The doctor was puzzled. His patient had ordinary symptoms that many infections could cause – fever, sweating, swollen lymph nodes, and a rash. But the usual tests yielded no answers. And the usual medications didn’t make him better.
Concerned about his worsening condition and the lack of a diagnosis, Dr. Benjamin Davis admitted his patient to Massachusetts General Hospital, where a team led by Dr. Nesli Basgoz, an infectious disease specialist, took over his care.
Now he was Basgoz’s puzzle to solve.
What happened next would challenge the team’s diagnostic skills and test two decades of preparations for the spread of new and exotic diseases around the globe, diseases like COVID-19.
Basgoz, who is Mass. General’s associate chief and clinical director of the Infectious Disease Division, met the patient the day he was admitted, May 12.
She was troubled that a shot of penicillin and antiviral pills had failed to alleviate his symptoms while he was an outpatient. What could he have?
Infectious disease specialists, Basgoz explains, are actually generalists in the sense that they must understand the whole body and think broadly about what can go wrong. An infection can affect any organ and it can take many forms – viruses, bacteria, fungi, parasites. Complicating matters, the immune system can act in ways that mimic an infection.
“The detective work really starts with listening very carefully to what people say and letting them tell their stories,” Basgoz said.
Those stories include the many ways a patient might have been exposed to an infectious agent. Does their dog lick their face? Do they eat raw seafood? Where have they traveled?
Now, this puzzling new patient told her that he had traveled to Canada and very rapidly became sick after his return. And he reported that he has sex with men.
His illness had many features of sexually transmitted infections, and they were the top suspect. But the team had to consider other possibilities. Taking blood and skin samples, Basgoz tested for common viral infections, including chickenpox and other herpes viruses. She considered an allergic reaction or an immune disorder – but this illness was progressing like an infection.
The tests continued to come back negative. The team of doctors, nurses, trainees, and microbiologists put their heads together. They re-did tests that had been done, just to make sure. And they gave the patient intravenous versions of the drugs he had taken as an outpatient, in the hope they would be more effective that way. They weren’t.
All the most likely hypotheses were eliminated. What else could it be?
Basgoz contacted the Boston Public Health Commission and the state Department of Public Health to see if they’d had reports of similar illnesses. They had not.
The patient, meanwhile, wasn’t getting worse. But he wasn’t getting better.
After a few days, Basgoz noticed a telling change. The patient’s rash consisted of fluid-filled blisters on parts of his body, including his scalp, palms, and soles. But now some of those blisters had a dent in the center known as umbilication (because the blister resembles a navel). His rash looked like smallpox. Basgoz had never seen smallpox, but recognized it from her training.
Still, the patient couldn’t possibly have smallpox, because the virus has been eradicated from the planet. And he wasn’t nearly as sick as a smallpox patient would be.
Basgoz knew there were related pox viruses – but these are endemic to Africa. They had rarely been seen in the United States — and only in people who had traveled to Africa or had come in contact with infected animals imported from Africa. This man had done neither.
The doctor woke very early the next morning, May 17, thinking about the patient. She went to her computer and started searching for pox viruses around the world.
Soon, she came across an advisory issued just the previous day by the United Kingdom, describing four new cases of monkeypox, a virus found chiefly in central and western African countries. Health authorities in Britain were concerned because the infected men had not traveled to Africa, suggesting undetected local transmission. And they identified as gay, bisexual, or as men who have sex with men.
That’s when a rarely seen illness came onto the diagnostic radar. It was one of those “aha moments,” Basgoz said.
Around 5 a.m., she sent an e-mail to Dr. Erica Shenoy, associate chief of the Infection Control Unit, asking her to read the UK report and give her a call. The two conferred before 6 and within two hours they were on a conference call with state health officials: Dr. Catherine Brown, state epidemiologist; Dr. Lawrence Madoff, medical director of the Bureau of Infectious Disease and Laboratory Sciences; laboratory officials, and others at the Department of Public Health.
This process – the sharing of disease information internationally, the swift access to public health authorities locally, the openness to the possibility of off-the-beaten path diseases – results from preparations that started when a new illness, severe acute respiratory syndrome (the first SARS), spread from China to four countries in 2002, Shenoy said. These preparations accelerated when an Ebola outbreak in West Africa sparked worries (but little illness) in the United States in 2014, and came into play with the arrival of SARS-Cov-2, the virus that causes COVID-19, in 2020.
These systems “would have been in place had COVID-19 not happened,” Shenoy said. “But COVID required strengthening of these networks and responses.”
So by the time monkeypox arrived at Mass. General this month, the system was poised for action.
A sample from the patient’s blisters was sent to the state laboratories for testing.
Meanwhile, the patient was moved into the hospital’s Regional Emerging Special Pathogens Treatment Center, one of 10 such facilities around the country supported by the US Department of Health and Human Services. There, negative air pressure would prevent any germs from escaping, and the staff is specially trained and equipped to avoid infection.
By late Tuesday, May 17, the state labs had results: The patient was infected with a category of viruses that could include monkeypox. Further testing at the CDC would be needed to narrow the results, and by the next afternoon the CDC had confirmed monkeypox – the first case in the United States in this year’s outbreak.
“The state and the CDC were incredibly responsive and the work was done with astonishing rapidity,” Basgoz said. “This was a very big success story.”
Since then, other monkeypox cases have been identified in the United States, for a total of 12 as of late Saturday, as well as about 300 confirmed and suspected cases in 19 other countries, often involving gay men and people who have not traveled to Africa.
The recent outbreaks outside of Africa happened to have occurred in networks of men who have sex with men, but “no one community is biologically more at risk than any other,” said a statement from the Infectious Diseases Society of America.
Unlike COVID-19, monkeypox doesn’t spread easily. Transmission occurs through contact with bodily fluids, respiratory droplets, monkeypox sores, or items like bedding or clothes that have been contaminated with the virus.
Most people recover on their own after two to four weeks. The strain that infected the Massachusetts man tends to be mild.
And indeed, he gradually got better. When he was deemed improved and no longer infectious on May 20, he left the hospital.