We have seen how the Spanish conquistadors were able to bring down large empires in North and South America with a handful of men. Jared Diamond...

Any culture, even now, would have trouble mounting a defense from an invader given an epidemic--this is why germ warfare is taken so seriously in America today.  The Japanese army experimented with germ warfare in WWII by releasing bubonic plague in China in 1937.  The effects were devastating, but not devastating enough to cause the surrender of China.  Other nations have had success using germ warfare--the British intentionally used smallpox in Pontiac's Rebellion and the Mongols used animal carcasses to cause epidemics in besieged cities.  Even naturally-occurring diseases can hasten the demise of an empire--the Plague of Justinian in the sixth century led to the weakening of the Byzantine Empire.  

America is well-aware of these lessons and takes precautions against germ warfare.  It has participates in diplomacy which makes germ warfare illegal but also develops vaccines against diseases such as bubonic plague and smallpox.  Soldiers going into Iraq both in the First and Second Gulf Wars had to be vaccinated in the event of germ warfare.  Germs used for warfare are also classified as "weapons of mass destruction" and are a cause of U.S. diplomatic and military interventions.