Fièvre Jaune
• DTP
• Rougeole
• Grippe
• Hepatite A
• Pneumocoque (pélerins à risque + > 60 ans)
The Saudi Thoracic Society pneumococcal
vaccination guidelines-2016
N. S. Alharbi, A. M. Al-Barrak,1 M. S. Al-
Moamary,2 M. O. Zeitouni,3 M. M. Idrees,1
M. O. Al-Ghobain,2 A. A. Al-Shimemeri,2
and Mohamed S. Al-Hajjaj
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854068/
All persons at ≥50 year are recommended to
receive combined vaccination with PCV13 and
PPSV23 before the Hajj. However, for those
planning immediately before Hajj, it is
recommended to administer one dose of
PPSV23 [Evidence Category D]
Immunocompetent persons <50 years with
risk factors are recommended to receive
single dose PPSV23 at least 3 weeks before
the Hajj [Evidence Category D]
Because of lack of evidence, it is not
recommended to provide a pneumococcal
vaccine routinely to healthy persons aged <50
years.
Meningococcal vaccines
= mandatory
• A, and A + C
• [Polysaccharide
A, C, Y, W135
– Mencevax]
• Conjugated
A, C, Y, W135
–Menveo
–Nimenrix
Visitors from the African meningitis belt
• Ciprofloxacin or rifampicin for children
chemoprophylaxis will be administered at the
port of entry.
Marseille vaccination strategy
for Hajj pilgrims
• Meningococcal (mandatory)
• Yellow fever: no need
• DTP vaccine (booster every 10 y in older adults, update recommended for all travelers)
• Influenza vaccine
• Pneumococcal (> 60 y or risk factors)
• Hep A (French born, > 1945)
• Hep B : no evidence : avoid unlicensed barbers
• Pertussis : one study only, need further evidence
• Mumps and Measles : no data available
MERS Coronavirus
• Hand washing (soap and water – disinfectant)
• Disposable tissues
• Avoiding hand contact with eyes, nose and mouth
• Avoiding direct contact with ill people
• Wearing masks
• Maintaining good personnal hygiene
• Hajj post-ponment (>65 y, chronic diseases, pregnancy, <12 y)
• Avoiding unpasteurized
camel milk concumption
• Avoiding contact
with farm or wild animals
• Prevention of heat stress– Rituals at night time
– Umbrellas / shade
– Drinking water
– Sun block cream
Grand
Magal
Le Grand Magal de Touba
• Commémoration annuelle du départ en exil de Cheikh Ahamadou Bamba (1895) fondateur du Mouridisme (Soufisme - Islam)
• 4-5 millions de pèlerins du Sénégal, d’Afrique, d’Europe, d’Amérique du Nord (diaspora)
• Touba 750,000 habitants
• Journée commémorative (visite de la Mosquée et des mausolées des leaders successifs du mouvement Mouride)
• Visite des Marabouts
• Grande réunion de famille
• Activités commerciales
et culturelles
Touba
N’Diop/Dielmo
Transport/hébergement
• Routier essentiellement jusqu’à Touba (moto,
voiture, minibus, cars, camions…)
• Transport intérieur en charrette à mulet
• Déplacements de foule à pied vers la mosquée
• Hébergement dans les familles (ouvert à tous)
• Hébergement dans les maisons de Marabout
Conséquences
• Augmentation majeure du trafic routier à
destination de Touba
• Surpopulation transitoire dans et autour de
Touba
• Abattage massif de bétail
• Suractivité médicale
• …
Premiers résultats
Moyens médicaux mobilisés en 2015
78 médecins
481 lits
Analyse des registres des structures de
santé – Magal 2015
• 32,229 consultations
• 3.4% hospitalisation
• <0.1% mortalité
• 0.7% transfert Dakar
• 6.1% biologie
• 2.5% radiologie
MALADIES INFECTIEUSES ?
?
• 154 public healthcare structures
around Touba
• November 16 to 21 (6 days)
• Demographics, symptoms, treatment,
outcome
Syndromic surveillance during the
2016 Grand Magal in Senegal
• 20,850 heath care encounters
• Median age: 26 years (IQR 11-45 years,
range 0-96 years)
• 30.9% individuals <15 years and 11.4%
>60 years
• 11694 patients were female (56.1%),
8960 were male (43.1%), 170
undocumented
181383271217
0-4
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85+
Male Female
Symptoms Number of
patients
Proportion of all patients (%)
Headache 5913 28.4
Fever 3593 17.2
Fatigue 3277 15.7
Vertigo 1476 7.1
High blood pressure 1398 6.7
Diffuse pain 1216 5.8
Arthralgia 567 2.7
Myalgia 566 2.7
Gastrointestinal symptoms 4591 22.0
Respiratory symptoms 3563 17.1
Skin symptoms 1589 7.6
Dental pain 750 3.6
Trauma 607 2.9
Conjunctivitis 300 1.5
Heat stress 282 1.4
Urinary symptoms 227 1.1
Table 1. Main symptoms presented by patients (N=20850 patients)
Gastrointestinal symptoms 4591 22.0
Abdominal pain 1509 7.2
Vomiting or nausea 1223 5.9
Epigastric pain 1222 5.9
Diarrhea 803 3.9
Constipation 340 1.6
Anorexia 288 1.4
Respiratory symptoms 3563 17.1
Cough 3126 15.0
Rhinitis 1791 8.6
Influenza-like illness 446 2.1
Sore throat 194 0.9
Dyspnea 153 0.7
Skin symptoms 1589 7.6
Wound 1039 5.0
Dermatitis 454 2.2
Skin abscess 146 0.7
Treatment Number of patients Proportion of all patients (%)
Antibiotics 6210 29.8
Beta-lactam 4122 19.8
Quinolone 1098 5.3
Cotrimoxazole 1072 5.1
Cycline 12 0.06
Cephalosporine 9 0.04
Macrolide 8 0.04
Antiparasitic drugs other than
antimalarials
2384 11.4
Mebendazole 1085 5.2
Metronidazole 866 4.2
Albendazole 529 2.5
Praziquantel 3 0.01
Antimalarials 549 2.6
Artemisinin-based combination 502 2.4
Quinine 69 0.3
Table 2. Main anti-infectious treatments prescribed to patients
(N=20850 patients)
Malaria
• 624/20850 (3.0%) patients were considered
suffering malaria including the 508 confirmed
by malaria RDT, 48 with negative malaria RDT
likely considered as non-falciparum malarial
infections and 68 based on clinical criteria
only.
Outcome
• 312 (1.5%) patients were hospitalized,
including 201 who were transferred to Dakar
hospitals (1.0%). Only 1 death was recorded.
Etude de cohorte au départ des villages
(N’Diop et Dielmo – Magal 2017
• Suivi prospectif
• Inclusion au village (questionnaires,
écouvillons systématiques, nez,
pharynx, selles)
• Au retour (questionnaires,
écouvillons systématiques, nez,
pharynx, selles)
Résultats questionnaires
(N=110)
• F/M: 56.4/43.6%
• Age med: 20 ans (1-76)
• <15 ans: 26.4% - >60 ans: 4.5%
• Pathologies chroniques: diabètes 0.9%;
HTA 1.8%, MRespC: 8.2%, MCardC: 1.8%
• Durée moyenne séjour : 3 jours (2-9)
Preventives measures n (N = 110) %
Influenza vaccination 1 0.9
Face mask No 104 94.6
Sometimes 3 2.7
Often 3 2.7
Hand washing As usual 59 53.6
Much more 51 46.4
Disinfectant gel No 10 9.1
Sometimes 30 27.3
Often 70 63.6
Disposable
handkerchiefs
No 44 40.0
Sometimes 30 27.3
Often 36 32.7
Table 2: Prevalence of adherence with preventive measures
during the stay in Touba
• Symptômes respiratoires: 41.8%, pre-
Magal 6.4%, pendant et post-Magal:
30.9% [X 4.8] = toux (24.6%), d pharyngée
(10%), rhinite (30%), expectoration (4.6%),
fièvre (10%), ATBQ (2.7%).
• Symptômes digestifs: 14.6%, pre-Magal
3.6%, pendant et post-Magal: 10.9% [X 3]
= diarrhée (4.6%), vom (9.1%), ATBQ
(1.8%).
• Hospitalisation: 0
Acquisition pathogènes respiratoires
• Influenza 0.9%
• Rhinovirus 13%
• Adenovirus 4.6%
• Coronaviruses 16.7%
• S. aureus 13.9%
• S. pneumoniae 3.7%
• H. influenzae 26.9%
• K. pneumoniae 6.5%
Acquisition pathogènes intestinaux
• Norovirus 2.2%
• Adenovirus 4.4%
• Giardia 2.2%
• Salmonella 2.2%
• Shigella 4.4%
• EHEC 17.8%
• EPEC 33.3%
• EAEC 24.4%
• Campylobacter 2.2%
