Plague of Athens: Another Medical Mystery Solved at University of Maryland

For immediate release: January 01, 1999

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Another medical mystery -- the Plague of Athens, which contributed to the end of the Golden Age of Greece -- may have been solved at the fifth annual medical conference dedicated to notorious case histories of the past.

It was probably typhus fever that killed the Greeks and their military and political leader, Pericles, according to "detectives" David Durack, M.B., D.Phil., and Robert Littman, M.Litt. Ph.D.

Each year since 1995, the University of Maryland School of Medicine and the Veterans Affairs Maryland Health Care System have held a special historical "clinicopathologic conference," an exercise in which the history of an unnamed patient's illness is presented to an experienced clinician for discussion in an academic setting. This method teaches medical students and residents how experienced clinicians would approach a difficult or challenging case.

"We present an unusual modern case on a weekly basis, but once a year we stray from our modern lives and discuss a historical figure," said Philip A. Mackowiak, M.D., professor and vice chair of medicine at the University of Maryland School of Medicine and director of medical care at the VA Maryland Health Care System. "Over the past four years we have discussed the deaths of Edgar Allan Poe, Alexander the Great, and Ludwig van Beethoven, as well as the mental health of General George A. Custer." This year, the historical figure was Pericles, the military and political leader of the Golden Age of Athens.

For the first time, the conference was broadcast over the World Wide Web, with the help of Condor Technology Solutions, Inc. and SOBO Video Productions, Inc., as an interactive forum for hundreds of medical investigators around the world. It was broadcast from the School of Medicine's Davidge Hall, the oldest building in the United States continuously used for medical education, dating to 1812.

Dr. Durack is consulting professor of medicine at Duke University, where he had been chief of the Division of Infectious Diseases before becoming vice president, medical affairs at Becton Dickinson Microbiology Systems. Dr. Littman is Professor of Classical Languages at the University of Hawaii, Manoa. His expertise is in ancient medicine and the social and political history of Athens.

Both scholars doubt previous theories that the Plague of Athens was caused by ebola, bubonic plague, dengue fever, influenza or measles because the symptoms described in ancient historical records do not match those diseases. Despite evidence that it was typhus fever spread either by lice or by air, Dr. Durack and Dr. Littman do not rule out the possibility the Plague of Athens was caused by something else.

"Epidemic typhus fever is the best explanation," said Dr. Durack. "It hits hardest in times of war and privation, it has about 20 percent mortality, it kills the victim after about seven days, and it sometimes causes a striking complication: gangrene of the tips of the fingers and toes. The Plague of Athens had all these features."

Dr. Durack explains: "The Plague of Athens is a medical and historical classic, which has fascinated doctors and historians for centuries. Even if we can never be absolutely sure what caused the plague, the story is still relevant today because we continue to experience the outbreak of new emerging infectious diseases. The Plague of Athens can give us insights on how to respond to AIDS, Legionnaire's Disease, drug-resistant organisms, toxic shock, hantavirus infections and other emerging diseases."

Dr. Littman elaborates: "Plagues are a recurring phenomenon in human history and they are something that is a constant fear of mankind ? being struck by an unknown disease. This plague was of tremendous importance because it signaled the downfall of the Golden Age of Athens, caused the death of Pericles and 25 percent of the population, weakened Athens at the beginning of its 27-year war with Sparta and became the first medical outbreak so thoroughly recorded by historians."

"This kind of medical detective work on famous cases is interesting and even fun, yet it is no more important than the kind of intensive scrutiny that goes on every day for every patient at an academic medical center like Maryland," said R. Michael Benitez, M.D., assistant professor of cardiology and cofounder with Dr. Mackowiak of the event.

Here are the facts of the case given to Dr. Durack and Dr. Littman for their diagnosis:

A 65 year old man is seen because of fever, headache, sore throat and vomiting. He had been in excellent health until approximately one week earlier when he noted a sudden onset of a headache, ocular erythema and halitosis. On the third day of his illness, he began sneezing and coughing, and noted bilateral pleuritic chest pain. On the sixth day of his illness, the patient began projectile vomiting productive of dark bilious fluid.

At this time, he complained of fever so intense that he would not allow himself to be covered with even the lightest clothing. He also complained repeatedly of insatiable thirst. Although he drank copious amounts of water, he obtained little relief from his thirst, at least in part, because of persistent vomiting. The patient has had no prior serious illnesses. He drinks wine in moderation and does not use tobacco. He is taking no medications and has no known allergies.

The patient is a resident of Athens, Greece, where he has lived his entire life, except for short excursions throughout the eastern Mediterranean. His early years were spent in the military where he rose to the rank of commanding general of the armed forces. In recent years he has devoted himself to politics.

The patient is married. Both of his children by this marriage, sons aged 30 and 25 years, have died recently of illnesses similar to the patient's. Another son (by his mistress), aged 10 years, is alive and well. The patient's father died in battle at 47 years of age. The condition of his mother is unknown. He has a brother and a sister. His sister recently died in her mid-60s of an illness similar to the patient's. The condition of his brother, who is also approximately 60 years of age, is unknown.

An illness similar to the patient's has afflicted large numbers of his fellow residents of Athens. The epidemic began roughly a year prior to the onset of the patient's illness, one year after the outbreak of hostilities with a neighboring city state. Interestingly, although enemy forces have besieged Athens continuously during this period, their troops appear not to have been affected by the illness raging within the city proper. Refugees entering the city from the surrounding countryside, however, have been quickly affected.

The disease attacks all age groups and socioeconomic strata, with the highest attack rates occurring among physicians and other care givers. The illness, which is reported to have originated in sub Saharan Africa, had not been seen in Athens prior to the current epidemic. It is believed to have entered Athens through Piraeus, the city's port. In addition to Athens, much of the eastern Mediterranean is now afflicted with the disease.

The current epidemic has waxed and waned since its appearance without apparent seasonality. Of those who have contracted the disease, approximately a quarter have died. Persons recovering exhibit immunity to further attacks of the disease. Unfortunately, such persons are sometimes permanently disabled by residua of the disease, such as encephalopathy, blindness, and/or distal necrosis of extremities. Although there have been reports of dogs and birds dying after feeding on the corpses of those succumbing to the illness, these reports are unsubstantiated.

The patient is alert and oriented and extremely weak. He appears well nourished, although moderately dehydrated. The pulse is rapid and thready. Respirations are deep. The patient complains of an intense fever, and yet his skin is moist and normothermic to the touch. The head is dolichocephalic. The conjunctivae are injected. The oropharynx is red, inflamed and covered with clotted blood. The breath is fetid. Diffuse rales, ronchi and wheezes are heard throughout both the lungs. There is a generalized, erythematous, maculopapular rash.

Supportive therapy consisting of cool baths is administered without relief. On the 9th day of illness, the patient develops profuse diarrhea, which unfortunately, is not examined for blood or inflammatory cells. Progressive dehydration and debilitation ensues. Cardiovascular collapse occurs on the 11th day of illness, and the patient dies.

More information on the conference and previous cases is available at www.va-umd.org

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