Saturday, January 4, 2025

Plague

 

                                        Plague.

                                     P.K.Ghatak, M.D.



Plague is an infectious disease of rodents and small wild mammals. It is caused by a bacterium, Yersinia pestis. Rats are the natural victims and also hosts of Yersinia pestis. Y. pestis spreads among the animals from the bites of the infected fleas known as Xenopsylla cheopis. Humans are accidental victims. Besides the bites of infected rat fleas, humans can also contract the infection while handling dead, infected animals with open skin lesions, consuming dead animals, and occasionally from a patient by inhaling aerosolized bacteria.

The bacteria:

Yersinia pestis belongs to the family of Enterobacteria.




Yersinia pestis evolved from Y. pseudotuberculosis. Y. pestis has acquired three important Plasmids over the years, which have made Y. pestis more aggressive, invasive, and successfully defeat host immune defense, weakening the endothelial adhesion between cells and producing extensive subcutaneous hemorrhage.

Y. pestis is a coccobacillus, measuring 0.5 to 1.0 micrometers by 3 micrometers. It has a rigid cell wall composed of peptoglycan, and another outer wall made with lipopolysaccharide, which secretes a biofilm, which enables Y. pestis to adhere to the cells of the victims. When stained with Giemsa stain, the bacterium resembles a safety pin due to the presence of metachromatic granules at both ends. Y. pestis is non motile. It grows in most culture media and prefers 28 degrees C, but can also remain active at 40 degrees C. It thrives equally well in high and low oxygen environments.


The Flea.

Out of two thousand fleas, only about 100 species of fleas are known to carry Yersinia and then, only three species are related to plague outbreaks. The most universal is Xenopsylla cheopis; the second one is X. brasiliensis, common in Africa, South America, and India; and the last one is X. astia, seen in Southeast Asia. In endemics,  Pulex irritants, a human flea and Ctenocephalides canis and felis, cat and dog fleas, also act as vectors.

The fleas are ectoparasites. The insect is small in size and grows to a maximum size of 6 mm. It is flat from side to side, has 3 body parts, but only the larger abdomen is visible without magnification. There are two appendages in the mouth with saw like serrated edges, used in cutting the skin of victims for blood. It can jump up to 2 feet with its long hind legs. Flea also finds house cats and dogs as good hosts, and the fleas can also infest humans.

Both male and female fleas must have a twice-daily blood meal for survival. The female fleas must have a blood meal before laying eggs in the rat holes. Fleas take 0.1 to 0.2 microM of blood from the victim. The fleas do not search for their prey; they wait till a victim arrives, and detect by sensing temperature and humidity variations. Then it jumps and lands on the victim. 

If the rat is not infected, the fleas keep on living on that rat for 100 days; if infected, the fleas die. Only the female flea drops to the ground to lay eggs and then waits for her next victim. When the rat has plague bacilli, the bacillus starts to grow in the rat's gut, and the growing colony produces a biofilm in the gut. The lumen of the esophagus is narrow due to a sphincter, and the biofilm produces a complete block and intestinal obstruction. The fleas feel starved and change hosts and bite repeatedly but fail to swallow, instead regurgitate their gut content and thereby spreading the infection among the rats, small mammals and humans.

Life cycle of the flea.

The flea undergoes 4 stages to complete a life cycle:  egg, larva, pupa, and imago or adult. Each gravid flea lays 30 eggs in the dart of the rat hole, every day for 50 to 100 days. In a week, the eggs hatch. The larva eats rat feces, unhatched eggs, and organic compounds. It molts twice in 10 days. A cocoon is formed in which a pupa grows and 14 days later, an imago or adult flea is born. The young flea must have a blood meal before it can sexually mature.

The rat.

The common household black rat, the Rattus rattus, and the brown sewer rat, the Rattus norvegicus, act both as the reservoir and victims of the plague bacillus.

When an infected flea bites the rat, if the inoculum is small, the rat becomes sick but recovers and then develops a kind of immune -understanding with Yersinia pestis. The bacterium multiplies in the rat and the rat survives. This creates a permanent rat reservoir of the plague bacillus. If the rat gets a heavy dose of Yersinia, it dies.

The humans.

The incubation period of plague is 2 to 8 days. At the site of a flea bite, an eschar develops. But it may be missed. A papule, nodule, vesicle, or pustule may be visible in some patients. The initial symptoms are chills, high fever, headaches, and prostration. The course of illness may take one of the three forms – Bubonic plague, Septicemic plague, or Pneumonic plague.

Bubonic plague:

In 24 hours after a flea bite and the beginning of fever, many marble-sized axillary or inguinal lymph nodes develop. These enlarging nodes are painful and warm to touch. After the initial regional lymph node enlargement, the nodes in the axilla and the cervical areas also enlarge. The nodes become matted together. The enlargement of the liver and spleen is common. Blochy subcutaneous hemorrhage develops at various places, and the fingers and toes turn black from the development of gangrene. This gives the patients a black appearance and so the bubonic plague was also called Black Death. Without the use of antibiotics, the death rate from bubonic plague is 30 %.

If the initial immune reaction fails to limit the infection, the bacteria enter the blood vessels. The bacteria become widespread and septicemia develops. The signs indicating a poor outcome of septicemia are: hypotension, circulatory collapse, hypoxemia, and cerebral symptoms dominate. In the days with no antibiotics, the death rate was 100%.

Septicemic plague:

Septicemia develops from bubonic plague, but septicemic plague may also develop without the bubonic stage.

Pneumonic plague:

The Yersinia pestis can be airborne in droplets when a patient coughs. The bacteria enter the victim's body through the nose and throat. The symptoms are: high fever, sore throat, and cervical adenopathy. This is followed by cough, chest pain, shortness of breath, hypoxemia, and hemoptysis. Within a day or two, septicemia develops. Mortality was 100 percent in pre-antibiotic days.

Diagnosis of plague:

The CBC and other tests reveal an aggressive acute infection. A sample of fluid obtained from the base of a bubo detects pestis on stained smears. In septicemia, blood cultures and in pneumonic plague tracheal aspirates grow Yersinia on culture.. In endemic areas of the world, the immunofluorescence assay of the capsular F1 antigen of Y. pestis is available and utilized. In more affluent countries, the Y. pestis antigen by PSA is performed. In the USA, Plague must be reported to the local health authorities and the CDC, and cultures are sent to the CDC for confirmation.

Treatment:

Gentamycin is generally prescribed; in some countries, Streptomycin is still in use. In addition, quinolines and tetracyclines are also effective. In meningoencephalitis, chloramphenicol is recommended.

The Scientists:

In 1894, two bacteriologists, Alexander Yersin, a Frenchman, and a Japanese associate, Ketasoto Shibasaburo, working independently, during an outbreak of bubonic plague in Hong Kong, identified a bacterium in the fluid taken from a bubo. Yersin confirmed the organism as the plague bacillus by injecting the fluid in an animal and subsequently recovering the same organism from its tissues after sacrificing it. He named the bacillus Pasteurella pestis. In 1970, the bacterium was renamed Yersinia pestis.

Another pair of French and Japanese, working independently, identified the rat as the reservoir and fleas as the vector. In 1897, Dr. Orgata Masanori found rat fleas carried the plague bacillus in Formosa, now called Taiwan. In 1898, a French investigator, Paul-Louis Simond from the Pasteur Institute, working in India, demonstrated the transmission of plague by the bites of infected fleas.

The Nobel Prize:

None of the above scientists was awarded the Nobel Prize in medicine, but in 1957, a French novelist, Albert Camus, was awarded the Nobel Prize in literature for his novel The Stranger and The Plague         ( 1947).

The Pandemics of Plague:

The earliest recorded history of the black death is present in ancient Buddhist texts. An outbreak of plague in Vasali (in Bihar province), India, and also been recorded its spread to Sri Lanka.

Scientists believe a mild variety of plague within rat colonies in Central Asia has persisted from ancient times. No one is sure when and how it became virulent and jumped to humans. In the early days, the disease was called pestilence. The priests blamed people for living a sinful life for pestilence and God punished them with pestilence. The priests recommended penance, self-flagellation, prayers, and puja to please God. No solution came from above, but a temporary relief was obtained from the inhalation of fragrant herbs and flowers.

The First Pandemic:

The first pandemic occurred in Rome in the time of the Roman emperor Justinian during the years 541 to 544. The disease originated in Abyssinia, Africa ( now Ethiopia and Eritrea). It spread westwards to Alexandria and to the east to Jerusalem and to Constantinople (Istanbul). In Constantinople alone, 10,000 people died every day. Eventually, the plague reached Denmark, Ireland, the Middle East, and Asia Minor. In 542 estimated total deaths in Europe, Asia, and Africa were 100 000. It was the bubonic plague.

Plague continued to smolder with local endemics for another 200 years.

The Second Pandemic of 1342 to 1352. It is better known as The Black Death.

The black death originated in Asia Minor. The disease was carried to Kaffa (Fedosya in Ukraine) by the Tatar army of Khan Janibeg. It then spread to the port city of Crimea. By ship with rats and sick people carried the plague to Genoa and then to all the port cities of the Mediterranean, England, and Norway. The war ended in a stalemate and the Tatars returned home and carried the plague with them to Russia and then to India. A quarter of the population of India perished from the Bubonic plague, and  10 to 20 percent of people died in Europe.

A second wave of bubonic plague occurred in 1361 in England and took another 10% of the population with it.

The Quarantine. The 40 days of isolation.

The officials in Venice prohibited ships from unloading goods and did not allow people to leave the ships for 30 days, in order to control the spread of plague (the Trenta).

 However, not achieving the desired results, they extended the prohibition to 40 days. Soon, quarantine became a tool for the containment of any infectious disease. Different States in Europe restricted the movements of people from traveling during the period, and it became known as the Cordon Sanitaire.

The Great Plague of London of 1665 to 1666.

A major outbreak of Pneumonic plague occurred in London, England, in 1665, and 7,000 people died daily. The severity of the illness is aptly expressed in a nursery rhyme :

Ring, a-ring o'rosies

A pocketful of posies

Atishoo, atishoo

We all fell down.


In a simple form:

A red blistering rash

Fragrant herbs and flowers

Sneezing and coughing

All are dead.


The Third Pandemic of 1894.

In 1855, in Yunnan, China, a local outbreak of plague took place. It spread near and far along the opium smuggling routes. In 1984, Canton and then Honk Honk saw an increasing number of bubonic plague victims. The plague arrived in Bombay, India ( Mumbai) via cargo ships. It produced panic in Bombay, and people scattered out of the city; the plague went along with them wherever they went. This plague killed a third of the Indian population.

In 1900, the plague reached Australia, and local outbreaks continued till 1925.

The 3rd pandemic ended in 1959. The total death is estimated to be 15 million.

It is not over:

In 1990, the island of Madagascar saw multi-drug resistant Plague. The island is a potent source of new plague.

The Final Word:

From the very beginning, humanity faced an uncertain future on Earth. Infection took a major toll on sick children and the elderly; childbirth was a horror story. No one recorded the untimely demise of so many young mothers, leaving behind their families. The progress in medical science, public health, and vaccination were able to eliminate Smallpox and put Cholera out of most countries and cornered Plague with very effective antibiotics and public health measures.

However, like Heisenberg's uncertainty principle, the present generation is both here and there in their belief in public health and particularly in vaccination.

 In case a multi-drug resistant laboratory-engineered airborne plague bacillus delivered and exploded over densely populated cities by a terrorist group, that action will take us back to the days of Penance, Payer, and Puja.

edited: June 2025.

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