Worst Epidemic Diseases in History


CASUALTIES: 300-500 million

When a worldwide vaccination effort eradicated smallpox in nature, it was hailed as one of the most significant medical achievements of the 20th century.

For at least 500 years, the disease had ravaged the world; in South America alone, it almost wiped out the entire

Inca population. Characterized by distinctive large pustules, the ordinary form of the virus attacked the major organs and, on average, killed more than 30 percent of those infected; more extreme forms were invariably fatal. Most survivors were scarred with pockmarks.

Black Death

CASUALTIES: 200 million

Vomiting blood, painful growths the size of apples, gangrene of the extremities — these were the gruesome effects of the plague, which repeatedly wiped out large swaths of the population of Europe from the 13th through the 17th centuries. The disease is caused by Yersinia pestis bacteria, which are transmitted to humans through flea bites. The bacteria attack the lymph nodes in the neck, armpit or groin, causing them to swell into buboes, hence the name bubonic plague.

Spanish FluSpanish Flu

CASUALTIES: 50-100 million

Just as World War I was ending, in 1918, young veterans suddenly began collapsing from a mysterious flu. The worldwide epidemic raged over the next two years, with 1 in 4 people contracting the virulent influenza strain. Studies have since found that the virus caused the victim’s immune system to overreact, setting some 150 antibodies in motion simultaneously, in a cytokine storm that attacked the organs. Young adults with strong immune systems fared the worst, in a reversal of typical flu strains that are deadlier to the immunosuppressed, such as children and the elderly.


CASUALTIES: 200,000 annually

It’s the color of rice water and has a foul, fishlike smell — this is how cholera victims describe the nearly five gallons of diarrhea that flow out of their bodies every day. The disease is transmitted through drinking water, which harbors the Vibrio cholerae bacteria that attack their victims small intestines, causing severe cramps and diarrhea — and initiating a vicious cycle of infection when the diarrhea carries the cholera bacteria back into the water supply, where it can infect others. Those infected are most at risk of dying from dehydration, particularly in areas with limited access to clean water, but cholera is often survivable with timely rehydration treatment.


CASUALTIES: 650,000 annually

Every year, 200 to 300 million people are infected with malaria. It’s the most common cause of death among children younger than 5 throughout Africa. Within eight to 10 days after being bitten by an infected mosquito, the victim experiences fever, headaches, shivering, vomiting and pain in the joints. A particularly severe form attacks the central nervous system, causing paralysis and coma. Because it is so widespread, it has been notoriously difficult to control; drug therapy is available, but there is no vaccine.


CASUALTIES: 3 million annually

Tuberculosis is the most common of the world’s deadly infectious diseases. It has been afflicting humans for thousands of years; TB bacteria have even been found in Egyptian mummies. The disease primarily attacks the lungs, causing the characteristic violent cough that helps it spread to new victims. Although deadly in up to 50 percent of untreated cases, tuberculosis can be cured with antibiotics — but multiple drug-resistant types are emerging.


CASUALTIES: 10 million

Typhus is also known as jail fever because of its propensity for sweeping through prison camps and other places where people live close together in unsanitary conditions. It can be cured by antibiotics when caught early, but if left untreated, typhus can kill up to 60 percent of those infected through pneumonia or kidney or cardiac failure.


CASUALTIES: 25 million

U.S. doctors recorded the first AIDS case in 1981; in the 32 years since then, more than 25 million people have been infected with the virus that causes it: human immunodeficiency virus (HIV). A strict drug regimen keeps the retrovirus in check, but untreated victims can die from conditions that a healthy immune system would easily defeat.

Yellow FeverYellow Fever

CASUALTIES: 30,000 annually

Like malaria, yellow fever is spread by mosquitoes; the World Health Organization estimates that it kills 30,000 people annually. In mild cases, the patient experiences only fever and muscle pain, but in deadly cases may suffer hemorrhaging and liver failure. When the latter occurs, jaundice colors the skin yellow, hence the disease’s name.



Poliovirus typically spreads via fecal contamination of food or water. Once it enters the bloodstream, it can affect the central nervous system, causing paralysis in the arms, legs and diaphragm; the latter can impair breathing and lead to death. Polio primarily infects children under 5.

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