- Email: [email protected]
Predictive value of interferon-γ release assays for incident active tuberculosis: a systematic review and meta-analysis
Comment
new meta-analysis1 estimated a pooled inactivated vaccine efficacy against influenza infection in adults of 59% (95% CI 51–67), compared with estimated efficacy in healthy adults of 73% (54–84) in the Cochrane review2 for years when circulating and vaccine strains were wellmatched and 44% (23–59) in years when they were not. The median vaccine effectiveness of the monovalent pandemic vaccine against medically attended pH1N1 influenza was 69%, whereas in another study9 effectiveness was estimated to be 90% (95% CI 48–100) against hospital admission due to laboratory-confirmed pH1N1 infection. However, other studies have reported lower vaccine effectiveness for the same outcome. In Australia in 2010, when pH1N1 influenza made up 79% of documented infections, vaccine effectiveness against hospital admission was 49% (13–70).10 A study undertaken in the Navarra region of Spain in 2010–11 estimated vaccine effectiveness against hospital admission to be 58% (16–79) with a cohort analysis and 59% (4–83) with a test-negative design (J Castilla, Public Health Institute Navarra, Spain; personal communication). Because of these estimates of seasonal and pandemic vaccine effectiveness, Osterholm and his coauthors have understandably joined the call for improved influenza vaccines. Acknowledging the burden of influenza, they also support the use of current vaccines while improved vaccines are developed. In the interim, they emphasise the need for routine effectiveness studies of presently licensed influenza vaccines with virus-confirmed endpoints. For inactivated vaccines, these endpoints should be RT-PCR diagnosed infection, because culture will miss cases and serology alone will overestimate vaccine efficacy and effectiveness.5 Now might also be an appropriate time to use revised estimates of the most probable effectiveness
of influenza vaccines to re-examine the effectiveness and cost-effectiveness of some policy options. This reexamination would need to be done in conjunction with studies that, similar to the new meta-analysis of the effect of influenza vaccines, use highly specific laboratory-confirmed outcomes to assess influenza burden. *Heath Kelly, Marta Valenciano Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia (HK); and EpiConcept, Paris, France (MV) [email protected] We declare that we have no conflicts of interest. 1
2
3 4
5
6
7
8
9
10
Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2011; published online Oct 26. DOI:10.1016/S14733099(11)70246-0. Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E. Vaccines for preventing influenza in healthy adults (review). Cochrane Database Syst Rev 2010; 7: CD001269. Last JM. A dictionary of epidemiology, 4th edn. New York: Oxford University Press, 2001. Simonsen L, Taylor RJ, Viboud C, Miller M, Jackson LA. Mortality benefits of influenza vaccination in elderly people: an ongoing controversy. Lancet Inf Dis 2007; 7: 658–66. Petrie JG, Ohmit SE, Johnson E, Cross RT, Monto AS. Efficacy studies of influenza vaccines: effect of end points used and characteristics of vaccine failures. J Infect Dis 2011; 203: 1309–15. Valenciano M, Kissling E, Cohen J-M, et al. Estimates of pandemic influenza vaccine effectiveness in Europe, 2009–2010: results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) multicentre case-control study. PLoS Med 2011; 8: e1000388. Kelly H, Peck H, Laurie K, Peng N, Nishuria H, Cowling BJ. The age-specific cumulative incidence of infection with pandemic influenza H1N1 2009 was similar in various countries prior to vaccination. PLoS One 2011; 6: e21828. Hung IF, To KK, Lee CK, et al. Effect of clinical and virological parameters on the level of neutralising antibody against pandemic influenza A virus H1N1 2009. Clin Inf Dis 2010; 51: 274–79. Puig-Barberà J, Arnedo-Pena A, Pardo-Serrano F, et al. Effectiveness of seasonal 2008–2009, 2009–2010 and pandemic vaccines to prevent influenza hospitalisations during the autumn 2009 influenza pandemic wave in Castellon, Spain. A test-negative, hospital-based case-control study. Vaccine 2010; 28: 7460–67. Cheng A, Tosombis J, Kelly H, et al. Effectiveness of H1N1/09 monovalent and trivalent influenza vaccines against hospitalization with laboratoryconfirmed H1N1/09 influenza in Australia: a test-negative case control study. Vaccine 2011; 29: 7320–25.
Tests for prediction of active tuberculosis Published Online August 16, 2011 DOI:10.1016/S14733099(11)70215-8 See Articles page 45
6
In The Lancet Infectious Diseases, Molebogeng Rangaka and colleagues1 present findings from their systematic review and meta-analysis, showing that existing diagnostic devices for latent tuberculosis infection cannot accurately predict the development of active tuberculosis. They also show that interferon-γ release assays (IGRAs), like the tuberculin skin test (TST), have only a moderate predictive value.
Rangaka and colleagues chose progression to tuberculosis as the surrogate for patient-relevant outcome, as has been done elsewhere.2 Although their approach partly circumvents the absence of a gold standard for diagnosis of latent tuberculosis infection,3 disease rates varied widely across the studies included in their analysis—4–48 cases per 1000 personyears in IGRA-positive individuals and 2–24 cases per www.thelancet.com/infection Vol 12 January 2012
Comment
1000 person-years in IGRA–negative individuals—thus precluding pooling in meta-analysis.1 After internal comparison of disease risk between IGRA-positive and IGRA-negative individuals, the pooled cumulative incidence risk ratios (RR) was 3·54 (95% CI 2·23–5·60), but heterogeneity was high (I2=56·9%). The RR differed between studies with possible incorporation bias (IGRA considered in diagnosis of tuberculosis, mainly in high-income settings; RR 8·35, 95% CI 3·19–21·87) and studies without such concern (from low-income or middle-income countries; 2·22, 1·54–3·19). In the studies without such bias, the pooled incidence rate ratio (IRR) for IGRA (2·11, 95% CI 1·29–3·46) was only slightly higher than it was for TST (1·60, 0·94–2·72).1 Although the difference was not statistically significant, a type 2 error could not be excluded because of the small number of tuberculosis cases. Fewer individuals were IGRA-positive than were TST-positive, potentially reducing the need for treatment. In the assessment of a new diagnostic method, we should not lose sight of its design. IGRAs were designed a decade ago to overcome the poor specificity of TSTs, mainly with the use of more specific antigens for ex-vivo challenge.4 Studies have since confirmed that IGRAs are not affected by BCG vaccination.5 However, all existing diagnostic devices for latent tuberculosis infection detect host immune response, rather than the activity of the pathogen itself.3,6 Therefore, none of them are expected to overcome the intrinsic limitation imposed by the natural history of tuberculosis—the positive predictive value cannot exceed the lifetime disease risk of about 10%.3,6 Nor can they overcome the diagnostic difficulties posed by remote infection with low disease risk and ongoing transmission after testing. In highincome countries where such complications are scarce, IGRA seemed to perform very well.1 IGRA also showed a high IRR of 4·50 (95% CI 1·03–19·68) in patients with silicosis in Hong Kong where attending physicians were masked to test results.1,7 Differing prevalence of such complications, rather than incorporation bias, could therefore account for the differential predictive power of IGRAs between high-income settings and low-income or middle-income settings. In theory, IGRAs could be compared with TST in a randomised controlled trial of treatment for test-positive individuals, thereby circumventing the ethical hurdle of withholding interventions from individuals at risk of www.thelancet.com/infection Vol 12 January 2012
tuberculosis. However, a very large sample size would probably be needed, and with suboptimum acceptance, adherence, and effectiveness of available treatment regimens,3 the number of tuberculosis cases averted might well be too remote an endpoint for the efficient assessment of simple diagnostic devices. Nevertheless, randomised trials alone are not likely to improve existing technology. More basic research is needed to investigate the complex interaction between Mycobacterium tuberculosis and the human host to identify a suitable biomarker for progression to active disease.8 Until such a biomarker is available, a clear need exists to focus screening and treatment efforts on groups with high disease risk.3 Multivariate risk models for disease development might help to inform clinical decision making, as they do for the assessment of infection risk.9 Because both IGRAs and TST are directed at host immune responses, they are necessarily affected by host immune status, although possibly to different extents.10 IGRAs might be more sensitive for the detection of concurrent active tuberculosis in elderly people7,11 or immunocompromised individuals.12 Further studies are needed to substantiate these claims and delineate the specific clinical settings where the need for better sensitivity and specificity would justify their much higher costs compared with TST. Chi Chiu Leung Tuberculosis and Chest Service, Department of Health, Hong Kong, China [email protected] I declare that I have no conflicts of interest. 1
2
3 4
5
6
7
8
Rangaka MX, Wilkinson KA, Glynn JR, et al. Predictive value of interferon-γ release assays for incident active tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis 2011; published online Aug 16. DOI:10.1016/S1473-3099(11)70210-9. Brozek JL, Akl EA, Jaeschke R, et al. Grading quality of evidence and strength of recommendations in clinical practice guidelines: part 2 of 3—the GRADE approach to grading quality of evidence about diagnostic tests and strategies. Allergy 2009; 64: 1109–16. Leung CC, Rieder HL, Lange C, Yew WW. Treatment of latent infection with M tuberculosis: update 2010. Eur Respir J 2011; 37: 690–711. Lalvani A, Pathan AA, Durkan H, et al. Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Lancet 2001; 357: 2017–21. Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med 2008; 149: 177–84. American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000; 161: 221–47. Leung CC, Yam WC, Yew WW, et al. T-Spot.TB outperforms tuberculin skin test in predicting tuberculosis disease. Am J Respir Crit Care Med 2010; 182: 834–40. Walzl G, Ronacher K, Hanekom W, Scriba TJ, Zumla A. Immunological biomarkers of tuberculosis. Nat Rev Immunol 2011; 11: 343–54.
7
Comment
9
10
Bailey WC, Gerald LB, Kimerling ME, et al. Predictive model to identify positive tuberculosis skin test results during contact investigations. JAMA 2002; 287: 996–1002. Cattamanchi A, Smith R, Steingart KR, et al. Interferon-gamma release assays for the diagnosis of latent tuberculosis infection in HIV-infected individuals: a systematic review and meta-analysis. J Acquir Immune Defic Syndr 2011; 56: 230–38.
11
12
Kobashi Y, Mouri K, Yagi S, Obase Y, Miyashita N, Okimoto N, Matsushima T, Kageoka T, Oka M. Clinical utility of the QuantiFERON TB-2G test for elderly patients with active tuberculosis. Chest 2008; 133: 1196–202 Syed Ahamed Kabeer B, Sikhamani R, Swaminathan S, et al. Role of interferon gamma release assay in active TB diagnosis among HIV infected individuals. PLoS One 2009; 4: e5718.
Mass gatherings health Series See Series pages 56 and 66
In this issue we publish the first two in a Series of six articles on mass gatherings health. The remaining articles will be published online, before appearing in print in the February and March, 2012, issues of the journal. The Series has its origins in The Lancet conference on mass gatherings medicine, which took place in Jeddah, Saudi Arabia, in 2010 (Oct 23–25).1,2 The articles in the Series reflect the themes that emerged at that meeting. A consensus view among delegates at the meeting was that mass gatherings health was a better name for the discipline, since ensuring the wellbeing of people at mass gatherings required a far greater range of activities than encompassed by the traditional concept of medicine. Hence the title of our Series. Our thanks go to the expert advisors, Ziad Memish, Ministry of Health, Riyadh, Saudi Arabia, and Robert Steffen, University of Zurich, Switzerland. In the first Series article, Memish and colleagues describes the history and diversity (figure) of mass gatherings. The paper explores how efforts to ensure the safety and wellbeing of millions of Muslim pilgrims at the annual Hajj have prompted the emergence of mass gatherings health
Reuters/Toby Melville
See Correspondence page 10
Enjoying a musical mass gathering
8
as a science-based specialty. The authors also discuss how sharing knowledge and experience on managing mass gatherings can contribute to global health diplomacy, a notion that helps give mass gatherings health a distinctive character as a specialty. The risk of infectious diseases outbreaks at mass gatherings, and subsequent spread of infections when participants return to their homes, are described by Ibrahim Abubakar and colleagues in the second Series article. Abubakar and colleagues note that actions taken to mitigate the threat of contagious diseases at mass gatherings (by vaccination for example) can benefit both the place hosting the event and the communities to which participants return. Infections are probably not the greatest health risks associated with mass gatherings, as Steffen and colleagues describe in the third paper in the Series. Stampedes and heat-related illnesses have caused thousands of injuries and deaths at mass gatherings in the past 30 years. Organisers of such events must be ready for non-communicable health risks as diverse as minor traumas and terrorist attacks. To minimise health hazards at mass gatherings, it is essential to understand the behaviour of crowds. In the fourth article in the Series, Anders Johansson and colleagues review how crowd behaviour can be modelled, and how this knowledge has been used to manage the environments in which mass gatherings take place. The objective of mass gatherings is to bring people together, yet crowd management strategies aim to keep people apart. To resolve this paradox requires environmental engineering based on thorough research. Paper five in the Series, by Kamran Khan and colleagues, reviews the essential role of infectious diseases surveillance before, during, and after mass gatherings. To provide useful intelligence, such surveillance needs to be integrated at local and global levels. In anticipation of the summer 2012 Olympic and Paralympic Games in London, UK, Khan and colleagues describe how modelling of global www.thelancet.com/infection Vol 12 January 2012
new meta-analysis1 estimated a pooled inactivated vaccine efficacy against influenza infection in adults of 59% (95% CI 51–67), compared with estimated efficacy in healthy adults of 73% (54–84) in the Cochrane review2 for years when circulating and vaccine strains were wellmatched and 44% (23–59) in years when they were not. The median vaccine effectiveness of the monovalent pandemic vaccine against medically attended pH1N1 influenza was 69%, whereas in another study9 effectiveness was estimated to be 90% (95% CI 48–100) against hospital admission due to laboratory-confirmed pH1N1 infection. However, other studies have reported lower vaccine effectiveness for the same outcome. In Australia in 2010, when pH1N1 influenza made up 79% of documented infections, vaccine effectiveness against hospital admission was 49% (13–70).10 A study undertaken in the Navarra region of Spain in 2010–11 estimated vaccine effectiveness against hospital admission to be 58% (16–79) with a cohort analysis and 59% (4–83) with a test-negative design (J Castilla, Public Health Institute Navarra, Spain; personal communication). Because of these estimates of seasonal and pandemic vaccine effectiveness, Osterholm and his coauthors have understandably joined the call for improved influenza vaccines. Acknowledging the burden of influenza, they also support the use of current vaccines while improved vaccines are developed. In the interim, they emphasise the need for routine effectiveness studies of presently licensed influenza vaccines with virus-confirmed endpoints. For inactivated vaccines, these endpoints should be RT-PCR diagnosed infection, because culture will miss cases and serology alone will overestimate vaccine efficacy and effectiveness.5 Now might also be an appropriate time to use revised estimates of the most probable effectiveness
of influenza vaccines to re-examine the effectiveness and cost-effectiveness of some policy options. This reexamination would need to be done in conjunction with studies that, similar to the new meta-analysis of the effect of influenza vaccines, use highly specific laboratory-confirmed outcomes to assess influenza burden. *Heath Kelly, Marta Valenciano Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia (HK); and EpiConcept, Paris, France (MV) [email protected] We declare that we have no conflicts of interest. 1
2
3 4
5
6
7
8
9
10
Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2011; published online Oct 26. DOI:10.1016/S14733099(11)70246-0. Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E. Vaccines for preventing influenza in healthy adults (review). Cochrane Database Syst Rev 2010; 7: CD001269. Last JM. A dictionary of epidemiology, 4th edn. New York: Oxford University Press, 2001. Simonsen L, Taylor RJ, Viboud C, Miller M, Jackson LA. Mortality benefits of influenza vaccination in elderly people: an ongoing controversy. Lancet Inf Dis 2007; 7: 658–66. Petrie JG, Ohmit SE, Johnson E, Cross RT, Monto AS. Efficacy studies of influenza vaccines: effect of end points used and characteristics of vaccine failures. J Infect Dis 2011; 203: 1309–15. Valenciano M, Kissling E, Cohen J-M, et al. Estimates of pandemic influenza vaccine effectiveness in Europe, 2009–2010: results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) multicentre case-control study. PLoS Med 2011; 8: e1000388. Kelly H, Peck H, Laurie K, Peng N, Nishuria H, Cowling BJ. The age-specific cumulative incidence of infection with pandemic influenza H1N1 2009 was similar in various countries prior to vaccination. PLoS One 2011; 6: e21828. Hung IF, To KK, Lee CK, et al. Effect of clinical and virological parameters on the level of neutralising antibody against pandemic influenza A virus H1N1 2009. Clin Inf Dis 2010; 51: 274–79. Puig-Barberà J, Arnedo-Pena A, Pardo-Serrano F, et al. Effectiveness of seasonal 2008–2009, 2009–2010 and pandemic vaccines to prevent influenza hospitalisations during the autumn 2009 influenza pandemic wave in Castellon, Spain. A test-negative, hospital-based case-control study. Vaccine 2010; 28: 7460–67. Cheng A, Tosombis J, Kelly H, et al. Effectiveness of H1N1/09 monovalent and trivalent influenza vaccines against hospitalization with laboratoryconfirmed H1N1/09 influenza in Australia: a test-negative case control study. Vaccine 2011; 29: 7320–25.
Tests for prediction of active tuberculosis Published Online August 16, 2011 DOI:10.1016/S14733099(11)70215-8 See Articles page 45
6
In The Lancet Infectious Diseases, Molebogeng Rangaka and colleagues1 present findings from their systematic review and meta-analysis, showing that existing diagnostic devices for latent tuberculosis infection cannot accurately predict the development of active tuberculosis. They also show that interferon-γ release assays (IGRAs), like the tuberculin skin test (TST), have only a moderate predictive value.
Rangaka and colleagues chose progression to tuberculosis as the surrogate for patient-relevant outcome, as has been done elsewhere.2 Although their approach partly circumvents the absence of a gold standard for diagnosis of latent tuberculosis infection,3 disease rates varied widely across the studies included in their analysis—4–48 cases per 1000 personyears in IGRA-positive individuals and 2–24 cases per www.thelancet.com/infection Vol 12 January 2012
Comment
1000 person-years in IGRA–negative individuals—thus precluding pooling in meta-analysis.1 After internal comparison of disease risk between IGRA-positive and IGRA-negative individuals, the pooled cumulative incidence risk ratios (RR) was 3·54 (95% CI 2·23–5·60), but heterogeneity was high (I2=56·9%). The RR differed between studies with possible incorporation bias (IGRA considered in diagnosis of tuberculosis, mainly in high-income settings; RR 8·35, 95% CI 3·19–21·87) and studies without such concern (from low-income or middle-income countries; 2·22, 1·54–3·19). In the studies without such bias, the pooled incidence rate ratio (IRR) for IGRA (2·11, 95% CI 1·29–3·46) was only slightly higher than it was for TST (1·60, 0·94–2·72).1 Although the difference was not statistically significant, a type 2 error could not be excluded because of the small number of tuberculosis cases. Fewer individuals were IGRA-positive than were TST-positive, potentially reducing the need for treatment. In the assessment of a new diagnostic method, we should not lose sight of its design. IGRAs were designed a decade ago to overcome the poor specificity of TSTs, mainly with the use of more specific antigens for ex-vivo challenge.4 Studies have since confirmed that IGRAs are not affected by BCG vaccination.5 However, all existing diagnostic devices for latent tuberculosis infection detect host immune response, rather than the activity of the pathogen itself.3,6 Therefore, none of them are expected to overcome the intrinsic limitation imposed by the natural history of tuberculosis—the positive predictive value cannot exceed the lifetime disease risk of about 10%.3,6 Nor can they overcome the diagnostic difficulties posed by remote infection with low disease risk and ongoing transmission after testing. In highincome countries where such complications are scarce, IGRA seemed to perform very well.1 IGRA also showed a high IRR of 4·50 (95% CI 1·03–19·68) in patients with silicosis in Hong Kong where attending physicians were masked to test results.1,7 Differing prevalence of such complications, rather than incorporation bias, could therefore account for the differential predictive power of IGRAs between high-income settings and low-income or middle-income settings. In theory, IGRAs could be compared with TST in a randomised controlled trial of treatment for test-positive individuals, thereby circumventing the ethical hurdle of withholding interventions from individuals at risk of www.thelancet.com/infection Vol 12 January 2012
tuberculosis. However, a very large sample size would probably be needed, and with suboptimum acceptance, adherence, and effectiveness of available treatment regimens,3 the number of tuberculosis cases averted might well be too remote an endpoint for the efficient assessment of simple diagnostic devices. Nevertheless, randomised trials alone are not likely to improve existing technology. More basic research is needed to investigate the complex interaction between Mycobacterium tuberculosis and the human host to identify a suitable biomarker for progression to active disease.8 Until such a biomarker is available, a clear need exists to focus screening and treatment efforts on groups with high disease risk.3 Multivariate risk models for disease development might help to inform clinical decision making, as they do for the assessment of infection risk.9 Because both IGRAs and TST are directed at host immune responses, they are necessarily affected by host immune status, although possibly to different extents.10 IGRAs might be more sensitive for the detection of concurrent active tuberculosis in elderly people7,11 or immunocompromised individuals.12 Further studies are needed to substantiate these claims and delineate the specific clinical settings where the need for better sensitivity and specificity would justify their much higher costs compared with TST. Chi Chiu Leung Tuberculosis and Chest Service, Department of Health, Hong Kong, China [email protected] I declare that I have no conflicts of interest. 1
2
3 4
5
6
7
8
Rangaka MX, Wilkinson KA, Glynn JR, et al. Predictive value of interferon-γ release assays for incident active tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis 2011; published online Aug 16. DOI:10.1016/S1473-3099(11)70210-9. Brozek JL, Akl EA, Jaeschke R, et al. Grading quality of evidence and strength of recommendations in clinical practice guidelines: part 2 of 3—the GRADE approach to grading quality of evidence about diagnostic tests and strategies. Allergy 2009; 64: 1109–16. Leung CC, Rieder HL, Lange C, Yew WW. Treatment of latent infection with M tuberculosis: update 2010. Eur Respir J 2011; 37: 690–711. Lalvani A, Pathan AA, Durkan H, et al. Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Lancet 2001; 357: 2017–21. Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med 2008; 149: 177–84. American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000; 161: 221–47. Leung CC, Yam WC, Yew WW, et al. T-Spot.TB outperforms tuberculin skin test in predicting tuberculosis disease. Am J Respir Crit Care Med 2010; 182: 834–40. Walzl G, Ronacher K, Hanekom W, Scriba TJ, Zumla A. Immunological biomarkers of tuberculosis. Nat Rev Immunol 2011; 11: 343–54.
7
Comment
9
10
Bailey WC, Gerald LB, Kimerling ME, et al. Predictive model to identify positive tuberculosis skin test results during contact investigations. JAMA 2002; 287: 996–1002. Cattamanchi A, Smith R, Steingart KR, et al. Interferon-gamma release assays for the diagnosis of latent tuberculosis infection in HIV-infected individuals: a systematic review and meta-analysis. J Acquir Immune Defic Syndr 2011; 56: 230–38.
11
12
Kobashi Y, Mouri K, Yagi S, Obase Y, Miyashita N, Okimoto N, Matsushima T, Kageoka T, Oka M. Clinical utility of the QuantiFERON TB-2G test for elderly patients with active tuberculosis. Chest 2008; 133: 1196–202 Syed Ahamed Kabeer B, Sikhamani R, Swaminathan S, et al. Role of interferon gamma release assay in active TB diagnosis among HIV infected individuals. PLoS One 2009; 4: e5718.
Mass gatherings health Series See Series pages 56 and 66
In this issue we publish the first two in a Series of six articles on mass gatherings health. The remaining articles will be published online, before appearing in print in the February and March, 2012, issues of the journal. The Series has its origins in The Lancet conference on mass gatherings medicine, which took place in Jeddah, Saudi Arabia, in 2010 (Oct 23–25).1,2 The articles in the Series reflect the themes that emerged at that meeting. A consensus view among delegates at the meeting was that mass gatherings health was a better name for the discipline, since ensuring the wellbeing of people at mass gatherings required a far greater range of activities than encompassed by the traditional concept of medicine. Hence the title of our Series. Our thanks go to the expert advisors, Ziad Memish, Ministry of Health, Riyadh, Saudi Arabia, and Robert Steffen, University of Zurich, Switzerland. In the first Series article, Memish and colleagues describes the history and diversity (figure) of mass gatherings. The paper explores how efforts to ensure the safety and wellbeing of millions of Muslim pilgrims at the annual Hajj have prompted the emergence of mass gatherings health
Reuters/Toby Melville
See Correspondence page 10
Enjoying a musical mass gathering
8
as a science-based specialty. The authors also discuss how sharing knowledge and experience on managing mass gatherings can contribute to global health diplomacy, a notion that helps give mass gatherings health a distinctive character as a specialty. The risk of infectious diseases outbreaks at mass gatherings, and subsequent spread of infections when participants return to their homes, are described by Ibrahim Abubakar and colleagues in the second Series article. Abubakar and colleagues note that actions taken to mitigate the threat of contagious diseases at mass gatherings (by vaccination for example) can benefit both the place hosting the event and the communities to which participants return. Infections are probably not the greatest health risks associated with mass gatherings, as Steffen and colleagues describe in the third paper in the Series. Stampedes and heat-related illnesses have caused thousands of injuries and deaths at mass gatherings in the past 30 years. Organisers of such events must be ready for non-communicable health risks as diverse as minor traumas and terrorist attacks. To minimise health hazards at mass gatherings, it is essential to understand the behaviour of crowds. In the fourth article in the Series, Anders Johansson and colleagues review how crowd behaviour can be modelled, and how this knowledge has been used to manage the environments in which mass gatherings take place. The objective of mass gatherings is to bring people together, yet crowd management strategies aim to keep people apart. To resolve this paradox requires environmental engineering based on thorough research. Paper five in the Series, by Kamran Khan and colleagues, reviews the essential role of infectious diseases surveillance before, during, and after mass gatherings. To provide useful intelligence, such surveillance needs to be integrated at local and global levels. In anticipation of the summer 2012 Olympic and Paralympic Games in London, UK, Khan and colleagues describe how modelling of global www.thelancet.com/infection Vol 12 January 2012