The parasite, Toxoplasma gondii, is thought to have been transmitted to approx half the people on the planet.T. gondii is a species of parasitic protozoa that can be carried by all known mammals. It causes toxoplasmosis, a usually minor and self-limiting disease. It can, however, have serious or even fatal effects on an unborn foetus if the mother contracts toxoplasmosis during pregnancy.
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It is known that toxoplasmosis rarely leads to various liver pathologies, most common of which is granulomatose hepatitis in patients having normal immune systems. Patients who have cirrhosis of the liver are subject to a variety of cellular as well as immunity disorders. Therefore, it may be considered that toxoplasmosis can cause more frequent and more severe diseases in patients with cirrhosis and is capable of changing the course of the disease. Cirrhotic patients are likely to form a toxoplasma risk group.
Researchers Study the Dangers of Toxoplasma Parasites
Jan 4 2010
About one-third of the human population is infected with a parasite called Toxoplasma gondii, but most people don't know it. Although Toxoplasma causes no symptoms in most people, it can be harmful to individuals with suppressed immune systems, and to fetuses whose mothers become infected during pregnancy. Toxoplasma spores are found in dirt and easily infect farm animals such as cows, sheep, pigs and chickens. Humans can be infected by eating undercooked meat or unwashed vegetables.
Jeroen Saeij, an assistant professor of biology at MIT is investigating a key question: why certain strains of the Toxoplasma parasite (there are at least a dozen) are more dangerous to humans than others. He and his colleagues have focused their attention on the type II strain, which is the most common in the United States and Europe, and is also the most likely to produce symptoms. In a paper appearing in the Jan. 3 online edition of the Journal of Experimental Medicine, the researchers report the discovery of a new Toxoplasma protein that may help explain why type II is more virulent than others.
Toxoplasma infection rates vary around the world. In the United States, it's about 10 to 15 percent, while rates in Europe and Brazil are much higher, around 50 to 80 percent. However, these are only estimates — it is difficult to calculate precise rates because most infected people don't have any symptoms.
After an infection is established, the parasite forms cysts, which contain many slowly reproducing parasites, in muscle tissue and the brain. If the cysts rupture, immune cells called T cells will usually kill the parasites before they spread further. However, people with suppressed immune systems, such as AIDS patients or people undergoing chemotherapy, can't mount an effective defense.
"In AIDS patients, T cells are essentially gone, so once a cyst ruptures, it can infect more brain cells, which eventually causes real damage to the brain," says Saeij.
The infection can also cause birth defects, if the mother is infected for the first time while pregnant. (If she is already infected before becoming pregnant, there is usually no danger to the fetus.)
There are drugs that can kill the parasite when it first infects someone, but once cysts are formed, it is very difficult to eradicate them.
A few years ago, Saeij and colleagues showed that the Toxoplasma parasite secretes two proteins called rhoptry18 and rhoptry16 into the host cell. Those proteins allow the parasite to take over many host-cell functions.
In the new study, the MIT team showed that the parasite also secretes a protein called GRA15, which triggers inflammation in the host. All Toxoplasma strains have this protein, but only the version found in type II causes inflammation, an immune reaction that is meant to destroy invaders but can also damage the host's own tissues if unchecked. In the brain, inflammation can lead to encephalitis. This ability to cause inflammation likely explains why the type II strain is so much more hazardous for humans, says Saeij.
Saeij and his team, which included MIT Department of Biology graduate students Emily Rosowski and Diana Lu, showed that type II GRA15 leads to the activation of the transcription factor known as NF-kB, which eventually stimulates production of proteins that cause inflammation. The team is now trying to figure out how that interaction between GRA15 and NF-kB occurs, and why it is advantageous to the parasite.
Ultimately, Saeij hopes to figure out how the parasite is able to evade the immune system and establish a chronic infection. Such work could eventually lead to new drugs that block the parasite from establishing such an infection, or a vaccine that consists of a de-activated form of the parasite.
MIT Department of Biology graduate students Emily Rosowski and Diana Lu are the paper's two first authors and contributed equally to the research. Other authors include MIT postdoc Kirk Jensen, lab technician Lindsay Julien, MIT undergraduate student Lauren Rodda, and Rogier Gaiser, a graduate student at Wageningen University in the Netherlands.
Reference: Strain-specific activation of the NF-kB pathway by GRA15, a novel Toxoplasma gondii dense granule protein, by Emily E. Rosowski, Diana Lu, Lindsay Julien, Lauren Rodda, Rogier A. Gaiser, Kirk D.C. Jensen, Jeroen P.J. Saeij. Journal of Experimental Medicine, 3 January 2011.
Credit: Image courtesy of E. Prandovszky and University of LeedsToxoplasma cyst outlined in red fluorescent cyst dye in mouse brain section. Hundreds of parasites are visible in cyst as blue dots (nuclei stained blue) and in surrounding brain tissue.
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Update March 23 2011
.Toxoplasmosis in a Patient who was Immunocompetent: A Case Report
Aneta K Taila; Ameet S Hingwe; Laura E Johnson
Authors and Disclosures
Posted: 03/23/2011; J Med Case Reports. 2011;5(1) © 2011 BioMed Central, Ltd.
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Case Presentation
A 20-year-old previously healthy man, a student by occupation and a non-smoker not on any medications, presented to his primary care physician with a history of swollen glands for a 'couple of months'. On further review it was found that for one month prior to presentation, our patient had noticed multiple enlarged cervical, occipital, and right inguinal lymph nodes. No constitutional symptoms were reported.
Our patient was of Middle Eastern heritage, but was born and raised in the USA. He had not travelled recently, nor had he had any recent contact with sick people or any occupational exposure. On physical examination, our patient was afebrile with normal vital signs. Enlarged, non-tender, freely mobile bilateral cervical and occipital lymph nodes were palpable and measured up to 4cm. His right inguinal lymph nodes were similarly enlarged.
The left palatine tonsil was slightly erythematous and enlarged. A monospot test was negative for Epstein-Barr virus infection. Given these findings, the primary care physician prescribed a course of antibiotics for a possible infectious etiology consisting of a three-day course of azithromycin followed by amoxicillin-clavulanate one week later due to persistent symptoms. Initial investigative tests showed normal blood counts and serum electrolytes. An HIV antibody enzyme-linked immunosorbent assay (ELISA) test was also negative.
Our patient returned to the clinic for re-evaluation. With the exception of the enlarged lymph nodes, he remained otherwise clinically asymptomatic. On physical examination, the lymph nodes appeared unchanged, and there were no newly involved nodal chains. Upon more thorough investigation, our patient indicated that approximately once month ago he ate raw kibbe, a Middle Eastern dish that consists of spiced uncooked beef or lamb with grains. Additional laboratory studies were ordered and are listed in Table 1.
Our patient was diagnosed with acute toxoplasmosis and counseled regarding dietary habits and risk factors. No specific treatment was administered, and close follow-up was planned to ensure resolution of the lymphadenopathy.
Discussion
Infection of humans with T. gondii is common worldwide, with the prevalence varying according to environment, eating habits, and age.[2] Contact with this obligate intracellular protozoan occurs through direct ingestion of food or water contaminated with cat feces containing oocysts, ingestion of tissue cysts in uncooked meat, transplacental infection of the fetus, white blood cell transfusion or organ transplantation. Our patient was probably exposed to T. gondii by eating raw lamb. Prior case reports have shown that the disease has a higher prevalence among men (79% versus 63.4% in women) and that age-dependent seroprevalence reaches > 92% in the age 40 to 50 group.[3] In seroepidemiological surveys in the USA, 11% of persons aged 6 to 49 are seropositive for T. gondii.[4]
Clinical presentation of T. gondii infection depends on the age and immune status of the patient. In the majority of patients who are immunocompetent, both adult and pediatric, primary infection is usually asymptomatic. In approximately 10% of this patient group, a non-specific and self-limiting illness is manifested most typically by isolated cervical or occipital lymphadenopathy lasting for less than four to six weeks. The lymph nodes are usually discreet, non-tender, and do not suppurate. Differential diagnoses include Epstein-Barr virus and other mononucleosis-like illnesses including cytomegalovirus and HIV with acute retroviral syndrome. Though not as common, hematological malignancies, cat scratch disease, leishmaniasis and syphilis can also cause lymphadenopathy. Very infrequently immunocompetent hosts might also suffer from myocarditis, polymyositis, pneumonitis, hepatitis, or encephalitis. After the acute phase, almost all patients will remain chronically infected with tissue cysts that are dormant and cause no clinical symptoms.
In contrast, toxoplasmosis in patients who are immunocompromised can be a life-threatening infection. In this population, toxoplasmosis almost always occurs as a result of reactivation of chronic disease and most typically affects the central nervous system. Toxoplasmic encephalitis has a varied clinical presentation, ranging from an acute confusional state with or without focal neurological deficits evolving over days to a subacute gradual process evolving over weeks. Other presentations of toxoplasmosis in patients who are immunocompromised include chorioretinitis, pneumonitis, or multi-organ failure.
Diagnosis of T. gondii infection can be made via a number of methods, both directly via polymerase chain reaction (PCR), hybridization, isolation, and histology and indirectly via serological methods. In our patient, serology was helpful. In patients who are immunocompetent, indirect serological methods are more widely used as they are readily available, faster, and cheaper. However, testing for IgG antibodies to T. gondii should also be performed in asymptomatic patients who are immunocompromised, as this allows identification of those at risk for reactivation of latent infection. Additionally, an absence of IgG antibodies in pregnant women allows identification of those at risk of acquiring infection during gestation.
Serological methods used to detect antibodies include the Sabin-Feldman dye test, immunofluorescent antibody test, ELISA, IgG avidity test, and agglutination tests. Assays for functional affinity of these antibodies have become standard as they help discriminate between recently acquired and more chronologically distant infections. The presence of high avidity antibodies essentially excludes infection acquired in the past three to four months; however, low avidity antibodies may persist beyond three months of infection and therefore do not necessarily indicate recent infection.[5]
In patients who are immunocompromised, direct methods of detection must be employed. Body fluids and tissues can be subjected to PCR amplification of T. gondii genes (specifically, the B1 gene). Assuming appropriate sample collection, handling, and storage, sensitivity is no greater than 50% but highly specific.[6] Isolation of T. gondii directly from blood or body fluids is indicative of acute infection, whether newly acquired or reactivation of latent infection. Direct diagnosis can also be made with tissue sections or body fluid smears that demonstrate tachyzoites.
Treatment with pyrimethamine, sulfadiazine and folinic acid is usually reserved for patients who are immunocompromised and those patients who are immunocompetent who have severe or persistent symptoms. Duration of treatment varies from two to four months depending upon resolution of clinical signs and symptoms. Alternatively, trimethoprim/sulfamethoxazole is equivalent to pyrimethamine/sulfadiazine.[7] Maintenance therapy should be started after the acute phase has resolved and should consist of the same regimen as in the acute phase but at half dose. This should continue for the life of the patient or until the immunosuppression has resolved.[8]
Conclusion
We present a case of acute toxoplasmosis manifesting as generalized lymphadenopathy with the leading risk factor in this case being the consumption of raw meat. For the general internist, a broad differential should be kept in mind when patients present with lymphadenopathy and appropriate testing should be performed. When the diagnosis is made, treatment is rarely required for asymptomatic patients who are immunocompetent. Proper education and counseling regarding risk factors can reduce the incidence and risk of acquiring the infection.
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Toxoplasmosis Parasite May Trigger Schizophrenia And Bipolar Disorders
Science Daily - Scientists have discovered how the toxoplasmosis parasite may trigger the development of schizophrenia and other bipolar disorders. The team from the University of Leeds' Faculty of Biological Sciences has shown that the parasite may play a role in the development of these disorders by affecting the production of dopamine -- the chemical that relays messages in the brain controlling aspects of movement, cognition and behaviour. Toxoplasmosis, which is transmitted via cat faeces (found on unwashed vegetables) and raw or undercooked infected meat, is relatively common, with 10-20% of the UK population and 22% of the US population estimated to carry the parasite as cysts.
Most people with the parasite are healthy, but for those who are immune-suppressed -- and particularly for pregnant women -- there are significant health risks that can occasionally be fatal. Dr Glenn McConkey, lead researcher on the project, says: "Toxoplasmosis changes some of the chemical messages in the brain, and these changes can have an enormous effect on behaviour. Studies have shown there is a direct statistical link between incidences of schizophrenia and toxoplasmosis infection and our study is the first step in discovering why there is this link."
The parasite infects the brain by forming a cyst within its cells and produces an enzyme called tyrosine hydroxylase, which is needed to make dopamine. Dopamine's role in mood, sociability, attention, motivation and sleep patterns are well documented and schizophrenia has long been associated with dopamine, which is the target of all schizophrenia drugs on the market. The team has recently received $250,000 (£160,000) to progress its research from the US-based Stanley Medical Research Institute, which focuses on mental health conditions and has a particular emphasis on bipolar illnesses. Dr McConkey says: "It's highly unlikely that we will find one definitive trigger for schizophrenia as there are many factors involved, but our studies will provide a clue to how toxoplasmosis infection - which is more common than you might think - can impact on the development of the condition in some individuals. "In addition, the ability of the parasite to make dopamine implies a potential link with other neurological conditions such as Parkinson's Disease, Tourette's syndrome and attention deficit disorders, says Dr McConkey. "We'd like to extend our research to look at this possibility more closely."
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