It Ain’t Over Till It’s Over…but It’s Never Over — Emerging and Reemerging Infectious Diseases

As I prepare to step down from my dual position at the National Institute of Allergy and Infectious Diseases (NIAID), where I have been a physician-scientist for 54 years and director for 38, some reflection is inevitable. When I look back on my career, what stands out most is the dramatic evolution of the field of infectious diseases and the changing perception of the importance and relevance of the field by both the academic community and the public.

I completed my residency training in internal medicine in 1968 and decided to take a 3-year combined fellowship in infectious disease and clinical immunology at NIAID. Unbeknownst to me as a young physician, some academics and scholars in the 1960s opined that with the advent of highly effective vaccines for many childhood diseases and the ever-growing array of antibiotics, the threat of — and perhaps, necessity — infectious disease. For infectious-pathologists – was disappearing fast.1 Despite my passion for the field I was entering, I might have reconsidered my choice of a subspecialty if I had known about this skepticism about the future of the discipline. Of course, at the time, malaria, tuberculosis and other diseases were killing millions of people every year in low- and middle-income countries. Oblivious to this inherent contradiction, I happily pursued my clinical and research interests in host defense and infectious diseases.

When I was several years into my fellowship, I was somewhat surprised when Dr. Robert Petersdorff, an icon in the field of infectious diseases, published a provocative article in the journal. Journal Infectious diseases as a subspecialty of internal medicine suggests fading into oblivion.2 In an article titled “The Physician’s Dilemma,” he wrote of 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 more 309 infectious-disease specialists. Unless they spend their time in each other’s culture.”

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Of course, we all aspire to be a part of a dynamic field. Was my selected field fixed now? Dr. Petersdorff (who would become my friend and part-time mentor as we and others co-edited Harrison’s Principles of Internal Medicine) voiced a general view that lacked a full understanding of the truly dynamic nature of infectious diseases, particularly regarding the potential for newly emerging and resurgent infections. In the 1960s and 1970s, most physicians were aware of the possibility of a pandemic in light of the known precedent of the historic influenza pandemic of 1918, as well as the more recent influenza pandemics of 1957 and 1968. New infectious diseases that could dramatically affect society were still a purely speculative idea.

All that changed in the summer of 1981 with the recognition of the first cases of what would become known as AIDS. The global impact of the disease is staggering: since the start of the epidemic, 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 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 yet to be 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 manageable chronic disease associated with an almost normal life expectancy. Due to the lack of global equity in accessibility to these life-saving drugs, HIV/AIDS continues, 41 years after it was first recognized, to exact a terrible toll in morbidity and mortality.

If there is a silver lining to the emergence of HIV/AIDS, it is that the disease has sharply increased interest in infectious diseases among young people entering the field of medicine. Indeed, with the rise of HIV/AIDS, we desperately needed those 309 infectious-disease trainees about whom Dr. Petersdorff was concerned — and more. To his credit, years after his article was published, Dr. Petersdorff readily admitted that he had not fully grasped the potential impact of emerging infections and became a cheerleader for young physicians pursuing careers in infectious disease and HIV/AIDS practice in particular. and research.

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Selected landmark events of the infectious-disease outbreak up to and including the author’s four-decade tenure as NIAID director.

DRC stands for Democratic Republic of Congo, MERS Middle East Respiratory Syndrome, SARS severe acute respiratory syndrome and XDR extensively drug-resistant.

Of course, the threat and reality of emerging infections did not stop with HIV/AIDS. During my tenure as NIAID director, we were challenged with the emergence or resurgence of numerous infectious diseases with varying degrees of regional or global impact (see timeline) included the first known human cases of H5N1 and H7N9 influenza; The first pandemic of the 21st century (in 2009) was caused by H1N1 influenza; multiple outbreaks of Ebola in Africa; Zika in America; severe acute respiratory syndrome (SARS) caused by a novel coronavirus; Middle East Respiratory Syndrome (MERS) is caused by another emerging coronavirus; And of course Covid-19, the loudest wake-up call in over a century to our vulnerability to an emerging infectious disease outbreak.

The devastation that Covid-19 has wreaked globally is truly historic and highlights the overall lack of global public health preparedness for an outbreak of this magnitude. A highly successful component of the response to Covid-19, however, was the rapid development — through 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. Design vaccine immunogens. The unprecedented speed with which a safe and highly effective Covid-19 vaccine has been developed, proven effective and distributed has saved millions of lives.3 Over the years, many subspecialties of medicine have greatly benefited from breathtaking technological advances. The same can now be said for infectious diseases, especially with the tools we now have for responding to emerging infectious diseases, such as rapid and high-throughput sequencing of viral genomes; development of rapid, highly specific multiplex diagnostics; and the use of structure-based immunogen design combined with novel platforms for vaccines.4

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If one doubts the dynamic nature of infectious diseases and, by extension, the chain of infectious diseases, Our experience in the four decades since the recognition of AIDS has completely dispelled such doubts. Today, there is no reason to believe that the threat of emerging infections will diminish, since their underlying causes are present and likely increasing. The emergence of new infections and the resurgence of old ones are largely the result of human interaction and encroachment on nature. As human societies expand into an increasingly interconnected world and human-animal interfaces are disrupted, opportunities arise for the emergence of unstable infectious agents, species jumps, and in some cases adaptation to spread between humans, often aided by climate change.5

An inescapable conclusion of my reflections on the evolution of the field of infectious diseases is that the scholars of a few years ago were wrong and the discipline is certainly not static; It’s really dynamic. In addition to the obvious need to continue improving our capacity to deal with established infectious diseases such as malaria and tuberculosis, it is now clear that emerging infectious diseases are indeed a perennial challenge. One of my favorite pundits, Yogi Berra, once said, “It ain’t over till it’s over.” Obviously, we can now extend that axiom: when it comes to emerging infectious diseases, It doesn’t end. As infectious-pathologists, we must be perpetually prepared and able to respond to perpetual challenges.

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