Sherif Zaki, who was the chief pathologist at the Centers for Disease Control and Prevention and helped diagnose previously unknown infectious diseases around the world, including influenza and other viral and bacterial illnesses, died Nov. 21 at an Atlanta hospital. He was 65.

He had complications from an accidental fall at home, said his wife, Nadia Zaki.

Dr. Zaki, who was both a physician and a PhD scientist, combined clinical know-how with the expertise of a laboratory investigator as he sought to solve a host of medical mysteries. As the founder and chief of the CDC’s Infectious Disease Pathology Branch, he was at the forefront of efforts to identify numerous deadly diseases, including the hantavirus, West Nile virus, the Ebola and Zika viruses, severe acute respiratory syndrome (SARS) and the current global pandemic of covid-19.

“Dr. Zaki was critical in diagnosing unexplained illness and outbreaks that allowed CDC and public health to respond more quickly and save lives,” CDC Director Rochelle Walensky said in a statement.

Frederick A. Murphy, a former CDC scientist who discovered the Ebola virus, once called Dr. Zaki “a national treasure … absolutely the best of his kind.”

On one level, Dr. Zaki practiced the medical specialty of pathology the way it has been done for more than a century: by examining specimens under a microscope, searching for clues about the origins of a disease that led to a patient’s unexplained death.

“We go into the basic[s] of how a disease happens, the mechanism,” he said in a 2016 interview with Stat, a medical and health news website. “Putting pieces together. Solving puzzles. Looking at the unknown and trying to figure out what it is.”

When Dr. Zaki started working at the CDC in 1988, some people at the agency were skeptical that the agency needed a pathology department. But he soon developed a formidable laboratory, with about 40 scientists equipped with powerful electron microscopes, and devised increasingly effective techniques to trace the course of disease inside the body.

Through the use of immunohistochemistry, a method of staining microscopic cells to identify foreign pathogens that can cause illness, Dr. Zaki made advances in identifying little-known or mutating diseases.

“Time and time again, he and his team used this fundamental technique to make diagnoses that couldn’t be made anywhere else in the world,” Chris Paddock, a CDC pathologist who worked in Dr. Zaki’s laboratory for 11 years, said in an interview. “He realized this is an important way to diagnose diseases and to understand outbreaks.”

Dr. Zaki and his staff were the first to identify the hantavirus (later called the Sin Nombre virus) that led to the deaths of several people in the Navajo nation in the Southwest in 1993. He helped discover the Zika virus in the brain tissue of babies stricken with the mosquito-borne virus in Brazil, proving that it could be transmitted during pregnancy.

In 2001, Dr. Zaki determined that several Americans who had handled letters containing a white powder had died from anthrax, either through inhalation or by exposure on the skin. Law enforcement called the anthrax letters a bioterrorist attack.

“We get involved in things that are very uncommon,” Paddock said. “We are establishing diagnoses where no one else could. I think that’s where Sherif excelled.”

Dr. Zaki also helped identify the mechanisms that made Ebola and SARS so contagious and lethal.

“I don’t see any reason why it shouldn’t come back,” Dr. Zaki told Smithsonian magazine in 2003, after studying the coronavirus that caused SARS, a respiratory illness that killed hundreds of people worldwide. “We can learn from history. If it happened once, it can happen again.”

For the past 18 months, he and his staff were working overtime on SARS-CoV-2 — the coronavirus that causes covid-19, which has left more than 775,000 Americans dead so far. Among other things, CDC scientists sought to understand the effects of covid-19 on pregnancy and the various ways the disease could be fatal.

“He really was kind of the secret weapon for a lot of what was done at CDC on emerging diseases,” James LeDuc, Dr. Zaki’s onetime colleague, told the Stat website.

“The point is, it didn’t matter what the pathogen was,” LeDuc added. “He was able to use the tools and to partner with one of the experts at CDC or outside CDC and really provide critical information in a very, very timely manner.”

Sherif Ramzy Zaki was born Nov. 24, 1955, in Alexandria, Egypt. He spent the first six years of his life in Chapel Hill, N.C., where his father was attending graduate school.

His father later worked for a United Nations organization, and the family lived at various times in the United States, Europe and the Middle East.

Dr. Zaki attended Egypt’s Alexandria University, from which he received his medical degree in 1978 and a master’s degree in pathology. He did his medical residency in Egypt, then came to United States and eventually became a naturalized U.S. citizen. He received a doctorate in experimental pathology in 1989 from Emory University in Atlanta.

In addition to his work at the CDC, Dr. Zaki taught at Emory, contributed chapters to medical books and was the author or co-author of more than 400 scientific papers. He traveled around the world, helping other pathologists learn his research methods.

At the CDC, he was seen as a quiet mentor who seldom drew attention to his own work. He received the Department of Health and Human Services’ highest honor, the Secretary’s Award for Distinguished Service, nine times.

“There is a tremendous sense of loss at the agency,” Paddock said. “He touched a lot of people.”

Survivors include his wife of 38 years, the former Nadia Abougad of Atlanta; two children; and two sisters.

“There are so many viruses and bacteria we don’t know anything about, that we don’t have tests for,” Dr. Zaki told the New York Times in 2007.

“We think we know everything,” he added, “but we don’t know the tip of the iceberg.”