2. case presentaion 姓名 :I1 余陳瑋 日期 :94/12/12

3. Chief complaint, present illness, & personal/past/family history A 37-year-old man with AIDS had been suffering from headache, fever, and fatigue for several weeks. He also had a history of seizures. He was brought to his family physician by his roommate. The roommate reported that the patient had been disoriented and confused for several weeks.

4. Physical examination headache, fever, and fatigue for several weeks.

5. Laboratory tests The patient's CD4 T-lymphocyte count was determined to be 50/mm3 Serological tests for Toxoplasma- specific immunoglobulin G were negative.

6. Imagine finding A computed tomogram revealed multiple cerebral lesions.

8. After being treated with a combination of pyrimethamine and clarithromycin, the patient appeared to recover from his infection.

9. Taxoplasmosis Tissue protozoa( 組織原蟲 ) --Toxoplasma gondii ( 弓蟲 )

10. ETIOLOGY T. gondii is an intracellular coccidian that infects both birds and mammals. There are two distinct stages in the life cycle of T. gondii: the nonfeline and feline stages. These tissue cysts occur in a variety of host organs but persist principally within the central nervous system (CNS) and muscle. The principal stage in the life cycle of the parasite takes place in the cat (the definitive host) and its prey.

11. EPIDEMIOLOGY T. gondii infects a wide range of mammals and birds. Its seroprevalence depends on the locale and the age of the population. In the United States and most European countries, the prevalence of seroconversion increases with age and exposure. In Central America, France, Turkey, and Brazil, the seroprevalence is higher.

12. CLINICAL MANIFESTATIONS In persons whose immune systems are intact, acute toxoplasmosis is usually asymptomatic and self- limited. This condition can go unrecognized in 80 to 90% of adults and children with acquired infection. Toxoplasmosis in the Immunocompetent Person -The most common manifestation of acute toxoplasmosis is cervical lymphadenopathy. Between 20 and 40% of patients with lymphadenopathy also have headache, malaise, fatigue, and fever [usually with a temperature of <40C (<104 F)].small portion are myalgia, sore throat, abdominal pain, maculopapular rash, meningoencephalitis, and confusion.

13. CLINICAL MANIFESTATIONS Infection of the Immunocompromised Person -In most of these cases, encephalitis develops when the CD4+ cell count falls below 100/uL. More than 50% of patients with clinical manifestations have intracerebral involvement. These findings include encephalopathy, meningoencephalitis, and mass lesions.(altered mental status (75%), fever (10 to 72%), seizures (33%), headaches (56%), and focal neurologic findings (60%), including motor deficits, cranial nerve palsies, movement disorders, dysmetria, visual-field loss, and aphasia.)

14. DIAGNOSIS Serology -Diagnosis of acute infection with T. gondii can be established by detection of the simultaneous presence of IgG and IgM antibody to Toxoplasma in serum. The presence of circulating IgA favors the diagnosis of an acute infection. The Sabin-Feldman dye test, the indirect fluorescent antibody test, and the enzyme-linked immunosorbent assay (ELISA) all satisfactorily measure circulating IgG antibody to Toxoplasma.

15. TREATMENT Pyrimethamine and sulfadiazine are active only against the tachyzoite stage of the parasite. after immunocompromised patients complete the initial 4- to 6-week course, they must receive lifelong suppressive therapy with pyrimethamine (25 to 50 mg/d) and sulfadiazine (2 to 4 g/d). Immunologically competent adults and older children who have only lymphadenopathy do not require specific therapy unless they have persistent and severe symptoms. Patients with ocular toxoplasmosis should be treated for 1 month with pyrimethamine plus either sulfadiazine or clindamycin.

16. TREATMENT Congenital Infection -daily oral pyrimethamine (0.5 to 1 mg/kg) and sulfadiazine (100 mg/kg) for 1 year. In addition, therapy with spiramycin (100 mg/kg per day) plus prednisone (1 mg/kg per day). Infection in Immunocompromised Patients - Administered together for 4 to 6 weeks or until radiologic improvement is documented, pyrimethamine (a 200-mg loading dose followed by 50 to 75 mg/d) and sulfadiazine (4 to 6 g/d in four divided doses). Leucovorin (calcium folinate, 10 to 15 mg/d) is given as an adjunct to prevent the bone marrow toxicity associated with pyrimethamine.

17. Question 1 What is the likely diagnosis of this patient's parasitic illness?

18. Answer 1 Taxoplasmosis ( Taxoplasma gondii )

19. Question 2 What is the association between the patient's history of AIDS and this infection?

20. Answer 2 In individuals with AIDS, more than 95% of cases of Toxoplasma encephalitis are believed to be due to recrudescent infection. In most of these cases, encephalitis develops when the CD4+ cell count falls below 100/uL. Toxoplasmosis is a principal opportunistic infection of the CNS in persons with AIDS.

21. Question 3 Which other group of individuals is at risk when infected with this parasite?

22. Answer 3 Congenital infection Immunocompromissed Malignance Organ transplant AIDS

23. Question 4 How is this infection transmitted?

24. Answer 4 Oral Transmission Transmission via Blood or Organs Transplacental Transmission

25. Question 5 Why was serology negative for this patient? How is the diagnosis of this illness made for immunocompromised patients including AIDS patients, transplant recipients, and patients with cancers or autoimmune diseases?

26. Answer 5 Positive IgG titers (>1:10) can be detected as early as 2 to 3 weeks after infection. These titers usually peak at 6 to 8 weeks and decline slowly to a new baseline level that persists for life. In patients with AIDS, the presence of IgG and radiologic findings consistent with toxoplasmosis are grounds for a presumptive diagnosis

27. Question 6 Describe the life cycle of this parasite.

28. Answer 6

30. Question 7 What effect have the new antiretroviral therapies for AIDS (known as highly active antiretroviral therapy [HAART]) had on the frequency of this infection?

31. Answer 7 Therapy is generally for life; however, with the advent of highly active antiretroviral therapy (HAART), it may be possible to discontinue therapy in patients with sustained suppression of HIV replication and CD4+ T cell counts >100/uL for >6 months. Primary prophylaxis for MAC is indicated in patients with HIV infection and CD4+ T cell counts 100/uL for 3 to 6 months.

32. Question 8 How might this patient be treated?

33. Answer 8 The mainstay of treatment for Toxoplasma encephalitis in immunocompromised patients is a combination regimen. Administered together for 4 to 6 weeks or until radiologic improvement is documented, pyrimethamine (a 200-mg loading dose followed by 50 to 75 mg/d) and sulfadiazine (4 to 6 g/d in four divided doses) block folic acid metabolism and reduce the parasite burden. Leucovorin (calcium folinate, 10 to 15 mg/d) is given as an adjunct to prevent the bone marrow toxicity associated with pyrimethamine. Both pyrimethamine and sulfadiazine cross the blood-brain barrier.

34. Sabin-Feldman dye test The Sabin-Feldman dye test, the indirect fluorescent antibody test, and the enzyme- linked immunosorbent assay (ELISA) all satisfactorily measure circulating IgG antibody to Toxoplasma. 1. 弓蟲 + normal serum + methylene blune = 染藍色 2. 弓蟲 + Anti-serum + methylene blune = 染不 出藍色

35. Diagnosis is made by CT scan with contrast or by MRI scan, which typically shows multiple enhancing brainstem lesions. Treatment consists of sulfadiazine and pyrimethamine. Lesions on MRI scan are multiple and are located in both hemispheres, with the basal ganglia and corticomedullary junction most commonly involved Histologic examination of lymph nodes may suggest the characteristic changes described above. Demonstration of tachyzoites in lymph nodes establishes the diagnosis of acute toxoplasmosis.

36. Although in patients with AIDS T. gondii infection is believed to be recrudescent, determination of antibody titers is not helpful in establishing reactivation. Because of the severe depletion in CD4+ T cells, quite frequently there is no observed increase in antibody titer during exacerbation of infection. T cells from AIDS patients with reactivation of toxoplasmosis fail to secrete both IFN-g and IL-2. This alteration in the production of these critical immune cytokines contributes to the persistence of infection. Toxoplasma infection frequently develops late in the course of AIDS, when the loss of T cell- dependent protective mechanisms, particularly CD8+ T cells, becomes most pronounced.

37. Lesions are multiple and are located in both hemispheres, with the basal ganglia and corticomedullary junction most commonly involved.

38. Toxoplasma gondii Infections (Toxoplasmosis). A 3-day-old boy presented with a seizure. His computed tomography scan demonstrated hydrocephalus and periventricular calcification, suggestive of toxoplasmosis, other agents, rubella, cytomegalovirus, herpes simplex (TORCH) infection. Toxoplasma serology was positive and the infant was treated for congenital toxoplasmosis with pyrimethamine, sulfadiazine, and folinic acid.

39. Toxoplasma gondii, pseudocyst in myocardium, microscopic

40. Alveolar pneumocytes are infected by Toxoplasma gondii

41. Pseudocysts are seen here in cerebrum in a microglial nodule

42. THANK YOU FOR YOUR ATTENTION

43. Reference Harrison's Principles of Internal Medicine - 16th Ed. (2005) Diagnostic medical parasitology - 4th Ed.