AIDS; 25 million from 1981 to present

Acquired immune deficiency syndrome or acquired immunodeficiency syndrome (AIDS) is a disease of the human immune system caused by the human immunodeficiency virus (HIV).
This condition progressively reduces the effectiveness of the immune system and leaves individuals susceptible to opportunistic infections and tumors. HIV is transmitted through direct contact of a mucous membrane or the bloodstream with a bodily fluid containing HIV, such as blood, semen, vaginal fluid, preseminal fluid, and breast milk.
This transmission can involve anal, vaginal or oral sex, blood transfusion, contaminated hypodermic needles, exchange between mother and baby during pregnancy, childbirth, breastfeeding or other exposure to one of the above bodily fluids.
AIDS is now a pandemic. In 2007, it was estimated that 33.2 million people lived with the disease worldwide, and that AIDS killed an estimated 2.1 million people, including 330,000 children. Over three-quarters of these deaths occurred in sub-Saharan Africa, retarding economic growth and destroying human capital.
Genetic research indicates that HIV originated in west-central Africa during the late nineteenth or early twentieth century. AIDS was first recognized by the U.S. Centers for Disease Control and Prevention in 1981 and its cause, HIV, identified in the early 1980s.
Although treatments for AIDS and HIV can slow the course of the disease, there is currently no vaccine or cure. Antiretroviral treatment reduces both the mortality and the morbidity of HIV infection, but these drugs are expensive and routine access to antiretroviral medication is not available in all countries. Due to the difficulty in treating HIV infection, preventing infection is a key aim in controlling the AIDS pandemic, with health organizations promoting safe sex and needle-exchange programmes in attempts to slow the spread of the virus.

AIDS is a mix of infections and complications as a result of progressive damage to the body’s immune system caused by HIV. AIDS is now considered a pandemic.

Influenza; 36,000 deaths annually

Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae (the influenza viruses), that affects birds and mammals. The name influenza is Italian and means "influence" (Latin: influentia). The most common symptoms of the disease are chills, fever, sore throat, muscle pains, severe headache, coughing, weakness and general discomfort. Sore throat, fever and coughs are the most frequent symptoms. In more serious cases, influenza causes pneumonia, which can be fatal, particularly for the young and the elderly. Although it is often confused with other influenza-like illnesses, especially the common cold, influenza is a much more severe disease than the common cold and is caused by a different type of virus. Influenza may produce nausea and vomiting, particularly in children, but these symptoms are more common in the unrelated gastroenteritis, which is sometimes called "stomach flu" or "24-hour flu".
Typically, influenza is transmitted through the air by coughs or sneezes, creating aerosols containing the virus. Influenza can also be transmitted by direct contact with bird droppings or nasal secretions, or through contact with contaminated surfaces. Airborne aerosols have been thought to cause most infections, although which means of transmission is most important is not absolutely clear. Influenza viruses can be inactivated by sunlight, disinfectants and detergents. As the virus can be inactivated by soap, frequent hand washing reduces the risk of infection.
Influenza spreads around the world in seasonal epidemics, resulting in the deaths of hundreds of thousands worldwide annually, and millions in pandemic years. On average 41,400 people died each year in the United States between 1979 and 2001 from influenza. Three influenza pandemics occurred in the 20th century and killed tens of millions of people, with each of these pandemics being caused by the appearance of a new strain of the virus in humans. Often, these new strains appear when an existing flu virus spreads to humans from other animal species, or when an existing human strain picks up new genes from a virus that usually infects birds or pigs. An avian strain named H5N1 raised the concern of a new influenza pandemic, after it emerged in Asia in the 1990s, but it has not evolved to a form that spreads easily between people. In April 2009 a novel flu strain evolved that combined genes from human, pig, and bird flu, initially dubbed "swine flu" and also known as influenza A/H1N1, emerged in Mexico, the United States, and several other nations. The World Health Organization officially declared the outbreak to be a "pandemic" on June 11, 2009 (see 2009 flu pandemic). The WHO's declaration of a pandemic level 6 was an indication of spread, not severity.

Influenza, which is more commonly known as flu, is a highly infectious disease that is caused by influenza virus. Transmission of the disease is by airborne and through physical contact.

Spanish Flu, 1918-19; 100 million deaths

The 1918 flu pandemic (commonly referred to as the Spanish Flu) was an influenza pandemic that spread to nearly every part of the world. It was caused by an unusually virulent and deadly influenza A virus strain of subtype H1N1. Historical and epidemiological data are inadequate to identify the geographic origin of the virus. Most of its victims were healthy young adults, in contrast to most influenza outbreaks which predominantly affect juvenile, elderly, or otherwise weakened patients. The flu pandemic has also been implicated in the sudden outbreak of encephalitis lethargica in the 1920s.
The pandemic lasted from March 1918 to June 1920, spreading even to the Arctic and remote Pacific islands. It is estimated that anywhere from 50 to 100 million people were killed worldwide which is from three to seven times the casualties of the First World War (15 million).An estimated 50 million people, about 3% of the world's population (approximately 1.6 billion at the time), died of the disease. An estimated 500 million, or 1/3 were infected.
Scientists have used tissue samples from frozen victims to reproduce the virus for study. Given the strain's extreme virulence there has been controversy regarding the wisdom of such research. Among the conclusions of this research is that the virus kills via a cytokine storm (overreaction of the body's immune system) which explains its unusually severe nature and the concentrated age profile of its victims. The strong immune systems of young adults ravaged the body, whereas the weaker immune systems of children and middle-aged adults caused fewer deaths.

The flu pandemic that happened in 1918 is termed as a category 5 flu pandemic which was caused by the flu virus strain A with subtype H1N1.

Bubonic Plague; 250 million deaths

Bubonic plague is the best known manifestation of the bacterial disease plague, caused by the Gram-negative bacterium Yersinia pestis (formerly known as Pasteurella pestis). It belongs to the family Enterobacteriaceae. The term "bubonic plague" was often used synonymously for plague, but it does in fact refer specifically to an infection that enters through the skin and travels through the lymphatics, as is often seen in flea-borne infections. Bubonic plague kills about half of infected patients in 3–7 days without treatment, and may be the Black Death that swept through Europe in the 1340s, killing tens of millions.

This disease outbreak was mainly caused by fleas and rodents infected with Xenopsylla cheopsis. Humans were infected after being bitten by an affected rodent.