Image from the National Museum of Health & Medicine

The 5 most lethal diseases in history—smallpox, measles, tuberculosis (TB), plague, and malaria—currently pose little threat to the US. From this list, TB is the one you’re most likely to catch, and even the odds of that are slim (1 in 21,730). You have a better chance of being murdered in a year in the US (1 in 18,690).

The disease you are least likely to catch—smallpox—may well have the distinction of being the most lethal in history. As a matter of fact, you can’t catch it, as it’s the first and only communicable human disease to have been totally eliminated thanks to international vaccination campaigns.

The last casualty of smallpox, Englishwoman Janet Parker, died in 1978. Today, the only known samples of the virus still in existence reside in half-inch plastic vials held in isolation chambers and bathed in -94 degree F liquid nitrogen: one set lies in the Centers for Disease Control and Prevention in Atlanta, GA, the other in the Russian State Center of Virology and Biotechnology, outside Novosibirsk.

Although some worry these samples could accidentally or intentionally be released back into the world, scientists have argued that they could be useful research tools.

By virtually any count, smallpox has taken more human lives than any other communicable disease. In the 20th century alone, smallpox caused roughly 300-500 million deaths. Considering that the virus has existed for up to 68 millennia, the total number of smallpox casualties—however one wants to calculate it—must be truly staggering.

Measles is No. 2

The second most deadly disease in history is measles, but again, you don’t have to worry too much about coming down with it. The odds a person in the US will be diagnosed with measles in a year are 1 in 5,444,000. It’s more likely a Powerball ticket holder will win $200,000 (1 in 5,138,000).

In the last 150 years, measles has caused an estimated 200 million deaths worldwide. Of worldwide measles deaths—roughly 242,000 in 2006—most occur in developing nations in sub-Saharan Africa that have inadequate medical care, crowding, and widespread starvation. The odds a person will die of measles in the US in a year are 1 in 296,400,000.

You can thank the development of an effective vaccine 46 years ago for those odds.

TB Still a Threat

John Keats, Andrew Jackson, Elizabeth Barrett Browning, John Calvin, Doc Holliday, George Orwell, and Emily and Anne Brönte: these are just a few of the major figures throughout history killed by tuberculosis, the mother of all lung infections (though it can infect any part of the body). And history is not done—tuberculosis is still being fought, even in developed nations. It is also still one of the four deadliest communicable diseases in the US.

Treating tuberculosis involves extensive courses of antibiotics, though the disease is often antibiotic-resistant. Luckily, only about 5% of diagnosed cases in the US are fatal. The odds a person will die of tuberculosis in the US in a year are only 1 in 457,400. It’s more likely a person will die from suffocating in bed in a year (1 in 452,900).

Scientists estimate that tuberculosis was responsible for 100 million deaths in the 20th century alone, and it continues to cause about 1 million deaths each year, making it the third most deadly disease in history.

Bubonic Plague is No. 4

Although it’s very unlikely you’ll get the plague (also called the bubonic plague or Black Death), it’s still possible. The odds a person in the US will be diagnosed with plague in a year are 1 in 17,610,000. In fact, you’re more likely to get the plague than you are of being diagnosed with rubella, also known as German measles (1 in 24,660,000).

To date, this bacteria (which causes bubonic, pneumonic, and septicemic plague) has cost humanity about 200 million lives. The plague bacterium Yersinia pestis, spread by flea bites, attacks the lymph nodes (in its bubonic manifestation), and in its other forms infects the blood and lungs. Untreated, plague victims can die in less than a week.

The Black Death wiped out nearly a third of Europe's population between 1348 and 1350, but today, because it is treatable with antibiotics, it is fatal in only about 1 in 7 US cases.

Some Claim Malaria May Be Most Deadly

Although there are no firm statistics, some scientists in the 1950s-1970s claimed malaria, which is spread from person to person by mosquitoes or any blood-to-blood contact, may beat out smallpox as the deadliest disease in history. What is known is that it kills about 1 million people annually.

The odds a person in the US will be diagnosed with malaria in a year are 1 in 203,100. And the odds a person in the US will die of malaria in a year are 1 in 49,400,000, about the same odds a person will die from contact with hot steam in a year (1 in 49,900,000).

Other countries, though, still suffer extremely high fatality rates from malaria even though there are vaccines and other treatments. Many of the victims are children: the Centers for Disease Control estimates that a child dies from malaria every 30 seconds in Africa.

Spanish Flu, Most Deadly in US History

Deserving of a dishonorable mention is Spanish flu (Influenza A/H1N1 subtype).

Estimates of the worldwide death toll during the 1918-1920 pandemic have been adjusted up several times, with a 2002 report suggesting more than 50 million lives may have been lost.

These days, the odds a person in the US will die from influenza in a year are 1 in 345,100. You're not much more likely to die from the flu than you are from tuberculosis, but the Spanish flu epidemic of 1918-1919 displayed a virulence that is unmatched in American history: during its brief tenure, 1 in 152.9 Americans died of the disease.