• 1.

    World Health Organization, 2016. Global Tuberculosis Report 2016. Geneva, Switzerland. November 16, 2016. Available at: http://apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf?ua=1. Accessed January 16, 2017.

  • 2.

    Zumla A et al. 2016. Tuberculosis and mass gatherings-opportunities for defining burden, transmission risk, and the optimal surveillance, prevention, and control measures at the annual Hajj pilgrimage. Int J Infect Dis 47: 8691.

    • Search Google Scholar
    • Export Citation
  • 3.

    Al-Orainey IO, 2013. Tuberculosis infection during Hajj pilgrimage. The risk to pilgrims and their communities. Saudi Med J 34: 676680.

    • Search Google Scholar
    • Export Citation
  • 4.

    Gautret P, Benkouiten S, Griffiths K, Sridhar S, 2015. The inevitable Hajj cough: surveillance data in French pilgrims, 2012–2014. Travel Med Infect Dis 13: 485489.

    • Search Google Scholar
    • Export Citation
  • 5.

    Alzeer A, Mashlah A, Fakim N, Al-Sugair N, Al-Hedaithy M, Al-Majed S, Jamjoom G, 1998. Tuberculosis is the commonest cause of pneumonia requiring hospitalization during Hajj (pilgrimage to Makkah). J Infect 36: 303306.

    • Search Google Scholar
    • Export Citation
  • 6.

    Helb D et al. 2010. Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, near-patient technology. J Clin Microbiol 48: 229237.

    • Search Google Scholar
    • Export Citation
  • 7.

    Wilder-Smith A, Foo W, Earnest A, Paton NI, 2005. High risk of Mycobacterium tuberculosis infection during the Hajj pilgrimage. Trop Med Int Health 10: 336339.

    • Search Google Scholar
    • Export Citation
  • 8.

    Aldridge RW, Yates TA, Zenner D, White PJ, Abubakar I, Hayward AC, 2014. Pre-entry screening programmes for tuberculosis in migrants to low-incidence countries: a systematic review and meta-analysis. Lancet Infect Dis 14: 12401249.

    • Search Google Scholar
    • Export Citation
  • 9.

    Ayles H, Schaap A, Nota A, Sismanidis C, Tembwe R, de Haas P, Muyoyeta M, Beyers N, Peter Godfrey-Faussett for the ZAMSTAR Study Team, 2009. Prevalence of tuberculosis, HIV and respiratory symptoms in two Zambian communities: implications for tuberculosis control in the era of HIV. PLoS One 4: e5602.

    • Search Google Scholar
    • Export Citation
  • 10.

    Hoa NB, Sy DN, Nhung NV, Tiemersma EW, Borgdorff MW, Cobelens FG, 2010. National survey of tuberculosis prevalence in Viet Nam. Bull World Health Organ 88: 273280.

    • Search Google Scholar
    • Export Citation
  • 11.

    Onozaki I, Law I, Sismanidis C, Zignol M, Glaziou P, Floyd K, 2015. National tuberculosis prevalence surveys in Asia, 1990–2012: an overview of results and lessons learned. Trop Med Int Health 20: 11281145.

    • Search Google Scholar
    • Export Citation
  • 12.

    Golub JE, Bur S, Cronin WA, Gange S, Baruch N, Comstock GW, Chaisson RE, 2006. Delayed tuberculosis diagnosis and tuberculosis transmission. Int J Tuberc Lung Dis 10: 2430.

    • Search Google Scholar
    • Export Citation
  • 13.

    Nanoo A, Izu A, Ismail NA, Ihekweazu C, Abubakar I, Mametja D, Madhi SA, 2015. Nationwide and regional incidence of microbiologically confirmed pulmonary tuberculosis in South Africa, 2004–2012: a time series analysis. Lancet Infect Dis 15: 10661076.

    • Search Google Scholar
    • Export Citation
  • 14.

    Shisana O et al. 2014. South African National HIV Prevalence, Incidence and Behaviour Survey, 2012. HSRC Press. Available at: http://www.hsrc.ac.za/en/research-data/view/6871. Accessed January 16, 2017.

  • 15.

    Muntingh L, 2013. Race, Gender and Socioeconomic Status in Law Enforcement in South Africa—Are There Worrying Signs? Available at: http://cspri.org.za/publications/research-reports/Inequality%20paper.pdf. Accessed January 16, 2017.

  • 16.

    Sanchez-Barriga JJ, 2015. Mortality trends and risk of dying from pulmonary tuberculosis in the 7 socioeconomic regions and the 32 States of Mexico, 2000–2009. Arch Bronconeumol 51: 1623.

    • Search Google Scholar
    • Export Citation
  • 17.

    Needham DM, Foster SD, Tomlinson G, Godfrey-Faussett P, 2001. Socio-economic, gender and health services factors affecting diagnostic delay for tuberculosis patients in urban Zambia. Trop Med Int Health 6: 256259.

    • Search Google Scholar
    • Export Citation
  • 18.

    Gelaw SM, 2016. Socioeconomic factors associated with knowledge on tuberculosis among adults in Ethiopia. Tuberc Res Treat 2016: 6207457.

  • 19.

    Dogar OF, Shah SK, Chughtai AA, Qadeer E, 2012. Gender disparity in tuberculosis cases in eastern and western provinces of Pakistan. BMC Infect Dis 12: 244.

    • Search Google Scholar
    • Export Citation
  • 20.

    Memish ZA et al. 2014. Prevalence of MERS-CoV nasal carriage and compliance with the Saudi health recommendations among pilgrims attending the 2013 Hajj. J Infect Dis 210: 10671072.

    • Search Google Scholar
    • Export Citation
  • 21.

    Marais BJ et al. 2013. Tuberculosis comorbidity with communicable and non-communicable diseases: integrating health services and control efforts. Lancet Infect Dis 13: 436448.

    • Search Google Scholar
    • Export Citation
  • 22.

    Bates M et al. 2012. Evaluation of the burden of unsuspected pulmonary tuberculosis and co-morbidity with non-communicable diseases in sputum producing adult inpatients. PLoS One 7: e40774.

    • Search Google Scholar
    • Export Citation
  • 23.

    Pan SC, Ku CC, Kao D, Ezzati M, Fang CT, Lin HH, 2015. Effect of diabetes on tuberculosis control in 13 countries with high tuberculosis: a modelling study. Lancet Diabetes Endocrinol 3: 323330.

    • Search Google Scholar
    • Export Citation
  • 24.

    The Lancet DE, 2014. Diabetes and tuberculosis—a wake-up call. Lancet Diabetes Endocrinol 2: 677.

  • 25.

    Ebrahim SH, Memish ZA, Uyeki TM, Khoja TA, Marano N, McNabb SJ, 2009. Public health. Pandemic H1N1 and the 2009 Hajj. Science 326: 938940.

  • 26.

    Lin HH, Ezzati M, Murray M, 2007. Tobacco smoke, indoor air pollution and tuberculosis: a systematic review and meta-analysis. PLoS Med 4: e20.

  • 27.

    Leung CC et al. 2015. Smoking adversely affects treatment response, outcome and relapse in tuberculosis. Eur Respir J 45: 738745.

  • 28.

    World Health Organization, 2007. Tuberculosis Care and Control in Refugee and Displaced Populations. An Interagency Field Manual. Geneva, Switzerland: WHO. Available at: http://apps.who.int/iris/bitstream/10665/43661/1/9789241595421_eng.pdf. Accessed May 30, 2017.

Past two years Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 326 131 2
PDF Downloads 121 65 0
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 

 

Undiagnosed Active Pulmonary Tuberculosis among Pilgrims during the 2015 Hajj Mass Gathering: A Prospective Cross-sectional Study

View More View Less
  • 1 The Global Centre for Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia;
  • | 2 Center for Clinical Microbiology, Division of Infection and Immunity, University College London and NIHR Biomedical Research Centre at UCL Hospitals, London, United Kingdom;
  • | 3 National Health Laboratory, Ministry of Health, Riyadh, Saudi Arabia;
  • | 4 Liverpool School of Tropical Medicine, Liverpool, United Kingdom;
  • | 5 Makkah Regional Health Affairs, Ministry of Health, Jeddah, Saudi Arabia

Mass gatherings pose a risk for tuberculosis (TB) transmission and reactivation of latent TB infection. The annual Hajj pilgrimage attracts 2 million pilgrims many from high TB-endemic countries. We evaluated the burden of undiagnosed active pulmonary TB in pilgrims attending the 2015 Hajj mass gathering. We conducted a prospective cross-sectional study in Mecca, Kingdom of Saudi Arabia, for nonhospitalized adult pilgrims from five high TB-endemic countries. Enrollment criteria were the presence of a cough and the ability to produce a sputum sample. Sputum samples were processed using the Xpert MTB-RIF assay. Data were analyzed for drug-resistant TB, risk factors, and comorbidities by the country of origin. Of 1,164 consenting pilgrims enrolled from five countries: Afghanistan (316), Bangladesh (222), Nigeria (176), Pakistan (302), and South Africa (148), laboratory results were available for 1,063 (91.3%). The mean age of pilgrims was 54.5 (range = 18–94 years) with a male to female ratio of 2.6:1; 27.7% had an underlying comorbidity, with hypertension and diabetes being the most common, 20% were smokers, and 2.8% gave a history of previous TB treatment. Fifteen pilgrims (1.4%) had active previously undiagnosed drug-sensitive pulmonary TB (Afghanistan [12; 80%], Pakistan [2; 13.3%], and Nigeria [1; 6.7%]). No multidrug-resistant TB cases were detected. Pilgrims from high TB-endemic Asian and African countries with undiagnosed active pulmonary TB pose a risk to other pilgrims from over 180 countries. Further studies are required to define the scale of the TB problem during the Hajj mass gathering and the development of proactive screening, treatment and prevention guidelines.

INTRODUCTION

Tuberculosis (TB) remains a global public health problem with significant morbidity and mortality. In 2015, the World Health Organisation (WHO) estimated that 10.4 million people developed active TB of whom 480,000 developed multidrug-resistant TB (MDR-TB) with additional 100,000 cases of rifampicin-resistant TB (RR-TB).1 Mortality from TB in 2015 reached 1.8 million, making it one of the top ten causes of death worldwide.1,2

International travel, mass gathering events, and migration facilitate the spread of TB. In this context, the Kingdom of Saudi Arabia (KSA) is particularly relevant because of its hosting of the Hajj, where annually around 2 million pilgrims from over 180 countries visit KSA. Many of these pilgrims are elderly, have underlying health conditions, and originate from high TB-endemic countries. Living together in close proximity during the Hajj may facilitate TB transmission including TB from pilgrims with active pulmonary TB.3 There is a large burden of undiagnosed TB in high TB-endemic countries.1 Pilgrims are not screened for TB before entry into the KSA, and it is likely that some may enter the Kingdom with active TB. Because respiratory tract infections and cough are common among pilgrims,4 patients are often diagnosed with upper respiratory tract infections and only those requiring hospitalisation may be thoroughly investigated.3 Pilgrims infected during Hajj may also spread the infection to contacts in their countries including potential MDR strains.

Scanty data are available on the prevalence of active TB during Hajj, and there have been no specific studies to define the burden of TB during the pilgrimage.2 Evidence of TB in pilgrims comes from clinical studies of causes of hospital admissions during Hajj which reported the isolation of Mycobacterium tuberculosis from 5% to 28% of patients with pneumonia during the event.2,5 Given the short duration of the Hajj pilgrimage, these active TB cases are likely to be either imported or reactivated.3 We conducted a cross-sectional study to evaluate the burden of undiagnosed active pulmonary TB in pilgrims arriving in the KSA for the 2015 Hajj.

MATERIALS AND METHODS

Study population and setting.

The study was a prospective cross-sectional design study conducted in Mecca, KSA, over a 2-week period from September 14 to 29, 2015 (1–15 Dhul Hijja 1436H in the Islamic calendar). The study enrolled 1,164 consenting nonhospitalized adult pilgrims (> 18 years of age) who had cough and could voluntarily produce sputum samples. Pilgrims were selected from five countries in Africa and South Asia and chosen because they are endemic to TB, have high MDR/RR-TB rates, and large pilgrims’ population (Table 1).

Table 1

Target countries from which pilgrims were enrolled

CountryTB endemicity* incidence/100,000 populationPrevalence of MDR/RR-TB* (% among new cases)Estimated number of Hajj pilgrims in 2015
South Asia
 Afghanistan1893.925,037
 Bangladesh2251.6102,795
 Pakistan2704.2160,611
Africa
 Nigeria3224.375,212
 South Africa8343.52,435

RR-TB = rifampicin-resistant tuberculosis (TB); MDR-TB = multidrug-resistant TB.

2015 data (www.who.int/tb/data).

Data and samples collection.

Pilgrims were enrolled at their place of residence during the Hajj. Face to face interviews and review of pilgrims’ entry documents were used to fill in study questionnaires designed to collect data regarding pilgrims’ contact information, demographics, and TB risk factors. Sputum samples were collected in sterile containers from each pilgrim and maintained in cold conditions (2–8°C) until storage at −80°C for later processing.

Samples processing.

All sputum samples were processed after Hajj at the Saudi National TB Laboratory (Riyadh, KSA) using the WHO-endorsed Xpert MTB/RIF assay for the rapid diagnosis of TB and MDR-TB as described previously.6

Data analysis.

Characteristics of the study population were summarized as frequencies and percentages for qualitative variables and as means, range, and standard deviations (SDs) for quantitative variables. The association between demographic variables and TB was evaluated by χ2 test or Fisher’s exact test as appropriate. In addition, odds ratios (ORs) and their CIs were calculated. Multiple logistic regression analysis, using penalized likelihood (Firth method), was performed to examine the potential impact of the variables that were identified as being significant with P ≤ 0.1 in the univariate analysis. A Stata ado program written by Coveney (2015) was used to fit the multiple logistic regression model. All other tests for significance were two-sided and P values < 0.05 were considered statistically significant. All analyses were done using the SPSS 22.0 (SPSS Inc., Chicago, IL) software program.

Ethics approval and consent to participate.

The study was approved by the King Fahad Medical City Ethics Committee and the Institutional Review Board. All participants gave verbal consent before enrolment, and the study was conducted in accordance with the Ethics Committee’s guidelines.

RESULTS

The study enrolled 1,164 pilgrims originating from five TB-endemic countries in Africa and South Asia (Table 1). The characteristics of the study population are summarized in Table 2. The mean age of pilgrims was 54.5 (SD = 12.1 years, range = 18–94 years) with a male to female ratio of 2.6:1. Over half of the respondents had no formal education, and 27.7% declared having an underlying health condition. Hypertension and diabetes were the most common comorbidities (Table 3).

Table 2

Demographic characteristics of the enrolled pilgrims’ population

VariableNumber (n)Percentage (%)
Pilgrims enrolled1,164
Gender1,140
 Male82372.2
 Female31727.8
Age1,106
Mean (range)54.5 (18–94)
 ≤ 4730227.3
 > 47–5527524.9
 > 55–6429626.8
 > 6423321.1
Country of residence1,164
 Afghanistan31627.1
 Bangladesh22219.1
 Nigeria17615.1
 Pakistan30225.9
 South Africa14812.7
Level of education1,155
 No formal education59751.7
 Primary education16314.1
 Secondary education21718.8
 University-higher education17815.4
Occupation1,130
 Health care worker343.0
 Miner20.2
 Laboratory personnel141.2
 Refugee camp worker70.6
 Prison staff70.6
 None of the above1,06694.3
Underlying health conditions1,069
 Yes29627.7
 No77372.3
Pregnancy1,036
 Yes10.01
 No1,03599.9
Tobacco smoker (currently or in the past)1,145
 Yes22419.6
 No92180.4
Travel outside current country of residence in the past year1,129
 Yes18316.2
 No94683.8
Recently (past month) lived in a household with an adult with a cough1,145
 Yes13812.0
 No1,00788.0
Any of close contacts ever diagnosed or treated for TB1,149
 Yes575.0
 No76866.8
 Unsure32428.2
Currently coughing up blood1,150
 Yes332.8
 No1,11797.2
Ever been treated for TB1,124
 Yes312.8
 No96185.5
 Unsure13211.7
Currently receiving TB treatment957
 Yes00.0
 No957100

TB = tuberculosis.

Table 3

Underlying health conditions among enrolled pilgrims

Underlying health conditionsN = 296Percentage (%)
Hypertension17458.8
Diabetes12542.2
Chronic kidney disease62.0
Chronic lung disease134.4
Chronic liver disease72.4
Cardiovascular disease4715.9
Stroke10.3
Cancer20.7
Immunosuppressive illness00.0
Other3612.1

A fifth of the respondents declared that they had smoked or were current smokers of tobacco products such as cigarettes, cigars, or pipes, and 5.7% had occupations associated with increased risk of TB infection (Table 2). Travel information indicated that 183 (16.2%) respondents have traveled outside their country of residence in the previous year visiting countries in Africa, Asia, the Middle East, Europe, and North America. The most common destinations visited were Pakistan (50.2%), India (13.1%), KSA (8.7%), Malaysia (5.0%), UK (4.4%), and France (4.4%). While no pilgrim declared that they were receiving TB treatment at the time of enrolment, 31 (2.8%) revealed that they had been treated for TB in the past, all of whom confirmed that they had completed their TB treatment. The latter ranged in duration from 2 to 4 months, which is shorter than the standard treatment duration for TB, and may affect persistence of the disease and risk for MDR-TB. The majority (84%) of those previously treated for TB originated from Bangladesh.

Xpert MTB/RIF assay results were available for 1,063 (91.3%) of the samples, 15 (1.4%) of which were positive for TB. No rifampicin resistance was detected in any of the positive samples, hence by proxy no MDR-TB was detected. The characteristics of pilgrims with positive TB are summarized in Table 4. Most originated from Afghanistan (12, 80%), were male (10, 66.6%) and had no formal education (13, 86.6%). Their age ranged from 44 to 74 years old and they had spent 7–23 days in the KSA at the time of enrolment in the study. Four pilgrims (26.6%) traveled to Pakistan in the previous year, five (33.3%) declared having an underlying health condition but none worked in one of the TB risk occupations in the survey. There were no current tobacco smokers among the TB cases but two (13.3%) had smoked such products in the past. None of the TB-positive pilgrims declared having a history of TB themselves or in a close contact.

Table 4

Characteristics of the tuberculosis-positive pilgrims

PilgrimCountry of residenceAgeGenderTime in KSA (days)Highest level of educationAt risk occupation*Country traveled to in the last yearTobacco smokerUnderlying health condition(s)Previously treated for TBCurrently coughing up bloodRecently (past month) lived in a household with an adult with a coughAny of close contacts ever diagnosed or treated for TBRifampicin resistance
1Nigeria50F10NFENoNoneNeverNoneNoNoNDNoNo
2Pakistan44F7SENoNoneNeverNoneNoNoYesNoNo
3Pakistan57M7NFENoNoneNeverNoneNoNoNoUnsureNo
4AfghanistanNDF23NFENoNoneNeverHypertensionUnsureNoNoNoNo
5Afghanistan54F14NFENoPakistanNeverNDNoNoNoNoNo
6Afghanistan65F12NFENoNoneNeverCLDNoNoNoNoNo
7Afghanistan74M21NFENoNoneNeverNDNoNoNoNoNo
8Afghanistan49M19NFENoNoneNeverNDNoNoNoNoNo
9Afghanistan57M15NFENoPakistanNeverDiabetesNoNoNoNoNo
10Afghanistan58M12NFENoPakistanPastHypertensionNoNoNoNoNo
11Afghanistan63M11NFENDPakistanPastDiabetesNoNoNoUnsureNo
12Afghanistan50M9SENoNoneNeverNDNoNoNoNoNo
13Afghanistan68M9NFENoNoneNeverNoneNoNoNoNoNo
14Afghanistan67M9NFENoNoneNeverNoneNoNoNoNoNo
15Afghanistan63M8NFENoNoneNeverNoneNoNoNoNoNo

KSA = Kingdom of Saudi Arabia; F = female; M = male; NFE = no formal education; SE = secondary education; ND = not determine; CLD = chronic lung disease.

Health care worker, miner, laboratory personnel, refugee camp worker, prison staff.

The result of the univariate analysis showing the association between TB and demographic variables are summarized in Table 5 and reveal that only education showed a statistically significant association (P = 0.01). Pilgrims with no formal education were over six times more likely to be TB positive compared with those with some form of education (primary, secondary, or higher education) [(OR = 6.17; 95% CI = 1.38–27.4)]. The prevalence of active TB was lowest among the youngest age group (≤ 47 year old) and increased with age. TB prevalence was higher among females, pilgrims residing in South Asia, those with underlying health conditions, and those who traveled outside their current country of residency in the previous year, but the association was not statistically significant for any of these factors. Similarly, no significant association was found between tobacco smoking or recently living in the same household as an adult with cough and TB.

Table 5

Association between tuberculosis and demographic variables

VariablenTB+ve%OR (95% CI)P
Gender0.68
 Female28951.731
 Male752101.330.76 (0.25, 2.25)
Age0.48
 ≤ 4727310.371
 > 47–5525841.554.28 (0.47, 38.5)
 > 55–6427451.825.05 (0.58, 43.5)
 > 6420841.925.33 (0.59, 48.0)
Geographic area of residence0.09
 Africa30410.331
 South Asia759141.845.69 (0.74, 43.4)
Education0.01
 Primary or higher education50820.391
 No formal education546132.386.17 (1.38, 27.4)
Underlying health conditions0.20
 No70460.851
 Yes27351.832.17 (0.65, 7.17)
Tobacco smoker (currently or in the past)0.54
 Yes20520.981
 No839131.550.62 (0.14, 2.79)
Traveled outside current country of residence in the past year0.27
 No863111.271
 Yes16742.401.90 (0.59, 6.04)
Recently (past month) lived in a household with an adult with a cough0.57
 No918131.421
 Yes12710.790.55 (0.07, 4.25)

Only variables found to be significant at the 1% level in the univariate analysis (geographic area of residency and education) were considered as candidates for the multiple logistic regression analysis. Penalized likelihood (Firth method) was used for the fitting of the logistic regression as the maximum likelihood estimation of the logistic regression was not appropriate for our study with such a small number of events. The results indicated that only education was marginally significant after adjusting for geographic area of residency (P = 0.052) and that pilgrims with no formal education were nearly four times more likely to develop active TB than those with some form of education (adjusted OR = 3.9; 95% CI = 0.98–16.0).

DISCUSSION

Pilgrims attending Hajj maybe at a risk of acquiring TB infection.7 Our study is the first to screen Hajj pilgrims with productive cough for undiagnosed pulmonary TB and has several important findings. We found that 1.4% of Hajj pilgrims with cough from TB-endemic countries had undiagnosed active TB. This prevalence is within the range found among migrants to low-incidence countries (0.1–10%),8 yet it means that potentially 14 out of each 1,000 pilgrims from TB-endemic countries symptomatic for cough could have active TB during Hajj. This is concerning given that the estimated total number of pilgrims attending the 2015 Hajj from the WHO’s top 20 TB burden countries was 1,450,000, and the prevalence of cough among Hajj pilgrims can reach 80%.4 Considering the short time pilgrims spent in KSA at the time of enrolment in the study, it is likely that the identified active TB cases are imported or reactivation of latent TB infection.3

During the 2015 Hajj season, 44 cases of TB among pilgrims and residents were diagnosed in Mecca hospitals. We detected active TB among pilgrims symptomatic for cough but not seriously ill to be hospitalized or require medical attention and therefore not diagnosed. This is in accordance with previous TB prevalence surveys which have shown that an important proportion of infectious individuals with bacteriologically positive sputum do not experience symptoms or symptoms of sufficient severity to prompt health-seeking behavior.911 Also, screening only individuals who meet the TB screening criteria of cough over 2 or 3 weeks may result in a sizable proportion of active TB cases to be missed.

Most (80%) TB cases detected in the study were in pilgrims from Afghanistan and none were from South Africa. This is surprising given that among the countries included in the study, Afghanistan has the lowest TB burden and South African has nearly 4.5 times its TB incidence rate.1 Afghanistan is one of the poorest countries in the world with some of the lowest indicators of socioeconomic and human development indices ratings. As a consequence, health services coverage and delivery, including TB services, may be limited resulting in TB cases being not diagnosed, notified, treated, or in these processes being delayed which leads to persistent transmission.1,12 In addition, underreporting of TB cases from the country may also be a factor. The epidemiology of TB in South Africa is closely related to that of the human immunodeficiency virus (HIV).13 Most of the Muslim population in South Africa are of Asian (mostly Indian) descent which represent around only 2.5% of the population.14 The difference in the socioeconomic status, behavioural factors, and lower prevalence of HIV among this ethnic group may also explain the results observed in our study.14,15

Education was strongly associated with TB prevalence and pilgrims with no formal education were four times more likely to have TB. TB is associated with socioeconomic status of which education is one indicator. Individuals with low socioeconomic status, including low or no education, have higher TB risk and prevalence, are less likely to seek medical care, have longer diagnosis delay time, and are at higher risk of death from TB.16,17 Populations with little or no education are generally disadvantaged from a social, geographic, or economical point of view, all factors that are associated with TB morbidity and mortality.16 In addition, low education is associated with poor knowledge of TB and attitude to the disease, which can facilitate transmission and can lead to delaying health-seeking behavior, lack of adherence to treatment regimes, treatment failure and disease complications, and death.18

Worldwide, TB is more prevalent in males than females, and males tend to have higher prevalence of undiagnosed TB than females.1,9 This is contrary to the results in our study. A possible explanation for this observation is that most (14/15) of the TB cases in our study were from Afghanistan or Pakistan, where the prevalence of TB is reported to be higher among females.1,19 The reported male:female TB ratio in Afghanistan, where most of our identified cases came from, is 0.71, which is similar to the ratio found in our study.

Underlying health conditions were present among a sizable number of pilgrims with hypertension and diabetes being the most common conditions. This is in accordance with other surveys conducted among Hajj pilgrims.4,20 Although not statistically significant, we found that pilgrims with underlying health conditions were twice more likely to have TB. Noncommunicable diseases are risk factors for TB,21and there is a growing awareness of the influence of TB comorbidity with these conditions as well as the burden of unsuspected TB.22 The management of noncommunicable disease is essential to reduce the burden of these diseases during Hajj and could avoid a significant number of TB cases and related deaths.23 As such, the WHO has incorporated the management of noncommunicable diseases into its End-TB strategy.24

Extremes of age are also risk factors for TB.21 Prevalence of TB in our study increased with age which is in accordance with other TB surveys.1,10,11 We found that pilgrims aged over 64 years were 5.3 times more likely to be TB positive than those aged 47 years old or less. This is significant given that elderly pilgrims represent a sizable proportion of the Hajj population (roughly 25% are at least 65 years old) and that TB has been mainly reported in elderly pilgrims during the event.5,25

We found no significant association between tobacco smoking and TB. This is in contrast with the strong evidence that smoking, active or passive, is significantly associated with increased risks of TB infection and disease, TB transmission, TB mortality, and recurrent TB.26,27 Smoking also influences the clinical manifestations and outcomes of TB adversely affecting baseline disease severity, bacteriological response, treatment outcome, and relapse in TB and leading to a faster and more severe progression to TB.27

The results of our study highlight the need for more attention toward TB and its burden during Hajj, including formulation of appropriate policies and interventions to prevent infection and transmission. Such interventions may include increase in education and awareness regarding TB and its prevention among pilgrims through targeted campaigns to encourage health-seeking behavior in case of symptoms and adherence to treatment and to general infection prevention measures. There may also be a need for a pre-Hajj TB screening for pilgrims from certain endemic countries to prevent TB importation by prompt detection of cases and initiation of effective treatment before arrival to the KSA. Although under a different context, TB screening programs are already in effect in a number of high-income and low-TB incidence countries as pre-entry requirements for immigrants and were shown to have the highest impact and be most cost effective if they are targeted toward arrivals from high TB-endemic countries.8 TB screening for prevention and control is also implemented in refugee situations and among displaced populations.28

The introduction of such screening programs for Hajj pilgrims will require further research and considerations into the target countries as well as to the practicalities, benefits, and cost of such undertakings. These include the establishment, management, and sustainability of such screening programs as well as the availability and accessibility to TB health services for those identified to have active TB. Given that most countries likely to require a pre-Hajj TB screening are also those with the lowest income and least developed infrastructures to manage and sustain such screening programs, international engagement and collaboration, funding, and investment will be required. Nevertheless, the development and deployment of new and rapid point-of-care molecular TB diagnostic technologies, which could be subsidized in low-income countries to reduce the cost,1 would be most beneficial.

Our study has some limitations. We only screened 1,164 pilgrims from five countries which represent only a small proportion of the Hajj pilgrims’ population. We did not include some countries with the largest number of Hajj pilgrims such as Indonesia and India as well as countries with the highest MDR-TB burden in the world such as the Russian Federation and many former Soviet Union countries1 which also send pilgrims to Hajj. Finally, because of cultural and ethical considerations, our study did not collect data on the HIV status or on alcohol or substance abuse among pilgrims, which are established risk factors for TB.21

CONCLUSIONS

In summary, we found that a proportion of Hajj pilgrims have undiagnosed and untreated active TB which may represent an important source of transmission. In light of these results, further studies investigating TB during Hajj and the impact of this mass gathering on TB transmission and epidemiology worldwide are warranted. These investigations will help inform public health policies and direct interventions for the optimal awareness, surveillance, screening, treatment and management, prevention, and control of TB during Hajj and other mass gatherings worldwide. TB prevention at Hajj is an important priority and will go a long way toward achieving the WHO’s End-TB strategy goals.

REFERENCES

  • 1.

    World Health Organization, 2016. Global Tuberculosis Report 2016. Geneva, Switzerland. November 16, 2016. Available at: http://apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf?ua=1. Accessed January 16, 2017.

  • 2.

    Zumla A et al. 2016. Tuberculosis and mass gatherings-opportunities for defining burden, transmission risk, and the optimal surveillance, prevention, and control measures at the annual Hajj pilgrimage. Int J Infect Dis 47: 8691.

    • Search Google Scholar
    • Export Citation
  • 3.

    Al-Orainey IO, 2013. Tuberculosis infection during Hajj pilgrimage. The risk to pilgrims and their communities. Saudi Med J 34: 676680.

    • Search Google Scholar
    • Export Citation
  • 4.

    Gautret P, Benkouiten S, Griffiths K, Sridhar S, 2015. The inevitable Hajj cough: surveillance data in French pilgrims, 2012–2014. Travel Med Infect Dis 13: 485489.

    • Search Google Scholar
    • Export Citation
  • 5.

    Alzeer A, Mashlah A, Fakim N, Al-Sugair N, Al-Hedaithy M, Al-Majed S, Jamjoom G, 1998. Tuberculosis is the commonest cause of pneumonia requiring hospitalization during Hajj (pilgrimage to Makkah). J Infect 36: 303306.

    • Search Google Scholar
    • Export Citation
  • 6.

    Helb D et al. 2010. Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, near-patient technology. J Clin Microbiol 48: 229237.

    • Search Google Scholar
    • Export Citation
  • 7.

    Wilder-Smith A, Foo W, Earnest A, Paton NI, 2005. High risk of Mycobacterium tuberculosis infection during the Hajj pilgrimage. Trop Med Int Health 10: 336339.

    • Search Google Scholar
    • Export Citation
  • 8.

    Aldridge RW, Yates TA, Zenner D, White PJ, Abubakar I, Hayward AC, 2014. Pre-entry screening programmes for tuberculosis in migrants to low-incidence countries: a systematic review and meta-analysis. Lancet Infect Dis 14: 12401249.

    • Search Google Scholar
    • Export Citation
  • 9.

    Ayles H, Schaap A, Nota A, Sismanidis C, Tembwe R, de Haas P, Muyoyeta M, Beyers N, Peter Godfrey-Faussett for the ZAMSTAR Study Team, 2009. Prevalence of tuberculosis, HIV and respiratory symptoms in two Zambian communities: implications for tuberculosis control in the era of HIV. PLoS One 4: e5602.

    • Search Google Scholar
    • Export Citation
  • 10.

    Hoa NB, Sy DN, Nhung NV, Tiemersma EW, Borgdorff MW, Cobelens FG, 2010. National survey of tuberculosis prevalence in Viet Nam. Bull World Health Organ 88: 273280.

    • Search Google Scholar
    • Export Citation
  • 11.

    Onozaki I, Law I, Sismanidis C, Zignol M, Glaziou P, Floyd K, 2015. National tuberculosis prevalence surveys in Asia, 1990–2012: an overview of results and lessons learned. Trop Med Int Health 20: 11281145.

    • Search Google Scholar
    • Export Citation
  • 12.

    Golub JE, Bur S, Cronin WA, Gange S, Baruch N, Comstock GW, Chaisson RE, 2006. Delayed tuberculosis diagnosis and tuberculosis transmission. Int J Tuberc Lung Dis 10: 2430.

    • Search Google Scholar
    • Export Citation
  • 13.

    Nanoo A, Izu A, Ismail NA, Ihekweazu C, Abubakar I, Mametja D, Madhi SA, 2015. Nationwide and regional incidence of microbiologically confirmed pulmonary tuberculosis in South Africa, 2004–2012: a time series analysis. Lancet Infect Dis 15: 10661076.

    • Search Google Scholar
    • Export Citation
  • 14.

    Shisana O et al. 2014. South African National HIV Prevalence, Incidence and Behaviour Survey, 2012. HSRC Press. Available at: http://www.hsrc.ac.za/en/research-data/view/6871. Accessed January 16, 2017.

  • 15.

    Muntingh L, 2013. Race, Gender and Socioeconomic Status in Law Enforcement in South Africa—Are There Worrying Signs? Available at: http://cspri.org.za/publications/research-reports/Inequality%20paper.pdf. Accessed January 16, 2017.

  • 16.

    Sanchez-Barriga JJ, 2015. Mortality trends and risk of dying from pulmonary tuberculosis in the 7 socioeconomic regions and the 32 States of Mexico, 2000–2009. Arch Bronconeumol 51: 1623.

    • Search Google Scholar
    • Export Citation
  • 17.

    Needham DM, Foster SD, Tomlinson G, Godfrey-Faussett P, 2001. Socio-economic, gender and health services factors affecting diagnostic delay for tuberculosis patients in urban Zambia. Trop Med Int Health 6: 256259.

    • Search Google Scholar
    • Export Citation
  • 18.

    Gelaw SM, 2016. Socioeconomic factors associated with knowledge on tuberculosis among adults in Ethiopia. Tuberc Res Treat 2016: 6207457.

  • 19.

    Dogar OF, Shah SK, Chughtai AA, Qadeer E, 2012. Gender disparity in tuberculosis cases in eastern and western provinces of Pakistan. BMC Infect Dis 12: 244.

    • Search Google Scholar
    • Export Citation
  • 20.

    Memish ZA et al. 2014. Prevalence of MERS-CoV nasal carriage and compliance with the Saudi health recommendations among pilgrims attending the 2013 Hajj. J Infect Dis 210: 10671072.

    • Search Google Scholar
    • Export Citation
  • 21.

    Marais BJ et al. 2013. Tuberculosis comorbidity with communicable and non-communicable diseases: integrating health services and control efforts. Lancet Infect Dis 13: 436448.

    • Search Google Scholar
    • Export Citation
  • 22.

    Bates M et al. 2012. Evaluation of the burden of unsuspected pulmonary tuberculosis and co-morbidity with non-communicable diseases in sputum producing adult inpatients. PLoS One 7: e40774.

    • Search Google Scholar
    • Export Citation
  • 23.

    Pan SC, Ku CC, Kao D, Ezzati M, Fang CT, Lin HH, 2015. Effect of diabetes on tuberculosis control in 13 countries with high tuberculosis: a modelling study. Lancet Diabetes Endocrinol 3: 323330.

    • Search Google Scholar
    • Export Citation
  • 24.

    The Lancet DE, 2014. Diabetes and tuberculosis—a wake-up call. Lancet Diabetes Endocrinol 2: 677.

  • 25.

    Ebrahim SH, Memish ZA, Uyeki TM, Khoja TA, Marano N, McNabb SJ, 2009. Public health. Pandemic H1N1 and the 2009 Hajj. Science 326: 938940.

  • 26.

    Lin HH, Ezzati M, Murray M, 2007. Tobacco smoke, indoor air pollution and tuberculosis: a systematic review and meta-analysis. PLoS Med 4: e20.

  • 27.

    Leung CC et al. 2015. Smoking adversely affects treatment response, outcome and relapse in tuberculosis. Eur Respir J 45: 738745.

  • 28.

    World Health Organization, 2007. Tuberculosis Care and Control in Refugee and Displaced Populations. An Interagency Field Manual. Geneva, Switzerland: WHO. Available at: http://apps.who.int/iris/bitstream/10665/43661/1/9789241595421_eng.pdf. Accessed May 30, 2017.

Author Notes

Address correspondence to Badriah Alotaibi, Global Centre for Mass Gatherings Medicine (GCMGM), Ministry of Health, Riyadh, Saudi Arabia. E-mail: otaibi_b1@yahoo.com

Authors’ addresses: Saber Yezli, Yara Yassin, and Badriah Alotaibi, The Global Centre for Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia, E-mails: saber.yezli@gmail.com, yyassin@moh.gov.sa, and otaibi_b1@yahoo.com. Alimuddin Zumla, Center for Clinical Microbiology, Division of Infection and Immunity, University College London and NIHR Biomedical Research Centre at UCL Hospitals, London, United Kingdom, E-mail: a.i.zumla@gmail.com. Ali M. Al-Shangiti, National Health Laboratory, Ministry of Health, Riyadh, Saudi Arabia, E-mail: Aalshangiti@moh.gov.sa. Gamal Mohamed, Liverpool School of Tropical Medicine, Liverpool, United Kingdom, E-mail: olagamal99@gmail.com. Abdulhafiz M. Turkistani, Makkah Regional Health Affairs, Ministry of Health, Jeddah, Saudi Arabia, E-mail: aturkistani@moh.gov.sa.

Save