It’s not over until it’s over… but it’s never over — Emerging and re-emerging infectious diseases | NEJM

As I prepare to leave my dual role at the National Institute of Allergy and Infectious Diseases (NIAID), where I served as a physician-scientist for 54 years and as a director for 38, a little thought is in order. . Looking back on my career, what stands out most is the striking evolution of the field of infectious diseases and the changing perception of the importance and relevance of the field by the academic community and the public.

I completed my residency training in internal medicine in 1968 and decided to undertake a combined 3-year fellowship in infectious diseases and clinical immunology at NIAID. Unbeknownst to me as a young doctor, some academics and experts in the 1960s were of the opinion that with the advent of highly effective vaccines against many childhood diseases and an expanding range of antibiotics, the threat of infectious disease – and perhaps, with it, the need for infectious disease specialists – was rapidly disappearing.¹ Despite my passion for the field I was entering, I might have reconsidered my choice of subspecialty if I had known this skepticism about the future of the discipline. Of course, at the time, malaria, tuberculosis and other diseases in low- and middle-income countries were killing millions of people a year. Unaware of this inherent contradiction, I happily pursued my clinical and research interests in host defenses and infectious diseases.

Having been away from my fellowship for several years, I was somewhat surprised when Dr. Robert Petersdorf, an icon in the field of infectious diseases, published a provocative article in the Log suggesting that infectious diseases as a subspecialty of internal medicine were falling into oblivion.² In an article titled “The Physician’s Dilemma,” he wrote of the number of young physicians undertaking training in the various subspecialties of internal medicine: “Even with my strong personal loyalty to infectious disease, I cannot conceive the need for 309 more infectious disease specialists. experts unless they spend their time cultivating each other.

Of course, we all aspire to be part of a dynamic field. Was my chosen field now static? Petersdorf (who was to become my part-time friend and mentor as we and other co-publishers Harrison’s Principles of Internal Medicine) expressed a common view that lacked a full appreciation of the truly dynamic nature of infectious diseases, particularly with respect to the potential for emerging and re-emerging infections. In the 1960s and 1970s, most physicians were aware of the possibility of pandemics, in light of the well-known precedent of the historic 1918 influenza pandemic, as well as the more recent influenza pandemics of 1957 and 1968. However, the emergence of a truly new infectious disease that could significantly affect society was still a purely hypothetical concept.

Everything changed in the summer of 1981 with the recognition of the first cases of what was to become AIDS. The global impact of this disease is staggering: since the start of the pandemic, more than 84 million people have been infected with HIV, the virus that causes AIDS, of which 40 million have died. In 2021 alone, 650,000 people died of AIDS-related illnesses and 1.5 million were newly infected. Today, more than 38 million people are living with HIV.

Although a safe and effective vaccine against HIV has not yet been developed, advances in science have led to the development of highly effective antiretroviral drugs that have transformed HIV infection from an almost always fatal disease into a disease manageable chronic condition associated with an almost normal life expectancy. Given the global inequity in the accessibility of these life-saving drugs, HIV/AIDS continues, taking a terrible toll in terms of morbidity and mortality, 41 years after it was first recognized.

If there is a positive side to the emergence of HIV/AIDS, it is that the disease has greatly increased interest in infectious diseases among young people entering the field of medicine. Indeed, with the emergence of HIV/AIDS, we badly needed those 309 infectious disease trainees that Dr. Petersdorf cared about — and many more. To his credit, years after the publication of his paper, Dr. Petersdorf readily admitted that he had not fully appreciated the potential impact of emerging infections and became something of a ringleader for young doctors to pursue careers. in infectious diseases and more particularly in the practice of HIV/AIDS. and research.

Selected milestones in the emergence of infectious diseases before and during the author’s four decades as director of NIAID.

DRC stands for Democratic Republic of Congo, Middle East MERS Respiratory Syndrome, SARS Severe Acute Respiratory Syndrome and Extremely Drug Resistant XDR.

Of course, the threat and reality of emerging infections did not end with HIV/AIDS. During my tenure as Director of NIAID, we have faced the emergence or re-emergence of many infectious diseases with varying degrees of regional or global impact (see chronology). Among these were the first known human cases of H5N1 and H7N9 influenza; the first pandemic of the 21st century (in 2009) caused by the H1N1 flu; multiple Ebola outbreaks in Africa; Zika in the Americas; severe acute respiratory syndrome (SARS) caused by a novel coronavirus; Middle East respiratory syndrome (MERS) caused by another emerging coronavirus; and of course Covid-19, the loudest wake-up call in over a century about our vulnerability to outbreaks of emerging infectious diseases.

The devastation that Covid-19 has inflicted on a global scale is truly historic and highlights the general lack of public health preparedness around the world for an outbreak of this magnitude. A very successful element of the response to Covid-19, however, has been the rapid development – ​​made possible by years of investment in basic and applied research – of highly adaptable vaccine platforms such as mRNA (among others) and the use of structural biology tools to design immunogenic vaccines. The unprecedented speed with which safe and highly effective Covid-19 vaccines have been developed, proven effective and distributed has saved millions of lives.³ Over the years, many sub-specialties of medicine have benefited greatly from mind-boggling technological advancements. The same is true today in the field of infectious diseases, in particular with the tools we now have to respond to emerging infectious diseases, such as the rapid and high-throughput sequencing of viral genomes; the development of rapid and highly specific multiplex diagnostics; and the use of structure-based immunogen design combined with novel vaccine platforms.⁴

If anyone had any doubts about the dynamic nature of infectious diseases and, by extension, the discipline of infectious diseases, our experience in the four decades since AIDS was recognized should have completely dispelled such skepticism. Today, there is no reason to believe that the threat of emerging infections will diminish, since their underlying causes are present and most likely increasing. The emergence of new infections and the re-emergence of old ones are largely the result of human interactions with and encroachments on nature. As human societies expand into a progressively interconnected world and the human-animal interface is disrupted, opportunities are created, often aided by climate change, for unstable infectious agents to emerge, jump species and, in some cases, adapt to spread among humans.⁵

An inescapable conclusion from my reflections on the evolution of the infectious disease field is that the experts of years ago were incorrect and the discipline is certainly not static; it’s really dynamic. Along with the obvious need to continue to improve our capabilities to deal with established infectious diseases such as malaria and tuberculosis, among others, it is now clear that emerging infectious diseases are truly a perpetual challenge. As one of my favorite experts, Yogi Berra, once said, “It’s not over until it’s over.” Of course, we can now extend this axiom: when it comes to emerging infectious diseases, it’s never over. As infectious disease specialists, we must be perpetually prepared and able to respond to the perpetual challenge.