Thursday, October 3, 2013

Tuberculosis

Tuberculosis! Not an eradicated disease. In fact, it's making a large comeback, due to the combined factors of the HIV epidemic and consequences of people thinking they'd eradicated it. People thought it was a dying disease, stopped funding research and public health efforts against it, and suddenly the numbers were rising rapidly. Also, as Kaitlyn pointed out, TB has many animal reservoirs (including elephants!), and so it is very hard to eradicate completely.

Tuberculosis is transmitted primarily through tiny airborne droplets (called droplet nuclei!). These can remain in  the air for several hours after someone sneezes or coughs them out. Typically you need about 8 hours with an actively infected person to become infected yourself. An open case of TB will infect 12-15 people per year.

TB lives mainly in the lungs. The primary infection will form a necrosing granuloma, which is frequently described as "cheesy" in appearance.

TB evades the immune system by forcing the cells that would normally kill it to increase their pH's. This allows the TB to keep living inside the body. Once infected, a person will stay infected for years, sometimes even for life. 90% of people will never show symptoms. The only evidence is a positive test.

Risk of TB is 10% for a normal healthy person over their lifetime. However, if a person has HIV, this risk increases to 10% per year!

Without treatment, after 5 years, 50% of people with TB will die, 25% will be self cured, and 25% will remain ill with chronic, infectious TB.

The most common symptoms of TB are coughs that persist for over 3 weeks, sputum production, and unexplained weight less. It will show up on x-rays as a blob in the lung called the Ghon focus, or in apical scarring.

Photo Credit: wikipedia.org


Skin tests are the most common way to test for TB. Since the bacterium grows so slowly, several days are required to allow the arm to swell to its full extent. A generation of TB will grow in 12-24 hours - typically bacteria have a generation of 20 minutes! A full culture in the lab takes about 6 weeks. Healthy people need to swell over 15mm to be considered positive, Children over 10mm, and people with HIV only 5mm.

TB is also having a problem because it's becoming drug resistant. For this reason, treatment must be given every day for a very long period of time. If any time is skipped, the risk of the bacterium mutating more and becoming more drug resistant is high. For this reason, many people are needed to help monitor TB drug administration.

There are about 9 million new cases of TB a year, and 1.8 million fail to get treatment of any sort. 50-70% of people with untreated TB will die from the disease. 98% of deaths are in low and mid income countries. TB is the leading cause of death amongst people with HIV.

People are trying to prevent TB spread through the use of directly observed therapy, to make sure that people take all of their drugs on time every day. What really needs to happen is people need to train in HIV treatment AND TB treatment, as both diseases often happen simultaneously.

River Blindness

River blindness is a disease described by it's most devastating side effect, though not everyone who encounters the parasite will become blind. It's caused by the Onchocerca volvulus worm, and it's estimated to infect 18 million people worldwide, of which 800,000 are visually impaired, and 270,000 are completely blind.

Onchocerca is found widely in Central Africa and Central and South America, though the Americas have shown great progress in eradication. It's transmitted by riverine blackflies, which, surprise, hang out by rivers! Typically fast flowing ones, exactly the type people would live to build their settlements by. The adults live in nodules in the human skin, which are typically raised. Interestingly, these nodules favor the lower regions of the body in Africa and the upper regions of the body in the Americas. The microfilaria of this species migrate through the skin, which causes a very intense itching effect, to the extent that people frequently get permanently disfigured skin from the intensity of their scratching. Because they migrate through the skin, blood samples won't tell you anything. Instead, skin samples must be taken and processed to see if there's any microfilaria hanging out there. Fun!

Photo Credit: Emedicine.com


The most serious manifestation of Onchocerca volvulus is ocular lesions that lead to blindness. The microfilaria enter the eye, which causes irritation, which makes a tiny patch of scar tissue in the eye. Too many of these can lead to progressive blindness. These in the eye are diagnosed in an interesting manner - the patient is made to wait for a while with their eyes parallel with the floor. They then quickly raise their head up, and a doctor shines a light in their eyes and looks for falling particles.

Photo Credit: eyewiki.org


Mass Drug Administration has reduced the disease in many areas to the point that it can't be sustained anymore. Go public health!

Wednesday, October 2, 2013

Filaria!

Filaria (which causes Human Filariasis) are a group of parasites that are found in pretty different areas of the world, all of which cause different symptoms. However, they're grouped together because most of them look very similar in diagnostics. The three big ones are Wucheria bancrofti, Brugia malayi, and Onchocerca volvulus. Wucheria bancrofti and Brugia malayi produce pretty similar symptoms, while Onchocerca volvulus creates a syndrome known as River Blindness, which I'll go over in the next post.

The filariasis causing worms are unique in that they create microfilaria instead of the traditional eggs. These are basically motile eggs - they aren't yet larva, but they do move around. They can be sheathed or unsheathed, and they can display periodicity which corresponds to the preferred intermediate host. (Pretty cool!) They tend to be circulating in the blood during these periods, but can be completely undetectable when they're not in this period.

Wucheria bancrofti live in the tropical and sub-tropical regions of the world. Humans are the only known definitive host, which means if we get rid of it in humans it won't come back! However, this is kind of hard, because not everyone who has this infestation shows symptoms, or the microfilaria might not be present when a blood sample is taken.

The adult forms of Wucheria bancrofti lives in the lymph nodes. They tend to like those closest to the groin, which will become important in a minute. The microfilaria migrate into the blood, where they display a nocturnal periodicity. It is hypothesized that they go to the lungs when they're not in the blood.

Most often Wucheria bancrofti is transmitted by Culex quinqefasciatus mosquitoes, though several other species can transmit it. The mosquito takes a blood meal, ingesting the microfilaria. These mature to infective larva inside the mosquito. When the mosquito takes a meal from a human, these wiggle their way down the proboscis of the mosquito, infecting the human. They migrate to the human lymph nodes, where they mature.

The adults can live up to 5 years in the body. The microfilaria can live 1-2, during which time the person is actively infectious.

The most common pathology is asymptomatic microfilaremia. This means that the microfilaria are just chilling out and circulating in the blood. They'll show up on a slide, but won't really cause any problems. People can develop lymphangitis. However, in cases of long infections or large infections, people can develop chronic lymphadema and eventual elephantiasis (the most well known characteristic of Filariasis). Wucheria bancrofti in particular can cause hydrocele and scrotal elephantiasis, which I'm not going to put a picture of, but if you're interested I suggest looking up.

What tends to happen is adults living in the lymphatic channels cause dilation and chronic edema due to gravity. As the worms die, collagen builds around them, forcing the lymph nodes open even farther. This causes the lymph to not drain properly, which makes it collect in the extremities. Unfortunately, even if the worms are taken care of (with DEC), this process is irreversible, as extensive damage has been done to the lymph nodes.

Diagnosis is done through looking at the blood in a lab (which must be done over several hours, as the microfilaria could show up at different times), or through using an ultrasound to examine the lymph nodes. They create a characteristic "Filaria Dance Sign", which can be seen in this video: http://www.youtube.com/watch?v=d3KWh6xqQm0

Brugia malayi is very similar to Wucheria bancrofti, but its geographic distribution is limited to Southeast Asia. Differentiation is done based on the microfilaria, as the adults look quite similar. It has reservoir hosts in macaques and  leaf monkeys. It creates similar pathology, except that hydrocele is not seen. It's also primarily transmitted by Mansonia species of mosquitoes.

Photo Credit: Stanford.edu
On the left: Wucheria bancrofti microfilaria
On the right: Brugia malayi microfilaria

These are nicely stained so they look really different. They usually don't. 

Monday, September 16, 2013

HIV History

HIV was discovered in 1981, though retrospective studies have discovered cases in Africa as early at the 1930s. In 1981, 26 cases of Kaposi's sarcoma were found in male patients in the US, all of whom identified as homosexual. These cases were centered around San Francisco and New York. Previously, Kaposi's sarcoma had only infected elderly men of Jewish or Mediterranean ancestry. In addition, this new version was much more aggressive than had previously been seen, leading doctors to seek a link between these new cases.

Photo Credit: http://www.meddean.luc.edu/

Above is a normal case of Kaposi's sarcoma. Below is an advanced case in a HIV positive patient.

Photo Credit: wikipedia.com

Within the same population that were getting these infections, other diseases that were normally only associated with immunocompromised patients were occurring, most notable non-Hodgkins lymphoma Pneumocystis pneumonia, which do not normally infect healthy people. Since the doctors did not know what to look for, or how to look for it, they did not know what was causing these infections.

The virus was isolated in 1983 and 1984 by two people, both using the same strain of virus. No other infectious agent has been isolated in such a short time. Luc Montagnier and Robert Gallo, a French scientist and an American scientist respectively, were the two discoverers of the virus.

Never before had an infection been found that so completely destroyed the hosts immune system. The hidden nature of the virus, as well as its rapid evolution time, are both key factors working against the discovery of a cure.

HIV Prevalence and Transmission

Okay, not a parasite. But it is probably the most well known microbial infection of our time. Human Immunodeficiency Virus infects an estimated 35 million people worldwide. There are two main types, HIV-1 and HIV-2, both of which can have sub-types. Subtype B is most common in the Americas and Europe, while Subtype C is the most common in Africa and Asia. HIV-1 is found worldwide, while HIV-2 is endemic to West Africa. They are retroviruses, which are a family of enveloped viruses that replicate in the host cell through a process of reverse transcriptase.

HIV is of zoonotic origin. HIV-1 probably came from Chimpanzees, while HIV-2 came from Sooty mangabeys (another primate). What likely occurred was that a hunter was butchering the primate, which was infected, and their blood entered the hunter, transmitting the disease. Phylogenic evidence indicates that viruses have been transmitted to humans this way on at least 8 occasions.

 As most know, HIV is transmitted through sexual contact. Interestingly, heterosexual sex is the most common transmitter worldwide, while homosexual sex is the most common transmitter in the US. However, being the receptive partner in either act can have as high as a 30% risk of transmission. HIV can also be transmitted through IV drug use, from mother to child, from blood transfusion, and from transplanted tissue. Being pricked with a needle that had previously been in contact with HIV positive blood, such as a nurse being accidentally stuck, is only 0.3%. Having other STIs greatly increases the risk of infection.

When the virus first enters the body, the innate immune system does what it would do for any unknown pathogen - it binds the virus to dendritic cells, which then carry it to the lymph nodes. Once here, the virus infects the helper T cells, which were supposed to be recruiting the antibodies to fight it. Because of host immune responses against the cells, after the initial infection the infected person may go into a period of latency, in which they have no symptoms, for as long as 15 years.

When a person is first infected, this viral load is very high. Initial infections often produce flu-like symptoms. This continues for approximately a year after initial infection, but then drops and remains extremely low until a time at which both T cells and anti-HIV antibodies become low in the body. T cells decrease fairly regularly over time in an untreated person, while anti-HIV antibodies remain at a fairly high level until the T-cell count drops too low, at which point they plummet.

When the T-cell count goes down too far, other symptoms begin occurring. This includes unexplained weight loss (over 10% of body weight), recurrent respiratory tract infections, Angular cheilitis, oral ulcerations, fungal infection of nails, and pruritic eruptions on the skin.

Once the host becomes immunocompromised, which means that they no longer have enough T cells to fight off any sort of infection, opportunistic infections start. This means that things which would not normally be able to grow in a healthy person can grow in them, such as Oral Hairy Leukoplaikia, a condition in which the tongue takes on a hairy appearance. Tuberculosis rates are also much higher in patients with HIV.

HIV testing is now much better than it initially was, but it can still take up to 2 weeks for antibodies to appear in the blood at such an extent that a test would show positive, making it very necessary for those doing the test to ask when the most recent day in which a person could have become infected was. Before the new rapid tests were invented, which can give results in under an hour, it is estimated that 90% of people with HIV did not know their status. In one South Africa study done in the 80s, only 17% of people who came to be tested came back for their results. Even now that we have the rapid tests, it is estimated that as many as 50% of people living with HIV do not know their status.


If you'd like to see a visual of HIV infecting host cells, this video is pretty cool: http://www.youtube.com/watch?v=RO8MP3wMvqg

Sunday, September 15, 2013

Trichuris trichuria

Trichuris trichuria is the last of the intestinal nematodes for now! It's also known as whipworm. It's also the first one in a few posts where humans are the definitive hosts. It's found worldwide, especially in tropics and subtropics. Co-infections with ascaris are quite common.

Adult Trichuris trichuria live in the colon, caecum, and appendix. Their anterior end is buried in the mucosal epithelium, allowing their posterior ends to move freely in the intestine. Adults can live for several years inside the body.

Photo Credit: medicine.cmu.ac.edu


The female whipworm produces a ton of eggs. These are passed out of the body unembryonated, then develop for 3 weeks in the soil. Again, these are easily preventable if feces are not allowed to sit around in places for weeks where people can come by and touch them again! The eggs are barrel-shaped, with a thick smooth shell, and bi-polar plugs. Once they're swallowed, they hatch in the upper small intestine, undergo further development, and make their way down to where they really want to live, where they embed themselves.

Photo Source: wikipedia.com

The adults have an interesting feature called the stichosome,which is a collection of secretory cells that line the esophagus and produce proteins. It's been theorized that these aid in the ingestion of nutrients from the intestinal mucosa, since the Trichuris mouths are embedded.

Signs only occur when a person is highly infected. It may cause abdominal pain, diarrhea, weight loss, and tenesmus, which basically means a feeling of having to go to the bathroom all the time. There may be Charcot-Leyden crystals in the stool, which are little pink crystals caused by allergic reactions. Anemia is much less common than with hookworm infections. They can cause prolapse of the rectum, especially in children, as they weaken the rectum at the same time as they create an urge to push.

They may also produce long term deficits in development and cognitive functions.

Diagnosis can be made though seeing the eggs in feces, or the adult worms may be seen during sigmoidoscopy. Treatment is done with albendazole and mebendazole, and is done a lot with school children.

Saturday, September 14, 2013

Metastrongyles - Lung Worms!

Two versions of these lovely worms. The first is Angiostrongylus cantonensis, adults of which live in, you guessed it, the lungs! Typically rat lungs though, not human lungs. They lay their eggs in the lungs, and when the larva hatch, they break into the respiratory tract and migrate up the trachea, where they are then swallowed and pass out of the rat body. They are then ingested by snails or slugs. In these hosts, the larva progress from L1 stage to L3 stage, at which point they are infective again. New rats then either eat the snails, or eat food that the snails have passed over, which deposits it on the new food source. Once they are eaten, the larva migrate to the central nervous system, where they can develop in the brain. They then migrate back to the lung.

Humans are infected either when they eat the infected snail or slug, or when they eat something such as lettuce that the slug has passed over. When the larva tries to migrate to the brain, it causes eosiniphilic meningitis and meningoencephilitics. Most larva die in the brain, which can cause an even worse inflammatory reaction. The only real treatment for this one is corticosteriods, as apart from surgery there is no real way to get the larva out of the brain.


Photo Credit: ajtmh.org

The other kind is Angiostrongylus costaricensis. These are also typically found in rats, though they live in the mesenteric arteries. The female Angiostrongylus costaricensis deposits eggs in the rat intesten, which are passed with the feces. Again, slugs/snails are the intermediate hosts, and once they are ingested again by rats, they migrate via the lymph system and blood to the mesenteries. This one presents pretty differently, typically as acute abdominal pain, low-grade fever for 2-4 weeks, a tumor like painful mass, and high eosiniphilia. Surgery is possible, as are anti-helminthic treatments.

Both adult worms look pretty similar. They are slender with a reduced or rudimentary buccal capsule. 3-5 cm in length. The females have a spiral shape down their length, caused by uterine branches.

Photo Credit: Wikipedia.com

Friday, September 13, 2013

Stronglyes

This post contains two pretty different Strongyles, one of which can have severe repercussions, the other of which is often asymptomatic. However, what connects them is that they both typically infect animals, they're pretty rare in humans, and human infections are typically found in Africa/the Middle East.

The first is a true strongyle (as opposed to our fake strongyle, Strongyloides), Oesophagostomum bifurcum. These can be found in pigs and ruminants all over the world, but the focus of their human infections seems to be in West Africa. They are called nodular worms because they produce nodule-like abscesses in the host's bowel wall.

They are quite robust little worms, up to 3cm, with eggs very similar to hookworms. They have a short, muscular, club shaped esophagus.

Photo Credit: wikipedia.com

Eggs will pass with the feces of the infected animal, then molt in the ground to become infectious. When the larva are ingested, they burrow into the large intestine, forming an abscess or nodule. The larva then spends approximately 2 weeks in the nodule. After it become an adult, it re-enters the lumen of the bowel and attaches to the mucosa.

This will present as appendicitis like pain. Notably there may be abdominal masses, which are caused by the nodule progressing out of the intestine and attaching itself to things around it, including the interior of the skin. In rare cases the nodule may even burst out of the skin.

Diagnosis can be made from eggs in the feces, which must be allowed to hatch so that they can be differentiated from hookworm eggs. The nodules are also a pretty big give away. Treatment is done with albendazole.

Photo Credit: stanford.edu


Trichostrongyles rarely infect humans, but when they do it tends to be in the Middle East. They're a common parasite of livestock. They are soil transmitted and adults live in the intestinal mucosa. They lack a buccal cavity, but they do have a well developed bursa, which makes them true stongyles.

They have a similar infection cycle to hookworms, though there is no pulmonary aspect. It's typically asymptomatic. Any sort of anti-helminthic drug will take care of it.

Thursday, September 12, 2013

Nurse Cells

The companion piece to Trichinella spiralis! Nurse cells are something that are formed exclusively by Trichinella spiralis. They're what happens once the larva finally make it to the muscle cells. They find their nice homey cell that they want, but then, it's not quite right. So they somehow release stimulants that undifferentiate the muscle cell, allowing them to shape it to their needs. They're even able to re-direct the blood supply to the cell, so they can keep themselves living. These typically show up 14-16 days after infection with Trichinella spiralis. They've been shown to survive for up to 30 years inside these nurse cells! Most, however, calcify and die.

These are also an interesting case of worms immunosurppressing the host, as there seems to be little immune response to the nurse cells themselves. Repeated oral ingestion of Trichinella spiralis seems to break down the previous immunosurppression, resulting in larva from previous infections being killed.

Photo Credit: trichinella.org

Trichinella spiralis

Continuing the theme of incidental host infections, we have Trichinella spiralis. This is a problem found in pork, and is one of the reasons it is always recommended to cook your pork thoroughly.

This is a problem found worldwide (though obviously not in countries where pork is not eaten), though it is becoming much less common in the US, as regulations make it very hard for any commercial pork to get the infection in the US.

The adult Trichinella spiralis live in the intestinal mucosa of pigs. The larva hatch within the intestine, then migrate to columnar epithelial cells (as in those commonly found in skeletal muscles). Here they wait patiently for the pig to get eaten, where they can be released from the muscle tissue. They can become encapsulated in muscle tissue and remain dormant there for a very long time - sometimes several months!

Prey and carrion are reservoir hosts. In the past, the most common way to get this infestation was through uncooked pork, but now it is more commonly associated with wild pigs or bears, or even polar bears.

When humans eat the infected pork muscle tissue (yum), the larva travel to the gut, where they become adults. These then begin producing tons of little baby Trichinella spiralis, which migrate through the intestinal wall in search of muscle tissue. These larva are quite small - they actually move THROUGH the cells, rather than between them like most larva that travel through body systems. Unfortunately, this means that the cells they do pass through die. This can be quite a problem if they are moving through places like the brain or the lungs in search of their preferred muscle tissue. Peri-orbital edema is also characteristic of this infection.

In cases where the worm load is small, problems rarely present. However, in cases of high worm burden, the cellular death and subsequent eosiniphilic (allergic) reactions can be quite severe. In the brain, this can cause meningitis, or brain damage due to damaged tissue. Once the larva reaches its preferred skeletal muscle cell, it goes through an interesting process to make what is called a nurse cell, which I'll detail in the next post. These cells can live in the muscle for years. However, once it gets to this stage, there is really no point in treating the infection, as they aren't causing any problems. They do sometimes show up on unrelated muscle biopsies though, causing a big surprise for whoever's analyzing the tissue!
Photo Credit: trichinella.org


Treatment is given to halt the production of larva in the gut, to stop the tissue death caused by migrating larva. Corticosteroids can also be given, to lessen the eosiniphilic reaction caused by the migration of the larva.

This problem presents as gastro-intestinal pain., and may mimic food poisoning. There can be some muscular pain, caused by the migrating larva and the dying cells. It can also present as myositis, facial edema, fever, and/or peripheral eosiniphilia. Myocarditis can occur in severe infections. It can cause death.

Diagnosis is most often serological, meaning it is done with blood serum in the lab. Antibodies can be detected approximately 12 days after infection. Larva can also be found in biopsied muscle, but by that point it is often beyond the point of treatment. On the plus side, if the person has survived to that point, they're not likely to die from it!

Photo Credit: trichinella.org

Wednesday, September 11, 2013

Capillaria hepatica

This name might look similar, as it is also a Capillaria type nematode. However, it presents very differently than Capillaria philippenensis! Instead of living inside fish eating birds, the adults of Capillaria hepatica lives in rat livers. Humans are the accidental (incidental) hosts.

This problem is found worldwide, but it is not very common. The adult worms get up to about 1 cm. The adults lay the eggs in the liver, where they stay in stasis until the rat is eaten by another animal. The purpose of this host is just to digest the liver - after this, the eggs pass out with the feces into the soil. The eggs hatch and then mature outside in the soil, where they are eaten again (hopefully by a rat), where they then migrate to the liver to complete their life cycle.

Humans typically get this infection by accidentally touching an area where the eggs have passed out. Most often this happens when a pet has eaten an infected rat. In humans, severe infections may result in fever, hepatomegaly, and hyper eosiniphilia, similar to a VLM infection. The eggs are then trapped in the liver, where they may cause an allergic reaction. This is a dead end stage for this parasite, unless the human's liver gets eaten and digested. (Hannibal situation?)

Diagnosis is made though liver biopsies, which will typically present adult worms and eggs. Usually humans will not pass any eggs in the feces. If they are, you know they got the infection in a different way- possibly if they ate an infected rat!

Photo Credit: cdc.gov
This is a liver section with eggs!

Eggs are similar to Capillaria philippenensis, in that they have bipolar prominences and a thick pitted shell.

Capillaria philippinensis

This one is near and dear to my heart, as it was first discovered in the Philippines, and is frequently found in Thailand! I actually first learned about these this summer at the Parasitology Museum at Siriraj Hospital in Thailand, which is where this blurry picture of the fish most likely to carry helminths comes from:


Even though they have Philippines in the name, they're found in all areas where fresh fish is eaten, though they do tend to be most common in the Philippines. Fish eating birds are their definitive hosts, which once again means that they do not want to be living inside of us! In the natural life cycle of Capillaria philippinensis, the adult worms live in the intestines of birds, their eggs are passed out with feces, these hatch in water, and then they are eaten by progressively larger and larger fish until they get back to a bird. (By the way, a host in which a parasite exists but does not progress in life stages is called a paratenic host, which is what most of the larger fish are!)

Unlike most species which cause problems for humans because they don't want to be in humans, Capillaria philippinensis can progress from a larva (which is the point at which it is swallowed) to an adult worm. This is where the real problems begin with this helminthic infection. Since it adapts to living in humans, it creates a cycle of auto-infections within the human bowel. This means that worm loads can become very high within the intestine, leading to abdominal pain, persistent permanent diarrhea, and intestinal crypts. It can lead to deaths because of bowel obstructions, diarrhea, and malabsorption of nutrients.  

Adult worms are 28-47mm, and inhabit the small intestine. Eggs are peanut shaped, and rather small. They have a thin shell. They exhibit flattened bipolar prominences, and they are typically unembryonated when passed.

Photo Credit: Wikipedia.com


Diagnosis here really relies on knowing the patients history, such as living in/traveling to areas where this parasite is prevalent and eating a lot of raw fish. Also, unlike Anisakiasis, which presents within a day of fish ingestion, Capillaria philippenensis takes 3-6 weeks to mature to adults in the intestine.

Treatment must be given over a longer course of time, since the parasite can exist in many stages within the intestine, and most anti-helminthics only target one life stage. It is important to stop the cycle of auto-infection early, as worm burdens can get very high very quickly.

Tuesday, September 10, 2013

Anisakiasis

Another of our favorite worms that really don't want to be in humans! Anisakiasis is a problem caused by Anisakid nematodes, typically Anisakis spp. or Pseudoterranova spp. Their preferred host (principal host) are fish eating mammals, such as dolphins. While we don't see many cases of humans becoming infected from eating dolphin meat, what we do see is people getting infected from eating raw fish, especially in the case of sushi. While any restaurant in the US that serves sushi must serve sushi grade fish, which has been frozen to a degree that any parasites die, restaurants outside of the US do not have this same regulation. While this infection has been found worldwide, it is obviously more common in areas where raw fish is frequently consumed.

Pathology with Anisakiasis most often presents in one of two ways, typically corresponding with the two most common types of species, though either can present in either way. The non-invasive type, typically found with Pseudoterranova spp., usually is asymptomatic until the infected person coughs up a worm. (Surprise!) There is no tissue penetration in this type of infection. Once the worm is coughed up, no further action needs to be taken, apart from some possible counseling to deal with having coughed a fully formed half centimeter worm out of your throat.

Photo Credit: Stanford.edu
These can get up to 2cm!


The other type of infection is invasive, and is typically caused by the Anisakis spp. With the invasive type of infection, the larvae attach to, embed themselves in, and penetrate tissues, typically in the intestine. This presents as extremely severe pain in the abdomen, similar to a ruptured appendix, though it can be sometimes more mild. In these cases, the worm is typically removed with surgery, as most anti-helminthic drugs are not useful once the larva has penetrated an organs. This can be differentiated from other types of abdominal pain because it comes on extremely suddenly and strongly a few hours after ingesting the infected fish.

Unless you want to carefully inspect every piece of sushi before you eat it, not eating raw fish outside of the US can prevent this infection. Proper freezing, cooking, and preparation of seafood will prevent this infection.

In the US, there tend to be less than 10 cases per year, due to the restrictions placed on fish. In places where this is more common, however, doctors know what to look for, and are often much more likely to treat the infection as a parasitic nematode from the beginning.

Photo Credit: stanford.edu
Look at that lovely y-shaped lateral chord! It's one of the best ways to recognize an Anisakid nematode larva.

Monday, September 9, 2013

Visceral Larva Migrans

Visceral larva migrans are what happens when human organs are invaded by nematode larva. Toxocara canis (typically found in dogs) and Toxocara cati (cats) are the most common forms of this infection. The eggs are passed out of the body of the host in feces, and are then ingested. When they accidentally get into humans, they hatch in the small intestine, and then permeate the intestinal mucosa, from which they migrate through the blood and lymph systems to the major organs, such as liver and lungs. This problem is rarely fatal, and is indeed very often asymptomatic. Unless one gets into somewhere really bad, it may only present as slightly high levels of eosiniphils in the blood, which can also be caused by allergies or asthma. Problems can occur, however, when a larva invades the eye. This can look like a retinoblastoma. Since the cure for retinoblastomas is removing the eye, and the cure for visceral larva migrans is a simple course of anti-helminthics (and possibly surgical removal of the larva), this can be an important distinction to make! One clue is that this typically presents in older kids than those commonly infected with retinoblastomas. Just something to look out for!




A MUCH larger problem can occur when the visceral larva migrans are due to Baylisascaris procyonis. These helminths are found in the intestinal system of raccoons. They have become more of a problem lately, as raccoons are moving closer and closer into where people live. They are an ascarid-type nematod (remember Ascaris lumbracoides, the intestinal roundworm!). They need to live in raccoon feces in the soil for around one month before they are infectious. Seems pretty easy to avoid raccoon feces, right? The problem is, raccoons like to have one spot that they designate the "toilet", traditionally in the crook of tree branches. As raccoons are moving closer to humans, they are more and more frequently building their "toilets" on top of buildings, which causes the feces to get swept down to the ground when it rains. Since the majority of the debris will be washed away, it can be difficult to tell where eggs might be! Once the Baylisascaris larva are ingested, they really go crazy. They go straight to the eggs and the brain. Unlike most other lost baby worms, these actually do grow up to adults - in your brain. This causes both an eosiniphilic allergic reaction (meningitis) AND severe brain damage, as you now have a worm carving tunnels in your brain. Unfortunately, the only real prevention for this one is washing your hands if you think you've been anywhere near a raccoon toilet.

Photo Credit: Flickr.com

Sunday, September 8, 2013

Gnathostomatoidea

To go along with the lovely larva currens of Strogyloides infections and the CLM of Ancylostoma, we have Gnathostomatoidea! This helminth comes in two sub types - hispidium (commonly found in pigs) and spinigerum (found in cats and dogs). We're not this worm's preferred host - they'd much rather be in animals. However, we can ingest them accidentally. These worms go from their preferred hosts to being little eggs in the soil, which only hatch once they are in water. These are then ingested by copepods, or small crustaceans. What the larva are hoping will happen is that the copepods will be eaten by fish, and then eaten by something else, so that they can eventually get back to their preferred host to start the cycle all over again.

But what happens when we eat the copepod, or even the fish, that the larva are living in? The larva has no idea what to do, because, as it so happens, our insides are quite different from pigs and cats and dogs. This results in the larva migrating around the body. When it comes to the skin surface, it causes large red swellings that seem to migrate around the body, forming, disappearing, then re-appearing somewhere else. Problems can occur when the worm dives into the body - it can cause severe problems in any organ it enters, which might include the brain, which can cause eosiniphilic meningitis.

                                               Photo Credit: http://www.medicine.cmu.ac.th/

This problem was first seen in Asia, but is more frequently being found in Central and South America. This may be because cerviche made with freshwater fish, as opposed to saltwater, is becoming more economical. This particular helminth only lives in freshwater fish, making the connection likely. Treatment is done with Albendazole or Ivermectin, but the worm is apparently quite difficult to kill. You can also try to surgically remove the worm.

Strongyloides stercoralis

Strongyloides are not true strongyles - an interesting and strange quirk of naming. Because they lack a copulatory bursa on the males, they are technically not in the same genus. But, they got named before this was found out. So Strongyloides they shall remain!

Many people mistake these wormies for hookworms. They are not, though they do at times have very similar presentations. To complicate things further, their geographic distributions are quite similar - they both enjoy tropical and subtropical humid areas. Their L1 larva even look extremely similar to hookworm L1 larva! However, strongyloides have a large genital prominence in the L1 stage, while hookworms have a small one.

These worms tend to infect less people than hookworms, with only 100-200 million people infected worldwide. They live in areas where sanitation is poor. (Another worm that could be prevented with a flush toilet, shoes, or a deep shaft toilet!) Like the hookworms, they transmit though the soil, entering out pores as infective larva. They also go through the blood and lymph streams to the lungs, where they grow, are coughed up, and eventually enter the small intestine. They tend to cause less irritation to the lungs than other worms with this cycle, likely because one is more likely to have a chronic ongoing Strongyloides infection. People have been shown to carry Strongyloides infections for several decades, for reasons I'm about to go into.

Strongyloides can have a method of entry into the host that is very similar to hookworms, in that they are passed with feces, grow up in the ground, and then re-enter the body through pores. However, a key difference is that the eggs hatch while still inside the body. This is important for diagnosis, as it means you will almost never find Strongyloides eggs in a stool sample. It also means that sometimes, the larvae will progress to their infective stage while still inside the body, allowing for a constant source of re-infection. They also have a very strange trait in the soil - while most helminths who follow the host->soil->larvae->reinfection pattern cannot live in the soil longer than 1 generation, Strongyloides can. They will become free-living adults (known as Rhabditiform adults), who can then mate and lay their own eggs in the soil, meaning that the ground can stay infected for a much longer time than with most helminths.

While most people living with Strongyloides will have few symptoms (perhaps some vague intestinal pain or some wheezing, or alternating diarrhea and constipation), problems occur when the outbreak becomes more severe. This can happen in two ways - disseminated infection or hyperinfection. While most literature will use these two interchangeably, there are symptoms that really apply more to one than the other.

With a hyperinfection, the worms have become too prolific within the gut. Most of the time, parasites have an innate sense of how many of them can survive in the host at any given time, and will plan accordingly. They don't want to kill the host, because then they would most likely die as well. However, hyperinfection can occur. This will often result in severe diarrhea, malabsorption, and weight loss. It can be fatal.

With a disseminated infection, the larvae start fleeing to other parts of the body that they would not normally be found in. This is often the result of steroids - either ones that have been given to a patients, or ones that the body makes naturally, such as in cases of extreme malnutrition. Diagnosis can be made by finding larvae in organs through biopsies and finding rhabditiform larva in sputum (normally never found inside the body). This is typically only seen in previously immunocompromised patients. In these cases, it is very important NOT to administer more steroids, even though that is what would usually be done in a case where larvae were being found in places that they normally would not be. This is because the steroids actually act as a signal for them to go wandering about the body, and will exacerbate the problem. Interestingly, even though this is found in immunocompromised patients, it is not associated with AIDS. Researchers think that the immune system factors associated with keeping levels of Strongyoides down are not the same as those affected by AIDS, and as such the patients have no greater chance of getting one of these worse infections.

Disseminated infections can also be diagnosed when a condition called Larva Currens happens. Larva currens shows up similarly to cutaneous larva migrans, in that it is a long red streak left in the wake of the larva. However, these move much faster - they can sometimes go several mm in an hour! These tend to show up near the chest and butt areas, and it is important to seek anti-helminthic treatment for these.

Photo Credit: Institute of Tropical Medicine, Antwerp


Diagnosis with a Strongyoides infection can be very difficult, as the symptoms in infections that are not severe include atypical bronchitis, followed a few weeks later with some diarrhea and epi-gastric pain. L1 larva may be found in the feces, but it can also be confused with hookworm, as a stool sample with hookworm eggs will hatch if not attended to quickly enough. However, if a patient has a history of being in an area where these helminths are prevalent, it is important for doctors to check and treat them before preforming surgeries such as organ transplants, where steroids would normally be given.

Ascaris lumbricoides

Ascaris lumbricoides are a roundworm that inhabit the small intestine. They are the most common helminthic infection on Earth, with an estimated 1.4 billion people worldwide having some sort of Ascaris burden. In the US, they are most commonly found in the Southern states (they like warmer climates), but they are found all over the world. We are their favorite hosts, which makes us the principal hosts for Ascaris! They can be spread anywhere there is poor sanitation.

Ascaris are one of the larger worms that infect humans. (My personal favorite, Guinea Worm, are much longer, but I'll get to those later.) The females can reach lengths of 40 cm inside the intestine. They are typically found in younger children, as those are the most likely to be ingesting dirt. (Accidentally or purposefully.)

Ascaris have to live in the soil for a few weeks before they can reach their infective stage. They have very thick eggs, with distinctive "mammilations" on the outside (this means the outer surface is very bumpy). This allows them to survive for a longer time, and in worse conditions than an egg with a thin shell, like hookworm eggs. The eggs are passed out with feces, and mature in the soil. They can then be eaten by their preferred host, us! The eggs then travel to the upper small intestine, where they hatch. These small larva then penetrate the gut wall, and move through the blood and lymph systems to the lungs. Here they enter the alveoli and continue to grow. Once they have reached the final larva form, the begin to irritate the lungs, causing coughing. This allows them to travel up the windpipe, where they can then be swallowed, so they eventually end up where they wanted to be - the small intestine. Here they mate and start producing lots of little baby Ascaris eggs.

                                                      Photo Credit: Wikipedia.com

The irritation of the lungs can cause a symptom known as Loefflers. It closely resembles asthma, and can easily be mis-diagnosed. It is caused by an allergic reaction to the worms.

Most cases of Ascaris lumbricoides infection go unnoticed. There is little chance for re-infection, so once the adult worms have all died (sometimes this can take as long as 2 years), the original infection will go away. Since they are only eating the fecal stream (yum), they rarely take away noticeable amounts of nutrients from the body. However, problems can occur when there are massive infections, as the worms may cause blockages in the intestine. This is also why it is important to know which worms you have, as some anti-helminthic medicines work by causing the worms to clump together, which you would not want to do if you had a mega infection. Moderate infections can cause upset stomachs, some stomach pain, and some nausea. More problems can occur when the worms migrate out of the intestine, something which does not normally happen. However, Ascaris REALLY don't like anesthesia. In the case of the host being anesthetized, the worms will suddenly start to flee the body via any opening they can find. Unfortunately, this can include the nose, mouth, tear ducts, and anus. They can also try to flee into other organs, such as the appendix, which can cause appendicitis.

Diagnosis involves searching for the eggs in feces, or by seeing the adult worms coming out of the body. If a lung infestation is suspected, a biopsy can be taken of lung tissue and examined for worms.

Drugs that paralyze the worm and allow them to pass out of the body, such as piperazine, are the best. Surgery may be required in cases of obstruction, or if the worm has migrated to an unusual spot.

                                                  Photo Credit: Wikipedia.com


The easiest way to prevent Ascaris infection is flush toilets. If human feces are not allowed to sit around long enough for the eggs to develop, and then for people to ingest them again, then the worm cannot spread.

Saturday, September 7, 2013

Pinworms

Pinworms (Enterobius vermicularis) are the most common helminthic infection in the US! Aren't we special. Worldwide it is in the top 5 of the worst worm infections. It affects approximately 400 million people worldwide, of which 40 million of those are in the States. The tails of the females are quite thin and pointy, which, combined with their small size, have led to their name. Interestingly, they're called threadworms in the UK, where the term pinworm is used to describe a Strongyloides infection.

Enterobius vermicularis are very hard to control and get rid of, for reasons that will soon become apparent. First off, they can survive in much more temperate climates than most helminths (though they still really like tropical and sub-tropical zones). It doesn't primarily affect low-income people either, the way most worms do. The most important reason pinworms are so common is who is most commonly infected. It's children ages ~2-5, right around the age where they're going to daycare, but before the time that they've (hopefully) learned proper hand washing and sanitation techniques. This is because pinworms eggs are spread when people scratch their peri-anal region (aka their butt) and then touch other people/surfaces without washing their hands!

The lifecycle of the pinworm is quite simple. They are small worms, rarely reaching more than 13mm long. The worms mate in the small intestine, and the females settle themselves in the intestinal mucosa down by the colon. Here they live happily, rarely causing any problems. Then, the females, drawn by some sort of biological clock, creep out of the colon through the anus, and explode themselves all over the peri-anal region, leaving sticky egg clusters in their wake. (Hope you weren't eating while reading that bit of info).

Pinworms are easily identifiable from their esophagus. It has a distinct corpus- isthmus-bulb structure, which is easily seen under a microscope.

                                              Photo Credit: Vet-parasitology.com

These egg clusters then itch quite a bit, causing the infected host to scratch. The sticky eggs rapidly form into infective L3 larva, which attach to the hosts fingers, where they can then be swallowed again to repeat the lifecycle, or passed onto others. The larva are quite robust, and can survive for several days hanging out on places like doorknobs and telephones. This means that re-infection is very likely, as is infection of the whole household.

It's very rare to see adult worms outside of the body, as they mostly explode once they leave. In many cases, the only symptom is very scientifically described as "itchy butt". However, in small children it may also present as irritability and insomnia. In other words, exactly how little kids act all the time.

If one suspects a pinworm attack, you can check yourself at home, so long as you have a microscope. Simply apply some clear scotch tape to the peri-anal region, preferably in the morning before bathing has occurred, and then examine it under a microscope. The eggs are very clearly visible in clusters. They are think shelled and oval shape, typically flattened on one side. It may be possible to see the developing larva inside the egg.

                                               Photo Credit: Standford.edu

Prevention includes frequent hand washing and education. Clearing up these infections can take a while, because the chances for re-infection are so high. However, repeated doses of Albendazole or Mebendazole over a few weeks should be sufficient!

Severe problems only occur with pinworm infections when the adult females accidentally migrate too far, and re-enter the body via the vagina. There, the females and their eggs can cause a granulomatous lesion which can obstruct fallopian tubes. However, most people with pinworms are asymptomatic!

Cutaneous Larva Migrans

Since Liz said that her dog was going through a hookworm infection , this was the next logical post! Cutaneous larva migrans (CLMs) are what happens when worms get into us that don't want to be in us. This can happen especially often with Ancylostoma braziliense, which is the hookworm that most often infects dogs and cats.

                                                      Photo Credit: cdc.gov

Ancylostoma braziliense really would rather be in a dogs intestinal system. However, the mode of transmission is the same - adult worms lay eggs in the small intestine that get passed out, the eggs hatch and mature over 1-3 weeks in the soil (which is why hookworms are most prevalent in moist areas - if the eggs dry out they die), and then the infective larva wriggle their way into the circulatory system of whoever steps on them. The worms are hoping this is a dog!

However, when humans step on the area where infected dogs went to the bathroom a few weeks ago, they are at risk for getting the larva too. Fortunately for the humans (but unfortunately for the baby larva), they don't know what to do when faced with a human internal system. This causes them to stay close to the surface of the skin, and flail around in confusion.

What that means is that people will present with lines on their skin that look like someone colored on them with a red marker. It will start off as a bump that perhaps looks like a mosquito bite. Over the next few weeks, the bump will spread outwards in a long and winding line, which will eventually become dry and itchy. Typically the line will progress 1-2mm per day. While it's most common to show up on the feet, it can also be present in any area where bare skin made contact with the ground - since the infection is quite common on beaches, this can mean these lines showing up on any areas people were trying to tan! Moral of this story : wear shoes and put down a towel when you sunbathe.

While it might be tempting to try and "dig out" the worm yourself, don't! The red line does not show up for several hours after the worm has moved on. Also, it's microscopic.

Best treatments for this condition are typical anti-helminth drugs (thiabendazole), or a topical solution containing an anti-helminthic drug.

                                          Photo Credit: Stanford.edu
                   

                                               Photo Credit: Infectionnet.org

These are both pretty mild cases, you can easily see the path of a single wandering worm in each! Luckily, this is rarely a bad problem, as it is very visible and easily treatable, and the worm stays fairly close to the skin surface.

Friday, September 6, 2013

Eustrongylides spp.

"When you're drunk this weekend, don't go around eating raw minnows!"
       This was the rather odd start to a lecture. However, as I will explain, it makes a lot of sense!


Eustrongylides are a group of worms (Helminths) that present the same way in humans. These worms do not want to be in humans - they would much prefer to be in fish eating birds! However, sometimes they find their way into humans. This is very sad for them, as they freak out and have no idea what to do, human anatomy being pretty different from bird anatomy! Humans in this instance are "incidental" hosts, or hosts which the parasite does not want to be in!

This worm typically lives in the gut of birds. It is passed out with feces into the water, where it is eaten by fish. The eggs hatch in the fish and develop into infective larvae. If all goes according to plan, the fish is then eaten by the bird, and the Eustrongylides can happily grow up and reproduce in the birds gut, just like it always wanted.

Problems happen when humans eat the fish that the larvae are living in. Cooking will kill the worm, which is why it is always important to thoroughly cook any fish that you catch yourself! Fish in the US that is sold as "sushi-grade" will be deep frozen beforehand, so the parasitic worm will be killed. However, sushi that's homemade from non-sushi grade fish, or sushi (or cerviche) in other parts of the world are likely hosts!

Patients with this worm come into the ER with severe stomach pain, at times similar to a ruptured appendix. This is because the worm has hatched in their intestine, and is burrowing it's way out into the body through the intestinal wall. Exploratory surgeons in this situation are often met with the worm coming out at them, similar to that scene in Alien. Poor little worm!

Photo Credit: fcps.edu

Ancylostoma duodenale

"Ancylostoma duodenale looks like an adorable little vampire!"
       After saying this to a friend, she suggested I start this blog. It will feature information about various parasites that infect humans!


                                                 Photo Credit : Nematode.net
                                                 Interesting fact: The teeth are actually coming out of the ventral, or                                                         bottom, side of the worm, so it's basically bent back on itself

This first post is about Ancylostoma duodenale and it's close relative, Necator americanus. These are both geo-helminths, which mean they are worms that live in the soil! Both of them are commonly known as hookworm!

These worms typically live in areas of the world around the equator. They like warm, humid climates. Ancylostoma duodenale is sometimes known as the "Old World Worm", as opposed to Necator americanus's "New World Worm", but this is not altogether true, as their habitats often overlap.

Hookworms can cause chronic anemia in patients with bad infections. In children, this can mean cognitive development problems and growth issues. Ancylostoma can also be transmitted via breastmilk, so even tiny babies are at risk!

Hookworms enter the skin through the pores in the skin. The larvae are tiny, and can easily enter through hair follicles. From here, they enter the bloodstream, and eventually come to reside in the lungs. The larvae go through a molt in the alveoli to become bigger, which irritates the lungs, causing them to be coughed up. They are then swallowed, which allows them to go right where they wanted to be - the small intestine!

Once in the small intestine, the now-adult worms bite into the lining, drawing blood, which they eat. This understandably causes a lot of irritation. It can present in patients as acute abdomen or with symptoms similar to food poisoning. Ancylostoma infections are typically more severe, both because the worm is bigger, and because they can send larvae to hid out in stasis in the muscle tissue, allowing for re-infection to occur. They can cause up to a 0.2 ml blood loss per day per worm. Since infections can get over 100 worms, this can be quite a lot of blood!

Worms can be diagnosed by looking in the stool for eggs. The eggs have thin shells and are sort of oval shaped. Both species have eggs that are indistinguishable.

Both can easily be treated with anti-helminthic drugs and with iron replacement therapy.

Hookworms get into the soil by the eggs being passed out with the feces. They then lay in the ground for approximately 2 weeks, until they reach the appropriate stage to seek out a new host.

Hookworm infestation can be prevented by using flush toilets, wearing shoes, and educating people!