The fever and runny nose sounds like a flu or coronavirus. And that leaves you weak and tired. Look at brain fog and other such things reported with coronavirus. The high death rate in the indigenous groups versus the resilience of the Castillians tells me it’s not tropical or vector borne. They would have taken it back to Spain if it was something new to them too. I wonder if other Spanish territories reported something similar in the Americas or Asia? That would give hints about transmission and incubation periods. I immediately thought of Trypanosomiasis, African Sleeping Sickness, but the runny nose doesn’t fit. I feel like a rabbit hole is about to swallow me up on this one. That, and a trip to the Historical Medical Library in Philly.