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The battle never ends: Horrifying pandemics in human history

Painting by Michel Serre (1658-1733) representing the town hall of Marseille during the plague of 1720. (Wikipedia)

By Ang Li

In a pandemic era when COVID-19 death toll has reached 2 million worldwide, everyone has been anxiously waiting for the vaccines reaching those in need and actually turning things around. But if you think twice about it, the whole human history is actually a continuous battle between us and different kinds of pandemics. Among these battles, some have been eventually won by human beings, some are no longer major concerns for most of us, and others are something people still fighting hard against. By studying the history of pandemics, we are also getting to know how we should learn from experiences and be better prepared in the lengthy battle against coronavirus.

1. Black Death

Yersinia pestis (200× magnification), the bacterium which causes plague (Wikipedia)

Dubbed as "The Great Plague", Black Death was a devastating pandemic of bubonic plague that struck Europe and Asia in the mid-1300s. The plague is thought to have originated in Asia over 2,000 years ago and was likely spread by trading ships. In 1347, it arrived in Europe when 12 ships from the Black Sea docked at the Sicilian port of Messina. People gathered on the docks were met with a horrifying scene: Most sailors aboard the ships were dead, and those still alive were gravely ill and covered in black boils that oozed blood and pus. Over the following five years, this pandemic killed more than 20 million people in Europe—almost one-third of the continent's population. In total, the plague may have reduced the world population from an estimated 475 million to 350–375 million in the 14th century.

Symptoms & How was it spread?

The Great Plague killed about a quarter of the capital's population. (Hulton Archive)

Symptoms of the disease include a fever of 38–41 °C, headaches, painful aching joints, nausea and vomiting, and a general feeling of malaise. Left untreated, of those that contract the bubonic plague, 80 percent die within eight days.

The Italian poet Giovanni Boccaccio has depicted the appalling situations of those infected, "At the beginning of the malady, certain swellings, either on the groin or under the armpits…waxed to the bigness of a common apple, others to the size of an egg, some more and some less, and these the vulgar named plague-boils."

Blood and pus seep out of these strange swellings, which are followed by a host of other unpleasant symptoms—fever, chills, vomiting, diarrhea, terrible aches and pains—and then, in short order, death.

Black Death attacks the lymphatic system, causing swelling in the lymph nodes. If untreated, the infection can spread to the blood or lungs.

The disease is typically spread through the bite of infected fleas, frequently carried by rats. It is terrifyingly, indiscriminately contagious, and just as Boccaccio described, "the mere touching of the clothes appeared to communicate the malady to the toucher." It's also shockingly efficient. People who were perfectly healthy when they went to bed at night could be dead by morning.

Necrosis of the nose, the lips, and the fingers and residual bruising over both forearms in a person recovering from bubonic plague that disseminated to the blood and the lungs. (Wikipedia)
Spread of Black Death (Wikipedia)

How did it end?

The officials in the Venetian-controlled port city of Ragusa were able to slow its spread by keeping arriving sailors in isolation until it was clear they were not carrying the disease, which is similar to nowadays' social distancing to slow the spread of pandemic. The sailors were held on their ships for 40 days, which is also the origin of the term "quarantine" used today.

Although Black Death had run its course by the early 1350s, the plague reappeared every few generations for centuries. Modern sanitation and public-health practices have greatly mitigated the impact of the disease but have not eliminated it. While antibiotics are available to treat the Black Death, according to the World Health Organization (WHO), there are still 1,000 to 3,000 cases of this plague every year.

2. Leprosy

M. leprae, one of the causative agents of leprosy: As an acid-fast bacterium, M. leprae appears red when a Ziehl-Neelsen stain is used. (Wikipedia)

Leprosy, also known as Hansen's disease, is a chronic infectious disease caused by Mycobacterium leprae. The disease mainly affects the skin, the peripheral nerves, mucosal surfaces of the upper respiratory tract and the eyes. Leprosy is known to occur at all ages ranging from early infancy to very old age. Leprosy is curable and treatment in the early stages can prevent disability.

Symptoms & How was it spread?

Father Damien, taken in 1889, weeks before his death by William Brigham at a sidewall of the St. Philomena Catholic Church on the settlement. He was nearly disfigured by leprosy. (Wikipedia)

Symptoms may occur within one year but can also take as long as 20 years or even more to occur. Clinical signs are easy to observe. Skin lesion has usually a different pigmentation than the surrounding normal skin (less pigmented, reddish or copper-colored) and may have various aspects (flat, raised or nodules). The skin lesion can be single or multiple and may show a loss of sensation in the skin. Skin smears are also used to diagnose leprosy.

Leprosy is spread between people, although extensive contact is necessary. About 95% of people who contract M. leprae do not develop the disease. Spread is thought to occur through a cough or contact with fluid from the nose of a person infected by leprosy. Genetic factors and immune function play a role in how easily a person catches the disease. Leprosy does not spread during pregnancy to the unborn child, or through sexual contact.

Leprosy occurs more commonly among people living in poverty. There are two main types of the disease – paucibacillary and multibacillary, which differ in the number of bacteria present. A person with paucibacillary disease has five or fewer poorly pigmented numb skin patches while a person with multibacillary disease has more than five skin patches.

How did it end?

New cases of leprosy in 2016. (Wikipedia)

Leprosy is curable with a combination of drugs known as multidrug therapy, as the treatment of leprosy with only one antileprosy drug (monotherapy) will result in the development of drug resistance to that drug. The combination of drugs used in the MDT depends on the classification of the disease (paucibacillary or multibacillary leprosy). Treatment of paucibacillary leprosy is with the medications dapsone, rifampicin, and clofazimine for six months, while treatment for multibacillary leprosy uses the same medications for 12 months. These treatments are provided free of charge by the WHO.

Having affected humans for thousands of years, Leprosy is relatively rare nowadays. Although the number of cases worldwide continues to fall, there are parts of the world where leprosy is more common, including Brazil, South Asia (India, Nepal, Bhutan), some parts of Africa (Tanzania, Madagascar, Mozambique), and the western Pacific.

3. Smallpox

This transmission electron micrograph depicts a number of smallpox virions. (Wikipedia)

Smallpox is an acute contagious disease caused by the variola virus, a member of the orthopoxvirus family. It was one of the most devastating diseases known to humanity and caused millions of deaths before it was eradicated. It is believed to have existed for at least 3,000 years.  

Symptoms & How was it spread?

A child with smallpox in Bangladesh in 1973. The bumps filled with thick fluid and depression or dimple in the center are characteristic. (Wikipedia)

Early symptoms of smallpox include high fever, fatigue and severe back pain, and less often, abdominal pain and vomiting. Two to three days later, the virus produces a characteristic rash with bumps full of a clear liquid, which later fill with pus and finally develop a crust that dries and falls off. The rash begins on the face and hands, then spreads to the rest of the body. Lesions develop in the mucous membranes of the nose and mouth and ulcerate soon after formation.

Smallpox is transmitted from person to person via infective droplets during close contact with infected people who have symptoms of the disease, or in some cases through contaminated clothing and bedding. It has an incubation period of 7–17 days after exposure and only becomes infectious once a fever develops. People remain infectious until the last scabs fall off.

Smallpox was fatal in up to 30% of cases. Often those who survived had extensive scarring of their skin, and some were left blind.

How did it end?

Three former directors of the Global Smallpox Eradication Program read the news that smallpox had been globally eradicated, 1980. (Wikipedia)

The smallpox vaccine, created by Edward Jenner in 1796, was the first successful vaccine to be developed. He observed that milkmaids who previously had caught cowpox did not catch smallpox and showed that a similar inoculation could be used to prevent smallpox in other people.

The WHO launched an intensified plan to eradicate smallpox in 1967. Widespread immunization and surveillance were conducted around the world for several years. The last known natural case was in Somalia in 1977. In 1980, WHO declared smallpox eradicated – the only infectious disease to achieve this distinction. This remains among the most notable and profound public health successes in history.

4. Ebola

Electron micrograph of an Ebola virus virion (Wikipedia)

Ebola virus disease (EVD), formerly known as Ebola hemorrhagic fever, is a severe, often fatal illness affecting humans and other primates. The average EVD case fatality rate is around 50%. Case fatality rates have varied from 25% to 90% in past outbreaks.

The first EVD outbreaks occurred in remote villages in Central Africa, near tropical rainforests. The 2014–2016 outbreak in West Africa was the largest and most complex Ebola outbreak since the virus was first discovered in 1976. There were more cases and deaths in this outbreak than all others combined. It also spread between countries, starting in Guinea then moving across land borders to Sierra Leone and Liberia.

It is thought that fruit bats of the Pteropodidae family are natural Ebola, virus hosts.

Symptoms & How was it spread?

Two nurses standing near Mayinga N'Seka, a nurse with Ebola virus disease in the 1976 outbreak in Zaire. N'Seka died a few days later. (Wikipedia)

The virus is transmitted to people from wild animals (such as fruit bats, porcupines and non-human primates) and then spreads in the human population through direct contact with the blood, secretions, organs or other bodily fluids of infected people, and with surfaces and materials (e.g. bedding, clothing) contaminated with these fluids.

The incubation period, that is, the time interval from infection with the virus to onset of symptoms, is from 2 to 21 days. A person infected with Ebola cannot spread the disease until they develop symptoms.

Symptoms of EVD can be sudden and include: fever, fatigue, muscle, pain, headache, and sore throat. This is followed by vomiting, diarrhea, rash, symptoms of impaired kidney and liver function, and in some cases internal and external bleeding (e.g. oozing from the gums, blood in the stools). Laboratory findings include low white blood cell and platelet counts and elevated liver enzymes.

How did it end?

VHF isolation precautions poster (Wikipedia)

There is no proven treatment for Ebola but simple interventions early on can significantly improve chances of survival. This includes rehydration with fluids and body salts (given orally or intravenously), and treatment of specific symptoms such as low blood pressure, vomiting, diarrhea and infections.

A range of potential treatments including blood products, immune therapies and drug therapies are currently being evaluated. Hand hygiene is the most effective way to prevent the spread of the Ebola virus.

An experimental Ebola vaccine known as rVSV-ZEBOV proved highly protective against the deadly virus in a major trial in Guinea in 2015. It is being used in response to the current outbreak in the Democratic Republic of the Congo (DRC) using a ring vaccination protocol.

After lasting for nearly six months, and infecting 130 people including 55 deaths, the DRC declared its eleventh Ebola outbreak over on Nov. 18, 2020. Although this outbreak is now over, it is important to maintain vigilance against a resurgence of Ebola.



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