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 second term 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. When I think back on my career, the most important thing is the 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 do a 3-year joint fellowship in infectious disease and clinical immunology at NIAID. Unbeknownst to me as a young doctor, scholars and certain experts in the 1960s argued that with the advent of highly effective vaccines for many childhood diseases and various antibiotics, the threat of infectious diseases – and perhaps, the need for infectious disease specialists – quickly disappeared .1 Despite my passion for the field I entered, I might have reconsidered my choice of subspecialty if I had known about the 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 every year. Unaware of this contradiction, I am happy to pursue my clinical and research interests in host defense and infectious diseases.

When a few years out of the fellowship, I was a little surprised when Dr. Robert Petersdorf, an icon in the field of infectious diseases, published a provocative article on Journal suggesting that infectious disease as a subspecialty of internal medicine has disappeared.2 In an article titled “The Doctors’ Dilemma,” he wrote about the number of young doctors involved in training in the various subspecialties of internal medicine, “Even with my great personal loyalty to infectious diseases, I cannot help but think of the need for 309 diseases other infectious diseases. experts unless they spend time to nurture.”

Of course, we all want to be a part of this dynamic field. Is the currently selected field static? Dr. Petersdorf (who would become my friend and part-time mentor when we and others coedited Harrison’s Principles of Internal Medicine) gives voice to a common viewpoint that lacks a full appreciation of the dynamic nature of infectious diseases, particularly with regard to the potential for newly emerging and re-emerging infections. In the 1960s and 1970s, most doctors were aware of the possibility of a pandemic, due to the well-known precedent of the influenza pandemic in 1918, as well as the more recent influenza pandemics of 1957 and 1968. the concept is purely hypothetical.

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That all changed in the summer of 1981 with the recognition of the first case of what would become known as AIDS. The global impact of this disease is staggering: since the beginning 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 will die of AIDS, and 1.5 million new people will be infected. Today, more than 38 million people are living with HIV.

Although a safe and effective HIV vaccine has not yet been developed, scientific progress has led to the development of highly effective antiretroviral drugs that transform HIV infection from an almost always fatal disease into a manageable chronic disease associated with an almost normal life expectancy. Due to the lack of global equity in the accessibility of these life-saving medicines, HIV / AIDS continues, causing terrible morbidity and mortality, 41 years after it was first recognized.

If there is some silver lining to the emergence of HIV / AIDS, it is a disease that greatly increases the interest in infectious diseases among young people entering the field of medicine. Indeed, with the emergence of HIV/AIDS, we desperately need 309 infectious disease trainees that Dr. Petersdorf – and others. To his credit, many years after his article was published, Dr. Petersdorf readily admits that he had not appreciated the potential impact of emerging infections and is an advocate for young doctors to pursue careers in infectious diseases and specialize in HIV/AIDS practice. and research.

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Selected Landmark Events in the Emerging Infectious Diseases Up to and During His Four Decades as Director of NIAID.

DRC refers to the Democratic Republic of the Congo, Middle East respiratory syndrome MERS, severe acute respiratory syndrome SARS, and drug-resistant XDR.

Of course, the threat and reality of emerging infections does not stop with HIV/AIDS. During my tenure as director of NIAID, we were challenged with the emergence or re-emergence of infectious diseases with varying degrees of regional or global impact (see timeline). Included among them are the first human cases of H5N1 and H7N9 influenza; the first pandemic of the 21st century (in 2009) caused by H1N1 influenza; several 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 to our vulnerability to emerging infectious disease outbreaks.

The devastation wrought by Covid-19 globally is historic and highlights the overall lack of public health preparedness for an outbreak of this magnitude. However, one of the elements of the very successful response to Covid-19 is the rapid development – enabled by years of investment in basic and applied research – highly adaptable vaccine platforms such as mRNA (among others) and the use of structural biology tools. designing vaccine immunogens. The pace is not over before a safe and highly effective Covid-19 vaccine is developed, proven effective, and distributed resulting in millions of lives being saved.3 Over the years, many subspecialties of medicine have greatly benefited from the amazing advances in technology. The same can now be said about the field of infectious diseases, especially with the tools now available to respond to emerging infectious diseases, such as rapid and high-throughput sequencing of viral genomes; development of rapid and specific multiplex diagnostics; and using structure-based immunogen design combined with novel platforms for vaccines.4

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If anyone doubts the dynamic nature of infectious diseases and, by extension, the discipline of infectious diseases, our experience in the forty years since the recognition of AIDS should have dispelled that skepticism.. Currently, there is no reason to believe that the emerging threat of infection will decrease, because the cause is there and the probability is increasing. The emergence of new infections and the re-emergence of old ones are the result of human interaction with nature. As human societies develop in an 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

The inescapable conclusion of my reflections on the evolution of the field of infectious diseases is that the experts of many years ago were wrong and that the discipline is certainly not static; it’s really dynamic. In addition to the need to continue to improve our ability to deal with established infectious diseases such as malaria and tuberculosis, among others, it is now clear that emerging infectious diseases are an ongoing challenge. As one of my favorite experts, Yogi Berra, once said, “It’s not over until it’s over.” Clearly, we can now go beyond that axiom: when it comes to emerging infectious diseases, it never ends. As infectious disease specialists, we must be constantly prepared and able to respond to ongoing challenges.

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