How is Toxoplasma transmitted?

Toxoplasma can be spread through the consumption of raw or undercooked meat of an intermediate host, (animals such as sheep, rabbits, etc.), or contact with feces from infected cats, the definitive host. According to The Toxoplasma oocysts shed in cat feces are extremely hardy, and can survive outside of an intermediate host for an entire year. These oocysts can exist in cat litter boxes, get onto grass, can contaminate water systems, and can even survive on vegetables in gardens that grow near cat feces. The hardiness of the oocysts, paired with the great number of intermediate hosts is part of the reason why Toxoplasma is such a successful parasite, and helps to explain the prevalence of Toxoplasma in humans.

How Prevalent is Toxoplasma?

The scanning electron micrograph shows a tissue cyst with its many bradyzoites within the brain of an infected mouse. Photo courtesy of David Ferguson, Oxford University. From John Boothroyd’s lab page

http://cmgm.stanford.edu/micro/boothroyd/boothroydlabdesc.html#INTRO

Toxoplasma infects a wide number of mammal and bird species, as well as infecting humans. Although it is present in almost every human population, prevalence rates vary between 15-85%, most likely because of cultural practices surrounded undercooked meat consumption and the amenability of the climate towards the Toxoplasma oocysts survival in soil. For example, South Korea has a prevalance rate of only 4.3%, while Brazil's rate is 66.9%. Parisian women have the highest recorded prevalence of Toxoplasma, most likely due to cultural practices surrounded undercooked and raw meat (John and Petri, 2006).

In the United States, about a quarter of all American adults are infected with T. gondii. According to the Third National Health and Nutrition Examination Survey, a study of 17,658 people from 1988 to 1994, the overall age-adjusted seroprevalence was 22.5%, and among women aged 15–44 years, seroprevalence was 15.0%. Interestingly, Age-adjusted seroprevalence was higher in the Northeast (29.2%) than in the South (22.8%), Midwest (20.5%), or West (17.5%) (p < 0.05).

The most common test for T. gondii is to use a blood sample to determine the presence of Toxoplasma antibodies in the blood.

What is the Lifecycle of Toxoplasma?

According to Joe Dan Dunn, a postdoctoral fellow in the Boothroyd lab at Stanford, Toxoplasma is related to Plasmodium, the protozoan parasite that causes Malaria. It uses the same cell-surface machinery that Plasmodium does to enter cells. However, Plasmodium can only infect liver cells and red blood cells. Toxoplasma, on the other hand, can infect almost any type of body cell. In addition to this ability to infect many different types of cells, Toxoplasma can spread from definitive host to definitive host, or from intermediate host to intermediate host. It does not need to undergo asexual reproduction everytime it enters a new host in order to spread. In intermediate hosts, it is most commonly seen in skeletal muscle, myocardium, and brain tissue.

Sexual Lifecycle:

The sexual stage of the lifecycle begins when a cat ingests an intermediate host infected with Toxoplasma. A zygote is formed when the organism produces schizonts and gametocytes, and eventually oocysts in the intestinal epithelium. This zygote becomes an immature oocyst, and will be shed into the environment through cat feces. Outside of the cat this oocyst develops into a robust mature oocyst that contains 8 sporozoites (specifically, two sporocysts each enclosing 4 sporozoites.)

Tachyzoite invasion of macrophages (http://www.sibleylab.wustl.edu/ToxoMovies/TgMovie3.mov) (Hiroshi Morisaki) Courtesy of The Sibley Lab Video Archive at Washington University St. Louis Medical School.

Asexual Lifecycle:

Text Box: microscopical features of tachizoites of Toxoplasma gondii and peritoneal macrophages of mouse in peritoneal exudate. (SEM)  Courtesy of the Carlo Denegri Foundation http://www.cdfound.to.it/HTML/at_ind_t.htm#tOnce in an intermediate host cell, Toxoplasma oocysts and cysts become tachyzoites and rapidly multiply until they reach about 128 copies, then they burst out of the infected cell and individual parasites will move on to another cell. In order to travel around the body and gain access to immunologically privileged sites, such as the brain, they generally infect dendritic cells, a major sentinel of the human immune system (Lambert et Al., 2006). In humans, a Toxoplasma infection is generally asymptomatic, and will occasionally cause a mild flu. After a few days, Toxoplasma parasites will wall themselves off in cysts, called bradyzoites, where they remain protected from the host’s immune system, and unable to cause any damage. Occasionally, these cysts will break and parasites will break out and infect new cells and replicate, and then re-form new cysts. The host’s immune system generally mounts a strong attack and inflammatory T cells and macrophages will mediate a response that destroys any extracellular parasites existing outside of a cyst, preventing a massive invasion of many host cells that could eventually lead to the death of the host. This is another factor contributing to the great success and prevalence of Toxoplasma as a parasite. In addition to this safety mechanism, John Boothroyd’s lab has shown that Toxoplasma has proteins that can manipulate a cell in such a way that it does not try to evoke a strong immune response against the invading intracellular pathogen. This protects both the host and the parasite, since a strong immune response to a persistent pathogen can overwhelm the body and can be fatal. Toxoplasma injects a particular protein called ROP16 into the cell it infects. This protein is a kinase, which means it is one of the class of enzymes that regulates many of the physiological processes in the host cell, one of which is responding to an infection by an outside invader. These researchers found that ROP16 travels to the cell's nucleus and is able to block the signal that would lead to a rapid immune response form an intracellular pathogen (Saeij et Al, 2007). Since it does not interfere with the host’s immune system or overtake too many host cells too quickly, it is able to live as a benign infection within a healthy intermediate host almost indefinitely, without killing the host and destroying it’s niche. In this way, it can lie undetected in an intermediate host long enough for them to possibly be devoured by a cat, another factor that plays into the success and spread of this parasite.

What does Toxoplasma do?

T. gondii changes the behavior of its intermediate host to enhance this transmission rate and complete its life cycle. It is extremely important for Toxoplasma to keep it’s host alive long enough to encounter a cat, the definitive host, and be devoured by them so it can undergo sexual reproduction and produce new oocysts. In normal rats, the scent of cat urine sets off a serious physiological response that activates an anxiety signal in the rat’s brain and prevents them from traveling to areas where cats frequent, thereby protect them from being eaten. In the lab, infected rats showed much less aversion than normal ones to bobcat urine, and in some cases seem to revisit sites that have been sprayed with bobcat urine when compared to sites sprayed with rabbit urine, and sites covered in nest material, and straw. However, the other fear responses were not affected. (Vyas et al., 2007)

The adaptive advantage of this behavior change to the parasite is quite clear, and has led to the great success of Toxoplasma in it’s ability to manipulate it’s intermediate host to reach it’s final host. Some researchers have suggested Toxoplasma can manipulate human behavior in similar ways to rats, but evidence about this is not as clear as the evidence for rats. However, it is explored in the analysis section of this website.

 


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