Posted on 01/21/2006 10:26:35 AM PST by blam
Secret of ancient Athens plague is being unraveled
Kerameikos, Athens’s ancient cemetery, has yielded conclusive evidence as to the nature of the plague that decimated a third of the population of the ancient city and influenced the outcome of the Peloponnesian Wars.
Scientists at Athens University’s School of Dentistry have used molecular biology to help solve the riddle of one of history’s biggest mysteries.
Greek scientists find typhoid after excavating graves
By Dr Manolis Papagrigorakis (1)
Recent findings from a mass grave in the Ancient Cemetery of Kerameikos in central Athens show typhoid fever may have caused the plague of Athens, ending centuries of speculation about what kind of disease killed a third of the city’s population and contributed to the end of its Golden Age.
Examined by a group of Greek scientists coordinated by Dr Manolis Papagrigorakis of Athens University’s School of Dentistry, the findings provide clear evidence that Salmonella enterica serovar Typhi was present in the dental pulp of teeth recovered in remains from the mass grave.
The plague that decimated the population of Athens in 430-426 BC was a deciding factor in the outcome of the Peloponnesian Wars, ending the Golden Age of Pericles and Athens’s predominance in the Mediterranean.
It broke out during the siege of the city by the Spartans in the early summer of 430 BC; after a brief hiatus in 428 BC, the epidemic returned in the winter of 427 BC and lasted until the winter of the following year. It is assumed that one-third of the Athenians, including one-fourth of their army and their charismatic leader, Pericles, perished in the epidemic.
All data pertaining to the disease’s outbreak and its clinical characteristics were until now based on the account by the fifth-century-BC Greek historian Thucydides, who himself fell ill with the plague but recovered. In his famous history of the Peloponnesian Wars, Thucydides gives detailed descriptions that have formed the basis of several hypotheses regarding its nature. However, researchers had never managed to agree on the identity of the plague due to the lack of definite microbiological proof in the absence of paleopathologic evidence. Several pathogens have been putatively implicated in the emergence and spreading of the disease.
In recent decades, molecular biology tools (DNA PCR and sequencing techniques) have made it possible to detect and, furthermore, specifically identify microbial DNA fragments in ancient human skeletal remains, thus making possible the retrospective diagnoses of ancient diseases.
In 1994-1995, under the supervision of archaeologist Effi Baziotopoulou-Valavani for the Fourth Prehistoric and Classical Antiquities Ephorate, excavations of a mass burial pit unearthed in the Ancient Cemetery of Kerameikos in Athens provided the required skeletal material for the investigation of ancient microbial DNA.
The grave yielded the remains of about 150 individuals and were dated, through archaeological site documentation, to around the time of the plague outburst between 430-426 BC. The remains were found piled up in a manner that indicated a hasty burial without the usual care dictated by the respect that ancient Greeks usually showed for the dead.
Dental pulp was the material of choice in this research, as its good vascularization, durability and natural sterility has proven to be an ideal source of ancient DNA, also providing for the recovery of adequate genetic material of specific septicemic microorganisms which after death remain trapped in the dental pulp and become mummified.
Using modern laboratory methods under strict sterile conditions at the molecular neurobiology laboratory at Athens University’s medical school, the research team first found the existence of microbial DNA in the dental pulp. This DNA was then separated and subjected to successive tests to identify which of the possible microbes was linked in the past with the Athens plague.
Teeth from three different skeletons were examined. After six negative results from six candidate microbes, a positive reaction was found for Salomonella enterica serovar Typhi, which is responsible for the appearance of typhoid fever.
The correspondence with the genes examined in the ancient DNA with known sequences of the contemporary form of the microbe was as high as 99 percent.
This evidence allowed for a definite conclusion regarding the microbes found in the teeth of the three bodies from the mass burial pit — the presumed victims of the Athens plague.
Typhoid fever almost certainly played a part in causing the Athens plague, either exclusively or in combination with another — and so far unknown — infection.
Even today, typhoid fever is a major health problem on a global scale. Every year there are about 20 million new cases that lead to about 600,000 deaths in the developing world where overpopulation, inadequate water supplies and hygiene, as well as poor access to health services, allow epidemics to spread with tragic results.
Overcrowding and resultant public health problems — as well as standards of personal hygiene — in the besieged city of Athens in 430 BC as described by Thucydides would have been sufficient to allow the disease to appear and then develop into a deadly epidemic.
The scientifically documented diagnosis of typhoid fever is in accordance with many of the clinical characteristics of the Athens plague as described by Thucydides. The differences in the modern form of the disease from Thucydides’ references pose another challenge for the Greek research team.
Studying the historical aspects of infectious diseases can be a powerful tool for several disciplines to learn from. We believe this report to be of outstanding importance for many scientific fields, since it sheds light on one of the most debated enigmas in medical history. Archaeology, paleontology, history, paleopathology, certain fields of medicine, anthropology and even genetics, molecular biology and studies on evolution are clearly implicated in such matters and can benefit from relevant studies.
The results of this particular study are extremely important as they shed light on one of the greatest mysteries in world history. Also important is the fact that the research was organized, carried out and completed by Greek scientists at Greek research centers, under the aegis of Athens University.
(1) Dr Papagrigorakis is an assistant professor at Athens University’s School of Dentistry.
The other authors of the study, published today in the International Journal of Infectious Diseases, are geneticist Christos Yiapitzakis, orthodontist Philippos Synodinos and archaeologist Effi Baziotopoulou-Valavani.
GGG Ping.
Fascinating!
Cholera? Pretty common under the same conditions that support typhus.
Wow!
I've always felt that as much as people think we're ancient Rome, that Athens is a far better parallel... and that we could one day lose it all the way Athens did, through arrogance and overweening hubris.
Huh?
Well, just a Happy Saturday to you, too! :-)
One of my pet peeves as well. Decimated means 'killed exactly 10 out of exactly 100'.
This is an interesting article but it leaves out one significant piece of information for the reader. That is, how did Thucydides describe the plague and how does that correspond and differ from our current understanding of typhoid fever? Also, what were some of the other theories and, based on what evidence were those theories put forth? Talk about leaving the reader guessing!
And none of these bad guys ever go away....
From the American Heritage Dictionary:
Usage Note: Decimate originally referred to the killing of every tenth person, a punishment used in the Roman army for mutinous legions. Today this meaning is commonly extended to include the killing of any large proportion of a group. Sixty-six percent of the Usage Panel accepts this extension in the sentence The Jewish population of Germany was decimated by the war, even though it is common knowledge that the number of Jews killed was much greater than a tenth of the original population. However, when the meaning is further extended to include large-scale destruction other than killing, as in The supply of fresh produce was decimated by the nuclear accident at Chernobyl, only 26 percent of the Panel accepts the usage.
Obviously, there is some disagreement on the appropriate use of this word.
Thucydides gives a very detailed description of the symptoms, probably accurate since he had it. I can recall reading some time ago, that his description did not match any known disease exactly. I guess, as the article states, the disease could have mutated.
Salmonella Infections
(Salmonelloses)
The 2200 known serotypes of Salmonella may be grouped into those (1) highly adapted to human hosts, (2) adapted to nonhuman hosts, or (3) unadapted to specific hosts. The first group includes S. typhi and S. paratyphi A, B (S. schottmuelleri), and C (S. hirschfeldii), which are pathogenic only in humans and commonly cause enteric fever. The second group causes disease almost exclusively in animals, although two strains within this group, S. dublin and S. choleraesuis, also cause disease in humans. The third group, designated S. enteritidis, includes > 2000 serotypes that cause gastroenteritis and accounts for 85% of all Salmonella infections in the USA.
TYPHOID FEVER
A systemic disease caused by S. typhi and characterized by fever, prostration, abdominal pain, and a rose-colored rash.
Epidemiology and Pathology
About 400 to 500 cases of typhoid fever are reported annually in the USA. Typhoid bacilli are shed in the feces of asymptomatic carriers or in the stool or urine of those with active disease. Inadequate hygiene after defecation may spread S. typhi to communal food or water supplies. In endemic areas where sanitary measures are generally inadequate, S. typhi is transmitted more frequently by water than by food. In developed countries, transmission is chiefly by food that has been contaminated by healthy carriers during preparation. Flies may spread the organism from feces to food. Occasional transmission by direct contact (anal-oral route) may occur in children during play and in adults during sexual practices. Rarely, hospital personnel who have not taken adequate enteric precautions have acquired the disease when changing soiled bedclothes.
The organism enters the body via the GI tract and gains access to the bloodstream via the lymphatic channels. Monocytic inflammation occurs in the ileum and colon, within the lamina propria and Peyer's patches, where local tissue necrosis is common. Ulceration, hemorrhage, and intestinal perforation may result in severe cases.
About 3% of untreated patients shed organisms in their stool for > 1 yr and are referred to as chronic enteric carriers. Some carriers have no history of clinical illness and apparently were asymptomatically infected. Obstructive uropathy related to schistosomiasis may predispose certain typhoid patients to developing a urinary carrier state. Most of the estimated 2000 carriers in the USA are elderly women with chronic biliary disease. Epidemiologic data indicate that typhoid carriers are more likely than the general population to acquire hepatobiliary cancer.
Symptoms and Signs
The incubation period (usually 8 to 14 days) is inversely related to the number of organisms ingested. Onset is usually gradual, with fever, headache, arthralgias, pharyngitis, constipation, anorexia, and abdominal pain and tenderness. Less common symptoms include dysuria, nonproductive cough, and epistaxis.
If no therapy is begun, the temperature rises in steps over 2 to 3 days, remains elevated (usually to 39.4 to 40° C [103 to 104° F]) for another 10 to 14 days, begins to fall gradually at the end of the 3rd wk, and reaches normal levels during the 4th wk. Prolonged fever is often accompanied by relative bradycardia and prostration, and CNS symptoms such as delirium, stupor, or coma occur in severe cases. In about 10% of patients, discrete pink, blanching lesions (rose spots) appear in crops on the chest and abdomen during the 2nd wk and resolve in 2 to 5 days. Intestinal perforation, usually involving the distal ileum, occurs in 1 to 2% of patients. An acute abdomen and leukocytosis during the 3rd wk of illness may suggest perforation. Splenomegaly, leukopenia, anemia, liver function abnormalities, proteinuria, and a mild consumption coagulopathy are common. Acute cholecystitis and hepatitis may occur. Late in the disease, when intestinal lesions are most prominent, florid diarrhea may occur, and the stool may contain blood (20% occult, 10% gross). In about 2% of patients, severe bleeding occurs during the 3rd wk, with a mortality rate of about 25%. Pneumonia may develop during the 2nd or 3rd wk and is usually due to pneumococcal infection, although S. typhi can also cause infiltrates. Atypical presentations such as pneumonitis, fever only, or symptoms consistent with UTI may delay diagnosis. Convalescence may last several months. In addition, bacteremia occasionally leads to focal infections such as osteomyelitis, endocarditis, meningitis, soft tissue abscesses, glomerulitis, or GU tract involvement.
In 8 to 10% of untreated patients, symptoms and signs similar to the initial clinical syndrome may recur about 2 wk after defervescence. For unclear reasons, antibiotic therapy during the initial illness increases the incidence of febrile relapse to 15 to 20%. If antibiotic therapy is reinstituted at the time of relapse, the fever abates rapidly, unlike the slow defervescence seen during the primary illness. Occasionally, a second relapse occurs.
Diagnosis
Diagnosis is ultimately based on isolation of typhoid bacilli in cultures, although the clinical setting and hematologic abnormalities may suggest typhoid fever. Typhoid bacilli are usually isolated from cultures of blood or bone marrow only during the first 2 wk of illness, while stool cultures are usually positive during the 3rd to 5th wk. Urine cultures are often positive. Cultures of liver biopsies or rose spots may also yield the organism.
Typhoid bacilli contain antigens (O and H) that stimulate the host to form corresponding antibodies. A fourfold rise in O and H antibody titers in paired specimens acquired 2 wk apart suggests S. typhi infection. However, this test (Widal's agglutination reaction) is only moderately sensitive (30% of culture-proven cases have negative tests) and lacks specificity (many nontyphoidal Salmonella strains have cross-reacting O and H antigens; cirrhosis is associated with nonspecific antibody production, causing a falsely positive Widal's reaction). Tests such as an enzyme immunoassay for detection of S. typhi antigens in the serum or urine early in the course of the illness are under study.
Differential diagnosis includes other Salmonella infections causing enteric fever, the major rickettsioses, leptospirosis, disseminated TB, malaria, brucellosis, tularemia, infectious hepatitis, psittacosis, Yersinia enterocolitica infection, and lymphoma. Early in its clinical course, typhoid fever may resemble viral URI or UTI.
Prognosis
Without antibiotics, the mortality rate is about 12%; with prompt therapy, the mortality rate is < 1%. Most deaths occur in malnourished persons, infants, and the elderly. Stupor, coma, or shock reflects severe disease and a poor prognosis. Complications occur mainly in patients who are untreated or in whom treatment is delayed.
Prophylaxis
For prevention, drinking water should be purified, sewage should be effectively disposed of, milk should be pasteurized, chronic carriers should avoid food handling, and adequate patient isolation precautions should be implemented. Special attention to enteric precautions is important. Travelers in endemic areas should avoid eating raw leafy vegetables, other foods stored or served at room temperature, and unbottled water. Unless water is known to be safe, it should be boiled or chlorinated before drinking.
A live, attenuated oral typhoid vaccine is available (Ty21a strain) and is about 70% effective. It is administered every other day for a total of 4 doses. Because the vaccine contains living S. typhi organisms, it is contraindicated in patients who are immunosuppressed. In the USA, the Ty21a vaccine is not approved for children < 6 yr. An alternative is the single dose, parenteral Vi polysaccharide vaccine, which is 64 to 72% effective and is well tolerated. This vaccine is given as a single IM injection.
Treatment
Antibiotics markedly decrease the severity and duration of illness and also reduce complications and mortality. Ceftriaxone and cefoperazone are first-choice drugs. Ceftriaxone is given 30 mg/kg/day IM or IV in 2 divided doses for 2 wk (eg, 1 g IV q 12 h for adults), and cefoperazone is given 60 mg/kg/day IV in 2 divided doses for 2 wk. Chloramphenicol is still widely used throughout the world, but resistance is increasing. Quinolones may be helpful. They might be used as follow-up oral therapy (eg, ciprofloxacin 500 mg po q 12 h) after initial parenteral therapy with a 3rd-generation cephalosporin. Quinolones are not recommended in prepubertal children. An alternative therapy, depending on in vitro sensitivity, is ampicillin 100 mg/kg/day IV or IM in 4 divided doses for 14 days.
So many stupid people have used it incorrectly for so long that people's understanding of the word has changed. What the American Heritage Dictionary did is change the definition of the word in order to accomodate the stupid.
Fortunately, I'm not common. (Hubris on display). ;0)
Just providing a little bit of information. Do with it what you may.
Killed off 1/30 of them. It was 1/10 of a particular third of the population. Since they know which part of the population was affected they should tell us that, too.
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Dictionaries nowadays tend to be descriptive (tell you how people use the word) rather that prescriptive (tell you how the word ought to be used.)
Language is dynamic, and the use of the word decimate actually was lifted from a Roman military punishment where every 10th soldier was beat to death by the other nine as a punishment for mutiny (so that the entire unit was punished, not just the man selected for death. It was not actually created to mean let's have a word that describes killing 1/10th of a group, but first, probably, to refer to the Roman practice, but then by extension, to have a word to describe a horrid reduction.
Requiring a metaphoric use of a word to fit a prescriptive definition that no longer has any real model in the world is an interesting thing in and of it's own right, perhaps worthy of scientific study....
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