Toxoplasmosis research papers

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Toxoplasmosis research papers

Postby rdybowski » Sun Oct 01, 2006 4:20 am


Can anyone please provide me with references to the latest research papers that link lymphedema with toxoplasmosis?

Many thanks,

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Postby patoco » Sun Oct 01, 2006 4:22 am

Hi Richard and welcome to our forums.

This is coincidental as I was doing some reading and research on this the other day.

Be glad to pull together what I can.

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Postby patoco » Thu Oct 05, 2006 1:00 pm


Lymphedema People


I ran across Toxoplasmosis, ironically, while I was actually doing some research on parasitic infections of the lymph system. We are all familiar with the condition known as lymphatic filariasis, but almost no one has heard of this common condition right here in the United States.

Unfortunately with this condition, I have not been able to find any studies that concretely say toxoplasmosis will cause lymphedema.

However, I believe it may and that perhaps this is an area of misdiagnosed or underdiagnosed lymphedema, particularly in those who are immunocompromised.

I make that claim based on a couple factors.

First, it stems from a single-celled parasite that will inhabit the lymph nodes. When it does so, this causes lymphadenopathy (enlargement of the nodes). If it is severe enough it may damage the node and cause hyperplaysia (dilation) of the node. This type of damage limits the lymph system from properly carrying out its function of removing excess fluid, hence, lymphedema.


What is toxoplasmosis?

A single-celled parasite called Toxoplasma gondii causes a disease known as toxoplasmosis. While the parasite is found throughout the world, more than 60 million people in the United States may be infected with the Toxoplasma parasite. Of those who are infected, very few have symptoms because a healthy person's immune system usually keeps the parasite from causing illness. However, pregnant women and individuals who have compromised immune systems should be cautious; for them, a Toxoplasma infection could cause serious health problems.

How do people get toxoplasmosis?

A Toxoplasma infection occurs by:

· Accidentally swallowing cat feces from a Toxoplasma-infected cat that is shedding the organism in its feces. This might happen if you were to accidentally touch your hands to your mouth after gardening, cleaning a cat's litter box, or touching anything that has come into contact with cat feces. Eating contaminated raw or partly cooked meat, especially pork, lamb, or venison; by touching your hands to your mouth after handling undercooked meat.

· Contaminating food with knives, utensils, cutting boards and other foods that have had contact with raw meat.
· Drinking water contaminated with Toxoplasma.
· Receiving an infected organ transplant or blood transfusion, though this is rare.

What are the symptoms of toxoplasmosis?

Symptoms of the infection vary.

· Most people who become infected with Toxoplasma are not aware of it.
· Some people who have toxoplasmosis may feel as if they have the "flu" with swollen lymph glands or muscle aches and pains that last for a month or more.
· Severe toxoplasmosis, causing damage to the brain, eyes, or other organs, can develop from an acute Toxoplasma infection or one that had occurred earlier in life and is now reactivated. Severe cases are more likely in individuals who have weak immune systems, though occasionally, even persons with healthy immune systems may experience eye damage from toxoplasmosis.
· Most infants who are infected while still in the womb have no symptoms at birth, but they may develop symptoms later in life. A small percentage of infected newborns have serious eye or brain damage at birth.
Who is at risk for developing severe toxoplasmosis?
People who are most likely to develop severe toxoplasmosis include:
· Infants born to mothers who became infected with Toxoplasma for the first time during or just before pregnancy.
· Persons with severely weakened immune systems, such as individuals with HIV/AIDS, those taking certain types of chemotherapy, and those who have recently received an organ transplant.

What should I do if I think I am at risk for severe toxoplasmosis?

If you are planning to become pregnant, your health care provider may test you for Toxoplasma. If the test is positive it means you have already been infected sometime in your life. There usually is little need to worry about passing the infection to your baby. If the test is negative, take necessary precautions to avoid infection (See below).

If you are already pregnant, you and your health care provider should discuss your risk for toxoplasmosis. Your health care provider may order a blood sample for testing.

If you have a weakened immune system, ask your doctor about having your blood tested for Toxoplasma. If your test is positive, your doctor can tell you if and when you need to take medicine to prevent the infection from reactivating. If your test is negative, it means you have never been infected and you need to take precautions to avoid infection. (See below).

What should I do if I think I may have toxoplasmosis?

If you suspect that you may have toxoplasmosis, talk to your health care provider. Your provider may order one or more varieties of blood tests specific for toxoplasmosis. The results from the different tests can help your provider determine if you have a Toxoplasma infection and whether it is a recent (acute) infection.

What is the treatment for toxoplasmosis?

Once a diagnosis of toxoplasmosis is confirmed, you and your health care provider can discuss whether treatment is necessary. In an otherwise healthy person who is not pregnant, treatment usually is not needed. If symptoms occur, they typically go away within a few weeks to months. For pregnant women or persons who have weakened immune systems, medications are available to treat toxoplasmosis.

How can I prevent toxoplasmosis?

There are several general sanitation and food safety steps you can take to reduce your chances of becoming infected with Toxoplasma.

· Wear gloves when you garden or do anything outdoors that involves handling soil. Cats, which may pass the parasite in their feces, often use gardens and sandboxes as litter boxes. Wash your hands well with soap and water after outdoor activities, especially before you eat or prepare any food.
· When preparing raw meat, wash any cutting boards, sinks, knives, and other utensils that might have touched the raw meat thoroughly with soap and hot water to avoid cross-contaminating other foods. Wash your hands well with soap and water after handling raw meat.
· Cook all meat thoroughly; that is, to an internal temperature of 160° F and until it is no longer pink in the center or until the juices become colorless. Do not taste meat before it is fully cooked.

For further information on safe food handling to help reduce food borne illness visit the Fight BAC! ® Web site at

If I am at risk, would I be able to keep my cat?

Yes, you may keep your cat if you are a person at risk for a severe infection (e.g., you have a weakened immune system or are pregnant); however, there are several safety precautions to avoid being exposed to Toxoplasma:

· Keep your cat healthy and help prevent it from becoming infected with Toxoplasma. Keep your cat indoors and feed it dry or canned cat food rather than allowing it to have access to wild birds and rodents or to food scraps. A cat can become infected by eating infected prey or by eating raw or undercooked meat infected with the parasite. Do not bring a new cat into your house that might have spent time out of doors or might have been fed raw meat. Avoid stray cats and kittens and the area they have adopted as their "home." Your veterinarian can answer any other questions you may have regarding your cat and risk for toxoplasmosis.

· Have someone who is healthy and not pregnant change your cat's litter box daily. If this is not possible, wear gloves and clean the litter box every day, because the parasite found in cat feces needs one or more days after being passed to become infectious. Wash your hands well with soap and water afterwards.

Once infected with Toxoplasma is my cat always able to spread the infection to me?

No, cats only spread Toxoplasma in their feces for a few weeks following infection with the parasite. Like humans, cats rarely have symptoms when first infected, so most people do not know if their cat has been infected. The infection will go away on its own; therefore it does not help to have your cat or your cat's feces tested for Toxoplasma.

This fact sheet is for information only and is not meant to be used for self-diagnosis or as a substitute for consultation with a health care provider. If you have any questions about the disease described above or think that you may have a parasitic infection, consult a health care provider.
Revised September 20, 2004 ... smosis.htm




Toxoplasmosis, caused by the protozoan parasite Toxoplasma gondii, is one of the most common parasitic infections of man and other warm-blooded animals. It has been found worldwide from Alaska to Australia. Nearly one-third of humanity has been exposed to this parasite. In most adults it does not cause serious illness, but it can cause blindness and mental retardation in congenitally infected children and devastating disease in immunocompromised individuals.

Stages of Toxoplasma gondii. Scale bar in A-D= 20 µm, in E-G = 10 µm.

A. Tachyzoites in impression smear of lung. Note crescent-shaped individual tachyzoites (arrows), dividing tachyzoites (arrowheads) compared with size of host red blood cells and leukocytes. Giema stain.

B. Tissue cysts in section of muscle. The tissue cyst wall is very thin (arrow) and encloses many tiny bradyzoites (arrowheads). Hematoxylin and eosin stain.

C. Tissue cyst separated from host tissue by homogenization of infected brain. Note tissue cyst wall (arrow) and hundreds of bradyzoites (arrowheads). Unstained.

D. Schizont (arrow) with several merozoites (arrowheads) separating from the main mass. Impression smear of infected cat intestine. Giemsa stain.

E. A male gamete with two flagella (arrows). Impression smear of infected cat intestine. Giemsa stain.

F. Unsporulated oocyst in fecal float of cat feces. Unstained. Note double layered oocyst wall (arrow) enclosing a central undivided mass.

G. Sporulated oocyst with a thin oocyst wall (large arrow), 2 sporocysts (arrowheads). Each sporocyst has 4 sporozoites (small arrow) which are not in complete focus. Unstained.

Life Cycle

Humans become infected by ingesting food and water contaminated with oocysts from infected cat feces, or by ingesting tissue cysts in under cooked or uncooked meat. Contamination of the environment by oocysts is widespread, as oocysts are shed by domestic cats and other members of the Felidae. Domestic cats are probably the major source of contamination since oocyst formation is greatest in domestic cats.

Cats may excrete millions of oocysts after ingesting as few as 1 bradyzoite or 1 tissue cyst, and many tissue cysts may be present in one infected mouse. Generally, only about 1% of cats in a population are found to be shedding oocysts at any given time. Oocysts are shed for only a short period (1-2 weeks) in the life of the cat, however, the enormous numbers shed assure widespread contamination of the environment. Under experimental conditions, infected cats can shed oocysts after reinoculation with tissue cysts. It is not known whether repeated shedding of oocysts occurs in nature, but this would greatly facilitate oocyst spread.

Sporulated oocysts survive for long periods under most ordinary environmental conditions. They can survive in moist soil, for example, for months and even years. Oocysts in soil do not always stay there, as invertebrates like flies, cockroaches, dung beetles, and earthworms can mechanically spread these oocysts and even carry them onto food.

Congenital infection can occur in cats, and congenitally infected kittens can excrete oocysts, providing another source of oocysts for contamination. Infection rates in cats reflect the rate of infection in local avian and rodent populations because cats are thought to become infected by eating these animals. The more oocysts there are in the environment, the more likely it is that prey animals will become infected, and this results in increased infection rates in cats.

Clinical Disease

In the United States and the United Kingdom, it is estimated that 16 to 40% of people are infected with T. gondii, whereas in Central and South America and continental Europe, estimates of infection range from 50 to 80%. Most infections in humans are asymptomatic, but at times the parasite can produce devastating disease. Infection may be congenitally or postnatally acquired. Congenital infection occurs only when a woman becomes infected during pregnancy. Congenital infections acquired during the first trimester are more severe than those acquired in the second and third trimester. While the mother rarely has symptoms of infection, she does have a temporary parasitemia. Focal lesions develop in the placenta and the fetus may become infected.

At first there is generalized infection in the fetus. Later, infection is cleared from the visceral tissues and may localize in the central nervous system. A wide spectrum of clinical diseases occur in congenitally infected children.

Mild disease may consist of slightly diminished vision, whereas severely diseased children may have the full tetrad of signs: retinochoroiditis, hydrocephalus, convulsions, and intracerebral calcification. Of these, hydrocephalus is the least common but most dramatic lesion of toxoplasmosis. By far the most common sequel of congenital toxoplasmosis is ocular disease.

The socio-economic impact of toxoplasmosis in human suffering and the cost of care of sick children, especially those with mental retardation and blindness, are enormous. The testing of all pregnant women for T. gondii infection is compulsory in some European countries, including France and Austria. The cost benefits of such mass screening are being debated in many other countries.

Postnatally acquired infection may be localized or generalized. Oocyst-transmitted infections may be more severe than tissue cyst-induced infections. Enlarged lymph nodes are the most frequently observed clinical form of toxoplasmosis in humans. Lymphadenopathy may be associated with fever, fatigue, muscle pain, sore throat, and headache. Although the condition may be benign, its diagnosis is vital in pregnant women because of the risk to the fetus. In a British Columbia outbreak, of 100 people who were diagnosed with acute infection, 51 had lymphadenopathy and 20 had retinitis.

Encephalitis is the most important manifestation of toxoplasmosis in immunosuppressed patients as it causes the most severe damage to the patient. Infection may occur in any organ. Patients may have headache, disorientation, drowsiness, hemiparesis, reflex changes, and convulsions, and many become comatose. Encephalitis caused by T. gondii is now recognized with great frequency in patients treated with immunosuppressive agents.

Toxoplasmosis ranks high on the list of diseases which lead to death of patients with acquired immunodeficiency syndrome (AIDS); approximately 10% of AIDS patients in the U.S. and up to 30% in Europe are estimated to die from toxoplasmosis. Although in AIDS patients any organ may be involved, including the testis, dermis, and the spinal cord, infection of the brain is most frequently reported. Most AIDS patients suffering from toxoplasmosis have bilateral, severe, and persistent headache which responds poorly to analgesics. As the disease progresses, the headache may give way to a condition characterized by confusion, lethargy, ataxia, and coma. The predominant lesion in the brain is necrosis, especially of the thalamus.

Sulfadiazine and pyrimethamine (Daraprim) are 2 drugs widely used for treatment of toxoplasmosis. While these drugs have a beneficial action when given in the acute stage of the disease process when there is active multiplication of the parasite, they will usually not eradicate infection. It is believed that these drugs have little effect on subclinical infections, but the growth of tissue cysts in mice has been restrained with sulfonamides. Certain other drugs, diaminodiphenylsulfone, atovaquone, spiramycin, and clindamycin are also used to treat toxoplasmosis in difficult cases.


To prevent infection of human beings with T. gondii, especially pregnant women, children, and immunocompromised individuals, contact with cats, soil, and raw meat should be avoided, and people should be made aware of the dangers of toxoplasmosis . Pet cats should be fed only dry, canned, or cooked food. The cat litter box should be emptied every day, a task to be avoided by susceptible groups listed above. Gloves should be worn while gardening. Vegetables should be washed thoroughly before eating because they may have been contaminated with cat feces. The hands of people handling meat should be washed thoroughly with soap and water before they begin other tasks. All cutting boards, sink tops, knives, and other materials coming in contact with uncooked meat should be washed with soap and water also. Toxoplasma gondii organisms in meat can be killed by exposure to extreme heat or cold. Tissue cysts in meat are killed by heating the meat throughout to 67C or by cooling to -13C. Toxoplasma in tissue cysts are also killed by exposure to 0.5 kilorads of gamma irradiation. Meat of any animal should be cooked to 67C before consumption, and tasting meat while cooking or while seasoning should be avoided. At present, there is no vaccine to prevent toxoplasmosis in humans.


Diagnosis of toxoplasmosis in humans is made by biologic, serologic, histologic, or molecular methods, or by some combination of the above. Clinical signs of toxoplasmosis are non-specific and are not sufficiently characteristic for a definite diagnosis. Toxoplasmosis in fact mimics several other infectious diseases.

Detection of T. gondii antibody in patients may aid diagnosis. There are numerous serologic procedures available for detection of humoral antibodies; these include the Sabin-Feldman dye test, the indirect hemagglutination assay, the indirect fluorescent antibody assay (IFA), the direct agglutination test, the latex agglutination test (LAT), the enzyme-linked immunoabsorbent assay (ELISA), and the immunoabsorbent agglutination assay test (IAAT). The IFA, IAAT and ELISA have been modified to detect IgM antibodies. The IgM antibodies appear sooner after infection than the IgG antibodies and the IgM antibodies disappear faster than IgG antibodies after recovery.

The finding of antibodies to T. gondii in one serum sample only establishes that the host has been infected at some time in the past. It is best to collect 2 samples from the same individual, the second collected 2 to 4 weeks after the first. A 16-fold higher antibody titer in the second sample indicates an acute infection. A high antibody titer sometimes persists for months after infection. A rise in antibody titer may not be associated with clinical symptoms, for as indicated earlier, most infections in humans are asymptomatic. The fact that titers persist in infected people after clinical recovery complicates the interpretation of the results of serological tests. Establishing recency of infection in pregnancy is of clinical importance with respect to medical intervention to minimize damage to the fetus, and there is no one test that can achieve this at the present time.

Toxoplasma gondii can be isolated from patients by inoculation of laboratory animals and tissue cultures with secretions, excretions, body fluids, tissues taken by biopsy, and tissues with macroscopic lesions taken postmortem. Using such specimens, one may not only attempt isolation of T. gondii, but one may search for T. gondii microscopically using traditional histochemical stains or by immunohistochemical staining of parasites with fluorescent or other types of labeled T. gondii. Recent studies have shown that monoplex and multiplex PCR can be useful for specifically identifying T. gondii (using the B1 gene as the target sequence) from tissue biopsies, cerebrospinal fluid, vitreous from patients with undiagnosed uveitis, fetal blood, and amniotic fluid.


Although T. gondii has been isolated from soil, there is no simple method for oocyst isolation from soil that is useful on an epidemiological scale. Although attempts to recover T. gondii oocysts from water samples in the British Columbia outbreak were unsuccessful, methods to detect oocysts were reported. At present, there are no commercial reagents available to detect T. gondii oocysts in the environment.

Toxoplasma gondii infection is common in many animals used for food including sheep, pigs, and rabbits, and infection in humans often results from ingestion of tissue cysts contained in undercooked meat. Infection in cattle, horses, and water buffaloes is less prevalent than is infection in sheep or pigs. Toxoplasma gondii in tissue cysts survive in food animals for years.

Virtually all edible portions of an animal can harbor viable T. gondii. In one study, viable T. gondii was isolated from 17% of 1,000 adult pigs (sows) from a slaughter plant in Iowa. T. gondii infection is also prevalent in game animals. Among wild game, T. gondii infection is most prevalent in black bears and in white-tailed deer. Approximately 80% of black bears are infected in the U. S., and about 60% of raccoons have antibodies to T. gondii. Because raccoons and bears scavenge for their food, infection in these animals is a good indicator of the prevalence of T. gondii in the environment.

The number of T. gondii tissue cysts in meat from food animals is very low. It is estimated that as few as 1 tissue cyst may be present in 100 grams of meat. Therefore, without using a concentration method, it is not practical to detect this low level of T. gondii infection. The detection of T. gondii DNA in meat samples by PCR has been reported, but there are no data on specificity and sensitivity of this method to detect T. gondii in meat samples. A highly sensitive method using a Real-Time PCR and fluorogenic probe was found to detect T. gondii DNA from as few as 4 bradyzoites.



Toxoplasma and the Lymph System

Toxoplasmic Lymphadenopathy

Studies on the serodiagnosis of toxoplasmic lymphadenitis.


Toxoplasmic Lymphadenopathy Clinically Presenting as Lymphoma ... ment4.html

Evidence based criteria for the histopathological diagnosis of toxoplasmic lymphadenopathy

2005 ... 58/11/1143

Isolated Mediastinal Lymphadenitis Caused by Toxoplasma Infection in an Immunocompetent Adult

2004 ... hp3?id=379

Evaluation of the immunoglobulin G avidity test for diagnosis of toxoplasmic lymphadenopathy.

2004 ... 7&fid=4047


Toxoplasmosis Complications

Toxoplasmosis can sometimes spread to the eyes (toxoplasmosis of the eye). This causes inflammation and scarring of the retina (the nerve tissue lining the back of the eye) and choroid (the layer behind the retina that contains major blood vessels), which can cause many eye conditions and problems.

These include:

· loss of eyesight,
· a squint,
· clouding on the eye lens (cataract),·
· eye shrinking (microphthalmia), and
· loss of cells and tissue from the optic nerve (which connects the eye to the brain), resulting in poor vision (optic atrophy).

It is important to treat any complications of the scarring quickly to prevent further damage to the retina. Antibiotics and steroid tablets are often used, and if treated quickly, symptoms usually settle within a few weeks.

The actual scarring caused by toxoplasmosis will not clear up, but treatment will prevent it getting worse. However, the parasite can lie dormant (asleep) in the retina for many years, and ‘wake up’ at any time, starting a new infection.

Complications in unborn babies

The risk and severity of your baby’s infection depends on when in the pregnancy you were infected. Your baby is least likely to be affected if you become infected in the first 12 weeks of pregnancy (the first trimester). However, this is also the time when infection can prove most serious for your baby – with early infections there is an increased risk of miscarriage and even stillbirth, or severe health problems with the newborn baby.

These include:

· jaundice,
· a large or abnormally shaped head due to excess fluid in the brain,
· learning disabilities,
· seizures, and
· an enlarged liver or spleen.

Babies whose mothers are infected during the last 28 weeks of pregnancy are more at risk of developing the condition, and may also develop serious health problems – although only a small percentage of these babies experience any problems or symptoms at birth.

Instead, complications of the infection may develop in their 20s or 30s, such as:

· learning disabilities,
· hearing loss, and
· toxoplasmosis of the eye.

The chances of contracting toxoplasmosis during pregnancy are low — only about one in 500 women in the UK. Studies also show that a large number of women have become immune to toxoplasmosis before getting pregnant, so the parasite cannot go on to harm your baby. ... onId=19603


If you have a strong immune system, you're not likely to experience any complications of toxoplasmosis, although otherwise healthy people sometimes develop eye infections. But if your immune system is compromised, especially as a result of HIV/AIDS, toxoplasmosis can lead to seizures and life-threatening illnesses such as encephalitis — a serious brain infection. In people living with AIDS, untreated encephalitis resulting from toxoplasmosis is always fatal. Relapse also is a constant concern for immunocompromised people with toxoplasmosis.

Children with congenital toxoplasmosis may develop disabling complications, including hearing loss, blindness and mental retardation. ... DSECTION=7


Toxoplasmosis in pregnancy

Diagnosis of congenital Toxoplasma gondii infection by polymerase chain reaction (PCR) on amniotic fluid samples. The Norwegian experience.

1998 ... ds=9740505

Follow-up of infants with congenital toxoplasmosis detected by polymerase chain reaction analysis of amniotic fluid.

1998 ... s=10052549

Prenatal diagnosis of congenital toxoplasmosis: a multicenter evaluation of different diagnostic parameters.

1999 ... s=10521739

Neonatal screening for congenital toxoplasmosis in a cohort of 165 women infected during pregnancy and influence of in utero treatment on the results of neonatal tests.

2001 ... s=11134824

Treatment of toxoplasmosis in pregnancy: concentrations of spiramycin and neospiramycin in maternal serum and amniotic fluid.

2002 ... s=11913495

Primary Toxoplasma gondii infection in a pregnant human immunodeficiency virus-infected woman.

2002 ... s=12400531

Prevention of congenital toxoplasmosis in Slovenia by serological screening of pregnant women.

2002 ... s=12030394

Congenital toxoplasmosis: prevention in the pregnant woman and management of the neonate


Toxoplasmosis--epidemiology, clinical manifestation and infection in pregnant women

2006 ... med_docsum
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