Throughout human history, four infectious diseases have dominated as the leading killers: , , , and . While tuberculosis claims the highest death toll across history, , smallpox follows closely behind, killing before its .
Malaria: The G.O.A.T.?
Malaria has been a persistent threat since ancient times. One statistic often used is that malaria killed half of all humans to have ever lived. . The true number may never be known because of lack of understanding of the disease until the . Today, malaria still causes over 600,000 deaths annually, primarily affecting children in Africa. (And that’s just malaria... .)
What About The Black Death?
The plague, infamous for causing the Black Death in medieval Europe, killed up to 200 million people in the 14th century alone, . That many deaths in a relatively short period led to an almost “reset” of society in Europe. It opened the continent up to invasions from Northern Africa and the Middle East, while societies as far away as China . Historians claim the impacts of the bubonic plagues of that era were felt for hundreds of years, well into the 1700s.
Return of the King?
During the COVID-19 pandemic, the Novel Coronavirus 2 (NCov-2) that caused COVID disease . That distinction lasted until 2023, when tuberculosis retook the crown and . Tuberculosis was first described in ancient texts, . Today, tuberculosis is highly treatable, but overuse of some antibiotics has given some strains of the bacteria enough resistance to become a threat.
Not One, But Many
The thing about infectious diseases is that they do not exist in a vacuum. Other diseases and conditions, along with social determinants of health, inform how deadly an infectious disease is. For example, tuberculosis is not a big burden in the United States, where prevalence of the disease is low, access to antibiotics is reasonably good, and laboratory testing for it is highly efficient. But tuberculosis in Sub-Saharan Africa, where there is an ongoing HIV/AIDS pandemic... Now we’re talking millions of complicated cases and hundreds of thousands of deaths. Another example of “it depends” when it comes to infectious disease can be seen when a malnourished child will have a difficult time fending off childhood diseases like measles or even chickenpox. But even healthy adults can have .
As you can imagine, these diseases also disproportionately affect low-income countries, creating a cycle of poverty and illness. If you’re too sick to work, you fall into poverty. If you’re in poverty, you can’t afford medical care. In the end, everyone in the region of a highly endemic disease suffers. For example, controlling malaria in the African continent would translate to hundreds of millions () of dollars in savings that could be invested in other areas.
Prevention and Control
Due to the different contributing factors to lethality, each disease we’ve talked about requires different control strategies. Tuberculosis prevention focuses on improved living conditions, early detection, and complete treatment courses. Malaria control combines mosquito nets, insecticide spraying, and antimalarial medications. Modern plague outbreaks are controlled through antibiotics and improved sanitation. Smallpox eradication succeeded through a coordinated global vaccination campaign.
All of that is not cheap, so it requires investment from governments and institutions. Changes in laws and regulations may also be needed to allow more access to care. Cultural changes could be part of strategies to reduce stigma and allow people to seek the care they need without feeling guilty for the diseases they live with.
The Future, Maybe?
Modern medicine has provided tools to combat these ancient killers. Vaccines, antibiotics, and improved public health measures have dramatically reduced their impact. However, challenges remain, including drug resistance, inadequate healthcare infrastructure, and limited access to treatments in many regions. While some of these challenges can be overcome relatively quickly, others take generations to achieve. In the 1980s, people living with HIV and succumbing to AIDS were deemed “immoral” and part of the undesirables whose punishment for their behaviors was death.
Today, there is more acceptance (at least in the United States) of a person with an HIV infection diagnosis, and there are medications to make that diagnosis not a death sentence anymore. Unfortunately, that is not the case in other parts of the world, where a tuberculosis diagnosis could lead to stigma if it is believed to be due to an advanced HIV infection. And people with low resources may not afford nets or repellents to keep malaria, dengue, Yellow Fever, Zika, West Nile, and other mosquito-borne infections at bay.
But There Is Always Hope
The successful eradication of smallpox proves that defeating these diseases is possible with global cooperation, sustained funding, and political will. Current initiatives focus on eliminating malaria and tuberculosis, though progress varies by region. The key lies in combining medical advances with improvements in living conditions, nutrition, and healthcare access. And, as mentioned above, destigmatization.
The story of these diseases reminds us that public health requires both scientific advancement and social progress. As we face new health challenges, the lessons learned from controlling these historic killers remain crucial for protecting future generations. And, while it may be fascinating to rank these killers, it is truly saddening to think that all those millions lost were mourned and missed by millions more who loved them.
(Special thanks to “” on Instagram for pointing out that smallpox may not have been the biggest infectious disease killer of all time.)
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