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

As I prepare to step down from my dual positions at the National Institute of Allergy and Infectious Diseases (NIAID), where I have been a physician-scientist for 54 years and director for 38 years, some reflection is inevitable. As I reflect on my career, what stands out most is the astonishing 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 in internal medicine in 1968 and decided to do a three-year combined fellowship in infectious disease and clinical immunology at NIAID. Unbeknownst to me as a young doctor, certain scientists and experts in the 1960s believed that with the advent of highly effective vaccines for many childhood diseases and an increasing number of antibiotics, the danger of infectious diseases – and perhaps, with it, the need for infectious disease specialists — was quickly disappearing.¹ Despite my passion for my field, 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 defense and infectious diseases.

When I was a few years out of fellowship, I was somewhat taken aback when Dr. Robert Petersdorf, an icon in the field of infectious diseases, published a provocative article in Magazine suggesting that infectious disease as a subspecialty of internal medicine is fading into oblivion.² In an article titled “The Physician’s Dime,” he wrote regarding the number of young physicians entering training in the various subspecialties of internal medicine, “Even with my great personal devotion to infectious diseases, I cannot imagine the need for 309 more infectious diseases. experts unless they spend their time cultivating each other.”

Of course, we all tend to be part of a dynamic field. Was my selected field static now? dr. Petersdorf (who would become my friend and part-time mentor as we and others edited together Harrison’s Principles of Internal Medicine) gave voice to a common view that lacked full appreciation of the truly dynamic nature of infectious diseases, particularly with regard to the potential for emerging and re-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 influenza pandemic of 1918, as well as the recent influenza pandemics of 1957 and 1968. However, the emergence of a truly new infectious disease that could dramatically affect to society was still a purely hypothetical concept.

Everything changed in the summer of 1981 with the recognition of the first cases of what would become known as AIDS. The global impact of this disease is incredible: since the beginning of the pandemic, more than 84 million people have been infected with HIV, the virus that causes AIDS, of whom 40 million have died. In 2021 alone, 650,000 people died from AIDS-related conditions, and 1.5 million were newly infected. Today, more than 38 million people are living with HIV.

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

If there is any upside to the emergence of HIV/AIDS, it is that the disease has sharply increased interest in infectious diseases among young people entering the medical field. Indeed, with the advent of HIV/AIDS, we desperately needed those 309 infectious disease interns that Dr. Petersdorf was concerned about—and more. To his credit, years after his article was published, Dr. Petersdorf readily admitted that he did not fully understand the potential impact of newly emerging infections and became something of a cheerleader for young doctors to pursue careers in infectious diseases, especially HIV/AIDS practice. and research.

Selected significant events in the emergence of infectious diseases leading up to and during the author’s four decades as director of NIAID.

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

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

The devastation caused globally by Covid-19 is truly historic and highlights the overall lack of public health preparedness worldwide for an outbreak of this magnitude. One highly successful element of the response to Covid-19, however, has been the rapid development—enabled by years of investment in basic and applied research—of highly customizable vaccine platforms such as mRNA (among others) and the use of structural biology tools to design vaccine immunogens. The unprecedented speed with which safe and highly effective vaccines against Covid-19 have been developed, proven effective and distributed has resulted in millions of lives being saved.³ Over the years, many subspecialties of medicine have benefited greatly from astonishing technological advances. The same can now be said for the field of infectious diseases, especially with the tools we now have to respond to emerging infectious diseases, such as rapid and high-throughput sequencing of viral genomes; development of fast, highly specific multiplex diagnostics; and the use of structure-based immunogenic design in combination with novel vaccine platforms.⁴

If anyone doubted the dynamic nature of infectious diseases and, more broadly, the discipline of infectious diseases, our experience during the four decades since the recognition of AIDS should have completely dispelled such skepticism. Today, there is no reason to believe that the risk of new infections will decrease, because their underlying causes are present and most likely increasing. The appearance of new infections and the reappearance of old ones are largely the result of human interaction with nature and encroachment on it. As human societies expand in a progressively interconnected world and the interface between humans and animals is disrupted, opportunities are created, often aided by climate change, for unstable infectious agents to emerge, species to jump, and in some cases to adapt to spread among humans.⁵

The inescapable conclusion of my reflections on the evolution of the infectious disease field is that the experts of many years ago were incorrect and that the discipline is certainly not static; it is truly dynamic. With the obvious need to continue improving our capabilities to deal with established infectious diseases such as malaria and tuberculosis, among others, it is now clear that emerging infectious diseases are indeed an ongoing challenge. As one of my favorite experts, Yogi Berra, once said, “It ain’t over until it’s over.” It is clear that we can now extend that axiom: when it comes to emerging infectious diseases, it’s never over. As specialists in infectious diseases, we must be constantly ready and able to respond to the constant challenge.