In 1576, in southern and central Mexico highlands, near modern day Puebla city (4) there was the emergence of an epidemic that would be known as the Cocoliztli epidemic. Between the years 1576 to 1580 it would kill around 2-2.5 million in total, around 50% of the Mexican population, just 800,000 being in the Valley of Mexico (1). However, the exact mortality count is not confirmed, with estimates going as high as 15 million people, and 80% of the population (2). It lasted 3 to 5 days before death, and was characterized by high fevers, bleeding, vertigo, red eyes, large painful nodules behind the ears, chest and abdominal pain, and dysentery (12), a description which does not fit the symptoms of any old or new world disease known today. This explains the origin of the name, the Nahuatl word for pest, or disease, illness, and plague (3). The ambiguity around the cause of the epidemic has prompted many theories, however I believe the most scientifically or historically plausible are the theories it was caused by either a salmonella serotype (strain) Paratyphi C as Åshild Vågene suggests, or RNA viruses and other non-bacterial pathogens proposed by María Ávila-Arcos. In the following essay I will explain which theory is more plausible, along with reasons why it targeted the Aztec populations significantly more than the Spanish, the effects on the societies, and even a likely explanation of where it came from. 

Firstly, to explain how the transfer of Salmonella enterica bacteria is most plausible there must be background and context of the Mexican society established. Firstly, are the effects of the Spanish conquest in 1519, which weakened the population, meaning the Aztecs were easily governed and controlled by the Spanish. This had the following effects on the indigenous population; They were poorly fed and clothed, and greatly overworked (3). The policy of congregación  imposed forced relocations (into reducciones) and affected living relations to consider the Spanish conquerors, focusing on agriculture and conversion to Christianity. New subsistence farming was arranged due to drought conditions in the years prior (6). Lack of water in the facilities decreased sanitation and resulted in poor hygiene habits, which was hazardous and promoted the spread of disease since now the Aztec population lived in much closer proximity than previously, but also shared living spaces with animals from the new world, such as rats, chickens, pigs, and cattle (3) (Alpacas being the exception). Therefore, it is a significant fact that many of the old-world pathogens being investigated use the most common species of old-world mammalian livestock as carriers (5). The drought, mentioned previously, has very strong links to the epidemic as Cocoliztli usually appears within two years of a major drought, with this one in 1576 after a drought stretching from Venezuela to Canada (3), the worst to hit the region in 500 years. When the climatic conditions improved it would have promoted the invasion of rats into farm fields and homes, where diseases would have been transmitted via inhalation of pathogens from the rodent faeces. This would have preferentially infected the Aztec natives as they worked and lived in the infested areas, due to the congregación (1). This explains why the diseases mainly effected indigenous populations, despite coexisting alongside the Spanish population in markets and other areas of work (3). 

In the next two paragraphs we will look at how we know about the potential biological causes of the epidemic, and the research techniques used in the process. These include many methods and sources such as first-hand accounts, DNA evidence, demographic documentation, and scientific evidence. Firstly, we will look at the evidence in primary sources from the period, then the applications of modern scientific techniques to refine the theories. There were two nationwide census’ performed, one in 1570 and one between 1579 and 1580. This is a great resource to see the decline in population, in what demographics, and what areas (12). In his article titled “When half of the population died: the epidemic of hemorrhagic fevers of 1576 in Mexico”, Rodolfo Acuna-Soto, from the department of microbiology and Parasitology at the Universidad Nacional Autonoma de Mexico, confirmed that they “indicated that from the four million inhabitants that lived in México before the outbreak, two million died.…. The results indicated that in 1570, a total of 2,098,426 individuals lived in those 157 communities. Two years after the epidemic, by 1580, the population in the same places was reduced to 1,020,524. This represents 1,077,902 deaths, or a population loss of 51.36%. These results indicate that the initial estimates of the 16th century were correct, and that the epidemic of 1576 did indeed kill half of the population of Mexico.” (12). According to Rodolfo Acuna-Soto, “The majority of firsthand accounts regarding the outbreak come from Aztec informants, who were primarily concerned with the diseases’ novelty and pronounced symptoms”. One of these informants was Francisco Hernandez, one of the best physicians, and former personal physician to King Phillip II. He witnessed and chronicled the symptoms with “clinical accuracy” (1). So, I believe his accounts are reliable enough to still be valuable and detailed descriptions that can be used to aid in a potential diagnosis as we would go about starting a diagnosis today. The cause of the epidemics in both 1545 and 1576 were thought to have been caused by diseases such as smallpox, measles, and typhus, as, like Francisco Hernandez described, they killed native Mexicans significantly more than the Spanish, who would have encountered them before and introduced the diseases into the population (6). This is a point made in all accounts dated during the epidemic, and Rodolfo Acuna-Soto's analysis of the census’ supports it. The dissemination pattern of the Cocoliztli epidemic also resembles other diseases that spread human-to-human such as smallpox, measles, and cholera (12). 

One example of scientific advances uncovering information about epidemics of the past is tree ring data, which confirmed the outbreaks occurred in the period after a megadrought (1). The biggest breakthrough, however, came in the form of genetics, DNA, and a tool called MALT. An evolutionary geneticist at the Max Planck Institute for the Science of Human History, Johannes Krause, and Åshild Vågene, obtained DNA samples from teeth of 29 16th century skeletons in Teposcolula-Yucundaa, Oaxaca in southern Mexico. 24 of which were dated from post-contact with the Spanish/Europeans, and the other 5 pre-contact, as a control group. Using the MEGAN alignment tool (MALT) they figured ten of the teeth dated to the Cocoliztli epidemic period contained Salmonella enterica, Paratyphi C, the cause of paratyphoid fever, a breakthrough as they had the first scientific evidence behind the cause of the Cocoliztli epidemic, and none of the five individuals had any DNA evidence of salmonella (2)(8)(7)(6). Åshild Vågene expands on this discovery in her paper titled “Salmonella Enterica Genomes Recovered from Victims of a Major 16th Century Epidemic in Mexico.”. She explains that Salmonella enterica wasn’t detected in any pre-contact churchyard samples, soil samples, or any remaining negative controls. As a result, Paratyphi C was likely introduced during the contact era between the old world and the native Mexicans (6), as there is evidence by the discovery of Paratyphi C in a 1200CE Norwegian cemetery, dated 300 years before any sign of it in Mexico (10). Even up to today, with modern healthcare Paratyphi C causes enteric fevers, and has a mortality rate up to 15%, which would have been significantly higher in the 16th century where there was little to no knowledge about germ theory or how to treat such a disease. As I mentioned in the opening paragraph, evolutionary geneticist María Ávila-Arcos doesn’t believe the theory, as modern Paratyphi C symptoms are poorly matched with the disease described (7). Åshild Vågene takes this into account in her paper however, saying “While historical descriptions of infectious disease symptoms can be very detailed, they are subject to cultural biases, suffer from inaccuracies in translation, lack a foundational knowledge of germ theory, and describe historical forms of a condition that may differ from modern manifestations” (6). This does not rule out María Ávila-Arcos’ theory that RNA viruses, and other non-bacterial pathogens may be the cause, however until they are researched further, Paratyphi C is the definite most likely candidate. 

How did the communities handle the epidemic? The period was chronicled by Franciscan historian Fray Juan de Torquemada, saying “In the cities and large towns, big ditches were dug, and from morning to sunset the priests did nothing else but carry the dead bodies and throw them into the ditches,” (2). The contact with the corpses carries great risk if they are still infectious, however we know from bare hand autopsies performed that the physicians never contracted the disease, so luckily it was not infectious after death (12). If the priests had carried the bodies to the ditches without knowing this fact it shows they may have carried out other unrecommendable practices during the epidemic, and not handled it appropriately, which would explain the massive death toll and rate of spread. There are accounts from an encomendero, named Gonzalo de Ortiz, about the Spanish population’s reaction to the epidemic. From his accounts, they used the indigenous fears to force christianity on them even further,"envió Dios tal enfermedad sobre ellos que de quarto partes de indios que avia se llevó las tres" (God sent down such sickness upon the Indians that three out of every four of them perished) (4). There were contradictions of Ortiz’s remarks, including from Toribio de Benavente Motolinia, an early Spanish missionary, as he noted that 60-90% of “New Spain's!” population decreased. Also examples of Spaniards contracting Cocoliztli, like Bernardino de Sahagún -author of the Florentine Codex-, and African slaves and colonists being equally as susceptible as the native population during the end of the second outbreak, noted by Sahagún (11). Scientifically, we currently have no evidence to support or contradict this, however looking at these statements, it would seem to suggest that the differences in infectivity were due to environment and quality of life, rather than race. The Mexican natives living in the reducciones mentioned prior, and the colonists living in relative luxury (large houses, servants and slaves, and much better hygiene). 

The overall effect on the population was a harsh change from overall native Mexican/Aztec demographic to a predominantly Spanish culture, destroying the native way of life even further. The void in land ownership was then exploited further by the Spanish colonists. It took 350 years for the population to return to the numbers in 1544, the growth slowed by lack of native labour (20-40 deaths daily in small towns, and hundreds in cities), leading to food shortages for all areas of the population (12). 

1. Acuna-Soto, Rodolfo, et al. “Megadrought and Megadeath in 16th Century Mexico.” Emerging Infectious Diseases, Centers for Disease Control and Prevention, Apr. 2002, www.ncbi.nlm.nih.gov/pmc/articles/PMC2730237/. 

2. France-Presse, Agence. “500 Years Later, Scientists Discover What Probably Killed the Aztecs.” The Guardian, Guardian News and Media, 16 Jan. 2018, www.theguardian.com/world/2018/jan/16/mexico-500-years-later-scientists-discover-what-killed-the-aztecs. 

3. Schober, Otto. “Cocoliztli y Matlazahuatl: Periódico Zócalo: Noticias De Saltillo, Piedras Negras, Monclova, Acuña.” Periódico Zócalo | Noticias De Saltillo, Piedras Negras, Monclova, Acuña, May 2021, www.zocalo.com.mx/cocoliztli-y-matlazahuatl-2/. 

4. Prem, Hanns. Secret Judgments of God: Old World Disease in Colonial Spanish America, by Noble David Cook and W. George Lovell, University of Oklahoma Press, 2001, pp. 20–48. 

5. Wolfe, Nathan D. “ORIGINS OF MAJOR HUMAN INFECTIOUS DISEASES.” Improving Food Safety Through a One Health Approach: Workshop Summary., U.S. National Library of Medicine, 1 Jan. 1970, www.ncbi.nlm.nih.gov/books/NBK114494/. 

6. Vågene, Åshild J., et al. “Salmonella Enterica Genomes Recovered from Victims of a Major 16th Century Epidemic in Mexico.” BioRxiv, Cold Spring Harbor Laboratory, 1 Jan. 2017, www.biorxiv.org/content/10.1101/106740v2. 

7. Gibbens, Sarah. “Deadly Aztec Epidemic ‘Cocoliztli’ Linked to Salmonella.” History, National Geographic, 3 May 2021, www.nationalgeographic.com/history/article/cocoliztli-salmonella-outbreak-mexico-dna-spd. 

8.  Hersher, Rebecca. “Salmonella May Have Caused Massive Aztec Epidemic, Study Finds.” NPR, NPR, 15 Jan. 2018, www.npr.org/sections/thetwo-way/2018/01/15/577681552/salmonella-may-have-caused-massive-aztec-epidemic-study-finds?t=1625563438608. 

9. Callaway, Ewen. “Collapse of Aztec Society Linked to Catastrophic Salmonella Outbreak.” Nature News, Nature Publishing Group, 23 Feb. 2017, www.nature.com/articles/nature.2017.21485. 

10. Z Zhou, Zhemin, et al. “Millennia of Genomic Stability within the Invasive Para C Lineage of Salmonella Enterica.” BioRxiv, Cold Spring Harbor Laboratory, 1 Jan. 2017, www.biorxiv.org/content/10.1101/105759v3. 

11. Lovell, W George. Secret Judgments of God: Old World Disease in Colonial Spanish America, by Noble David Cook and W George Lovell, University of Oklahoma Press, 2001, pp. 49–83. 

12. Acuna-Soto, Rodofo, et al. “When Half of the Population Died: the Epidemic of Hemorrhagic Fevers of 1576 in Mexico.” OUP Academic, Oxford University Press, 1 Nov. 2004, academic.oup.com/femsle/article/240/1/1/536409. 

13. Somolinos A.G.(1956) Hallazgo del Manuscrito Sobre el Cocoliztli. Original del Dr. Francisco Hernández. Prensa Med. Mex.21, 115–123