Toxoplasmosis and Associated Diseases and Disorders

Toxoplasmosis is considered to be the third leading cause of death attributed to foodborne illness in the United States. More that 60 million men, women, and children in the U.S. carry the Toxoplasma parasite, but very few have symptoms because the immune system usually keeps the parasite from causing illness. However, women newly infected with Toxoplasma during pregnancy and anyone with a compromised immune system should be aware that toxoplasmosis can have severe consequences for them.[22]

The parasitic zoonosis toxoplasmosis, which was poorly understood before the advent of the HIV epidemic, has become a major clinical problem worldwide. Toxoplasmosis is caused by a coccidian parasite Toxoplasma gondii. Humans acquire toxoplasmosis from cats, from consuming raw or undercooked meat, water, transfusion of infected blood, organ transplantation, and from vertical transmission to the fetus through the placenta during pregnancy. Studies of the unique environmental factors in various communities indicate the important roles that eating habits and culture have on the transmission of this infection [2], [3].

Recent advances in understanding toxoplasmosis have been made in the areas of the basic biology of the parasite and the host-parasite interaction, especially the cellular immune response. There is new insight into the biology of the cyst stage that is responsible for meat-associated transmission of infection and for the reactivation of disease in chronically infected humans. Fewer recent advances have been made in clinical diagnosis and treatment of toxoplasmosis. The fascinating revelation that Toxoplasma gondii contains an organelle--now known as the apicoplast--that derives from an algal endosymbiont, has opened many avenues of basic investigation. An understanding of the fundamental biology of T. gondii promises future progress in prevention or treatment of toxoplasmosis [4].

Cases of 2 consecutive siblings with bilateral macular lesions, for which there is strong clinical and laboratory evidence supporting the diagnosis of congenital ocular toxoplasmosis. These cases raise the possibility of maternal parasitemia during Toxoplasma gondii reinfection, leading to transmission to the fetus and congenital ocular toxoplasmosis despite prior immunity and lack of an immune disturbance in the mother. A 38-year-old woman who had been treated for ocular toxoplasmosis 20 years earlier delivered a newborn who presented with a focal necrotizing retinochoroiditis characteristic of toxoplasmosis, as well as positive immunoglobulin (Ig) G and M serology for toxoplasmosis. The workup was negative for other entities. CONCLUSION: This case suggests that women with old retinal scars due to toxoplasmosis and long-standing IgG antibodies to toxoplasmosis are also at risk of transmitting this disease to the fetus. [4]

The development of glomerulonephritis as a complication of neonatal lupus or congenital toxoplasmosis is extremely rare. We report a case of membranous glomerulonephritis occurring in a neonate with toxoplasmosis and atypical congenital lupus, including high-titer antinuclear antibodies and hypocomplementemia. This case illustrates that glomerulonephritis in the neonate may be induced by passively transferred maternal antibodies.[5]

Congenital toxoplasmosis is a potentially serious infection which usually affects infants born to non immune women. It may lead to severe visual impairment or neurological complications in the child. Neonatal screening is of importance to diagnose children with no clinicl signs as treatment has been shown to reduce long-term complications. Ophthalmological investigations should start early and continue in co-operation with paediatricians.[6] A baby with congenital toxoplasmosismay be born to a normally immunocompetent woman previously immunized against toxoplasmosis. Therefore, toxoplasmosis cannot be excluded on the ground of maternal immunity status and must be quickly investigated, given the emergency of appropriate treatment [7].

Congenital toxoplasmosis secondary to maternal primary infection acquired late during pregnancy is generally can be easily diagnosed at birth. A newborn infant was born to a woman who had been infected between the 27th and the 33rd week of gestation. No treatment had been given during gestation. The infant had a disseminated form of toxoplasmosis with hepatosplenomegaly, pneumonitis, purpura, hepatitis. On the third day of life, he developed shock. The patient died early despite therapy. Septic shock is unusual in congenital toxoplasmosis, although it has been described in immunocompromised patients, notably in patients infected with the human immunodeficiency virus [8].

Reactivation of ocular toxoplasmosis after LASIK . A 34-year-old man who underwent bilateral LASIK developed a toxoplasmosis scar in the retinal periphery of the right eye. After an operation, his vision improved, however, 52 days after the procedure, he complained of loss of visual acuity in his right eye. Examination revealed signs of anterior uveitis, vitreitis, and active chorioretinal lesion satellite of the old toxoplasmosis scar. The patient was treated with a multidrug regiment [9].

Toxoplasmosis is the most common cause of infectious retinochoroiditis in otherwise healthy individuals. Most cases of Toxoplasma infection in the immunocompetent adult have no clinical signs. The most common clinical presentation is localized enlarged lymph nodes. Ocular signs, which are common in congenitally acquired toxoplasmosis, may rarely be the only manifestation of acquired systemic toxoplasmosis. It has been suggested that concomitant infection with a DNA virus, such as CMV or herpes simplex virus, may facilitate the penetration of protozoa into cells, or that antigenic stimulation from toxoplasma antigens may activate hidden CMV in the affected person. In case of systemic toxoplasmosis, patients usually present with enlarged lymph nodes, general malaise and rash which progress to ocular signs and symptoms of retino choroiditis. Affected individuals are treated with several medications (pyrimethanime, sulfadiazone and folic acid, plus prednisone) for several weeks, during which the illness usually resolves. [10]

Toxoplasmosis with Subsequent Hearing Loss. In immunocompetent patients the acquired toxoplasmosis is usually a mild or disease with no clinical signs. central nervous system manifestations are rare, most often in patients with HIV infection or in patients with other types of immunosuppression. However, it can also affect children and adults with normal immune system. In one case, a 9-year old healthy boy, who was hospitalized after one week with subfebrile temperatures and headache with clinical signs of encephalitis and unilateral deafness. He was diagnosed with toxoplasmosis and treated pyrimethamine and sulfadiazine. While most of the signs and symptoms disappeared rapidly the deafness persisted [11].

Toxoplasmosis Transmitted by Blood Transfusions. Blood from humans collected into heparin or citrate was inoculated with toxoplasma organisms. After storage at 4 C up to 28 days, samples were injected into the ear veins of rabbits. The test rabbits developed toxoplasmosis. Similar results were obtained by transfusing rabbits with blood obtained from rabbits subcutaneously injected with toxoplasma organisms [12].

Acquired Ocular Toxoplasmosis In Deer Hunters. Five young men presented with flu-like symptoms followed by visual loss due to a unilateral, focal necrotizing retinitis. All five men gave a history of ingesting undercooked or uncooked venison. All five had elevated toxoplasma, and all five improved clinically with an antitoxoplasma treatment. In previously healthy young men, flu-like symptoms associated with visual loss and retinitis should prompt questioning about hunting and raw game meat ingestion, especially when toxoplasmosis is suspected [13].

Children with malignancy and Toxoplasmosis. In one study aimed at the diagnosis of toxoplasmosis in 73 children with malignancy, 31 children had lymphoma (22 with Hodgkin's and 9 with non-Hodgkin's lymphoma) and 42 children had leukemia (34 with acute lymphoblastic leukemia and 8 with acute myelogenic leukemia). In positive cases toxoplasmosis was manifested by any of the following: fever, lymph node enlargement, neurological manifestations and/or enlargement of the liver and spleen. The indirect hemagglutination test (IHA) for toxoplasmosis detected 4 (5.4%) positive cases with malignancy, 2 with Hodgkin's lymphoma, one with non-Hodgkin's lymphoma and one with acute lymphoblastic leukemia [14].

Toxoplasmosis and Cryptogenic Epilepsy. Recently, toxoplasmosis has been linked the cryptogenic epilepsies. Neuropathophysiology findings from various studies show a common physical relationship of microglial nodule formation in Toxoplasma gondii infection and epilepsy. This analysis raises the possibility that one of the many causes of epilepsy may be an infectious agent, or that cryptogenic epilepsy may be a consequence of latent toxoplasmosis infection. This raises the possibility that public health measures to reduce toxoplasmosis infection may also result in a reduction in epilepsy. [15]

Toxoplasmosis and Risk of Schizophrenia. Because toxoplasmosis is known to adversely affect fetal brain development, some experts have suggested the relationship between maternal antibody to toxoplasmosis and the risk of schizophrenia and other schizophrenia spectrum disorders in the offspring. The findings may be explained by reactivated infection or an effect of the antibody on the developing fetus. Given that toxoplasmosis is a preventable infection, the findings, if replicated, may have implications for reducing the incidence of schizophrenia [16].

Toxoplasmosis and Cirrhosis. 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 [19].

Toxoplasmosis and Lung Disease. Pulmonary toxoplasmosis is relatively rare in otherwise healthy subjects. In one case, a 41-year-old previously healthy male patient who presented to the emergency department of a hospital with a life-threatening case of pneumonia due to Toxoplasma gondii infection, which responded to specific therapy. Clinical and image-based findings overlap with those for atypical pneumonias, and toxoplasmosis should be considered in the differential diagnosis--especially if immunoglobulin M-specific antibodies are detected [20].

Toxoplasmosis Can Mimic SLE . Toxoplasmosis may present with clinical signs usually characteristic of other diseases. A 48-year-old woman with a recent diagnosis of SLE was admitted to the hospital because of a fever, confused state, and convulsive episode. Her symptoms were interpreted as being compatible with lupus cerebritis. Treatment with methylprednisolone resulted in a temporary improvement in the patient's condition. Nevertheless, during the next few weeks, her physical and mental condition deteriorated, and she died of massive pulmonary emboli. An autopsy revealed no signs of lupus cerebritis; however, disseminated cerebral toxoplasmosis was found. Cerebral toxoplasmosis is a rare complication of SLE that may be misdiagnosed as lupus cerebritis [20].

Toxoplasmosis and Neuroretinitis. Neuroretinitis is an eye disease usually seen in young healthy adults, that is characterized by rapid profound loss of vision and includes optic nerve head swelling, splinter hemorrhages, and variable eye inflammation. There are numerous causes that can cause a picture of neuroretinitis ranging from vascular to infectious to autoimmune. Patients with neuroretinitis caused by Toxoplasma infection respond well to treatment with systemic antibiotics and corticosteroids. Visual acuity may return in the range of 60-to 100 percent. Infectious causes of neuroretinitis, including toxoplasmosis, should be kept in mind in order to maintain visual acuity by early diagnosis and appropriate therapy [21].

Toxoplasmosis and Increased Risk of Traffic Accidents. The parasite Toxoplasma gondii infects 30-60% of humans worldwide. Latent toxoplasmosis, i.e., the life-long presence of Toxoplasma cysts in neural and muscular tissues, leads to prolongation of reaction times in infected individuals. It is not know, however, whether the changes observed in laboratory influence the performance of subjects in real-life situations. Researchers analyzed the presence of hidden toxoplasmosis in people involved in traffic accidents (total 146 accidents) and in the general population living in the same area (total 446 individuals) and found that relative risk of traffic accidents decreases with the duration of infection. These results suggest that 'asymptomatic' (having no signs) acquired toxoplasmosis might in fact represent a serious and highly underestimated public health as well as economic problem [18].

DIAGNOSIS OF TOXOPLASMOSIS

Enlargement of lymph nodes of the neck, slightly elevated body temperature and discomfort are symptoms characteristic of many illnesses. One of these can be toxoplasmosis. Sometimes toxoplasmosis may be last to be recognized. In many cases absence of specific additional examination guidelines can contribute to several problems with correct diagnosis. At the present time, the most reliable sample analysis methods are the examination of levels of antibodies IgG and IgM, and the histopathological verification. The authors also indicate that varying therapeutic effects using prophilactic treatment and insufficient additional examination could lead to diagnostic problems.

PREVENTION OF TOXOPLASMOSIS

In utero infection with Toxoplasma gondii may result in congenital defects such as hydrocephalus, chorioretinitis and mental retardation; these defects may be present at birth or may develop later in life. Prevention of this disease can be achieved in different ways.

• The most effective measure is to prevent the acquisition of the disease during pregnancy by avoiding risk factors for Toxoplasma gondii infection. Health education may decrease the incidence of toxoplasmosis during pregnancy by 60 %.
• Serologic screening during pregnancy is a preventive measure is based on to identify infected women. Treatment during pregnancy results in a significant reduction in the incidence of sequelae including severe handicaps. A third possible intervention is treating infected neonates.

Antibiotic treatment of infected children has a beneficial effect on the development of sequelae and the sooner therapy is started after birth, the better the outcome. This overview presents the potential benefits and harms of these different options available for the prevention of congenital toxoplasmosis [17].

Adapted from:
1. Toxoplasmosis, an overview with emphasis on ocular involvement. KlarenVincent N.A. In: Ocular immunology and inflammation., 10(1):1-26 2002
2. Toxoplasmosis: beyond animals to humans. Yaowalark Sukthana. In: Source Trends in Parasitology, 22(3):137-142 2006
3. Mother-to-child transmission and diagnosis of toxoplasma gondii infection during pregnancy. Singh S. In: Indian Journal of Medical Microbiology, 21(2):69-76 2003
4. Toxoplasmosis transmitted to a newborn from the mother infected 20 years earlier. Claudio Silveira, Rosane Ferreira, Cristina Muccioli, Robert Nussenblatt, Rubens Belfort In: American Journal of Ophthalmology, 136(2):370-371 2003
5. Glomerulonephritis in a neonate with atypical congenital lupus and toxoplasmosis. L. Chun, Lisa Imundo, Daniel Hirsch, Zhimin Yu, V. DAgati. In: Source Pediatric Nephrology, 13(9):850-853 1999
6. Ophthalmological findings in children with congenital toxoplasmosis. Report from a Swedish prospective screening study of congenital toxoplasmosis with two years of follow-up. K. T. Fahnehjelm, G. Malm, J. Ygge, M. L. Engman, E. Maly, B. Evengard. In: Source acta Ophthalmologica Scandinavica 78(5):569-575 2001
7. Congenital toxoplasmosis: infection during pregnancy in an immune and immunocompetent woman. F. Lebas, S. Ducrocq, V. Mucignat, L. Paris, P. Mégier, J-J. Baudon, F. Gold. In: Archives de Pediatrie, 11(8):926-928 2004
8. A septic shock due to congenital disseminated toxoplasmosis? F. Cneude, R. Deliège, C. Barbier, I. Durand-Joly, A. Bourlet, M. Sonna, G. Vittu, A. Decoster, A. Locquet, R. El Kohen. In: rchives de Pediatrie, 10(4):326-328 2003
9. Reactivation of ocular toxoplasmosis after LASIK. Author/s Adel Barbara, Raneen Shehadeh-Masha'Our, Gil Sartani, Hanna J Garzozi. In: Source Journal of Refractive Surgery, 21(6):759-761 2005
10. Ocular involvement in systemic toxoplasmosis. da Mota .S Sasaki M, J. Arana, Gurgel Batista Leite. In: Brazilian Journal of Infectious Diseases, 4(6):301-306 2001
11. Acquired toxoplasmosis with cerebral involvement and subsequent hearing loss. D. Rosch, R. Blatz. In: Klinische Padiatrie, 210(3):125-127 1998
12. Toxoplasmosis transmitted by blood transfusions. S. Raisanen. In: Transfusion, 18(3):329-332 1998
13. Presumed acquired ocular toxoplasmosis in deer hunters. R. D. Ross, L. A. Stec, J. C. Werner, M. S. Blumenkranz, L. Glazer, G. A. Williams. In: Retina, 21(3):226-229 2001
14. Diagnosis of toxoplasmosis in children with malignancy. H. E. Abdel Aaty, M. M. Abdel Latif, N. I. Ramadan. Egyptian Society of Parasitology, 30(2):523-536 2000
15. Meta-analysis of three case controlled studies and an ecological study into the link between cryptogenic epilepsy and chronic toxoplasmosis infection. Bret Sheldon Palmer. In: Seizure: The Journal of the British Epilepsy, 16(8):657-663 2007
16. Maternal Exposure to Toxoplasmosis and Risk of Schizophrenia in Adult Offspring. Brown, Alan S., Schaefer, Catherine A., Quesenberry, Charles P., Liu, Liyan, Babulas, Vicki P., Susser, Ezra S. In: American Journal of Psychiatry, 162(4):767-773 2005
17. Prevention of congenital toxoplasmosis. Foulon, Walter, Naessens, Anne, Ho-Yen, Darrel. In: Journal of Perinatal Medicine, 28(5):337-345 2000
18. Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospective case-control study. Jaroslav Flegr, Jan Havlicek, Petr Kodym, Marek Maly, Zbynek Smahel. In: BMC Infectious Diseases, 2(1):11 2002
19. Incidence of toxoplasmosis in patients with cirrhosis. Sebnem Ustun, Umit Aksoy, Hande Dagci, Galip Ersoz. In: World Journal of Gastroenterology, 10(3):452-454 2004
20. Systemic lupus erythematosus mimicking lupus cerebritis. D Zamir, M Amar, G Groisman, P Weiner. In: Mayo Clinic Proceedings, 74(6):575-578 1999
21. Ocular toxoplasmosis presenting as neuroretinitis: report of two cases. Cem Küçükerdonmez, Yonca Akova, Gursel Yilmaz. In: Ocular immunology and inflammation., 10(3):229-234 2002
22. Centers for Disease Control and Prevention: Toxoplasmosis

Animal Calendars