Epidemics
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The rampant spread of disease was common in the days before penicillin and other "wonder drugs" of the twentieth century. Our ancestors lived in fear of epidemics, and many of them died as the result of simple diseases that could be cured today with an injection or a prescription.
If you ever wondered why a large number of your ancestors disappeared during a certain period in history, you may want to investigate the possibility of an epidemic. Many cases of people disappearing from records can be traced to dying during an epidemic or moving away from the affected area.