Parasite Lost

Ernst Haeckel's illustration of parasitic worms from the 1904 edition of Kunstformen der Natur. A Taenia solium rectangular proglottid and round scolex can be seen in the middle right of this image.

Ernst Haeckel’s illustration of parasitic worms from the 1904 edition of Kunstformen der Natur. A Taenia solium rectangular proglottid and round scolex can be seen in the middle right of this image.

While parasites are fantastically well-adapted to life in their specific hosts, that usually means they are somewhat lacking in the “living literally anywhere else” department. Thus, when natural selection has nixed the ability to read a map and a parasite finds itself in unfamiliar territory, it is rarely very good at improvising.

Years of co-evolution with their hosts have helped many parasites find a happy medium between harming its host and causing just enough damage to happily feed, reproduce, and spread to a new host. After all, it’s ill-advised to destroy your meal ticket. However, if a parasite finds itself in a host that is not a usual part of its lifecycle – an incidental infection – the usual rules no longer apply.

CREEPING ERUPTION

As a parasite’s attempts to MacGyver its way out of an incidental host to a more familiar one often aren’t pretty, incidental infections can be more severe, or simply more bizarre, than the normal course of infection.

Take, for example, the case of cutaneous larval migrans. Cutaneous larval migrans, also known by the appetizing names “creeping eruption” and “sandworm,” occurs when a human becomes infected with canine hookworm larvae. These parasites have evolved to infect the intestines of dogs and other canids, and so become very confused when they find themselves in a two-legged, hairless ape instead of a loveably dopey quadruped.

A leg with the red, itchy trails characteristic of cutaneous larval migrans. Image: Grook Da Oger

A leg with the red, itchy trails characteristic of cutaneous larval migrans.
Image: Grook Da Oger

Rather than stopping to ask for directions, the now very lost larvae short-circuit and meander in the upper layers of the skin, trying to find their way to the gut. This aimless rambling gives the disease its name – though it uses more SAT words than necessary to say so, “cutaneous larval migrans” just means “worm larvae that wander in the skin.”

The result of the larvae’s migration through the skin is an angry, red, very itchy rash. The little worms actually leave behind tiny, visible trails on the skin in their search for a familiar environment (someone call Kevin Bacon.)

On the bright side, since the parasites are not well-adapted to life in a human host, they cannot complete their life cycle and survive in people. As a result, the larvae die within a few weeks and the rash clears up on its own, though treatment with standard anthelmintic drugs can speed up the process.

An 1831 illustration of Taenia solium by Johann Gottfried Bremser

An 1831 illustration of Taenia solium by Johann Gottfried Bremser

MUTUALLY-ASSURED DESTRUCTION

Sometimes meeting a familiar host at an unfamiliar time can be equally as disastrous for the parasite and the host.

The pork tapeworm, Taenia solium, is a very common human intestinal worm. If a person eats undercooked pork that is infected with hard, spherical cysticerci – encysted T. solium larvae – the digestive proteins in the intestines propel the worm into the next stage of its lifecycle.

During this stage, the worm latches onto the intestinal lining, feeds itself on the nutrients in its surroundings, and sheds eggs in the feces of their human host. Pigs, who are not particularly known for their discerning palates, become infected upon eating these eggs, completing the worm’s lifecycle.

While not pretty, a normal Taenia infection is not severe; if any symptoms show up at all, the worst of them include indigestion and mild anemia. However, when it comes to parasites, timing is everything. Even a relatively harmless parasite can be thrown for a loop if a host enters the mix at the wrong stage of its lifecycle.

If a human ingests T. solium eggs instead of its larvae, that person effectively takes the place of the pig in the lifecycle. This means that cysticerci form in the tissues of the human instead of the pig.

This MRI image shows the brain of a patient suffering from Neurocysticercosis. Each dark round spot is an encysted Taenia solium larva.

This MRI image shows the brain of a patient suffering from Neurocysticercosis. Each dark, round spot is an encysted Taenia solium larva.

This isn’t ideal for the parasite; as cannibalism is typically frowned upon in polite society, a human host at this stage of the lifecycle is a dead-end for the worm. As a result, pork tapeworms haven’t had a chance to evolve to become as good at forming cysticerci in humans as they are in pigs.

These misplaced, inexperienced tapeworms have a penchant for forming cysts in brain tissue in people, as opposed to muscle tissue in pigs. The resulting disease – called neurocysticercosis – causes severe neurological problems.

Though neurocysticercosis is preventable through proper sanitation and hygiene practices, the lack of basic sanitation infrastructure and sufficient medical care has allowed this disease to persist as one of the leading causes of epileptic seizures in the developing world.

STRANGER IN A STRANGE LAND

West Nile Virus is an arbovirus of simple tastes – give it a warm environment populated by birds and mosquitoes, and it will be happy to cycle back and forth between those two hosts. It doesn’t feel the need to make life difficult with an overly complex lifecycle like some pathogens (…we’re looking at you, Dicrocoelium dendriticum.)

Sadly, you know what they say about the best-laid plans of mice and Flaviviridae. If a West Nile Virus-infected mosquito takes a blood meal from a human instead of a bird, the virus enters this strange host and finds itself trapped.

Though it passes into this new host easily enough, it cannot reproduce efficiently in it, and so only achieves low levels of virus in the bloodstream. This means that even if another mosquito feeds on one of these incidental hosts, it cannot pick up enough of the virus to become infected.

A transmission electron micrograph of West Nile Virus. This image has been colored - the original would have been in black and white. Image: Cynthia Goldsmith (CDC)

A transmission electron micrograph of West Nile Virus. This image has been colored – the original would have been in black and white.
Image: Cynthia Goldsmith (CDC)

Despite the fact that West Nile Virus does not replicate well in people, the virus still causes disease in about 20% of infected human hosts. Most people who develop West Nile fever experience mild symptoms that soon resolve themselves, such as headache and fever.

However, in some rare cases the virus causes encephalitis – inflammation of the brain – or meningitis – inflammation of the brain, spinal cord, and surrounding tissues. Encephalitis and meningitis cause serious neurological problems, including paralysis in the limbs or, worse, the muscles needed to breathe.

A PARASITE WITHIN THEE, HAPPIER FAR.

In the end, things rarely go well for a parasite that has been cast out of its intended host and into unfamiliar territory. Whether they end up in the right place at the wrong time, or simply go where they never should have gone in the first place, parasites that have lost their way are far from paradise.

The Curious Case of Tiny Tim Cratchit

Norman Rockwell’s illustration of Tiny Tim and Bob Cratchit for the cover of the Saturday Evening Post, 1934.

Though it’s been a little more than a century and a half since Charles Dickens published his beloved Christmas tale of compassion and karmic retribution, the unstated cause of Tiny Tim Cratchit’s crippling illness still sparks debate among scientists and medical doctors who have had a little too much scotch at holiday parties.

Though a definitive diagnosis has yet to be made for Tiny Tim’s condition, several promising theories have been created to explain what ails him.

THE FACTS

Here is what we know from the text of Charles Dickens’ novella:

  1. Tiny Tim is exceptionally small for his age (hence the nickname), and most likely has a growth defect.
  2. Bob Cratchit occasionally carries his son, suggesting Tim suffers from muscle fatigue.
  3. Tim uses a single crutch, indicating the disease is unilateral – only one side of his body is affected.
  4. Tiny Tim’s illness could be treated using the medical knowledge and technology available in Dickens’ London, as Scrooge’s intervention prevents his death.
  5. If left untreated, Tiny Tim’s disease would have killed him within a year.

POLIO

One popular theory is that Tiny Tim had polio, a paralytic disease caused by a poliovirus infection. Polio can cause paralysis if the infection spreads to the central nervous system and replicates in motor neurons, the cells responsible for sending signals for movement from the brain to the muscles.

Iron Lungs in the Hynes Memorial Hospital in Boston, 1955. Iron lungs kept polio victims breathing despite the paralysis of muscle groups in the chest. Image courtesy of the FDA

Iron Lungs in the Hynes Memorial Hospital in Boston, 1955. Iron lungs kept polio victims breathing despite the paralysis of muscle groups in the chest.
Image courtesy of the FDA

Polio, however, is the easiest diagnosis to refute; there is no cure for polio, and the supportive therapies required to keep Tiny Tim alive while his body fought the disease were not available at this point in history.

DISTAL RENAL TUBULAR ACIDOSIS

Dr. Donald Lewis proposes Tiny Tim suffered from Type I distal renal tubular acidosis, or dRTA. dRTA occurs when the body doesn’t excrete acids properly because the kidneys cannot efficiently remove them from blood. As a result, acids build up the blood stream, causing low levels of potassium, kidney stones, calcium deposits in the kidney, and bone demineralization.

This is a promising diagnosis, as it fits nearly every symptom presented by Tiny Tim. Bone demineralization, which causes rickets in children, results in stunted growth, muscle pain, and skeletal deformity. The low levels of potassium, also called hypokalemia, can cause muscle weakness, pains, cramps, and flaccid paralysis. Calcium deposition in the kidney, particularly when combined with skeletal muscle breakdown due to hypokalemia, causes kidney failure and is fatal if left untreated.

dRTA was also treatable at the time; tonics containing fish oil and the Victorian equivalent of Alka-Seltzer would give Tim the basic compounds and Vitamin D needed to counteract the buildup of acid in his bloodstream and the problems that acidity causes.

Many of the characteristics of dRTA fit the illness crippling Tiny Tim with one exception: Tim’s more obvious symptoms are always bilateral when caused by dRTA, meaning they would affect both sides of the body. However, Dickens’ story suggests Tiny Tim’s disease is a UNI-lateral one. Thus, dRTA probably isn’t what was ailing Tiny Tim.

Children of Oklahoma drought refugees on highway near Bakersfield, California, 1935. The young girl on the right has "bone tuberculosis," or Pott's Disease. Photo by Dorothea Lange

Children of Oklahoma drought refugees on highway near Bakersfield, California, 1935. The girl on the right has “bone tuberculosis,” or Pott’s Disease.
Photo by Dorothea Lange

POTT’S DISEASE

Dr. Russell Chesney disagreed with Dr. Lewis’s theory, so much so that he wrote a commentary in the American Journal of Diseases of Children in response to Lewis’s paper titled simply, “Bah! Humbug!” Chesney proposes instead that Tiny Tim suffered simultaneously from Pott’s disease and rickets.

Pott’s disease is a special manifestation of tuberculosis in which the infection spreads to the spine, causing the discs between vertebrae to break down and completely collapse. Eventually, it can cause spinal cord compression and paralysis of one or both of the legs.

Rickets is caused by deficiencies in necessary minerals like Vitamin D, phosphate, and calcium, and can result from poor nutrition and lack of exposure to sunlight.

Chesney puts particular emphasis on considering the environmental conditions of Victorian London when attempting to diagnose Tim. Factors such as the thick, coal-polluted air, the high population density in tenements, woeful nutrition in lower income households, and the general filthiness of the city at that time made London prime real estate for infectious disease and overall poor health. Approximately 50% of Victorian London’s population had some level of tuberculosis infection, and rickets afflicted nearly 60% of its children.

If helped by Mr. Scrooge, Tiny Tim could have received better food, cod liver oil, and more fresh air, exercise, and sunlight to help him recover from rickets. Vitamin D deficiency also worsens tuberculosis, in large part because it weakens the innate immune response to the disease. Thus, treating this deficiency could have helped Tiny Tim fight his tuberculosis infection, as well.

THE VERDICT

Though tuberculosis was difficult to treat at this time, Dr. Chesney’s is the most likely of the hypotheses presented. This scientist’s diagnosis, however, is that Tiny Tim Cratchit suffered from an acute metaphor for societal neglect compounded with a particularly potent manifestation of Dickensian pathos.

As Pretty as a Milkmaid

blossom color

Blossom the Cow.
Image: Edward Jenner Museum, Berkeley, UK

Whether you realize it or not, you owe a lot to a very special cow named Blossom. In 1796, Blossom was a humble dairy cow like any other on a Gloucestershire farm. Around this time, Blossom had a neighbor by the name of Edward Jenner, a well-respected physician and naturalist, who was beginning to consider an idea that first struck him some 35 years prior.

When he was 13 years old, Jenner was apprenticed to a country surgeon, where he overheard a dairymaid discussing her perfect complexion with a friend. “I shall never have smallpox,” she apparently said, “for I have had cowpox. I shall never have an ugly pockmarked face.

Field Marshal The Right Honourable Jeffery Amherst, 1st Baron Amherst KCB, contemplating an act of biological warfare.  Joshua Reynolds, 1765

Field Marshal The Right Honourable Jeffery Amherst looking pensive. “To smallpox blanket, or not to smallpox blanket…”
Joshua Reynolds, 1765

“THE SPECKLED MONSTER”

The disease from which the vain dairymaid claimed protection, smallpox, is caused by Variola viruses, from the Latin varius or varus, meaning “stained” and “mark on the skin.” At that time, smallpox killed an average of one-third of those infected, and blinded or extensively scarred those that survived. It was also so contagious as to have been used in early forms of biological warfare, most infamously by General Jeffery Amherst during Pontiac’s Rebellion.

As its Latin name suggests, smallpox causes painful pimples on the skin known as macules. The most common progression of the disease is the development of macules into raised papules spread across the face, torso, and limbs, and then into fluid-filled vesicles, large, painful skin lesions filled with debris from tissues destroyed by the virus.

AN INVITATION TO THE WORLDWIDE POX PARTY

Though no one yet understood why, it was well known that smallpox survivors never suffered from the disease again. People in Africa, Asia, and the Middle East independently developed techniques to take advantage of this fact, collectively called variolation.

The idea behind variolation is the same as that behind a chicken pox party – a grosser, even more dangerous chicken pox party. By inoculating with matter from the sores of an infected person, a previously uninfected person would get a (hopefully) mild smallpox infection. After the infection, the inoculated person would be protected from future, more severe bouts of smallpox.

Variolation begun in 15th century China involved the ritualized administration of smallpox matter to the nostrils by blowing it through a silver pipe.

Variolation begun in 15th century China involved the ritualized administration of smallpox matter to the nostrils by blowing it through a silver pipe.

The Turks and eventually Europeans practiced variolation by sticking a lancet into an open sore of a person with a mild smallpox infection, then jabbing it into the arm of the person to whom they are trying to confer protection. The Chinese took a slightly different approach, first documented around the 15th century CE. Rather than administer the virus under the skin, the Chinese would take scabs from healing vesicles, grind them up, and snort them up their noses. Those Chinese sure knew how to party.

While variolation conferred effective immunity against smallpox, it was still less than ideal as a method of protection. Because it caused an actual smallpox infection, those who were variolated could spread smallpox to other people. The variolated were also at risk of secondary infections resulting from the jab, as other bugs would be glad to hitch a ride on the lancet (syphilis comes to mind.) Worst of all, up to 2% of people who were variolated actually died from the resulting infection.

Despite the risks, the significant difference between a 2% and 35% fatality rate helped variolation become a widespread practice. It even made its way to America to play an important role at a critical moment of the American Revolution.

A MORALLY QUESTIONABLE TURN OF THE TIDE

Jenner, the physician fortunate enough to be Blossom’s neighbor, realized that the cowpox-infected dairymaid bragging about her lovely skin was describing protection similar to that resulting from variolation. If protection could be conferred by purposely infecting a person with smallpox, couldn’t the same also be done with cowpox?

The hand of Sarah Nelmes infected with Cowpox.  Image: Wellcome Images

The Cowpox-infected hand of Sarah Nelmes.
Image: Wellcome Images

Inspired by the vain milkmaid and variolation, Jenner asked Blossom and her cowpox-infected dairymaid, Sarah Nelmes, for their assistance. Jenner took material from a sore on Nelmes’s hand and inoculated his gardener’s eight-year-old son. After a mild fever and discomfort, the boy recovered. When exposed to smallpox a few months later, he was found to have complete protection against the disease.

While today this experiment would be considered illegal at best and wildly unethical at worst, it was the first documented case of what would eventually be called vaccination. Though Jenner did not know it at the time, cowpox is caused by the Vaccinia virus, a close relative of smallpox’s Variola. By infecting Sarah Nelmes with cowpox, Blossom had exposed her to a virus that causes a very mild disease, but that is similar enough to Variola that Sarah’s immune system built up defenses against both viruses.

The key difference between vaccination and variolation is the use of a less virulent virus to induce immunity, rather than the actual, dangerous smallpox virus itself. As we have come to further understand disease and immune responses to it, vaccination has come to include the use of weakened or killed pathogens, or even just pieces of them, to stimulate a protective immune response.

Ali Maow Maalin, who contracted the world’s last known case of smallpox, in Merka, Somalia, 1977. After recovering from Smallpox, Maalin dedicated the rest of his life to the eradication of Polio.

Ali Maow Maalin, the world’s last known smallpox victim, in Merka, Somalia, 1977. After recovering from Smallpox, Maalin dedicated the rest of his life to the eradication of Polio.
Image: CDC

DEATH OF A SCOURGE

With the help of connections in London and abroad, by 1800 Jenner’s vaccine had spread through most of Europe. Word of it had even reached Thomas Jefferson, who began the United States’ first vaccination program, through Harvard professor and vaccine proponent Benjamin Waterhouse.

A century and a half of global vaccination campaigns later, in 1980, smallpox was officially declared by the World Health Organization to be the first, and so far only, human disease to be eradicated.

BLOSSOM’S LEGACY

While most of the credit rightfully goes to Jenner, there should still be an International Blossom Day to celebrate the source of the Vaccinia that made up the first vaccine. Chick-Fil-A would give out free sandwiches and milk would flow like a stream down a mountainside. Alas, there’s no such love for poor Blossom.

At least our appreciation for the role she played in eradicating one of the world’s most deadly diseases is displayed in one small way; “vaccination” comes from the Latin word vacca – “cow.”