Page:Interim Staff Report on Investigation into Risky MPXV Experiment at the National Institute of Allergy and Infectious Diseases.pdf/52

As prepared

Steven Holland, MD

My name is Dr. Steven Holland. I am an infectious disease physician and serve as the Director of the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases (NIAID). I received my MD from Johns Hopkins in 1983 and stayed there to serve as a resident in internal medicine before becoming a chief resident and then a fellow in infectious disease. I came to the NIAID in 1989 and have remained here ever since. I have been Director of the Division of Intramural Research since 2016. Previously I served as Chief of the Laboratory of Clinical Infectious Diseases. The intramural program of NIAID consists of about 130 scientists and about 1500 total employees. Our portfolio includes basic and clinical investigation into viral, fungal, and bacterial diseases as well as the underlying immunologic defects that make these diseases severe. We are particularly lucky to have Dr. Bernard Moss as one of our most prestigious tenured faculty. Dr. Moss has been the preeminent pox virologist in the world for decades and his work has materially increased our understanding of pox viruses in general and mpox in particular. My goal today is to tell you about some of our work around mpox.

Just last year, in 2022, more than 86,000 people in more than 100 countries were infected with mpox. This constituted a true public health emergency of international concern. This was not entirely new, the incidence of mpox has been rising over the last 50 years in Africa and infected travelers have been identified in many countries. Mpox was first discovered in captive monkeys in 1958. Human infections derived from animals were identified first in the 1970s. Mpox ashas [sic] an incubation period of 5 to 21 days and is evidenced by fever, rash, and lymph node swelling. Although it looks a lot like smallpox, it is not: the mortality from mpox in Africa ranges from 4 to 10%, while that of smallpox is about 30%. Most cases of mpox have been in the Democratic Republic of the Congo. Mpox is less severe in West Africa than Central Africa but the West African incidence has been increasing. Importantly, this is a disease that can have outbreaks. After 39 years without any cases there was an outbreak in Nigeria in 2017, affecting 2635 people. Although the animal source of mpox is still somewhat unclear, it is apparent that many different rodents, primates and other animals can harbor and transmit it.

Let me spend a moment on nomenclature. There are different strains of mpox that are typically referred to as clades. Currently three clades are identified: clade I is in Central Africa, whereas clades IIa and IIb are in West Africa. Only about 5% of the genomes of clades I and II differ, while the differences between clades IIa and IIb are even less. Clade IIb has a particular activity (APOBEC3B cytosine deaminase activity) that may be relevant to human transmission.

While the occurrence of mpox outside of Africa has been uncommon until recently, the outbreak beginning in 2022 has been dramatic and severe. Luckily, the mortality from this outbreak has been relatively low except in those with underlying immune deficiencies. Sequencing of these viruses has indicated that they arise from clade IIb and likely arose from Nigeria.

We are lucky to have Dr. Bernard Moss as a member of our institute. Dr. Moss has devoted his career to studying pox viruses and has pioneered this area. In fact, it was his brilliant insight to