CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Rabies transmission through solid organ transplantation, 2013. Courtesy Sherif Zaki, MD, PhD.
This syndrome continues to pop up. An outbreak occurred in Cambodia in 2012. “We still see two or three kids on the West Coast of the U.S. dying of this disease each year,” he added.
In 1998–1999 an outbreak of severe encephalitis arose in Singapore and Malaysia among those who had close contact with pigs, particularly farmers. Initially it was suspected to be due to Japanese encephalitis virus. However, electron microscopy in Dr. Zaki’s laboratory revealed the presence of paramyxovirus nucleocapsids. Further investigation showed it was a new encephalitis virus cross-reacting with the recently identified Hendra virus. The new agent was named Nipah virus. (Bats were the source.) About 1 million pigs had to be culled to break the transmission cycle.
When SARS was recognized, Cynthia Goldsmith, MS, in Dr. Zaki’s laboratory was the first to visualize the responsible coronavirus. “She was the first person to identify this virus as the cause of the outbreak,” Dr. Zaki said. The coronavirus result was quickly confirmed at the CDC by a number of other techniques, including IHC, serology, and molecular methods.
In the investigation of Middle East Respiratory Syndrome, or MERS, important information was obtained from a single autopsy of the first patient identified, in Abu Dhabi. While initial reports had characterized this patient as healthy, Dr. Zaki said the autopsy showed he was “far from healthy.” He had bad kidneys, heart disease, liver disease, and atheromas. Getting permission for an autopsy in that part of the world is particularly difficult, he said, and only considerable pressure on the government made it possible. There was a clustering of cases, which raised concern that the virus may have been transmitted by person-to-person contact, inciting a high level of fear. While the autopsy could not prove or refute this possibility (it turned out to be unfounded), it did show that healthy people are not at high risk, a suggestion borne out in subsequent cases. This remains the only autopsy done on a MERS patient.
Randall Hayden, MD, director of clinical and molecular microbiology at St. Jude Children’s Research Hospital, was a moderator for the symposium session in which Dr. Zaki spoke. Two points stand out, he said in a recent interview. “One was the role of the pathologist as one of the first lines in terms of recognizing there is something unusual and knowing how to apply appropriate methods for diagnosis or to forward specimens to someone like Dr. Zaki who has a wealth of stains and immunohistochemical techniques in his laboratory.”
The second: the availability of newer technologies such as next-generation sequencing that can complement existing technologies like immunohistochemistry “or clues from light microscopy or culture or electron microscopy.
“All of that is in the context that we are seeing more frequent emergence of new infections, so NGS will take on increasing significance for practicing pathologists and the health care system,” Dr. Hayden says.
West Nile virus (left, histopath; right, IHC). Courtesy Sherif Zaki, MD, PhD.
Of the transplant-related clusters, Dr. Hayden says: “We [at St. Jude] see patients from all over the world. We get a donor history asking whether they have been in situations where they could have been exposed. The relevance of a donor history is probably universal, but more pointed for places with immunocompromised patients and those who come from a variety of social settings.”
Vigilance—which Dr. Zaki defines as “expect the unexpected”—is the watchword to identifying and solving mysterious outbreaks, he says. “The key to . . . [detecting] a lot of these outbreaks is not just one person or one group but a combination or team effort,” he told the assembled infectious disease experts. An alert clinician, or veterinarian or pathologist, may recognize something out of the ordinary. “We all work together in these outbreaks.”
Even more important given the zoonotic linkages with many of the diseases he spoke about—hantavirus, Nipah virus, and filoviruses (the viral hemorrhagic fever agents Ebola and Marburg). It’s the One Health concept, an initiative that arose around 1999 during the outbreak of West Nile virus, Dr. Zaki says. Vital information was available from deaths of crows, but it was slow in coming to the attention of the medical community. “It became apparent that the veterinary community and the medical community were not communicating well,” he says. A government report issued in 2003 stressed the need for public health workers to collaborate with clinicians, veterinarians, and scientists in academia.
While scientists in the CDC’s Infectious Diseases Pathology Branch are often in the middle of the investigation of such viral outbreaks, there is also a role for pathologists in the community. “My message is that people in the medical community should always be aware,” Dr. Zaki says. “Sometimes you see very unusual infections associated with transplants. Everyone needs to be aware of those and know how to screen for them.” Laboratories in hospitals that perform transplants have assays for the more common viral pathogens, such as herpesvirus and adenovirus. For uncommon pathogens, one might look in the literature for information about transplant-associated infections, such as rabies, which can be diagnosed by a neuropathology exam and confirmed by special stains. “What is most important,” Dr. Zaki says, “when you become aware of an unexplained or unusual infection, is to refer such cases to a place such as CDC. The bottom line is that some diagnostic tests are only available at CDC or other specialized laboratories.”
But there and elsewhere it’s critical to remember, he says, “the frontline role of pathology” in diagnosing unexplained deaths, recognizing emerging diseases, and guiding epidemiologic investigations.
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William Check is a writer in Ft. Lauderdale, Fla.