So I’ve delve into my historical medical books (and Google!) to look further into the unknown pandemic of Cocoliztli.
It is well known that imported infections from Europe with the Spanish Conquistadors caused many deaths; Smallpox for example was imported in about 1520 and killed about 8 million people. In fact during the 16th Century about 90% of the native population of Mexico was wiped out by disease. But as if Smallpox wasn’t enough, this was followed in 1545 by the first Cocoliztli epidemic which killed a further 15 million people. Local people called this disease Cocoliztli or “pest” and as pandemics go this one seems pretty bad! A further Cocoliztli epidemic in 1576 killed another 50% of the population, so by this time more than 90% of the natives had been killed in just over 50 years!
So what DO we know about Cocoliztli?
There were 12 epidemics of Cocoliztli between 1520 and 1642; the worst 2 epidemics were 1545-1548 and 1576-1578 which were responsible for most of the deaths. All of the epidemics started in the northern and central Mexican Highlands and spread from there; it remained rare in the warm lowland areas of the Gulf of Mexico and the Pacific coast. This is significance for two reasons; 1) it suggests mosquitoes which prefer lowlands were not the vector, and 2) it was unlikely to have been introduced from Europe as you’d expect to see disease start in the coastal areas where the Europeans first entered Mexico, and where most of them stayed and lived, before seeing it spread wider from the coasts. Cocoliztli was occurring at altitude and on high plateaus.
Cocoliztli did however occur shortly after the arrival of the Europeans; there was no evidence of the disease before. This provides counter evidence suggesting it was an imported disease.
At this time the native population had already been exposed to, and devastated by, Smallpox. Those unaffected were often enslaved forcing the population together into situations of overcrowding, poor sanitation, poor nutrition and forced labour. This type of enslaved population would have been poorly nourished. Even if the population didn’t look emaciated they could still have been severely lacking in important vitamins and minerals that are essentially for good health e.g. vitamins A, B3, B12, C etc. The social conditions would have made them prone to acquiring diseases and their chances of fighting off new diseases would have been poor. Although there is documentation that Cocoliztli appears to have affected both native Aztecs and Europeans alike.
Another aspect of the Cocoliztli epidemics is that they occurred during the worst droughts in Mexico for 600 years as shown by studies of tree rings over that time. However what is particular intriguing is that Cocoliztli occurred during the brief periods of wetter weather interspersed between the severe droughts, although this didn’t happen with every epidemic. This suggests that either Cocoliztli was associated with the consequences of drought such as malnutrition, poor sanitation and the congregation of people to remaining water sources OR maybe the relieving of the drought with rains lead to a rapid expansion of an insect or animal vector that then spread the disease through the population. Support for the animal vector theory comes from the observation of the Sin Nombre Virus outbreak in Colorado in 1993 when a period of drought broke and there was an explosion in rodent population numbers which is the host for the Hantavirus, the cause of this infection.
So if historical documentation cannot identify the cause of Cocoliztli, are there any clues from the clinical features?
Clinical features of Cocoliztli
Based upon descriptions by Spanish doctors who observed the Cocoliztli epidemics the main clinical features were:
- High fever
- Severe headache
- Black tongue
- Dark urine
- Severe abdominal and chest pain
- Large nodules behind the ears that often invaded the face
- Acute neurological disorders
- Profuse bleeding from the nose, eyes and mouth
- Death within 3-4 days (golly that’s quick!)
For me there are some key features to Cocoliztli:
- There is no obvious prodromal illness (the period between the appearance of initial symptoms and the illness’ full development), people rapidly developed symptoms and then swiftly died! – This is unusual and not a normal feature of human pathogens; as quickly killing the host will actually limit the infection’s ability to spread. It suggests humans are not the normal target of this disease.
- There is no respiratory component – this suggests the disease is not spread by the respiratory or droplet route.
- Bleeding is a significant feature – very few infections have major haemorrhages as a specific and consistent feature, although any form of sepsis can cause bleeding if the patient goes into Disseminated Intravascular Coagulation (DIC). However DIC is not that common whereas bleeding appears to occur in almost all cases of Cocoliztli.
- This is a dam-scary-sounding infection!
What are the current theories as to the cause of Cocoliztli?
Salmonella paratyphi C
The current theory for the cause of Cocoliztli is that it was a type of enteric fever caused by the bacterium Salmonella paratyphi C (SpC). In 2018 a team lead by Johannes Krause looked at skeletons from a Mexican cemetery dating from the time of the 1545-1548 epidemic, they found SpC DNA in 10 out of 29 dental DNA samples and concluded this was evidence of the cause of Cocoliztli. There is no evidence of SpC in earlier skeletons in Mexico however it has been shown that SpC was also present in Europe around this time.
I’m not sure this is conclusive, it’s only 1/3 of the skeletons and really only shows that SpC was present at this time; there are a number of strong arguments against it as a cause of Cocoliztli including:
- No prodromal period – SpC normally has a prodrome of a week
- Rapid death – SpC normally takes 3-4 weeks to kill its hosts and is only fatal in a relatively smaller percentage (up to 40%)
- Bleeding is not a common feature of SpC except when it causes DIC
- Cocoliztli was not common in coastal areas – SpC would have occurred in all port areas of Mexico, it wouldn’t have been confined to the Highlands
- Common disease – once introduced into the population SpC is likely to have become quite common and there would be a large number of chronic carriers within that population
Viral Haemorrhagic Fever
Prior to the discovery of SpC in the teeth of Cocoliztli victims, the main theory was that it was caused by a virus causing a Viral Haemorrhagic Fever (VHF).
The main evidence for the VHF theory is that the clinical symptoms described by the doctors in the 16th Century are very typical of the VHFs we see in the World today. Cocoliztli looks very similar to infections like Yellow Fever, Crimean Congo Haemorrhagic Fever, Ebola and Marburg; all scary, bloody and rapidly fatal.
However, Cocoliztli isn’t likely to be any of these named VHFs as all of them are diseases of Eastern Europe, Asia or Africa; it wasn’t until the 17th Century that slaves we taken to Mexico and took with them Yellow Fever. So it’s more likely that whatever the cause of the VHF, “it” was already in Mexico at the time. Then when the environmental or socioeconomic conditions forced humans into contact with the VHF’s normal host it crossed the species barrier and ran rampant in an immunologically naïve population… sound familiar?!
So what do I think is the cause of Cocoliztli?
For me the clinical story is everything, it is usually the story that tells me what is wrong with my patients in my normal daily practice; I tend to avoid looking too closely at their teeth!
I think Cocoliztli was caused by a zoonotic virus either transmitted by an insect or directly from an animal, via its urine or faeces, which was forced in to contact due to the socioeconomic and environmental situations in 16th Century Mexico…“so DON’T blame the Conquistadors!”
My reasons for thinking Cocoliztli is a VHF are:
- The only contemporary infections which have the same symptoms and signs as Cocoliztli are the VHFs, and these are all zoonotic
- The lack of prodrome, rapid death and excessive mortality (90% of the population) suggest the cause was not something the people of Mexico had any immunity to or had ever come in to contact with before
- The resurgence of Cocoliztli within the population on average every 7 years (range 2-11 years) suggest multiple reintroductions of the cause rather than on going circulation within the population
- Malnutrition, over-crowding and socioeconomic oppression made a bad situation even worse! “OK so DO blame the Conquistadors!”
- I suspect the reason Cocoliztli concentrated in the Highlands was due to an animal host or vector confined to that geographical area, although I accept it could also be because the rapid death of those infected did not allow sufficient time for them to transfer it to the lowland regions.
It is very hard to find evidence of viruses in historical remains. Most VHFs are caused RNA viruses and these are unlikely to survive for long periods within the environment; SARS CoV2, the RNA virus that causes of Covid-19, doesn’t survive on surfaces for more than a few days even under ideal circumstances.
In order to try and find the cause of Cocoliztli I think archaeologists would need to find the preserved remains of those who died who still had some of their lymphoreticular systems intact (such as spleen or liver) or even their bone marrow where there might be fragments of viral RNA still to be recovered. However I think these “finds” are very unlikely as the RNA may be long gone. If it was me, I would look for those buried in the Highlands, especially in very arid areas, where the victim might be mummified and perhaps better preserved.
Another technique to use would be good old-fashioned electron microscopy to see if there is anything in the tissue that looks like a virus. Most modern day novel viruses are actually still initially identified by electron microscopy before using PCR to narrow down on the species. Most of the time PCR is used once you know what your target organism is.
Another possibility would be to look for the vector of whatever virus might have been spread, such as rodents and insects, within the mummified record of the Mexican Highlands. That’s not as crazy as it sounds! Apparently mummified rodents are found quite regularly within archaeological digs, and they would be ideal to study as, if they were the natural host, the virus is unlikely to have caused them harm and would be present in large numbers of the animals. It’s a thought… “I do love historical medicine…”
Oh maybe this is another possible topic for my “pie-in-the-sky” future PhD… oh no just heard "more Covid-19 restrictions introduced” and www.gov.uk/foreign-travel-advice is advising against all but essential travel, dang it! Another great idea bites the dust….
Perhaps the most concerning aspect of Cocoliztli is this: is there a possibility of its re-emergence and how vulnerable are we to this disease? Cancel the trip to Mexico!!!