TOXOPLASMOSISI.ppt
- 1. TOXOPLASMOSIS DR.HAMISI MKINDI,MD. TO DOWNLOAD CONTACT: hermyc@live.com
- 2. OVERVIEW Toxoplasmosis is caused by infection with the protozoan Toxoplasma gondii, an obligate intracellular parasite. Certain individuals, are at high risk of severe or life- threatening disease due to this parasite. These include congenitally infected fetuses, newborns and immunologically impaired individuals Congenital toxoplasmosis is the result of maternal infection acquired during gestation.
- 3. In immunodeficient patients,toxoplasmosis most often occurs in persons with defects in T cell–mediated immunity such as those receiving corticosteroids, anti–tumor necrosis factor (TNF) therapies, or cytotoxic drugs and those with malignance, organ transplants, or acquired immunodeficiency syndrome (AIDS).
- 4. In immunocompetent individuals, primary or chronic (latent) infection with T. gondii is asymptomatic; after the acute infection, a small percentage has chorioretinitis, lymphadenitis, or, even more rarely, myocarditis and polymyositis In 1983, the first report of toxoplasmosis in AIDS patients appeared.Toxoplasmic encephalitis (TE) subsequently was recognized as the major cause of space- occupying lesions in the brains
- 5. ETIOLOGY AND LIFE CYCLE T. gondii is a coccidian parasite of felids with humans and other warm blooded animals serving as intermediate hosts. It belongs to the subphylum Apicomplexa, class Sporozoa Its infectious frorms includes the oocyst, the tachyzoites(group or claster of oocyst) and tissue cyst (which contains and may release bradyzoites),
- 6. Most organisms isolated from both animals and humans can be grouped into one of three clonal genotypes (types I to III) Type III strains are common in animals but observed significantly less often in cases of human toxoplasmosis; most cases in humans are caused by type II strains. Both type I and II strains have been associated with human congenital toxopl
- 7. 1. OOCYST Cats sheds oocysts after they ingest any of the three forms of the parasite, at which time an enteroepithelial cycle begins. This sexual form of reproduction begins when the parasites penetrate the epithelial cells of the small intestine and initiate development of asexual and sexual (gametogony) forms of the parasite. Oocyst wall, oocysts are discharged into the intestinal lumen by rupture of intestinal epithelial cells.
- 8. 2. TACHYZOITE Tachyzoites are seen in both primary and reactivated infection; their presence is the hallmark of active infection. Once the tachyzoite has invaded the target cell, it can undergo stage conversion into the bradyzoite form.
- 9. 3. TISSUE CYST Tachyzoites multiply rapidly and synchronously, forming more slowly replicating bradyzoites which forms tissue cysts.
- 10. VIRULENCE FACTORS Its anterior end consist Conoid assist parasites entrace into host cells Rhoptries which has secretory functions for parasitic invasion. It has Dense granules in its cytoplasm which release parasitophorous vacuole,which also assist its entry.
- 14. The oocysts survive better in environments with hot,humid climate and lower altitude. Infection rate is often highest in this area. EPIDEMIOLOGY
- 17. T.gondii can favor mother to child transmission HCV,HBV and HIV verticle transimmision. According to this study,336 pregnant women were enrolled for investigation on the presence of serum antibodies agaist T.gondii,HCV,HBV and HIV using ELISA, the prevlance of T.gondii,HCV and HBV was 25.3%,5.4%,9.8% respectively HIV serostatus 61.6 % seems to be associated with greater prevalance rate of both T. gondii 28.5% vs 20.2% and HBV 11.6% vs 7%.
- 18. Untreated T.gondii infection are often fatal in AIDS patients, IgG agglutination and PCR was used to analyse blood samples from 130 HIV positive patient in Uganda. Anti T.gondii were detected in 54% of the patient,while 23% had parasites in the paripheral blood.
- 19. This study reveals 30.9% of 350 pregnant women were seropositive for toxoplasma gondii specific antibodies
- 21. The Study done by Elichilla Shao et al ‘sero-prevalence and factors associated with Toxoplasma gondii infection among pregnant women antending ANC at KCMC in 2015 revealed 60 of 144(41.7%) pregnant women were seropostive for T.gondii specific Abs
- 22. PATHOGENESIS Attachment to the host cell membrane requires the calcium-dependent secretion of adhesins. T. gondii multiplies intracellularly at the site of invasion (the gastrointestinal tract is the major route for and the initial site of infection in nature) Invasion is an active process relying on parasite motility and the sequential secretion of proteins from secretory
- 23. Organisms may spread first to the mesenteric lymph nodes and then to distant organs by invasion of lymphatics and blood Tissue cyst formation takes place in multiple organs and tissues during the first week of infection, which are responsible for chronic or residual or latent infection and persists primarily in the brain, skeletal and heart muscle, and eye.
- 24. In immunocompetent individuals, the initial infection and the resultant seeding of different organs lead to a chronic or latent infection without clinical significance Toxoplasmosis in immunodeficient individuals may be caused by primary infection It most often is the result of reactivation of a latent infection.
- 25. It is widely held that reactivation is the result of disruption of the tissue cyst form followed by uncontrolled proliferation of organisms and tissue destruction. After invasion, the humoral and cellular immunity become activated Only those parasites protected by an intracellular habitat or within tissue cysts survive.
- 26. An effective immune response reduces the number of tachyzoites in all tissues. Tachyzoites are killed by reactive oxygen intermediates,acidification,osmotic fluctuations and reactive nitrogen intermediates and specific antibody combined with complement
- 27. PATHOLOGY 1/3 CENTRAL NERVOUS SYSTEM •Damage to the CNS o Multiple foci of enlarging necrosis and microglial nodules. o Periaqueductal and periventricular vasculitis with necrosis •Hydrocephalus o Obstruction of the aqueduct of Sylvius or foramen of Monro. •Multiple brain abscesses • Severely immunodeficient
- 28. EYE •Chorioretinitis in AIDS patients is characterized by segmental panophthalmitis and areas of coagulative necrosis associated with tissue cysts and tachyzoites LUNGS •Interstitial pneumonitis, necrotizing pneumonitis, consolidation, pleural effusion, empyema, or all of these. SKELETALAND HEART MUSCLES •Myositis & Myocarditis has been reported in some HIV-infected patients who present with neuromuscular symptoms LYMPH NODES •Frequently distinctive and often diagnostic, a reactive follicular hyperplasia is seen always PATHOLOGY 2/3
- 29. CLINICAL FEATURES 1/2 Imunocompetent patients • Only 10% to 20% of cases of T. gondii infection in adults and children are symptomatic, benign and self-limited (Symptoms, if present, usually resolve within a few months) • Cervical lymphadenopathy discrete and nontender, are rarely greater than 3 cm in diameter, may vary in firmness, and do not suppurate.The nodes may be tender or matted. • Fever, malaise, night sweats, myalgias, sore throat, maculopapular rash, hepatosplenomegaly, and small numbers of atypical lymphocytes (<10%) may be present.
- 30. Immunocompromised Patients • In HIV-infected patients, the incidence of toxoplasmosis is closely related to CD4 T cell counts, with an increasing risk when the count falls under 100 cells/l. • Toxoplasmic encephalitis (TE): o Most predominant manifestation, symptoms ranging from headache,lethargy, incoordination, or ataxia to hemiparesis, loss of memory, dementia, or focal to major motor seizures, usually associated with fever • Other organs: lungs, the eyes, and the heart, but the isolation of Toxoplasma from many other sites, such as liver, pancreas, bone marrow, bladder, lymph nodes, kidney, spleen, and skin has been documented CLINICAL FEATURES 2/2
- 31. • Classically, Primary acquired maternal infection during gestation. • Risk • Less than 10%, 30%, 60-70% of cases during the first trimester, 2nd and 3rd Trimester respectively • Major sequelae: o Mental retardation, seizures, microcephalus , hydrocephalus, deafness, and psychomotor deficiency. o Eye: Microphthalmia, cataract, increased intraocular pressure, strabismus, optic neuritis, and retinal necrosis, uveitis and retinochoroiditis can be observed • Characteristic triad: Chorioretinitis, Hydrocephalus and Cerebral calcification Congenital toxoplasmosis
- 32. DIAGNOSIS
- 33. Isolation • Mouse inoculation or inoculation in tissue cell cultures • Isolation of T. gondii from blood or body fluids establishes that the infection is acute
- 34. Histio & Cytopathology Cytology Eg CSF, BAL, Amniotic fluid • Tachyzoites may be identified Tissue biopsy (H&E) - Difficult immunohistiochemistry- better • Multiple tissue cysts near an inflammatory necrotic lesion
- 35. Imaging Studies CT scanning in cerebral toxoplasmosis (general) •Multiple bilateral cerebral lesions but may be solitary. MRI has superior sensitivity Ultrasonography •Ultrasonographic diagnosis of congenital toxoplasmosis in a fetus is available at 20-24 weeks' gestation.
- 36. Ct scan images Unilateral lesion Symmetrical lesion
- 37. Treatment 1/3 Acute infection •Sulphadiazine tabs 1 gm 6 hourly + Pyrimethamine tabs 100mg loading dose, then 50mg /day + Folic acid tabs 10mg /day for 6 weeks. •Clindamycin capsules 450mg -600mg 6 hourly + Pyrimethamine tabs 100mg loading dose, then 50mg /day for 6 weeks. Source: Tanzania, National guidelines for the management of HIV and AIDS
- 38. Treatment 2/3 After six weeks of treatment • Give prophylaxis therapy with Sulphadiazine tabs 500mg 6 hourly + Pyrimethamine tabs 25- 50mg /day + Folic acid tabs 10mg /day. For those allergic to sulphur replace Sulphadiazine tabs with Clindamycin capsules 450mg 6 hourly • Discontinue maintenance therapy when CD4 count is >200cells/ml, initial therapy is completed and patient is asymptomatic. Source: Tanzania, National guidelines for the management of HIV and AIDS
- 39. • Primary prophylaxis therapy for toxoplasmosis can be accomplished with Trimethoprim– Sulphamethoxazole (TMP-SMX) tabs 160/800mg administered orally/day. • For those allergic to sulphur, give Dapsone tabs 50mg/day + Pyrimethamine tabs 50mg per week + Folic Acid tabs 10mg 3 times a week Treatment 3/3
- 41. • Treatment of pregnant women to reduce parasite transmission. • Screening o Prenatal screening and treatment to limit fetal damage. o Postnatal screening of neonates to promote early treatment. o Screening Immunocompromised Patients • Prophylaxis of TE in Toxoplasma-seropositive AIDS patients is rather consensual, and Cotrimoxazole prophylaxis should be administered when the CD4 T cell count falls below 100 cells/l. since it is also suited for(PCP) prophylaxis. Secondary Prevention
- 42. REFERENCES • Mandell,Bennett &Dolin,Principels and Practice of Infectious Diseases 6th edition • Epidemiology of and Diagnostic Strategies for Toxoplasmosis-Florence Robert-Gangneuxa,b and Marie-Laure Dardéc 2012 • Sero-prevalence and factors associated with Toxoplasma gondii infection among pregnant women attending antenatal care in Mwanza, Tanzania- Mwambe et al. Parasites & Vectors 2013, 6:222 • High seroprevalence of specific Toxoplasma gondii IgG antibodies among HIV/AIDS patients with immunological failure attending a tertiary hospital in northwestern Tanzania-Mirambo et al 2013 • Sero-Prevalence and Factors Associated with Toxoplasma Gondii Infection among Pregnant Women Attending Antenatal Care in the Referral Hospital in Tanzania: Cross Sectional Study-Shao et al 2014 • Tanzania, National guidelines for the management of HIV and AIDS, 7th Edition, 2019
Editor's Notes
- #11: Conoid –coneshaped Roptries – specialized secretory organel
- #33: Antibodies can be detected by ELISA or ISAGAs and Indirect Fluorescent antibody Test(IFAT) Amniopuncture at 16wks of GA or atleast 4wks after maternal infection Sabin-Feldman test detects IgG as early as 1-2 weeks,reaching peak at 6-8 weeks and then gradually decline over 1 to 2 years.It needs an alive organism.