This is a tricky one. It seems quite random as to when these popups appear, other than the fact that your virus needs at least one symptom and must not have been noticed yet. Unlike some other achievements, there may not be a guide that can guarantee a high probability of success due to the randomness of whatever it is that triggers the pop ups.
This worked for me on first try though.
Use Prion on
normal difficulty with the following gene set up:
Metabolic Hyjack (so you can put it on fast forward and not worry about popping bubbles; DNA amount not an issue here)
Creationist
Native Biome
Extremophile (though Hydrophile should be fine)
I left the last one empty.
I started in the Caribbean but really any island country with only sea access should work. The reason for this is I had read from a few people that there may be a bug associated with the pop ups not triggering when multiple countries have been infected. So you want to limit transmission beyond your starting country. It also doesn't seem to trigger when a majority of the world has become infected. I had 2 other countries infected when I got the first pop up though.
Now this may be the key:
After starting in your country, don't evolve anything. The virus will spread on its own without transmissions or symptoms, although slower. Play on highest speed (Metabolic Hyjack pops bubbles for you).
Devolve any symptoms that may mutate right away.Now,
once your starting country is 100% infected, evolve any
ONE of Coughing, Nausea or Rash. Again,
ONLY ONE. I went with Nausea. You want to use one of these because they have a very low chance of being detected by a doctor.
Now, sit back and don't do anything other than devolving other symptoms. For me, the first pop up of
"Rumors of a mystery plague in *starting country*." came quickly after evolving Nausea. Hit OK and wait some more. Don't do anything else except devolving any other symptoms that may mutate.
The second pop up of
"Mystery Plague has been recommended to be investigated in *starting country*." should come. Still don't do anything other than devolving other symptoms that may mutate.
The third pop up will be
"Riots in *starting country*.". This 3rd one may take several in game months to come. And again, you don't need to do anything after this one either other than devolving other symptoms that may mutate.
Finally, the last pop up comes that says
"Mystery Plague is Real".
Boom. Achievement unlocked!
Partial credit to: Unknown author at
http://plagueinc.wikia.com/wiki/Strategy_Guides/Peer_Pressur...