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7 Deadliest Diseases in History: Where are they now?

Medically reviewed by Carmen Pope, BPharm. Last updated on May 14, 2023.

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Plague, smallpox, SARS, Leprosy, Polio... do you think these deadly diseases have been eliminated because we don't hear about them any more? Think again. Some of them may even be lurking in your own backyard!

1. The Black Death: Bubonic Plague

The Black Death ravaged most of Europe and the Mediterranean from 1346 until 1353. Over 50 million people died, more than 60% of Europe's entire population at the time.

Many historians believe it started in the Steppes of Central Asia, a vast area of grassland that even today still supports one of the world's biggest plague reservoirs - an area where rodents live in great numbers and density (also called a plague focus).

Plague is mainly spread through the bite of a flea infected with the plague-causing bacterium, Yersinia pestis. Fleas typically live on small animals such as rats, gerbils, marmots, and squirrels, and periodically, explosive outbreaks of plague occur among these susceptible hosts. Huge numbers of animals succumb to infection and die. Hungry fleas turn to humans and within three to five days of a bite, fever, headache, chills, and weakness develop. Lymph nodes closest to the bite site swell to form a painful bubo in the variant of the plague known as bubonic plague. Infection may spread throughout the bloodstream and affect respiration in the lungs. Without prompt antibiotic treatment, 30% to 100% of infected people die.

Is Plague Lurking In A Town Near You?

The epidemic of plague in the 14th century was not the only significant plague outbreak recorded in human history. The first reported pandemic broke out in Egypt in 541 and was designated “The Plague of Justinian”. The last major plague event began in the war-torn Yunnan province of China, reaching Hong Kong in 1894.

Plague has never been eradicated, but thanks to vaccination and antibiotics, few people die of it. Plague foci are found on every continent except Oceania and Antarctica and it still circulates among mammals such as prairie dogs, jackrabbits, coyotes, black-footed ferrets, and even domestic pets.

Between 2010 and 2015 there were 3248 cases of plague reported worldwide, including 584 deaths. Most cases have occurred in Madagascar, The Democratic Republic of Congo, and Peru, where the plague is endemic.

From 1st August through until the 30th April 2018, Madagascar experienced a plague outbreak, with 2671 confirmed, probable and suspected cases of plague, including 239 deaths reported. This was at least six times the usual annual average of around 400 cases.

In the United States alone, 1040 confirmed or probable cases of plague occurred between 1900 and 2016; 80% of which were classified as the bubonic form and most of these cases occurred in the rural West. Between 2016 and 2019, just 11 cases were reported. In 2021, a dead chipmunk tested positive for the bubonic plague in Lake Tahoe, and a New Mexico resident was diagnosed with the plague, likely from a flea brought home by a pet. 9 cases were reported in the U.S. in 2020, with 2 deaths.

2. The Speckled Monster: Smallpox

The origins of smallpox have been lost in prehistory but research suggests it first appeared around 10,000 BC. Telltale pockmarks adorn the mummified remains of the great Egyptian Pharaoh Ramses V (dated 1156 BC) and the disease is described in ancient Sanskrit texts.

Smallpox is caused by the variola virus. Humans are the only natural hosts of smallpox and transmission depends upon direct contact with an infected person or infected bodily fluids, contaminated bedding, or clothing. Airborne transmission is rare, although is more likely in enclosed settings such as buildings, buses, and trains.

An incubation period of up to 17 days (average 12 to 14 days) follows exposure to the virus and people are not contagious at this time. Initial symptoms are generally flu-like before small spots start to develop inside the mouth and on the tongue. Within 24 hours a rash starts on the face and quickly spreads before evolving into raised volcano-like pustules filled with a thick, opaque fluid. These pustules may take up to two weeks to scab over, leaving marks on the skin that eventually become pitted scars.

The yearly Death Rate In The 1800s Was 400,000 From Smallpox

During the 18th century, over 400,000 people died annually in Europe from smallpox. Overall fatality rates were around 30%; however, rates were much higher in infants (80-98%), and one-third of all survivors went blind.

One thing was obvious among survivors of the disease - they never caught it again. This observation started the human fight against smallpox. First came variolation which involved blowing dried smallpox scabs up a person's nose, deliberately infecting them with the disease.

Inoculation used a lancet to transfer the contents of a smallpox pustule under the skin of a non-immune person. It was a bit risky - some people developed smallpox from the procedure or contracted other diseases such as tuberculosis or syphilis. But fatality rates associated with inoculation were 10 times lower than those associated with naturally occurring smallpox.

In the late 1700s, at least two people acted on the observation that dairymaids who had cowpox, never contracted smallpox. In 1774, Benjamin Jesty used material from cows with cowpox to inoculate his wife and two young sons. In 1796, Dr. Edward Jenner used matter from a cowpox-infected young dairymaid to protect an 8-year-old boy. Two months later he inoculated the same boy with smallpox, and no disease developed. Dr. Jenner's work paved the way for vaccination as we know it today.

A Victory For Vaccination. The Smallpox Vaccine Also Works For Mpox

The last known case of smallpox was in Birmingham in 1978 when 40-year-old medical photographer Janet Parker caught the virus from the anatomy department she worked in at Birmingham Medical School. According to the World Health Organization (WHO), smallpox has been successfully eradicated worldwide. This global success is attributed to a mass vaccination campaign that began in 1967 and continued until the WHO announced that the disease had been eliminated.

Although the disease has been eliminated, both the Centers for Disease Control and Prevention (CDC) and the WHO have concerns that the virus could be used for bioterrorism. This topic has been dramatized in movies, books, and TV shows. Although the possibility of smallpox being used as a biological weapon deserves consideration, the actual risk is likely very low. However, strategies are in place to protect the public should this ever happen and large quantities of the smallpox vaccine have been stockpiled.

The virus that causes smallpox is closely related to the virus that causes Mpox (previously called monkeypox), and in 2022, an outbreak of Mpox occurred which the World Health Organization declared a public health emergency of international concern (PHEIC). Although Mpox is not as deadly as smallpox, it can still lead to medical complications and death in 3% to 6% of cases reported, and in severe cases, pneumonia, confusion, and vision loss have occurred.

Data has shown that the smallpox vaccine can protect against Mpox, and there are two vaccines available to protect against people at risk of exposure to Mpox: ACAM2000 (recommended for laboratorians working with certain orthopoxviruses and military personnel), and Jynneos (also known as Imvamune or Imvanex) for other people at risk for exposure. When properly administered before exposure or within 4 days of exposure, these vaccines are up to 85% effective at preventing disease. Vaccination given within 4–14 days after exposure to the virus may reduce the symptoms of the disease, but not prevent it.

Tecovirimat (TPOXX) is a treatment for smallpox that is also effective against Mpox. It was tested in animals with Mpox, not smallpox because the use of the smallpox virus is highly controlled and not considered ethical. Because it was only FDA-approved for smallpox treatment, it is used off-label for Mpox, under the CDC Investigational New Drug protocol. It offers significant relief from Mpox symptoms.

3. Severe Acute Respiratory Syndrome (SARS)

The history of SARS was short but not so sweet.

SARS generated widespread panic in 2003 and was caused by a previously unknown coronavirus (SARS-CoV-1) - the same family of viruses that causes Covid-19.

Symptoms of SARS began two to ten days after coming into contact with the virus and included a high fever, headache, body aches, and sometimes diarrhea. But the main symptom of concern was the severe breathing difficulties associated with SARS, and almost all those infected developed pneumonia. By the end of 2003, 774 people had died out of the 8,098 infected people notified to WHO. Many more people need to be hospitalized for breathing assistance.

SARS is spread through close contact with infectious droplets released during a cough or sneeze. SARS started in Asia, and researchers have identified the most likely source as wild Chinese Horseshoe bats that had been caught and brought to market. These bats harbored a SARS-like virus that subsequently infected civets before mutating; which meant that humans were now susceptible to the virus. Within a year, the infection had spread to more than two dozen countries before it was contained through public health measures.

SARS Prepared Us For MERS But Not COVID-19

One of the most concerning facts about viruses, particularly those of the coronavirus virus family, is their ability to rapidly mutate (change).

Although surveillance is ongoing for another outbreak of SARS there have only been a small number of cases reported; mostly from laboratory accidents or, possibly, through animal-to-human transmission (Guangdong, China).

Middle East Respiratory Syndrome (MERS), is another coronavirus infection that can be fatal. A total of 2574 laboratory-confirmed cases of MERS were reported up until the end of May 2021. This figure included 886 associated deaths (a fatality rate of over 34%). The majority of cases were reported in Saudi Arabia and are linked to contact with camels, their dung, milk, or meat. MERS can cause severe respiratory and kidney failure.

In late 2019, early 2020, SARS-CoV-2 started to create havoc around the world. Initially, experts thought it was just another "flu" virus, but the speed and ease of its spread coupled with its high fatality rates quickly proved them wrong. The impact of the condition caused by SARS-CoV-2 called Covid-19, not only forced unprecedented lockdowns worldwide but its social and economic impacts will be felt for years to come.

We should have been better prepared. Another corona-type virus was always on the cards. But possibly SARS and MERS gave us a false sense of security that new viruses were easy to contain and beat, even if they did have high fatality rates, such as MERS. Here's hoping the lessons we have learned from COVID-19 will make reactions to future animal-transferred viruses quicker and more effective.

4. Avian Influenza: Not Just One For The Birds

Just like humans, birds get the flu.

Bird flu - also called Avian influenza - is common and several major outbreaks have occurred sporadically worldwide since the disease was first recorded in Italy in 1878. It took until 1955 to discover that the virus causing bird flu was an influenza type A virus.

Avian influenza occurs naturally among wild aquatic birds and can easily spread to more susceptible farmed poultry - millions of chickens, geese, and turkeys were destroyed to prevent further spread of the disease following the outbreaks that occurred in 2015 and 2016. Between January 2022 and March 15, 2023, ten sporadic human cases of A(H5N1) were reported from seven countries, and two died. The latest case was reported in Chile in April, 2023.

The H7N9 and H5N1 of Avian influenza are the most likely strains to infect humans, although other strains have caused small outbreaks. H7N9 is considered the influenza A virus with the greatest potential public health impact.

5. Ebola: On The Radar Again

Ebola is a severe, often fatal disease (death rates average 50% [range 25-90%]), caused by the Ebola filovirus. There are five different types of Ebola virus, four of which are known to cause disease in humans.

Ebola was first discovered in 1976 and bats are thought to be the most likely reservoir (natural permanent host) of the virus. The virus readily spreads to humans and from human to human. Direct contact (through broken skin or mucous membranes) with an infected person or animal (either living or dead), or with objects such as contaminated needles and syringes is the most common way Ebola is spread. Cases of sexual transmission from people who have survived the virus have also been reported, months after their recovery.

Symptoms may appear from two to 21 days (average 8-10 days) after exposure to the virus and include fever, severe headache, muscle pain and weakness, diarrhea, vomiting, bleeding and bruising, and death. Survivors develop antibodies that protect them from further infection for at least 10 years. The most significant outbreak of Ebola in recorded history occurred from 2014 to 2016, predominantly in Guinea, Sierra Leone, and Liberia.

Ebola: Risk is Low As Long As Sensible Precautions Are Taken

Reports issued by the CDC indicate that 28,616 people were infected with confirmed or probable Ebola, and 11,310 died throughout the 2014-2016 outbreak. In the U.S., eleven people were documented as having Ebola; four of whom had developed symptoms once back in the United States. Seven of the 14 had been medically evacuated from other countries. Two died.

Even though the World Health Organization (WHO) declared the end of the Ebola outbreak in Liberia on the 9th of June, 2016, there is always a risk of Ebola in countries with very weak health systems and where the virus is prevalent in wild animals. Small outbreaks continue to happen and efforts to contain them are often hampered by conflict and violence in the area. The latest outbreak occurred in Uganda between 20 September 2022 and 11 January 2023 and involved a total of 164 people with a case fatality rate of 34%.

In December 2019, Ervebo (Ebola Zaire Vaccine, live) was approved for adults over the age of 18. Ervebo is administered as a single dose, intramuscularly. It is not known how long Ervebo protects against Ebola.

In October 2020, Inmazeb became the first treatment to be approved by the FDA for Zaire ebolavirus. Inmazeb is a mixture of three monoclonal antibodies: atoltivimab, maftivimab, and odesivimab-ebgn, and may be given to treat infection in adults and children, including newborns of mothers who have tested positive for the virus. It is administered as a single intravenous infusion (a one-off dose) and it is not known if Inmazeb is effective for other species of Ebolavirus or Marburgvirus.

6. Leprosy: A Feared Disease That Features In The Old Testament

Leprosy is an infection caused by the slow-growing bacterium, Mycobacterium lepraehas. It has a long incubation period - two to five years (range 6 months to 40 years) and symptoms usually start as a numbness or loss of feeling in a defined area of skin - reflecting the affinity of the bacterium for nerve cells.

Despite not being very contagious, leprosy has been feared and misunderstood throughout its history. Initially thought to be a curse or a punishment from God, leprosy sufferers were stigmatized and forced to wear special clothing or ring bells to warn others when they were approaching. Symptoms vary from person to person and tend to progress with time; ranging from mild, indeterminate hypopigmented skin lesions to blindness, deformity, and severe facial disfigurement.

Still Prevalent, But Curable With Prolonged Treatment

Leprosy is still prevalent today but usually goes by the name of Hansen's disease. Globally, nearly 200,000 cases of Hansen's disease are reported to the World Health Organisation (WHO) every year, and it mainly affects people living in low-lying, humid, tropical, and subtropical areas near the equator, such as India. About 100 new cases occur annually in the U.S., most of which involve immigrants from developing countries. However, in 2015, two people acquired leprosy after contact with a nine-banded armadillo. Approximately 15% of armadillos in southern Texas and Louisiana have been found to harbor the bacteria.

Drug treatment of leprosy is prolonged and complicated and usually involves a combination of antibiotics (such as dapsone, rifampin, and clofazimine) for at least six months, in most cases longer. In some countries, thalidomide - a drug most famous for causing birth defects in the 1950s and 60s - is used to treat complications of leprosy such as erythema nodosum leprosum.

Although leprosy is curable, deformities and nerve damage that occur before treatment begins are often irreversible.

7. Polio: The Most Dreaded Childhood Disease Of The 1940-50s

Polio is a crippling infectious disease that is often fatal. Children under the age of five are especially susceptible. Although periodic epidemics occurred during the late 19th century, it was the spike in prevalence that occurred in the 1940s and early 1950s that triggered the start of the worldwide campaign of polio vaccination.

Polio is caused by the very contagious and resilient poliovirus and spreads from person to person, most commonly through contact with infected feces. Feces can remain infectious for several weeks, as can food, water, or objects contaminated by feces. Approximately 72% of people who catch polio show no symptoms. Twenty-five percent develop flu-like symptoms (for example, sore throat, fever, tiredness, headache, nausea, abdominal pain) within a week or two after infection. A small proportion of these people will go on to develop more severe symptoms such as paresthesia (burning or prickling limb pain), meningitis (infection of the brain and spinal cord), limb weakness, and paralysis that may lead to permanent disability and death if the respiratory muscles are affected.

Polio: Vaccination Is Key To Global Eradication

Polio can be prevented through immunization, and since 1988, the World Health Assembly has resolved to eradicate polio worldwide. Since 1988 when the Global Polio Eradication Initiative was launched, the annual number of wild poliovirus cases has declined by more than 99.9% worldwide. Of the three serotypes of wild poliovirus, type 2 was certified as eradicated in 2015 and type 3 was certified as eradicated in 2018. Only two polio-endemic countries remain, Afghanistan and Pakistan since Nigeria recorded the last case of wild poliovirus type 1 transmission in September 2018.

However, in recent years there has been a spike in polio cases, with over 200 cases of wild polio being reported in 2020, mostly in Afghanistan and Pakistan. Rogue viruses, lockdowns, and the Taliban are thought to be to blame.

Worryingly, polio seems to have re-emerged in both the U.S. and the United Kingdom. On July 21, 2022, the public was alerted to a case of polio in an adult in Rockland County, making it the first U.S. polio case since 2013. Rockland County has a very low polio vaccination rate. Then on August 4, 2022, researchers found wastewater samples positive for the polio virus genetically linked to the Rockland County resident diagnosed with polio, indicating community spread. The U.S. has not reported a case of naturally occurring paralytic polio (wild poliovirus) since 1979 when an outbreak occurred among the Amish in several Midwestern states. Of the previously notified polio cases that have occurred some were acquired outside of the U.S. and most were vaccine-associated, mostly caused by contact with feces contaminated with the live oral poliovirus vaccine (OPV).

OPV is no longer used as a polio vaccine in the U.S., although several overseas countries still use it. The inactivated poliovirus vaccine (IPV) is now the preferred vaccine.

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