In the year 430 BCE, at the peak of the Peloponnesian War between Athenian and Spartan coalitions, a plague of devastating proportions, possibly originating on the African continent, spread across the Greek-speaking world and wreaked its greatest devastation on the populace of the besieged and crowded city of Athens. Although physicians of his time never identified the disease or figured out how to combat it, the Athenian general and historiographer Thucydides painstakingly recorded the signs, symptoms, and course of the illness, hoping that future generations of physicians would succeed where those of his time did not. Thucydides' hopes in this regard have, alas, yet to find fruit. Many scholars and scientists have accepted the challenge and attempted to decode the historian's account, but no one has been able with any certitude to match that description to a known disease, one that would fit all the salient features of the plague enumerated by Thucydides. Among an assortment of possible infectious etiologies that have been proposed thus far are smallpox, chicken pox, streptococcal infections, and Ebola virus, to name just a few. Each of us has our favorite, usually picked by focusing on a particular combination of the signs and symptoms described and the likelihood that such disease could account for the rapid spread and high degree of morbidity and mortality that Thucydides witnessed among the Athenian population.
After informing us first that there was general agreement at the time that the year in which the plague struck had been otherwise unusually free of other types of diseases, Thucydides notes that, if an individual did happen to contract some other illness, inevitably this disease, too, would evolve into the plague. Employing jargon familiar to us from other medical texts, including those of the Hippocratic authors, he describes the course of the plague with an attention to detail so vivid as to lend credence to his claim to have seen and experienced the illness first-hand. It began, Thucydides' description reveals, with a feverish feeling in the head, inflammation of the eyes, throat, and tongue, and progressed in a generally cephalocaudal direction to involve the lungs, the intestines, and essentially every known bodily system, including the skin, which erupted in a vesicular or pustular rash (that has made many suspect that smallpox is still the most likely candidate for the identity of the plague). Anywhere during this process the affected individual might either succumb (particularly during the debilitating diarrheal phase of the illness) or potentially—like Thucydides himself—recover.
How does the Thucydidean account of the Athenian plague teach us about our recent challenge with pandemic influenza? H1N1 presents a diagnostic dilemma: Here again is a disease with various combinations of signs and symptoms (fever, headache, rhinorrhea, cough, pharyngitis, myalgias, dizziness, vomiting, diarrhea) which are common to many other viral and bacterial illnesses and for which no readily available, rapid, accurate diagnostic test exists. Teasing out the true H1N1 cases from the look-alikes, especially in mild to moderate presentations of the disease, tests the clinical judgment of even the most observant and meticulous physician. Particularly at the peak of a pandemic wave, distinguishing a disease such as H1N1 from other entities is a tremendous challenge for practitioners on the front lines, who are inundated with patients demonstrating a constellation of the aforementioned symptoms. Indeed, the higher the prevalence and greater the potential severity of an epidemic or pandemic disease, the more likely it is to cause the illusion that there is a dearth of other seasonal illnesses around and that these other diseases, when present, seem to act as precursors to or literally “turn into” this new, more serious illness.
This was certainly the situation faced by Athenian physicians (and by Thucydides himself) in 430 BCE. The reason we have so much trouble solving the riddle of the Athenian plague is not that too little information is contained in Thucydides' account but, rather, that there is too much detail! The common wisdom to which he alludes—that the Athenian landscape was atypically free of other diseases that year—is doubtful; the incidence of other seasonal and common illnesses had likely not decreased, but these illnesses were obscured and in a way subsumed by the more dangerous threat that had descended on the Athenian polis. Thucydides' observations are so detailed that he unwittingly conflates features of the plague with those of other illnesses, since, as we observed at the peak of this recent wave of H1N1, everything starts to look as though it's part of the same disease process. This is the major challenge for the thoughtful physician on the front lines today. Faced with a pandemic disease for which there is no easy route to diagnosis, the physician must strike a delicate balance. He or she must craft inclusion criteria, which are sensitive enough to encompass as many cases as are likely to be H1N1 yet specific enough to avoid drawing in too many of the mimicking disorders, ever vigilant as well of defining cases with such narrow criteria that too many true cases of H1N1 evade detection. This is the real “art” of medicine, and Thucydides reminds us that we are in good company as we struggle to practice it.
Bruce H. Kraut, MD, PhD