J Immigrant Minority Health DOI 10.1007/s10903-014-0059-y
ORIGINAL PAPER
Effect of Influenza Vaccination on Acute Respiratory Symptoms in Malaysian Hajj Pilgrims Habsah Hasan • Zakuan Zainy Deris • Siti Amrah Sulaiman Mohd Suhaimi Abdul Wahab • Nyi Nyi Naing • Zulkefle Ab Rahman • Nor Hayati Othman
•
Ó Springer Science+Business Media New York 2014
Abstract Respiratory illness were a major problem and caused high hospital admission during hajj seasons. One of the contributing cause to this illness is infection. Various measures had been implemented to reduce respiratory infections. The aim on the study is to determine the effect of influenza vaccination against acute respiratory illness among Malaysian Hajj pilgrims. This is an observational cohort study. Influenza vaccination was given to pilgrims at least 2 weeks prior to departure. The occurrence of symptoms for respiratory illness such as cough, fever, sore throat and runny nose was monitored daily for 6 weeks
This research has been presented partly in the 2nd National seminar on Hajj Best Practices Through Advances in Science and Technology, July, 2008 at Universiti Sains Malaysia, Penang, Malaysia. H. Hasan (&) Z. Z. Deris Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia e-mail: [email protected] S. A. Sulaiman M. S. Abdul Wahab Department of Pharmacy, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia N. N. Naing Unit of Biostatistics and Research Methodology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia Z. Ab Rahman Institut Perguruan Malaysia, Kampus Sultan Mizan, Besut, Terengganu, Malaysia N. H. Othman Clinical Research Platform, School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kubang Kerian, Malaysia
during pilgrimage using a health diary. A total of 65 vaccinated hajj pilgrims and 41 controls were analyzed. There was no significant difference in pattern of occurrence of symptoms of respiratory illness by duration of pilgrimage as well as the number of symptoms between both groups. Hajj pilgrims have frequent respiratory symptoms. We were unable to document benefit from influenza vaccination, but our study was limited by a small sample size and lack of laboratory testing for influenza. Keywords Hajj Acute respiratory symptoms Influenza vaccine Influenza like illness
Introduction Respiratory problems account for 74 % of all medical illness reported during hajj seasons [1]. Respiratory disease was the most common cause (57 %) of admission to hospital and pneumonia being the main cause of admission [2]. Pulmonary complications resulting from pneumonia are responsible for the second (after cardiovascular disease) greatest number of deaths during Hajj resulting in a considerable burden on patients and the healthcare system [3]. A cohort study of all critically ill hajj patients, of over 40 nationalities, admitted to 15 hospitals in two cities in 2009 and 2010 found that out of 452 patients who developed critical illness admitted to intensive care unit during hajj, pneumonia was the primary cause of critical illness (27.2 %) [4]. Pneumonia was community (Hajj)-acquired in 66.7 %, aspirationrelated in 25.2 %, nosocomial in 3.3 %, and tuberculous in 4.9 % [4]. Most of the pilgrims suffer from acute respiratory symptoms and cough was the main symptoms of the
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pilgrims [5]. The incidence of Malaysian hajj pilgrims having acute respiratory symptoms was very high. Almost 90 % of the 394 Malaysian hajj pilgrims surveyed had cough and 40 % had influenza like illness (ILI) [6]. Hajj is one of the pillars in Islam. It is a spiritual journey that must be performed at least once in a lifetime for every Muslims. Approximately 2.5 million pilgrims from all over the world will congregate at these places during the season [7]. Hajj activities include Tawaaf (seven circuits around the Holy Kaabah approximately 200 m each round) and Sa’i (seven times between Mount Safa and Mount Marwa approximately 2.1 km in total). The peak of congregation is on the 9th, 10th, 11th, 12th and 13th Zulhijjah, when all pilgrims from all over the world must gather at the same time and location i.e. Mina, Muzdalifah and Arafah. Most of the Malaysian pilgrims stayed in overcrowded tents in Mina and Arafah. Some pilgrims also perform umrah which include tawaf and sa’i several times before or after the peak of congregation. Every year, at least 26,000 Malaysian hajj pilgrims will travel by air to perform hajj. Malaysian pilgrims usually stay for at least 42 days (6 weeks) in Makkah and Madinah to perform Hajj. Malaysian Hajj Pilgrims stay longer than most of pilgrims from other countries because the package include other activities such as performing umrah in which they try to perform seven umrahs during their stay and a 10-day visit to Madinah which is about 400 km from Makkah. The pilgrims will arrive at Kingdom of Saudi Arabia daily in batches and the first batch usually arrives at about 3–4 weeks prior to the peak of congregation. The mass gathering and constant movement of pilgrims increased the risk of transmission of infectious diseases especially viral respiratory infections [8]. There are many factors promoting the spread of respiratory pathogens, including close contact among pilgrims, shared sleeping tents and dense air pollution [8, 9], Physical exhaustion due to the long journey, climatic weather change and the air pollution worsen the fate of the pilgrims who contracted the illness. Up to date, there are no effective protective measures for Hajj pilgrims against respiratory illnesses. Consumption of honey as daily supplement [10] and good hand hygiene [11] were shown to have some benefit in reducing the occurrence of respiratory symptoms. Whereas the use of surgical facemasks was found to be not effective in reducing respiratory symptoms [6, 11]. Saudi Ministry of Health recommended influenza vaccines to be given to hajj pilgrims before hajj as a protective measure [7]. The aim of this study is to determine the indirect effect of influenza vaccination on symptoms of acute respiratory illness in Malaysian hajj pilgrims.
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Table 1 Demography of Malaysian hajj pilgrims Characteristics
Control (n = 41)
Vaccine (n = 65)
4 (9.7)
1 (1.5)
v2
p valuea
7.07
0.273b
0.24
0.627
2.21
0.137
6.48
0.214b
Age group 21–30 31–40
6 (14.6)
7 (10.8)
41–50
20 (48.8)
28 (43.1)
51–60
9 (22.0)
25 (38.5)
61–70
2 (4.9)
3 (4.6)
71–80 Gender
0 (0.0)
1 (1.5)
Male
19 (46.3)
27 (41.5)
Female
22 (53.7)
38 (58.5)
Package Government
21 (65.6)
44 (80.0)
Private travel agencies
11 (34.6)
11 (20.0)
29 (72.5)
45 (77.6)
2 (5.0)
7 (12.1)
Pre-morbid illness No Hypertension (HPT) Diabetes (DM)
1 (2.5)
0 (0.0)
Respiratory diseases (mild) (RD) HPT ? DM
7 (17.5)
5 (8.6)
0 (0.0)
1 (1.7)
HPT ? RD
1 (2.5)
0 (0.0)
a
Pearson Chi square
b
Fisher’s Exact
Methods An observational cohort study was conducted among Malaysian hajj pilgrims during December, 2007 hajj season. The subjects were Malaysian pilgrims who went to Makkah under the National Pilgrim Management and Fund Board, locally known as Lembaga Urusan & Tabung Haji (LUTH). Pilgrims aged 18 years and above were included. Subjects with severe pre-morbid respiratory illness (e.g. chronic obstructive airway disease, asthma) and immunocompromised state (e.g. HIV, cancer patient, chronic renal failure, on steroid therapy or chemotherapy) were excluded. In the intervention group, influenza vaccine FluarixÒ (GalaxoSmithKline Pharmaceutical) comprised of influenza strains A/Solomon Islands/3/06 (H1N1) (new), A/Wisconsin/67/05 (H3N2), and B/Malaysia/2506/04 was given intramuscularly, single dose, to the pilgrims at least 2 weeks prior departure to Makkah. The control group was hajj pilgrims who did not receive influenza vaccination, however they were allowed to practice other protective measures such as face mask as advised by the LUTH personnel. The selection for control were based on those who volunteered to participate in the study but refused influenza vaccination and also recruited from pilgrims at Makkah who did not receive influenza vaccination based
Control n = 35 Mean (SD)
Vaccine n = 53 Mean (SD)
F stat
p valuea
1
0.51 (0.95)
0.45 (1.01)
1.24
0.291
2
1.14 (1.24)
0.96 (1.25)
3
1.26 (1.38)
1.09 (1.27)
4
0.91 (1.12)
1.21 (1.42)
5
0.80 (0.90)
1.04 (1.24)
6
0.66 (0.87)
0.92 (1.22)
a
RM Anova
Table 4 Comparison of average score between control group and vaccinated group in Malaysian Hajj pilgrims Group
Control Mean (SD)
Intervention Mean (SD)
F stat
p valuea
Control vs vaccine
0.88 (0.69)
0.95 (0.91)
0.13
0.718
Fisher’s Exact b
Pearson Chi square analysis
a
a
8 (14.8) 46 (85.2) 14 (25.9) 40 (74.1) 22 (40.7) 32 (59.3) Vaccine
There was no association between the influenza vaccination pilgrims intervention and cough, runny nose, sore throat and fever among Malaysia Hajj pilgrims in 2007
49 (90.7)
5 (9.3)
0.235b 1.38 5 (8.8) 52 (91.2)
34 (97.1) 0.163b 1.76
12 (21.1)
2 (5.7) 33 (94.3)
45 (78.9)
0.191 1.71 14 (24.6) 43 (75.4)
5 (14.3) 15 (42.9) 20 (57.1)
32 (56.1) Vaccine
Control 6
25 (43.9)
0.04
0.843
30 (85.7)
0.50 17 (28.8)
7 (18.4) 31 (81.6)
42 (71.2)
0.933 0.01 28 (47.5)
17 (44.7) 21 (55.3)
31 (52.5) Vaccine
Control 5
1 (2.9)
0.415b 0.41 2 (5.3) 2.97 3 (7.9)
15 (25.4) 44 (74.6)
0.480
35 (92.1)
2.3 14 (23.7)
5 (12.8) 34 (87.2)
45 (76.3)
0.948 0.004 19 (32.2)
11 (28.2) 28 (71.7)
40 (67.8)
0.707 0.14 24 (40.7)
17 (43.6) 22 (56.4)
35 (59.3) Vaccine
Control 4
36 (94.7) 0.085
50 (84.7)
9 (15.3)
0.107b 2.42 2 (5.1) 0.13
37 (94.9)
56 (94.9)
3 (5.1)
0.464b 0.24 3 (7.5) 0.18 12 (21.1)
11 (27.5) 29 (72.5)
45 (78.9)
0.426 0.63 17 (29.8)
16 (40.0) 24 (60.0)
40 (70.2)
0.161 1.96 21 (36.8)
22 (55.0) 18 (45.0)
36 (63.2) Vaccine
Control 3
1.67 20 (50.0) 20 (50.0) Control 2
37 (92.5) 0.672
53 (93.0)
4 (7.0)
0.612b 0.01 37 (92.5) 0.462 0.54 11 (27.5) 0.597 0.197
26 (65.0)
14 (35.0)
0.29
0.02 8 (13.6)
5 (12.5) 35 (87.5)
51 (86.4)
0.247 1.34 8 (13.6)
31 (77.5)
51 (86.4)
Control
Vaccine
1
9 (22.5)
29 (72.5)
1.9 6 (10.2)
8 (20.0) 32 (80.0) 0.878
53 (89.8)
Yes n (%) No n (%) Yes n (%) No n (%) Yes n (%) No n (%)
3 (7.5)
0.466b 0.41 1 (2.5) 39 (97.5) 0.168
56 (94.9)
No n (%)
Fever p valuea v2 Sore throat p valuea v2 Runny nose p valuea v2 Cough Group Week
Table 2 Association of respiratory symptoms by duration of stay between control and vaccinated groups in Malaysian hajj pilgrims
3 (5.1)
Week
Yes n (%)
p value
Table 3 Comparison of score of acute respiratory symptoms between control group and vaccinated group in Malaysian Hajj pilgrims
v2
J Immigrant Minority Health
RM Anova
on the health record. All pilgrims had their health records with them which include information on their vaccination status. Subjects for both groups were asked to record the respiratory symptoms (cough, sore throat, runny nose and fever) daily for 6 weeks in the health diary provided. For analysis purposes, the number of symptoms was scored from 1 to 5 where score 1 is when they have one symptom only; score 2 when they have two symptoms; score 3 having three symptoms and score 4 when they have all the four symptoms. Score 5 was given if the subject is hospitalized due to any of the above symptoms. Score 5 indicates seriousness of disease. The sample size was determined using two proportion formula, alpha = 0.05, power 80 % and m = 1. We assumed that the incidence of influenza among hajj pilgrims would be 25 % in the unvaccinated group and 10 % in those vaccinated (60 % vaccine effectiveness) [12, 13]. The required sample size was 100 in the vaccine and 100 in the unvaccinated. The outcome was measured in symptoms score and evaluated statistically using Pearson Chi square or Fisher’s exact test for categorical outcome and repeated measures ANOVA for numerical outcome by SPSS software. Level of significance was set at \0.05. Ethical approval was obtained from the Research and Ethics Committee of Universiti Sains Malaysia. Written informed consent was taken from all eligible participants. A short briefing on the study was given to all participants. Both groups were monitored so that they comply with the study protocol. To ensure compliance, the researchers went along to Makkah with the subjects.
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J Immigrant Minority Health 60
30
25
percentage of hajj pilgrims
percentage of hajj pilgrims
50
40
30
20
control vaccinnated 10
20
15
10
control
5
vaccinnated 0 1
2
3
4
5
0
6
1
2
Length of stay (week)
3
4
5
6
Length of stay (week)
Fig. 1 Comparison for occurrence of cough between control and vaccinated group
Fig. 3 Comparison for occurrence of sore throat between control and vaccinated group
45 40
18 16
Percentage of hajj pilgrims
Percentage of hajj pilgrims
35 30 25 20 15
control
10
vaccinnated
control
14
vaccinnated 12 10 8 6 4 2
5
0 1
0 1
2
3
4
5
6
Length of stay (week)
Fig. 2 Comparison for occurrence of runny nose between control and vaccinated group
Results There were 65 pilgrims in the vaccinated group and 41 pilgrims in the control group who completed and returned the health diary for analysis. The age ranged from 21 to 80 years old (Table 1). There was no significant difference in the demographic factor between the two groups. Table 2 showed a comparison between vaccinated and control groups on the percentage of pilgrims having acute
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2
3
4
5
6
Length of stay (week)
Fig. 4 Comparison for occurrence of fever between control and vaccinated group
respiratory symptoms by length of stay in Makkah or Madinah. There were no significant difference in the percentage of pilgrims having cough, runny nose, sore throat and fever. The mean symptom-score for vaccinated group was 0.95 (SD 0.91) and the control group was 0.88(SD 0.69) however the difference was not statistically significant (Table 3, 4). Figures 1, 2, 3, 4 showed the pattern of symptoms for both groups by duration of pilgrimage. From the 1st to 3rd weeks, there were a lower percentage of pilgrims in both
J Immigrant Minority Health Table 5 Treatment for respiratory illness in control and intervention group Treatment modality
Self-treatment
No
Control (n = 41) n (%)
Vaccine (n = 65) n (%)
v2
p valuea
32 (78.0)
55 (84.6)
2.349
0.503
10 (15.4) 3.347
0.341
5.236
0.155b
Yes
9 (22.0)
Treatment from clinic
No
11 (26.8)
11 (16.9)
Yes
30 (73.2)
54 (83.1)
Require hospital admission
No
41 (100.0)
63 (0.97)
a
Pearson Chi square
b
Fisher’s Exact
Yes
0 (0)
2 (0.03)
groups who developed cough, runny nose or sore throat. The peak of symptoms in the vaccinated groups was delayed to the fourth week compared to 2nd or 3rd week in the control group. The percentage of pilgrims who developed runny nose, sore throat and fever were higher in the vaccinated groups after the fourth week of pilgrimage. Nevertheless the pattern of respiratory symptoms acquired over the 6 week periods were not statistically significant. Table 5 showed treatment for respiratory illness in the intervention and control groups. The number of pilgrims received treatment from clinics were high in both groups. However there is no significant difference between intervention and control groups seen in pilgrims with selftreatment, treatment from clinics and those admitted to hospital.
Discussions Acute respiratory illnesses are major health issues among health pilgrims. These symptoms could be due to infective or non-infective causes. Among the infective causes, influenza is an important disease that needs to be controlled because of potential cause of outbreak and it causes high morbidity and mortality. Influenza vaccine was found to be 50–60 % effective in preventing hospitalization and pneumonia and 80 % effective in preventing death from the flu in the over 65 age group [14]. In Malaysia, influenza vaccination was not compulsory for hajj pilgrims but strongly recommended at their own initiative. Length of stay during hajj also contributes to infection. Valerio et al. [15] showed that the risk factors which were independently correlated with the presence of respiratory tract infections were ‘‘number of days in Saudi Arabia’’ and ‘‘taking part in the Hajj compared with the Umrah’’. In our study, we found a unique pattern of acute respiratory symptoms among the hajj pilgrims. The symptom-score for hajj pilgrims in both groups showed an increasing pattern
in the 1st and 2nd week, peaked in the 3rd and 4th weeks and declined in the 5th and 6th week. The peak for vaccinated group was delayed compared to the control group. Even though the different was not significant, the pattern indicates that both groups were exposed to a similar kind of hazards and influenza vaccine might have protective effect in the initial period. However, the longer the pilgrim stayed the more exposure to the hazards that resulted in increased occurrence of respiratory illnesses which were not related to influenza. Dust, heavy particles in air and air pollution could induce respiratory symptoms among healthy individuals, trigger asthmatic attack and aggravate symptoms of patients already having chronic pulmonary diseases. Studies on the effectiveness of influenza vaccination showed variable results. Among the UK pilgrims, the rate of influenza was lower in vaccinated group as compared to unvaccinated group (7 and 14 %, respectively) [8]. On the other hand, studies among the French Hajj pilgrims and Australian pilgrims found that influenza vaccination was not significantly associated with reduction in ILI and other acute respiratory symptoms among their hajj pilgrims [6, 11, 16]. In our study we found that influenza vaccination was not associated with reduction in the occurrence and number of acute respiratory symptoms nor any relation with length of stay. This finding is supported by Deris et al. [6] in which he found that influenza vaccination has no significant protective measures against ILI in Malaysian hajj pilgrims. This study has limitation in term of very small sample size. At the beginning of the study, a total of 100 pilgrims were recruited in the vaccinated group and 100 for the control group but unfortunately many of them did not complete the health diary. Poor response rate were also seen in previous study [6]. This study also depends solely on self-reporting, therefore there could be possibility of recall bias. To reduce this problem, the pilgrims were reminded on the importance of giving as accurate data as possible for good rewards hereafter in line with Islamic teaching hence this is their biggest spiritual journey. Furthermore, only patient reports were used to document symptoms, and no lab testing was done for influenza. A nonspecific outcome will make it hard to document a significant vaccine effect. In conclusion, respiratory symptoms can be caused by a variety of infectious and noninfectious etiologies and a much larger and more carefully performed study would be needed to document the benefit of influenza vaccine. Nevertheless we hope that this study could provide information on the occurrence of respiratory illness in both groups. The decision for a mandatory policy on influenza vaccination for Malaysian Hajj Pilgrims should be based on the prevalence of influenza as a causative agent for respiratory illness, the cost-effectiveness and the practicality of such vaccination
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programme. The Saudi Arabia Ministry of Health recommends influenza vaccination for all Hajj pilgrims [17], and our study was inadequate to evaluate this recommendation. Acknowledgments This study was funded by Ministry of Higher Education, Malaysia through Universiti Sains Malaysia Hajj Research Cluster. We would like to acknowledge the support given by The Custodian of the Two Holyland Hajj Research Center, Umm al Qura University, Makkah and Lembaga UrusanTabung Haji Malaysia. Conflict of interest We would like to declare that there are no potential conflicts of interest.
References 1. Yousuf M, AlSaudi DA, Sheikh RA, Lone MS. Pattern of medical problems among Haj pilgrims admitted to King Abdul Aziz Hospital, Madinah Al-Munawarah. Ann Saudi Med. 1995;15(6): 619–21. 2. Al-Ghamdi SM, Akbar HO, Qari YA, Fathaldin OA, Al-Rashed RS. Pattern of admission to hospitals during Muslim pilgrimage (Hajj). Saudi Med J. 2003;24(10):1073–6. 3. Madani TA, Ghabrah TM, Albarrak AM, Alhazmi MA, Alazraqi TA, Althaqafi AO, et al. Causes of admission to intensive care units in the Hajj period of the Islamic year 1424 (2004). Ann Saudi Med. 2007;27(2):101–5. 4. Mandourah Y, Al-Radi A, Ocheltree AH, Ocheltree SR, Fowler RA. Clinical and temporal patterns of severe pneumonia causing critical illness during Hajj. BMC Infect Dis. 2012;12:117. 5. Gautret P, Soula G, Delmont J, Parola P, Brouqui P. Common health hazards in French pilgrims during the Hajj of 2007: a prospective cohort study. J Travel Med. 2009;16(6):377–81. 6. Deris ZZ, Hasan H, Sulaiman SA, Wahab MSA, Naing NN, Othman NH. The prevalence of acute respiratory symptoms and role of protective measures among Malaysian Hajj pilgrims. J Travel Med. 2010;17(2):82–8.
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7. Ahmed QA, Arabi YM, Memish ZA. Health risks at the Hajj. Lancet. 2006;367(9515):1008–15. 8. Rashid H, Shafi S, Haworth E, El Bashir H, Memish ZA, Sudhanva M, et al. Viral respiratory infections at the Hajj: comparison between UK and Saudi pilgrims. Clin Microbiol Infect. 2008;14(6):569–74. 9. Memish ZA. The Hajj: communicable and non-communicable health hazards and current guidance for pilgrims. Euro Surveill. 2010;15(39):19671. 10. Sulaiman SA, Hasan H, Deris ZZ, Wahab MSA, Yusof RC, Naing NN, et al. The benefit of Tualang honey in reducing acute respiratory symptoms among Malaysian Hajj pilgrims: a preliminary study. J ApiProduct ApiMedical Sci. 2011;3(1):38–44. 11. Gautret P, Hai VV, Sani S, Doutchi M, Parola P, Brouqui P. Protective measures against acute respiratory symptoms in French pilgrims participating in the Hajj of 2009. J Travel Med. 2011;18(1):53–5. 12. Nichol KL, Lind A, Margolis KL, Murdoch M, McFadden R, Hauge M, et al. The effectiveness of vaccination against influenza in healthy, working adults. N Engl J Med. 1995;333(14):889–93. 13. Gross PA, Hermogenes AW, Sacks HS, Lau J, Levandowski RA. The efficacy of influenza vaccine in elderly persons. A metaanalysis and review of the literature. Ann Intern Med. 1995; 123(7):518–27. 14. Centers for Disease C, Prevention. Updated interim influenza vaccination recommendations—2004–05 influenza season. MMWR Morb Mortal Wkly Rep. 2004;53(50):1183–4. 15. Valerio L, Arranz Y, Hurtado B, Roure S, Reina MD, MartinezCuevas O, et al. Epidemiology and risk factors associated with religious pilgrimage to Saudi Arabia. Results of a prospective cohort 2008–2009. Gac Sanit. 2012;26(3):251–5. 16. Haworth E, Barasheed O, Memish ZA, Rashid H, Booy R. Prevention of influenza at Hajj: applications for mass gatherings. J R Soc Med. 2013;106(6):215–23. 17. Ministry of Health, Kingdome of Saudi Arabia. Hajj and Umrah e-portal, Health Regulation (http://www.moh.gov.sa/en/hajj/ pages/healthregulations.aspx). Retrieved on June 2014.
ORIGINAL PAPER
Effect of Influenza Vaccination on Acute Respiratory Symptoms in Malaysian Hajj Pilgrims Habsah Hasan • Zakuan Zainy Deris • Siti Amrah Sulaiman Mohd Suhaimi Abdul Wahab • Nyi Nyi Naing • Zulkefle Ab Rahman • Nor Hayati Othman
•
Ó Springer Science+Business Media New York 2014
Abstract Respiratory illness were a major problem and caused high hospital admission during hajj seasons. One of the contributing cause to this illness is infection. Various measures had been implemented to reduce respiratory infections. The aim on the study is to determine the effect of influenza vaccination against acute respiratory illness among Malaysian Hajj pilgrims. This is an observational cohort study. Influenza vaccination was given to pilgrims at least 2 weeks prior to departure. The occurrence of symptoms for respiratory illness such as cough, fever, sore throat and runny nose was monitored daily for 6 weeks
This research has been presented partly in the 2nd National seminar on Hajj Best Practices Through Advances in Science and Technology, July, 2008 at Universiti Sains Malaysia, Penang, Malaysia. H. Hasan (&) Z. Z. Deris Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia e-mail: [email protected] S. A. Sulaiman M. S. Abdul Wahab Department of Pharmacy, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia N. N. Naing Unit of Biostatistics and Research Methodology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia Z. Ab Rahman Institut Perguruan Malaysia, Kampus Sultan Mizan, Besut, Terengganu, Malaysia N. H. Othman Clinical Research Platform, School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kubang Kerian, Malaysia
during pilgrimage using a health diary. A total of 65 vaccinated hajj pilgrims and 41 controls were analyzed. There was no significant difference in pattern of occurrence of symptoms of respiratory illness by duration of pilgrimage as well as the number of symptoms between both groups. Hajj pilgrims have frequent respiratory symptoms. We were unable to document benefit from influenza vaccination, but our study was limited by a small sample size and lack of laboratory testing for influenza. Keywords Hajj Acute respiratory symptoms Influenza vaccine Influenza like illness
Introduction Respiratory problems account for 74 % of all medical illness reported during hajj seasons [1]. Respiratory disease was the most common cause (57 %) of admission to hospital and pneumonia being the main cause of admission [2]. Pulmonary complications resulting from pneumonia are responsible for the second (after cardiovascular disease) greatest number of deaths during Hajj resulting in a considerable burden on patients and the healthcare system [3]. A cohort study of all critically ill hajj patients, of over 40 nationalities, admitted to 15 hospitals in two cities in 2009 and 2010 found that out of 452 patients who developed critical illness admitted to intensive care unit during hajj, pneumonia was the primary cause of critical illness (27.2 %) [4]. Pneumonia was community (Hajj)-acquired in 66.7 %, aspirationrelated in 25.2 %, nosocomial in 3.3 %, and tuberculous in 4.9 % [4]. Most of the pilgrims suffer from acute respiratory symptoms and cough was the main symptoms of the
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pilgrims [5]. The incidence of Malaysian hajj pilgrims having acute respiratory symptoms was very high. Almost 90 % of the 394 Malaysian hajj pilgrims surveyed had cough and 40 % had influenza like illness (ILI) [6]. Hajj is one of the pillars in Islam. It is a spiritual journey that must be performed at least once in a lifetime for every Muslims. Approximately 2.5 million pilgrims from all over the world will congregate at these places during the season [7]. Hajj activities include Tawaaf (seven circuits around the Holy Kaabah approximately 200 m each round) and Sa’i (seven times between Mount Safa and Mount Marwa approximately 2.1 km in total). The peak of congregation is on the 9th, 10th, 11th, 12th and 13th Zulhijjah, when all pilgrims from all over the world must gather at the same time and location i.e. Mina, Muzdalifah and Arafah. Most of the Malaysian pilgrims stayed in overcrowded tents in Mina and Arafah. Some pilgrims also perform umrah which include tawaf and sa’i several times before or after the peak of congregation. Every year, at least 26,000 Malaysian hajj pilgrims will travel by air to perform hajj. Malaysian pilgrims usually stay for at least 42 days (6 weeks) in Makkah and Madinah to perform Hajj. Malaysian Hajj Pilgrims stay longer than most of pilgrims from other countries because the package include other activities such as performing umrah in which they try to perform seven umrahs during their stay and a 10-day visit to Madinah which is about 400 km from Makkah. The pilgrims will arrive at Kingdom of Saudi Arabia daily in batches and the first batch usually arrives at about 3–4 weeks prior to the peak of congregation. The mass gathering and constant movement of pilgrims increased the risk of transmission of infectious diseases especially viral respiratory infections [8]. There are many factors promoting the spread of respiratory pathogens, including close contact among pilgrims, shared sleeping tents and dense air pollution [8, 9], Physical exhaustion due to the long journey, climatic weather change and the air pollution worsen the fate of the pilgrims who contracted the illness. Up to date, there are no effective protective measures for Hajj pilgrims against respiratory illnesses. Consumption of honey as daily supplement [10] and good hand hygiene [11] were shown to have some benefit in reducing the occurrence of respiratory symptoms. Whereas the use of surgical facemasks was found to be not effective in reducing respiratory symptoms [6, 11]. Saudi Ministry of Health recommended influenza vaccines to be given to hajj pilgrims before hajj as a protective measure [7]. The aim of this study is to determine the indirect effect of influenza vaccination on symptoms of acute respiratory illness in Malaysian hajj pilgrims.
123
Table 1 Demography of Malaysian hajj pilgrims Characteristics
Control (n = 41)
Vaccine (n = 65)
4 (9.7)
1 (1.5)
v2
p valuea
7.07
0.273b
0.24
0.627
2.21
0.137
6.48
0.214b
Age group 21–30 31–40
6 (14.6)
7 (10.8)
41–50
20 (48.8)
28 (43.1)
51–60
9 (22.0)
25 (38.5)
61–70
2 (4.9)
3 (4.6)
71–80 Gender
0 (0.0)
1 (1.5)
Male
19 (46.3)
27 (41.5)
Female
22 (53.7)
38 (58.5)
Package Government
21 (65.6)
44 (80.0)
Private travel agencies
11 (34.6)
11 (20.0)
29 (72.5)
45 (77.6)
2 (5.0)
7 (12.1)
Pre-morbid illness No Hypertension (HPT) Diabetes (DM)
1 (2.5)
0 (0.0)
Respiratory diseases (mild) (RD) HPT ? DM
7 (17.5)
5 (8.6)
0 (0.0)
1 (1.7)
HPT ? RD
1 (2.5)
0 (0.0)
a
Pearson Chi square
b
Fisher’s Exact
Methods An observational cohort study was conducted among Malaysian hajj pilgrims during December, 2007 hajj season. The subjects were Malaysian pilgrims who went to Makkah under the National Pilgrim Management and Fund Board, locally known as Lembaga Urusan & Tabung Haji (LUTH). Pilgrims aged 18 years and above were included. Subjects with severe pre-morbid respiratory illness (e.g. chronic obstructive airway disease, asthma) and immunocompromised state (e.g. HIV, cancer patient, chronic renal failure, on steroid therapy or chemotherapy) were excluded. In the intervention group, influenza vaccine FluarixÒ (GalaxoSmithKline Pharmaceutical) comprised of influenza strains A/Solomon Islands/3/06 (H1N1) (new), A/Wisconsin/67/05 (H3N2), and B/Malaysia/2506/04 was given intramuscularly, single dose, to the pilgrims at least 2 weeks prior departure to Makkah. The control group was hajj pilgrims who did not receive influenza vaccination, however they were allowed to practice other protective measures such as face mask as advised by the LUTH personnel. The selection for control were based on those who volunteered to participate in the study but refused influenza vaccination and also recruited from pilgrims at Makkah who did not receive influenza vaccination based
Control n = 35 Mean (SD)
Vaccine n = 53 Mean (SD)
F stat
p valuea
1
0.51 (0.95)
0.45 (1.01)
1.24
0.291
2
1.14 (1.24)
0.96 (1.25)
3
1.26 (1.38)
1.09 (1.27)
4
0.91 (1.12)
1.21 (1.42)
5
0.80 (0.90)
1.04 (1.24)
6
0.66 (0.87)
0.92 (1.22)
a
RM Anova
Table 4 Comparison of average score between control group and vaccinated group in Malaysian Hajj pilgrims Group
Control Mean (SD)
Intervention Mean (SD)
F stat
p valuea
Control vs vaccine
0.88 (0.69)
0.95 (0.91)
0.13
0.718
Fisher’s Exact b
Pearson Chi square analysis
a
a
8 (14.8) 46 (85.2) 14 (25.9) 40 (74.1) 22 (40.7) 32 (59.3) Vaccine
There was no association between the influenza vaccination pilgrims intervention and cough, runny nose, sore throat and fever among Malaysia Hajj pilgrims in 2007
49 (90.7)
5 (9.3)
0.235b 1.38 5 (8.8) 52 (91.2)
34 (97.1) 0.163b 1.76
12 (21.1)
2 (5.7) 33 (94.3)
45 (78.9)
0.191 1.71 14 (24.6) 43 (75.4)
5 (14.3) 15 (42.9) 20 (57.1)
32 (56.1) Vaccine
Control 6
25 (43.9)
0.04
0.843
30 (85.7)
0.50 17 (28.8)
7 (18.4) 31 (81.6)
42 (71.2)
0.933 0.01 28 (47.5)
17 (44.7) 21 (55.3)
31 (52.5) Vaccine
Control 5
1 (2.9)
0.415b 0.41 2 (5.3) 2.97 3 (7.9)
15 (25.4) 44 (74.6)
0.480
35 (92.1)
2.3 14 (23.7)
5 (12.8) 34 (87.2)
45 (76.3)
0.948 0.004 19 (32.2)
11 (28.2) 28 (71.7)
40 (67.8)
0.707 0.14 24 (40.7)
17 (43.6) 22 (56.4)
35 (59.3) Vaccine
Control 4
36 (94.7) 0.085
50 (84.7)
9 (15.3)
0.107b 2.42 2 (5.1) 0.13
37 (94.9)
56 (94.9)
3 (5.1)
0.464b 0.24 3 (7.5) 0.18 12 (21.1)
11 (27.5) 29 (72.5)
45 (78.9)
0.426 0.63 17 (29.8)
16 (40.0) 24 (60.0)
40 (70.2)
0.161 1.96 21 (36.8)
22 (55.0) 18 (45.0)
36 (63.2) Vaccine
Control 3
1.67 20 (50.0) 20 (50.0) Control 2
37 (92.5) 0.672
53 (93.0)
4 (7.0)
0.612b 0.01 37 (92.5) 0.462 0.54 11 (27.5) 0.597 0.197
26 (65.0)
14 (35.0)
0.29
0.02 8 (13.6)
5 (12.5) 35 (87.5)
51 (86.4)
0.247 1.34 8 (13.6)
31 (77.5)
51 (86.4)
Control
Vaccine
1
9 (22.5)
29 (72.5)
1.9 6 (10.2)
8 (20.0) 32 (80.0) 0.878
53 (89.8)
Yes n (%) No n (%) Yes n (%) No n (%) Yes n (%) No n (%)
3 (7.5)
0.466b 0.41 1 (2.5) 39 (97.5) 0.168
56 (94.9)
No n (%)
Fever p valuea v2 Sore throat p valuea v2 Runny nose p valuea v2 Cough Group Week
Table 2 Association of respiratory symptoms by duration of stay between control and vaccinated groups in Malaysian hajj pilgrims
3 (5.1)
Week
Yes n (%)
p value
Table 3 Comparison of score of acute respiratory symptoms between control group and vaccinated group in Malaysian Hajj pilgrims
v2
J Immigrant Minority Health
RM Anova
on the health record. All pilgrims had their health records with them which include information on their vaccination status. Subjects for both groups were asked to record the respiratory symptoms (cough, sore throat, runny nose and fever) daily for 6 weeks in the health diary provided. For analysis purposes, the number of symptoms was scored from 1 to 5 where score 1 is when they have one symptom only; score 2 when they have two symptoms; score 3 having three symptoms and score 4 when they have all the four symptoms. Score 5 was given if the subject is hospitalized due to any of the above symptoms. Score 5 indicates seriousness of disease. The sample size was determined using two proportion formula, alpha = 0.05, power 80 % and m = 1. We assumed that the incidence of influenza among hajj pilgrims would be 25 % in the unvaccinated group and 10 % in those vaccinated (60 % vaccine effectiveness) [12, 13]. The required sample size was 100 in the vaccine and 100 in the unvaccinated. The outcome was measured in symptoms score and evaluated statistically using Pearson Chi square or Fisher’s exact test for categorical outcome and repeated measures ANOVA for numerical outcome by SPSS software. Level of significance was set at \0.05. Ethical approval was obtained from the Research and Ethics Committee of Universiti Sains Malaysia. Written informed consent was taken from all eligible participants. A short briefing on the study was given to all participants. Both groups were monitored so that they comply with the study protocol. To ensure compliance, the researchers went along to Makkah with the subjects.
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J Immigrant Minority Health 60
30
25
percentage of hajj pilgrims
percentage of hajj pilgrims
50
40
30
20
control vaccinnated 10
20
15
10
control
5
vaccinnated 0 1
2
3
4
5
0
6
1
2
Length of stay (week)
3
4
5
6
Length of stay (week)
Fig. 1 Comparison for occurrence of cough between control and vaccinated group
Fig. 3 Comparison for occurrence of sore throat between control and vaccinated group
45 40
18 16
Percentage of hajj pilgrims
Percentage of hajj pilgrims
35 30 25 20 15
control
10
vaccinnated
control
14
vaccinnated 12 10 8 6 4 2
5
0 1
0 1
2
3
4
5
6
Length of stay (week)
Fig. 2 Comparison for occurrence of runny nose between control and vaccinated group
Results There were 65 pilgrims in the vaccinated group and 41 pilgrims in the control group who completed and returned the health diary for analysis. The age ranged from 21 to 80 years old (Table 1). There was no significant difference in the demographic factor between the two groups. Table 2 showed a comparison between vaccinated and control groups on the percentage of pilgrims having acute
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2
3
4
5
6
Length of stay (week)
Fig. 4 Comparison for occurrence of fever between control and vaccinated group
respiratory symptoms by length of stay in Makkah or Madinah. There were no significant difference in the percentage of pilgrims having cough, runny nose, sore throat and fever. The mean symptom-score for vaccinated group was 0.95 (SD 0.91) and the control group was 0.88(SD 0.69) however the difference was not statistically significant (Table 3, 4). Figures 1, 2, 3, 4 showed the pattern of symptoms for both groups by duration of pilgrimage. From the 1st to 3rd weeks, there were a lower percentage of pilgrims in both
J Immigrant Minority Health Table 5 Treatment for respiratory illness in control and intervention group Treatment modality
Self-treatment
No
Control (n = 41) n (%)
Vaccine (n = 65) n (%)
v2
p valuea
32 (78.0)
55 (84.6)
2.349
0.503
10 (15.4) 3.347
0.341
5.236
0.155b
Yes
9 (22.0)
Treatment from clinic
No
11 (26.8)
11 (16.9)
Yes
30 (73.2)
54 (83.1)
Require hospital admission
No
41 (100.0)
63 (0.97)
a
Pearson Chi square
b
Fisher’s Exact
Yes
0 (0)
2 (0.03)
groups who developed cough, runny nose or sore throat. The peak of symptoms in the vaccinated groups was delayed to the fourth week compared to 2nd or 3rd week in the control group. The percentage of pilgrims who developed runny nose, sore throat and fever were higher in the vaccinated groups after the fourth week of pilgrimage. Nevertheless the pattern of respiratory symptoms acquired over the 6 week periods were not statistically significant. Table 5 showed treatment for respiratory illness in the intervention and control groups. The number of pilgrims received treatment from clinics were high in both groups. However there is no significant difference between intervention and control groups seen in pilgrims with selftreatment, treatment from clinics and those admitted to hospital.
Discussions Acute respiratory illnesses are major health issues among health pilgrims. These symptoms could be due to infective or non-infective causes. Among the infective causes, influenza is an important disease that needs to be controlled because of potential cause of outbreak and it causes high morbidity and mortality. Influenza vaccine was found to be 50–60 % effective in preventing hospitalization and pneumonia and 80 % effective in preventing death from the flu in the over 65 age group [14]. In Malaysia, influenza vaccination was not compulsory for hajj pilgrims but strongly recommended at their own initiative. Length of stay during hajj also contributes to infection. Valerio et al. [15] showed that the risk factors which were independently correlated with the presence of respiratory tract infections were ‘‘number of days in Saudi Arabia’’ and ‘‘taking part in the Hajj compared with the Umrah’’. In our study, we found a unique pattern of acute respiratory symptoms among the hajj pilgrims. The symptom-score for hajj pilgrims in both groups showed an increasing pattern
in the 1st and 2nd week, peaked in the 3rd and 4th weeks and declined in the 5th and 6th week. The peak for vaccinated group was delayed compared to the control group. Even though the different was not significant, the pattern indicates that both groups were exposed to a similar kind of hazards and influenza vaccine might have protective effect in the initial period. However, the longer the pilgrim stayed the more exposure to the hazards that resulted in increased occurrence of respiratory illnesses which were not related to influenza. Dust, heavy particles in air and air pollution could induce respiratory symptoms among healthy individuals, trigger asthmatic attack and aggravate symptoms of patients already having chronic pulmonary diseases. Studies on the effectiveness of influenza vaccination showed variable results. Among the UK pilgrims, the rate of influenza was lower in vaccinated group as compared to unvaccinated group (7 and 14 %, respectively) [8]. On the other hand, studies among the French Hajj pilgrims and Australian pilgrims found that influenza vaccination was not significantly associated with reduction in ILI and other acute respiratory symptoms among their hajj pilgrims [6, 11, 16]. In our study we found that influenza vaccination was not associated with reduction in the occurrence and number of acute respiratory symptoms nor any relation with length of stay. This finding is supported by Deris et al. [6] in which he found that influenza vaccination has no significant protective measures against ILI in Malaysian hajj pilgrims. This study has limitation in term of very small sample size. At the beginning of the study, a total of 100 pilgrims were recruited in the vaccinated group and 100 for the control group but unfortunately many of them did not complete the health diary. Poor response rate were also seen in previous study [6]. This study also depends solely on self-reporting, therefore there could be possibility of recall bias. To reduce this problem, the pilgrims were reminded on the importance of giving as accurate data as possible for good rewards hereafter in line with Islamic teaching hence this is their biggest spiritual journey. Furthermore, only patient reports were used to document symptoms, and no lab testing was done for influenza. A nonspecific outcome will make it hard to document a significant vaccine effect. In conclusion, respiratory symptoms can be caused by a variety of infectious and noninfectious etiologies and a much larger and more carefully performed study would be needed to document the benefit of influenza vaccine. Nevertheless we hope that this study could provide information on the occurrence of respiratory illness in both groups. The decision for a mandatory policy on influenza vaccination for Malaysian Hajj Pilgrims should be based on the prevalence of influenza as a causative agent for respiratory illness, the cost-effectiveness and the practicality of such vaccination
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programme. The Saudi Arabia Ministry of Health recommends influenza vaccination for all Hajj pilgrims [17], and our study was inadequate to evaluate this recommendation. Acknowledgments This study was funded by Ministry of Higher Education, Malaysia through Universiti Sains Malaysia Hajj Research Cluster. We would like to acknowledge the support given by The Custodian of the Two Holyland Hajj Research Center, Umm al Qura University, Makkah and Lembaga UrusanTabung Haji Malaysia. Conflict of interest We would like to declare that there are no potential conflicts of interest.
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7. Ahmed QA, Arabi YM, Memish ZA. Health risks at the Hajj. Lancet. 2006;367(9515):1008–15. 8. Rashid H, Shafi S, Haworth E, El Bashir H, Memish ZA, Sudhanva M, et al. Viral respiratory infections at the Hajj: comparison between UK and Saudi pilgrims. Clin Microbiol Infect. 2008;14(6):569–74. 9. Memish ZA. The Hajj: communicable and non-communicable health hazards and current guidance for pilgrims. Euro Surveill. 2010;15(39):19671. 10. Sulaiman SA, Hasan H, Deris ZZ, Wahab MSA, Yusof RC, Naing NN, et al. The benefit of Tualang honey in reducing acute respiratory symptoms among Malaysian Hajj pilgrims: a preliminary study. J ApiProduct ApiMedical Sci. 2011;3(1):38–44. 11. Gautret P, Hai VV, Sani S, Doutchi M, Parola P, Brouqui P. Protective measures against acute respiratory symptoms in French pilgrims participating in the Hajj of 2009. J Travel Med. 2011;18(1):53–5. 12. Nichol KL, Lind A, Margolis KL, Murdoch M, McFadden R, Hauge M, et al. The effectiveness of vaccination against influenza in healthy, working adults. N Engl J Med. 1995;333(14):889–93. 13. Gross PA, Hermogenes AW, Sacks HS, Lau J, Levandowski RA. The efficacy of influenza vaccine in elderly persons. A metaanalysis and review of the literature. Ann Intern Med. 1995; 123(7):518–27. 14. Centers for Disease C, Prevention. Updated interim influenza vaccination recommendations—2004–05 influenza season. MMWR Morb Mortal Wkly Rep. 2004;53(50):1183–4. 15. Valerio L, Arranz Y, Hurtado B, Roure S, Reina MD, MartinezCuevas O, et al. Epidemiology and risk factors associated with religious pilgrimage to Saudi Arabia. Results of a prospective cohort 2008–2009. Gac Sanit. 2012;26(3):251–5. 16. Haworth E, Barasheed O, Memish ZA, Rashid H, Booy R. Prevention of influenza at Hajj: applications for mass gatherings. J R Soc Med. 2013;106(6):215–23. 17. Ministry of Health, Kingdome of Saudi Arabia. Hajj and Umrah e-portal, Health Regulation (http://www.moh.gov.sa/en/hajj/ pages/healthregulations.aspx). Retrieved on June 2014.
