Plague

 

                                        Plague.

                                     P.K.Ghatak, M.D.

Plague is an infectious disease of the 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 get infected while handling dead infected animals having open skin lesions, eating 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. Over the thousands of years Y. pestis has acquired three important Plasmids, which made Y. pestis more aggressive, invasive, successfully counteract host immune defense and weaken the endothelial adhesion between the cells and produce extensive subcutaneous hemorrhage.

Y. pestis is a coccobacillus, measuring 0.5 to 1.0 micrometer by 3 micrometers. It has a rigid cell wall composed of peptoglycan, which protects it and it has another outer wall made with lipopolysaccharide, which secretes a biofilm, enhancing Y. pestis to adhere to the cells of the victims. When stained with Giemsa stain it 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 in 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.brasilences, common in Africa, South Americas 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, grows to a maximal 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 from the pets, the fleas also can infest humans.

Both male and female fleas must have a twice-daily blood meal for survival and females must have a blood meal before laying eggs in the rat holes. At each bite it takes 0.1 to 0.2 2microM of blood of the victim. The fleas do not search for their prey, they wait till a victim arrives, which they detect by sensing temperature and humidity variations. Then it jumps and lands on the victim. From this point on the lives of fleas take different paths:

If the rat is not infected with Yersinia, then the fleas keep on living on that rat for 100 days. Only the female flea drops to the ground to lay eggs and then waits for her next victim. If the rat has plague bacillus, the bacillus starts to grow in the rat's gut and the growing colony produces a biofilm in the gut. At the esophagus and midgut junction, the lumen is narrow due to a sphincter; 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 spread 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 and yet- to - hatch other eggs and organic compounds; and molts twice in 10 days. After that, it develops into a cocoon 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 ratus, 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 on the other hand, 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 not be noticed. A papule, nodule, vesicle, 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 enlarged nodes are painful and warm to touch. After the initial regional lymph node enlargement, usually in the groin, the nodes in the axilla and the cervical areas also enlarge. The nodes become matted together. The enlargement of the liver and spleen are common. Blochy subcutaneous hemorrhage develops at various places and the fingers and toes turn black due to 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 in bubonic plague is 30 %.

In some unfortunate patients, the initial immune reaction fails to limit the infection at the local site and the bacteria enter the blood vessels. The bacteria now become widespread and the septicemia develops. The usual symptoms and signs of septicemia develop, among them -  hypotension, circulatory collapse, hypoxemia and cerebral symptoms dominate and also determine the course of the illness. In the days with no antibiotics, the death rate was 100%.

Septicemic plague:

Septicemia may develop as indicated above, following a bubonic plague onset, but septicemic plague may also develop without the bubonic stage.

Pneumonic plague:

The Yersinia pestis can be airborne with the 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 is parallel with septicemic plague.

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 are performed and in pneumonic plague tracheal aspirates are cultured. 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, Y. pestis antigen by PSA is performed. In the USA, Plague must be reported to the local health authorities and CDC and cultures are sent to 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 an associate of Koch, a Japanese national, 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 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 describing the time of Buddha. An outbreak of plague in Vasali in India, now in Bihar province, India, was documented and also noted its subsequent spread to Sri Lanka.

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

However, even at that time, the spread of plague along the silk route was well known.

The First Pandemic:

The first pandemic occurred in Rome in the time of 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 was 100, 000. The type of plague was bubonic.

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 Deaths.

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, the plague reached Genoa and then to all the port cities of the Mediterranean. England and Norway were next victims. The Tartars could not win the war and returned home and they carried plague with them to Russia and to India. A quarter of the population of India perished from Bubonic plague, 10 to 20 % 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, initially for a period of 30 days, 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 containment of any infectious disease. Different States in Europe, restricted movements of people from traveling east to west 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. 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 blistery rash

Fragrant herbs and flowers

Sneezing and coughing

All are dead.

The Third Pandemic of 1894.

In 1855, 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 of that time.

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

The 3^rd pandemic ended in 1959. Total death 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 early beginning, humanity faced an uncertain future on the earth. Infection took a major toll on sick children and the elderly; the childbirth was a horror story. No one recorded the untimely demise of so many young mothers leaving behind their families. The progress of the 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 the public health and particularly in vaccination.

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

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