Numerous 16th century accounts detail the outbreak’s devastation, but the symptoms do not match any known pathogen. Shortly after 1548, the Spanish started calling the disease tabardillo (typhus), which had only been recognized in Spain since the late 15th century. However, the symptoms of<unk>  were still not identical to the typhus, or spotted fever, observed in the Old World at that time. Perhaps, this is why Francisco Hernández de Toledo, a Spanish physician, insisted on using the Nahuatl word when describing the disease to correspondents in the Old World. Centuries later, in 1970, a historian named Germain Somolinos d'Ardois took a systematic look at all the proposed explanations at the time, including haemorrhagic influenza, leptospirosis, malaria, typhus, typhoid and yellow fever. According to Somolinos d'Ardois, none of these quite matched the 16th century accounts of<unk> , leading him to conclude the disease was a result of "viral process of hemorrhagic influence." In other words, Somolinos d'Ardois believed<unk>  was not the result of any known Old World pathogen, but possibly, a virus of either European or New World origins. It has been speculated that it might have been an indigenous viral hemorrhagic fever as there are accounts of similar diseases having struck Mexico in Precolumbian times. The Codex Chimalpopoca states that an outbreak of bloody diarrhea occurred in Colhuacan in 1320. If the disease was indigenous, it was perhaps exacerbated by the worst droughts to affect that region in 500 years and living conditions for indigenous peoples of Mexico in the wake of Spanish conquest (c. 1519). Some historians have suggested it was typhus, measles, or smallpox, though the symptoms did not match. Marr and Kiracofe (2000) attempted to build off this work by reexamining Hernandez’s account of<unk>  and comparing them with various clinical descriptions of other diseases. They suggested that scholars consider "New World arenaviruses" and the role these pathogens may have played in colonial disease outbreaks. Rebelling against the universal acceptance of Post-Contact epidemics being "Old-World importations," Marr and Kiracofe theorized that arenaviruses, which mainly affect rodents, were largely kept away from Pre-Columbian people. Consequently, rat and mice infestations brought upon by the arrival of the Spanish may, combined with climatic and landscape change, have brought these arenaviruses into much closer contact with people. Subsequent studies seemed to have accepted the viral haemorrhagic fever diagnosis, and became more interested in assessing how the disease became so widespread. In 2018, Johannes Krause, an evolutionary geneticist at the Max Planck Institute for the Science of Human History, and colleagues discovered new evidence for an Old World culprit. DNA samples from the teeth of 29 sixteenth-century skeletons in the Oaxaca region of Mexico were identified as belonging to a rare strain of the bacterium Salmonella enterica (subsp. enterica) which causes paratyphoid fever, suggesting that paratyphoid was the underlying fever behind the disease. The team extracted ancient DNA from the teeth of 29 individuals buried at Teposcolula-Yucundaa in Oaxaca, Mexico. The Contact-era site has the only cemetery to be conclusively linked to victims of the<unk>  Outbreak of 1545–1548. Using the MEGAN alignment tool (MALT), a program that attempts to match fragments of extracted DNA with a database of bacterial genomes, the researchers were able to recognize nonlocal microbial infections. Within 10 individuals, they identified Salmonella enterica subsp. enterica serovar Paratyphi C, which causes enteric fevers in humans. This strain of Salmonella is unique to humans, and was not found in any soil samples or pre-Contact individuals that were used as controls. Enteric fevers, also known as typhoid or paratyphoid, are similar to typhus, and were only distinguished from one another in the 19th century. Today, S. Paratyphi C continues to cause enteric fevers, and if untreated, has a mortality rate up to 15%. Infections are largely limited to developing nations in Africa and Asia, although enteric fevers, in general, are still a health threat world wide. Infections with S. Paratyphi C are rare, as the majority of cases reported (about 27 million in 2000) were the result of the serovars S. Typhi and S. Paratyphi A. These findings are boosted by the recent discovery of S. Paratyphi C within a 13th century Norwegian cemetery. A young female, who likely died from an enteric fever, is proof that the pathogen was present in Europe over 300 years before the epidemics in Mexico. Thus, it is possible that healthy carriers transported the bacteria to the New World, where it thrived. Those who unknowingly possessed the bacteria were likely aided from generations of contact with it, as it is believed that S. Paratyphi C may have first transferred over to humans from swine in the Old World during, or, shortly after the Neolithic period. Some, including evolutionary geneticist, María Ávila-Arcos, have questioned this evidence, since S. enterica symptoms are poorly matched with the disease. Both Ávila-Arcos, and even Krause’s team and authors of earlier historical analyses, point out that RNA viruses, among other non-bacterial pathogens, had not been investigated. Others have highlighted the fact that certain symptoms described, including gastrointestinal hemorrhaging, are not present in current observations of S. Paratyphi C infections. Ultimately, a more definitive proposal for the cause of any of the<unk>  of 1545–1548 and 1576-81 awaits further developments in ancient RNA analysis and the causes of different outbreaks may prove to differ.
Cocoliztli epidemics
Tanganyika laughter epidemic
Native American disease and epidemics
Virgin soil epidemic
Death rattle
symptoms of Yellow fever
Asclepiades of Bithynia
Flavescence dorée