Downloaded from http://rstb.royalsocietypublishing.org/ on March 29, 2015
The science of infectious diseases Christopher Dye1 and Anne O’Garra2,3 1
Office of the Director General, World Health Organization, Avenue Appia, 1211 Geneva 27, Switzerland Division of Immunoregulation, MRC National Institute for Medical Research, London, UK 3 National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK 2
rstb.royalsocietypublishing.org
Preface Cite this article: Dye C, O’Garra A. 2014 The science of infectious diseases. Phil. Trans. R. Soc. B 369: 20140055. http://dx.doi.org/10.1098/rstb.2014.0055 One contribution of 12 to a Theme Issue ‘After 2015: infectious diseases in a new era of health and development’.
The United Nations (UN) Millennium Development Goals (MDGs) have provided a framework for accelerating the decline of infectious diseases, backed by a massive injection of foreign investment in low-income countries. The MDG era is credited with numerous successes: between 1990 and 2012 the proportion of people living in extreme poverty was halved, and the proportion of slum dwellers in cities is also in decline. Over 2 billion people gained access to clean drinking water. Malaria death rates fell by more than a quarter, and deaths in childhood (less than 5 years) by almost one half [1]. Despite these accomplishments, infectious diseases (plus maternal and nutritional disorders) remain the commonest cause of death in the world’s poorest countries, whose inhabitants still suffer greatly from diarrhoeal diseases, pneumonia, HIV/AIDS, tuberculosis, malaria and helminth infections, among others. One hundred and fifty years after Europe’s ‘sanitation revolution’, an astonishing 2.4 billion people (more than one in three) still do not have piped drinking water, and more than 1 billion people are without sanitation. Adding to the predictable burden of endemic disease, the threat of pandemics from domestic and wild animals is ever-present and global. Under-nutrition, intimately linked to infection, still affects hundreds of millions of people worldwide. The eradication of polio and Guinea worm, repeatedly promised, hang in the balance. Infections are contributing to the growing burden of chronic diseases, notably cancers associated with hepatitis B and C viruses (liver), human papilloma virus (cervix) and Helicobacter pylori (stomach). Infectious diseases have been quelled, but they are far from conquered. After 2015, the MDGs will be replaced by a new set of goals that focus on poverty reduction and sustainable development [2,3]. Health is central to the well-being of individuals and to the development of populations, and the post2015 agenda will put health in broad context. More explicitly than the MDGs, it will take on non-communicable diseases, nutritional disorders, mental health and injuries. There will be a marked shift in political support and funding, and infectious diseases are likely to have a lower profile. At this critical juncture, this issue of papers1 explores the frontiers of infection biology at the level of individuals (molecular, cellular, genetic, immune) and populations (demography, ecology, epidemiology). It asks how efforts to investigate and control infections will fare in the era of sustainable development, and how science can help to meet the challenge. The introductory paper [4] sets the scene by offering, among other things, a reminder that UN development goals are part of a much longer process in public health: they are the latest and biggest, concerted effort to accelerate the demographic and epidemiological transitions, setting a course towards optimal fertility and minimal premature mortality in stable populations. Then the first group of four papers examines the disease process within individual hosts. With reference to diseases caused by a major bacterial (tuberculosis) and viral infection (HIV/AIDS), these reviews discuss how studying changes in gene expression during infection could lead to new diagnostic and prognostic tests [5], how investigating genetic variation could mitigate pathogenicity [6], how understanding latent infection could stop the progression to active disease [7] and how immunology provides insights into viral cure [8]. The second group of six papers is concerned with the development of interventions against infectious diseases, and how they can be deployed at
& 2014 The Author(s) Published by the Royal Society. All rights reserved.
Downloaded from http://rstb.royalsocietypublishing.org/ on March 29, 2015
income countries? Could insecticide resistance be as big a threat to malaria control as resistance to artemisinin-based drug combinations? Is a cure for HIV/AIDS a fantasy or the realistic outcome of current research? At a time when infectious diseases must compete for attention on a crowded international health agenda, these papers send out the message that infection biology, at the level of pathogen, host and population, is as exciting and challenging as ever, and that the ensuing discoveries could be profoundly important for public health.
1
Several of these papers [4,5,9,11–13] were presented at a meeting held at the Royal Society on 27 February 2013, with the same title as this issue; the others were commissioned to add depth and breadth.
References 1.
2.
3.
4.
5.
6.
United Nations. 2013 Prevention and control of noncommunicable diseases. In United Nations General Assembly 68th session. New York, NY, USA: United Nations. Sustainable Development Solutions Network. 2013 An action agenda for sustainable development. Report for the UN Secretary General. New York, NY, USA: Sustainable Development Solutions Network. United Nations. 2013 A new global partnership: eradicate poverty and transform economies through sustainable development. New York, NY, USA: United Nations. Dye C. 2014 After 2015: infectious diseases in a new era of health and development. Phil. Trans. R. Soc. B 369, 20130426. (doi:10.1098/rstb.2013.0426) Blankley S, Berry MPR, Graham CM, Bloom CI, Lipman M, O’Garra A. 2014 The application of transcriptional blood signatures to enhance our understanding of the host response to infection: the example of tuberculosis. Phil. Trans. R. Soc. B 369, 20130427. (doi:10.1098/rstb.2013.0427) Abel L, El-Baghdadi J, Bousfiha AA, Casanova J-L, Schurr E. 2014 Human genetics of tuberculosis: a
long and winding road. Phil. Trans. R. Soc. B 369, 20130428. (doi:10.1098/rstb.2013.0428) 7. Esmail H, Barry CE 3rd, Young DB, Wilkinson RJ. 2014 The ongoing challenge of latent tuberculosis. Phil. Trans. R. Soc. B 369, 20130437. (doi:10.1098/ rstb.2013.0437) 8. Saez-Cirion A, Jacquelin B, Barre´-Sinoussi F, Mu¨llerTrutwin M. 2014 Immune responses during spontaneous control of HIV and AIDS: what is the hope for a cure? Phil. Trans. R. Soc. B 369, 20130436. (doi:10.1098/rstb.2013.0436) 9. Cole ST. 2014 Who will develop new antibacterial agents? Phil. Trans. R. Soc. B 369, 20130430. (doi:10.1098/rstb.2013.0430) 10. Webster JP, Molyneux DH, Hotez PJ, Fenwick A. 2014 The contribution of mass drug administration to global health: past, present and future. Phil. Trans. R. Soc. B 369, 20130434. (doi:10.1098/rstb. 2013.0434) 11. Anderson R, Truscott J, Hollingsworth TD. 2014 The coverage and frequency of mass drug administration required to eliminate persistent transmission of soiltransmitted helminths. Phil. Trans. R. Soc. B 369, 20130435. (doi:10.1098/rstb.2013.0435)
12. Greenwood B. 2014 The contribution of vaccination to global health: past, present and future. Phil. Trans. R. Soc. B 369, 20130433. (doi:10.1098/rstb.2013.0433) 13. Hemingway J. 2014 The role of vector control in stopping the transmission of malaria: threats and opportunities. Phil. Trans. R. Soc. B 369, 20130431. (doi:10.1098/rstb.2013.0431) 14. Burt A. 2014 Heritable strategies for controlling insect vectors of disease. Phil. Trans. R. Soc. B 369, 20130432. (doi:10.1098/rstb.2013.0432) 15. Lightfoot N, Rweyemamu M, Heymann DL. 2013 Preparing for the next pandemic. BMJ Open 346, f364. (doi:10.1136/bmj.f364) 16. Bhatt S, Gething PW, Brady OJ et al. 2013 The global distribution and burden of dengue. Nature 496, 504–507. (doi:10.1038/nature12060) 17. Blaser M, Bork P, Fraser C, Knight R, Wang J. 2013 The microbiome explored: recent insights and future challenges. Nat. Rev. Microbiol. 11, 213–217. (doi:10.1038/nrmicro2973) 18. Jamison DT, Breman JG, Measham AR, Alleyne G, Evans D, Claeson M, Jha P, Mills A, Musgrove P. 2006 Disease control priorities in developing countries, 2nd edn. New York, NY: Oxford University Press.
Phil. Trans. R. Soc. B 369: 20140055
Endnote
2
rstb.royalsocietypublishing.org
population level. These are drugs for bacterial [9] and helminth infections [10,11], vaccines for pathogens of all kinds [12], and insecticides [13] and the manipulation of heritable characteristics for mosquito control [14]. This short collection of papers is inevitably selective, both with respect to the topics covered and the choice of pathogens and their vectors. There is little mention of, for example, the risk of pandemic influenza [15], the geographical spread of dengue [16], the role of the microbiome in health [17] or the economics of disease control [18]. Nonetheless, the chosen subjects home in on some key questions about the control of infectious diseases today. Where will the next generation of antibiotics come from? How can we improve diagnosis and drug efficacy to improve the control of infectious diseases? Why has not low-cost, mass treatment of helminth infections already been more successful? Can highly efficacious vaccines bypass some of the limitations of weak health systems in low-
The science of infectious diseases Christopher Dye1 and Anne O’Garra2,3 1
Office of the Director General, World Health Organization, Avenue Appia, 1211 Geneva 27, Switzerland Division of Immunoregulation, MRC National Institute for Medical Research, London, UK 3 National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK 2
rstb.royalsocietypublishing.org
Preface Cite this article: Dye C, O’Garra A. 2014 The science of infectious diseases. Phil. Trans. R. Soc. B 369: 20140055. http://dx.doi.org/10.1098/rstb.2014.0055 One contribution of 12 to a Theme Issue ‘After 2015: infectious diseases in a new era of health and development’.
The United Nations (UN) Millennium Development Goals (MDGs) have provided a framework for accelerating the decline of infectious diseases, backed by a massive injection of foreign investment in low-income countries. The MDG era is credited with numerous successes: between 1990 and 2012 the proportion of people living in extreme poverty was halved, and the proportion of slum dwellers in cities is also in decline. Over 2 billion people gained access to clean drinking water. Malaria death rates fell by more than a quarter, and deaths in childhood (less than 5 years) by almost one half [1]. Despite these accomplishments, infectious diseases (plus maternal and nutritional disorders) remain the commonest cause of death in the world’s poorest countries, whose inhabitants still suffer greatly from diarrhoeal diseases, pneumonia, HIV/AIDS, tuberculosis, malaria and helminth infections, among others. One hundred and fifty years after Europe’s ‘sanitation revolution’, an astonishing 2.4 billion people (more than one in three) still do not have piped drinking water, and more than 1 billion people are without sanitation. Adding to the predictable burden of endemic disease, the threat of pandemics from domestic and wild animals is ever-present and global. Under-nutrition, intimately linked to infection, still affects hundreds of millions of people worldwide. The eradication of polio and Guinea worm, repeatedly promised, hang in the balance. Infections are contributing to the growing burden of chronic diseases, notably cancers associated with hepatitis B and C viruses (liver), human papilloma virus (cervix) and Helicobacter pylori (stomach). Infectious diseases have been quelled, but they are far from conquered. After 2015, the MDGs will be replaced by a new set of goals that focus on poverty reduction and sustainable development [2,3]. Health is central to the well-being of individuals and to the development of populations, and the post2015 agenda will put health in broad context. More explicitly than the MDGs, it will take on non-communicable diseases, nutritional disorders, mental health and injuries. There will be a marked shift in political support and funding, and infectious diseases are likely to have a lower profile. At this critical juncture, this issue of papers1 explores the frontiers of infection biology at the level of individuals (molecular, cellular, genetic, immune) and populations (demography, ecology, epidemiology). It asks how efforts to investigate and control infections will fare in the era of sustainable development, and how science can help to meet the challenge. The introductory paper [4] sets the scene by offering, among other things, a reminder that UN development goals are part of a much longer process in public health: they are the latest and biggest, concerted effort to accelerate the demographic and epidemiological transitions, setting a course towards optimal fertility and minimal premature mortality in stable populations. Then the first group of four papers examines the disease process within individual hosts. With reference to diseases caused by a major bacterial (tuberculosis) and viral infection (HIV/AIDS), these reviews discuss how studying changes in gene expression during infection could lead to new diagnostic and prognostic tests [5], how investigating genetic variation could mitigate pathogenicity [6], how understanding latent infection could stop the progression to active disease [7] and how immunology provides insights into viral cure [8]. The second group of six papers is concerned with the development of interventions against infectious diseases, and how they can be deployed at
& 2014 The Author(s) Published by the Royal Society. All rights reserved.
Downloaded from http://rstb.royalsocietypublishing.org/ on March 29, 2015
income countries? Could insecticide resistance be as big a threat to malaria control as resistance to artemisinin-based drug combinations? Is a cure for HIV/AIDS a fantasy or the realistic outcome of current research? At a time when infectious diseases must compete for attention on a crowded international health agenda, these papers send out the message that infection biology, at the level of pathogen, host and population, is as exciting and challenging as ever, and that the ensuing discoveries could be profoundly important for public health.
1
Several of these papers [4,5,9,11–13] were presented at a meeting held at the Royal Society on 27 February 2013, with the same title as this issue; the others were commissioned to add depth and breadth.
References 1.
2.
3.
4.
5.
6.
United Nations. 2013 Prevention and control of noncommunicable diseases. In United Nations General Assembly 68th session. New York, NY, USA: United Nations. Sustainable Development Solutions Network. 2013 An action agenda for sustainable development. Report for the UN Secretary General. New York, NY, USA: Sustainable Development Solutions Network. United Nations. 2013 A new global partnership: eradicate poverty and transform economies through sustainable development. New York, NY, USA: United Nations. Dye C. 2014 After 2015: infectious diseases in a new era of health and development. Phil. Trans. R. Soc. B 369, 20130426. (doi:10.1098/rstb.2013.0426) Blankley S, Berry MPR, Graham CM, Bloom CI, Lipman M, O’Garra A. 2014 The application of transcriptional blood signatures to enhance our understanding of the host response to infection: the example of tuberculosis. Phil. Trans. R. Soc. B 369, 20130427. (doi:10.1098/rstb.2013.0427) Abel L, El-Baghdadi J, Bousfiha AA, Casanova J-L, Schurr E. 2014 Human genetics of tuberculosis: a
long and winding road. Phil. Trans. R. Soc. B 369, 20130428. (doi:10.1098/rstb.2013.0428) 7. Esmail H, Barry CE 3rd, Young DB, Wilkinson RJ. 2014 The ongoing challenge of latent tuberculosis. Phil. Trans. R. Soc. B 369, 20130437. (doi:10.1098/ rstb.2013.0437) 8. Saez-Cirion A, Jacquelin B, Barre´-Sinoussi F, Mu¨llerTrutwin M. 2014 Immune responses during spontaneous control of HIV and AIDS: what is the hope for a cure? Phil. Trans. R. Soc. B 369, 20130436. (doi:10.1098/rstb.2013.0436) 9. Cole ST. 2014 Who will develop new antibacterial agents? Phil. Trans. R. Soc. B 369, 20130430. (doi:10.1098/rstb.2013.0430) 10. Webster JP, Molyneux DH, Hotez PJ, Fenwick A. 2014 The contribution of mass drug administration to global health: past, present and future. Phil. Trans. R. Soc. B 369, 20130434. (doi:10.1098/rstb. 2013.0434) 11. Anderson R, Truscott J, Hollingsworth TD. 2014 The coverage and frequency of mass drug administration required to eliminate persistent transmission of soiltransmitted helminths. Phil. Trans. R. Soc. B 369, 20130435. (doi:10.1098/rstb.2013.0435)
12. Greenwood B. 2014 The contribution of vaccination to global health: past, present and future. Phil. Trans. R. Soc. B 369, 20130433. (doi:10.1098/rstb.2013.0433) 13. Hemingway J. 2014 The role of vector control in stopping the transmission of malaria: threats and opportunities. Phil. Trans. R. Soc. B 369, 20130431. (doi:10.1098/rstb.2013.0431) 14. Burt A. 2014 Heritable strategies for controlling insect vectors of disease. Phil. Trans. R. Soc. B 369, 20130432. (doi:10.1098/rstb.2013.0432) 15. Lightfoot N, Rweyemamu M, Heymann DL. 2013 Preparing for the next pandemic. BMJ Open 346, f364. (doi:10.1136/bmj.f364) 16. Bhatt S, Gething PW, Brady OJ et al. 2013 The global distribution and burden of dengue. Nature 496, 504–507. (doi:10.1038/nature12060) 17. Blaser M, Bork P, Fraser C, Knight R, Wang J. 2013 The microbiome explored: recent insights and future challenges. Nat. Rev. Microbiol. 11, 213–217. (doi:10.1038/nrmicro2973) 18. Jamison DT, Breman JG, Measham AR, Alleyne G, Evans D, Claeson M, Jha P, Mills A, Musgrove P. 2006 Disease control priorities in developing countries, 2nd edn. New York, NY: Oxford University Press.
Phil. Trans. R. Soc. B 369: 20140055
Endnote
2
rstb.royalsocietypublishing.org
population level. These are drugs for bacterial [9] and helminth infections [10,11], vaccines for pathogens of all kinds [12], and insecticides [13] and the manipulation of heritable characteristics for mosquito control [14]. This short collection of papers is inevitably selective, both with respect to the topics covered and the choice of pathogens and their vectors. There is little mention of, for example, the risk of pandemic influenza [15], the geographical spread of dengue [16], the role of the microbiome in health [17] or the economics of disease control [18]. Nonetheless, the chosen subjects home in on some key questions about the control of infectious diseases today. Where will the next generation of antibiotics come from? How can we improve diagnosis and drug efficacy to improve the control of infectious diseases? Why has not low-cost, mass treatment of helminth infections already been more successful? Can highly efficacious vaccines bypass some of the limitations of weak health systems in low-
