Great Plague
The timing was especially bad, as it kept Gondor from recovering from the Kin Strife 200 years earlier. Just the year before, the King of Gondor was killed by Corsairs. The new king and his heirs died in the epidemic.
Flu is particularly or note to us here. The Shire and Arnor both are more northern areas. Meanwhile, it does not appear that the suothern reaches of Gondor or Harad suffered too much from it. In fact, the Southrons are never mentioned in the list of victims - but the Easterlings were. We know that the Easterlings and Southrons had contact as they were directly allied with each other during the Wainrider invasion of Gondor. So it is not like there was no shot of transmission between the two regions. The Flu is more easily spread in the North because the Northern Hemisphere has better environmental conditions for it.
Hedlund C, Blomstedt Y, Schumann B (2014). "Association of climatic factors with infectious diseases in the Arctic and subarctic region – a systematic review". Glob Health Action. 7: 24161. doi:10.3402/gha.v7.24161. PMC 4079933. PMID 24990685.
Now, the question becomes does the flu have the proper lethality needed to have the horrific effects we see? Yes it does. We only need to look at the Spanish Flu of 1918. This was a H1N1 version that affected 3-5% of the world population. Apparently it was so brutal that it is considered the deadliest natural disasters in world history. 500 million were infected and 50 to 100 million died. Life Expectancy in the US dropped by 12 years as a result of it.
Patterson KD, Pyle GF (1991). "The geography and mortality of the 1918 influenza pandemic". Bulletin of the History of Medicine. 65 (1): 4–21. PMID 2021692.
Taubenberger JK, Reid AH, Janczewski TA, Fanning TG (December 2001). "Integrating historical, clinical and molecular genetic data in order to explain the origin and virulence of the 1918 Spanish influenza virus". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 356 (1416): 1829–39. doi:10.1098/rstb.2001.1020. PMC 1088558. PMID 11779381.
"Life expectancy in the USA, 1900–98". demog.berkeley.edu. Archived from the original on 8 June 2003. Retrieved 31 March 2016.
Transmission & Vectors
It came via an "evil wind from the East", so probably it was airborne. This means it is like the flu or common cold - spread with coughs or sneezes. Well, at least that is the cliff notes version.
Cities naturally would be harder hit because of higher population density and building walls trapping in air. Also, high population density (like what one sees in cities) are critical for high transmission rates. But also important transmission sources are garbage and sewage not properly dealt with. The relatively poor by modern standards of medieval cities would see more human excretion and waste in the streets, which would explain why Gondor's cities were so hard hit.
Part of the reason that the Spanish Flu was so damaging was the concentration of men in army bases, transport vessels, POW camps and so forth. Poor hygene typical in trenches and the poor nutrition affecting many areas due to World War One also contributed. But poor nutrition, insufficient food and poor sanitation/hygene were features of the medieval world - just not for the same reasons we see in World War One.
Causes
But its appearance coincided with Sauron setting up shop in Dol Goldur and evil creatures becoming more common. It is suggested then that the Witch King or Sauron had a hand in creating it. It must be noted this plan somewhat backfired for Mordor. If we assume that Sauron was responsible, he did gain a lot from it. Sauron was able to retake Mordor and conquer new lands as a result. But the losses in Rhun meant his Easterling allies were too weak to be a mjor player either. The result was he had the opportunity to deal a death blow to Gondor but did not have enough troops to capitalize on that weakness. Similarly, Arnor was destroyed but not taken.
Symptoms
Because the respiratory system is how airborne diseases enter the body, symptoms can be expected to concentrate in the nose, throat, sinuses and the lungs. This would be the first and/or the worst hit areas.
One of the major problems with the Spanish Flu is that is caused the body's immune system to become overly aggressive. This means that those with the healthiest immune systems become more likely to die. Meanwhile those who are somewhat less healthy see their immune systems increased enough to be saved by the same disease. This means that the young adults that typically are the least likely to die due to infections are the most likely to die in the Spanish Flu. Death came not from normal progression of typical flu symptoms but the overactive immune response.
Symptoms of this "cytokine storms" include fever, fatigue, loss of appetite, muscle and joint pain, nausea, vomiting, diarrhea, rashes, fast breathing, rapid heartbeat, low blood pressure, seizures, headache, confusion, delirium, hallucinations, tremor, and loss of coordination. This would be on top of the normal flu symptoms. We
Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL (July 2014). "Current concepts in the diagnosis and management of cytokine release syndrome". Blood. 124 (2): 188–95. doi:10.1182/blood-2014-05-552729. PMC 4093680. PMID 24876563.
Prognosis
So, it appears that the Spanish Flu killed between 3-5% of the global population. It appears to have infected 500 million people. This is out of an estimated world population of 1,860 million people. That is 26.88% of the population getting infected. Between 10 and 20% of those infected died. I would guess that similar figures would apply to Middle Earth.
Affected Groups
Hobbits and virtually all human cultures suffered terribly from it as well. Geographically, the kingdom of Arnor, Gondor and Rhovanion were all hard hit. As many as 100,000 died and half of the Kingdom of Rhovanion was estimated to have died. Osgiliath and Minas Ithil both saw major population drops as a result of it. The Shire and Rhun were also hard hit.
Hosts & Carriers
Due to the fact that humans and hobbits appear to be the only species mentioned that died because of it, we can assume then that hobbits are more similar biologically to humans that dwarves or elves.
Epidemiology
It first devastated Rhun, then Rhovanion. When it hit Gondor, it was not kind there either. Further north, the Kingdom of Arnor suffered greatly as well. The losses there made the destruction of it by the Witch King much easier.
History
So, one of the most important events for the coming War of the Ring was the Great Plague.
The losses were so great that it set the stage for Minas Ithil being conquered and renamed Minas Morgul. The capital was moved from Osgiliath to Minas Tirith as a result of the Great Plague too. Just as important was the many watch towers Gondor built and maintained around Mordor had to be adandoned. Whole garrisons died due to the disease. The result was Sauron was able to move in with his army of orcs. Only after this was the opportunity at Minas Morgul was capitalized on and Sauron was able to begin building his forces for the War of the Ring. Symbolically, the White Tree of Gondor died, reflecting the decline of Gondor.
Type
Viral
Origin
Divine
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